ORCID Profile
0000-0002-6044-7328
Current Organisations
Sir Charles Gairdner Hospital
,
University of Western Australia
,
Perron Institute for Neurological and Translational Science
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Publisher: BMJ
Date: 04-01-2012
DOI: 10.1136/BJSPORTS-2011-090529
Abstract: Regular physical activity is associated with reduced risk of mortality in middle-aged adults however, associations between physical activity and mortality in older people have been less well studied. The objective of this study was to compare relationships between physical activity and mortality in older women and men. The prospective cohort design involved 7080 women aged 70-75 years and 11 668 men aged 65-83 years at baseline, from two Australian cohorts - the Australian Longitudinal Study on Women's Health and the Health in Men Study. Self-reported low, moderate and vigorous intensity physical activity, socio-demographic, behavioural and health characteristics were assessed in relation to all-cause mortality from the National Death Index from 1996 to 2009 the median follow-up of 10.4 (women) and 11.5 (men) years. There were 1807 (25.5%) and 4705 (40.3%) deaths in women and men, respectively. After adjustment for behavioural risk factors, demographic variables and self-reported health at baseline, there was an inverse dose - response relationship between physical activity and all-cause mortality. Compared with women and men who reported no activity, there were statistically significant lower hazard ratios for women who reported any activity and for men who reported activities equivalent to at least 300 metabolic equivalent.min/week. Risk reductions were 30-50% greater in women than in men in every physical activity category. Physical activity is inversely associated with all-cause mortality in older men and women. The relationship is stronger in women than in men, and there are benefits from even low levels of activity.
Publisher: Wiley
Date: 20-01-2019
DOI: 10.1111/CEN.13918
Abstract: Telomeres protect chromosomes from damage, and shorter leucocyte telomere length (LTL) is a marker of advancing biological age. The association between testosterone (T) and its bioactive metabolites, dihydrotestosterone (DHT) and oestradiol (E2) with telomere length, particularly in older men, is uncertain. The study aimed to clarify associations of sex hormones with LTL in older men. We used cross-sectional data from 2913 men aged 76.7 ± 3.2 years with morning blood s les assayed for T, DHT, E2 (mass spectrometry), and sex hormone-binding globulin (SHBG, immunoassay), to correlate sex hormones with LTL measured using PCR and expressed as T/S ratio in multivariable linear regression models adjusted for age, cardiometabolic risk factors and cardiovascular disease history. Average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r = 0.038, P = 0.039) and SHBG was inversely correlated (r = -0.053, P = 0.004). After multivariable adjustment, E2 was associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, P = 0.043), T and DHT were not associated. When E2 and SHBG were simultaneously included, E2 remained positively (coefficient 0.014, P = 0.014) and SHBG inversely (coefficient -0.013, P = 0.037) associated with T/S ratio. In older men, neither T nor DHT is associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated, thus relating sex hormone exposure to lower biological age. Further research is needed to determine causality and clarify the role of sex hormones in male ageing.
Publisher: American College of Physicians
Date: 17-10-2017
Publisher: Wiley
Date: 27-01-2010
DOI: 10.1111/J.1532-5415.2009.02677.X
Abstract: To examine in an older population all-cause and cause-specific mortality associated with underweight (body mass index (BMI) or =30.0). Cohort study. The Health in Men Study and the Australian Longitudinal Study of Women's Health. Adults aged 70 to 75, 4,677 men and 4,563 women recruited in 1996 and followed for up to 10 years. Relative risk of all-cause mortality and cause-specific (cardiovascular disease, cancer, and chronic respiratory disease) mortality. Mortality risk was lowest for overweight participants. The risk of death for overweight participants was 13% less than for normal-weight participants (hazard ratio (HR)=0.87, 95% CI=0.78-0.94). The risk of death was similar for obese and normal-weight participants (HR=0.98, 95% CI=0.85-1.11). Being sedentary doubled the mortality risk for women across all levels of BMI (HR=2.08, 95% CI=1.79-2.41) but resulted in only a 28% greater risk for men (HR=1.28 (95% CI=1.14-1.44). These results lend further credence to claims that the BMI thresholds for overweight and obese are overly restrictive for older people. Overweight older people are not at greater mortality risk than those who are normal weight. Being sedentary was associated with a greater risk of mortality in women than in men.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-12-2018
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.JAD.2011.05.045
Abstract: To determine if complaints of poor sleep are associated with incident depression in older men. Cohort study with an average follow up period of 6 years (range 3 months to 8.5 years). Participants were 5127 community-dwelling Western Australian older men aged 70-90 years who provided information about sleep problems. The primary outcome of interest of the study was a recorded diagnosis of depressive episode, recurrent depressive disorder or dysthymia in the Western Australian Data Linkage System. Participants completed a health questionnaire that included questions assessing difficulty falling asleep, remaining awake, as well as early morning awakening. Other measured factors included age, education, country of birth, living arrangements, social support, smoking, body mass index, and prevalent diabetes, hypertension, arthritis, chronic respiratory diseases, coronary artery disease, stroke, and cancer. Biochemical measurement of C-reactive protein, testosterone and plasma homocysteine were available for 3800 men. We found that 60% of men reported at least one sleep problem and that the unadjusted hazard ratio (HR) of depression was higher in men who complained of difficulties to initiate sleep (HR = 2.19, 95% confidence interval--95% CI = 1.47-3.27) or who remained awake most of the night (HR = 1.94, 95% CI = 1.15-3.27). There was no association between early morning awakening and incident depression. The association between incident depression and subjective difficulty falling asleep remained after the analyses were adjusted for other measured factors (HR = 1.83, 95% CI = 1.20-2.79). The association between depression and remaining awake was no longer significant once the analyses were adjusted for confounding (HR = 1.43, 95% CI = 0.81-2.53). A sensitivity analysis confirmed these results. The evaluation of the exposure (sleep disturbance) was limited to self-rating questions that were not externally validated. The diagnosis of depression was based on administrative record linkage rather than structure clinical interviews. The observational nature of the study limits our ability to ascribe a causal relationship between complaints of poor sleep and incident depression. Complaints of difficulty falling asleep increase the risk of incident depression in older men. Clarifying the mechanisms that underlie this association should become an international research priority, as they may contribute to guide interventions designed to decrease the burden of depression in later life.
Publisher: Public Library of Science (PLoS)
Date: 20-06-2014
Publisher: Massachusetts Medical Society
Date: 14-05-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2017
Publisher: BMJ
Date: 19-04-1997
Publisher: Elsevier BV
Date: 07-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2009
DOI: 10.1161/STROKEAHA.108.522631
Abstract: Background and Purpose— Risk for both intracranial aneurysms (IAs) and aortic aneurysms (AAs) is thought to be heritable with mounting evidence for genetic predisposition. The concept of shared risk for these conditions is challenged by differences in age of diagnosis and demographic characteristics. We performed a genomewide linkage analysis in multiplex families with both IA and AA from the Familial Intracranial Aneurysm study. Methods— Available medical records of subjects who reported IA or abdominal/thoracic AA were reviewed with adjudication as definite robable, possible, or not a case. To identify genes contributing to the susceptibility for IA and AA, genomewide linkage analysis was performed in the 26 multiplex IA families who had members who also had thoracic or abdominal AA. In iduals (n=91) were defined as affected if they had an IA (definite robable) or an aortic or thoracic AA (definite robable). Results— Maximum logarithm of odds (LOD) scores were found on chromosomes 11 (144 cM LOD=3.0) and 6 (33 cM LOD=2.3). In both chromosomal regions, analyses of these same 26 families considering only IA as the disease phenotype produced LOD scores of 1.8 and 1.6, respectively. Conclusions— Our linkage analysis in these 26 families using the broadest disease phenotype, including IA, abdominal AA, and thoracic AA, supports the concept of shared genetic risk. The chromosome 11 locus appears to confirm earlier independent associations in IA and AA. The chromosome 6 finding is novel. Both warrant further investigation.
Publisher: SAGE Publications
Date: 14-05-2019
Abstract: A thinner cerebral cortex is associated with higher white matter hyperintensity burden and cognitive impairment in community-dwelling and dementia cohorts. It is important to assess these associations in people with ischemic stroke because their cerebrovascular disease profiles are different to these cohorts. We aimed to determine whether cortical thickness was related to white matter hyperintensity burden and cognition after ischemic stroke. We measured cortical thickness using advanced normalization tools' “KellyKapowski” function in 244 patients with ischemic stroke or transient ischemic attack from the Virtual International Stroke Trials Archive. We measured white matter hyperintensity burden via quantitative volumes and Fazekas score. We extracted data on vascular risk factors at baseline and Mini Mental State Examination scores at one year. We assessed associations between imaging and clinical data using correlation and multiple linear regression. Pairwise correlation showed that higher white matter hyperintensity Fazekas score was associated with a thinner cortex (rho = −0.284, P 0.0001). White matter hyperintensities were generally distributed adjacent to and above the lateral ventricles. Voxel-wise analyses showed statistically significant negative associations between cortical thickness and white matter hyperintensities across fronto-temporal and inferior parietal cortical regions. Mean cortical thickness was positively related to Mini Mental State Examination in pair-wise correlation (r = 0.167, P = 0.0088) but there was no independent association after adjustment for age and white matter hyperintensities (beta = 0.016, P = 0.7874). Cortical thickness was not an independent predictor of cognition after ischemic stroke. Further work is required to understand how white matter hyperintensities are associated with a thinner cortex in temporal regions but less so in more superior regions where white matter hyperintensities are generally found in people with stroke.
Publisher: Wiley
Date: 08-2008
DOI: 10.1111/J.1445-5994.1987.TB00085.X
Abstract: In contrast to the scarcity of recorded cases of radiologically studied venous angiomas, venous angiomas are the most common of the four basic types of congenital intracranial vascular malformations encountered incidentally at autopsy. Their clinical significance remains unclear. When symptomatic, they are associated mainly with hemorrhage or mechanical pressure on cranial nerves by anomalously enlarged veins, however, it is, as yet, impossible to predict what course an asymptomatic cerebellar venous angioma will take. The risks of surgery appear to exceed those of the natural history of the disorder. The following two cases of asymptomatic cerebellar venous angioma are recorded because of the rarity of the condition's diagnosis and the possibility of controversy in its conservative management.
Publisher: BMJ
Date: 08-2015
Publisher: Frontiers Media SA
Date: 22-01-2015
Publisher: Wiley
Date: 02-1995
Publisher: Elsevier BV
Date: 12-2022
Publisher: BMJ
Date: 17-02-2016
Publisher: Elsevier BV
Date: 06-2008
Publisher: Oxford University Press (OUP)
Date: 08-1999
DOI: 10.1177/204748739900600403
Abstract: Up to one quarter of all strokes are directly attributable to cigarette smoking, which independently increases the relative risk of stroke about three-fold. The risk is dependent upon the amount of cigarettes smoked, is consistent for all subtypes of stroke, and is strongest for subarachnoid haemorrhage and cortical ischaemic stroke caused by arterial atherothromboembolism. The relative risk of stroke is equally high among male and female smokers, and is maximal (compared with non-smokers) n middle age, declining with advancing years. Evidence is also accumulating to implicate pipe and cigar smoking as a risk factor for stroke, and passive exposure to environmental smoke as a risk factor for atherogenesis. The risk of stroke declines considerably and rapidly after stopping smoking, thus supporting a causal relationship, even though it has proved impossible to perform a satisfactory randomised controlled trial. The mechanisms by which smoking causes stroke remain uncertain, but are probably multifactorial and primarily atherogenic.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-03-2014
Abstract: Time in therapeutic range ( TTR ) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (c TTR ) since such analysis preserves randomized comparisons. TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio ( INR ) values performed during warfarin initiation. Measurements during warfarin interruptions days were excluded. INR s were performed via standardized finger‐stick point‐of‐care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non‐central nervous system embolism) was examined by quartiles of c TTR and by c TTR as a continuous function. Centers with the highest c TTR s by quartile had lower‐risk patients as reflected by lower CHADS 2 scores ( P .0001) and a lower prevalence of prior stroke or transient ischemic attack ( P .0001). Sites with higher c TTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of c TTR s ( P value for interaction=0.71). The hazard of major and non‐major clinically relevant bleeding increased with c TTR ( P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold c TTR values. The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of c TTR .
Publisher: Wiley
Date: 02-1989
DOI: 10.1111/J.1440-1673.1989.TB03249.X
Abstract: Inactivating mutations in glucokinase (GCK) cause mild fasting hyperglycemia. Identification of a GCK mutation has implications for treatment and prognosis therefore, it is important to identify these in iduals. A significant number of patients have a phenotype suggesting a defect in glucokinase but no abnormality of GCK. We hypothesized that the GCK beta-cell promoter region, which currently is not routinely screened, could contain pathogenic mutations therefore, we sequenced this region in 60 such probands. The beta-cell GCK promoter was sequenced in patient DNA. The effect of the identified novel mutation on GCK promoter activity was assessed using a luciferase reporter gene expression system. Electrophoretic mobility shift assays (EMSAs) were used to determine the impact of the mutation on Sp1 binding. A novel -71G>C mutation was identified in a nonconserved region of the human promoter sequence in six apparently unrelated probands. Family testing established cosegregation with fasting hyperglycemia (> or = 5.5 mmol/l) in 39 affected in iduals. Haplotype analysis in the U.K. family and four of the Slovakian families demonstrated that the mutation had arisen independently. The mutation maps to a potential transcriptional activator binding site for Sp1. Reporter assays demonstrated that the mutation reduces promoter activity by up to fourfold. EMSAs demonstrated a dramatic reduction in Sp1 binding to the promoter sequence corresponding to the mutant allele. A novel beta-cell GCK promoter mutation was identified that significantly reduces gene expression in vitro through loss of regulation by Sp1. To ensure correct diagnosis of potential GCK-MODY (maturity-onset diabetes of the young) cases, analysis of the beta-cell GCK promoter should be included.
Publisher: Elsevier BV
Date: 09-2023
Publisher: MDPI AG
Date: 13-03-2021
DOI: 10.3390/IJMS22062931
Abstract: Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8 MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001 Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001 Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger s le sets are required.
Publisher: Elsevier BV
Date: 03-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
DOI: 10.1161/STROKEAHA.107.497271
Abstract: For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in 000 patients with recent ( days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P 2 Y 12 ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348).
Publisher: American Medical Association (AMA)
Date: 20-03-2013
Publisher: Wiley
Date: 04-1989
DOI: 10.1111/J.1445-5994.1989.TB00227.X
Abstract: A 27-year-old woman is described who suffered an acute left hemiplegia at the age of three years and 20 years later she noted the onset of unilateral left limb dystonic movements. Her cranial CT scan showed an area of low density, consistent with longstanding infarction, in the right lentiform nucleus. Cerebral angiography demonstrated aneurysmal dilatation of the terminal portion of the right internal carotid artery, minor irregularity of the lenticulostriate branches of the right middle cerebral artery (suggestive of Moya Moya disease) and occlusion of the right anterior cerebral artery. The dystonic movements improved with levodopa therapy. Clinico-radiological correlation in this case supports recent evidence for a disruption of pathways between the caudate nucleus, lentiform nucleus and thalamus in the pathophysiology of hemidystonia.
Publisher: BMJ
Date: 06-1989
Abstract: Three young adults are described who presented during early childhood with a seizure disorder due to an underlying intracerebral tumour. The tumours were excised incompletely 14-19 years later. The histological findings were those of a temporal lobe benign capillary haemangioblastoma (Case 1), parietal lobe subependymoma (Case 2), and parietal lobe ganglioglioma (Case 3). After a mean period of follow-up of 22 years (range 18-26), only mild residual physical disabilities exist in each patient. These three cases illustrate (1) the need promptly to investigate children who present with focal seizures or whose EEG shows definite focal abnormalities, (2) the relevant investigations should include cranial CT or MRI in such cases and (3) that certain supratentorial tumours have a favourable outcome due to their benign biological behaviour rather than their location.
Publisher: Elsevier BV
Date: 2000
Publisher: Springer Science and Business Media LLC
Date: 07-05-2020
DOI: 10.1186/S13063-020-04327-W
Abstract: Following publication of the original article [1], we were notified that one of the corresponding author’s affiliations was omitted.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2022
DOI: 10.1186/S13063-022-06433-3
Abstract: Treatment fidelity is inconsistently reported in aphasia research, contributing to uncertainty about the effectiveness of types of aphasia therapy following stroke. We outline the processes and outcomes of treatment fidelity monitoring in a pre-specified secondary analysis of the VERSE trial. VERSE was a 3-arm, single-blinded RCT with a 12-week primary endpoint comparing Usual Care (UC) to two higher intensity treatments: Usual Care-Plus (UC-Plus) and VERSE, a prescribed intervention. Primary outcome results were previously reported. This secondary analysis focused on treatment fidelity. Video-recorded treatment sessions in the higher intensity study arms were evaluated for treatment adherence and treatment differentiation. Treatment components were evaluated using a pre-determined fidelity checklist. Primary outcome: prescribed amount of therapy time (minutes) secondary outcomes: (i) adherence to therapy protocol (%) and (ii) treatment differentiation between control and high intensity groups. Two hundred forty-six participants were randomised to Usual Care ( n =81), Usual Care-Plus ( n =82), and VERSE ( n =83). One hundred thirty-five (82%) participants in higher intensity intervention arms received the minimum prescribed therapy minutes. From 10,805 (UC 7787 UC-Plus 1450 VERSE 1568) service events, 431 treatment protocol deviations were noted in 114 participants. Four hundred thirty-seven videos were evaluated. The VERSE therapists achieved over 84% adherence to key protocol elements. Higher stroke and aphasia severity, older age, and being in the UC-Plus group predicted more treatment deviations. We found high levels of treatment adherence and differentiation between the intervention arms, providing greater confidence interpreting our results. The comprehensive systems for intervention fidelity monitoring and reporting in this trial make an important contribution to aphasia research and, we argue, should set a new standard for future aphasia studies. ACTRN 12613000776707
Publisher: The Endocrine Society
Date: 20-08-2018
Abstract: Diabetes mellitus is associated with increased fracture risk despite preservation of bone density and reduced bone turnover. We tested the hypothesis that circulating advanced glycation end products (AGEs) and endogenous secretory receptor for AGEs (esRAGE) differentially modulate bone turnover and predict fracture risk in older men. A total of 3384 community-dwelling men aged 70 to 89 years. Collagen type I C-terminal cross-linked telopeptide, N-terminal propeptide of type I collagen (P1NP), and total osteocalcin (TOC) were assayed using immunoassay and undercarboxylated osteocalcin (ucOC) following hydroxyapatite binding. Plasma N-carboxymethyllysine (CML) and esRAGE were assayed using immunoassay. Methylglyoxal and glyoxal were assayed using mass spectrometry. Incident hip fractures were ascertained. Median age was 76.3 years (interquartile range, 74.2 to 79.1 years). Plasma CML was measured in 3011 men, methylglyoxal and glyoxal in 766 men, and esRAGE in 748 men. Plasma CML, methylglyoxal, glyoxal, and esRAGE were similar in men without and with diabetes (all P > 0.05). CML was positively associated with fasting glucose (r = 0.06, P < 0.001), and esRAGE was inversely associated (r = -0.08, P = 0.045). esRAGE was positively associated with bone formation (P1NP, r = 0.17, P < 0.001 ucOC, r = 0.11, P = 0.008 TOC, r = 0.16, P < 0.001). Incident hip fractures occurred in 106 men during follow-up. Men with CML in the third quartile of values had reduced incidence of hip fracture compared with men in the lowest quartile (hazard ratio, 0.49 95% CI, 0.24 to 0.99 P = 0.045). Glycemia associates positively with CML and reciprocally with esRAGE in older men. Circulating esRAGE modulates bone turnover in older men, whereas CML predicts incidence of hip fracture.
Publisher: BMJ
Date: 10-2001
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2021
Publisher: Oxford University Press (OUP)
Date: 20-07-2017
Abstract: In older adults, thyroid-stimulating hormone (TSH) concentrations are raised and higher free thyroxine (FT4) is associated with poorer health outcomes. As use of nonage-appropriate reference ranges could lead to suboptimal management, we aimed to define reference intervals for TSH and FT4 in older men. We conducted the study on community-dwelling men aged 70-89 years. Baseline TSH and FT4 levels were assayed (Elecsys 2010, Roche Diagnostics). Conventional reference intervals for TSH and FT4 were 0.4-4.0 mIU/L and 10-23 pmol/L, respectively. Incident deaths were ascertained using data linkage. Of the 3,885 men included in the analysis, the 2.5th and 97.5th centiles for TSH and FT4 were 0.64-5.9 mIU/L and 12.1-20.6 pmol/L (0.94-1.60ng/dL), respectively. Of the 411 very healthy men defined by excellent or very good self-rated health and absence of major medical comorbidities, 2.5th to 97.5th centiles for TSH and FT4 were 0.67-4.98 mIU/L and 12.1-20.5 pmol/L (0.94-1.59ng/dL), respectively. TSH was not associated with mortality, whereas higher FT4 was associated with increased mortality. Applying intervals based on very healthy older men to the cohort as a whole led to the reclassification of 310 men (8.0%). More men were classified as being hyperthyroid or hypothyroid, or having subclinical hyperthyroidism, and fewer as having subclinical hypothyroidism. In older men, the reference interval for TSH in older men is shifted upward, whereas the reference interval for FT4 is compressed compared with the conventional reference ranges. Applying reference intervals based on healthy older men identifies a substantial number of older men as having overt thyroid disease or subclinical hyperthyroidism and reduces the number classified as having subclinical hypothyroidism.
Publisher: Wiley
Date: 10-11-2017
DOI: 10.1111/DME.13274
Abstract: To investigate behavioural, physical and biochemical characteristics associated with diabetes in the oldest age group of elderly men. We conducted a cross-sectional analysis of community-dwelling men aged 79-97 years from Perth, Western Australia. Lifestyle behaviours, self-rated health, physical function, and fasting glucose and HbA Of 1426 men, 315 had diabetes (22%). Men with diabetes were of similar age to men without (84.9 vs 84.5 years P = 0.14). Only 26.5% of men with diabetes self-rated their health as excellent or very good, compared with 40.6% of men without diabetes (P < 0.001). Diabetes was associated with less involvement with recreational walking (32.7 vs 41.0% P < 0.01) and leisure activities (19.0 vs 26.5% P < 0.01). Men with diabetes had poorer physical function on multiple measures, including longer times for the Timed Up-and-Go test (15.0 ± 6.9 s vs 13.4 ± 5.3 s P < 0.001) and weaker knee extension (20.2 vs 21.9 kg P < 0.001). In multivariate analyses, diabetes was associated with an increased prevalence of myocardial infarction (odds ratio 1.80, 95% CI 1.25-2.60 P < 0.001) and falls resulting in injury (odds ratio 1.55, 95% CI 1.06-2.26 P = 0.02). Average HbA In older men, diabetes is associated with poorer self-perceived health, reduced healthy lifestyle behaviours and physical function, heart disease and injurious falls. The majority of these men with diabetes had good glycaemic control. Encouraging healthy lifestyle behaviours and improving physical function should be evaluated as interventions to improve quality-of-life and health outcomes.
Publisher: Springer Science and Business Media LLC
Date: 02-05-2017
DOI: 10.1038/TP.2017.90
Publisher: Elsevier BV
Date: 12-2012
Publisher: SAGE Publications
Date: 27-05-2021
DOI: 10.1177/17474930211019568
Abstract: Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization–World Health Organization– Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p 0.001). Acute stroke treatments were offered in ∼ 60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol. There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.
Publisher: Wiley
Date: 08-1997
DOI: 10.1111/J.1445-5994.1997.TB02201.X
Abstract: Reversible ischaemic attacks of the brain or eye (RIA) are a risk factor for stroke. Strategies of stroke prevention include vascular risk factor control, antithrombotic therapy, and carotid surgery. To determine the effectiveness, risks and costs of each stroke prevention strategy for patients with RIA and the Australian community, and the effect of treating people with RIA on the incidence of stroke in Australia. Review of data from prospective community-based studies to determine the prevalence of RIA, the incidence of stroke, and the proportion of stroke patients who report a RIA before their stroke and data from randomised trials to determine the effectiveness, risks and costs of treatments for RIA. About 111,000 Australians have had a prior RIA. Each year, about 37,000 Australians suffer a stroke, of whom up to 8000 (22%) have had a prior ('warning') RIA. Targeting effective stroke prevention strategies to RIA patients with relevant treatable conditions may reduce the in idual's stroke risk by two-thirds (in idual strategies) and possibly further (combination strategies). However, because the attributable risk of RIA for stroke is only about 22% (and may be less, given the role of other causal risk factors for stroke), strategies of stroke prevention in RIA patients can only reduce stroke incidence by up to 15% (from 22% to 7%). The potential benefits of the 'high risk' approach to stroke prevention appear to be less than the 'population' approach, but both approaches are necessary and complementary. Indeed, the cost of implementing the 'high risk' approach may be less than the cost of the strokes prevented ($255 million i.e. 15% of $1.7 billion).
Publisher: Elsevier BV
Date: 02-2011
Publisher: Elsevier BV
Date: 10-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-01-2016
DOI: 10.1161/CIRCULATIONAHA.115.018544
Abstract: Patients with atrial fibrillation (AF) often take multiple medications. We examined characteristics and compared adjusted outcomes between rivaroxaban and warfarin according to number of concomitant baseline medications and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study. At baseline, 5101 patients (36%) were on 0 to 4 medications, 7298 (51%) were on 5 to 9, and 1865 (13%) were on ≥10. Although polypharmacy was not associated with higher risk of stroke or non–central nervous system embolism (adjusted hazard ratio, 1.02 for ≥10 versus 0–4 medications 95% confidence interval, 0.76–1.38), it was associated with higher risks of the combined end point of stroke, non–central nervous system embolism, vascular death, or myocardial infarction (adjusted hazard ratio, 1.41 for ≥10 versus 0–4 medications 95% confidence interval, 1.18–1.68) and nonmajor clinically relevant or major bleeding (adjusted hazard ratio, 1.47 for ≥10 versus 0–4 medications 95% confidence interval, 1.31–1.65). There was no significant difference in primary efficacy (adjusted interaction P =0.99) or safety outcomes (adjusted interaction P =0.87) between treatment groups by number of medications. Patients treated with 0 to 4 medications had lower rates of major bleeding with rivaroxaban (adjusted hazard ratio, 0.71 95% confidence interval, 0.52–0.95 interaction P =0.0074). There was no evidence of differential outcomes in those treated with ≥1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors. In a population of patients with atrial fibrillation, two thirds were on ≥5 medications. Increasing medication use was associated with higher risk of bleeding but not stroke. Rivaroxaban was tolerated across complex patients on multiple medications. URL: www.clinicaltrials.gov . Unique identifier: NCT00403767.
Publisher: Elsevier BV
Date: 09-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2021
Publisher: Elsevier BV
Date: 07-2022
Publisher: Georg Thieme Verlag KG
Date: 22-03-2018
Abstract: With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke.
Publisher: The Endocrine Society
Date: 03-2015
DOI: 10.1210/JC.2014-3339
Abstract: The impact of older age and duration of diabetes mellitus on macrovascular complications is unclear. We tested the hypothesis that in older men, diabetes duration predicts incident cardiovascular events and death, differently from prior myocardial infarction (MI) or stroke. This was a longitudinal cohort study of 11 728 community-dwelling men aged ≥ 65 years in Perth, Western Australia, recruited in 1996-1999. We assessed all-cause mortality, and deaths or hospital admissions with MI or stroke between recruitment and December 2010, analyzing age-specific hazard and adjusting for smoking, education, alcohol, exercise, BMI, hypertension, and hypercholesterolemia. Among 1433 (12.2%) men with diabetes, 208 (14.5%) reported age of onset of diabetes 74 years. Diabetes independently predicted increased all-cause mortality with hazard ratio (HR) of 1.37 (95% confidence interval [CI] = 1.15-1.62) for a duration of 5-9 years, 1.35 (1.18-1.55) for 10-14 years, 1.42 (1.22-1.66) for 15-19 years, and 1.75 (1.45-2.11) for 20-24 years. Mortality from MI was increased for diabetes duration up to 25 years, while stroke-specific mortality increased progressively with diabetes duration. Prior MI or stroke predicted increased risk of subsequent events peaking after 10-20 years. In older men, increasing duration of diabetes predicts stable increases in all-cause and MI-related mortality and a progressively higher risk of stroke deaths. Prior MI was associated with increased risk of subsequent MI, and prior stroke with subsequent stroke, particularly in the 10-20 years following the first event. Diabetes is a duration-dependent risk factor for cardiovascular events which influences outcomes differently from prior vascular disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2004
DOI: 10.1161/01.STR.0000115751.45473.48
Abstract: Background and Purpose— This study was undertaken to better clarify the risks associated with cigarette smoking and subarachnoid hemorrhage (SAH). Methods— The study included 432 incident cases of SAH frequency matched to 473 community SAH-free controls to determine dose-dependent associations of active and passive smoking (at home) and smoking cessation with SAH. Results— Compared with never smokers not exposed to passive smoking, the adjusted odds ratio for SAH among current smokers was 5.0 (95% confidence interval [CI], 3.1 to 8.1) for past smokers, 1.2 (95% CI, 0.8 to 2.0) and for passive smokers, 0.9 (95% CI, 0.6 to 1.5). Current and lifetime exposures showed a clear dose-dependent effect, and risks appeared more prominent in women and for aneurysmal SAH. Approximately 1 in 3 cases of SAH could be attributed to current smoking, but risks decline quickly after smoking cessation, even among heavy smokers. Conclusions— A strong positive association was found between cigarette smoking and SAH, especially for aneurysmal SAH and women, which is virtually eliminated within a few years of smoking cessation. Large opportunities exist for preventing SAH through smoking avoidance and cessation programs.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
DOI: 10.1161/STROKEAHA.107.502930
Abstract: Background and Purpose— Evidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA. Methods— Multiplex families having at least 2 in iduals with “definite” or “probable” IA were ascertained through an international consortium. First-degree relatives of in iduals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped in iduals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene×smoking (pack-years) interaction. Results— The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5 156 cM), 7 (LOD=1.7 183 cM), 8 (LOD=1.9 70 cM), and 12 (LOD=1.6 102 cM) using the broad disease definition. Using the average pack-years for the affected in iduals in each family, the genes on chromosomes 4 (LOD=3.5 P =0.03), 7 (LOD=4.1 P =0.01) and 12 (LOD=3.6 P =0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking. Conclusions— We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene×smoking interaction with 3 of the loci.
Publisher: American Medical Association (AMA)
Date: 1997
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.NEUROIMAGE.2011.01.063
Abstract: Observational studies investigating the association between smoking, cognitive decline and dementia have produced conflicting results. We completed this trial to determine if smoking cessation decreases the progression of cognitive decline in later life. We recruited older smokers (n=229) and never smokers (n=98) and invited smokers to join a smoking cessation trial. The primary outcome of interest was change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) scores over 24 months. Secondary measures included the Logical Memory test and changes in gray matter density. Successful smoking cessation was defined as a minimum of 547 smoking free days during follow up. The ADAS-cog scores of unsuccessful quitters (UQ) increased (i.e., became worse) 1.1±0.3 and 1.2±0.4 points more than the scores of never smokers (NS) (p=0.001) and successful quitters (SQ) (p=0.006) respectively over the 24 months of follow up. Similarly, the scores of UQ declined (i.e., became worse) relative to NS on measures of immediate (p=0.004) and delayed recall (p=0.029). All analyses were adjusted for age, years of education, baseline cognitive performance, alcohol use, depression scores, and the presence of chronic respiratory disease. Thirty-six NS, 18 SQ and 48 UQ completed the imaging substudy. Compared with NS, UQ showed a disproportional loss of gray matter density in the right thalamus, right and left inferior semi-lunar lobule, as well as left superior and inferior parietal lobule over 24 months. SQ showed loss of gray matter compared with NS in the right middle and inferior occipital gyri, right and left culmen, and the left superior frontal gyrus. We did not find any brain regions in which UQ had lost more gray matter than SQ over 2 years. These results are consistent with the hypothesis that smoking causes cognitive decline and loss of gray matter tissue in the brain over time.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1161/STROKEAHA.116.013378
Abstract: Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Of 2144 patients with ischemic stroke, 590 (28% 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%) only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years SD, 11.5 years 10% 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years SD, 15.58 years 4% 95% confidence interval, 3.3–5.4 P .001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF ( r =0.76 P =0.0002). This cross-sectional global s le of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly ( years old) and more often women.
Publisher: Public Library of Science (PLoS)
Date: 20-08-2008
Publisher: Oxford University Press (OUP)
Date: 25-09-2020
DOI: 10.1002/BJS.12050
Publisher: BMJ
Date: 18-05-2006
Publisher: AMPCo
Date: 07-2016
DOI: 10.5694/MJA16.00526
Abstract: The National Heart Foundation of Australia has updated the Guide to management of hypertension 2008: assessing and managing raised blood pressure in adults (updated December 2010). Main recommendations For patients at low absolute cardiovascular disease risk with persistent blood pressure (BP) ≥ 160/100 mmHg, start antihypertensive therapy. The decision to treat at lower BP levels should consider absolute cardiovascular disease risk and/or evidence of end-organ damage, together with accurate BP assessment. For patients at moderate absolute cardiovascular disease risk with persistent systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, start antihypertensive therapy. Treat patients with uncomplicated hypertension to a target BP of < 140/90 mmHg or lower if tolerated. Changes in management as a result of the guideline Ambulatory and/or home BP monitoring should be offered if clinic BP is ≥ 140/90 mmHg, as out-of-clinic BP is a stronger predictor of outcome. In selected high cardiovascular risk populations, aiming for a target of < 120 mmHg systolic can improve cardiovascular outcomes. If targeting < 120 mmHg, close follow-up is recommended to identify treatment-related adverse effects including hypotension, syncope, electrolyte abnormalities and acute kidney injury. Why the changes have been made A 2015 meta-analysis of patients with uncomplicated mild hypertension (systolic BP range, 140-169 mmHg) demonstrated that BP-lowering therapy is beneficial (reduced stroke, cardiovascular death and all-cause mortality). A 2015 trial comparing lower with higher blood pressure targets in selected high cardiovascular risk populations found improved cardiovascular outcomes and reduced mortality, with an increase in some treatment-related adverse events.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 07-2019
Publisher: Elsevier BV
Date: 10-2022
Publisher: Elsevier BV
Date: 11-2020
Publisher: Elsevier BV
Date: 10-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2011
DOI: 10.1161/STROKEAHA.110.603480
Abstract: This study aimed to determine, among older men, the risk and independent significant baseline prognostic factors for first-ever stroke and MI. We performed a prospective cohort study of 4382 community-dwelling older men (mean age, 75.4±4.2 years) with no history of stroke or MI. Baseline data comprised questionnaire responses, clinical measurements, and comorbidity. After a median of 6 years (interquartile range, 5.2–7.2) of follow-up, the overall rate of stroke/MI was 2.61 (95% CI, 2.42–2.81) per 100 person-years. Among major traditional risk prediction variables, only age and smoking were significantly associated with stroke/MI. In our final multivariate model, the independent significant predictors of stroke/MI were age (HR for age older than 85, 3.18 95% CI, 2.05–4.93), diastolic blood pressure mm Hg (Hazard ratio [HR], 1.45 95% CI, 1.18–1.78), high-sensitivity C-reactive protein mg/L (HR, 1.29 95% CI, 1.05–1.59), homocysteine umol/L (HR, 1.35 95% CI, 1.09–1.67), waist-to-hip ratio (HR, 1.47 95% CI, 1.20–1.18), and fair or poor self-reported health (HR, 1.52 95% CI, 1.19–1.94). A new risk model incorporating these variables performed well compared with the Framingham risk equation (Harrell C of 0.660 versus C of 0.620 integrated discrimination improvement of 1.85% z=4.95 P .001 net reclassification index of 0.08 z=2.0 P =0.023). The model was used to develop an 8- point clinical risk score comprising the independent predictors of stroke/MI among this population. Traditional vascular risk factors did not optimally predict stroke/MI among this cohort of community-dwelling older men. We have constructed a new risk score that requires validation in other data sets.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Wiley
Date: 20-08-2009
Publisher: Cambridge University Press (CUP)
Date: 12-2011
Abstract: There is evidence that in iduals with an acquired brain injury (ABI) are at increased risk of developing psychological problems and that they commonly experience difficulties in social communication, associated with poorer long-term outcomes. Although several relevant group interventions have been evaluated, there has been limited exploration of the feasibility of an ABI inpatient intervention. This nonrandomised pilot study tested the feasibility of an inpatient multidisciplinary social communication and coping skills group intervention within 1-year post traumatic/nontraumatic ABI. Seven participants completed a 4-week group program (3 × 1 hour sessions per week) facilitated by a speech pathologist and clinical psychologist and were assessed pre ost intervention and at 3 months with the La Trobe Communication Questionnaire, Correct Information Unit analysis, Hospital Anxiety and Depression Scale, Mini International Neuropsychiatric Interview, Coping Self-Efficacy scale and World Health Organization Quality of Life assessment. Most participants improved between baseline and 3 months post intervention in terms of greater informativeness and efficiency of connected speech and reduced anxiety and they provided positive feedback about the group program. Despite the challenges and limitations of this pilot study, the findings are encouraging and support both the value and feasibility of developing such a program into routine inpatient rehabilitation services.
Publisher: American College of Physicians
Date: 18-03-2014
Publisher: Wiley
Date: 20-02-2015
DOI: 10.1002/GPS.4276
Abstract: The incidence of traumatic brain injury (TBI) is rising, as are its neuropsychiatric complications. This study aims to determine (1) the prevalence of TBI, (2) the association between history of past TBI and sociodemographic, lifestyle and clinical factors, and (3) the risk of depression and cognitive impairment in later life associated with exposure to TBI. Cross-sectional study of a community-derived s le of 5486 Australian men aged 70-89 years. Information on TBI was retrieved from the Western Australian Data Linkage System (WADLS) and via self-report. We used the WADLS and self-report to ascertain history of past depression, and the Geriatric Depression Scale 15-items to assess current clinically significant symptoms of depression, defined by score ≥7. We defined cognitive impairment by a mini-mental state examination score <24 or a WADLS diagnosis of dementia. Nine hundred fifty-three men had history of TBI (17.4%). Factors associated with TBI included coronary heart disease, stroke, poor self-perceived physical health and falls. TBI increased the odds ratio of past (odds ratio (OR) = 1.55, 95% confidence interval (CI) = 1.21, 1.99) and current depression (OR = 1.77, 95% CI = 1.36, 2.32), as well as of cognitive impairment (OR = 1.23, 95% CI = 1.00, 1.51). The population fractions of depression and cognitive impairment attributable to TBI were 6.9% (95% CI = 3.3%, 10.3%) and 3.4% (95% CI = 0.0%, 6.9%). History of TBI is common in older men, and is associated with increased risk of depression and cognitive impairment. If this association is truly causal, then the effective reduction of events leading to TBI (e.g., motor vehicle accidents and falls) may also decrease the prevalence of depression and cognitive impairment in later life.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-07-2019
DOI: 10.1212/WNL.0000000000007937
Abstract: To determine whether early and more frequent mobilization after stroke affects health-related quality of life. A Very Early Rehabilitation Trial (AVERT) was an international, multicenter (56 sites), phase 3 randomized controlled trial, spanning 2006–2015. People were included if they were aged ≥18 years, presented within 24 hours of a first or recurrent stroke (ischemic or hemorrhagic), and satisfied preordained physiologic criteria. Participants were randomized to usual care alone or very early and more frequent mobilization in addition to usual care. Quality of life at 12 months was a prespecified secondary outcome, evaluated using the Assessment of Quality of Life 4D (AQoL-4D). This utility-weighted scale has scores ranging from −0.04 (worse than death) to 1 (perfect health). Participants who died were assigned an AQoL-4D score of 0. No significant difference in quality of life at 12 months between intervention (median 0.47, interquartile range [IQR] 0.07–0.81) and usual care (median 0.49, IQR 0.08–0.81) groups was identified ( p = 0.86), nor were there any group differences across the 4 AQoL-4D domains. The same lack of group difference in quality of life was observed at 3 months. When cohort data were analyzed (both groups together), quality of life was strongly associated with acute length of stay, independence in activities of daily living, cognitive function, depressive symptoms, and anxiety symptoms (all p 0.001). Quality of life in AVERT participants was substantially lower than population norms, and the gap increased with age. Earlier and more frequent mobilization after stroke did not influence quality of life. anzctr.org.au ACTRN12606000185561 This study provides Class II evidence that for people with stroke, earlier and more frequent mobilization did not influence quality of life over the subsequent year.
Publisher: Wiley
Date: 02-12-2015
Abstract: CT perfusion is increasingly utilised in hyperacute stroke to facilitate diagnosis and patient selection for reperfusion therapies. This review article demonstrates eight ex les of how CT perfusion can be used to diagnose stroke mimics and small volume infarcts, which can be easily missed on non-contrast CT, and to suggest the presence of an ischaemic penumbra. Radiologists involved in stroke management must understand the importance of rapid imaging acquisition and be confident in the prospective interpretation of this powerful diagnostic tool as we move into a new era of hyperacute stroke care.
Publisher: Elsevier BV
Date: 2006
Publisher: Wiley
Date: 08-1987
DOI: 10.1111/J.1445-5994.1987.TB00087.X
Abstract: Hemorrhage from an intrinsic vascular malformation of the optic chiasm (chiasmal apoplexy) is an uncommon cause of sudden visual loss with chiasmal visual field defects. This paper describes one case of sudden visual loss with an anterior chiasmal visual field defect due to rupture of an intrachiasmatic venous angioma and contrasts it with the clinical presentation of a case of hemorrhage from an intrachiasmatic arteriovenous malformation causing severe headache and a less apoplectic onset of visual symptoms. The variable clinical presentation and the accuracy of high resolution post-contrast cranial CT scan in the diagnosis of intrachiasmal hemorrhage is highlighted.
Publisher: Elsevier BV
Date: 03-2017
Publisher: Elsevier BV
Date: 02-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-1988
Abstract: The clinical manifestations of thalamic hemorrhage frequently comprise hemiparesis, hemianesthesia, and oculomotor abnormalities. Since the advent of computed tomography, an amnestic syndrome following thalamic hemorrhage has been recognized, but the thalamic structures involved and the mechanism of amnesia have remained uncertain. We report a patient with sudden memory dysfunction following hemorrhage into the anterior nucleus of the left thalamus that was shown neuropathologically to disrupt the mamillothalamic fasciculus, one of the principal components of the limbic system. It is considered that the amnestic syndrome following thalamic (anterior nucleus) hemorrhage is due to interruption of the mamillothalamic fasciculus.
Publisher: BMJ
Date: 20-10-2013
Abstract: Small vessel disease is reported to be a more common cause of ischaemic stroke in people with diabetes than in others. However, population based studies have shown no difference between those with and those without diabetes in the subtypes of stroke. We determined the rates and predictors of risk of stroke and its subtypes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. 9795 patients aged 50-75 years with type 2 diabetes were followed up for a median of 5 years. Annual rates were derived by the Kaplan-Meier method and independent predictors of risk by Cox proportional hazards regression analyses. The annual rate of stroke was 6.7 per 1000 person years 82% were ischaemic and caused by small artery disease (36%), large artery disease (17%) and embolism from the heart (13%) 10% were haemorrhagic. Among the strongest baseline predictors of ischaemic or unknown stroke were age (60-65 years, HR 1.98 >65 years, HR 2.35) and a history of stroke or transient ischaemic attack (TIA) (HR 2.06). Other independent baseline predictors were male sex, smoking, history of hypertension, ischaemic heart disease, nephropathy, systolic blood pressure and blood low density lipoprotein (LDL) cholesterol, HbA(1c) and fibrinogen. A history of peripheral vascular disease, low high density lipoprotein, age and history of hypertension were associated with large artery ischaemic stroke. A history of diabetic retinopathy, LDL cholesterol, male sex, systolic blood pressure, smoking, diabetes duration and a history of stroke or TIA were associated with small artery ischaemic stroke. Older people with a history of stroke were at highest risk of stroke, but the prognosis and prognostic factors of subtypes were heterogeneous. The results will help clinicians quantify the absolute risk of stroke and its subtypes for typical diabetes patients.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.JACC.2007.03.025
Abstract: The purpose of this study was to determine the possible benefit of dual antiplatelet therapy in patients with prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease (PAD). Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the settings of acute coronary syndromes and coronary stenting. The value of this combination was recently evaluated in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial, where no statistically significant benefit was found in the overall broad population of stable patients studied. We identified the subgroup in the CHARISMA trial who were enrolled with documented prior MI, ischemic stroke, or symptomatic PAD. A total of 9,478 patients met the inclusion criteria for this analysis. The median duration of follow-up was 27.6 months. The rate of cardiovascular death, MI, or stroke was significantly lower in the clopidogrel plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01). Additionally, hospitalizations for ischemia were significantly decreased, 11.4% versus 13.2% (HR 0.86, 95% CI 0.76 to 0.96, p = 0.008). There was no significant difference in the rate of severe bleeding: 1.7% versus 1.5% (HR 1.12, 95% CI 0.81 to 1.53, p = 0.50) moderate bleeding was significantly increased: 2.0% versus 1.3% (HR 1.60, 95% CI 1.16 to 2.20, p = 0.004). In this analysis of the CHARISMA trial, the large number of patients with documented prior MI, ischemic stroke, or symptomatic PAD appeared to derive significant benefit from dual antiplatelet therapy with clopidogrel plus aspirin. Such patients may benefit from intensification of antithrombotic therapy beyond aspirin alone, a concept that future trials will need to validate. (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA] t/show/NCT00050817?order=1 NCT00050817).
Publisher: BMJ
Date: 07-1993
Abstract: The prognosis of in idual patients with transient ischaemic attacks (TIAs) is extremely variable some patients are at high risk and others at low risk of a serious vascular event. Prediction equations of outcome were developed, based on eight clinical prognostic factors, from a cohort of 469 hospital-referred TIA patients ("training" data set), that enable high (and low) risk patients to be identified and for whom costly and risky treatments may (or may not) be targeted. The study aimed to determine whether these equations are externally valid and can predict outcome, with reliability and discrimination, in two independent cohorts of TIA patients ("test" data sets): 1653 TIA patients in the UK-TIA aspirin trial and 107 TIA patients in the Oxfordshire Community Stroke Project. Predicted outcomes agreed closely with the observed outcomes in the "test" data sets (reliability) for all outcome events at low five year risk ( 40%). The prediction equations were fairly accurate in discriminating between patients who subsequently suffered the outcome event of interest and those who survived free of the event at five years after the TIA, particularly at lower cut-off levels distinguishing high and low risk (for ex le, 30% at five years). It is very difficult to achieve perfect discrimination because there is no single important prognostic factor for TIA patients that indicates whether a patient is going to suffer an event or not. These equations can be used to provide a reliable estimate of the absolute five year risk of a serious vascular event in hospital-referred TIA patients but they cannot, as yet, be used with confidence to distinguish patients at high risk from patients at low risk.
Publisher: Oxford University Press (OUP)
Date: 02-2012
Publisher: Elsevier BV
Date: 07-2012
Publisher: Wiley
Date: 28-06-2023
DOI: 10.1002/ECY.4101
Abstract: The exchange of material and in iduals between neighboring food webs is ubiquitous and affects ecosystem functioning. Here, we explore animal foraging movement between adjacent, heterogeneous habitats and its effect on a suite of interconnected ecosystem functions. Combining dynamic food web models with nutrient‐recycling models, we study foraging across habitats that differ in fertility and plant ersity. We found that net foraging movement flowed from high to low fertility or high to low ersity and boosted stocks and flows across the whole loop of ecosystem functions, including biomass, detritus, and nutrients, in the recipient habitat. Contrary to common assumptions, however, the largest flows were often between the highest and intermediate fertility habitats rather than highest and lowest. The effect of consumer influx on ecosystem functions was similar to the effect of increasing fertility. Unlike fertility, however, consumer influx caused a shift toward highly predator‐dominated biomass distributions, especially in habitats that were unable to support predators in the absence of consumer foraging. This shift resulted from both direct and indirect effects propagated through the interconnected ecosystem functions. Only by considering both stocks and fluxes across the whole loop of ecosystem functions do we uncover the mechanisms driving our results. In conclusion, the outcome of animal foraging movements will differ from that of dispersal and diffusion. Together we show how considering active types of animal movement and the interconnectedness of ecosystem functions can aid our understanding of the patchy landscapes of the Anthropocene.
Publisher: American Medical Association (AMA)
Date: 07-2019
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.MATURITAS.2019.06.009
Abstract: It is uncertain whether depression and exposure to antidepressants increase the risk of cardiovascular events in later life. This study attempts to clarify whether the risk of cardiovascular events associated with exposure to antidepressant medications varies according to history of depression. Cohort study of 5522 Australian men aged 70-89 years living in the metropolitan region of Perth, Western Australia, who were followed for novel cardiovascular events over 12 years. Clinical diagnoses followed the International Classification of Diseases (ICD) codes for ischaemic heart disease, cerebrovascular events and depressive disorders. Participants self-reported their use of medications. Other study measures included age, schooling, smoking history and the following concurrent morbidities: diabetes, hypertension, cancer, dementia, and respiratory diseases, gastrointestinal and renal diseases. 374 men (6.8%) had a recorded or current diagnosis of depression and 365 (6.6%) were using an antidepressant. Prevalent depression and antidepressant use were associated with increased mortality hazard, but not the interaction between them (hazard ratio, HR = 0.46, 95%CI = 0.33, 0.65). Depression (HR = 1.50, 95%CI = 1.21, 1.86) and antidepressants (HR = 1.52, 95%CI = 1.20, 1.93) were associated with an increased risk of cardiovascular events, but the interaction term was associated with decreased risk (HR = 0.51, 95%CI = 0.30, 0.87). All analyses were adjusted for other study measures. Depression and antidepressant use were associated with an increase in the 12-year risk of cardiovascular events, while antidepressants were associated with a decrease in the risk of cardiovascular events among older men with depression, but not among those without. This suggests that the effect of this interaction on the risk of cardiovascular events may be driven by the ability of antidepressants to lead to clinical improvements in mood.
Publisher: American College of Physicians
Date: 07-12-2010
DOI: 10.7326/0003-4819-153-11-201012070-00002
Abstract: Knowledge about sexuality in elderly persons is limited, and normative data are lacking. To determine the proportion of older men who are sexually active and to explore factors predictive of sexual activity. Population-based cohort study. Community-dwelling men from Perth, Western Australia, Australia. 3274 men aged 75 to 95 years. Questionnaires from 1996 to 1999, 2001 to 2004, and 2008 to 2009 assessed social and medical factors. Sex hormones were measured from 2001 to 2004. Sexual activity was assessed by questionnaire from 2008 to 2009. A total of 2783 men (85.0%) provided data on sexual activity. Sex was considered at least somewhat important by 48.8% (95% CI, 47.0% to 50.6%), and 30.8% (CI, 29.1% to 32.5%) had had at least 1 sexual encounter in the past 12 months. Of the latter, 56.5% were satisfied with the frequency of activity, whereas 43.0% had sex less often than preferred. In cross-sectional analyses, increasing age, partner's lack of interest, partner's physical limitations, osteoporosis, prostate cancer, diabetes, antidepressant use, and β-blocker use were independently associated with reduced odds of sexual activity. Living with a partner and having a non-English-speaking background were associated with increased odds. In longitudinal analyses, higher testosterone levels were associated with increased odds of being sexually active. Other factors were similar to the cross-sectional model. Response bias may have influenced findings because sexuality can be a sensitive topic. Attrition may have resulted in a healthier-than-average s le of older men. One half of elderly men consider sex important, and one third report being sexually active. Men's health problems were associated with lack of sexual activity. Key modifiable risk factors include diabetes, depression, and medication use. Endogenous testosterone levels predict sexual activity, but the role of testosterone therapy remains uncertain. National Health and Medical Research Council of Australia.
Publisher: SAGE Publications
Date: 20-02-2019
Abstract: After an initial stroke, the risk of recurrent stroke is high. Models that implement best-practice recommendations for risk factor management in stroke survivors to prevent stroke recurrence remain elusive. We examined a model which focuses on vascular risk factor management to prevent stroke recurrence in survivors returning to their primary care physicians. This model is coordinated from the stroke unit, integrates specialist stroke services with primary care physicians, and directly involves patients and carers in risk factor management. It is underpinned by the shared care principle in which there is joint participation of specialists as well as primary care physicians in a planned, integrated delivery of care with ongoing involvement of patients and carers, a structure which encourages implementation of best-practice recommendations as well as transferability and sustainability. We hypothesized that an integrated, multimodal intervention based on a shared-care model which supports joint participation of stroke specialists and primary care physicians would improve the implementation of best-practice recommendations for risk factor management in stroke survivors returning to the community. We undertook a double-blind randomized controlled trial, testing the model in three Australian cities using stroke survivors admitted to stroke units and discharged from hospital to return to their primary care physicians. The model was a shared care, multifaceted integrated program which included bidirectional feedback between general practitioner and specialist unit, education, and engagement of patient and carer in self-management with ongoing input from a multidisciplinary team. The primary endpoint was improvement or abolition of risk factors such as raised blood pressure, diabetes, hyperlipidemia, the modification of adverse life-style factors such as lack of exercise, smoking and alcohol abuse and adherence to preventive medication at one year. Intermediate measurement points were scheduled at three monthly intervals. Analysis was by intention to treat, evaluated by covariance or a linear model adjusting for confounding factors or variance of base-line risk factors. The study was registered as ACTRN = 1261100026498. The study population was as follows: intervention ( n = 112), control ( n = 137). At baseline, there was no statistical difference between the groups for any variable. At the 12-month evaluation, there was a significant decrease in systolic blood pressure from baseline in the intervention group of 5.2 mmHg ( p 0.01). This change was not observed in the control group ( p = 0.29). Moreover, at 12 months the mean systolic blood pressure in the intervention group was 129.4 mmHg (SD 14.7), a result which was not obtained in controls. Fasting total cholesterol as well as triglycerides was reduced significantly in the intervention group (both p 0.01) but this was not the case in the control group ( p = 0.11 and p = 0.27, respectively). At 12 months, there was no change in BMI in the intervention group but there was a significant increase in BMI ( p = 0.02) in the control group. At 12 months in the intervention group, the mean distance walked with ease compared to the baseline measurements was increased by a mean distance of 600 m while in the control group the distance walked with ease was reduced compared to that measured at baseline. At 12 months, the Barthel index in the intervention group demonstrated improved function ( p = 0.01), but no change was observed in controls. At 12 months in the intervention group, there was a significant decrease in number of standard alcoholic drinks consumed per week compared to the baseline ( p = 0.04). This was not observed in the control group ( p = 0.34). In stroke survivors, the ICARUSS (Integrated Care for the Reduction of Secondary Stroke) model is superior to usual care with respect to best-practice recommendations for traditional risk factors as well as behavioral and functional outcomes.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000324938
Abstract: i Background: /i It is uncertain whether the location and size of a ruptured intracranial aneurysm (IA) independently influences the outcome of subarachnoid hemorrhage (SAH). i Objective: /i To determine the independent relationship of location and size of a ruptured IA with serious clinical outcomes after SAH in an Australasian population-based study. i Methods: /i From 432 first-ever cases of primary SAH registered prospectively over 12 months in 4 Australasian cities between 1995 and 1998, the demographics, clinical features, risk factors and results of investigations were obtained, including the location and size of any ruptured IA as assessed by cerebral angiography, computed tomography and/or magnetic resonance imaging. Location was classified as either anterior (i.e. anterior communicating artery, internal carotid artery and middle cerebral artery) or posterior circulation (i.e. posterior communicating artery, posterior inferior cerebellar artery, basilar artery and vertebral artery), and size was classified as , 5–9 and ≧10 mm. Outcomes recorded during hospitalization were rebleeding, delayed ischemia, hydrocephalus, residual neurological impairment and in-hospital death. Logistic regression analysis was used to evaluate the effects of IA location and size on outcome, independent of other potential prognostic factors. Data are reported with odds ratios (OR) and 95% confidence intervals (CI). i Results: /i IA location and size were confirmed separately in 299 and 252 patients, respectively. Patients with a posterior circulation IA had a lower rate of rebleeding than those with an anterior circulation IA (adjusted OR: 0.11 95% CI: 0.02–0.87), but otherwise there was no significant relationship between IA location and outcome. Patients with a larger ruptured IA had higher risks of rebleeding (p = 0.02 for trend) and in-hospital death (p = 0.001) after controlling for age, sex, ethnicity, location of the ruptured IA and neurosurgical intervention. i Conclusion: /i IA location in the posterior circulation was associated with a lower risk of rebleeding than IA in the anterior circulation. A larger IA size was associated with higher risks of rebleeding and in-hospital death.
Publisher: American Medical Association (AMA)
Date: 11-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2012
DOI: 10.1161/STROKEAHA.111.632075
Abstract: Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Despite having power to detect odds ratio of 1.09–1.14 for overall IS and 1.20–1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.
Publisher: Wiley
Date: 03-2001
DOI: 10.1046/J.1442-2026.2001.00183.X
Abstract: The assessment and management of patients with a suspected transient ischaemic attack of the brain or eye is a daily task in busy emergency departments. They are common, affecting about 50 per 100,000 population each year. Conditions which mimic a transient ischaemic attack are even more common (e.g. migraine aura, partial seizures, benign paroxysmal positional vertigo, hysteria). This comprehensive review outlines an approach to the management of this complex and challenging problem.
Publisher: Royal Society of Chemistry (RSC)
Date: 1990
DOI: 10.1039/DT9900001417
Publisher: Wiley
Date: 15-08-2006
DOI: 10.1002/ANA.20942
Abstract: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.
Publisher: BMJ
Date: 11-2020
DOI: 10.1136/BMJOPEN-2020-040492
Abstract: Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results. In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019. UK stroke services. 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms the remaining participants had died (380), withdrawn consent or did not respond. Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email. It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future. ISRCTN83290762 Post-results.
Publisher: BMJ
Date: 21-07-2012
DOI: 10.1136/HEARTJNL-2012-302181
Abstract: To examine temporal trends in the incidence and recurrence of hospitalised coronary heart disease (CHD), cerebrovascular disease (CeVD) and peripheral arterial disease (PAD) separately and combined, and by the history of all forms of atherothrombotic disease (ATD). Population-based longitudinal data linkage study. Western Australia. All patients aged 35-84 years hospitalised in Western Australia for CHD, CeVD or PAD from 2000 to 2007. Age-standardised incidence and recurrence rates of CHD, CeVD and PAD stratified by ATD history, sex and age. 107 576 events (65.9% men) were identified 70% of all admissions were for CHD. In patients without a history of any ATD, incidence rates declined significantly in all groups, although the reduction in incident CHD in women was marginal (-0.7%/year, 95% CI -1.5 to +0.1%). The largest annual reductions in incidence rates were for PAD (men, -6.4%/year, 95% CI -7.7 to -5.0% women, -5.4%/year, 95% CI -7.2 to -3.6%) and CeVD in women (-4.0%/year, 95% CI -5.0 to -3.0%). Falls in overall recurrence rates were greatest for CeVD (men, -3.2%/year, 95% CI -4.7 to -1.6% women -4.6%/year, 95% CI -6.4 to -2.7%). Trends across all categories of polyvascular ATD were generally downward, although not all changes were statistically significant. The incidence and recurrence rates of hospitalised ATD have decreased over time, including in patients with disease involving multiple vascular territories. This implies that primary and secondary prevention strategies have been broadly effective. However, high absolute rates of recurrence and limited reduction in 35-54-year-old in iduals highlight patient groups to target to reduce further the burden of ATD.
Publisher: S. Karger AG
Date: 1998
DOI: 10.1159/000047512
Abstract: The IST, CAPRIE and ESPS-2 have shown that large collaborative randomised trials can be conducted in stroke medicine and can provide statistically and clinically significant results. They, and other concurrent studies, have highlighted the potential hazards of early anticoagulation, and the effectiveness and safety of early (and continuous) antiplatelet therapy in limiting early stroke recurrence and its consequences. In addition, they have shown that antiplatelet agents with differing mechanisms of action can have different effects, and perhaps additive effects when combined. The ESPRIT trial should delineate the roles of oral anticoagulant therapy, and the combination of aspirin and dipyridamole, in the prevention of stroke due to arterial disease. Future trials will hopefully determine the role in secondary stroke prevention of inhibitors of the platelet GPIIb/IIIa complex (the final common pathway of platelet aggregation), the combination of anitplatelet agents with different mechanisms of action (e.g. aspirin and clopidogrel, aspirin and IIb/IIIa inhibitors), the combination of antiplatelet agents and oral anticoagulants (which may simultaneously modify platelet function and fibrin production), and the combination of antithrombotic and cholesterol-lowering (statin) medications.
Publisher: The Endocrine Society
Date: 07-2010
DOI: 10.1210/JC.2009-2754
Abstract: The prevalence of frailty increases, whereas testosterone decreases, as men age. Low testosterone may be a risk factor for development of this syndrome. Our objective was to determine whether testosterone levels are associated with frailty. We conducted a prospective cohort study. Between 2001 and 2004, frailty was assessed in 3616 community-dwelling men aged 70-88 yr. Frailty was reassessed in 1586 men aged 76-93 yr in 2008-2009. Frailty was assessed with the FRAIL scale, comprising five domains: fatigue, difficulty climbing a flight of stairs, difficulty walking more than 100 m, more than five illnesses present, or weight loss greater than 5%. Testosterone, SHBG, and LH were assayed at baseline. Free testosterone was calculated using mass action equations. At baseline, 15.2% of men (n = 548) were frail (at least three deficits), increasing to 23.0% (n = 364) at follow-up. At baseline, each 1 sd decrease in total or free testosterone level was associated with increased odds of frailty [odds ratio (OR) = 1.23 95% confidence interval (CI) = 1.11-1.38, and OR = 1.29 95% CI = 1.15-1.44 for total and free testosterone, respectively]. Lower LH was associated with reduced odds of frailty (OR = 0.88 95% CI = 0.81-0.95). Adjustments were made for age, body mass index, smoking, diabetes, social support, and other covariates. At follow-up, only lower free testosterone levels (OR = 1.22 95% CI = 1.05-1.42) predicted frailty. Lower free testosterone was independently associated with frailty at baseline and follow-up. Randomized trials should explore whether testosterone therapy can prevent the development of frailty.
Publisher: Wiley
Date: 05-10-2018
DOI: 10.1111/ADD.14424
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2003
Publisher: Elsevier BV
Date: 03-2013
Publisher: American Medical Association (AMA)
Date: 09-12-2022
DOI: 10.1001/JAMANETWORKOPEN.2022.44836
Abstract: Psychosocial stress is considered a modifiable risk factor for stroke. Given the prevalence of chronic and acute exposure to stress, it represents a potentially attractive target for population-health interventions. To determine the association of psychosocial stress with the risk of acute stroke and explore factors that might modify the association of stress with risk of acute stroke in a large international population. INTERSTROKE is an international retrospective case-control study of risk factors for first acute stroke in 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa. A total of 13 462 patients with stroke and 13 488 matched controls were recruited between January 11, 2007, and August 8, 2015. The present analyses were performed from June 1 to 30, 2021, and included 13 350 cases and 13 462 controls with available data on psychosocial stress. Psychosocial stress and occurrence of stressful life events within the preceding year were measured using a standardized questionnaire of self-reported stress at home and work. The association of stress with acute stroke and its subtypes was examined using multivariable conditional logistic regression and factors that might modify the association, particularly self-reported locus of control. Among 26 812 participants included in the analysis, the mean (SD) age of cases was 62.2 (13.6) years that of controls, 61.3 (13.3) years 7960 cases (59.6%) and 8017 controls (59.6%) were men. Several periods of stress and permanent stress were reported for 2745 cases (20.5%) and 1933 controls (14.4%), with marked regional variation in prevalence, with the lowest in China (201 of 3981 [5.0%] among controls and 364 of 3980 [9.1%] among cases) and highest in South East Asia (233 of 855 [26.1%] among controls and 241 of 782 [30.8%] among cases). Increased stress at home (odds ratio [OR], 1.95 [95% CI, 1.77-2.15]) and at work (OR, 2.70 [95% CI, 2.25-3.23]) and recent stressful life events (OR, 1.31 [95% CI, 1.19-1.43]) were associated with an increased risk of acute stroke on multivariable analyses (vs no self-reported stress). Higher locus of control at home was associated with a reduced odds of all stroke (OR, 0.73 [95% CI, 0.68-0.79]), and higher locus of control both at work and at home were associated with a lower odds of acute stroke and significantly diminished the association with stress at work (OR, 2.20 [95% CI, 1.88-2.58] P = .008 for interaction) and home (OR, 1.69 [95% CI, 1.44-1.98] P & .001 for interaction) for acute stroke. Psychosocial stress is a common risk factor for acute stroke. The findings of this case-control study suggest that higher locus of control is associated with lower risk of stroke and may be an important effect modifier of the risk associated with psychosocial stress.
Publisher: American Medical Association (AMA)
Date: 18-10-2022
Publisher: Korean Stroke Society
Date: 31-05-2022
Abstract: Background and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes.Methods Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH).Results Our analysis included 11,898 matched case-control pairs 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4% 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P .0001). Conclusions The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-02-2019
Publisher: Springer Science and Business Media LLC
Date: 07-01-2016
Publisher: S. Karger AG
Date: 2002
DOI: 10.1159/000047761
Abstract: i Background: /i Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B sub /sub and vitamin B sub /sub , it is not known whether lowering tHcy, by means of multivitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. i Purpose: /i To determine whether vitamin supplements (folic acid 2 mg, B sub /sub 25 mg, B sub /sub 500 µg) reduce the risk of stroke, and other serious vascular events, in patients with recent stroke or transient ischaemic attacks of the brain or eye (TIA). i Methods: /i An international, multi-centre, randomised, double-blind, placebo-controlled clinical trial. i Results: /i As of November 2001, more than 1,400 patients have been randomised from 10 countries in four continents. i Conclusion: /i VITATOPS aims to recruit and follow up 8,000 patients between 2000 and 2004, and provide a reliable estimate of the safety and effectiveness of dietary supplementation with folic acid, vitamin B sub /sub , and vitamin B sub /sub in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke.
Publisher: Elsevier BV
Date: 04-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2012
Publisher: Wiley
Date: 07-06-2022
DOI: 10.1002/IJC.34116
Abstract: Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone‐binding globulin (SHBG) with aggressive, overall and early‐onset prostate cancer. In blood‐based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse‐variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08‐1.40). In blood‐based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged years 1.14, CI = 1.02‐1.28 P het = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08‐1.34 blood‐based: 1.03, 1.01‐1.05) and early‐onset prostate cancer (MR: 1.37, 1.09‐1.73 blood‐based: 1.08, 0.98‐1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood‐based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
Publisher: Oxford University Press (OUP)
Date: 21-03-2014
Abstract: There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors. Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66) P < 0.0001]. Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non-central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin HR 0.89 95% CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin HR 0.69, 95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin (interaction P = 0.51 and 0.11). Among high-risk patients with atrial fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin.
Publisher: MDPI AG
Date: 17-12-2020
DOI: 10.3390/MET10121688
Abstract: The remelting method is introduced to improve the properties of the as-sprayed NiCrBSi coatings. In this work, tungsten carbide (WC) was selected as reinforcement and the as-sprayed and remelted NiCrBSi/WC composite coatings were investigated by X-ray diffraction, scanning electron microscopy, hardness test and tribology test. After spraying, WC particles are evenly distributed in the coating. The remelting process induced the decarburizing reaction of WC, resulting in the formation of dispersed W2C. The dispersed W2C particles play an important role in the dispersion strengthening. Meanwhile, the pores and lamellar structures are eliminated in the remelted NiCrBSi/WC composite coating. Due to these two advantages, the hardness and the high-temperature wear resistance of the remelted NiCrBSi/WC composite coating are significantly improved compared with those with an as-sprayed NiCrBSi coating the as-sprayed NiCrBSi coating, as-sprayed NiCrBSi/WC composite coating and remelted NiCrBSi/WC composite coating have average hardness of 673.82, 785.14, 1061.23 HV, and their friction coefficients are 0.3418, 0.3261, 0.2431, respectively. The wear volume of the remelted NiCrBSi/WC composite coating is only one-third of that of the as-sprayed NiCrBSi coating.
Publisher: American Medical Association (AMA)
Date: 05-2022
Publisher: Elsevier BV
Date: 02-1998
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2013
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.JSTROKECEREBROVASDIS.2019.05.014
Abstract: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.
Publisher: Bentham Science Publishers Ltd.
Date: 04-2021
DOI: 10.2174/0929867327999200819145327
Abstract: Chronic obstructive pulmonary disease (COPD) represents a heightened inflammatory response in the lung generally resulting from tobacco smoking-induced recruitment and activation of inflammatory cells and/or activation of lower airway structural cells. Several mediators can modulate activation and recruitment of these cells, particularly those belonging to the chemokines (conventional and atypical) family. There is emerging evidence for complex roles of atypical chemokines and their receptors (such as high mobility group box 1 (HMGB1), antimicrobial peptides, receptor for advanced glycosylation end products (RAGE) or toll-like receptors (TLRs)) in the pathogenesis of COPD, both in the stable disease and during exacerbations. Modulators of these pathways represent potential novel therapies for COPD and many are now in preclinical development. Inhibition of only a single atypical chemokine or receptor may not block inflammatory processes because there is redundancy in this network. However, there are many animal studies that encourage studies for modulating the atypical chemokine network in COPD. Thus, few pharmaceutical companies maintain a significant interest in developing agents that target these molecules as potential antiinflammatory drugs. Antibody-based (biological) and small molecule drug (SMD)-based therapies targeting atypical chemokines and/or their receptors are mostly at the preclinical stage and their progression to clinical trials is eagerly awaited. These agents will most likely enhance our knowledge about the role of atypical chemokines in COPD pathophysiology and thereby improve COPD management.
Publisher: American Medical Association (AMA)
Date: 10-2020
Publisher: Wiley
Date: 09-07-2010
DOI: 10.1111/J.1360-0443.2010.02972.X
Abstract: To compare the effect of alcohol intake on 10-year mortality for men and women over the age of 65 years. Two prospective cohorts of community-dwelling men aged 65-79 years at baseline in 1996 (n = 11 727) and women aged 70-75 years in 1996 (n = 12 432). Alcohol was assessed according to frequency of use (number of days alcohol was consumed per week) and quantity consumed per day. Cox proportional hazards models were compared for men and women for all-cause and cause-specific mortality. Compared with older adults who did not consume alcohol every week, the risk of all-cause mortality was reduced in men reporting up to four standard drinks per day and in women who consumed one or two drinks per day. One or two alcohol-free days per week reduced this risk further in men, but not in women. Similar results were observed for deaths due to cardiovascular disease. In people over the age of 65 years, alcohol intake of four standard drinks per day for men and two standard drinks per day for women was associated with lower mortality risk. For men, the risk was reduced further if accompanied with 1 or 2 alcohol-free days per week.
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0140-6736(05)70337-8
Abstract: Osteotomy of iliac-pubic and ischial bone in order to cover the lateralized femoral head with the acetabulum. With the restoration of the containment of the hip joint, the acetabulum functions as a template for the femoral head, thus, allowing it to keep its sphericity during the vulnerable stages of Legg-Calve-Perthes disease. Lateralized femoral head in severe Legg-Calve-Perthes disease and visible head at risk signs on the radiographs. Prerequisite is possible concentric reduction of the femoral head (confirmed by preoperative abduction radiograph or arthrography). Hinged abduction. Impossible concentric reduction of the femoral head. Hip arthrography to confirm the indication of the triple pelvic osteotomy is recommended. Osteotomy of the ischial bone by a modified Ludloff approach. Osteotomy of pubic and iliac bone by anterior approach (Smith Peterson/bikini incision). Turning the acetabulum over the femoral head allows improvement of the containment of the hip. Fixation of the acetabulum with fully threaded Kirschner wires or 3.5 mm cortical screws. Touch-down weight bearing with crutches (wheelchair in younger children) for 4-6 weeks depending on the age of the child. After radiologic evidence of consolidation, transition to full-weight bearing within 1-2 weeks. Promising results in our own practice. Good functional and radiological results in a to-date unpublished study of 30 patients with Legg-Calve-Perthes disease after an average 5‑year follow-up.
Publisher: Elsevier BV
Date: 08-2014
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 10-1999
Publisher: Oxford University Press (OUP)
Date: 06-1991
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.IJCARD.2011.06.122
Abstract: The prevalence of hospitalised atherothrombotic disease affecting the coronary, cerebrovascular and peripheral vasculature is expected to increase due to improving survival, ageing and changing risk factor profiles. This study determined sex, age-standardised and age-specific (35-54, 55-69, 70-84years) prevalence of atherothrombotic disease and its association with diabetes and chronic kidney disease in Western Australian residents from 2000 to 2007. In a cross-sectional and longitudinal study, person-linked hospitalisations for atherothrombotic disease were obtained using records from 1985. From 2000 to 2007, total and vasculature-specific prevalence of atherothrombotic disease (as a principal diagnosis) was calculated using a 15-year lead-in to determine prior disease and comorbidity. In 2007, 45,916 (8.6%) men and 22,782 (4.3%) women in Western Australia had established atherothrombotic disease and about 25% had diabetes, 10% had chronic kidney disease, and 5% had both. From 2000 to 2007 the estimated average annual change in age-standardised atherothrombotic disease prevalence was -0.6%/year (95% CI -0.8, -0.4) in men and -0.7%/year (95% CI -1.0, -0.4) in women. Similar modest declines were seen in age-standardised prevalence of monovascular and polyvascular atherothrombotic disease. The proportion of cases with diabetes increased by about 5%/year, the proportion having chronic kidney disease increased slowly in women (1.5%/year) and was stable in men, and the proportion with both comorbidities increased at about 9%/year. The age-standardised prevalence of atherothrombotic disease requiring hospitalisation has been in marginal decline in Western Australia this decade, despite the proportion of affected persons with diabetes and/or chronic kidney disease steadily rising.
Publisher: Elsevier BV
Date: 03-2003
DOI: 10.1053/JSCD.2003.16
Abstract: The possible role of C-reactive protein (CRP) in the etiology and prognosis of ischemic stroke remains to be clearly defined. The purpose of this study was to determine whether CRP levels are elevated in patients with stroke, whether they remain persistently elevated, and whether CRP levels are higher in patients with etiologic subtypes of stroke caused by large or small artery disease ("atherogenic hypothesis") or whether they may be higher in patients with more extensive cerebral infarction caused by large artery or cardiogenic embolism ("inflammatory hypothesis"). We conducted a case-control study of 199 hospital cases with a first-ever ischemic stroke and 202 randomly selected community controls. Cases of stroke were classified by etiologic subtype and the prevalence of conventional vascular risk factors and CRP levels were determined in cases and controls. Blood levels of CRP measured within 7 days of acute stroke were significantly higher in cases compared with controls (8.50 vs. 2.18 mg/L, P < .0001) and remained elevated in stroke survivors at 3 to 6 months of follow-up (3.35 vs. 2.18 mg/L, P = .003) although levels were significantly lower compared with the first 7 days (3.35 vs. 8.50 mg/L, P < .001-.003). Compared with the lowest quartile of CRP, the upper 3 quartiles were associated with an adjusted odds ratio (OR) of ischemic stroke of 1.9 (95% CI: 1.0-3.8) for the second quartile, 5.8 (95% CI: 2.9-11.4) for the third quartile, and 16.9 (95% CI: 7.9-36.1) for the fourth quartile (P for trend < .0001). Comparing the upper with the lower quartile, the strongest association was with etiologic stroke subtypes caused by large artery disease (OR 52.5 95% CI: 13.4-205) and embolism from the heart (OR 56.1 95% CI: 11.3-278), with a much weaker association with small artery disease (OR 2.4 95% CI: 0.8-6.0). The mean Oxford Handicap Scale score was lowest in small artery, intermediate in large artery and highest in cardioembolic stroke (2.8 vs. 3.1 vs. 3.6, respectively P = .001) while the mean Barthel Index was highest in small artery, intermediate in large artery, and lowest in cardioembolic stroke (13.5 vs. 11.5 vs. 8.6, respectively P = .002). Furthermore, there was a significant correlation between CRP levels during the first 7 days and stroke severity, as measured by the Oxford Handicap Scale score (P = .03) and Barthel index (P = .001). We conclude that there is a strong, independent relationship between elevated blood levels of CRP and ischemic stroke, particularly because of more severe strokes caused by large artery disease and embolism from the heart, which remains evident over the long term. These results are consistent with the inflammatory marker hypothesis of CRP as a marker of the extent of ischemic cerebral injury and its complications.
Publisher: Oxford University Press (OUP)
Date: 06-2011
Publisher: Springer Science and Business Media LLC
Date: 2001
DOI: 10.2165/00023210-200115060-00002
Abstract: High plasma levels of the amino acid homocysteine have been implicated in the development of vascular diseases, including stroke. Elevated plasma levels of total homocysteine (tHcy) above 15 micromol/L are present in less than 5% of the general population, but in as many as 50% of patients with stroke (and other atherothromboembolic vascular diseases). However, it remains uncertain whether a high tHcy level is a causal risk factor for stroke and should be lowered, or is a marker of another factor associated with stroke (e.g. acute tissue damage or tissue repair after an acute vascular event) and therefore should not be lowered. Plasma levels of tHcy can be lowered effectively by folic acid, vitamin B(6) and vitamin B(12) supplementation, and controlled trials have shown some beneficial effects on surrogate markers of vascular function. However, these markers are not established vascular risk factors or valid predictors of 'hard' clinical vascular outcome events. Until it has been shown in large randomised trials [such as the ongoing Vitamins to Prevent Stroke Study (VITATOPS) and the Vitamins in Stroke Prevention (VISP) study] that multivitamin therapy reduces the rate of recurrent stroke and other serious vascular events in patients with prior stroke or transient ischaemic attack, widespread screening for, and treatment of, high tHcy levels remains experimental and cannot be recommended.
Publisher: Oxford University Press (OUP)
Date: 09-10-2019
DOI: 10.1002/BJS.11326
Abstract: Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12 P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent P & 0·001). NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.IJCARD.2017.10.100
Abstract: The aim of this study was to assess the association of plasma free thyroxine (FT4) and serum thyroid stimulating hormone (TSH) concentrations with the past diagnosis of cardiovascular disease and incidence of new cardiovascular events in older men with no known thyroid disease. This study involved a cohort of community-recruited older men without known thyroid disease. Plasma FT4 and serum TSH were measured by immunoassay. Past cardiovascular disease diagnosis was defined through questionnaire data. The incidence of major cardiovascular events were assessed using the Western Australian Data Linkage System. The associations of plasma FT4 and serum TSH with the past diagnosis of cardiovascular disease and the incidence of new major cardiovascular events (cardiovascular death, myocardial infarction or stroke) were examined using logistic regression and Cox proportional hazard analyses. 3712 men were followed for a mean of 9.5years. Men with plasma FT4 in the upper quartile, compared to other men, were more likely to have been previously diagnosed with cardiovascular disease but this association did not persist after adjustment for other risk factors. Men with plasma FT4 in the upper quartile, compared to other men, had an increased incidence of major cardiovascular events (adjusted hazard ratio, HR, 1.15, 95% CI 1.00-1.31) and myocardial infarction alone (adjusted HR 1.29, 95% CI 1.06-1.54). This study suggests that older men with higher levels of plasma FT4 not meeting current criteria for the diagnosis of hyperthyroidism are at increased risk of major cardiovascular events.
Publisher: Elsevier BV
Date: 2003
DOI: 10.1016/S1474-4422(03)00267-9
Abstract: Very few trials of acute stroke treatments show efficacy of a tested agent on the prespecified primary outcome. We can learn many lessons from the studies that achieve only neutral results. Preclinical studies have been flawed by use of models of transient not permanent brain ischaemia, treatments that aim to protect cerebral grey matter independently of white matter, delivery of the study drug within too short a time window after ischaemic insult, use of surrogate outcome measures in the short term instead of function in the long-term, and small s le sizes. Clinical trials have been h ered by heterogeneity in causes of stroke and inability to classify subtypes of cause the short time available to rescue ischaemic brain tissue the haemorrhagic transformation that can cause severe functional consequences seen frequently in infarcted brain tissue the lack of valid, reliable, sensitive, and simple tools for assessment of functional outcome and, above all, small treatment effects that are difficult to detect or refute. In this review, we look at the designs and results of all controlled trials of treatments for ischaemic stroke, and try to identify opportunities to improve future treatment assessment.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2023
DOI: 10.1186/S12950-023-00333-2
Abstract: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic or cause a disease (COVID-19) characterized by different levels of severity. The main cause of severe COVID-19 and death is represented by acute (or acute on chronic) respiratory failure and acute respiratory distress syndrome (ARDS), often requiring hospital admission and ventilator support. The molecular pathogenesis of COVID-19-related ARDS (by now termed c-ARDS) is still poorly understood. In this review we will discuss the genetic susceptibility to COVID-19, the pathogenesis and the local and systemic biomarkers correlated with c-ARDS and the therapeutic options that target the cell signalling pathways of c-ARDS.
Publisher: SAGE Publications
Date: 23-01-2012
Publisher: Wiley
Date: 29-12-2010
DOI: 10.1111/J.1741-6612.2010.00498.X
Abstract: To review findings from the Men, Women and Ageing (MWA) longitudinal studies and consider their implications for national health guidelines. Guidelines for good health for older adults in the areas of body mass index (BMI), physical activity, alcohol consumption and smoking behaviours are compared with MWA findings. Findings from MWA suggest that current BMI guidelines may be too narrow because BMI in the overweight range appears to be protective for both older men and women. Across all levels of BMI, even low levels of physical activity decrease mortality risk compared with being sedentary. Our findings suggest that consideration should be given to having different alcohol guidelines for older men and women and should include recommendations for alcohol-free days. The benefit of quitting smoking at any age is apparent for both women and men. Current national guidelines in the areas discussed in this paper should be reviewed for older people.
Publisher: AMPCo
Date: 1987
DOI: 10.5694/J.1326-5377.1987.TB136277.X
Abstract: Peliosis hepatis is described in a renal transplant recipient and in a patient who was receiving long-term haemodialysis. This uncommon liver lesion has been reported in a number of patients, including 18 renal transplant recipients and two patients with chronic renal failure. However, its cause, clinical features, natural history and clinical significance remain to be determined. We emphasize that, although it is rare, peliosis hepatis should be considered in long-term haemodialysis and renal transplant patients who exhibit hepatomegaly and/or splenomegaly and/or disordered liver function (in particular, elevation of hepatic alkaline phosphatase levels).
Publisher: BMJ
Date: 09-1987
Abstract: The type VI secretion system of Pseudomonas aeruginosa has been shown to be responsible for the translocation of bacteriolytic effectors into competing bacteria. A mechanistic understanding of this widely distributed secretion system is developing and structural studies of its components are ongoing. Two representative structures of one highly conserved component, TssJ, from Escherichia coli and Serratia marcescens have been published. Here, the X-ray crystal structure of TssJ1 from P. aeruginosa is presented at 1.4 Å resolution. The overall structure is conserved among the three proteins. This finding suggests that the homologues function in a similar manner and bolsters the understanding of the structure of this family of proteins.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2019
DOI: 10.1161/STROKEAHA.119.026089
Abstract: Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81 95% CI, 0.98–3.35 P =0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P =0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57 95% CI, 1.05–6.25 P =0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81 95% CI, 0.95–3.46 P =0.08). We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent MR evidence suggestive of a possible effect on functional outcome after ischemic stroke. Given the widespread prevalence of depression-related morbidity, these findings could have implications for prognostication and personalized rehabilitation after stroke.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2013
Publisher: Hindawi Limited
Date: 13-07-2017
DOI: 10.1111/ANE.12637
Abstract: Post-stroke cognitive impairment (PSCI) occurs commonly and is linked with development of dementia. We investigated the relationship between demographic, clinical and stroke symptoms at stroke onset and the presence of PSCI at 1 and 3 years after stroke. We accessed anonymized data from the Virtual International Stroke Trial Archive (VISTA), including demographic and clinical variables. Post-stroke cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of ≤26. We assessed univariate relationships between baseline stroke symptoms and PSCI at 1 and 3 years following stroke, retaining the significant and relevant clinical factors as covariates in a final adjusted logistic regression model. We analysed data on 5435 patients with recent (median 33 days) stroke or transient ischaemic attack (TIA). Mean (±SD) age was 62.6 (±12.6) years 3476 (65%) patients were male. Follow-up data were available for 2270 and 1294 patients at 1 and 3 years, respectively. At 1 year, 781 (34%) patients had MMSE≤26 at 3 years, 391 (30%) had MMSE≤26. After adjusting for age, stroke severity, hypertension, diabetes and type of qualifying event, initial stroke impairment (leg paralysis) was associated with increased rate of PSCI at 1 year (OR=1.62 95% CI=1.20-2.20) and at 3 years (OR=1.95 95% CI=1.23-3.09). Associations were consistent on subgroup analysis restricted to ischaemic stroke and transient ischaemic attack (N=4992). Besides well-known determinants of PSCI such as age, stroke severity and the presence of vascular risk factors, also leg paralysis is associated with subsequent of PSCI up to 3 years after stroke.
Publisher: Wiley
Date: 09-03-2014
DOI: 10.1111/J.1754-9485.2012.02474.X
Abstract: Mechanical thrombectomy has the potential to revolutionise the treatment of acute stroke. The Solitaire AB device is used for clot retrieval with unprecedented revascularisation rates being reported. Our aim is to report our experiences of the safety and efficacy of the Solitaire AB device in acute ischaemic stroke. A retrospective dual-centre study of 21 patients with acute ischaemic stroke who underwent mechanical thrombectomy with the Solitaire AB device between 1 October 2010 and 1 December 2011 was carried out. Using clinical data recovered from patients' case notes, we identified time intervals from groin puncture to recanalisation, revascularisation rates, procedural complications and neurological status before and after treatment (using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) respectively). Successful revascularisation, defined as Thrombosis in Cerebral Ischemia Grade 2 or 3, was achieved in 81% of cases. The mean NIHSS score at presentation was 18.5. The mean number of passes required to achieve recanalisation was 1.95 and the median duration of the procedure from groin puncture to recanalisation was 65 min. Procedural events included distal emboli (n = 2), arterial dissection (n = 1) and arterial perforation (n = 1).There were three cases of asymptomatic intracranial haemorrhage. Forty-eight per cent of patients achieved a good functional outcome at 3 months (mRS score ≤2). The mortality rate at 3 months was 19% (n = 4). There was no procedure-related mortality. Mechanical thrombectomy with the Solitaire AB device is safe and achieves high rates of revascularisation in acute stroke with good clinical outcomes.
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Wiley
Date: 07-10-2009
Publisher: Elsevier BV
Date: 10-2023
Publisher: Informa UK Limited
Date: 12-2013
Publisher: Wiley
Date: 06-1987
DOI: 10.1111/J.1445-5994.1987.TB01239.X
Abstract: Primary position upbeating nystagmus has been associated clinically with intra-axial brainstem and cerebellar lesions but evidence for more precise localisation to the ponto-mesencephalic and ponto-medullary junctions is accumulating. We report the occurrence of primary position upbeating nystagmus in three patients who had clinical signs of pontine lesions at the ponto-mesencephalic and ponto-medullary junctions. Radiological confirmation was possible in two cases.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-01-2013
Abstract: Vitamin K antagonist ( VKA ) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range ( TTR ) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. TTR (international normalized ratio [ INR ] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the in idual patient level (i‐ TTR ) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐ TTR was 55.2% (SD 21.3%) and the median i‐ TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR was 29.1% and the mean time with an INR was 15.7%. While multiple clinical features were associated with i‐ TTR , dominant determinants were previous warfarin use (mean i‐ TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA ‐naïve patients) and geographic region where patients were managed (mean i‐ TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐ TTR s had INR distributions shifted toward lower INR values and had longer inter‐ INR test intervals. Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐ TTR in global studies of warfarin. Regional differences in mean i‐ TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. URL: ClinicalTrials.gov . Unique identifier: NCT 00403767.
Publisher: BMJ
Date: 10-1994
Abstract: The validity of a clinical classification system was assessed for subtypes of cerebral infarction for use in clinical trials of putative stroke therapies and clinical decision making in a population based stroke register (n = 536) compiled in Perth, Western Australia in 1989-90. The Perth Community Stroke Project (PCSS) used definitions and methodology similar to the Oxfordshire Community Stroke Project (OCSP) where the classification system was developed. In the PCSS, 421 cases of cerebral infarction and primary intracerebral haemorrhage (PICH), confirmed by brain imaging or necropsy, were classified into the subtypes total anterior circulation syndrome (TACS), partial anterior circulation syndrome (PACS), lacunar syndrome (LACS), and posterior circulation syndrome (POCS). In this relatively unselected population, relying exclusively on LACS for a diagnosis of PICH had a very low sensitivity (6%) and positive predictive value (3%). Comparison of the frequencies and outcomes (at one year after the onset of symptoms) for each subgroup of first ever cerebral infarction in the PCSS (n = 248) with the OCSP (n = 543) registers showed uniformity only for LACI. For ex le, there were 27% of cases of TACI in the PCSS compared with 17% in the OCSP (difference = 10% 95% confidence interval (95% CI) 4% to 16%) and 15% of cases in the PCSS compared with 24% in the OCSP were POCI (difference = 9% 95% CI 3% to 15%). Case fatalities and long-term handicap across the subgroups were not significantly different between studies, but the frequencies of recurrent stroke were significantly greater for POCI in the OCSP compared with the PCSS. Although this classification system defines subtypes of stroke with different outcomes, simple clinical measures-level of consciousness, paresis, disability, and incontinence at onset-are more powerful predictors of death or dependency at one year. It is concluded that simple clinical measures that reflect the severity of the neurological deficit should complement this classification system in clinical trials and practice.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2002
DOI: 10.1097/00041433-200212000-00008
Abstract: To establish the role of cholesterol-modifying therapy in stroke prevention. Population-based observational cohort studies show a variable weak positive relationship between increasing plasma total cholesterol concentrations and an increasing risk of ischaemic stroke, which is partly offset by a weaker negative association between decreasing total cholesterol concentrations and an increasing risk of with haemorrhagic stroke. However, randomized controlled trials show unequivocally that lowering plasma total cholesterol by approximately 1.2 mmol/l (and LDL-cholesterol by 1.0 mmol/l) is associated with a reduced relative risk of stroke and other serious vascular events by at least a quarter, and probably a third, without any increase in haemorrhagic stroke, in a wide range of men and women (including in iduals with previous stroke). The proportional reduction in stroke risk is consistent, irrespective of the patient's age, baseline plasma cholesterol concentration, and absolute risk of stroke (although perhaps less in very low-risk in iduals), but is increased with greater degrees of cholesterol lowering (15% or more), and thus with statin medications, which are more potent than non-statin interventions in lowering cholesterol levels. The absolute reduction in stroke risk achieved by statins is greatest among in iduals at highest risk of stroke. Preliminary evidence suggests that lowering total cholesterol levels by diet may be an effective adjunctive therapy to statins, and raising plasma HDL-cholesterol concentrations among patients with coronary heart disease and low HDL-cholesterol levels ( 1 mmol/l) by means of gemfibrozil may also effectively prevent stroke. Statin drugs are effective and safe in preventing initial and recurrent stroke. However, because they are costly, they should probably be restricted to in iduals with an annual risk of stroke and other serious vascular events of 3% or greater, and possibly as low as 1.5%, because routine monitoring of plasma cholesterol, and liver and muscle enzyme concentrations is probably no longer necessary.
Publisher: Elsevier BV
Date: 12-2013
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.AHJ.2008.08.031
Abstract: Atherothrombosis is a common condition affecting in iduals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy. This was a prospective observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months. The primary efficacy end point was the first occurrence of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was bleeding. The cohort comprised 12,502 (80.1%) white, 486 (3.1%) black, 775 (5.0%) Asian, and 1,613 (10.3%) Hispanic patients. There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups. Compared with Asians, cardiovascular and all-cause mortality occurred more frequently among black (adjusted hazard 2.19 and 2.04) and Hispanic (adjusted hazard, 1.83 and 1.69) patients. Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups, Asian (adjusted hazard, 2.21) and black (adjusted hazard, 3.06) patients were more likely to have moderate bleeding complications than Hispanic patients. In this trial of in iduals at risk of vascular events, ethnicity was not a significant, independent predictor of the primary composite cardiovascular event. However, ethnicity was a significant, independent predictor of the secondary outcomes, cardiovascular and all-cause mortality (blacks and Hispanics), and moderate bleeding complications (blacks and Asians).
Publisher: BMJ
Date: 05-1992
DOI: 10.1136/BJO.76.5.259
Abstract: A total of 2435 patients with transient ischaemic attack or minor ischaemic stroke were entered into the UK-TIA aspirin trial and randomised to treatment with aspirin 1200 mg/day, aspirin 300 mg/day, or placebo. At a single point in time during the trial patients were examined ophthalmoscopically for evidence of cataracts. The length of time that each patient had been participating in the trial at the time of ophthalmic examination varied from 1 to 5 years. The prevalence of cataracts was similar in patients allocated aspirin and patients allocated placebo irrespective of the length of time that they had been in the trial. These findings suggest that aspirin taken in a dose of 300 to 1200 mg daily for a few years does not prevent cataracts.
Publisher: Elsevier BV
Date: 08-2020
Publisher: American Society of Hematology
Date: 07-2001
Abstract: Platelets are pivotal to the process of arterial thrombosis resulting in ischemic stroke. Occlusive thrombosis is initiated by the interaction of von Willebrand factor (vWf) and platelet glycoprotein (GP) Ibα. Three polymorphisms have been described in GP Ibα (Kozak T/C polymorphism, variable number of tandem repeats [VNTR], and the human platelet antigen 2a [HPA-2a] [Thr] or HPA-2b [Met] at position 145), each of which may enhance the vWf and GP Ibα interaction. This study investigated whether these polymorphisms are candidate genes for first-ever ischemic stroke. A hospital-based case-control study was conducted of 219 cases of first-ever ischemic stroke and 205 community controls randomly selected from the electoral roll and stratified by age, sex, and postal code. The subtypes of stroke were classified, the prevalence of conventional risk factors was recorded, and blood was collected to perform genotyping analysis for Kozak C or T alleles, VNTR, and HPA-2a/b. It was found that the Kozak T/C genotype was over-represented in the stroke group (32.2%) compared with controls (22.8%) (odds ratio [OR], 1.6 95% confidence interval [CI], 1.03-2.54 P & .03), and the association was still present even after adjusting for conventional risk factors. There was a trend in the increased prevalence of HPA-2a/b in stroke patients (15%) compared with controls (9.9%) (adjusted OR, 1.8 95% CI, 0.94-3.4 P = .07). No associations were seen with the VNTR polymorphism or with any of the polymorphisms with stroke subtype. It was concluded that the Kozak T/C polymorphism, which is associated with an increase in platelet GP Ibα surface expression, is an independent risk factor for first-ever ischemic stroke.
Publisher: SAGE Publications
Date: 02-11-2012
DOI: 10.1111/J.1747-4949.2011.00653.X
Abstract: Cholesterol and blood pressure lowering therapies are effective in the secondary prevention of ischemic stroke. To determine whether 30 days of treatment with atorvastatin, or irbesartan, initiated within 96 h of symptom onset improves recovery from acute ischemic stroke. Eighty-one patients with acute ischemic stroke participated in this double-blind, placebo-controlled, randomized trial of atorvastatin (80 mg) vs. placebo, and/or irbesartan (150 mg) vs. placebo. Fifty-two patients (randomized 53 ± 22 h after onset of symptoms) completed the 30-day primary outcome follow-up. The primary outcome, maximal brain infarct size at days 3 and 30 measured by perfusion computed tomography, was not significantly altered by random assignment to irbesartan (1088 (IQR 216, 2594) mm 2 at day 3, compared with 398 (144, 2053) mm 2 among the placebo group, P=0·79 controlling for baseline values and 822 (159, 1717) mm 2 at day 30, cf 280 (76, 1330) mm 2 P=0·63) or atorvastatin (454 (107, 1765) mm 2 cf 825 (265, 2509) mm 2 at day 3 P=0·33 and 462 (43, 1399) mm 2 cf 280 (128, 1559) mm 2 at day 30, P=0·79). There were no other significant differences among the treatment groups with the exception of: • high sensitivity C-reactive protein concentrations, which were lower in the irbesartan treatment group at day 30 (mean difference 12·6 mg/L 95% CI: −25·1, −0·1 P=0·048) and • the mean cerebral blood flow in the affected cerebral hemisphere at 30 days after stroke, which was significantly reduced by random assignment to irbesartan compared with placebo in both the affected cerebral hemisphere (−7·5 mL/100 mL/min (95% CI: −1·7 to −13·4, P=0·01)) and in the unaffected hemisphere (−7·3 mL/100 mL/min (95% CI: −1·3, −13·4 P=0·02)). Atorvastatin therapy was well tolerated, but irbesartan therapy was associated with an increased rate of withdrawal from therapy ( n=10 (29%), compared with n=3 (9%) who withdrew from placebo, P=0·04). Treatment with atorvastatin and irbesartan, initiated on day 3 after acute ischemic stroke, did not appear to substantially modify infarct growth.
Publisher: Wiley
Date: 15-12-2016
Abstract: The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (ca. 200 nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association in vitro, but dramatically improves their lymphatic drainage in vivo. The functional relevance of these observations is further illustrated by the increased priming of antigen-specific T cells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds.
Publisher: Public Library of Science (PLoS)
Date: 30-09-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
DOI: 10.1161/STROKEAHA.113.001126
Abstract: Quality of life (QoL) is important to stroke survivors yet is often recorded as a secondary measure in acute stroke randomized controlled trials. We examined whether commonly used stroke outcome measures captured aspects of QoL. We examined primary outcomes by National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and modified Rankin Scale (mRS), and QoL by Stroke Impact Scale (SIS) and European Quality of Life Scale (EQ-5D) from the Virtual International Stroke Trials Archive (VISTA). Using Spearman correlations and logistic regression, we described the relationships between QoL mRS, NIHSS, and BI at 3 months, stratified by respondent (patient or proxy). Using χ 2 analyses, we examined the mismatch between good primary outcome (mRS ≤1, NIHSS ≤5, or BI ≥95) but poor QoL, and poor primary outcome (mRS ≥3, NIHSS ≥20, or BI ≤60) but good QoL. Patient-assessed QoL had a stronger association with mRS (EQ-5D weighted score n=2987, P .0001, r =−0.7, r 2 =0.53 SIS recovery n=2970, P .0001, r =−0.71, r 2 =0.52). Proxy responses had a stronger association with BI (EQ-5D weighted score n=837, P .0001, r =0.78, r 2 =0.63 SIS recovery n=867, P .0001, r =0.68, r 2 =0.48). mRS explained more of the variation in QoL (EQ-5D weighted score=53%, recovery by SIS v3.0=52%) than NIHSS or BI and resulted in fewer mismatches between good primary outcome and poor QoL ( P .0001, EQ-5D weighted score=8.5% SIS recovery=10% SIS-16=4.4%). The mRS seemed to align closely with stroke survivors’ interests, capturing more information on QoL than either NIHSS or BI. This further supports its recommendation as a primary outcome measure in acute stroke randomized controlled trials.
Publisher: Elsevier BV
Date: 07-2016
Publisher: Oxford University Press (OUP)
Date: 16-11-2020
DOI: 10.1093/AJH/HPAA176
Abstract: Although low sodium intake (& g/day) and high potassium intake (& .5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke. We obtained random urine s les from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. Compared with an estimated urinary sodium excretion of 2.8–3.5 g/day (reference), higher (& .26 g/day) (odds ratio [OR] 1.81 95% confidence interval [CI], 1.65–2.00) and lower (& .8 g/day) sodium excretion (OR 1.39 95% CI, 1.26–1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion & .26 g/day) was significantly greater (P & 0.001) for intracerebral hemorrhage (ICH) (OR 2.38 95% CI, 1.93–2.92) than for ischemic stroke (OR 1.67 95% CI, 1.50–1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (& .58 g/day) and moderate sodium intake (2.8–3.5 g/day) was associated with the lowest risk of stroke. The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake—rather than low sodium intake—combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2014
DOI: 10.1007/S11886-014-0480-9
Abstract: Intracranial hemorrhage (ICH) affects 0.2-0.5 % of atrial fibrillation (AF) patients taking a novel oral anticoagulant (NOAC) each year. About two thirds of ICHs are intracerebral and one quarter subdural. The 30-day case fatality of NOAC-associated ICH was similar to that of warfarin-associated ICH in two trials. Consistent predictors of ICH are increasing age, a history of prior stroke or TIA, and concomitant use of an antiplatelet drug. Compared to warfarin, the NOACs significantly reduce the risk of ICH by half (risk ratio = 0.44 95 % CI: 0.37 to 0.51). Compared to aspirin, apixaban has a similar risk of ICH (risk ratio = 0.84 95 % CI, 0.38 to 1.87). Current treatments for NOAC-associated ICH include nonactivated and activated prothrombin complex concentrate, which reverse the anticoagulant effects of the NOACs, but their effects on bleeding and patient outcome are not known. Future treatments for NOAC-associated ICH promise to include specific antidotes to dabigatran (e.g., aDabi-Fab, PER977) and factor Xa inhibitors (e.g., r-Antidote PRT064445, PER977).
Publisher: Cambridge University Press (CUP)
Date: 09-07-2009
DOI: 10.1017/S1041610209990457
Abstract: Background: Previous research has found an association between post-stroke depressive symptoms and premorbid personality. This study sought to investigate further the relationship between premorbid personality and a number of common post-stroke behavioral and psychological symptoms in a three-month follow-up study. Methods: This prospective study was conducted between May 2003 and January 2005 in a Perth metropolitan teaching hospital. The pre-stroke personality of stroke survivors was assessed by interviewing a close family member (informant) within four weeks of the index stroke using the NEO Personality Inventory-Revised. Three months after the stroke, patients were followed up and assessed with the Cambridge Cognitive examination and Hospital Anxiety and Depression Scale, and their informants completed the Neuropsychiatric Inventory-carer distress version (NPI) and instrumental activities of daily living scale. Results: Depressive symptoms were the most commonly reported post-stroke symptom (45.1%). Spearman's correlations showed that high neuroticism was positively correlated with NPI total scores ( ρ = 0.37, p = 0.007), NPI total distress scores ( ρ = 0.47, p = 0.001), and specifically with agitation and irritability NPI composite scores. Agreeableness was inversely correlated with agitation ( ρ = −0.40, p = 0.004) and irritability ( ρ = −0.37, p = 0.007) composite scores. Conclusions: Premorbid personality traits of high neuroticism and low agreeableness are associated with the presence of post-stroke agitation, irritability, and carer distress. This knowledge may contribute to the development of strategies designed to identify patients and families who require more intense supervision and support during post-stroke rehabilitation.
Publisher: Public Library of Science (PLoS)
Date: 23-06-2010
Publisher: American Medical Association (AMA)
Date: 10-04-2006
DOI: 10.1001/ARCHINTE.166.7.729
Abstract: The 2 most common genetic polymorphisms that predispose to a first episode of venous thromboembolism (VTE) are factor V Leiden (FVL) and prothrombin G20210A. However, the effect of these polymorphisms on the risk of recurrent VTE is unclear. We performed a meta-analysis to obtain best estimates of the relative risk of recurrent VTE associated with these genetic polymorphisms. Electronic and manual searches were used to identify cohort studies of patients with a first episode of VTE that reported the incidence of objectively confirmed recurrence following discontinuation of anticoagulation among those with or without heterozygous FVL or prothrombin G20210A polymorphism. Thirteen reports fulfilled our criteria for inclusion. Pooled results from 10 studies involving 3104 patients with first-ever VTE revealed that FVL was present in 21.4% of patients (95% confidence interval [CI], 20%-23%) and associated with an increased odds of recurrent VTE of 1.41 (95% CI, 1.14-1.75 P = .08 for heterogeneity). Pooled results from 9 studies involving 2903 patients with first-ever VTE revealed that prothrombin G20210A was present in 9.7% of patients (95% CI, 9%-11%) and associated with an increased odds of recurrent VTE of 1.72 (95% CI, 1.27-2.31 P = .19). The estimated population-attributable risk of recurrence for FVL was 9.0% (95% CI, 4.5%-13.2%) and for prothrombin G20210A was 6.7% (95% CI, 3.4%-9.9%). Heterozygous FVL and prothrombin G20210A are each associated with a significantly increased risk of recurrent VTE after a first event, but the magnitude of the increase in risk is modest and by itself is unlikely to merit extended-duration anticoagulation. These data call into question the cost-effectiveness of routine testing for these common inherited thrombophilic polymorphisms among patients with a first episode of VTE.
Publisher: S. Karger AG
Date: 16-12-2015
DOI: 10.1159/000442532
Abstract: b i Background: /i /b This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). b i Methods: /i /b Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP mm Hg) or guideline-based ( mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. b i Results: /i /b Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53% p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37 p = 0.049). b i Conclusions: /i /b The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH.
Publisher: Wiley
Date: 06-1988
DOI: 10.1111/J.1445-2197.1988.TB06245.X
Abstract: Median nerve compression in the carpal tunnel by a thrombosed persistent median artery and a large aberrant artery substituting for the radial artery has been described but there have been no reports of median nerve compression in the palm of the hand by an anomalously enlarged ulnar artery. A 46 year old man is described who presented with clinical and electrophysiological features consistent with a median neuropathy at the wrist but surgical exploration revealed median nerve compression in the palm of the hand by an anomalously enlarged palmar branch of the ulnar artery. This case highlights another treatable cause of median nerve compression and illustrates that symptoms suggestive of carpal tunnel syndrome may be produced by median nerve compression in the palm of the hand.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2000
Abstract: Background and Purpose —More data on the epidemiology of subarachnoid hemorrhage (SAH) are required to increase our understanding of etiology and prevention. This study sought to determine the incidence and case fatality of SAH from 4 prospective, population-based registers in Australia and New Zealand. Methods —We identified all cases of “aneurysmal” SAH from November 1995 to June 1998 in Adelaide, Hobart, Perth (Australia), and Auckland (New Zealand), a total population of approximately 2.8 million, using standard diagnostic criteria and uniform community-wide surveillance and data extraction procedures. Results —A total of 436 cases of SAH were registered, including 432 first-ever events and 4 recurrent events. The mean age of cases was 57 years (range, 16 to 94 years), and 62% were female. From the 400 first-ever events registered over whole years, the crude annual incidence for the total population was 8.1 per 100 000 (95% CI, 7.4, 9.0), with rates higher for females (9.7 95% CI, 8.6, 11.0) than for males (6.5 95% CI, 5.5, 7.6). Age-specific rates showed a continuous upward trend with age, although the shape and strength of this association differed between the sexes. Standardized annual incidence of SAH varied across centers, being highest in Auckland largely because of the high rate in Maori and Pacific people. The 28-day case fatality rate for the total population was 39% (95% CI, 34%, 44%), with little variation in ratios across centers. Conclusions —There is variation in the incidence of SAH in Australia and New Zealand, but the rates are consistently higher for females. A monotonic increase in incidence with age suggests that exposures with cumulative effects and long induction times may be less relevant in the etiology of SAH.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Wiley
Date: 04-2015
DOI: 10.1111/JPN.12313
Abstract: The current study aimed to determine the impact of acidified feed on apparent ileal starch digestibility, intestinal transport and barrier function and intestinal glucose transporter expression. The experiment included a control group and a treatment group with broilers fed a standard diet without or with 1.5% of a commercial organic acid product (64% formic acid, 25% propionic acid, 11% water). Broilers were fed with the experimental diets from hatching until days 32-35. Starch digestibility was determined using 0.2% titanium dioxide as ingestible marker. Gene expressions of the intestinal sodium glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2) were analysed using qPCR analysis. Additionally, SGLT-1 function and chloride secretion were analysed in Ussing chamber experiments. Jejunal s les were sequentially exposed to 10 mm glucose, 100 μm phloridzin, 100 μm histamine and 100 μm carbachol. Apparent ileal starch digestibility (±SEM) of the control group (97.5 ± 0.35%) and the acid-treated group (97.0 ± 0.59%) did not differ (p = 0.674). The mean tissue conductance of intestinal s les obtained from the control group and the treatment group was similar [10.6 mS/cm(2) (±0.68) and 9.4 mS/cm(2) (±0.80) respectively (p = 0.147)]. The mean short-circuit currents (ΔIsc ) of the s les exposed to glucose, phloridzin, histamine and carbachol did not differ (p > 0.05). Additionally, no differences in the expression of SGLT-1 and GLUT-2 could be observed (p = 0.942, p = 0.413). Based on this study, the consumption of feed supplemented with organic acids was not associated with effects on ileal starch digestibility and functional traits of jejunal tissues, indicating that these additives have no major impact on the small intestinal function in broilers.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2022
DOI: 10.1161/STROKEAHA.122.038640
Abstract: In this article, we discuss a problem in the most recent American Heart Association guideline on secondary stroke prevention that apparently arose from the rules of evidence imposed on the guideline panel. We are told by the cochair of the panel that American Heart Association rules about guidelines for secondary prevention prohibited consideration of primary prevention studies and secondary analyses of secondary prevention studies. However, evidence-based medicine should consider all the best external evidence available and also clinical judgement. The most important problem in the guideline was the recommendation that B vitamins to lower homocysteine do not prevent recurrent stroke. When considering all the best external evidence, it is clear that B vitamins do prevent stroke, but in the early secondary stroke prevention studies, the benefit of B vitamins in participants with good renal function was apparently offset by harm from cyanocobalamin among participants with renal failure (level B-R evidence). We review the evidence that B vitamins should be used to prevent stroke, both in primary and secondary stroke prevention (class 2a recommendation). We also review issues in folate metabolism that require further study, with regard to the form of folate to be used for stroke prevention. We recommend that the guideline be revised to say that B vitamins to lower homocysteine prevent stroke and that methylcobalamin or hydroxycobalamin should be used instead of cyanocobalamin.
Publisher: Elsevier BV
Date: 05-2019
Publisher: S. Karger AG
Date: 08-11-1991
DOI: 10.1159/000108809
Publisher: Elsevier BV
Date: 11-2004
Publisher: Oxford University Press (OUP)
Date: 09-12-2008
Abstract: We aimed to determine the relationship between body mass index (BMI) and cardiovascular events among in iduals with or at-risk of atherothrombotic disease. This was a prospective observational study of 15 532 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial who were randomly assigned to clopidogrel or placebo, and followed-up for a median of 28 months for the occurrence of the primary endpoint (cardiovascular death, myocardial infarction, or stroke), all-cause mortality, and bleeding complications. Compared with the highest BMI quartile, the primary endpoint, cardiovascular, and all-cause mortality all occurred more frequently among patients in the lowest BMI quartile (about a third lower). The relationship between continuous BMI and adverse cardiovascular outcomes were presented as two linear spline terms with 29 kg/m(2) as the cut-point for all-cause mortality. Lower BMI was associated with an increase in moderate and severe bleeding complications, largely accounted for by those receiving dual-antiplatelet agents with the highest tertile aspirin dose. Adverse cardiovascular events and bleeding complications occurred more frequently among in iduals with or at-risk for atherothrombotic disease and low BMI. Further studies should be directed to these patients to improve outcomes.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2021
DOI: 10.1186/S12911-021-01590-Y
Abstract: Data sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation s les from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally. Using cognitive testing data and data on functional limitations from Wave A (2001–2003) of the ADAMS study ( n = 744) and the 2000 wave of the HRS study ( n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all in iduals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS s le to calculate dementia prevalence by age and sex. Our algorithm had a cross-validated predictive accuracy of 88% (86–90), and an area under the curve of 0.97 (0.97–0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3–4) in in iduals 70–79, 11% (9–12) in in iduals 80–89 years old, and 28% (22–35) in those 90 and older. Our model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys.
Publisher: American Medical Association (AMA)
Date: 02-2019
Publisher: Wiley
Date: 08-12-2017
DOI: 10.1111/ADB.12340
Abstract: We designed this cohort study of men aged 70-89 years to determine if excessive alcohol use increases mortality. They reported history of alcohol use (never, past, ≤ two daily drinks, two to four daily drinks, four to six daily drinks, > six daily drinks) and donated a blood s le in 2001-2004. We determined the ADH1B rs1229984 G>A polymorphism and retrieved mortality data from the Western Australian Data Linkage System. Other study measures included age, education, body mass index, smoking, and history of hypertension, diabetes, chronic respiratory diseases, coronary heart disease and stroke. Of the 3496 participants, 225 (6.4 percent) carried the ADH1B rs1229984 G>A polymorphism. Carriers consumed significantly less alcohol than non-carriers. The adjusted mortality hazard ratio (MHR, 95 percent confidence interval-95%CI) over 8.0 years (range: 10 weeks to 11.2 years) relative to never drinkers was 1.15 (95%CI = 0.86, 1.55) for past drinkers, 0.98 (95%CI = 0.76, 1.25) for men consuming ≤ two daily drinks, 1.13 (95%CI = 0.85, 1.49) for two to four drinks, 1.18 (95%CI = 0.81, 1.71) for four to six drinks and 1.87 (95%CI = 1.11, 3.12) for those consuming more than six daily drinks on a regular basis. The MHR associated with the ADH1B rs1229984 G>A polymorphism was 0.68 (95%CI = 0.54, 0.87). Excessive alcohol use in later life is associated with increased mortality, and this association is likely to be causal. We found no evidence that light to moderate alcohol use decreases the mortality of older men. Health messages regarding the safe use of alcohol in older age may benefit from taking these findings into account.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2023
Publisher: Oxford University Press (OUP)
Date: 04-2011
DOI: 10.1530/EJE-10-1063
Abstract: Hypogonadism in men is associated with insulin resistance, elevations in pro-inflammatory cytokines and fibrinogen, and an atherogenic lipid profile. However, it is uncertain whether the age-related decline in testosterone is associated with ischaemic heart disease (IHD) events. To determine whether testosterone and its associated hormones, sex hormone-binding globulin (SHBG) and LH, predict IHD events in older men. Prospective cohort study. Between 2001 and 2004, 3637 community-dwelling men aged 70–88 years underwent a clinical assessment of cardiovascular risk factors and biochemical assessment of testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Participants were followed until December 2008 using electronic record linkage to capture IHD events (hospital admission or death). Mean follow-up was 5.1 years. During this period, 618 men (17.0% 95% confidence interval (CI) 15.8, 18.3%) experienced an event, of which 160 were fatal. Men with higher baseline total or free testosterone levels experienced fewer IHD events (hazard ratio (HR)=0.89 95% CI 0.82, 0.97 and HR=0.86 95% CI 0.79, 0.94 for each one s.d. increase in total and free testosterone respectively). These associations were maintained after adjustment for age and waist:hip ratio but did not persist after adjustment for prevalent IHD or other cardiovascular risk factors. SHBG was not associated with IHD events. In contrast, higher LH levels were associated with reduced event-free survival in both univariate (HR=1.15 95% CI 1.08, 1.22) and adjusted analyses (HR=1.08 95% CI 1.01, 1.15). Dysregulation of the hypothalamic–pituitary–gonadal axis may be a risk factor for IHD. Further studies of men with either elevated LH or low testosterone are warranted.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2003
DOI: 10.1161/01.STR.0000086466.32421.F4
Abstract: Background and Purpose— Activation of endothelial cells and platelets is an important mediator of atherothrombosis. Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma. We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebrand factor (vWF), primarily reflecting activation of endothelial cells, and increased concentrations of soluble P-selectin and platelet-derived microvesicles (PDM), primarily reflecting activation of platelets, compared with healthy controls. We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- and small-artery atherothrombosis compared with cardiogenic embolism. Methods— We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205 randomly selected community controls stratified by age, sex, and postal code. Using established criteria, we classified cases of stroke by etiological subtype in a blinded fashion. The prevalence of vascular risk factors and blood concentrations of E-selectin, P-selectin, vWF antigen, and PDM were determined in stroke cases within 7 days and at 3 to 6 months after stroke and in controls. Results— Mean blood concentrations of soluble E-selectin, P-selectin, and PDM within 7 days of stroke onset were all significantly higher in cases compared with controls. At 3 to 6 months after stroke, the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls, and PDM concentrations remained elevated. There was a strong, graded, and independent (of age, sex, and vascular risk factors) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke, particularly ischemic stroke caused by large-artery atherothrombosis. There was also a significant, graded, and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis. Conclusions— We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis. Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke.
Publisher: Springer Science and Business Media LLC
Date: 19-11-2022
DOI: 10.1186/S40814-022-01197-8
Abstract: Evidence for digital health programmes to support people living with stroke is growing. We assessed the feasibility of a protocol and procedures for the Re covery-focused C ommunity support to A void readmissions and improve P articipation after S troke (ReCAPS) trial. We conducted a mixed-method feasibility study. Participants with acute stroke were recruited from three hospitals (Melbourne, Australia). Eligibility: Adults with stroke discharged from hospital to home within 10 days, modified Rankin Score 0–4 and prior use of Short Message System (SMS)/email. While in hospital, recruited participants contributed to structured person-centred goal setting and completed baseline surveys including self-management skills and health-related quality of life. Participants were randomised 7–14 days after discharge via REDCap® (1:1 allocation). Following randomisation, the intervention group received a 12-week programme of personalised electronic support messages (average 66 messages sent by SMS or email) aligned with their goals. The control group received six electronic administrative messages. Feasibility outcomes included the following: number of patients screened and recruited, study retainment, completion of outcome measures and acceptability of the ReCAPS intervention and trial procedures (e.g. participant satisfaction survey, clinician interviews). Protocol fidelity outcomes included number of goals developed (and quality), electronic messages delivered, stop messages received and engagement with messages. We undertook inductive thematic analysis of interview/open-text survey data and descriptive analysis of closed survey questions. Between November 2018 and October 2019, 312 patients were screened 37/105 (35%) eligible patients provided consent (mean age 61 years 32% female) 33 were randomised (17 to intervention). Overall, 29 (88%) participants completed the12-week outcome assessments with 12 (41%) completed assessments in the allocated timeframe and 16 also completing the satisfaction survey (intervention=10). Overall, trial participants felt that the study was worthwhile and most would recommend it to others. Six clinicians participated in one of three focus group interviews while they reported that the trial and the process of goal setting were acceptable, they raised concerns regarding the additional time required to personalise goals. The study protocol and procedures were feasible with acceptable retention of participants. Consent and goal personalisation procedures should be centralised for the phase III trial to reduce the burden on hospital clinicians. Australian New Zealand Clinical Trials Registry, ACTRN12618001468213 (date 31/08/2018) Universal Trial Number: U1111-1206-7237
Publisher: Wiley
Date: 18-09-2020
DOI: 10.1111/CODI.15311
Abstract: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were ided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7% routine NGT 5.2% reactive NGT 10.6% prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56–1.87, P = 0.932). In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 06-2021
Publisher: AMPCo
Date: 04-2008
Publisher: American Medical Association (AMA)
Date: 28-04-2003
Publisher: BMJ
Date: 09-05-2016
DOI: 10.1136/NEURINTSURG-2016-012304
Abstract: To audit our institutional mechanical thrombectomy (MT) outcomes for acute anterior circulation stroke and examine the influence of workflow time metrics on patient outcomes. A database of 100 MT cases was maintained throughout May 2010—February 2015 as part of a statewide service provided across two tertiary hospitals (H1 and H2). Patient demographics, stroke and procedural details, blinded angiographic outcomes, and 90-day modified Rankin Scale (mRS) scores were recorded. The following time points in stroke treatment were recorded: stroke onset, hospital presentation, CT imaging, arteriotomy, and recanalization. Statistical analysis of outcomes, predictors of outcome, and differences between the hospitals was carried out. Thrombolysis in Cerebral Infarction (TICI) 2b/3 reperfusion was 79%. Forty-nine per cent of patients had good clinical outcomes (mRS 0–2). In a subgroup analysis of 76 patients with premorbid mRS 0–1 and first CT performed ≤4.5 h after stroke onset, 60% had good clinical outcomes. Patient and disease characteristics were matched between the two hospitals. H1 had shorter times between hospital presentation and CT (32 vs 55 min, p=0.01), CT and arteriotomy (33 vs 69 min, p=0.00), and stroke onset and recanalization (198 vs 260 min, p=0.00). These time metrics independently predicted good clinical outcome. Median days spent at home in the first 90 days was greater at H1 (61 vs 8, p=0.04) than at H2. A greater proportion of patients treated at H1 were independent (mRS 0–2) at 90 days (54% vs 42%) however, this was not statistically significant (p=0.22). Outcomes similar to randomized controlled trials are attainable in ‘real-world’ settings. Workflow time metrics were independent predictors of clinical outcome, and differed between the two hospitals owing to site-specific organizational differences.
Publisher: American Medical Association (AMA)
Date: 06-1999
DOI: 10.1001/ARCHNEUR.56.6.748
Abstract: Stroke is an enormous public health problem, the magnitude of which can be reduced mainly by effective stroke prevention and less so by effective treatment of acute stroke. The greatest effect is likely to be achieved by a mass approach to prevention, which consists of modification of lifestyle behaviors (eg, less smoking and less intake of salt, alcohol, and fat) among the general population through public education and, more importantly, government legislation. The appropriate identification and treatment of high-risk in iduals by neurologists is likely to have a smaller but complimentary impact on the population burden of stroke and a substantial impact on the burden of stroke among in iduals. The most cost-effective interventions for patients with transient ischemic attack and ischemic stroke are organized multidisciplinary acute care and rehabilitation in a stroke unit and early secondary prevention with aspirin, blood pressure control, smoking cessation, and, in the appropriate patient, oral anticoagulant therapy and carotid endarterectomy. The cost-effectiveness of carotid endarterectomy for asymptomatic carotid stenosis is highly questionable until data from ongoing trials (eg, Asymptomatic Carotid Surgery Trial) become available. Screening for asymptomatic carotid stenosis is more likely to be harmful than helpful, except perhaps among populations with a very high prevalence (pretest probability) of severe carotid stenosis. It is essential that the impact of these strategies on the incidence, outcome, and cost of stroke is measured and monitored. Currently, this is done simply, but unreliably, by examining changes in statistics that are already being measured, such as mortality (eg, among those younger than 70 years old, for greater accuracy). A growing priority in many countries is the development and implementation of valid, reliable, practical, and inexpensive methods of routinely collecting and evaluating data on stroke incidence, outcome, and cost.
Publisher: AMPCo
Date: 08-1997
DOI: 10.5694/J.1326-5377.1997.TB138808.X
Abstract: Pure polymers of polystyrene (PS), low-density polyethylene (LDPE) and polypropylene (PP), are the main representative of plastic wastes. Thermal cracking of mixed polymers, consisting of PS, LDPE, and PP, was implemented by thermal analysis technique "thermogravimetric analyzer (TGA)" with heating rate range (5-40 K/min), with two groups of sets: (ratio 1:1) mixture of PS and PP, and (ratio 1:1:1) mixture of PS, LDPE, and PP. TGA data were utilized to implement one of the machine learning methods, "artificial neural network (ANN)". A feed-forward ANN with Levenberg-Marquardt (LM) as learning algorithm in the backpropagation model was performed in both sets in order to predict the weight fraction of the mixed polymers. Temperature and the heating rate are the two input variables applied in the current ANN model. For both sets, 10-10 neurons in logsig-tansig transfer functions two hidden layers was concluded as the best architecture, with almost (R 0.99999). Results approved a good coincidence between the actual with the predicted values. The model foresees very efficiently when it is simulated with new data.
Publisher: BMJ
Date: 09-2016
DOI: 10.1136/BMJOPEN-2016-012027
Abstract: We are undertaking a randomised controlled trial (fAmily led rehabiliTaTion aftEr stroke in INDia, ATTEND) evaluating training a family carer to enable maximal rehabilitation of patients with stroke-related disability as a potentially affordable, culturally acceptable and effective intervention for use in India. A process evaluation is needed to understand how and why this complex intervention may be effective, and to capture important barriers and facilitators to its implementation. We describe the protocol for our process evaluation to encourage the development of in-process evaluation methodology and transparency in reporting. The realist and RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) frameworks informed the design. Mixed methods include semistructured interviews with health providers, patients and their carers, analysis of quantitative process data describing fidelity and dose of intervention, observations of trial set up and implementation, and the analysis of the cost data from the patients and their families perspective and programme budgets. These qualitative and quantitative data will be analysed iteratively prior to knowing the quantitative outcomes of the trial, and then triangulated with the results from the primary outcome evaluation. The process evaluation has received ethical approval for all sites in India. In low-income and middle-income countries, the available human capital can form an approach to reducing the evidence practice gap, compared with the high cost alternatives available in established market economies. This process evaluation will provide insights into how such a programme can be implemented in practice and brought to scale. Through local stakeholder engagement and dissemination of findings globally we hope to build on patient-centred, cost-effective and sustainable models of stroke rehabilitation. CTRI/2013/04/003557.
Publisher: Elsevier BV
Date: 08-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2000
Abstract: Background and Purpose —Elevated plasma homocyst(e)ine may be a causal and modifiable risk factor for ischemic stroke, but the results of previous studies have been conflicting. One possible explanation is that homocyst(e)ine may only be associated with certain pathophysiological subtypes of ischemic stroke. Methods —We conducted a case-control study of 219 hospital cases with a first-ever ischemic stroke and 205 randomly selected community control subjects stratified by age, sex, and postal code. With the use of established criteria, cases of stroke were classified by etiologic subtype in a blinded fashion. The prevalence of conventional vascular risk factors, fasting plasma homocyst(e)ine levels, vitamin levels, and nucleotide 677 methylene tetrahydrofolate reductase (MTHFR) genotypes were determined in cases and controls. Results —Increasing homocyst(e)ine was a strong and independent risk factor for ischemic stroke (adjusted OR 2.7, 95% CI 1.4 to 5.1 for a 5-μmol/L increase in fasting plasma homocyst(e)ine from 10 to 15 μmol/L). Compared with the lowest quartile, the highest quartile of homocyst(e)ine was associated with an adjusted OR of ischemic stroke of 2.2 (95% CI 1.1 to 4.2). Mean plasma homocyst(e)ine was significantly higher in cases of ischemic stroke due to large-artery disease (14.1 μmol/L, 95% CI 12.5 to 15.9, P .001) and small-artery disease (12.7 μmol/L, 95% CI 11.4 to 14.1, P =0.004) compared with control subjects (10.5 μmol/L 95% CI 10.0 to 11.0) but not in cardioembolic or other etiologic subtypes of ischemic stroke. Compared with the lowest quartile of homocyst(e)ine, the upper 3 quartiles were associated with an adjusted OR of ischemic stroke due to large-artery disease of 3.0 (95% CI 0.8 to 10.8) for the second quartile, 5.6 (95% CI 1.6 to 20) for the third quartile, and 8.7 (95% CI 2.4 to 32) for the fourth quartile ( P for trend=0.0005). However, despite a clear association between the TT MTHFR genotype and elevated fasting plasma homocyst(e)ine, there was no association between MTHFR genotype and ischemic stroke or subtype of ischemic stroke. Conclusions —There is a strong, graded association between increasing plasma homocyst(e)ine and ischemic stroke caused by large-artery atherosclerosis and, to a much lesser extent, small-artery disease, but not cardioembolic or other etiologic subtypes of ischemic stroke. Our results are consistent with the hypothesis that the deleterious effect of high homocyst(e)ine is mediated primarily via a proatherogenic effect.
Publisher: The Endocrine Society
Date: 16-10-2021
Abstract: Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase. To analyze associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men. The UK Biobank prospective cohort study of community-dwelling men aged 40–69 years old, followed for 11 years. All-cause, atherosclerotic cardiovascular disease (CVD) and cancer-related mortality. Cox proportional hazards regression was performed, adjusting for age, waist circumference, medical conditions, and other covariates. Models for testosterone included SHBG and vice versa. In a complete case analysis of 149 436 men with 10 053 deaths (1925 CVD and 4927 cancer-related), men with lower testosterone had a higher mortality rate from any cause (lowest vs highest quintile, Q1 vs Q5, fully-adjusted hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.06–1.22, overall trend P & 0.001), and cancer (HR = 1.20, CI = 1.09–1.33, P & 0.001), with no association for CVD deaths. Similar results were seen for cFT. Men with lower SHBG had a lower mortality rate from any cause (Q1 vs Q5, HR = 0.68, CI = 0.63–0.73, P & 0.001), CVD (HR = 0.70, CI = 0.59–0.83, P & 0.001), and cancer (HR = 0.80, CI = 0.72–0.89, P & 0.001). A multiply imputed dataset (N = 208 425, 15 914 deaths, 3128 CVD-related and 7468 cancer-related) and analysis excluding deaths within the first 2 years (9261, 1734, and 4534 events) yielded similar results. Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related, and cancer-related mortality. Confirmation and determination of causality requires mechanistic studies and prospective trials.
Publisher: BMJ
Date: 26-02-2004
Publisher: Elsevier BV
Date: 07-2021
Publisher: Springer Science and Business Media LLC
Date: 03-09-2014
DOI: 10.1038/MP.2013.113
Publisher: Wiley
Date: 25-07-2023
DOI: 10.1111/GEB.13735
Abstract: We have little understanding of how communities respond to varying magnitudes and rates of environmental perturbations across temporal scales. BioDeepTime harmonizes assemblage time series of presence and abundance data to help facilitate investigations of community dynamics across timescales and the response of communities to natural and anthropogenic stressors. BioDeepTime includes time series of terrestrial and aquatic assemblages of varying spatial and temporal grain and extent from the present‐day to millions of years ago. BioDeepTime currently contains 7,437,847 taxon records from 10,062 assemblage time series, each with a minimum of 10 time steps. Age constraints, s ling method, environment and taxonomic scope are provided for each time series. The database includes 8752 unique s ling locations from freshwater, marine and terrestrial ecosystems. Spatial grain represented by in idual s les varies from quadrats on the order of several cm 2 to grid cells of ~100 km 2 . BioDeepTime in aggregate currently spans the last 451 million years, with the 10,062 modern and fossil assemblage time series ranging in extent from years to millions of years. The median extent of modern time series is 18.7 years and for fossil series is 54,872 years. Temporal grain, the time encompassed by in idual s les, ranges from days to tens of thousands of years. The database contains information on 28,777 unique taxa with 4,769,789 records at the species level and another 271,218 records known to the genus level, including time series of benthic and planktonic foraminifera, coccolithophores, diatoms, ostracods, plants (pollen), radiolarians and other invertebrates and vertebrates. There are to date 7012 modern and 3050 fossil time series in BioDeepTime. SQLite, Comma‐separated values.
Publisher: Springer Science and Business Media LLC
Date: 10-09-2014
DOI: 10.1038/MP.2013.117
Abstract: Alcohol use, particularly alcohol abuse and dependence, are associated with increased risk of depression. Current diagnostic criteria suggest that the relationship is causal, but the evidence has only been derived from observational studies that are subject to confounding and bias. Given the logistic and ethical constraints that would be associated with a trial of alcohol use to prevent depression, we aimed to complete a Mendelian randomization study to determine if a genetic polymorphism associated with alcohol abuse and dependence (ADH1B rs1229984 G-->A) contributed to modulate the risk of depression in a community-derived cohort of older men. This retrospective analysis of a cohort of 3873 community-dwelling men aged 65-83 years living in the metropolitan region of Perth, Western Australia, investigated the triangular association between the rs1229984 G-->A polymorphism and alcohol use and, after 3.2-8.2 years, the presence of current depression or history of depression. The mean number of standard drinks consumed per week (n standard deviation range) according to genotype was AA 1.8 (17 2.7 0-7), GA 5.9 (262 7.5 0-35), GG 8.5 (3594 10.9 0-140) (GG>AA, GG>GA P A polymorphism was not associated with current or past depression (P=0.857). In addition, the presence of the A allele did not interact with the alcohol use to modulate the risk of depression (P=0.725). These results suggest that alcohol consumption does not cause or prevent depression in older men.
Publisher: Elsevier BV
Date: 02-1991
DOI: 10.1016/0140-6736(91)90953-M
Abstract: Lacunar ischaemic stroke syndromes are clinically, pathophysiologically, and prognostically distinguishable from cortical ischaemic stroke syndromes. Could cerebrovascular transient ischaemic attacks (TIAs) share similar heterogeneity? 130 patients with TIAs were prospectively studied, 71 of whom underwent carotid angiography. Symptoms were associated with a 50% or greater stenosis of the ipsilateral internal carotid artery in 36 (67%) of 54 patients with presumed cortical TIAs, but in only 1 (6%) of 17 patients with presumed lacunar TIAs (p less than 0.0001). These findings support the view that cortical TIAs are associated with ipsilateral extracranial internal carotid artery atheromatous disease, whereas patients with lacunar TIAs may have absent or insignificant large-vessel disease, and probable intracranial small-vessel disease. Accurate distinction between lacunar and cortical events may have implications for investigation and treatment of patients with TIAs.
Publisher: Wiley
Date: 02-2008
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.EJVS.2013.03.015
Abstract: This study aims to investigate the association between plasma 25-hydroxyvitamin D (25(OH)D) concentrations with the presence of abdominal aortic aneurysm (AAA) and aortic diameter. An observational study of 4233 community-dwelling men aged 70-88 years, who participated in a randomised controlled trial of screening for AAA. Infrarenal aortic diameter measured by ultrasound and 25(OH)D by immunoassay. A total of 311 men (7.4%) with AAA (defined as aortic diameter ≥ 30 mm) comprised the study. Multivariable models were adjusted for age, smoking, cardiovascular disease, hypertension, diabetes, dyslipidaemia, body mass index and serum creatinine concentration. Amongst men with the lowest 25(OH)D quartile of values compared with the highest quartile, the adjusted odds ratio of having an AAA increased in a graded fashion from 1.23 (95% confidence interval (CI) 0.87-1.73) for AAA ≥ 30 mm to 5.42 (95% CI 1.85-15.88) for AAA ≥ 40 mm. Similarly, there was a dose-response relationship between 25(OH)D concentrations and the size of the AAA: every 10-nmol l(-1) decrease in 25(OH)D levels was associated with 0.49 mm (95% CI 0.11-0.87) increase in mean aortic diameter. Low vitamin D status is associated with the presence of larger AAA in older men, and there is a graded inverse relationship between 25(OH)D concentrations and AAA diameter. Further research is needed to clarify the mechanisms underlying these associations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-07-2023
DOI: 10.1097/EE9.0000000000000255
Abstract: Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM 2.5 ) is associated with increased risk of heart disease, but less is known about the relationship at low concentrations. This study aimed to determine the dose-response relationship between long-term PM 2.5 exposure and risk of incident ischemic heart disease (IHD), incident heart failure (HF), and incident atrial fibrillation (AF) in older men living in a region with relatively low ambient air pollution. PM 2.5 exposure was estimated for 11,249 older adult males who resided in Perth, Western Australia and were recruited from 1996 to 1999. Participants were followed until 2018 for the HF and AF outcomes, and until 2017 for IHD. Cox-proportional hazards models, using age as the analysis time, and adjusting for demographic and lifestyle factors were used. PM 2.5 was entered as a restricted cubic spline to model nonlinearity. We observed a mean PM 2.5 concentration of 4.95 μg/m 3 (SD 1.68 μg/m 3 ) in the first year of recruitment. After excluding participants with preexisting disease and adjusting for demographic and lifestyle factors, PM 2.5 exposure was associated with a trend toward increased incidence of IHD, HF, and AF, but none were statistically significant. At a PM 2.5 concentration of 7 μg/m 3 the hazard ratio for incident IHD was 1.04 (95% confidence interval [CI] = 0.86, 1.25) compared with the reference category of 1 μg/m 3 . We did not observe a significant association between long-term exposure to low-concentration PM 2.5 air pollution and IHD, HF, or AF.
Publisher: BMJ
Date: 12-1987
Abstract: Cronbach coefficient alpha (CCA) is a classic measure of item internal consistency of an instrument and is used in a wide range of behavioral, biomedical, psychosocial, and health-care-related research. Methods are available for making inference about one CCA or multiple CCAs from correlated outcomes. However, none of the existing approaches effectively address missing data. As longitudinal study designs become increasingly popular and complex in modern-day clinical studies, missing data have become a serious issue, and the lack of methods to systematically address this problem has h ered the progress of research in the aforementioned fields. In this paper, we develop a novel approach to tackle the complexities involved in addressing missing data (at the instrument level due to subject dropout) within a longitudinal data setting. The approach is illustrated with both clinical and simulated data.
Publisher: American College of Physicians
Date: 07-09-1999
DOI: 10.7326/0003-4819-131-5-199909070-00008
Abstract: To review epidemiologic studies on the association between homocyst(e)ine level and risk for cardiovascular disease and the potential benefits of homocysteine-decreasing therapies. Computerized and manual searches of the literature on total homocysteine levels and cardiovascular disease. Prospective studies and major retrospective epidemiologic studies evaluating the association between homocyst(e)ine levels and cardiovascular disease and the association between blood levels or dietary intake of folate, vitamin B6, and vitamin B12 and cardiovascular disease. Relevant data on patient population, plasma homocyst(e)ine levels, duration of follow-up, and main results were extracted from studies that met the inclusion criteria. The designs and results of studies included in this review are summarized. A formal meta-analysis was not performed because the studies were heterogeneous in method and design. Results of epidemiologic studies suggest that moderately elevated plasma or serum homocyst(e)ine levels are prevalent in the general population and are associated with an increased risk for cardiovascular disease, independent of classic cardiovascular risk factors. Simple, inexpensive, nontoxic therapy with folic acid, vitamin B6, and vitamin B12 reduces plasma homocyst(e)ine levels. Although the association between homocyst(e)ine levels and cardiovascular disease is generally strong and biologically plausible, the data from the prospective studies are less consistent. In addition, epidemiologic observations of an association between hyperhomocyst(e)inemia and cardiovascular risk do not prove the existence of a causal relation. Therefore, the effectiveness of folate, vitamin B6, and vitamin B12 in reducing cardiovascular morbidity and mortality requires rigorous testing in randomized clinical trials. Several such trials are under way their results may greatly affect cardiovascular morbidity and mortality, given the simplicity and low cost of vitamin therapy.
Publisher: The Endocrine Society
Date: 12-2014
DOI: 10.1210/JC.2014-2664
Abstract: Older men have lower T levels, but whether differences in circulating T or its metabolites dihydrotestosterone (DHT) or estradiol (E2) contribute to cardiovascular disease remains controversial. We tested the hypothesis that plasma T, DHT, and E2 are differentially associated with the incidence of myocardial infarction (MI) and stroke in older men. Plasma total T, DHT, and E2 were assayed using liquid chromatography-mass spectrometry in early-morning s les from 3690 community-dwelling men aged 70-89 years. Outcomes of the first hospital admission or death due to MI or stroke were ascertained by data linkage. Mean follow-up was 6.6 years. Incident MI occurred in 344, stroke in 300, and neither in 3046 men. In a multivariate analysis adjusting for age and other risk factors, T, DHT, and E2 were not associated with incident MI [fully adjusted hazard ratio (HR) for T in quartile (Q) 4 vs Q1: 0.92, 95% confidence interval (CI) 0.66-1.28 DHT: 0.83, 95% CI 0.59-1.15 E2: 0.84, 95% CI 0.62-1.15]. Higher T or DHT was associated with a lower incidence of stroke (T: Q4: Q1 fully adjusted HR 0.56, 95% CI 0.39-0.81, P = .002 DHT: 0.57, 95% CI 0.40-0.81, P = .002). E2 was not associated with stroke (HR 0.76, 95% CI 0.54-1.08, P = .123). Higher plasma T or DHT is a biomarker for reduced risk of stroke but not MI. Androgen exposure may influence outcomes after rather than the incidence of MI, whereas androgens but not E2 are independent predictors of stroke risk. Randomized clinical trials are needed to clarify the impact of modifying T or DHT on the risk of stroke in aging men.
Publisher: American Medical Association (AMA)
Date: 05-07-2006
Publisher: AMPCo
Date: 06-2004
Publisher: Georg Thieme Verlag KG
Date: 06-07-2020
Abstract: With a lot of uncertainty, unclear, and frequently changing management protocols, COVID-19 has significantly impacted the orthopaedic surgical practice during this pandemic crisis. Surgeons around the world needed closed introspection, contemplation, and prospective consensual recommendations for safe surgical practice and prevention of viral contamination. One hundred orthopaedic surgeons from 50 countries were sent a Google online form with a questionnaire explicating protocols for admission, surgeries, discharge, follow-up, relevant information affecting their surgical practices, difficulties faced, and many more important issues that happened during and after the lockdown. Ten surgeons critically construed and interpreted the data to form rationale guidelines and recommendations. Of the total, hand and microsurgery surgeons (52%), trauma surgeons (32%), joint replacement surgeons (20%), and arthroscopy surgeons (14%) actively participated in the survey. Surgeons from national public health care/government college hospitals (44%) and private/semiprivate practitioners (54%) were involved in the study. Countries had lockdown started as early as January 3, 2020 with the implementation of partial or complete lifting of lockdown in few countries while writing this article. Surgeons (58%) did not stop their surgical practice or clinics but preferred only emergency cases during the lockdown. Most of the surgeons (49%) had three-fourths reduction in their total patients turn-up and the remaining cases were managed by conservative (54%) methods. There was a 50 to 75% reduction in the number of surgeries. Surgeons did perform emergency procedures without COVID-19 tests but preferred reverse transcription polymerase chain reaction (RT-PCR 77%) and computed tomography (CT) scan chest (12%) tests for all elective surgical cases. Open fracture and emergency procedures (60%) and distal radius (55%) fractures were the most commonly performed surgeries. Surgeons preferred full personal protection equipment kits (69%) with a respirator (N95/FFP3), but in the case of unavailability, they used surgical masks and normal gowns. Regional/local anesthesia (70%) remained their choice for surgery to prevent the aerosolized risk of contaminations. Essential surgical follow-up with limited persons and visits was encouraged by 70% of the surgeons, whereas teleconsultation and telerehabilitation by 30% of the surgeons. Despite the protective equipment, one-third of the surgeons were afraid of getting infected and 56% feared of infecting their near and dear ones. Orthopaedic surgeons in private practice did face 50 to 75% financial loss and have to furlough 25% staff and 50% paramedical persons. Orthopaedics meetings were cancelled, and virtual meetings have become the preferred mode of sharing the knowledge and experiences avoiding human contacts. Staying at home, reading, and writing manuscripts became more interesting and an interesting lifestyle change is seen among the surgeons. Unanimously and without any doubt all accepted the fact that COVID-19 pandemic has reached an unprecedented level where personal hygiene, hand washing, social distancing, and safe surgical practices are the viable antidotes, and they have all slowly integrated these practices into their lives. Strict adherence to local authority recommendations and guidelines, uniform and standardized norms for admission, inpatient, and discharge, mandatory RT-PCR tests before surgery and in selective cases with CT scan chest, optimizing and regularizing the surgeries, avoiding and delaying nonemergency surgeries and follow-up protocols, use of teleconsultations cautiously, and working in close association with the World Health Organization and national health care systems will provide a conducive and safe working environment for orthopaedic surgeons and their fraternity and also will prevent the resurgence of COVID-19.
Publisher: Cambridge University Press (CUP)
Date: 17-05-2007
DOI: 10.1017/S0033291707000827
Abstract: C-reactive protein (CRP) is a non-specific marker of inflammation that has been associated with depression and vascular disease, particularly in men. This study aimed to investigate the association between high CRP concentration and depression while taking physical health into account. A cross-sectional study of a community-dwelling s le of 5438 men aged 70+. Participants with scores ⩾7 on the 15-item Geriatric Depression Scale (GDS-15) were considered to display clinically significant depressive symptoms. We measured the serum concentration of CRP with a high-sensitivity assay. The assessment of physical co-morbidity included three components: the Charlson weighted index, self-report of major health events on a standardized questionnaire, and the physical component of the 36-item Short-Form Health Survey (SF-36). Other measured factors included age, native language, education, a standardized socio-economic index, smoking, prior or current history of depression treatment, cognitive impairment (Mini-Mental State Examination score ) and body mass index (BMI). Participants with depression ( n =340) were older than their controls without depression (age in years: 76·6±4·4 v . 75·4±4·1). Men with CRP concentration mg/l had an increased odds ratio (OR) [1·59, 95% confidence interval (CI) 1·20–2·11] of being depressed compared to men with CRP ⩽3 mg/l. This association became non-significant once we adjusted the analysis for the measures of physical co-morbidity and other confounding factors (OR 1·22, 95% CI 0·86–1·73). The physiological mechanisms that lead to the onset and maintenance of depressive symptoms in older men remain to be determined, but CRP concentration is unlikely to play a significant role in that process.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
Publisher: American Medical Association (AMA)
Date: 07-2015
Publisher: Oxford University Press (OUP)
Date: 10-2009
DOI: 10.1530/EJE-09-0348
Abstract: Insulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease. This relationship may be modulated to some extent by age-related changes in sex hormone status. We examined whether lower testosterone or sex hormone-binding globulin (SHBG) levels in older men are associated with insulin resistance independently of measures of central obesity. Cross-sectional analysis of 2470 community-dwelling non-diabetic men aged ≥70 years. Age, body mass index (BMI) and waist circumference were measured. Early morning sera were assayed for total testosterone, SHBG, LH and insulin levels. Free testosterone was calculated using mass action equations, and insulin resistance was assessed using a homeostatic model (HOMA2-IR). Total testosterone, free testosterone and SHBG declined progressively across increasing quintiles of HOMA2-IR (all P .001) and correlated inversely with log HOMA2-IR ( r =−0.27, −0.14 and −0.24 respectively, all P .001). After adjusting for age, BMI, waist circumference, high-density lipoprotein and triglyceride levels, total testosterone was independently associated with log HOMA2-IR ( β =0.05, P .001), while SHBG was not. Serum total testosterone nmol/l was associated with HOMA2-IR in the highest quintile (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.02–2.73) as was total testosterone ≥8 and nmol/l (OR 1.29, 95% CI 1.03–1.63). In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range. Further studies are needed to evaluate interventions that raise testosterone levels in men with reduced insulin sensitivity.
Publisher: Elsevier BV
Date: 10-2020
Publisher: John Wiley & Sons, Ltd
Date: 08-04-2016
Publisher: Public Library of Science (PLoS)
Date: 09-02-2016
Publisher: The Endocrine Society
Date: 09-2013
DOI: 10.1210/JC.2013-1702
Abstract: Hypovitaminosis D and frailty are common in the older population. We aimed to determine whether 25-hydroxyvitamin D [25(OH)D] concentrations are associated with frailty and mortality. We conducted a prospective cohort study. Participants included 4203 older men aged 70-88 years in Perth, Western Australia. 25(OH)D was measured by immunoassay. Frailty was assessed with the 5-point FRAIL (fatigue, resistance, ambulation, illness, and loss of weight) scale. Mortality was determined from the death registry via the Western Australian Data Linkage System. At baseline, 676 (16.1%) men were frail, as defined by having ≥3 deficits (FRAIL scale ≥ 3). In multivariate cross-sectional analysis, low vitamin D status, defined by the lowest quartile of 25(OH)D values ( 81.6 nmol/L). After a mean period of 5.3 years, the adjusted odds ratio of being frail at follow-up for men with low vitamin D and having zero deficit at baseline (FRAIL scale = 0) was 1.56 (95% CI, 1.07 to 2.27). Low vitamin D also predicted all-cause mortality over a period of up to 9.2 years (hazard ratio, 1.20 95% CI, 1.02 to 1.42), independent of baseline frailty and other covariates. Hypovitaminosis D is associated with prevalent and incident frailty in older men. Hypovitaminosis D also predicts all-cause mortality, independent of frailty. The association between vitamin D and mortality is not solely dependent on the occurrence of frailty.
Publisher: BMJ
Date: 10-07-2014
DOI: 10.1136/BMJ.G4164
Publisher: Massachusetts Medical Society
Date: 10-03-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
DOI: 10.1161/STROKEAHA.113.001564
Abstract: Patients with any type of stroke managed in organized inpatient (stroke unit) care are more likely to survive, return home, and regain independence. However, it is uncertain whether these benefits apply equally to patients with intracerebral hemorrhage and ischemic stroke. We conducted a secondary analysis of a systematic review of controlled clinical trials comparing stroke unit care with general ward care, including only trials published after 1990 that could separately report outcomes for patients with intracerebral hemorrhage and ischemic stroke. We performed random-effects meta-analyses and tested for subgroup interactions by stroke type. We identified 13 trials (3570 patients) of modern stroke unit care that recruited patients with intracerebral hemorrhage and ischemic stroke, of which 8 trials provided data on 2657 patients. Stroke unit care reduced death or dependency (risk ratio [RR], 0.81 95% confidence interval [CI], 0.471–0.92 P =0.0009 I 2 =60%) with no difference in benefits for patients with intracerebral hemorrhage (RR, 0.79 95% CI, 0.61–1.00) than patients with ischemic stroke (RR, 0.82 95% CI, 0.70–0.97 P interaction =0.77). Stroke unit care reduced death (RR, 0.79 95% CI, 0.64–0.97 P =0.02 I 2 =49%) to a greater extent for patients with intracerebral hemorrhage (RR, 0.73 95% CI, 0.54–0.97) than patients with ischemic stroke (RR, 0.82 95%, CI 0.61–1.09), but this difference was not statistically significant ( P interaction =0.58). Patients with intracerebral hemorrhage seem to benefit at least as much as patients with ischemic stroke from organized inpatient (stroke unit) care.
Publisher: BMJ
Date: 29-08-2013
DOI: 10.1136/BMJ.F5215
Publisher: Elsevier BV
Date: 06-2021
Publisher: AMPCo
Date: 02-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2011
DOI: 10.1161/STROKEAHA.110.602532
Abstract: Ischemic stroke induced by thrombosis may be triggered by atherosclerotic plaque rupture and collagen-induced platelet activation. Collagen induces glycoprotein VI shedding. We measured plasma-soluble glycoprotein VI (sGPVI) by enzyme-linked immunosorbent assay in 159 patients with acute ( -day) ischemic stroke and age/sex-matched community-based control subjects. sGPVI was elevated in stroke compared with controls ( P =0.0168). ORs were higher in Quartile 4 for stroke cases ( P =0.0121), and sGPVI was significantly elevated in stroke associated with large artery disease across Quartiles 2 to 4 and small artery disease in Quartile 4. sGPVI decreased 3 to 6 months after antiplatelet treatment, consistent with elevated sGPVI due to platelet activation during the thrombotic event. sGPVI correlated with P-selectin ( P =0.0007) and was higher in in iduals with the GPVI a haplotype ( P =0.024). Glycoprotein VI shedding is implicated in the pathology of acute ischemic stroke.
Publisher: John Wiley & Sons, Ltd
Date: 24-01-2000
Publisher: Wiley
Date: 12-03-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-08-2017
DOI: 10.1212/WNL.0000000000004289
Abstract: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. We combined in idual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%–4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S 2 TOP-BLEED). The S 2 TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60–0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45–54 years without additional risk factors to more than 10% in patients aged 75–84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59–0.63) and slightly underestimated major bleeding risk. The S 2 TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.
Publisher: Wiley
Date: 21-12-2019
DOI: 10.1111/CEN.13905
Abstract: Low endogenous sex hormones and low physical activity (PA) levels have been associated with CVD risk. Whether these interact to influence CVD outcomes remains unclear. We assessed whether sex hormone concentrations and PA were additively associated with lower central adiposity and CVD risk. 3351 community-dwelling men, mean age 77 years. Baseline testosterone (T), dihydrotestosterone (DHT) and oestradiol (E2) were assayed. Levels of PA were ascertained by questionnaire. Men were stratified using median splits into high hormone + high PA (H/H), high hormone + low PA (H/L) low hormone + high PA (L/H) and low hormone + low PA (L/L) groups. A total of 865 CVD events and 499 CVD deaths occurred during 10-year mean follow-up. Men with higher T, DHT or SHBG and higher PA had the lowest BMI, waist circumference and risk of metabolic syndrome. Men with higher T had the lowest risk of incident CVD events, irrespective of PA level. Men with higher T or DHT and higher PA had the lowest risk of dying from CVD (eg, hazard ratios for T/PA H/H 0.76 P = 0.031 H/L 0.85 P = 0.222 L/H 0.80 P = 0.075 L/L 1.00). Higher circulating androgens and higher PA were associated with less central adiposity at baseline and fewer CVD deaths during follow-up. These findings are consistent with a potential additive effect of androgens and PA on cardiometabolic outcomes in older men.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
Publisher: S. Karger AG
Date: 2003
DOI: 10.1159/000069936
Abstract: During the first 30 days after a stroke, the case fatality is about 25% and the major cause of death is the index stroke and its sequelae. The most consistent predictor of 30-day mortality after stroke is stroke severity. Other predictors include increasing age, a history of previous stroke, cardiac failure, and a high blood glucose concentration and white blood cell count. Other less common, but important, causes of early mortality are recurrent ischaemic stroke and a coronary event. The risk of a recurrent cerebrovascular event is highest in the first month (4%) and year (12%) after a stroke and transient ischaemic attack (TIA), probably reflecting the presence of active, unstable atherosclerotic plaque. Thereafter, the risk of a recurrent cerebrovascular event falls to about 5% per year, similar to the risk of a coronary event. During years 1–5 after a TIA and ischaemic stroke, cardiovascular disease increasingly becomes the major cause of death, reflecting the generalized nature of atherothrombosis, the most common cause of the index stroke. The most robust predictor of death within 1–5 years after stroke is increasing age, closely followed by cardiac failure. Additional baseline predictors of longer-term mortality include a history of previous symptomatic atherothrombosis (TIA, ischaemic stroke, peripheral arterial disease, and early-onset ischaemic heart disease), risk factors for atherothrombosis (smoking), other heart diseases (cardiac failure, atrial fibrillation) and increasing stroke severity. Lacunar syndromes can be predictive of relative longevity. At 5 years after stroke, survival is about 40%, and about half of survivors are disabled and dependent. The most robust predictors of disability at 5 years after stroke are increasing age, stroke severity, and recurrent stroke. The most powerful predictor of early recurrent stroke (within 30 days after stroke) is an atherosclerotic ischaemic stroke caused by large-artery atherosclerosis with % stenosis, whereas the strongest predictor of stroke recurrence over 5 years is diabetes. Other predictors of recurrent stroke include increasing age, previous TIA, atrial fibrillation, high alcohol consumption, haemorrhagic index stroke, and hypertension at discharge. The clinical implication of these findings is that strategies for optimizing long-term outcome after TIA and stroke should be directed toward reducing the high risk of recurrent stroke and coronary events by removing/recanalizing the symptomatic atherosclerotic plaque, controlling the underlying causal vascular risk factors, and administering long-term, effective antiplatelet therapy.
Publisher: S. Karger AG
Date: 2020
DOI: 10.1159/000509581
Publisher: American Medical Association (AMA)
Date: 05-2018
Publisher: Wiley
Date: 08-1997
DOI: 10.1111/J.1445-5994.1997.TB02203.X
Abstract: Interstitial cystitis/bladder pain syndrome (IC/BPS) is an immense burden to both patients and the American healthcare system it is notoriously difficult to diagnose. Prevalence estimates vary widely (150-fold range in women and >500-fold range in men). We aimed to create accurate national IC/BPS prevalence estimates by employing a novel methodology combining a national population-based dataset with in idual chart abstraction. In this epidemiological survey, all living patients, with ≥2 clinic visits from 2016 to 2018 in the Veterans Health Administration, with an ICD-9/10 code for IC/BPS ( Of the 5,203,529 patients identified, IC/BPS was confirmed in 541 of 1,647 s led charts with an IC/BPS ICD code, 10 of 382 charts with an ICD-like code, and 3 of 916 controls. After age- and gender-matching to the general US population, this translated to national prevalence estimates of 0.87% (95% CI: 0.32, 1.42), with female and male prevalence of 1.08% (95% CI: 0.03, 2.13) and 0.66% (95% CI: 0.44, 0.87), respectively. We estimate the prevalence of IC/BPS to be 0.87%, which is lower than prior estimates based on survey data, but higher than prior estimates based on administrative data. These potentially represent the most accurate estimates to date, given the broader and more heterogeneous population studied and our novel methodology of combining in-depth chart abstraction with administrative data.
Publisher: SAGE Publications
Date: 02-2008
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.MATURITAS.2022.08.011
Abstract: We investigated the cumulative prevalence of self-harm ideation among stroke survivors of the AFFINITY trial. We assessed these thoughts with the last item of the PHQ-9, and functional impairment with the modified Rankin Scale (mRS). Of 1221 participants (age 63.9 ± 12.3 years, 775 men), 11 reported wishing to die or self-harm at baseline. By week 52, 36 of 1159 surviving participants had reported wishing to die or self-harm. Treatment with fluoxetine for 26 weeks did not change the prevalence of these thoughts compared with placebo. Clinically significant symptoms of depression were present in 95 % of participants with recurrent self-harm thoughts. The study was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000774921.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-05-2014
DOI: 10.1161/CIRCULATIONAHA.113.005754
Abstract: During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days hazard ratio [confidence interval]=0.74 [0.36–1.50] P =0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days hazard ratio [confidence interval]=1.26 [0.80–2.00] P =0.32). TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. URL: www.clinicaltrials.gov . Unique identifier: NCT00403767.
Publisher: Elsevier BV
Date: 1988
DOI: 10.1016/S0009-9260(88)80011-4
Abstract: Thrombosis of the basilar artery is not uncommon and occurs in the elderly as well as in younger patients. The clinical diagnosis may be supported by the appearance on computed tomography enabling appropriate investigations and therapeutic measures to be taken which may lead to a favourable outcome. Four cases of basilar artery thrombosis are described in which the clinical diagnosis was assisted by computed tomography. The basilar artery, which is normally isodense in unenhanced studies, was seen as a hyperdense structure. Follow-up scans demonstrated a decrease in the density and size of the vessel consistent with resolution of a thrombus.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-07-2016
Publisher: BMJ
Date: 06-02-2019
DOI: 10.1136/BMJ.L94
Abstract: To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Systematic analysis. Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-07-2022
Publisher: Elsevier BV
Date: 05-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-02-2020
Abstract: Intravenous thrombolytic therapy ( IVT ) with tissue plasminogen activator for acute ischemic stroke is underutilized in many parts of the world. Randomized trials to test the effectiveness of thrombolysis implementation strategies are limited. This study aimed to test the effectiveness of a multicomponent, multidisciplinary tissue plasminogen activator implementation package in increasing the proportion of thrombolyzed cases while maintaining accepted benchmarks for low rates of intracranial hemorrhage and high rates of functional outcomes at 3 months. A cluster randomized controlled trial of 20 hospitals in the early stages of thrombolysis implementation across 3 Australian states was undertaken. Monitoring of IVT rates during the baseline period allowed hospitals (the unit of randomization) to be grouped into 3 baseline IVT strata—very low rates (0% to ≤4.0%) low rates ( .0% to ≤10.0%) and moderate rates ( .0%). Hospitals were randomized to an implementation package (experimental group) or usual care (control group) using a 1:1 ratio. The 16‐month intervention was based on behavioral theory and analysis of the steps, roles, and barriers to rapid assessment for thrombolysis eligibility and involved comprehensive strategies addressing in idual and system‐level change. The primary outcome was the difference in tissue plasminogen activator proportions between the 2 groups postintervention. The absolute difference in postintervention IVT rates between intervention and control hospitals adjusted for baseline IVT rate and stratum was not significant (primary outcome rate difference=1.1% (95% CI −1.5% to 3.7% P =0.38). Rates of intracranial hemorrhage remained below international benchmarks. The implementation package resulted in no significant change in tissue plasminogen activator implementation, suggesting that ongoing support is needed to sustain initial modifications in behavior. URL : www.anzctr.org.au Unique identifiers: ACTRN 12613000939796 and U1111‐1145‐6762
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2005
Publisher: Cambridge University Press (CUP)
Date: 03-01-2023
DOI: 10.1017/S1041610222001119
Abstract: Cancer has been associated with lower risk of dementia, although methodological issues raise concerns about the validity of this association. We recruited 31,080 men aged 65–85 years who were free of cancer and dementia, and followed them for up to 22 years. We used health record linkage to identify incident cases of cancer and dementia, and split time span to investigate this association. 18,693 (60.1%) and 6897 (22.2%) participants developed cancer and dementia during follow-up. The hazard ratio (HR) of dementia associated with cancer was 1.13 (95% CI = 1.07, 1.20) and dropped to 0.85 (95% CI = 0.80, 0.91) when 449 participants who developed dementia within 2 years were excluded. The diagnosis of cancer seems to facilitate the early detection of dementia cases. Older participants who survive cancer for 2 or more years have lower risk of receiving the diagnosis of dementia over time. The factors that mediate this association remain unclear.
Publisher: Massachusetts Medical Society
Date: 20-12-2012
Publisher: Elsevier BV
Date: 02-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2006
DOI: 10.1161/01.STR.0000229883.72010.E4
Abstract: Background and Purpose— About 60% to 80% of all ischemic strokes can be attributed to increasing blood pressure, blood cholesterol, cigarette smoking, carotid stenosis, and diabetes mellitus (atherosclerotic ischemic stroke), and atrial fibrillation and valvular heart disease (cardiogenic ischemic stroke). The aim of this review was to examine the potential role of other risk factors in the etiology of ischemic stroke. Summary of Review— About 10% to 20% of atherosclerotic ischemic strokes can probably be attributed to recently established, causal risk factors for ischemic heart disease: raised apoB/apoA 1 ratio, obesity, physical inactivity, pyschosocial stress and low fruit and vegetable intake. However, their causal role remains to be proven. The direct genetic contribution of any single gene towards ischemic stroke is likely to be modest and apply in selected patients only and in combination with environmental factors or via other epistatic (gene-gene or gene-environmental) effects. Conclusions— Research resources should not be allocated disproportionately to emerging novel risk factors that may account for up to only 20% of all strokes at the expense of researching the determinants of the relatively few established causal factors that account for up to 80% of all strokes.
Publisher: S. Karger AG
Date: 1991
DOI: 10.1159/000108851
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
Publisher: BMJ
Date: 03-1992
Abstract: 1. In the present study, in vitro electrophysiology and receptor autoradiography were used to determine whether rat vagal afferent neurones possess gamma-aminobutyric acid (GABA)A receptors. 2. GABA (1-100 microM) and isoguvacine (3-100 microM) caused a concentration-dependent depolarization of the rat isolated nodose ganglion preparation at room temperature. When applied to the tissue 20 min before the agonist, SR95531 (3 microM) and bicuculline (3 microM) caused a parallel shift to the right of the GABA and isoguvacine concentration-response curves, yielding shifts of 81 fold and 117 fold for SR95531 and 4 fold and 12 fold for bicuculline, respectively. 3. Baclofen (10 nM-100 microM) was unable to elicit a depolarization of the rat isolated nodose ganglion preparation at either room temperature or at 36 degrees C, whilst 5-aminovaleric acid (10 microM), a GABAB receptor antagonist, was unable to antagonize significantly the GABA-induced depolarization at either room temperature or at 36 degrees C. 4. [3H]-SR95531 (7.2 nM), a GABAA receptor-selective antagonist, bound topographically to sections of rat brainstem. Specific binding was highest in the medial nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve (DMVN). Binding was also observed in certain medullary reticular nuclei, in particular the parvocellular reticular nucleus. 5. Unilateral nodose ganglionectomy caused a reduction in GABAA binding site density in the medial NTS from 93 +/- 7 to 68 +/- 6 d.p.m./mm2. This procedure also caused a reduction in GABAA binding site density in the side of the NTS contralateral to the lesion, from 151 +/- 12 to 93 +/- 7 d.p.m./mm2. Sham surgery had no effect on the binding of [3H]-SR95531 in rat brainstem. 6. The present data provide evidence for the presence of GABAA receptors located on the soma and central terminals of rat vagal afferent neurones. Additionally, a population of GABAA receptors is evidenced postsynaptically in the rat NTS with respect to vagal afferent terminals. These data are discussed in relation to the functional pharmacology of GABA in this region of the NTS.
Publisher: The Endocrine Society
Date: 04-2019
Publisher: Hindawi Limited
Date: 28-07-2019
DOI: 10.1155/2019/2357107
Abstract: Background. One in three survivors of stroke experience poststroke depression (PSD). PSD has been linked with poorer recovery of function and cognition, yet our understanding of potential mechanisms is currently limited. Alterations in resting-state functional MRI have been investigated to a limited extent. Fluctuations in low frequency signal are reported, but it is unknown if interactions are present between the level of depressive symptom score and intrinsic brain activity in varying brain regions. Objective. To investigate potential interaction effects between whole-brain resting-state activity and depressive symptoms in stroke survivors with low and high levels of depressive symptoms. Methods. A cross-sectional analysis of 63 stroke survivors who were assessed at 3 months poststroke for depression, using the Montgomery–Åsberg Depression Rating Scale (MÅDRS-SIGMA), and for brain activity using fMRI. A MÅDRS-SIGMA score of was classified as high depressive symptoms. Fractional litude of frequency fluctuations (fALFF) data across three frequency bands (broadband, i.e., ~0.01–0.08 subbands, i.e., slow-5: ~0.01–0.027 Hz, slow-4: 0.027–0.07) was examined. Results. Of the 63 stroke survivors, 38 were classified as “low-depressive symptoms” and 25 as “high depressive symptoms.” Six had a past history of depression. We found interaction effects across frequency bands in several brain regions that differentiated the two groups. The broadband analysis revealed interaction effects in the left insula and the left superior temporal lobe. The subband analysis showed contrasting fALFF response between the two groups in the left thalamus, right caudate, and left cerebellum. Across the three frequency bands, we found contrasting fALFF response in areas within the fronto-limbic-thalamic network and cerebellum. Conclusions. We provide evidence that fALFF is sensitive to changes in poststroke depressive symptom severity and implicates frontostriatal and cerebellar regions, consistent with previous studies. The use of multiband analysis could be an effective method to examine neural correlates of depression after stroke. The START-PrePARE trial is registered with the Australian New Zealand Clinical Trial Registry, number ACTRN12610000987066 .
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1999
DOI: 10.1161/01.STR.30.10.2105
Abstract: Background and Purpose —This report describes trends in the key indices of cerebrovascular disease over 6 years from the end of the 1980s in a geographically defined segment of the city of Perth, Western Australia. Methods —Identical methods were used to find and assess all cases of suspected stroke in a population of approximately 134 000 residents in a triangular area of the northern suburbs of Perth. Case fatality was measured as vital status at 28 days after the onset of symptoms. Data for first-ever strokes and for all strokes for equivalent periods of 12 months in 1989–1990 and 1995–1996 were compared by age-standardized rates and proportions and Poisson regression. Results —There were 355 strokes in 328 patients and 251 first-ever strokes (71%) for 1989–1990 and 290 events in 281 patients and 213 first-ever strokes (73%) for 1995–1996. In Poisson models including age and period, overall trends in the incidence of both first-ever strokes (rate ratio=0.75 95% confidence limits, 0.63, 0.90) and all strokes (rate ratio=0.73 95% confidence limits, 0.62, 0.85) were obviously significant, but only the changes in men were independently significant. Case fatality did not change, and the balance between hemorrhagic and occlusive strokes in 1995–1996 was almost indistinguishable from that observed in 1989–1990. Conclusions —Our results, which are the only longitudinal population-based data available for Australia for key indices of stroke, suggest that it is a change in the frequency of stroke, rather than its outcome, that is chiefly responsible nationally for the fall in mortality from cerebrovascular disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2002
DOI: 10.1161/01.STR.0000012515.66889.24
Abstract: Background and Purpose — Few reliable estimates of the long-term functional outcome after stroke are available. This population-based study aimed to describe disability, dependency, and related independent prognostic factors at 5 years after a first-ever stroke in patients in Perth, Western Australia. Methods — All in iduals with a suspected acute stroke who were resident in a geographically defined region (population, 138 708) of Perth, Western Australia, were registered prospectively and assessed according to standardized diagnostic criteria over a period of 18 months in 1989 to 1990. Patients were followed up prospectively at 4 and 12 months and 5 years after the index event. Results — There were 370 cases of first-ever stroke, and 277 patients survived to 30 days. Of these early survivors, 152 (55%) were alive at 5 years, and among those who were neither institutionalized (n=146) nor disabled (n=129) at the time of their stroke, 21 (14%) were institutionalized in a nursing home, and 47 (36%) were disabled. The most important predictors of death or disability at 5 years were increasing age, baseline disability defined by a Barthel Index score of /20 (odds ratio [OR], 6.3 95% confidence interval [CI], 2.7 to 14), moderate hemiparesis (OR, 2.7 95% CI, 1.1 to 6.2), severe hemiparesis (OR, 4.5 95% CI, 1.1 to 19), and recurrent stroke (OR, 9.4 95% CI, 3.0 to 30). A low level of activity before the stroke was a significant predictor of institutionalization, and subsequent recurrent stroke was a consistent, independent predictor of institutionalization, disability, and death or institutionalization, increasing the odds of each of these 3 adverse outcomes by 5- to 15-fold. Conclusions — Among 30-day survivors of first-ever stroke, about half survive 5 years of survivors, one third remain disabled, and 1 in 7 are in permanent institutional care. The major modifiable predictors of poor long-term outcome are a low level of activity before the stroke and subsequent recurrent stroke. Efforts to increase physical activity among the elderly and to prevent recurrent stroke in survivors of a first stroke are likely to reduce the long-term burden of cerebrovascular disease.
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.JNS.2011.09.017
Abstract: Smoking, hypertension and alcohol excess are the major causal risk factors for subarachnoid haemorrhage (SAH) that are modifiable. We aimed to explore the hypothesis that other modifiable lifestyle factors, such as diet, may also underpin a substantial proportion of the population attributable risk (PAR) of SAH. In a multi-centre, population-based, case-control study, information on smoking status, history of hypertension, physical activity, dietary intake, alcohol consumption, body mass index, and family history of SAH, were obtained from 432 incident SAH cases and 473 frequency-matched community-based SAH-free controls without SAH. Multivariate analysis was used to identify significant risk factors and associated PARs for SAH, reported with 95% confidence intervals (CI). Smoking and history of hypertension accounted for 30% (95%CI 23-37%) and 21% (10-30%) of SAH, respectively. Additionally, 25% (11-37%) of SAH was attributed to drinking skim or reduced fat milk, 15% (5-24%) to eating fruit less than once weekly, and 13% (5-21%) to eating either the fat on meat or skin on chicken >4 times weekly. Alcohol excess was not associated with SAH. Smoking cessation and blood pressure control are the most important strategies to prevent SAH. However, drinking skimmed/reduced fat milk, eating fruits regularly, and removing the fat from meats and skin from chicken before consumption may also reduce the burden of SAH.
Publisher: BMJ
Date: 24-04-1993
DOI: 10.1136/BMJ.306.6885.1107
Abstract: The outcomes of each of three large cohorts of patients with transient ischaemic attacks, which were studied in the same country at much the same time with the same methods, were compared and found to be quite different from each other. The differences in outcome were related not only to different strategies of treatment but also to differences in the prevalence and level of important prognostic factors (for ex le, case mix) and other factors such a the time delay from transient ischaemic attack to entry into the study and the play of chance. The implications for purchasers of health care are that they cannot rely solely on non-randomised comparisons of outcome of patients treated in competing units as a measure of the quality of care (which has only rather modest effects) without accounting for other factors that may influence outcome such as the nature of the illness, the case mix, observer bias, and the play of chance.
Publisher: Public Library of Science (PLoS)
Date: 30-07-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1997
DOI: 10.1161/01.STR.28.11.2126
Abstract: Background and Purpose The surgical treatment of primary intracerebral hemorrhage (PICH) varies thoughout the world, mainly because of the lack of evidence of its safety and effectiveness. This study compares the outcome of patients with PICH who are treated surgically with those who are not. Methods We conducted a systematic overview (meta-analysis) of all studies of the outcome of surgery for PICH by means of a Medline search of relevant randomized trials and case series published since 1966. Cited references and presentations were also reviewed. Results The 15 case series of surgery for PICH involving a total of 1524 patients (654 treated surgically) are potentially confounded and the results inconclusive. The pooled results of the three randomized controlled trials of open craniotomy and one trial of endoscopic evacuation for supratentorial PICH in a total of 349 patients (173 treated surgically) indicate a nonsignificant increase in odds of death and dependency at 6 months for patients treated surgically (odds ratio, 1.23 95% confidence interval, 0.77 to 1.98). The odds of death or dependency at 6 months were 2.1 (1.1 to 4.1) for patients undergoing craniotomy and 0.45 (0.2 to 1.0) for endoscopic evacuation. Conclusions There is insufficient evidence of the risks and benefits of surgery for PICH. Further randomized trials are needed to identify whether there is a favorable treatment effect of surgery, the types of PICH and patients who are likely to benefit and not benefit, and the safety and effectiveness of the different surgical interventions.
Publisher: S. Karger AG
Date: 2014
DOI: 10.1159/000358583
Abstract: b i Background: /i /b Population-based studies, as well as clinicians, often rely on self-report and hospital records to obtain a history of stroke. This study aimed to compare the validity of the diagnosis of stroke by self-report and by hospital coding according to their cross-sectional association with prevalent vascular risk factors, and longitudinal association with recurrent stroke and major cardiovascular outcomes in a large cohort of older Australian men. b i Methods: /i /b Between 1996 and 1999, 11,745 older men were surveyed for a self-reported history of stroke as part of the Health in Men Study (HIMS). Previous hospitalization for stroke was obtained with consent from linked medical records via the Western Australian Data Linkage System (WADLS). Subjects were followed by WADLS until December 31, 2010, for hospitalization for stroke, cardiovascular events, and all-cause mortality. The primary outcome was hospitalisation for stroke during follow-up. Secondary outcomes included incident vascular events and composite vascular endpoints. b i Results: /i /b At baseline, a history of stroke was reported by 903 men (7.7%), previous hospitalisation for stroke was recorded in 717 (6.1%), both self-report and hospitalisation in 467 (4.0%), and no history of stroke in 10,696 men (91.1%). Prevalent cardiovascular disease and peripheral arterial disease were more common among men with previous hospitalisation for stroke than a history of self-reported stroke (p 0.001). In longitudinal analyses, incident aortic aneurysm was also more common among men with baseline history of hospitalization for stroke (adjusted hazard ratio (HR) 1.71, 95% CI 1.12-2.60) than among men with self-reported stroke (HR 0.88, 95% CI 0.56-1.36) compared to men with no history of stroke. With regard to the primary outcome, the rate of hospitalisation for stroke during follow-up was significantly higher among men with self-reported stroke (HR 2.44, 95% CI 2.03-2.94), hospital-coded stroke (adjusted HR 3.02, 2.42-3.78) and both self-reported and hospital-coded stroke (adjusted HR 3.33, 2.82-3.92) compared to participants with no previous stroke. Time to recurrent stroke was similar among different methods of initial stroke diagnosis (p = 0.067). b i Conclusions: /i /b Self-reported stroke and hospital-coded stroke have a similar prognostic value for predicting the risk of recurrent stroke. This supports the use of these ways of assessing a history of stroke for the clinical purposes of secondary prevention and for further epidemiological studies.
Publisher: BMJ
Date: 04-1996
Abstract: To test the design and feasibility of a very large randomised controlled trial assessing the efficacy and safety of antithrombotic therapy started within 48 hours of symptom onset in patients with suspected acute ischaemic stroke. Randomised controlled multicentre open study, with a 3 x 2 factorial design, allocating patients to: medium dose subcutaneous heparin (12,500 units twice per day), versus low dose subcutaneous heparin (5000 units twice per day) versus no heparin and aspirin (300 mg daily) versus no aspirin. Treatment was given for two weeks or until discharge from hospital if sooner. 984 patients were randomised. CT was performed in 924 (94%) (before randomisation in 622/984 (63%). Within 14 days: 97 patients had died (10%), 30 (3.0%) had a fatal or non-fatal recurrent ischaemic stroke, nine (0.9%) had fatal or non-fatal recurrent stroke due to intracranial haemorrhage, and eight (0.8%) had a fatal or non-fatal pulmonary embolus. At six months, vital status was known for 975 patients (99%), of whom 210 (22%) were dead, 373 (38%) were alive but dependent, and 225 (23%) were independent but not fully recovered. The trial procedures proved practicable and a wide variety of patients were recruited. S le size calculation based on the event rates confirmed that reliable evidence on the balance of risk and benefit of early antithrombotic therapy might require a study with more than 20,000 patients. Recruitment rates in the pilot study indicated that if about 200 hospitals participated, recruitment could be completed by 1997.
Publisher: Wiley
Date: 10-10-2018
DOI: 10.1111/CEN.13484
Abstract: Sex hormone trajectories in ageing men and their health implications remain unclear. We examined longitudinal trajectories and associations of testosterone (T), dihydrotestosterone (DHT), oestradiol (E2), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) in oldest old men. Prospective cohort study. We studied 1025 community-dwelling men median age 75.1 years at baseline with 8.6 years of follow-up. Baseline and follow-up T, DHT and E2 were assayed using mass spectrometry. Physical performance was assessed at follow-up. Correlations and covariate-adjusted P-values were determined. Longitudinal change in T was -2.0%/year, DHT -7.2%/year, LH +7.5%/year, SHBG +5.6%/year while E2 remained stable. Annualized increases in LH correlated with decreases in T and DHT (r = -.20, P 16 IU/L) at follow-up, 175 (17.4%) had high LH of whom 70 had low T (<6.4 nmol/L). Annualized increases in LH are associated with declines in T and DHT, and predict poorer subsequent physical performance in oldest old men. Men transitioning from 8th to 9th decades exhibit biochemical evidence of progressively impaired testicular endocrine function, warranting further evaluation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2006
DOI: 10.1161/01.STR.0000198815.07315.68
Abstract: Background and Purpose— A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger in iduals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. Methods— We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged ≥75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B 6 , and 400 μg of B 12 or placebo. The study groups were balanced regarding age (mean±SD, 78.9±2.8 years), B vitamins, and tHcy at baseline. Results— Among the 13% with B 12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 μmol/L (95% CI, 3.94 to 9.55 μmol/L) compared with 2.88 μmol/L (95% CI, 0.07 to 5.69 μmol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 μmol/L (95% CI, 0.6 to 4.9 μmol/L). Baseline vitamin B 12 , serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up ( r =0.252, r =0.522, and r =−0.903, respectively P =0.003, .001, and .001, respectively) in the vitamin group. Conclusions— The tHcy-lowering effect of B vitamins was maximal in those who had low B 12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B 12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.GENHOSPPSYCH.2013.08.009
Abstract: There is lack of information of the hospital costs related to depression. Here, we compare the costs associated with general hospital admissions over 2 years between older men with and without a documented past history of depression. A community-based cohort of older men living in Perth, Western Australia, was assessed at baseline between 2001 and 2004 and followed up for 2 years by prospective data linkage. The participants were selected randomly from the Australia electoral roll. Two-year hospital costs were estimated. Among 5411 patients, 75% of 339 men with depressive symptoms had at least one hospital admission compared with 61% of 5072 men without depression (P<.001). Two-year median hospital costs in the depressed group were A$4153 compared with A$1671 in participants free from depression (P<.001). In multivariate analysis, the presence of clinically significant depressive symptoms remained an independent predictor of higher cost [incident rate ratios (RR)=1.44, 95% confidence interval (CI): 1.23-1.68] and was associated with being a high-cost user of health services (RR=2.04, 95% CI: 1.43-2.92). The estimation of costs was solely based on the main diagnosis, potentially leading to underestimates of the real cost differences. Hospital care cost was higher for older men with documented evidence of past depression than those without. The issue of depression in later life must be tackled if we want to optimize the use of limited hospital resources available.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2011
Publisher: Wiley
Date: 08-07-2022
DOI: 10.1002/JBMR.4631
Abstract: Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk however, its relationship with all‐cause and cause‐specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all‐cause and cause‐specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N‐propeptide (PINP), and collagen type 1 C‐terminal cross‐linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community‐dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer‐related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all‐cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06–1.18, p 0.001 PINP HR = 1.06, 95% CI 1.01–1.11, p = 0.009 CTX HR = 1.13, 95% CI 1.08–1.19, p 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow‐up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05–1.22, p = 0.001 CTX HR = 1.12, 95% CI 1.04–1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01–1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all‐cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all‐cause and cancer‐related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.HLC.2018.07.007
Abstract: Patent foramen ovale (PFO) is a potential mechanism for paradoxical embolism in cryptogenic ischaemic stroke or transient ischaemic attack (TIA). PFO is typically demonstrated with agitated saline ("bubble study", BS) during echocardiography. We hypothesised that the BS is frequently requested in patients that have a readily identifiable cause of stroke, that any PFO detected is likely incidental, and its detection often does not alter management. This was a retrospective observational study of patients with recent ischaemic stroke/TIA referred for a BS. Patient demographics, stroke risk factors, vascular/cerebral imaging results and transoesophageal echocardiogram (TOE) reports were recorded. A "modified" Risk of Paradoxical Embolism (RoPE) score was calculated. Change in management was defined as antiplatelet/anticoagulant therapy alteration or referral for PFO closure. Bubble Study complications were recorded. Among 715 patients with ischaemic stroke/TIA referred for a BS, 8.7% had atrial fibrillation and 9.2% had carotid stenosis ≥70%. At least three stroke risk factors were present in 39.3% and only 47.1% of patients screened had a "modified" RoPE score of >5. A PFO was detected in 248 patients of whom only 31% (77/248) had a subsequent change in management. Of BS performed, 1/924 patients (0.1%) suffered a TIA as a complication. The echocardiographic BS is frequently performed in patients that have a readily identifiable cause of stroke and whose PFO unlikely relates to the stroke/TIA. Bubble Study findings resulted in a change in management in the minority. The procedure is safe but the complication rate warrants informed consent.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2005
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.CLINEURO.2011.12.023
Abstract: To compare systemic arterial inflammation in subjects with recent ischaemic stroke or TIA and controls with prior cerebrovascular disease. Systemic arterial inflammation was prospectively measured by (18)F-fluorodeoxygluose positron emission tomography in 11 cases with recent ischaemic stroke or TIA, and 11 sex matched controls with prior cerebrovascular disease. Hot spots (both carotid and non-carotid) of localised (18)FDG uptake were found in more than half of all patients with either recent (n = 6) or prior (n = 8) cerebrovascular disease. There was no significant difference in the total number of hotspots, or hotspots at specific sites, in cases compared with controls. Mean standard uptake values (SUV) were similar in the carotid arteries and aorta of cases and controls, and showed a trend toward higher values in the femoral arteries of the controls (median 1.8 IQR 1.6-2.2) compared to cases (median 1.5 IQR 1.4-1.7). Arterial inflammation was common, and appeared similar, in patients with recent stroke/TIA, and controls with stroke/TIA more than two years previously.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-08-2022
Abstract: Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated‐measures and single‐measure analyses of the mRS from a randomized clinical trial. Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double‐blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single‐measure (day 365) and repeated‐measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety‐five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke years no prestroke history of diabetes, coronary heart disease, or ischemic stroke prestroke history of depression, a relationship partner, living with others, independence, or paid employment no fluoxetine intervention ischemic stroke (compared with hemorrhagic) stroke treatment in Vietnam (compared with Australia or New Zealand) longer time since current stroke and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire‐9 scores. Direction of associations was largely concordant between single‐measure and repeated‐measures models. Association strength and variance was generally smaller in the repeated‐measures model compared with the single‐measure model. Repeated‐measures may improve trial precision in identifying trial associations and effects. Further repeated‐measures stroke analyses are required to prove methodological value. URL: www.anzctr.org.au Unique identifier: ACTRN12611000774921.
Publisher: Wiley
Date: 10-2015
DOI: 10.1002/CLC.22454
Publisher: Elsevier BV
Date: 03-2019
Publisher: Elsevier BV
Date: 06-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-09-2015
Publisher: AMPCo
Date: 04-1987
DOI: 10.5694/J.1326-5377.1987.TB120332.X
Abstract: Eight cases of postural focal cerebral ischaemia due to antihypertensive medications presented to one neurologist over an eight-month period. Most patients were elderly and suffered from chronic hypertension their symptoms resolved after the reduction or cessation of these medications. These findings re-emphasize that considerable caution is required when antihypertensive medications are used in elderly persons and in patients with chronic hypertension whose cerebral blood-flow autoregulatory curves are shifted to the right. We also draw attention to the fact that drug-induced hypotension may induce focal cerebral ischaemia rather than generalized cerebral ischaemia more frequently than is generally appreciated.
Publisher: BMJ
Date: 14-12-2020
DOI: 10.1136/HEARTJNL-2019-316515
Abstract: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity .0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25 4.53 to 6.10) than treated hypertension (OR 2.60 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years p .01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95 5.61 to 8.60) than ischaemic stroke (OR 4.76 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80 1.32 to 2.46). Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.
Publisher: Wiley
Date: 17-11-2018
DOI: 10.1111/CEN.13499
Abstract: Insulin-like growth factor 1 (IGF1) has anabolic and growth-promoting effects, raising concerns regarding its potential to promote tumour growth. Circulating IGF1 is bound to binding proteins, which modulate bioavailability of IGF1. This study assessed the associations of IGF1 and its binding proteins 1 (IGFBP1) and 3 (IGFBP3) with cancer risk. A prospective cohort study of 4042 men aged ≥70 years. Plasma total IGF1, IGFBP1 and IGFBP3 were measured between 2001 and 2004. Cancer-related outcomes were assessed until 20 June 2013 using data linkage. Analyses were performed using proportional hazards models with death as a competing risk, and adjustments were made for potential confounders. Results are expressed as subhazard ratios (SHR). There were 907 men who were diagnosed with cancer during a median of 9-year follow-up. Of these, there were 359, 139 and 125 prostate, colorectal and lung cancers, respectively. After adjustments, total IGF1 was not associated with the incidence of any cancer, prostate, lung or colorectal cancer. In the fully-adjusted model, higher IGFBP3 was associated with increased incidence of colorectal cancer (SHR = 1.20, 95% CI 1.01-1.43 P = .041 for every 1 standard deviation increase in IGFBP3) but not other cancers. This effect was not attenuated by inclusion of total IGF1 into the multivariate model (SHR = 1.28, 95% CI 1.03-1.58 P = .025). Neither total IGF1, IGFBP1 nor IGFBP3 were associated with cancer-related deaths. Higher IGFBP3 predicted increased incidence of colorectal cancer in older men independent of conventional risk factors and total IGF1. Further studies are warranted to explore potential underlying mechanisms.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2011
DOI: 10.1161/STROKEAHA.110.598599
Abstract: Small vessel disease plays a role in cerebral events. We aimed to investigate the prevalence and patterns of retinal microvascular signs (surrogates for cerebral small vessel disease) among patients with transient ischemic attack (TIA) or acute stroke and population control subjects. Patients with TIA or acute stroke aged ≥49 years admitted to hospitals in Melbourne and Sydney, Australia, were recruited to the Multi-Centre Retina and Stroke Study (n=693, 2005 to 2007). Control subjects were Blue Mountains Eye Study participants aged ≥49 years without TIAs or stroke (n=3384, 1992 to 1994, west of Sydney). TIA, ischemic stroke, or primary intracerebral hemorrhage was classified using standardized neurological assessments, including neuroimaging. Retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex) were assessed from retinal photographs masked to clinical information. Patients with TIA or acute stroke were older than control subjects and more likely to have stroke risk factors. After adjustment for study site and known risk factors, all retinal microvascular signs were more common in patients with TIA or acute stroke than in control subjects (OR, 1.9 to 8.7 P .001). Patients with TIA and those with ischemic stroke had similar prevalences of nondiabetic retinopathy (26.9% versus 29.5% OR, 0.8 95% CI, 0.5 to 1.6), diabetic retinopathy (55.5% versus 50.0% OR, 1.3 95% CI, 0.4 to 3.6), focal arteriolar narrowing (15.6% versus 18.4% OR, 0.8 95% CI, 0.4 to 1.5), and arteriovenous nicking (23.0% versus 17.8% OR, 1.4 95% CI, 0.7 to 2.7). Patients with TIA and acute stroke may share similar risk factors or pathogenic mechanisms.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
DOI: 10.1161/CIRCHEARTFAILURE.113.000212
Abstract: In Rivaroxaban Once daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), rivaroxaban was noninferior to warfarin for the prevention of stroke and systemic embolic events and significantly reduced intracranial bleeding in patients with nonvalvular atrial fibrillation. We explore the safety and efficacy of rivaroxaban in patients with heart failure (HF). A total of 9033 (63.7%) patients had HF. The primary efficacy analysis was rates of stroke or systemic embolism (per 100 patient-years) by intention to treat. The safety outcomes were major or nonmajor clinically relevant bleeding and hemorrhagic stroke during treatment. Patients with HF were younger (72 versus 74 years), more likely to have persistent atrial fibrillation (83.0% versus 77.6%), and had higher mean CHADS 2 scores (3.7 versus 3.1). The efficacy of rivaroxaban compared with warfarin was similar in patients with HF (1.90 versus 2.09) and without HF (2.10 versus 2.54 P -interaction=0.62). The risk of major or nonmajor clinically relevant bleeding with rivaroxaban was similar to warfarin in patients with HF (14.22 versus 14.02) and without HF (16.12 versus 15.35 P -interaction=0.99). A reduction in hemorrhagic stroke was observed with rivaroxaban in patients with HF as in the overall trial (adjusted hazard ratio, 0.38 95% confidence interval, 0.19–0.76 P -interaction=0.067). Among patients with HF, the efficacy of rivaroxaban was similar, irrespective of ejection fraction or ≥40% ( P -interaction=0.38), New York Heart Association class I-II versus III-IV ( P -interaction=0.68), HF preserved or reduced ejection fraction ( P -interaction=0.35), or CHADS 2 score 2 versus ≥3 ( P -interaction=0.48). Treatment-related outcomes were similar in patients with and without HF and across HF subgroups. These findings support the use of rivaroxaban as an alternative to warfarin in patients with atrial fibrillation and HF. URL: www.clinicaltrials.gov . Unique identifier: NCT00403767.
Publisher: Elsevier BV
Date: 03-2014
Publisher: SAGE Publications
Date: 10-07-2020
Abstract: Central adjudication of outcomes is common for randomised trials and should control for differential misclassification. However, few studies have estimated the cost of the adjudication process. We estimated the cost of adjudicating the primary outcome in nine randomised stroke trials (25,436 participants). The costs included adjudicators’ time, direct payments to adjudicators, and co-ordinating centre costs (e.g. uploading cranial scans and general set-up costs). The number of events corrected after adjudication was our measure of benefit. We calculated cost per corrected event for each trial and in total. The primary outcome in all nine trials was either stroke or a composite that included stroke. In total, the adjudication process associated with this primary outcome cost in excess of £100,000 for a third of the trials (3/9). Mean cost per event corrected by adjudication was £2295.10 (SD: £1482.42). Central adjudication is a time-consuming and potentially costly process. These costs need to be considered when designing a trial and should be evaluated alongside the potential benefits adjudication brings to determine whether they outweigh this expense.
Publisher: American College of Physicians
Date: 16-12-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1997
DOI: 10.1161/01.STR.28.11.2139
Abstract: Background and Purpose We sought to clarify the way in which organized inpatient (stroke unit) care can produce reductions in case fatality and in the need for institutional care after stroke. Methods We performed a secondary analysis of a collaborative systematic review of all randomized trials that compared organized inpatient (stroke unit) care with contemporary conventional care. Nineteen trials were included, of which 18 (3246 patients) could provide outcome data on death, place of residence, and final functional outcome. Data were less complete (but always available for at least 12 trials 1611 patients) for subgroup analyses examining timing and cause of death and outcomes in patients with different levels of severity of initial stroke. Results The reduction in case fatality of patients managed in a stroke unit setting developed between 1 and 4 weeks after the index stroke. The reduction in the odds of death was evident across all causes of death and most marked for those deaths considered to be secondary to immobility. However, data were insufficient to permit a firm conclusion. The relative increase in the number of patients discharged home from stroke units as opposed to conventional care was largely attributable to an increase in the number of patients returning home physically independent. Across the range of stroke severity, stroke unit care was associated with nonsignificant increases in the number of patients regaining independence. Conclusions Within the limitations of the available data, we conclude that organized inpatient stroke unit care probably benefits a wide range of stroke patients in a variety of different ways, ie, reducing death from secondary complications of stroke and reducing the need for institutional care through a reduction in disability.
Publisher: S. Karger AG
Date: 03-06-2023
DOI: 10.1159/000524916
Abstract: b i Introduction: /i /b In patients with acute ischemic stroke, the location and volume of an irreversible infarct core determine prognosis and treatment. We aimed to determine if automated CT perfusion (CTP) is non-inferior to diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) in predicting the acute infarct core. b i Methods: /i /b In this systematic review and meta-analysis, we searched MEDLINE and EMBASE from 1960 to December 2020. Five outcome measures were examined: volumetric difference, volumetric correlation, sensitivity and specificity at the patient level, Dice coefficient, and sensitivity and specificity at the voxel level. A random-effects meta-analysis was performed for volumetric difference and correlation. b i Results: /i /b From 3,986 studies retrieved, 48 studies met our inclusion criteria with 46 studies on anterior circulation, one study on posterior circulation, and one study on lacunar infarct strokes. In anterior circulation stroke, there were no significant mean volumetric differences between CTP and acute DWI (cerebral blood flow [CBF] 0.52 mL, 95% CI [−0.07, 1.11], i I /i sup /sup 0.0% relative CBF [rCBF] 3.01 mL, 95% CI [−0.46, 6.48], i I /i sup /sup 82.6% relative cerebral blood volume [rCBV] −12.84 mL, 95% CI [−38.56, 12.88], i I /i sup /sup 96.2%) and between CTP and delayed DWI or FLAIR (rCBF −1.29 mL, 95% CI [−6.49, 3.92], i I /i sup /sup 91.8% rCBV −5.80 mL, 95% CI [−16.20, 4.60], i I /i sup /sup 84.2%). Mean correlation between CTP and acute DWI was 0.90 (95% CI [0.80, 0.95], i I /i sup /sup 60.0%) for rCBF and 0.84 (95% CI [0.58, 0.94], i I /i sup /sup 93.5%) for rCBV. Mean correlation between CTP and delayed DWI or FLAIR was 0.74 (95% CI [0.57, 0.85], i I /i sup /sup 94.6%) for rCBF and 0.90 (95% CI [0.69, 0.97], i I /i sup /sup 93.1%) for rCBV. Sensitivity and specificity at the patient level were reported by three studies and Dice coefficient by four studies. Statistical analysis could not be performed for sensitivity and specificity at the voxel level. Limited evidence was available for posterior circulation or lacunar infarct strokes. b i Conclusion: /i /b Due to significant heterogeneity and insufficient high-quality studies reporting each outcome, there is insufficient evidence to reliably determine the accuracy of CTP prediction of the infarct core compared to DWI or FLAIR.
Publisher: The Endocrine Society
Date: 12-2012
DOI: 10.1210/JC.2012-2108
Abstract: Both hypothyroidism and subclinical hyperthyroidism hinder cognitive function. We aimed to determine whether more subtle alterations of thyroid hormone levels predict increased incidence of dementia in aging men. Community-dwelling men aged 70-89 yr participated in this prospective longitudinal study. The Standardized Mini-Mental State Examination was performed at baseline (2001-2004), and circulating TSH and free T(4) (FT(4)) were assayed. Men with known thyroid disease or dementia, or Standardized Mini-Mental State Examination scores below 24 were excluded from follow-up. New-onset dementia, defined by International Classification of Disease (ICD) codes, was ascertained using data linkage (2001-2009). During follow-up, 145 of 3401 men (4.3%) were diagnosed for the first time with dementia. Men who developed dementia had higher baseline FT(4) (16.5 ± 2.2 vs. 15.9 ± 2.2 pmol/liter, P = 0.004) but similar TSH (2.2 ± 1.4 vs. 2.3 ± 1.6 mU/liter, P = 0.23) compared with men who did not receive this diagnosis. After adjusting for covariates, higher FT(4) predicted new-onset dementia (11% increased risk per 1 pmol/liter increase in FT(4), P = 0.005 quartiles Q2-4 vs. Q1: adjusted hazard ratio = 1.76, 95% confidence interval = 1.03-3.00, P = 0.04). There was no association between TSH quartiles and incident dementia. When the analysis was restricted to euthyroid men (excluding those with subclinical hyper- or hypothyroidism), higher FT(4) remained associated with incident dementia (11% increase per unit increment, P = 0.03 Q2-4 vs. Q1: adjusted hazard ratio = 2.02, 95% confidence interval = 1.10-3.71, P = 0.024). Higher FT(4) levels predict new-onset dementia in older men, independently of conventional risk factors for cognitive decline. Additional studies are needed to explore potential underlying mechanisms and to clarify the utility of thyroid function testing in older men at risk of dementia.
Publisher: American College of Physicians
Date: 16-12-2014
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000515393
Abstract: b i Background: /i /b In light of the increasing trend in the global number of in iduals affected by dementia and the lack of any available disease-modifying therapies, it is necessary to fully understand and quantify the global burden of dementia. This work aimed to estimate the proportion of dementia due to Down syndrome, Parkinson’s disease, clinical stroke, and traumatic brain injury (TBI), globally and by world region, in order to better understand the contribution of clinical diseases to dementia prevalence. b i Methods: /i /b Through literature review, we obtained data on the relative risk of dementia with each condition and estimated relative risks by age using a Bayesian meta-regression tool. We then calculated population attributable fractions (PAFs), or the proportion of dementia attributable to each condition, using the estimates of relative risk and prevalence estimates for each condition from the Global Burden of Disease Study 2019. Finally, we multiplied these estimates by dementia prevalence to calculate the number of dementia cases attributable to each condition. b i Findings: /i /b For each clinical condition, the relative risk of dementia decreased with age. Relative risks were highest for Down syndrome, followed by Parkinson’s disease, stroke, and TBI. However, due to the high prevalence of stroke, the PAF for dementia due to stroke was highest. Together, Down syndrome, Parkinson’s disease, stroke, and TBI explained 10.0% (95% UI: 6.0–16.5) of the global prevalence of dementia. b i Interpretation: /i /b Ten percent of dementia prevalence globally could be explained by Down syndrome, Parkinson’s disease, stroke, and TBI. The quantification of the proportion of dementia attributable to these 4 conditions constitutes a small contribution to our overall understanding of what causes dementia. However, epidemiological research into modifiable risk factors as well as basic science research focused on elucidating intervention approaches to prevent or delay the neuropathological changes that commonly characterize dementia will be critically important in future efforts to prevent and treat disease.
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B908241G
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/AJAG.12419
Publisher: Springer Science and Business Media LLC
Date: 02-08-2019
Publisher: American Chemical Society (ACS)
Date: 05-1984
DOI: 10.1021/IC00178A003
Publisher: Elsevier BV
Date: 06-2007
Publisher: Royal Society of Chemistry (RSC)
Date: 1986
DOI: 10.1039/DT9860001531
Publisher: Oxford University Press (OUP)
Date: 15-10-2013
Abstract: Frailty and hyperhomocysteinemia are common in the older population. The researchers' objectives were to determine whether elevated homocysteine (tHcy) is associated with frailty and mortality. The researchers conducted a prospective cohort study. tHcy was measured by immunoassay in 4,248 community-dwelling men aged 70-88 years. Frailty was assessed with the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) scale. Mortality was determined from the death registry. At baseline, 1,117 men (26.3%) had high tHcy (≥15 µmol/L) and 685 (16.2%) were frail (ie, having three or more deficits in the FRAIL scale). There were 749 deaths during a follow-up duration of 5.1±1.3 years. In cross-sectional analysis, high tHcy was associated with increased prevalent frailty (odds ratio 1.49, 95% CI 1.22-1.81) after adjusting for confounding factors. After a period of 5.3±0.8 years, the longitudinal relationship between high tHcy and frailty was weakened in multivariate analysis (hazards ratio 1.25, 95% CI 0.95-1.65). When assessing the relationship between tHcy and incident frailty, the odds of being frail at follow-up for men with high tHcy and having zero deficit at baseline (ie, FRAIL scale = 0) were 1.59 (95% CI 0.88-2.89) in adjusted analysis. High tHcy also predicted all-cause mortality (hazards ratio 1.25, 95% CI 1.06-1.48) after adjusting for frailty and other covariates. Hyperhomocysteinemia is associated with the prevalence of frailty. It is also predictive of all-cause mortality, independent of frailty. The results suggest that the association between tHcy and mortality is largely not mediated through the occurrence of frailty.
Publisher: Elsevier BV
Date: 10-2009
Publisher: The Endocrine Society
Date: 10-2015
DOI: 10.1210/JC.2015-1899
Abstract: Undercarboxylated osteocalcin (ucOC) modulates insulin secretion and sensitivity in mice, and higher ucOC is associated with lower prevalence of diabetes in men. The influence of ucOC distinct from other markers of bone turnover on incidence of cardiovascular events is unclear. Community-dwelling men aged 70-89 years resident in Perth, Western Australia. Serum total osteocalcin (TOC), N-terminal propeptide of type I collagen (P1NP), and collagen type I C-terminal cross-linked telopeptide (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. The ratio ucOC/TOC was calculated. Hospital admissions and deaths from myocardial infarction (MI) and stroke were ascertained. There were 3384 men followed for 7.0 years, during which 293 experienced an MI, 251 stroke, and 2840 neither. In multivariate analyses, higher ratio of ucOC/TOC (expressed as %) was associated with lower incidence of MI (quartiles Q2-4, ≥ 49% versus Q1,<49%, hazard ratio 0.70, 95% confidence interval = 0.54-0.91), but not of stroke (0.99, 0.73-1.34). Higher P1NP was associated with higher incidence of MI (Q2-4, ≥ 28.2 μg/L versus Q1, <28.2 μg/L, hazard ratio 1.45, 95% confidence interval = 1.06-1.97), but not of stroke (0.94, 0.70-1.26). CTX was not associated with incident MI or stroke. A reduced proportion of undercarboxylated osteocalcin or higher P1NP are associated with increased incidence of MI. UcOC/TOC ratio and P1NP predict risk of MI but not stroke, in a manner distinct from CTX. Further studies are needed to investigate potential mechanisms by which bone turnover markers related to metabolic risk and to collagen formation could modulate cardiovascular risk.
Publisher: SAGE Publications
Date: 10-04-2012
Publisher: Oxford University Press (OUP)
Date: 21-06-2022
DOI: 10.1093/IJE/DYAC124
Abstract: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-s le Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24) associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15 1.10: 1.01, 1.20 and 1.13 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99) these associations were attenuated following adjustment for IGF-I. These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Publisher: Elsevier BV
Date: 10-1997
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1999
Abstract: Background and Purpose —Swallowing dysfunction (dysphagia) is common and disabling after acute stroke, but its impact on long-term prognosis for potential complications and the recovery from swallowing dysfunction remain uncertain. We aimed to prospectively study the prognosis of swallowing function over the first 6 months after acute stroke and to identify the important independent clinical and videofluoroscopic prognostic factors at baseline that are associated with an increased risk of swallowing dysfunction and complications. Methods —We prospectively assembled an inception cohort of 128 hospital-referred patients with acute first stroke. We assessed swallowing function clinically and videofluoroscopically, within a median of 3 and 10 days, respectively, of stroke onset, using standardized methods and diagnostic criteria. All patients were followed up prospectively for 6 months for the occurrence of death, recurrent stroke, chest infection, recovery of swallowing function, and return to normal diet. Results —At presentation, a swallowing abnormality was detected clinically in 65 patients (51% 95% CI, 42% to 60%) and videofluoroscopically in 82 patients (64% 95% CI, 55% to 72%). During the subsequent 6 months, 26 patients (20% 95% CI, 14% to 28%) suffered a chest infection. At 6 months after stroke, 97 of the 112 survivors (87% 95% CI, 79% to 92%) had returned to their prestroke diet. Clinical evidence of a swallowing abnormality was present in 56 patients (50% 95% CI, 40% to 60%). Videofluoroscopy was performed at 6 months in 67 patients who had a swallowing abnormality at baseline it showed penetration of the false cords in 34 patients and aspiration in another 17. The single independent baseline predictor of chest infection during the 6-month follow-up period was a delayed or absent swallowing reflex (detected by videofluoroscopy). The single independent predictor of failure to return to normal diet was delayed oral transit (detected by videofluoroscopy). Independent predictors of the combined outcome event of swallowing impairment, chest infection, or aspiration at 6 months were videofluoroscopic evidence of delayed oral transit and penetration of contrast into the laryngeal vestibule, age years, and male sex. Conclusions —Swallowing function should be assessed in all acute stroke patients because swallowing dysfunction is common, it persists in many patients, and complications frequently arise. The assessment of swallowing function should be both clinical and videofluoroscopic. The clinical and videofluoroscopic features at presentation that are important predictors of subsequent swallowing abnormalities and complications are videofluoroscopic evidence of delayed oral transit, a delayed or absent swallow reflex, and penetration. These findings require validation in other studies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2001
DOI: 10.1097/00041552-200105000-00013
Abstract: In the past year, evidence from epidemiological studies in patients with renal disease has confirmed associations between both elevated plasma total homocysteine concentrations and the inflammatory marker C-reactive protein with an increased risk of arteriosclerotic vascular disease. However, it remains to be determined whether lowering total homocysteine or reducing inflammation will prevent 'hard' clinical outcome events such as stroke, myocardial infarction, and vascular death. Randomized trials of homocysteine lowering are currently ongoing and should further clarify the nature of the observed association between elevated total homocysteine and cardiovascular risk in patients with or without renal disease, and whether it is causal and modifiable. There are currently no known therapeutic interventions that specifically lower C-reactive protein levels in in iduals or the prevalence of elevated C-reactive protein in the population but randomized trials of anti-inflammatory therapy (e.g. using selective cyclo-oxygenase-2 inhibitors) aimed at preventing cardiovascular disease are currently being planned.
Publisher: Public Library of Science (PLoS)
Date: 2013
Publisher: Wiley
Date: 12-1994
Publisher: Springer Science and Business Media LLC
Date: 06-2009
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.MATURITAS.2012.06.007
Abstract: To determine the relationship between high total homocysteine (tHcy) and self-perceived physical health, by investigating the associations between tHcy, the methylenetetrahydrofolate reductase (MTHFR) 677T polymorphism and physical health-related quality of life (HRQOL). We conducted a cross-sectional study using a cohort of 4248 community-dwelling men aged 70-88 years. In addition to clinical determinants of physical health, tHcy was measured by immunoassay, the MTHFR 677T polymorphism was detected by a polymerase chain reaction (PCR)-based method, and physical HRQOL were assessed with the SF-36 Health Survey. In multiple regression analyses, the odds of being in the lowest quartile of the physical component summary (PCS) scores (i.e. <35) was 1.47 (95% CI 1.21-1.78) for men with high tHcy (≥15 μmol/l), after adjusting for age, smoking, history of hazardous alcohol use, polypharmacy, prevalent falls and weighted Charlson co-morbidity index. When history of hypertension, heart disease, stroke, arthritis and osteoporosis were included in place of the Charlson's index, the result was unchanged (OR 1.45, 95% CI 1.20-1.75). Men with the MTHFR TT homozygosity had significantly higher tHcy concentration than those with the CC genotype (mean difference of 1.38 μmol/l, 95% CI 0.77-1.99). However, there was no apparent association between the MTHFR polymorphism and PCS. Elevated tHcy is associated with poorer self-perceived physical health in community-dwelling older men. The results of this study support further longitudinal investigations to assess this relationship prospectively.
Publisher: SAGE Publications
Date: 29-09-2023
Publisher: Elsevier BV
Date: 05-2005
Publisher: Elsevier BV
Date: 07-2017
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000199463
Abstract: i Background: /i Homocysteine may promote atherosclerosis by exacerbating inflammatory processes within the arterial wall. B-vitamin supplements reduce total plasma homocysteine concentrations (tHcy), but it is not known whether the treatment also reduces arterial wall inflammation. We used sup /sup F-fluorodeoxygluose positron emission tomography ( sup /sup F-FDG PET) to investigate whether long-term homocysteine-lowering treatment alters arterial wall inflammation in patients with a history of ischemic stroke. i Methods: /i 30 stroke patients were randomly assigned to B-vitamin therapy (folic acid 2 mg, vitamin B sub /sub 25 mg and vitamin B sub /sub 0.5 mg) or placebo in a double-blind clinical trial. After a mean treatment period of 4.0 ± 0.7 years, all subjects had tHcy, carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery measured and underwent an sup /sup F-FDG PET scan. Standardised uptake values (SUV) were measured at six sites in the carotid, femoral and aortic arteries. Areas of locally increased tracer uptake in the arterial wall (‘hot spots’) were also identified and counted. i Results: /i Long-term B-vitamin treatment significantly reduced tHcy compared with placebo (8.4 μmol/l, 95% confidence interval, CI, 7.2–9.6 vs. 11.6 μmol/l, 95% CI 10.0–13.4, p = 0.002). The treatment did not affect mean arterial SUV (2.0 ± 0.3 vitamins vs. 2.1 ± 0.3 placebo, p = 0.65) or the number of hot spots (n = 1.1 ± 1.0 vitamins vs. n = 1.2 ± 1.0 placebo, p = 0.65). There was no significant correlation between mean arterial SUV and CIMT or FMD. i Conclusions: /i These results suggest that a long-term Hcy reduction with B vitamins does not affect arterial wall inflammation assessed by sup /sup F-FDG PET.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.MATURITAS.2011.11.022
Abstract: Frailty is a syndrome characterized by diminished ability to re-establish homeostasis in response to stress. We hypothesized that deficient allostatic responses to physiological challenges may predispose to frailty, that C-reactive protein (CRP) and its genetic determinants may be a measure of the integrity of the allostatic response, and that genetic determinants of the allostatic response determine the risk of frailty. Cross-sectional study of 3778 community-dwelling older men identified by random s ling of the Australian electoral roll. Explanatory variables included demographic, clinical, lifestyle behaviors, serum high-sensitivity CRP (hsCRP), and CRP 1444C>T and 1846G>A genotypes. These respective polymorphisms increase and decrease the basal concentration of hsCRP. The study outcome was frailty defined by a score of ≥4 on the FRAIL scale. The mean age of participants was 77.1 years (SD: 3.6) and frailty was present in 196 (5.2%). The serum concentration of hsCRP was higher in frail than non-frail men (p A gene (z=3.93, p A AA compared with GG genotypes. The CRP 1444C>T was not associated with frailty. Frail people have raised serum concentrations of CRP, presumably in response to the stress of underlying cause(s). However, frail in iduals carrying the CRP1846G>A polymorphism seem less able to mount an efficient allostatic response, which may underpin their increased odds of frailty.
Publisher: Public Library of Science (PLoS)
Date: 2010
Publisher: Wiley
Date: 10-06-2019
DOI: 10.1002/DMRR.3172
Abstract: We examined associations of ferritin and 25-hydroxyvitamin D with fasting glucose and prevalent diabetes in older men. Cross-sectional analysis of 4153 community-dwelling men aged 70 to 89 years in Western Australia. Plasma ferritin, 25-hydroxyvitamin D, and glucose were assayed. Diabetes was ascertained from self-report, medications, and fasting glucose. There were 577 men with diabetes (13.9%). In the whole cohort, ferritin was associated with fasting glucose (0.051 mmol/L per 1 SD increase in ferritin, P = .006) and 25-hydroxyvitamin D was inversely associated (-0.085 mmol/L per 1 SD, P 225 vs 82 nmol/L vs <53 nmol/L: OR = 0.57, 95% CI = 0.43-0.75, P < .001). There was no interaction between ferritin and vitamin D on diabetes risk. In older men, ferritin is associated with fasting glucose but not prevalent diabetes. Higher 25-hydroxyvitamin D concentrations are independently associated with lower fasting glucose and reduced risk of diabetes. Clinical trials are required to determine whether interventions, which raise vitamin D concentrations, would reduce incidence of diabetes in this expanding demographic group.
Publisher: Elsevier BV
Date: 09-2014
Publisher: Public Library of Science (PLoS)
Date: 2010
Publisher: Public Library of Science (PLoS)
Date: 2010
Publisher: Massachusetts Medical Society
Date: 20-12-2018
Publisher: Public Library of Science (PLoS)
Date: 2010
Publisher: Public Library of Science (PLoS)
Date: 2010
Publisher: BMJ
Date: 02-03-1991
Abstract: To determine the prognosis and adverse prognostic factors in patients with retinal infarction due to presumed atheromatous thromboembolism or cardiogenic embolism. Prospective cohort study. University hospital departments of clinical neurology. 99 patients with retinal infarction, without prior stroke, referred to a single neurologist between 1976 and 1986 and evaluated and followed up prospectively until death or the end of 1986 (mean follow up 4.2 years). Cerebral angiography (55 patients), aspirin treatment (37), oral anticoagulant treatment (eight), carotid endarterectomy (13), cardiac surgery (six), and peripheral vascular surgery (two). Death, stroke, coronary events, contralateral retinal infarction survival analysis confined to 98 patients with retinal infarction due to presumed artheromatous thromboembolism or cardiogenic embolism (one patient with giant cell arteries excluded), and Cox's proportional hazards regression analysis, including age as a prognostic factor. During follow up 29 patients died (21 of vascular causes and eight of non-vascular or unknown causes), 10 had a first ever stroke, 19 had a coronary event, and only one developed contralateral retinal infarction. A coronary event accounted for more than half (59%) of the deaths whereas stroke was the cause of only one death (3%). Over the first five years after retinal infarction the actuarial average absolute risk of death was 8% per year of stroke 2.5% per year (7.4% in the first year) of coronary events 5.3% per year, exceeding that of stroke and of stroke, myocardial infarction, or vascular death 7.4% per year. Prognostic factors associated with an increased risk of death were increasing age, peripheral vascular disease, cardiomegaly, and carotid bruit. Adverse prognostic factors for serious vascular events were increasing age and carotid bruit for stroke, and increasing age, cardiomegaly, and carotid bruit both for coronary events and for stroke, myocardial infarction, or vascular death. Patients who present with retinal infarction due to presumed atherothromboembolism or cardiogenic embolism are at considerable risk of a coronary event. The risk of stroke, although high, is not so great. Not all strokes occurring after retinal infarction relate directly to disease of the ipsilateral carotid system, although this is probably the most common cause. Few patients experience contralateral retinal infarction. Non-arteritic retinal infarction should be diagnosed or confirmed by an ophthalmologist, and the long term care of patients with the condition should involve a physician who has an active interest in managing vascular disease.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-03-2017
Publisher: Wiley
Date: 17-07-2018
DOI: 10.1002/GPS.4957
Abstract: Older adults living with bipolar disorder (BD) include people with early and late onset of symptoms. This study aimed to clarify the cross-sectional and longitudinal clinical associations of BD with early and late onset. Cohort study of 38 173 men aged 65-85 years followed for up to 17.6 years. We used the Western Australian Data Linkage System to establish the presence of BD, as well as diabetes, cardiovascular and renal diseases, cancer, respiratory and gastrointestinal diseases, alcohol use disorder, dementia, and mortality. The causes of death were recorded according to the International Classification of Diseases. We defined late onset BD using 2 different cut-points: 50 and 60 years. The prevalence of medical morbidities was greater among participants with than without BD, and cardiovascular diseases were more frequent among those with onset before than after 50 years (odds ratio = 1.72, 95% confidence interval = 1.01, 2.94). Bipolar disorder was associated with increased hazard ratio of dementia and death, but there was no difference between early and late onset participants. Death by suicide or accidents occurred exclusively among BD participants with illness onset <60 years, whereas death associated with strokes and neurodegenerative diseases was more frequent among those with illness onset ≥60 years than in the general population (HR = 2.28, 95% confidence interval = 1.34, 3.88). Our results indicate that the clinical associations and outcomes of older adults living with BD are not markedly influenced by age of onset. However, mortality data suggest that differences between older adults with BD onset before and after age 60 years should continue to be explored.
Publisher: JMIR Publications Inc.
Date: 18-11-2022
Abstract: any people with harmful addictive behaviors may not meet formal diagnostic thresholds for a disorder. A dimensional approach, by contrast, including clinical and community s les, is potentially key to early detection, prevention, and intervention. Importantly, while neurocognitive dysfunction underpins addictive behaviors, established assessment tools for neurocognitive assessment are lengthy and unengaging, difficult to administer at scale, and not suited to clinical or community needs. The BrainPark Assessment of Cognition (BrainPAC) Project sought to develop and validate an engaging and user-friendly digital assessment tool purpose-built to comprehensively assess the main consensus-driven constructs underpinning addictive behaviors. he purpose of this study was to psychometrically validate a gamified battery of consensus-based neurocognitive tasks against standard laboratory paradigms, ascertain test-retest reliability, and determine their sensitivity to addictive behaviors (eg, alcohol use) and other risk factors (eg, trait impulsivity). old standard laboratory paradigms were selected to measure key neurocognitive constructs (Balloon Analogue Risk Task [BART], Stop Signal Task [SST], Delay Discounting Task [DDT], Value-Modulated Attentional Capture [VMAC] Task, and Sequential Decision-Making Task [SDT]), as endorsed by an international panel of addiction experts namely, response selection and inhibition, reward valuation, action selection, reward learning, expectancy and reward prediction error, habit, and compulsivity. Working with game developers, BrainPAC tasks were developed and validated in 3 successive cohorts (total N=600) and a separate test-retest cohort (N=50) via Mechanical Turk using a cross-sectional design. rainPAC tasks were significantly correlated with the original laboratory paradigms on most metrics ( i r /i =0.18-0.63, i P /i & .05). With the exception of the DDT k function and VMAC total points, all other task metrics across the 5 tasks did not differ between the gamified and nongamified versions ( i P /i & .05). Out of 5 tasks, 4 demonstrated adequate to excellent test-retest reliability (intraclass correlation coefficient 0.72-0.91, i P /i & .001 except SDT). Gamified metrics were significantly associated with addictive behaviors on behavioral inventories, though largely independent of trait-based scales known to predict addiction risk. purpose-built battery of digitally gamified tasks is sufficiently valid for the scalable assessment of key neurocognitive processes underpinning addictive behaviors. This validation provides evidence that a novel approach, purported to enhance task engagement, in the assessment of addiction-related neurocognition is feasible and empirically defensible. These findings have significant implications for risk detection and the successful deployment of next-generation assessment tools for substance use or misuse and other mental disorders characterized by neurocognitive anomalies related to motivation and self-regulation. Future development and validation of the BrainPAC tool should consider further enhancing convergence with established measures as well as collecting population-representative data to use clinically as normative comparisons.
Publisher: Wiley
Date: 14-11-2012
Publisher: Wiley
Date: 26-11-2019
Publisher: Wiley
Date: 12-12-2019
DOI: 10.1111/FAF.12431
Publisher: Wiley
Date: 15-11-2021
Publisher: American Chemical Society (ACS)
Date: 12-1985
DOI: 10.1021/IC00220A014
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 04-2014
Publisher: BMJ
Date: 08-1992
Abstract: The aims of this study were to determine the important prognostic factors at presentation which identify patients with transient ischaemic attacks (TIA) who are at high risk (and low risk) of serious vascular events and to derive a prediction model (equation) for each of the major vascular outcome events. A cohort of 469 TIA patients referred to a University hospital, without prior stroke, were evaluated prospectively and followed up over a mean period of 4.1 years (range 1-10 years). The major outcome events of interest were 1) stroke 2) coronary event and 3) stroke, myocardial infarction or vascular death (whichever occurred first). Prognostic factors and their hazard ratios were identified by means of the Cox proportional hazards multiple regression analysis. The significant adverse prognostic factors (in order of strength of association) for stroke were an increasing number of TIAs in the three months before presentation, increasing age, peripheral vascular disease, left ventricular hypertrophy and TIAs of the brain (compared with the eye) the prognostic factors for coronary event were increasing age, ischaemic heart disease, male sex, and a combination of carotid and vertebrobasilar TIAs at presentation and for stroke, myocardial infarction or vascular death they were increasing age, peripheral vascular disease, increasing number of TIAs in the three months before presentation, male sex, a combination of carotid and vertebrobasilar TIAs at presentation, TIAs of the brain (compared with the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the presence of residual neurological signs after the TIA. Prediction models (equations) of both the relative risk and absolute risk of each of the major outcome events were produced, based on the presence or level of the significant prognostic factors and their hazard. Before it can be concluded that our equations accurately predict prognosis and can be generalised to other populations, their predictive power needs to be validated in other, independent s les of TIA patients (which we are currently doing).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2020
DOI: 10.1161/STROKEAHA.120.031707
Abstract: The risks of stroke and dementia increase steeply with age, and both are preventable. At present, the best way to preserve cognitive function is to prevent stroke. Therapeutic nihilism based on age is common and unwarranted. We address recent advances in stroke prevention that could contribute greatly to prevention of stroke and dementia at a time when the aging of the population threatens to markedly increase the incidence of both. Issues discussed: (1) old patients benefit even more from lipid-lowering therapy than do younger patients (2) patients with stiff arteries are at risk from a target systolic blood pressure mm Hg (3) the interaction of the intestinal microbiome, age, and renal function has important dietary implications for older adults (4) anticoagulation with direct-acting oral anticoagulants should be prescribed more to old patients with atrial fibrillation (5) B vitamins to lower homocysteine prevent stroke and (6) most old patients in whom intervention is warranted for carotid stenosis would benefit more from endarterectomy than from stenting. An 80-year-old person has much to lose from a stroke and should not have effective therapy withheld on account of age. Lipid-lowering therapy, a more plant-based diet, appropriate anticoagulation or antiplatelet therapy, appropriate blood pressure control, B vitamins to lower homocysteine, and judicious intervention for carotid stenosis could do much to reduce the growing burden of stroke and dementia.
Publisher: American College of Physicians
Date: 20-09-2016
Publisher: AMPCo
Date: 04-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-10-2008
DOI: 10.1161/CIRCULATIONAHA.108.768283
Abstract: Background— Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydro thromboxane B 2 concentrations, has been associated with an increased risk of cardiovascular events. We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B 2 concentrations that could thereby reduce cardiovascular risk. Methods and Results— Urinary 11-dehydro thromboxane B 2 concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been randomly assigned to placebo or clopidogrel. Baseline urinary 11-dehydro thromboxane B 2 concentrations in the highest quartile were associated with an increased risk of stroke, myocardial infarction, or cardiovascular death compared with the lowest quartile (adjusted hazard ratio 1.66, 95% CI 1.06 to 2.61, P =0.03). Increasing age, female sex, history of peripheral artery disease, current smoking, and oral hypoglycemic or angiotensin-converting enzyme inhibitor therapy were independently associated with higher urinary concentrations of 11-dehydro thromboxane B 2 , whereas aspirin dose ≥150 mg/d, history of treatment with nonsteroidal antiinflammatory drugs, history of hypercholesterolemia, and statin treatment were associated with lower concentrations. Randomization to clopidogrel (versus placebo) did not reduce the hazard of cardiovascular events in patients in the highest quartile of urinary 11-dehydro thromboxane B 2 levels. Conclusions— In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B 2 are an externally valid and potentially modifiable determinant of stroke, myocardial infarction, or cardiovascular death in patients at risk for atherothrombotic events.
Publisher: Elsevier BV
Date: 09-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-02-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1998
Abstract: Background and Purpose —Because of the enormity of the burden of stroke globally, there is a real need to develop strategies to reduce its impact. With this in mind, the World Health Organization (Division of Mental Health and Prevention of Substance Abuse) together with the National Stroke Foundation (Australia) sponsored the Asia Pacific Consensus Forum on Stroke Management in Melbourne, Australia, in October 1997. Representatives from the European Stroke Council, American Heart Association, Canadian Heart Association, Stroke Society of Australasia, and South-East Asian Stroke Association were involved, together with other delegates from Southeast Asia, Asia, North America, Europe, the Middle East, South Africa, and the subcontinent. Contributions from delegates allowed a broad set of principles to be put in place concerning stroke management that may be generalizable globally and with specific emphasis on the Asia Pacific region. Summary of Report —The Melbourne Declaration on Stroke Management of October 29, 1997, consisted of 9 key points made in the areas of primary prevention, acute stroke, secondary prevention, organization of stroke services, economic aspects, issues relating to developing countries, remote and rural areas, evaluation of quality of care, rehabilitation, and public health/education issues. Conclusions —The consensus statement embodied in the Melbourne Declaration provides a framework for countries to establish minimum standards of stroke care and thus make a contribution toward reducing the global burden of stroke.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Elsevier BV
Date: 02-2007
Publisher: Elsevier BV
Date: 02-2012
Publisher: The Endocrine Society
Date: 10-03-2020
Abstract: Whether androgens, distinct from estrogen, maintain bone health during male aging has implications for understanding osteoporosis. We assessed associations of different sex hormones with incidence of any bone fracture or hip fracture in older men. Analysis of 3307 community-dwelling men aged 76.8 ± 3.5 years, median follow-up period of 10.6 years. Plasma testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) assayed by mass spectrometry, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) using immunoassay. Incident fractures determined via data linkage. We analyzed probability of fracture and performed Cox regression adjusted for age, medical comorbidities, and frailty. Incident fractures occurred in 330 men, including 144 hip fractures. Probability plots suggested nonlinear relationships between hormones and risk of any fracture and hip fracture, with higher risk at lower and higher plasma T, lower E2, higher SHBG, and higher LH. In fully adjusted models, there was a U-shaped association of plasma T with incidence of any fracture (Quartile 2 [Q2] versus Q1: fully adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] 0.51–0.94, P = .020 Q3: HR 0.59, 95% CI 0.42–0.83, P = .002) and hip fracture (Q2 versus Q1: HR 0.60, 95% CI 0.37–0.93, P = .043 Q3: HR 0.52, 95% CI 0.31–0.88, P = .015). DHT, E2, and LH were not associated with fracture. Higher SHBG was associated with hip fracture (Q4 versus Q1: HR 1.76, 95% CI 1.05–2.96, P = .033). Midrange plasma T was associated with lower incidence of any fracture and hip fracture, and higher SHBG with increased risk of hip fracture. Circulating androgen rather than estrogen represents a biomarker for hormone effects on bone driving fracture risk.
Publisher: Elsevier BV
Date: 2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-04-2005
Publisher: Elsevier
Date: 2006
Publisher: Wiley
Date: 03-2012
DOI: 10.1002/BRB3.32
Publisher: BMJ
Date: 09-1994
Publisher: Elsevier BV
Date: 2017
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1445-5994.1993.TB01737.X
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder with no clear causative event making the disease difficult to diagnose and treat. The pathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and widespread neuronal loss. Amyloid-beta has been extensively studied and targeted to develop an effective disease-modifying therapy, but the success rate in clinical practice is minimal. Recently, neuroinflammation has been focused on as the event in AD progression to be targeted for therapies. Various mechanistic pathways including cytokines and chemokines, complement system, oxidative stress, and cyclooxygenase pathways are linked to neuroinflammation in the AD brain. Many cells including microglia, astrocytes, and oligodendrocytes work together to protect the brain from injury. This review is focused to better understand the AD inflammatory and immunoregulatory processes to develop novel anti-inflammatory drugs to slow down the progression of AD.
Publisher: Elsevier BV
Date: 06-1987
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2004
Publisher: SAGE Publications
Date: 11-05-2023
DOI: 10.1177/17474930231172312
Abstract: Anti-inflammatory therapy using colchicine has reduced recurrent vascular events in patients with coronary heart disease. Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3) is a randomized, double-blind, placebo-controlled multicenter trial, in which 8,238 patients with acute minor-to-moderate ischemic stroke (NIHSS ⩽ 5) or high-risk transient ischemic attack (TIA) (ABCD 2 score ⩾4) and a high-sensitivity CRP (hsCRP) level of ⩾2 mg/L will be randomly assigned within 24 h of symptom onset to colchicine (1 mg daily on days 1–3, followed by 0.5 mg daily for a total of 90 days) or matching placebo, on a background of optimal medical therapy. The study will have 90% power to detect a 25% reduction in the primary efficacy outcome of any stroke within 3 months of randomization. Adverse events potentially related to the use of colchicine will also be analyzed. The primary analysis will be by intention to treat. Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3) URL: t2/show/NCT05439356?cond=CHANCE-3& draw=2& rank=1 Registration number: NCT05439356.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-03-2015
Abstract: In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average in idual patient time in the therapeutic range ( iTTR ) of the international normalized ratio ( INR ), were associated with longer inter‐ INR test intervals. The standard R osendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard R osendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INR s (“corrections”) versus INR s that were out of range in the opposite direction (“overshoots”). In ROCKET AF , the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. TTR , the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. URL: ClinicalTrials.gov. Unique identifier: NCT00403767.
Publisher: SAGE Publications
Date: 19-04-2017
Abstract: Genome-wide association studies have identified several novel genetic loci associated with stroke risk, but how genetic factors influence stroke outcome is less studied. The Genetics of Ischaemic Stroke Functional outcome network aims at performing genetic studies of stroke outcome. We here describe the study protocol and methods basis of Genetics of Ischaemic Stroke Functional outcome. The Genetics of Ischaemic Stroke Functional outcome network has assembled patients from 12 ischaemic stroke projects with genome-wide genotypic and outcome data from the International Stroke Genetics Consortium and the National Institute of Neurological Diseases Stroke Genetics Network initiatives. We have assessed the availability of baseline variables, outcome metrics and time-points for collection of outcome data. We have collected 8831 ischaemic stroke cases with genotypic and outcome data. Modified Rankin score was the outcome metric most readily available. We detected heterogeneity between cohorts for age and initial stroke severity (according to the NIH Stroke Scale), and will take this into account in analyses. We intend to conduct a first phase genome-wide association outcome study on ischaemic stroke cases with data on initial stroke severity and modified Rankin score within 60–190 days. To date, we have assembled 5762 such cases and are currently seeking additional cases meeting these criteria for second phase analyses. Genetics of Ischaemic Stroke Functional outcome is a unique collection of ischaemic stroke cases with detailed genetic and outcome data providing an opportunity for discovery of genetic loci influencing functional outcome. Genetics of Ischaemic Stroke Functional outcome will serve as an exploratory study where the results as well as the methodological observations will provide a basis for future studies on functional outcome. Genetics of Ischaemic Stroke Functional outcome can also be used for candidate gene replication or assessing stroke outcome non-genetic association hypotheses.
Publisher: Oxford University Press (OUP)
Date: 26-06-2015
Publisher: John Wiley & Sons, Ltd
Date: 17-10-2007
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.APMR.2022.07.004
Abstract: People with aphasia have been systematically excluded from stroke research or included without the necessary modifications, threatening external study validity. In this paper, we propose that 1) the inclusion of people with aphasia should be considered as standard in stroke research irrespective of discipline and that 2) modifications should be made to stroke research procedures to support people with aphasia to achieve meaningful and valid inclusion. We argue that outright exclusion of this heterogenous population from stroke research based purely on a diagnosis of aphasia is rarely required and present a rationale for deliberate inclusion of people with aphasia in stroke research. The purpose of this paper is fourfold: 1) to highlight the issue and implications of excluding people with aphasia from stroke research 2) to acknowledge the current barriers to including people with aphasia in stroke research 3) to provide stroke researchers with methods to enable inclusion, including recommendations, resources, and guidance and 4) to consider research needed to develop aphasia inclusive practices in stroke research.
Publisher: Wiley
Date: 28-02-2002
DOI: 10.1002/ANA.10134
Publisher: Informa UK Limited
Date: 31-07-2016
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000324386
Abstract: i Background: /i A healthy, balanced diet can prevent stroke, but little is known about dietary risk factors for subarachnoid hemorrhage (SAH). We aimed to determine the relationship between common dietary habits and risk of SAH. i Methods: /i In a population-based, case-control study of SAH undertaken across 4 Australasian cities, a standardized questionnaire was used to obtain information on the frequency of consumption of 15 common food items and alcohol in incident cases (n = 383) and frequency-matched community controls (n = 473). Logistic regression models were used to estimate the independent effects of these dietary factors, after adjusting for conventional risk factors for SAH. Data are reported with odds ratios (OR) and 95% confidence intervals (CI). i Results: /i The risk of SAH rose with increasing consumption of fat or skin on meat (p trend = 0.04), being highest in those with consumption times weekly compared with no fat or skin on meat (adjusted OR 1.70, 95% CI 1.09–2.66), while use of skim or reduced-fat milk (p trend = 0.01) and fruit (p trend = 0.04) was associated with a reduced risk of SAH compared with rare use. Among people with a history of hypertension, frequently adding salt to food was associated with an increased risk of SAH, irrespective of whether they were (OR 2.58, 95% CI 1.29–5.13) or were not (OR 2.88, 95% CI 1.46–5.70) currently taking antihypertensive treatment. i Conclusions: /i Frequent intake of fat appears to be associated with an increased risk of SAH, particularly in people with hypertension, while frequent use of skim or reduced-fat milk and fruit appears protective for SAH.
Publisher: AMPCo
Date: 07-2011
DOI: 10.5694/J.1326-5377.2011.TB03180.X
Abstract: To assess the influence of area-level socioeconomic status (SES) on incidence and case-fatality rates for stroke. Analysis of pooled data for 3077 patients with incident stroke from three population-based studies in Perth, Melbourne, and Auckland between 1995 and 2003. Incidence and 12-month case-fatality rates for stroke. Annual age-standardised stroke incidence rates ranged from 77 per 100,000 person-years (95% CI, 72-83) in the least deprived areas to 131 per 100,000 person-years (95% CI, 120-141) in the most deprived areas (rate ratio, 1.70 95% CI, 1.47-1.95 P < 0.001). The population attributable risk of stroke was 19% (95% CI, 12%-27%) for those living in the most deprived areas compared with the least deprived areas. Compared with people in the least deprived areas, those in the most deprived areas tended to be younger (mean age, 68 v 77 years P < 0.001), had more comorbidities such as hypertension (58% v 51% P < 0.001) and diabetes (22% v 12% P < 0.001), and were more likely to smoke (23% v 8% P < 0.001). After adjustment for age, area-level SES was not associated with 12-month case-fatality rate. Our analysis provides evidence that people living in areas that are relatively more deprived in socioeconomic terms experience higher rates of stroke. This may be explained by a higher prevalence of risk factors among these populations, such as hypertension, diabetes and cigarette smoking. Effective preventive measures in the more deprived areas of the community could substantially reduce rates of stroke.
Publisher: Wiley
Date: 03-01-2022
DOI: 10.1002/ALZ.12529
Abstract: The association of testosterone concentrations with dementia risk remains uncertain. We examined associations of serum testosterone and sex hormone–binding globulin (SHBG) with incidence of dementia and Alzheimer's disease. Serum total testosterone and SHBG were measured by immunoassay. The incidence of dementia and Alzheimer's disease (AD) was recorded. Cox proportional hazards regression was adjusted for age and other variables. In 159,411 community‐dwelling men (median age 61, followed for 7 years), 826 developed dementia, including 288 from AD. Lower total testosterone was associated with a higher incidence of dementia (overall trend: P = .001, lowest vs highest quintile: hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.13‐1.81), and AD ( P = .017, HR = 1.80, CI = 1.21‐2.66). Lower SHBG was associated with a lower incidence of dementia ( P .001, HR = 0.66, CI = 0.51‐0.85) and AD ( P = .012, HR = 0.53, CI = 0.34‐0.84). Lower total testosterone and higher SHBG are independently associated with incident dementia and AD in older men. Additional research is needed to determine causality.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-06-2009
Publisher: Springer Netherlands
Date: 2000
Publisher: Elsevier BV
Date: 06-2012
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000334176
Publisher: Springer Science and Business Media LLC
Date: 08-2001
DOI: 10.1007/S00455-001-0069-5
Abstract: Swallowing impairment (dysphagia) is a frequent sequela of acute stroke however, the ability to accurately detect dysphagia at the bedside and predict which patients may be at risk of dysphagic complications, such as aspiration, remains limited. Despite this, clinical assessment batteries continue to be the first point of assessment for acute dysphagia. We examined the predictive value of clinical factors suggestive of swallowing dysfunction in an attempt to identify the important independent clinical signs at initial presentation that are associated with dysphagia, aspiration, and the combined variable aspiration and/or penetration (ASPEN) in acute stroke patients. For the purposes of this study, dysphagia was defined as a disorder of bolus flow. Aspiration was defined as entry of swallowed material below the level of the true vocal cords which was not expectorated. The clinical items identified as independent predictors of dysphagia (measured radiographically) at initial presentation were age > 70 years, male gender, disabling stroke (Barthel score < 60), palatal weakness or asymmetry, incomplete oral clearance, and impaired pharyngeal response (cough/gurgle). The clinical predictors of aspiration (determined radiographically) at initial presentation were delayed oral transit and incomplete oral clearance. Incorporating clinical signs, such as those identified by this study, into clinical assessments of swallowing impairment may increase their predictive utility.
Publisher: Elsevier BV
Date: 09-2001
Publisher: Public Library of Science (PLoS)
Date: 24-03-2015
Publisher: AMPCo
Date: 04-2003
Publisher: Taylor & Francis
Date: 2001
Publisher: Oxford University Press (OUP)
Date: 09-2002
Abstract: The effectiveness of organized inpatient (stroke unit) care has been demonstrated in systematic reviews of clinical trials. However, the key components of stroke unit care are poorly understood. We conducted a survey of recent trials (published 1985-2000) of a stroke unit/ward which had demonstrated a beneficial effect consistent with the stroke unit systematic review. We identified 11 eligible stroke unit trials of which the majority described similar approaches to i) assessment procedures (medical, nursing and therapy assessments), ii) early management policies (e.g. early mobilization avoidance of urinary catheterization treatment of hypoxia, hyperglycaemia and suspected infection), iii) ongoing rehabilitation policies (e.g. co-ordinated multidisciplinary team care, early assessment for discharge). This survey provides a description of stroke unit care which can serve as a benchmark for general stroke patient care and future clinical research.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.JSTROKECEREBROVASDIS.2015.12.018
Abstract: Mood disorders are frequent after stroke and are associated with poorer quality of life. Previous studies have reported conflicting results as to stroke subtype in the incidence of poststroke mood disorders. We explored the relationship between subcortical ischemic stroke subtype (lacunar) and presence of such symptoms at 1 year after stroke. Anonymized data were accessed from the Virtual International Stroke Trials Archive. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Depression and anxiety symptoms were assessed using Hospital Anxiety and Depression Scale. We investigated independent predictors of depression and anxiety symptoms using a logistic regression model. Data were available for 2160 patients. Almost one fifth of the patients developed both anxiety and depression at 1-year follow-up. After adjusting for confounders, the lacunar subtype was least associated with both anxiety (odds ratio [OR] = .61 95% confidence interval [CI] = .46-.80) and depression symptoms (OR = .71 CI = .55-.93) versus other stroke subtypes. Lacunar strokes have a weaker association with presence of anxiety and depression symptoms compared with other subtypes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2010
DOI: 10.1161/STROKEAHA.110.589218
Abstract: Background and Purpose— Although the stroke rate associated with atrial fibrillation has declined over the last 10 years, the emerging atrial fibrillation epidemic threatens to increase the incidence of cardioembolic stroke. Summary of Review— Oral anticoagulants are superior antithrombotic agents but are underused due to fear of bleeding and uncertainty about which patients will benefit. In idualized decisions on antithrombotic therapy require balancing the competing risks of thromboembolism and bleeding. The CHADS 2 (Congestive heart failure, Hypertension, Age years, and Diabetes mellitus, and 2 points for prior Stroke/transient ischemic attack) score and other schemes provide an estimate of thromboembolic risk however, the external validity of these estimates in the context of well-controlled risk factors, or a hypercoagulable state, is uncertain. Moreover, it is very difficult to estimate bleeding risk. Recent studies highlight the need for meticulous international normalized ratio control to achieve optimal outcomes h ered by the high bleeding risk during oral anticoagulant inception and other limitations of warfarin. Dabigatran is at least as efficacious as warfarin in preventing stroke and systemic embolism for patients in whom the risk of thromboembolism outweighs bleeding risk. In addition, the results of ongoing trials evaluating alternative anticoagulants such as oral anti-Xa agents are awaited. In this review, we discuss emerging therapies including available and completed trials of direct antithrombins and anti-Xa agents, including ximelagatran, idraparinaux, and dabigatran and new device therapies including left atrial appendage occlusion devices. Conclusions— In light of these promising new therapies, it is likely that atrial fibrillation thromboembolism guidelines will need to be rewritten and frequently updated.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-05-2018
Publisher: BMJ
Date: 19-05-2015
DOI: 10.1136/BMJ.H2568
Publisher: Elsevier BV
Date: 2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-02-2016
Publisher: Informa UK Limited
Date: 09-02-2022
Publisher: BMJ
Date: 09-06-1990
DOI: 10.1136/BMJ.300.6738.1485
Abstract: To determine the safest, least costly, and most effective way to select patients with symptomatic carotid ischaemic events for carotid angiography before carotid endarterectomy. Prospective cohort study. University departments of clinical neurosciences and clinical neurology. 485 Patients with carotid territory transient ischaemic attacks of the brain (n = 224) or eye (n = 162) or retinal infarction (n = 99) were referred to a single neurologist between 1976 and 1986. Clinical examination by auscultation over the precordium, supraclavicular fossae, and neck vessels (all patients). Cerebral angiography of patients suitable for carotid endarterectomy. Financial cost and number of disabling strokes after angiography. 296 Patients were investigated by cerebral angiography. Ischaemic symptoms had occurred in the distribution of 298 internal carotid arteries (symptomatic) that were imaged, two patients having bilateral symptoms. The presence or absence of a carotid bruit and the maximum percentage diameter stenosis of the origin of the symptomatic internal carotid artery were correlated. The prevalence of mild disease (diameter stenosis greater than or equal to 25%) of the symptomatic internal carotid artery was 57%, and if an ipsilateral carotid bruit was heard the probability of mild stenosis rose to 92%. The prevalence of moderate disease of the symptomatic internal carotid artery (stenosis greater than or equal to 50%) was 39%, and if a bruit was heard the probability doubled to 78%. The prevalence of severe internal carotid disease (stenosis greater than or equal to 75%) was 22%, and if a bruit was heard the probability was more than double, at 49%. The direct cost to both the NHS and the private health sector of investigating patients with symptomatic carotid ischaemia was estimated for several strategies of carotid artery imaging and expressed in terms of financial cost and number of strokes after angiography incurred in detecting all patients with diameter stenosis of the symptomatic internal carotid artery of greater than or equal to 25%, 50%, or 75%. To detect diameter stenosis of the internal carotid artery of greater than or equal to 25% it is most cost effective to proceed directly to cerebral angiography in patients with a carotid bruit over the symptomatic carotid bifurcation and to screen patients without a carotid bruit by duplex carotid ultrasonography patients in whom duplex ultrasonography discloses stenosis of greater than or equal to 25% are then referred for cerebral angiography. To detect only more severe internal carotid disease (stenosis of greater than or equal to 50%) the same policy applies, unless the local duplex ultrasonographic service is particularly efficient and reliable, when it is probably most cost effective and safer to screen all patients by this method irrespective of the findings on cervical auscultation. To detect stenosis of 75% or greater it is most cost effective to screen all patients with duplex ultrasonography, whether a carotid bruit is present or not, because this approach reduces the number of angiograms required, is the least expensive, and results in the least number of strokes after angiography. Patients selection for cerebral angiography before carotid endarterectomy needs to be appropriate and cost effective. Sound clinical evaluation and duplex carotid ultrasound are required. The findings of this study should not be applied to other medical centres without first considering possible differences in the prevalence of carotid artery disease, the efficiency and reliability of duplex ultrasonography, the local complication rates of cerebral angiography, and the local costs of the imaging procedures.
Publisher: Wiley
Date: 2018
DOI: 10.1002/CLC.22846
Publisher: SAGE Publications
Date: 06-07-2010
DOI: 10.1111/J.1747-4949.2010.00442.X
Abstract: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Recommendations of the Synergium are: : There is a need to develop: ( 1 ) New systems of working together to break down the prevalent ‘silo’ mentality ( 2 ) New models of vertically integrated basic, clinical, and epidemiological disciplines and ( 3 ) Efficient methods of identifying other relevant areas of science. : ( 1 ) Establish a global chronic disease prevention initiative with stroke as a major focus. ( 2 ) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. ( 3 ) Develop, implement and evaluate a population approach for stroke prevention. ( 4 ) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. : Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. : ( 1 ) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. ( 2 ) Standardize poststroke rehabilitation based on best evidence. ( 3 ) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. ( 4 ) Carry out rigorous clinical research to advance stroke recovery. :( 1 ) Work toward global unrestricted access to stroke-related information. ( 2 ) Build centralized electronic archives and registries. (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. by using a ***‘Brain Health’ concept that enables promotion of preventive measures. To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.
Publisher: Springer Science and Business Media LLC
Date: 13-06-2013
DOI: 10.1007/S11883-013-0344-6
Abstract: Three novel oral anticoagulants (NOACS)-dabigatran etexilate, rivaroxaban, and apixaban-have been approved in many countries for stroke prevention in atrial fibrillation, because they are associated with the same or lower rates of stroke, bleeding (particularly intracranially) and death compared with warfarin and unlike warfarin, they can be given in fixed doses without routine coagulation monitoring. The effects of NOACs compared with warfarin are consistent in almost all populations and patient subgroups studied. Pharmacoeconomic analyses indicate that the NOACs are also cost-effective in Europe and North America. The lack of an antidote to the NOACs in patients who experience major bleeding has not been associated with a worse outcome among patients treated with NOACs compared with warfarin in secondary analyses. Multiple guidelines for the management of AF now recommend the NOACs for stroke prevention among atrial fibrillation (AF) patients at risk for stroke.
Publisher: Elsevier BV
Date: 06-2015
Publisher: Springer Science and Business Media LLC
Date: 10-01-2022
DOI: 10.1038/S41398-021-01773-1
Abstract: Compulsivity is a poorly understood transdiagnostic construct thought to underlie multiple disorders, including obsessive-compulsive disorder, addictions, and binge eating. Our current understanding of the causes of compulsive behavior remains primarily based on investigations into specific diagnostic categories or findings relying on one or two laboratory measures to explain complex phenotypic variance. This proof-of-concept study drew on a heterogeneous s le of community-based in iduals ( N = 45 18–45 years 25 female) exhibiting compulsive behavioral patterns in alcohol use, eating, cleaning, checking, or symmetry. Data-driven statistical modeling of multidimensional markers was utilized to identify homogeneous subtypes that were independent of traditional clinical phenomenology. Markers were based on well-defined measures of affective processing and included psychological assessment of compulsivity, behavioral avoidance, and stress, neurocognitive assessment of reward vs. punishment learning, and biological assessment of the cortisol awakening response. The neurobiological validity of the subtypes was assessed using functional magnetic resonance imaging. Statistical modeling identified three stable, distinct subtypes of compulsivity and affective processing, which we labeled “Compulsive Non-Avoidant”, “Compulsive Reactive” and “Compulsive Stressed”. They differed meaningfully on validation measures of mood, intolerance of uncertainty, and urgency. Most importantly, subtypes captured neurobiological variance on amygdala-based resting-state functional connectivity, suggesting they were valid representations of underlying neurobiology and highlighting the relevance of emotion-related brain networks in compulsive behavior. Although independent larger s les are needed to confirm the stability of subtypes, these data offer an integrated understanding of how different systems may interact in compulsive behavior and provide new considerations for guiding tailored intervention decisions.
Publisher: Elsevier BV
Date: 05-2003
DOI: 10.1046/J.1538-7836.2003.00179.X
Abstract: Several polymorphisms of integrin alpha2beta1 and glycoprotein (GP) VI that may modify platelet-collagen interactions or subsequent signaling have been described. We conducted a case-control study involving 180 stroke patients and 172 controls to determine whether the alpha2 C807T and GPVI Q317L polymorphisms were associated with an increased risk of ischemic stroke. We found no statistically significant differences in the distribution of alpha2 C807T and GPVI Q317L in patients and controls overall or after stratification by etiological subtype. The GPVI 317QQ genotype was found to be over-represented in a subgroup of patients >/=60 years compared to corresponding controls. However, this association did not remain significant after adjustment for other cardiovascular risk factors. Our results do not support a role for the integrin alpha2 C807T and GPVI Q317L polymorphisms in the development of first-ever ischemic stroke. However, larger studies are required to confirm this.
Publisher: Elsevier BV
Date: 08-2013
Publisher: BMJ
Date: 14-06-2023
Abstract: Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage (aSAH) affects up to 7.2% of patients even with ultra-early treatment within 24 hours. We retrospectively compared the utility of three published re-bleed prediction models and in idual predictors between cases who re-bled matched to controls using size and parent vessel location from a cohort of patients treated in an ultra-early, ‘endovascular first’ manner. On retrospective analysis of our 9-year cohort of 707 patients suffering 710 episodes of aSAH, there were 53 episodes of pre-treatment re-bleeding (7.5%). Forty-seven cases who had a single culprit aneurysm were matched to 141 controls. Demographic, clinical and radiological data were extracted and predictive scores calculated. Univariate, multivariate, area under the receiver operator characteristic curve (AUROCC) and Kaplan–Meier (KM) survival curve analyses were performed. The majority of patients (84%) were treated using endovascular techniques at a median 14.5 hours post-diagnosis. On AUROCC analysis the score of Liu et al. had minimal utility (C-statistic 0.553, 95% confidence interval (CI) 0.463 to 0.643) while the risk score of Oppong et al. (C-statistic 0.645 95% CI 0.558 to 0.732) and the ARISE-extended score of van Lieshout et al. (C-statistic 0.53 95% CI 0.562 to 0.744) had moderate utility. On multivariate modeling, the World Federation of Neurosurgical Societies (WFNS) grade was the most parsimonious predictor of re-bleeding (C-statistic 0.740, 95% CI 0.664 to 0.816). For aSAH patients treated in an ultra-early timeframe matched on size and parent vessel location, WFNS grade was superior to three published models for re-bleed prediction. Future re-bleed prediction models should incorporate the WFNS grade.
Publisher: Elsevier BV
Date: 03-2013
Publisher: Oxford University Press (OUP)
Date: 12-05-2016
Publisher: AMPCo
Date: 1996
Publisher: Elsevier BV
Date: 08-2016
Publisher: American Chemical Society (ACS)
Date: 06-1985
DOI: 10.1021/IC00206A008
Publisher: Springer Science and Business Media LLC
Date: 02-2017
DOI: 10.1038/NATURE21039
Publisher: Oxford University Press (OUP)
Date: 12-2021
DOI: 10.1093/EURHEARTJ/EHAB738
Abstract: In INTERSTROKE, we explored the association of anger or emotional upset and heavy physical exertion with acute stroke, to determine the importance of triggers in a large, international population. INTERSTROKE was a case–control study of first stroke in 32 countries. Using 13 462 cases of acute stroke we adopted a case-crossover approach to determine whether a trigger within 1 hour of symptom onset (case period), vs. the same time on the previous day (control period), was associated with acute stroke. A total of 9.2% (n = 1233) were angry or emotional upset and 5.3% (n = 708) engaged in heavy physical exertion during the case period. Anger or emotional upset in the case period was associated with increased odds of all stroke [odds ratio (OR) 1.37, 99% confidence interval (CI), 1.15–1.64], ischaemic stroke (OR 1.22, 99% CI, 1.00–1.49), and intracerebral haemorrhage (ICH) (OR 2.05, 99% CI 1.40–2.99). Heavy physical exertion in the case period was associated with increased odds of ICH (OR 1.62, 99% CI 1.03–2.55) but not with all stroke or ischaemic stroke. There was no modifying effect by region, prior cardiovascular disease, risk factors, cardiovascular medications, time, or day of symptom onset. Compared with exposure to neither trigger during the control period, the odds of stroke associated with exposure to both triggers were not additive. Acute anger or emotional upset was associated with the onset of all stroke, ischaemic stroke, and ICH, while acute heavy physical exertion was associated with ICH only.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.JAMDA.2021.09.033
Abstract: The recently developed Hospital Frailty Risk Score (HFRS) allows ascertainment of frailty from administrative data. We aimed to compare the HFRS against the widely used FRAIL Scale and Frailty Index. Population-based cohort study linked to Western Australian Hospital Morbidity Data Collection and Death Registrations. The Health in Men Study with frailty determined at Wave 2 (2001/2004), mortality in the 1-year period following Wave 2, and disability at Wave 3 (2008). Participants were 4228 community-based men aged ≥75 years, followed until Wave 3. We used multivariable regression to determine the association between each frailty measure and outcomes of length of stay (LOS), death, and disability. We also determined if the additional cases of frailty identified by one measure over the other was associated with these outcomes. Of 4228 men studied, the HFRS (n = 689) identified fewer men as frail than the FRAIL Scale (n = 1648) and Frailty Index (n = 1820). In the fully adjusted models, all 3 frailty measures were associated with longer LOS and mortality, whereas only the FRAIL Scale and Frailty Index were significantly associated with disability. The additional cases of frailty identified by the FRAIL Scale and Frailty Index had longer LOS and greater risks of death and disability. The fully adjusted hazard ratio for death among the additional cases of frailty identified by the FRAIL Scale (compared to being not frail on both HFRS and FRAIL Scale) was 2.14 (95% CI 1.48-3.08). The HFRS is associated with adverse outcomes. However, it identified approximately 60% fewer men who were frail than the FRAIL Scale and Frailty Index, and the additional cases identified were also at high risks of adverse outcomes. Users of the HFRS should be aware of the differences with other frailty measures.
Publisher: Elsevier BV
Date: 07-2008
Publisher: BMJ
Date: 02-2009
Publisher: Elsevier BV
Date: 03-2019
Publisher: American College of Physicians
Date: 20-08-2019
Publisher: Wiley
Date: 08-1992
Abstract: Electrically stimulated 5-hydroxytryptamine (5-HT) release was monitored in slices of rat dorsal raphé nucleus (DRN) by fast cyclic voltammetry. Pseudo-single pulse stimulations (5 pulses at 100 Hz) were used to enable the effect of various receptor agonists to be seen without competition from endogenously released transmitter. The selective 5-HT1A receptor agonist, (+)-8-OH-DPAT (1.0 microM) decreased stimulated 5-HT release to 31 +/- 3% of controls. This decrease was inhibited by the 5-HT1A receptor antagonists, (+)-WAY-100135 (1.0 microM) and WAY-100635 (0.1 microM) but not by the 5-HT1D/B antagonist, GR127935 (0.05 microM). The selective 5-HT1B receptor agonist, CP-93129 (0.3 microM) decreased stimulated 5-HT release to 61 +/- 4% of control. This effect was antagonized by the 5-HT1B receptor antagonist, isamoltane (0.5 microM) but not by (+)-WAY-100135. The 5-HT1D agonist, sumatriptan (0.5 microM) decreased stimulated 5-HT release to 52 +/- 2% of controls. This decrease was blocked by GR-127935 but not by WAY-100635. These results suggest that 5-HT release in the rat DRN is under the control of 5-HT1A, 5-HT1B and 5-HT1D autoreceptors.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2006
Publisher: Elsevier BV
Date: 05-2012
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.AHJ.2009.11.025
Abstract: Atrial fibrillation (AF), the most common significant cardiac arrhythmia, increases the risk of stroke, particularly in the elderly. Warfarin is effective in reducing stroke risk but is burdensome to patients and is difficult to control. Rivaroxaban is an oral direct factor Xa inhibitor in advanced development as an alternative to warfarin for the prevention and treatment of thromboembolic disorders. ROCKET AF is a randomized, double-blind, double-dummy, event-driven trial, which aims to establish the noninferiority of rivaroxaban compared with warfarin in patients with nonvalvular AF who have a history of stroke or at least 2 additional independent risk factors for future stroke. Patients are randomly assigned to receive rivaroxaban, 20 mg once daily (od), or dose-adjusted warfarin titrated to a target international normalized ratio (INR) of 2.5 (range 2.0-3.0, inclusive) using point-of-care INR devices to receive true or sham INR values, depending on the study drug allocation. The primary efficacy end point is a composite of all-cause stroke and noncentral nervous system systemic embolism. The primary safety end point is the composite of major and clinically relevant nonmajor bleeding events. Over 14,000 patients have been randomized at 1,100 sites across 45 countries, and will be followed until 405 primary outcome events are observed. The ROCKET AF study will determine the efficacy and safety of rivaroxaban as an alternative to warfarin for the prevention of thromboembolism in patients with AF.
Publisher: AMPCo
Date: 03-1995
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000215936
Abstract: i Background: /i Optimal treatment of carotid stenosis in patients not suitable for surgery is unclear. The Carotid and Vertebral Artery Transluminal Angioplasty study contained a trial comparing medical and endovascular treatment in patients not suitable for surgery. i Methods: /i Forty patients were randomised to medical or endovascular treatment in equal numbers, and patients were followed up for up to 10 years. The primary outcome measure was defined as stroke or death during follow-up, analysed by intention-to-treat. Secondary analyses included disabling stroke, death, any stroke, any stroke or transient ischemic attack (TIA), all during follow-up. i Findings: /i Baseline characteristics were similar. The risk of stroke, retinal infarction or death within 30 days of endovascular treatment was 5% (95% CI: 0.1–24.9%). By the study end, % of patients had suffered a recurrent TIA, stroke or died. One third of events were non-stroke deaths. Overall, there was no significant difference between medical and endovascular treatment in the primary outcome rate of stroke or death after randomisation (hazard ratio: 0.98, 95% CI: 0.39–2.48) or the rate of any stroke or TIA (hazard ratio: 1.43, 95% CI: 0.54–3.75). i Interpretation: /i We failed to show superiority of endovascular treatment above medical care alone for carotid stenosis in a very small group of patients not suitable for surgical treatment. However, the trial randomised only 40 patients, and was therefore severely underpowered to detect clinically relevant treatment differences. Ongoing trials of carotid stenting will need to demonstrate improved safety and efficacy before endovascular treatment should enter routine practice.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-12-2015
Publisher: Elsevier BV
Date: 10-2020
Publisher: Oxford University Press (OUP)
Date: 06-2008
DOI: 10.1530/EJE-07-0893
Abstract: Reduced circulating testosterone and sex hormone-binding globulin (SHBG) are implicated as risk factors for metabolic syndrome. As SHBG increases with age while testosterone declines, we examined the relative contributions of SHBG and testosterone to the risk of metabolic syndrome in older men. We conducted a cross-sectional study of 2502 community-dwelling men aged ≥70 years without known diabetes. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Early morning fasting sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. There were 602 men with metabolic syndrome (24.1%). The risk of metabolic syndrome increased for total testosterone nmol/l, SHBG nmol/l and free testosterone pmol/l. In univariate analyses SHBG was associated with all five components of metabolic syndrome, total testosterone was associated with all except hypertension, and free testosterone was associated only with waist circumference and triglycerides. In multivariate analysis, both total testosterone and especially SHBG remained associated with metabolic syndrome, with odds ratios of 1.34 (95% confidence interval (CI): 1.18–1.52) and 1.77 (95% CI: 1.53–2.06) respectively. Men with hypogonadotrophic hypogonadism (total testosterone nmol/l, LH ≤12 IU/l) had the highest prevalence of metabolic syndrome (53%, P .001). Lower SHBG is more strongly associated with metabolic syndrome than lower total testosterone in community-dwelling older men. SHBG may be the primary driver of these relationships, possibly reflecting its relationship with insulin sensitivity. Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men.
Publisher: Elsevier BV
Date: 05-2005
Publisher: BMJ
Date: 08-1987
Abstract: Low-voltage-activated (T-type) calcium channels are responsible for burst firing and transmitter release in neurons and are important for exocytosis and hormone secretion in pituitary cells. T-type channels contain an alpha1 subunit, of which there are three subtypes, Cav3.1, -3.2, and -3.3, and each subtype has distinct kinetic characteristics. Although 17beta-estradiol (E2) modulates T-type calcium channel expression and function, little is known about the molecular mechanisms involved. We used real-time PCR quantification of RNA extracted from hypothalamic nuclei and pituitary in vehicle and E2-treated C57BL/6 mice to elucidate E2-mediated regulation of Cav3.1, -3.2, and -3.3 subunits. The three subunits were expressed in both the hypothalamus and the pituitary. E2 treatment increased the mRNA expression of Cav3.1 and -3.2, but not Cav3.3, in the medial preoptic area and the arcuate nucleus. In the pituitary, Cav3.1 was increased with E2 treatment, and Cav3.2 and -3.3 were decreased. To examine whether the classical estrogen receptors (ERs) were involved in the regulation, we used ERalpha- and ERbeta-deficient C57BL/6 mice and explored the effects of E2 on T-type channel subtypes. Indeed, we found that the E2-induced increase in Cav3.1 in the hypothalamus was dependent on ERalpha, whereas the E2 effect on Cav3.2 was dependent on both ERalpha and ERbeta. However, the E2-induced effects in the pituitary were dependent on only the expression of ERalpha. The robust E2 regulation of T-type calcium channels could be an important mechanism by which E2 increases the excitability of hypothalamic neurons and modulates pituitary secretion.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.JAMDA.2014.10.023
Abstract: Depression is associated with increased mortality, but it is unclear if this relationship is truly causal. To determine the relative mortality associated with past and current depression, taking into account the effect of frailty. Prospective longitudinal cohort study of 2565 men aged 75 years or over living in metropolitan Perth, Western Australia, who completed the third wave of assessments of the Health In Men Study throughout 2008. All-cause mortality data were derived from Australian death records up to June 17, 2013. History of past depression and age of onset of symptoms were obtained from direct questioning and from electronic health record linkage. Diagnosis of current major depressive symptoms followed Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision guidelines. We considered that participants were frail if they showed evidence of impairment in 3 or more of the 5 domains on the fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale. Other measured factors included age, education, living arrangements, smoking and alcohol history, and physical activity. 558 participants died during mean period of follow-up of 4.2 ± 1.1 years. The annual death rate per thousand was 50 for men without depression, 52 for men with past depression, and 201 for men with major depressive symptoms at baseline. The crude mortality hazard was 4.26 (95% confidence interval = 2.98, 6.09) for men with depression at baseline compared with never depressed men, and 1.79 (95% confidence interval = 1.21, 2.62) after adjustment for frailty. Further decline in mortality hazard was observed after adjustment for other measured factors. Current, but not past, depression is associated with increased mortality, and this excess mortality is strongly associated with frailty. Interventions designed to decrease depression-related mortality in later life may need to focus on ameliorating frailty in addition to treating depression.
Publisher: Cambridge University Press (CUP)
Date: 22-03-2019
DOI: 10.1017/S003329171800065X
Abstract: Recent research has identified several potentially modifiable risk factors for dementia, including mental disorders. Psychotic disorders, such as schizophrenia and delusional disorder, have also been associated with increased risk of cognitive impairment and dementia, but currently available data difficult to generalise because of bias and confounding. We designed the present study to investigate if the presence of a psychotic disorder increased the risk of incident dementia in later life. Prospective cohort study of a community-representative s le of 37 770 men aged 65–85 years who were free of dementia at study entry. They were followed for up to 17.7 years using electronic health records. Clinical diagnoses followed the International Classification of Diseases guidelines. As psychotic disorders increase mortality, we considered death a competing risk. A total of 8068 (21.4%) men developed dementia and 23 999 (63.5%) died during follow up. The sub-hazard ratio of dementia associated with a psychotic disorder was 2.67 (95% CI 2.30–3.09), after statistical adjustments for age and prevalent cardiovascular, respiratory, gastrointestinal and renal diseases, cancer, as well as hearing loss, depressive and bipolar disorders, and alcohol use disorder. The association between psychotic disorder and dementia risk varied slightly according to the duration of the psychotic disorder (highest for those with the shortest illness duration), but not the age of onset. No information about the use of antipsychotics was available. Older men with a psychotic disorder have nearly three times greater risk of developing dementia than those without psychosis. The pathways linking psychotic disorders to dementia remain unclear but may involve mechanisms other than those associated with Alzheimer's disease and other common dementia syndromes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-11-2022
DOI: 10.1161/CIRCULATIONAHA.122.060700
Abstract: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Observational analyses were conducted using in idual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values or mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR mL·min –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2008
DOI: 10.1161/STROKEAHA.107.493643
Abstract: Background and Purpose— We studied temporal trends in major stroke outcomes in Perth, Western Australia (WA), comparing 3 12-month periods, roughly 5 years apart, between 1989 and 2001. Methods— The Perth Community Stroke Study (PCSS) used uniform definitions and procedures in a representative segment (approximately 143 000 people in the year 2000) of Perth, WA. Crude and age-standardized incidence and 28-day case fatality for stroke in the different study periods were compared using Poisson regression. We also undertook temporal comparisons of severity, risk factors, and management of stroke to define the basis for any changes in rates. Data are reported with 95% confidence intervals (CI). Results— There were 251, 213, and 183 first-ever strokes identified in the first, second, and third study periods, respectively, reflecting significant declines in stroke rates overall, for major age groups, and for both ischemic stroke and intracerebral hemorrhage. The decline in rates was greater in men than women. Compared with the 1989 to 1990 period, sex- and age-adjusted rates declined by 25% (95% CI 10% to 37%) in 1995 to 1996, and by 43% (95% CI 31% to 53%) in 2000 to 2001, corresponding to a 5.5% average annual decrease overall. There were correspondingly significant reductions in the frequencies of key risk factors among cases. However, early case fatality remained stable, both overall and for major pathological subtypes of stroke. Conclusions— These data confirm significant declines in the incidence of stroke on the western side of Australia, coincident with some improvement in the vascular risk profile of cases in the population. Decreasing risk rather than improving survival appears to be the main driver of falling mortality from stroke in this population.
Publisher: Elsevier BV
Date: 04-03-2005
Publisher: American College of Physicians
Date: 16-08-2016
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.PSYNEUEN.2018.08.013
Abstract: Low circulating testosterone has been associated with dementia in older men but existing evidence from prospective studies is inconsistent. We conducted a prospective longitudinal study of 4069 community-dwelling older men free of dementia aged 71-88 years at baseline. The main objective of the study was to determine if men with low circulating sex hormones were more likely to develop dementia over time. The main biochemical exposures of interest were collected at baseline between 2001 and 2004 and men were assessed for incident dementia via an electronic health records database to the 31 st of December 2013. Dementia developed in 499 men over a median of 10.5 years (range 9.4-12.2 years). The risk of developing dementia increased with decreasing total (hazard ratio [HR] 1.14, 95% confidence interval [95%CI] 1.03-1.26 per standard deviation decrease) and calculated free testosterone (HR 1.18, 95%CI 1.06-1.31 per standard deviation decrease) after adjustment for age, baseline cognitive function, depression, body mass, hypertension, cardiovascular disease and total plasma homocysteine. Men in the lowest quartiles of total (adjusted HR 1.39, 95%CI 1.04-1.85) and calculated free testosterone (adjusted HR 1.43, 95%CI 1.08-1.90) had increased risk of developing dementia compared to those in the highest quartiles. Lower plasma total and calculated free testosterone were associated with increased risk of developing dementia independent of relevant measured clinical and biochemical factors and was not explained due to differential mortality in those with lower testosterone levels. The association between low testosterone and dementia is biologically plausible but data on the role of testosterone treatment in preventing dementia is lacking and adequately powered trials in men at risk would be welcome.
Publisher: AMPCo
Date: 02-1987
DOI: 10.5694/J.1326-5377.1987.TB120158.X
Abstract: The aim of the present study was to assess the feasibility of identifying the primary hand sensory area and central sulcus in pediatric patients using the cortical potential imaging (CPI) method from the scalp recorded somatosensory evoked potentials (SEPs). The CPI method was used to reconstruct the cortical potential distribution from the scalp potentials with the boundary element (3-layer: scalp, skull and brain) head model based on MR images of in idual subjects. The cortical potentials estimated from the pre-operative scalp SEPs of four pediatric patients, were compared with the post-op subdural SEP recordings made in the same subjects. Estimated and directly recorded cortical SEP maps showed comparable spatial patterns on the cortical surface in four patients (spatial correlation coefficient >0.7 in the SEP spikes). For two of four patients, the estimated waveforms correlated significantly to the waveforms obtained by direct cortical recordings. The present results demonstrated the feasibility of the cortical potential imaging approach in noninvasive imaging spatial distribution and temporal waveforms of cortical potentials for pediatric patients. These also suggest that the CPI method may provide a promising means of estimating the cortical potential and noninvasive localizing the central sulcus to aid surgical planning for pediatric patients.
Publisher: American Medical Association (AMA)
Date: 03-2008
DOI: 10.1001/ARCHGENPSYCHIATRY.2007.33
Abstract: Serum concentrations of gonadal hormones have been associated with various measures of well-being, but it is unclear whether their association with mood is confounded by concurrent physical morbidity. To determine whether the association between serum testosterone concentration and mood in older men is independent of physical comorbidity. Cross-sectional study. Community of Perth, Western Australia. A community s le of men aged 71 to 89 years. We used the 15-item Geriatric Depression Scale (GDS-15) to assess depressed mood. Clinically significant depression was defined a priori as a GDS-15 score of 7 or greater. Physical health was assessed using the weighted Charlson index and the Physical Component Summary score of the 36-Item Short Form Health Survey. Of 3987 men included in the study, 203 (5.1% 95% confidence interval [CI], 4.4%-5.8%) had depression. Participants with depression had significantly lower total and free testosterone concentrations than nondepressed men (P < .001 for both). However, they were also more likely to smoke and to have low educational attainment, a body mass index categorized as obese, a Mini-Mental State Examination score less than 24, a history of antidepressant drug treatment, and greater concurrent physical morbidity. After adjusting for these factors and for age, men with depression were 1.55 (95% CI, 0.91-2.63) and 2.71 (95% CI, 1.49-4.93) times more likely to have total and free testosterone concentrations, respectively, in the lowest quintile. A free testosterone concentration in the lowest quintile is associated with a higher prevalence of depression, and this association cannot be adequately explained by physical comorbidity. A randomized controlled trial is required to determine whether the link between low free testosterone level and depression is causal because older men with depression may benefit from systematic screening of free testosterone concentration and testosterone supplementation.
Publisher: SAGE Publications
Date: 11-04-2016
Abstract: Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation ( n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years ( p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. This cross-sectional global s le of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.3382/PS/PEU070
Abstract: Feed production with different milling methods, thermal treatment, and particle size may influence mineral digestibility and retention in eggs. The present study investigated the impact of roller (R) and hammer (H) mills, mash (M) and expandate (E) with fine (F) and coarse (C) particle sizes, on apparent ileal absorption (AIA) and apparent total digestibility (ATD) and retention of calcium, phosphorus, magnesium, zinc, manganese, copper and iron in yolk, albumen, and shell. A total of 384 hens (Lohmann Brown), 19 weeks old, were assigned using a randomized design with a 2×2×2 factorial arrangement. Eight experimental diets were offered ad libitum during the whole experimental period and one week before for diet adaption. The AIA of magnesium, zinc, copper, and iron was higher in treatment R in comparison with treatment H (P<0.01, P≤0.03, P<0.01 and P<0.01, respectively). The AIA of magnesium was higher in treatment M than treatment E (P<0.01). The AIA of magnesium was higher in treatment C in comparison with treatment F (P≤0.05) due to particle size. The ATD of copper and iron was higher in treatment R than treatment H (P<0.01 and P≤0.03, respectively). The ATD was higher for phosphorus and lower for iron in treatment F than treatment C (P≤0.05 and P≤0.02. respectively). The copper concentration in yolk and albumen was higher in treatment C than treatment F (P<0.01 and P≤0.03, respectively). Besides a few overall interactions, the AIA and ATD of copper and manganese were lower in H+M group than R+M group (P≤0.05). The ATD of iron was higher in the M+C group compared to the M+F group (P<0.01), whereas the albumen zinc concentration was higher in the E+C group than E+F group (P < 0.01). In conclusion, the feed produced by hammer mill had negative effects on AIA and ATD for trace elements in particular, but mineral concentrations in egg contents were mostly comparable for all treatments. Therefore, milling methods, thermal treatment, and particle sizes used in the present study can be used for layer feed formulation without negatively affecting egg quality.
Publisher: Wiley
Date: 04-2008
DOI: 10.1111/J.1445-5994.1994.TB00551.X
Abstract: Stroke is a devastating complication of cardiopulmonary bypass (CPB) surgery which occurs in 1 to 5% of cases. Strategies to reduce its incidence require a knowledge of the underlying pathology and aetiology. To determine the incidence, pathology and aetiology of stroke complicating CPB. Prospective review of clinical, operative and cranial CT scan findings in all cases of stroke complicating CPB procedures in our institution over an 18 month period. Twenty-one (1.6%, 95% CI 0.9-2.3%) cases of stroke were identified from 1336 CPB procedures. Cranial CT scan, performed in all but one patient, was normal in three patients or consistent with ischaemic stroke in 17 patients. There were no cases of haemorrhagic infarction or intracerebral haemorrhage. It was difficult to differentiate embolic and borderzone infarcts in two cases. After considering the clinical, operative and CT scan features together, 12 (57%, 95% CI 36-78%) of the cases were felt to be embolic in origin and nine (43%, 95% CI 22-64%) due to hypoperfusion in a borderzone. This study demonstrates that stroke remains an important complication of CPB procedures with an incidence in our series of 1.6%. The pathologic type of stroke is predominantly ischaemic in nature due to either cerebral embolism or borderzone infarction. Strategies for stroke prevention in patients undergoing CPB should be targeted primarily at these two mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2018
DOI: 10.1038/MP.2017.152
Abstract: Insulin-like growth factor 1 (IGF-1) influences cell proliferation and survival. In the extracellular environment, IGF-1 circulates bound to proteins (IGF-binding proteins IGFBP), some of which have physiological effects that seem independent of IGF-1, including the brain (for ex le, IGFBP-3). We completed a systematic review of the association between dementia and IGF-1 and IGFBP-3, and a cross-sectional and longitudinal study designed to investigate if lower plasma concentration of these proteins increased the risk of prevalent and incident dementia. A total of 3967 men aged 71-89 years joined the study, of whom 535 (13.5%) showed evidence of prevalent cognitive impairment. The plasma concentrations of IGF-1 and IGFBP-3 were similar for men with and without cognitive impairment. The 3432 men free of cognitive impairment were then followed for up to 13 years. During this time 571 (16.6%) developed dementia. The plasma concentration of IGF-1 had no association with incident dementia. The doubling of the plasma concentration of IGFBP-3 decreased the hazard ratio of dementia by 23% (95% confidence interval=5-37%). The results were not affected by age, body mass index and history of smoking, diabetes, hypertension, coronary heart disease or stroke. If these findings are confirmed by others, the plasma concentration of IGFBP-3 could be used to improve the accuracy of predictive models of dementia and as a potential new factor to assist in the development of prevention and treatment strategies.
Publisher: BMJ
Date: 16-12-2008
Publisher: Elsevier BV
Date: 02-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-1990
Abstract: We review the eight prospective and seven retrospective studies from which it is possible to derive the complication rate of conventional cerebral angiography for patients with mild ischemic cerebrovascular disease who are potential candidates for carotid endarterectomy. Three studies of intravenous and one of intra-arterial digital subtraction angiography are also examined. An overview of the results suggests that the risk of a neurological complication (TIA or stroke) is about 4% and that a permanent neurological deficit (disabling stroke) occurs in about 1%. The mortality rate is very low (less than 0.1%). Systemic complications are not infrequent, particularly with intravenous digital subtraction angiography. The complication rate of cerebral angiography must be considered when evaluating the risks of carotid endarterectomy in patients with ischemic cerebrovascular disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-12-2017
Abstract: Understanding the relationship between body mass index (BMI) and vascular disease at older age has become increasingly important in the many countries where both average age and BMI are rising. In this prospective cohort study, 12 203 men (aged ≥65) were recruited in 1996–1999 from the general population in Perth, Australia. To limit reverse causality, analyses excluded those with past vascular disease and the first 4 years of follow‐up. During a further 8 (SD3) years of follow‐up, there were 1136 first‐ever major vascular events (nonfatal myocardial infarction, nonfatal stroke, or death from any vascular cause). Cox regression (adjusted for age, education, and smoking) related BMI at recruitment to incidence of major vascular events. At ages 65 to 94, the lowest risk of major vascular events was at ≈ 22.5 to 25 kg/m 2 . In the higher BMI range (≥25 kg/m 2 ), 5 kg/m 2 higher BMI was associated with 33% higher risk of major vascular events (hazard ratio, 1.33 [95% confidence interval, 1.18–1.49]): 24% higher risk of ischemic heart disease (1.24 [1.06–1.46]) 34% higher risk of stroke (1.34 [1.11–1.63]) and 78% higher risk of other vascular death (1.78 [1.32–2.41]). In the lower BMI range, there were fewer events and no strong evidence of an association (hazard ratio per 5 kg/m 2 higher BMI, 0.82 [95% confidence interval, 0.61–1.12]). In this population of older men, risk of major vascular events was lowest at ≈ 22.5 to 25 kg/m 2 . Above this range, BMI was strongly related to incidence of major vascular events, with each 5 kg/m 2 higher BMI associated with ≈30% higher risk.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1111/J.1538-7836.2011.04486.X
Abstract: Deep vein thrombosis (DVT) is an important complication of stroke, but the evidence to support commonly used prophylactic strategies is conflicting. To describe the incidence, extent, associated clinical features and evolution of DVT after stroke. The CLOTS trials 1 and 2 together randomized 5632 immobile stroke patients in 135 hospitals in nine countries. We screened patients for asymptomatic DVT with compression duplex ultrasound (CDU) at about 7-10 days and again at about 25-30 days after enrollment. Six hundred and forty-one (11.4%) of 5632 patients had DVT detected on the first CDU scan at a median of 8 days (interquartile range [IQR] 7-10 days) after enrollment, and an additional 176 (3.1%) had a DVT on the second CDU scan at a median of 28 days (IQR 26-30 days). Of the 817 with DVTs, 289 (35%) were symptomatic and 39 (5%) had pulmonary embolism (PE) confirmed by imaging. Six hundred and seventy-six (83%) were unilateral, 141 (17%) were bilateral, 322 (39%) were limited to calf veins, 172 (21%) were popliteal, and 323 (40%) were femoral. Among the 542 patients with DVT and a weak leg, the DVT affected the weaker leg in 396 (73%), the stronger leg in 59 (11%), and was bilateral in 87 (16%). Among the 318 patients with a DVT detected on the first CDU scan who had a second scan, the DVT regressed in 148 (47%), stayed the same in 140 (44%), and progressed in only 30 (9%). Although most DVTs develop within the first week, some develop later, and some early DVTs progress. Any prophylaxis needs to be started early but ideally continued for at least 4 weeks.
Publisher: Elsevier BV
Date: 02-2022
Publisher: BMJ
Date: 14-02-1998
DOI: 10.1136/BMJ.316.7131.628B
Abstract: A warming climate combined with frequent and severe fires cause permafrost to thaw, especially in the region of discontinuous permafrost, where soil temperatures may only be a few degrees below 0 °C. Soil thaw releases carbon (C) and nitrogen (N) into the actively cycling pools, and whereas C emissions following permafrost thaw are well documented, the fates of N remain unclear. Denitrification could release N from ecosystems as nitrous oxide (N
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.MATURITAS.2015.01.016
Abstract: Vitamin D deficiency has been associated with depression in later life, but it remains unclear whether this association is truly causal. Observational study examining the retrospective, cross-sectional and prospective associations between vitamin D concentration and depressed mood in a community-derived s le of 3105 older men living in metropolitan Perth, Western Australia. We measured the plasma concentration of 25-hydroxyvitamin D using standard procedures. Past depression was ascertained by direct questioning and through the use of administrative health data linkage. A geriatric depression scale score equal or greater 7/15 established the presence of current depression. Incident depression was established by a patient health questionnaire (PHQ-9) score ≥ 10 or by administrative health data linkage during the 6-year follow up (range 0.1-10.9 years). Vitamin D concentration <50 nmol/L was associated with greater odds of current (OR=1.65, 95% CI=1.13, 2.42) but not past depression (OR=1.15, 95% CI=0.83, 1.58). Of the 2740 men with no past or current history of depression, 81 developed clinically significant symptoms during follow up. The adjusted hazard ratio of incident depression for men with plasma vitamin D <50 nmol/L was 1.03 (95% CI=0.59, 1.79 adjusted for age, living arrangements, season, and prevalent cardiovascular diseases). Our results do not support a role for vitamin D in the causation of depression, although a small antidepressant effect of vitamin D cannot be entirely discarded. Large randomised placebo-controlled trials are required to dismiss or establish with certainty the causal link between vitamin D deficiency and depression.
Publisher: American College of Physicians
Date: 21-06-2016
Publisher: BMJ
Date: 09-2021
DOI: 10.1136/BMJOPEN-2020-045898
Abstract: Despite higher incidence of brain injury among Aboriginal compared with non-Aboriginal Australians, suboptimal engagement exists between rehabilitation services and Aboriginal brain injury survivors. Aboriginal patients often feel culturally insecure in hospital and navigation of services post discharge is complex. Health professionals report feeling ill-equipped working with Aboriginal patients. This study will test the impact of a research-informed culturally secure intervention model for Aboriginal people with brain injury. Design: Stepped wedge cluster randomised control trial design intervention sequentially introduced at four pairs of healthcare sites across Western Australia at 26-week intervals. Recruitment: Aboriginal participants aged ≥18 years within 4 weeks of an acute stroke or traumatic brain injury. Intervention: (1) Cultural security training for hospital staff and (2) local, trial-specific, Aboriginal Brain Injury Coordinators supporting participants. Primary outcome : Quality-of-life using EuroQOL-5D-3L (European Quality of Life scale, five dimensions, three severity levels) Visual Analogue Scale score at 26 weeks post injury. Recruitment of 312 participants is estimated to detect a difference of 15 points with 80% power at the 5% significance level. A linear mixed model will be used to assess the between-condition difference. Secondary outcome measures : Modified Rankin Scale, Functional Independence Measure, Modified Caregiver Strain Index, Hospital Anxiety and Depression Scale at 12 and 26 weeks post injury, rehabilitation occasions of service received, hospital compliance with minimum care processes by 26 weeks post injury, acceptability of Intervention Package, feasibility of Aboriginal Brain Injury Coordinator role. Evaluations : An economic evaluation will determine the potential cost-effectiveness of the intervention. Process evaluation will document fidelity to study processes and capture changing contexts including barriers to intervention implementation and acceptability/feasibility of the intervention through participant questionnaires at 12 and 26 weeks. The study has approvals from Aboriginal, university and health services human research ethics committees. Findings will be disseminated through stakeholder reports, participant workshops, peer-reviewed journal articles and conference papers. ACTRN12618000139279.
Publisher: Elsevier BV
Date: 07-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
DOI: 10.1161/STROKEAHA.113.004251
Abstract: Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2–3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P =0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36–1.61 P =0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P =0.013). Time in therapeutic range (67% of the time for international normalized ratio 2–3) analysis by tertiles showed no significant differences across groups. Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. URL: www.clinicaltrials.gov . Unique identifier: NCT00235248.
Publisher: Wiley
Date: 03-09-2008
DOI: 10.1111/J.1365-2265.2007.03055.X
Abstract: To determine the relationship of total and free serum testosterone to cognitive performance in older men. Cross-sectional study of a population-based s le. Participants A total of 2932 men aged 70-89 years. Cognitive function was assessed using the Standardized Mini-Mental State Examination (SMMSE). Early morning sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using the Vermeulen method. There were weak positive correlations between SMMSE score and serum free testosterone (Spearman's rho = 0.06, P = 0.001) and total testosterone (r = 0.04, P = 0.027), and a weak negative correlation with LH (r = -0.07, P or = 210 pmol/l was associated with reduced likelihood of poor cognitive performance on the SMMSE [odds ratio (OR) 0.71, 95% confidence interval (CI) 0.52-0.97]. In community-dwelling older men, serum free testosterone > or = 210 pmol/l is associated with better cognitive performance. In this context, calculated free testosterone seems to be a more informative measure of androgen status than total testosterone. Studies examining the contribution of androgens to age-related cognitive decline should incorporate an assessment of free testosterone concentration.
Publisher: Future Medicine Ltd
Date: 07-2014
DOI: 10.2217/FNL.14.30
Abstract: ABSTRACT: The global burden of stroke is large. Over the last 15 years significant advances have been made to improve acute stroke care and prevention management providing the ability to mitigate much of this burden. In this article, we describe the importance of two main elements of stroke care: stroke units to reduce death and disability and anticoagulation therapy to prevent recurrent, often fatal or disabling, cardioembolic stroke. We also describe the issues related to translating these interventions into practice and the related economic implications. Despite the proven effectiveness and cost–effectiveness of these and other interventions, many people experiencing stroke are not receiving these interventions. Effective evidence translation initiatives and routine monitoring of healthcare is needed to address important gaps in stroke management in promoting societal well-being.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JOCN.2016.09.011
Abstract: We previously reported on a 26-year-old patient who presented early during a large and eventually fatal cerebral infarct. Microarray analysis of blood s les from this patient demonstrated initially up-regulated and subsequently down-regulated Granzyme B (GzmB) expression, along with progressive up-regulation of genes for S100 calcium binding protein A12 (S100A12) and matrix metalloproteinase 9 (MMP-9). To confirm these findings, we investigated these parameters in patients with suspected stroke presenting within 6h of symptom onset to a single centre. Blood s les were taken at enrolment, then 1h, 3h and 24h post-enrolment for the examination of cellular, protein and genetic changes. Patients with subsequently confirmed ischaemic (n=18) or haemorrhagic stroke (n=11) showed increased intracellular concentrations of GzmB in all cell populations investigated (CD8
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-01-2007
DOI: 10.1212/01.WNL.0000250327.73031.54
Abstract: To assess the rate, degree, and predictors of recovery from a disabled to nondisabled state in patients disabled after recurrent ischemic stroke. Patients with ischemic stroke enrolled in the Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) Study underwent prospective assessment of their modified Rankin score (mRS) at 1, 3, 6, 12, and 18 months after enrollment and after recurrent stroke. Patients disabled (defined as mRS > or = 3) after recurrence were analyzed for recovery (defined as mRS < 3) during the 18 months, and predictors of recovery were sought using a Cox proportional-hazard multiple regression analysis. Three hundred forty-five (54%) of 637 patients were disabled after recurrent ischemic stroke 115 (33%) patients had been disabled and 230 (66%) nondisabled before stroke recurrence. At recurrence, the degree of disability was moderate (mRS 3) in 135 (39%) patients, severe (mRS 4) in 139 (40%), and very severe (mRS 5) in 71 (21%). After 12 months' median follow-up, 117 (34%, 95% CI: 29 to 39%) had recovered: 68 (50%, 42 to 59%) of 135 moderately disabled, 45 (32%, 25 to 41%) of 139 severely disabled, and 4 (6%, 2 to 14%) of 71 very severely disabled 70 (20.3%) patients died. From recurrence, median time to recovery was 6 months (mRS 3) and 18 months (mRS 4) 94% with very severe disability had not recovered at 18 months. Independent predictors of recovery were moderate disability at recurrence (mRS 3) compared with severe (mRS 4: hazard ratio [HR] 1.5 95% CI 1.04 to 2.3) or very severe disability (mRS 5: HR 7.6 2.7 to 20) and a nondisabled vs disabled state before recurrence (HR 4.0 2.3 to 6.8). The rate of recovery from recurrent ischemic stroke was greatest in the first 6 months one-third of patients recovered within 12 months. The significant predictors of recovery were a nondisabled state before recurrence and increasing severity of the recurrent stroke.
Publisher: BMJ
Date: 08-2008
DOI: 10.1136/EBM.13.4.113
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2017
DOI: 10.1161/HYPERTENSIONAHA.117.09150
Abstract: There is uncertainty about the relation between blood pressure and vascular disease at older age. We assessed the association of systolic blood pressure (SBP) and major vascular events in a prospective cohort study of 7564 men aged 65 to 94 years, recruited in 1996–1999 from the general population in Perth, Western Australia. SBP was measured at baseline and again at resurvey in 2001–2004. Participants were monitored for fatal and nonfatal vascular events. To limit the effect of reverse causality, analyses were restricted to men without previous vascular disease at baseline. Hazard ratios were estimated by Cox regression, with adjustment for age and education (further adjustment did not materially change the associations). During a mean follow-up of 11 years, there were 1557 major vascular events. Continuous log-linear associations were found between usual SBP and risk of major vascular events throughout the SBP range examined (145–170 mm Hg). Overall, 10 mm Hg higher usual SBP was associated with ≈20% higher risk of major vascular events (hazard ratio, 19% 95% confidence interval, 13%–26% mean age at event 80 years). There was evidence of positive associations with both ischemic heart disease and stroke and effect modification by age, with shallower associations at older ages. Even at 85 to 94 years, however, there was evidence of a positive association: 10 mm Hg higher usual SBP was associated with 14% (95% confidence interval, 1%–30%) higher risk of major vascular events.
Publisher: Hindawi Limited
Date: 15-12-2020
DOI: 10.1111/PEDI.13170
Abstract: To determine the relationship between periodontal disease and glycemic control in children with type 1 diabetes and to characterize the ersity and composition of their oral microbiota. Cross-sectional study including children with type 1 diabetes recruited from clinics at the Women's and Children's Hospital (Australia). Participants had a comprehensive dental assessment, periodontal examination, and buccal and gingival s les collected for 16S rRNA sequencing. Seventy-seven participants (age 13.3 ± 2.6 years, 38 males, BMI z-score 0.81 ± 0.75) had a diabetes duration of 5.6 ± 3.9 years and median HbA1c of 8.5% (range 5.8-13.3), 69.4 mmol/mol (range 39.9-121.9). Thirty-eight (49%) had early markers of periodontal disease. HbA1c was positively correlated with plaque index (Rho = 0.34, P = 0.002), gingival index (Rho = 0.30, P = 0.009), bleeding on probing (Rho = 0.44, P = 0.0001) and periodontal pocket depth >3 mm (Rho = 0.21, P = 0.06). A 1% increase in HbA1c was independently associated with an average increase in bleeding on probing of 25% (P = 0.002) and with an increase in the rate of sites with pocket depth >3 mm of 54% (P = 0.003). Higher HbA1c was independently related to increased phylogenetic alpha ersity (P = 0.008) and increased compositional variation (beta ersity P = 0.02) in gingival, but not buccal, microbiota. Brushing frequency, plaque index, and gingival index had a significant effect on microbiota composition, independent of HbA1c. Children with type 1 diabetes showed a continuous relationship between less favorable glycemic control and increased early markers of periodontal disease. Glycemic control was also related to the complexity and richness of the plaque microbiota, with ersity increasing as HbA1c levels increase.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JAD.2018.07.013
Abstract: The use of alcohol and drugs is common among people with bipolar disorder, but it is unclear if age of onset modifies this association. To determine the cross-sectional and longitudinal association between age of onset of bipolar disorder (BD) and disorders associated with the use of alcohol or other substances in later life, as well as their impact on mortality. Cohort study of a community-representative s le of 38,173 men aged 65-85 years at the start of the follow up period of 18 years. We used the Western Australian Data Linkage System to ascertain the presence of BD and substance use disorders according to the International Classification of Diseases (ICD). We also collected information on concurrent morbidities: diabetes, hypertension, ischaemic heart disease and stroke. 175 men had BD onset < age 60 years and 75 ≥ 60 years. Compared with older men without BD, the adjusted odds of alcohol use disorders were 3.87 (95%CI = 2.52, 5.93) for men with BD onset < 60 years and 2.38 (95%CI = 1.08, 5.25) for those with onset ≥ 60 years. The adjusted hazard ratio of incident disorders associated with the use of alcohol and other substances was 3.23 (95%CI = 1.87, 5.58) and 2.38 (95%CI = 1.38, 4.11) respectively for men with BD onset < 60 years. BD with onset ≥ 60 years was not associated with substance use disorders. The mortality hazard was not affected by the interaction between BD and the use of substances. Substance use disorders (alcohol or others) are more prevalent among older adults with than without BD, but new cases are only more frequent among men with BD onset < 60 years of age. Grouping BD into early and late onset is clinically informative and may affect approach to assessment and management.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1987
Abstract: A woman with herpes simplex encephalitis (HSE) in the third trimester of pregnancy is described. She was treated with acyclovir and recovered completely to deliver a normal child per vaginam at term. She had no evidence of genital or disseminated herpes virus infection. This paper illustrates that (1) the outcome of HSE in pregnancy can be favorable both for the mother and the offspring, (2) early diagnosis and use of acyclovir therapy is essential for successful outcome, and (3) the use of acyclovir in the third trimester of pregnancy was not harmful to the mother or fetus.
Publisher: S. Karger AG
Date: 24-05-2023
DOI: 10.1159/000530941
Abstract: b i Introduction: /i /b Diet quality is a marker of how closely eating patterns reflect dietary guidelines. The highest tertile for diet quality scores is associated with 40% lower odds of first stroke compared with the lowest tertile. Little is known about the diet of stroke survivors. We aimed to assess dietary intake and quality of Australian stroke survivors. b i Methods: /i /b Stroke survivors enrolled in the ENAbLE pilot trial (2019/ETH11533, ACTRN12620000189921) and Food Choices after Stroke study (2020ETH/02264) completed the Australian Eating Survey Food Frequency Questionnaire (AES), a 120-item, semiquantitative questionnaire of habitual food intake over the previous 3–6 months. Diet quality was determined by calculating the Australian Recommended Food Score (ARFS): a higher score indicates higher diet quality. b i Results: /i /b Eighty-nine adult, stroke survivors (female: i n /i = 45, 51%) of mean age 59.5 years (±9.9) had a mean ARFS of 30.5 (±9.9) (low diet quality). Mean energy intake was similar to the Australian population: 34.1% from noncore (energy-dense/nutrient-poor) and 65.9% from core (healthy) foods. However, participants in the lowest tertile for diet quality ( i n /i = 31) had significantly lower intake of core (60.0%) and higher intake from noncore foods (40.0%). Most participants did not meet daily requirements for fiber, potassium, or omega 3 fatty acids (2%, 15%, and 18%), nutrients important to reduce stroke risk. b i Conclusion: /i /b The diet quality of stroke survivors was poor, with inadequate intake of nutrients important for reducing recurrent stroke risk. Further research is needed to develop effective interventions to improve diet quality.
Publisher: Public Library of Science (PLoS)
Date: 2008
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000441098
Abstract: b i Background: /i /b Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working in iduals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. b i Objectives: /i /b This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. b i Methodology: /i /b Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. b i Results: /i /b In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. b i Conclusions: /i /b Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.PSYNEUEN.2015.11.012
Abstract: Depression in older men has been associated with low circulating testosterone concentration but data from prospective studies are limited. We conducted a prospective longitudinal study in a community representative cohort of 3179 older men free of clinically significant depressive symptoms at baseline. The main objective of this study was to determine if low serum testosterone, dihydrotestosterone and estradiol concentrations are associated with the development of depressive symptoms. Incident depression was assessed with the Patient Health Questionnaire and via an electronic health record database (The West Australian Data Linkage System). The main exposures of interest were serum testosterone, dihydrotestosterone and estradiol measured by liquid chromatography-mass spectrometry and calculated free testosterone in baseline blood s les (collected between 2001 and 2004). One hundred and thirty five men (4.2%) developed depression over a median follow up time of 9.4 years (range 8.4-10.9). Men with incident depression were older (median age 77.7 vs 76.1 years, z=-3.82, p=0<0.001) and were more likely to have cardiovascular disease (43.0% vs 32.6%, χ(2)=6.32, p=0.012) and diabetes (22.2% vs 13.2%, χ(2)=8.95, p=0.003). Low serum total testosterone (<6.4 nmol/L) was associated with incident depression (HR 2.07, 95%CI 1.17-3.68) and this remained significant after adjustment for relevant potential confounding factors (HR 1.86, 95%CI 1.05-3.31). Low serum dihydrotestosterone, estradiol and calculated free testosterone were not associated with risk of depression. Low serum total testosterone, but not calculated free testosterone, was associated with incident depression in this s le of older men.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.AMJCARD.2013.02.038
Abstract: Thrombospondin-1 and -2 (TSP-1 and -2) have been implicated in the regulation of angiogenesis, thrombosis, and inflammation, which are believed to be critical in the pathogenesis of cardiovascular events. The aim of this study was to assess whether serum TSP-1 and TSP-2 concentrations were associated with cardiovascular mortality in older men. A cohort of 992 elderly men was recruited between 2001 and 2004, and blood was collected for assessment of serum TSP-1 and TSP-2 by immunoassay. The men were followed by means of the Western Australia Data Linkage System until July 31, 2009. The association of TSP-1 and TSP-2 with mortality was assessed using Kaplan-Meier estimates and Cox proportional hazard analysis. Serum TSP-2 quartile was strongly positively associated with all-cause and cardiovascular mortality. Men with serum TSP-2 in the first, second, third, and fourth quartiles had a cumulative incidence of cardiovascular mortality of 3.3%, 8.0%, 9.7%, and 12.5% at 5 years, respectively, p = 0.001. Men with serum TSP-2 in the highest quartile had a 3.37-fold (95% confidence interval: 1.53-7.44, p = 0.003) increased risk of cardiovascular mortality after adjusting for other cardiovascular risk factors. Most deaths were secondary to cardiac causes, and serum TSP-2 was also independently associated with cardiac mortality (relative risk: 3.55, 95% confidence interval: 1.54-8.20 for men in the top compared with the lowest quartile). Serum TSP-1 was not associated with cardiovascular mortality. In conclusion, increased serum TSP-2 concentration is independently and significantly associated with the risk of cardiac mortality in older men.
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1111/J.1538-7836.2005.01640.X
Abstract: We aimed to determine whether adding clopidogrel to aspirin in patients at high risk of future cardiovascular events would suppress laboratory measures of the antiplatelet effects of aspirin and have greater platelet inhibitory effects in patients with the least inhibition of platelets by aspirin. We performed a randomized, double-blind, placebo-controlled, crossover trial, comparing clopidogrel 75 mg day(-1) versus placebo, in 36 aspirin-treated patients with symptomatic objectively confirmed peripheral arterial disease. The addition of clopidogrel to aspirin did not suppress platelet aggregation induced by arachidonic acid, urinary 11 dehydro thromboxane B2 concentrations, or soluble markers of platelet activation markers (P-selectin, CD40-ligand) and inflammation (high sensitivity serum C-reactive protein, interleukin-6). Clopidogrel significantly inhibited platelet aggregation induced by ADP (reduction 26.2% 95% CI: 21.3-31.1%, P < 0.0001) and collagen (reduction 6.2% 95% CI: 3.2-9.3%, P = 0.0003). The greatest inhibition of collagen-induced platelet aggregation by clopidogrel was seen in patients with the least inhibition of arachidonic acid induced aggregation by aspirin [lower tertile of arachidonic acid-induced platelet aggregation: 2.8% (95% CI: -0.8 to 6.3%) reduction in mean collagen-induced aggregation by clopidogrel middle tertile: 4.0% (95% CI: 0.4-7.6%) upper tertile 12.6% (95% CI: 4.5-20.8%) P-value for interaction 0.01]. The greatest platelet inhibitory effect of clopidogrel occurs in patients with the least inhibition of arachidonic acid-induced platelet aggregation by aspirin. This raises the possibility that the clinical benefits of adding clopidogrel to aspirin may be greatest in patients whose platelets are least inhibited by aspirin. Confirmation in clinical outcome studies may allow these patients to be targeted with antiplatelet drugs that inhibit the ADP receptor, thereby overcoming the problem of laboratory aspirin resistance.
Publisher: Elsevier BV
Date: 07-2009
Publisher: Springer Science and Business Media LLC
Date: 2006
DOI: 10.1038/NCPNEURO0093
Abstract: Increased levels of plasma total homocysteine (tHcy) can be caused by genetic mutations, vitamin deficiencies, renal and other diseases, and numerous drugs. Raised tHcy also correlate with increasing age, and are associated with laboratory evidence of atherogenesis (e.g. endothelial dysfunction) and thrombosis, and with epidemiological evidence of an increased risk of atherothrombotic vascular disease, including ischemic stroke. The association between raised tHcy and increased risk of ischemic stroke is independent of other known vascular risk factors and is biologically plausible however, randomized controlled trials have not revealed a causal relationship. The recently published Vitamins In Stroke Prevention (VISP) trial identified no significant reduction in the relative risk of stroke by lowering tHcy with B-vitamin therapy among 3,680 patients with recent ischemic stroke. It did not, however, reliably exclude a modest but important reduction of up to 20% in relative risk of stroke. Currently, there is insufficient evidence to confirm that homocysteine is a modifiable causal risk factor for stroke, or to recommend routine screening for, or treatment of, raised tHcy concentrations with folic acid and other vitamins, to prevent ischemic stroke.
Publisher: Elsevier BV
Date: 09-2017
Publisher: SAGE Publications
Date: 09-03-2015
DOI: 10.1111/IJS.12475
Abstract: The aim of this pilot study was to determine the feasibility of a multicenter, randomized, controlled trial in India of a family-led, trained caregiver-delivered, home-based rehabilitation intervention vs. routine care. A prospective, randomized (within seven-days of hospital admission), blinded outcome assessor, controlled trial of structured home-based rehabilitation delivered by trained and protocol-guided family caregivers (intervention) vs. routine care alone (control) was conducted in patients with residual disability. Key feasibility measures were recruitment, acceptance and adherence to assessment procedures, and follow-up of participants over six-months. CTRI/2014/10/005133. A total of 104 patients from the stroke unit at Christian Medical College, Ludhiana were recruited over nine-months. Recruitment was feasible and accepted by patients and their carers. Important observations were made regarding potential unblinding of the participants, contamination of therapy between the randomized groups, organization of home visits, and resources required for a multicenter study. The pilot study established the feasibility of conducting a large-scale study of family-led, trained caregiver-delivered, home-based stroke rehabilitation in a low resource setting. The main phase of the trial ‘ATTEND’ is currently underway in over 10 centers in India.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-02-2014
Publisher: Informa Healthcare
Date: 17-05-2007
Publisher: American College of Physicians
Date: 17-12-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-02-2020
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.MATURITAS.2017.04.005
Abstract: Klotho variants (KL-VS) have been associated with increased longevity and better cognitive function. It is unclear whether they modulate dementia risk. We recruited 527 men aged 71-87 years who were free of cognitive impairment. We used data linkage to track the onset of dementia over 10 years. KL-VS genotyping (rs9536314 T/G) followed standard procedures. The annual rate of dementia was 17.2‰ (95%CI=14.0-21.1 total=5053 person-years), and 14.0‰ (95%CI=10.6-18.4 3582 person-years), 23.5‰ (95%CI=16.6-33.2 1363 person-years) and 46.4‰ (95%CI=19.3-111.5 108 person-years) for men with the TT, TG and GG genotypes. Compared with the TT genotype, the sub-hazard ratios of dementia associated with the TG and GG genotypes were 1.6 (95%CI=1.0, 2.5 p=0.030) and 3.5 (95%CI=1.3, 9.1 p=0.011). The Klotho KL-VS variant is associated with an increase in the incidence of dementia in older men, in a dose-dependent fashion (intermediate for heterozygosis and highest for homozygosis).
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.JAGP.2013.09.007
Abstract: To determine the association between clinically significant depressive symptoms, routine function, and sexual interest and practice in a community-derived s le of octogenarian men. Cross-sectional study of 1,649 community-dwelling men aged 80 years or over with no history of terminal illnesses or neurodegenerative diseases. Men with Patient Health Questionnaire (PHQ-9) scores greater than or equal to 10 were deemed to be clinically depressed. Scores between 5 and 9 were considered indicative of subthreshold depression. We used standard procedures to collect self-reported sociodemographic, lifestyle, and clinical data, as well as basic and instrumental activities of daily living, and a structured questionnaire to ask men about their 12-month interest in sex, frequency, past experiences, and current sexual problems. 121 men (7.3%) had clinically significant depression and 239 (14.5%) had subthreshold depression. Depressive symptoms were associated with difficulties in basic and instrumental activities of daily living, but not with sexual practice. Decreased interest in sex and anxiety before sex were associated with subthreshold depression. Clinically significant depressive symptoms were independently and positively associated with past history of diabetes (odds ratio [OR]: 2.1, 95% confidence interval [CI]: 1.1-4.0), depression (OR: 9.0 95% CI: 4.6-17.3), impaired ability to groom (OR: 3.7, 95% CI: 1.2-11.0), carry out heavy housework duties (OR: 2.4, 95% CI: 1.1-5.1), manage finances (OR: 2.5, 95% CI: 1.1-5.7), or engage in leisure activities (OR: 4.1, 95% CI: 2.0-8.2). Ability to function effectively at home, financial autonomy, and leisure are associated with clinically significant depression in octogenarian men. Maintaining daily function and autonomy may be a suitable target for interventions that aim to reduce the prevalence and incidence of depression in older age.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JAD.2018.08.035
Abstract: Bipolar disorder (BD) has been associated with greater health morbidity burden, but it is unclear if this association is affected by age at the time of diagnosis and how this might impact on the use of general hospital services. Cross-sectional study investigating the prevalence of common medical morbidities among participants with early (EOBD) and late onset diagnosis of BD (LOBD - age at diagnosis ≥ 60 years) derived from a community-representative s le of 37,183 men aged 65-85 years. Cohort study over a follow up period of up to 17.7 years investigating the hazard of general hospital use among older men associated with EOBD and LOBD taking into account age and prevalent medical morbidities. 250 older men had a recorded diagnosis of BD, 75 of whom had LOBD. Diabetes, stroke and diseases of the respiratory and digestive systems were more frequent in men with than without BD. There were no differences in the distribution of medical morbidities between men with EOBD and LOBD. The adjusted hazard ratio (HR) of contact with general hospital services was significantly higher among men with EOBD (HR = 1.33 95%CI = 1.14, 1.54) and LOBD (HR = 1.27, 95%CI = 1.06, 1.51) compared with older men without BD. Older men with EOBD had the highest number of contacts with general hospital services during follow up, although men with EOBD and LOBD did not differ in the number of contacts due to episodes of mania or depression. The medical reasons for contact with general hospital services of men with EOBD and LOBD overlapped but were not identical. Older men with BD experience greater health morbidity than men without BD. Older men with BD access hospital services for the management of physical morbidities earlier and more frequently than men without BD. Age at the time of diagnosis of BD has limited impact on the risk of contact with general medical services, although subtle differences in the physical morbidity of men with EOBD and LOBD warrant further investigation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1998
DOI: 10.1161/01.STR.29.12.2491
Abstract: Background and Purpose —Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke. This study aimed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population-based series of people with first-ever stroke in Perth, Western Australia. Methods —Between February 1989 and August 1990, all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. Results —Three hundred seventy patients with a first-ever stroke were registered, of whom 351 survived days. Data were available for 98% of the cohort at 5 years, by which time 199 patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12 (23%) of which were fatal within 28 days. The 5-year cumulative risk of first recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8% (95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard ratio [HR], 2.6 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1 95% CL, 0.98, 4.4), and diabetes mellitus (HR, 2.1 95% CL, 0.95, 4.4). Conclusions —Approximately 1 in 6 survivors (15%) of a first-ever stroke experience a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days. The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88% of cases. The predictors of first recurrent stroke in this study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but numbers of recurrent events were modest. Because the risk of recurrent stroke is highest (8.8%) in the first 6 months after stroke, strategies for secondary prevention should be initiated as soon as possible after the index event.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-05-2007
DOI: 10.1212/01.WNL.0000260967.77422.97
Abstract: To determine the rate, degree, and predictors of recovery from disabling ischemic stroke. Patients with ischemic stroke enrolled in the Management of Atherothrombosis With Clopidogrel in High-Risk Patients (MATCH) study underwent long-term prospective assessment of their modified Rankin Scale (mRS) score. Disability (functionally dependent state) was defined as mRS > or = 3, and recovery (functionally independent state) was defined as mRS or = 3) at baseline (median of 14 [0 to 96] days after stroke onset). Disability was moderate (mRS 3) in 931 (56%) patients, severe (mRS 4) in 691 (42%), and very severe (mRS 5) in 40 (2%). By 18 months, 877 (52.8%, 95% CI 50% to 55%) patients had recovered, 589 (63%, 60% to 66%) with moderate disability, 281 (41%, 37% to 44%) with severe disability, and 7 (17%, 7 to 33%) with very severe disability. Median time to recovery was 3 months for patients with moderate disability and 18 months for severe disability 82.5% of severely disabled patients remained so at 18 months. Predictors of recovery were moderate disability (mRS 3) at baseline compared with severe (mRS 4: hazard ratio [HR] 2.13, 1.86 to 2.44) or very severe disabling stroke (HR 5.88, 2.86 to 12.5) younger women (aged or =75 years HR 1.85, 1.47 to 2.33) decreasing time (days) between the qualifying event and the baseline assessment (HR 1.01, 1.01 to 1.02) and the absence of previous ischemic stroke (HR 1.61, 1.35 to 1.92), concurrent peripheral artery disease (HR 1.61, 1.23 to 2.13), or diabetes (HR 1.30, 1.10 to 1.54). Half of patients with disabling ischemic stroke recovered within 18 months, and recovery was greatest within 6 months. Significant predictors of recovery included the severity of the index stroke and no history of ischemic stroke, peripheral artery disease, or diabetes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2004
Publisher: AMPCo
Date: 09-2002
DOI: 10.5694/J.1326-5377.2002.TB04807.X
Abstract: Several low molecular weight (LMW) heparin preparations, including dalteparin, enoxaparin and nadroparin, as well as the heparinoid danaparoid sodium, are approved for use in Australia. LMW heparins are replacing unfractionated heparin for the prevention and treatment of venous thromboembolism and the treatment of non-ST-segment-elevation acute coronary syndromes. The advantages of LMW heparins over unfractionated heparin include a longer half-life (allowing once-daily or twice-daily subcutaneous dosing), high bioavailability and predictable anticoagulant response (avoiding the need for dose adjustment or laboratory monitoring in most patients), and a low risk of heparin-induced thrombocytopenia and osteoporosis. Laboratory monitoring of LMW heparin therapy should be considered in newborns and children, patients with renal impairment, those who are pregnant, and those at the extremes of bodyweight (eg, 100 kg). LMW heparins should: be avoided or used with caution in patients undergoing neuraxial anaesthesia, owing to the potential for epidural haematoma formation not be used (ie, are contraindicated) in patients with immune heparin-induced thrombocytopenia, as they may cross-react with anti-heparin antibodies. Conventional unfractionated heparin retains a role in the management of patients at high risk of bleeding, undergoing invasive procedures, and patients with renal failure owing to its shorter half-life, reversibility with protamine sulfate, and extrarenal metabolism. The heparinoid danaparoid sodium is effective for the treatment of heparin-induced thrombocytopenia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2019
DOI: 10.1161/STROKEAHA.119.025019
Abstract: In randomized stroke trials, central adjudication of a trial’s primary outcome is regularly implemented. However, recent evidence questions the importance of central adjudication in randomized trials. The aim of this review was to compare outcomes assessed by central adjudicators with outcomes assessed by site investigators. We included randomized stroke trials where the primary outcome had undergone an assessment by site investigators and central adjudicators. We searched MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, and Google Scholar for eligible studies. We extracted information about the adjudication process as well as the treatment effect for the primary outcome, assessed both by central adjudicators and by site investigators. We calculated the ratio of these treatment effects so that a ratio of these treatment effects indicated that central adjudication resulted in a more beneficial treatment effect than assessment by the site investigator. A random-effects meta-analysis model was fitted to estimate a pooled effect. Fifteen trials, comprising 69 560 participants, were included. The primary outcomes included were stroke (8/15, 53%), a composite event including stroke (6/15, 40%) and functional outcome after stroke measured on the modified Rankin Scale (1/15, 7%). The majority of site investigators were blind to treatment allocation (9/15, 60%). On average, there was no difference in treatment effect estimates based on data from central adjudicators and site investigators (pooled ratio of these treatment effects=1.02 95% CI, [0.95–1.09]). We found no evidence that central adjudication of the primary outcome in stroke trials had any impact on trial conclusions. This suggests that potential advantages of central adjudication may not outweigh cost and time disadvantages in stroke studies if the primary purpose of adjudication is to ensure validity of trial findings.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.JVS.2013.01.046
Abstract: This study was conducted to determine whether plasma total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are associated with abdominal aortic aneurysm (AAA) and aortic diameter. This was a cross-sectional study set in Western Australia of 4248 community-dwelling men aged 70 to 88 years. Infrarenal aortic diameter was measured using ultrasound scan, tHcy was measured by immunoassay, and MTHFR 677T polymorphism was detected by polymerase chain reaction. Adjusted multinomial logistic regression analysis showed the odds of having an AAA (aortic diameter ≥ 30 mm) for men with high tHcy (≥ 15 μmol/L) compared with those with normal tHcy (<15 μmol/L) was 1.45 (95% confidence interval [CI], 1.10-1.91). Every 5-μmol/L increment in tHcy was associated with 0.15-mm (95% CI, 0.01-0.28 mm) increase in mean aortic diameter. The tHcy concentration was higher in MTHFR TT homozygote in iduals than in wild-type CC in iduals. There was, however, no apparent association between MTHFR C677T polymorphism with AAA (TT vs CC genotype: odds ratio, 0.97 95% CI, 0.72-1.31) or aortic diameter (TT vs CC genotype: mean increment of 0.01 mm 95% CI, -0.63 to 0.65 mm). Elevated tHcy is associated with the presence of AAA in older men. There is also a positive dose-response relationship between tHcy and abdominal aortic diameter. Longitudinal studies and clinical trials of lowering tHcy are required to assess whether these relationships are causal.
Publisher: SAGE Publications
Date: 03-01-2014
DOI: 10.1111/IJS.12240
Abstract: The most effective and efficient model for providing organized stroke care remains uncertain. This study aimed to compare the effect of two models in a randomized controlled trial. Patients with acute stroke were randomized on day one of admission to combined, co-located acute/rehabilitation stroke care or traditionally separated acute/rehabilitation stroke care. Outcomes measured at baseline and 90 days post-discharge included functional independence measure, length of hospital stay, and functional independence measure efficiency (change in functional independence measure score ÷ total length of hospital stay). Among 41 patients randomized, 20 were allocated co-located acute/rehabilitation stroke care and 21 traditionally separated acute/rehabilitation stroke care. Baseline measurements showed no significant difference. There was no significant difference in functional independence measure scores between the two groups at discharge and again at 90 days postdischarge (co-located acute/rehabilitation stroke care: 103·6 ± 22·2 vs. traditionally separated acute/rehabilitation stroke care: 99·5 ± 27·7 P = 0·77 at discharge co-located acute/rehabilitation stroke care: 109·5 ± 21·7 vs. traditionally separated acute/rehabilitation stroke care: 104·4 ± 27·9 P= 0·8875 at 90 days post-discharge). Total length of hospital stay was 5·28 days less in co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (24·15 ± 3·18 vs. 29·42 ± 4·5, P = 0·35). There was significant improvement in functional independence measure efficiency score among participants assigned to co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (co-located acute/rehabilitation stroke care: median 1·60, interquartile range: 0·87–2·81 traditionally separated acute/rehabilitation stroke care: median 0·82, interquartile range: 0·27–1·57, P = 0·0393). Linear regression analysis revealed a high inverse correlation ( R 2 = 0·89) between functional independence measure efficiency and time spent in the acute stroke unit. This proof-of-concept study has shown that co-located acute/rehabilitation stroke care was just as effective as traditionally separated acute/rehabilitation stroke care as reflected in functional independence measure scores, but significantly more efficient as shown in greater functional independence measure efficiency. Co-located acute/rehabilitation stroke care has potential for significantly improved hospital bed utilization with no patient disadvantage.
Publisher: S. Karger AG
Date: 02-05-2017
DOI: 10.1159/000470855
Abstract: b i Background and Purpose: /i /b Endovascular thrombectomy (EVT) improves the functional outcome when added to best medical therapy, including alteplase, in patients with acute ischaemic stroke secondary to large vessel occlusion (LVO) in the anterior circulation. However, the evidence for EVT in alteplase-ineligible patients is less compelling. It is also uncertain whether alteplase is necessary in patients with successful recanalization by EVT, as the treatment effect of EVT may be so powerful that bridging alteplase may not add to efficacy and may compromise safety by increasing bleeding risks. We aimed to survey the proportion of patients suitable for EVT who are alteplase-ineligible and to compare the safety and effectiveness of standard care of acute large artery ischaemic stroke by EVT plus thrombolysis with that of EVT alone in a tertiary hospital clinical stroke service. b i Methods: /i /b We performed a retrospective analysis of acute ischaemic stroke patients treated with EVT at our centre between October 2013 and April 2016, based on a registry with prospective and consecutive patient collection. In idual patient records were retrieved for review. Significant early neurological improvement was defined as a NIHSS score of 0–1, or a decrease from baseline of ≤8, at 24 h after stroke onset. b i Results: /i /b Fifty patients with acute ischaemic stroke secondary to LVO in the anterior circulation received EVT in this period, of whom 21 (42%) received concurrent alteplase and 29 (58%) EVT alone. The 2 groups had similar baseline characteristics and similar outcomes. Significant neurological improvement at 24 h occurred in 47.6% of the patients with EVT and bridging alteplase and in 51.7% of the patients with EVT alone ( i /i = 0.774). Mortality during acute hospitalization was 20% for the bridging alteplase group versus 7.1% for EVT alone ( i /i = 0.184). Intracranial haemorrhage rates were 14.3% for bridging alteplase versus 20.7% for EVT alone ( i /i = 0.716). Local complications, groin haematoma (23.8 vs. 10.3%) and groin pseudoaneurysms (4.8 vs. 0%) ( i /i = 0.170), were not significantly different. b i Conclusion: /i /b Our study highlights the relatively large proportion of patients suitable for EVT who have a contraindication to alteplase and raises the hypothesis that adding alteplase to successful EVT may not be necessary to optimize functional outcome. The results are consistent with observational data from other endovascular centres and support a randomised controlled trial of EVT versus EVT with bridging alteplase.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2021
DOI: 10.1161/STROKEAHA.120.033070
Abstract: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14] P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%] P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%] P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%] P =0.05), or seizures (11 [1.71%] versus 8 [1.25%] P =0.64) at 12 months. Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. URL: www.anzctr.org.au/ Unique identifier: ACTRN12611000774921.
Publisher: BMJ
Date: 08-1988
Abstract: Surgical robots have been appearing in operating rooms over the past decade, and neurosurgery has been one of the pioneers in this area. In neurosurgery, the clinical use of robots has been limited to stereotactic procedures and endoscopic manoeuvres, although the brain is a unique organ and well-suited for robotic application. The aim of this study was to assess the ability of our vision-guided robotic system to perform basic neurosurgical procedures. THE STUDY WAS DIVIDED INTO TWO PARTS: bone drilling and endoscopic manoeuvres. The robotic system was instructed to recognise targets on artificial skull models placed in different positions (supine, lateral, sitting, and prone) and to make burr holes. A total of 10 selected burr holes were used to assess the capability of the robot to insert an endoscope. The accuracy ranged 0.1-1.0 mm with repeatability ranged 0.03-0.92 mm. Generally, the present robotic system is able to perform the surgical tasks. However, further study is needed to refine the robotic system, including the safety mechanisms.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2003
DOI: 10.1161/01.STR.0000082382.42061.EE
Abstract: Background and Purpose— Very few studies have provided information regarding long-term prognosis after stroke. We aimed to determine the absolute and relative survival over 10 years among patients with first-ever stroke from a population-based study in Perth, Western Australia. Methods— For a 12-month period beginning February 1989, all in iduals with a suspected acute stroke or transient ischemic attack who were resident in a geographically defined and representative region of Perth, Western Australia, were registered prospectively and assessed according to standardized diagnostic criteria. Patients with a definite first-ever stroke were followed up prospectively at 4 months, 12 months, 5 years, and 10 years after the index event. Results— A total of 251 patients with first-ever stroke were registered, and 244 (97%) were followed up at 10 years, by which time 197 (79% 95% confidence interval [CI], 74 to 84) had died. The major causes of death were the direct effects of the initial stroke (27% 95% CI, 21 to 33) and cardiovascular disease (26% 95% CI, 20 to 32). Among 1-year survivors of stroke, the average annual case fatality was 4.8%, which was 2.3 (95% CI, 1.9 to 2.7) times greater than for the general population of the same age and sex. Conclusions— One in 5 patients with first-ever stroke survived to 10 years. The average annual case fatality was 4.8% between years 1 and 10 after stroke, which was twice that expected for the general population. Vascular disease is the major cause of death among long-term survivors of stroke.
Publisher: American Medical Association (AMA)
Date: 09-2021
Publisher: AMPCo
Date: 05-1996
DOI: 10.5694/J.1326-5377.1996.TB122211.X
Abstract: As the risks of adverse effects of warfarin and aspirin in certain patients with chronic atrial fibrillation are high, intervention with these agents should be targeted towards those who will derive most benefit. Clearer guidelines are emerging to identify those patients and to standardise current prescribing practices.
Publisher: Wiley
Date: 10-2010
DOI: 10.1002/ANA.22189
Abstract: The consumption of certain B-vitamins through diet or supplementation decreases the total plasma concentration of homocysteine (tHcy) and may enhance response to standard antidepressant treatment. It is unclear if treatment with B-vitamins can reduce the long-term prevalence of depression in people at risk, such as stroke survivors. The purpose of this research was to determine if treatment with B-vitamins reduces the hazard of poststroke depression compared with placebo. Randomized, double-blind, placebo-controlled trial of tHcy-lowering treatment with daily folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (0.5 mg) for 1 to 10.5 years in survivors of stroke. The primary endpoint was the onset of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) major depression after randomization. Secondary outcomes were the prevalence of DSM-IV major or minor depression at the end of treatment. Other measured factors included age, gender, poststroke handicap associated with stroke, recurrence of strokes, cognitive impairment, and use of antidepressants. Among 273 people who completed the final assessment after 7.1 ± 2.1 years (mean ± standard deviation) of follow up, random assignment to B-vitamins was associated with a lower hazard of major depression compared with placebo (18.4% vs 23.3%, adjusted hazard ratio [HR] = 0.48 95% confidence interval [CI] = 0.31-0.76) and a trend toward a lower odds of major or minor depression at the end of the trial compared with placebo (19.1% vs 27.7% adjusted odds ratio [OR] = 0.58 95%CI = 0.31-1.09). Long-term treatment of poststroke survivors with folic acid, B6, and B12 was associated with a reduction in the hazard of major depression in our patient population. If these findings can be validated externally, B-vitamin supplementation offers hope as an effective, safe, and affordable intervention to reduce the burden of poststroke depression.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2022
DOI: 10.1161/STROKEAHA.121.036400
Abstract: The stroke burden continues to grow across the globe, disproportionally affecting developing countries. This burden cannot be effectively halted and reversed without effective and widely implemented primordial and primary stroke prevention measures, including those on the in idual level. The unprecedented growth of smartphone and other digital technologies with digital solutions are now being used in almost every area of health, offering a unique opportunity to improve primordial and primary stroke prevention on the in idual level. However, there are several issues that need to be considered to advance development and use this important digital strategy for primordial and primary stroke prevention. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines we provide a systematic review of the current knowledge, challenges, and opportunities of digital health in primordial and primary stroke prevention.
Publisher: AMPCo
Date: 08-2008
DOI: 10.5694/J.1326-5377.2008.TB01947.X
Abstract: To determine the incidence of venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), in a well defined urban community broadly representative of the Australian population in terms of age, sex and ethnic distribution. A prospective, community-based study conducted over a 13-month period from 1 October 2003 to 31 October 2004. People in a population of 151 923 permanent residents of north-eastern metropolitan Perth, Western Australia, who developed VTE during the study period were identified prospectively and retrospectively through multiple overlapping sources. Number of cases of symptomatic, objectively verified DVT and PE. 137 patients had 140 VTE events (87 DVT and 53 PE). The crude annual incidence per 1000 residents was 0.83 (95% CI, 0.69-0.97) for VTE, 0.52 (95% CI, 0.41-0.63) for DVT, and 0.31 (95% CI, 0.22-0.40) for PE. The annual incidence per 1000 residents after age adjustment to the World Health Organization World Standard Population was 0.57 (95% CI, 0.47-0.67) for VTE, 0.35 (95% CI, 0.26-0.44) for DVT, and 0.21 (95% CI, 0.14-0.28) for PE. If the crude annual incidence of VTE in this area of metropolitan Perth is externally valid, then VTE affects about 17 000 Australians annually. Future studies of trends in VTE incidence will be needed to measure the effectiveness of VTE prevention strategies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-08-2018
Abstract: There is concern that selective serotonin reuptake inhibitors ( SSRI s) substantially increase bleeding risk in patients taking anticoagulants. We studied 737 patients taking SSRI s in the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Embolism and Stroke Trial in Atrial Fibrillation) trial of rivaroxaban compared with warfarin for the prevention of stroke/systemic embolism in patients with atrial fibrillation. These patients were propensity score matched 1:1 to 737 patients not taking SSRI s. The primary outcome measure was major and nonmajor clinically relevant bleeding events, the principal safety outcome in ROCKET AF . Over a mean 1.6 years of follow‐up, the rate of major/ nonmajor clinically relevant bleeding was 18.57 events/100 patient‐years for SSRI users versus 16.84 events/100 patient‐years for matched comparators, adjusted hazard ratio ( aHR ) of 1.16 (95% confidence interval [CI], 0.95–1.43). The aHR s were similar in patients taking rivaroxaban ( aHR 1.11 [95% CI, 0.82–1.51]) and those taking warfarin ( aHR 1.21 [95% CI, 0.91–1.60]). For the rarer outcome of major bleeding, the aHR for SSRI users versus those not taking SSRI s was 1.13 (95% CI, 0.62–2.06) for rivaroxaban for warfarin, the aHR was higher, at 1.58 (95% CI , 0.96–2.60) but not statistically significantly elevated. We found no significant increase in bleeding risk when SSRI s were combined with anticoagulant therapy, although there was a suggestion of increased bleeding risk with SSRI s added to warfarin. While physicians should be vigilant regarding bleeding risk, our results provide reassurance that SSRI s can be safely added to anticoagulants in patients with atrial fibrillation . URL : www.clinicaltrials.gov . Unique identifier: NCT 00403767.
Publisher: AMPCo
Date: 06-2010
DOI: 10.5694/J.1326-5377.2010.TB03663.X
Abstract: To assess the prevalence of and risk factors for claudication and its association with subsequent cardiovascular events. Observational cohort study of 12 203 Western Australian men aged 65 years and over, recruited from 1996 to 1999, and followed up from 2001 to 2004. Prevalence of claudication and incidence of peripheral arterial disease (PAD) risk factors for claudication and its association with subsequent cardiovascular events. The prevalence of claudication was 5.3% (638 of 11 970 men). At follow-up, after exclusion of 148 men with claudication at baseline and 76 with missing data at follow-up, the crude average annual incidence of new PAD (claudication or procedure for PAD) was 0.85% (95% CI, 0.72%-0.96%). The risk factors for prevalent claudication and incident PAD were similar, with age, smoking, hypertension, diabetes and history of cardiovascular disease dominating. Of the men with claudication at baseline, nearly half (47.5% 303 of 638) were not taking aspirin. At follow-up, 42.5% (82 of 193) of the men with incident PAD were not taking aspirin. Claudication at baseline was associated with twice the risk of cardiovascular death (hazard ratio, 2.00 95% CI, 1.52-2.64). There was a J-shaped relationship between aortic diameter, and both prevalent claudication and subsequent cardiovascular events. Among older men, claudication is prevalent and is associated with factors that can still be modified in older age, including smoking, exercise and diet. Relatively few men with claudication or at risk of PAD use aspirin. Claudication is a significant predictor of cardiovascular outcome.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 2016
DOI: 10.3382/PS/PEV316
Abstract: The grinding of cereals by various milling methods as well as thermal treatment of feed may influence mineral digestibility and egg quality. The present study investigated the effect of feed produced by disc mill (D) and wedge-shaped disc mill (WSD), as mash (M) or expandate (E) on apparent ileal absorption (AIA) and apparent total digestibility (ATD) of calcium, phosphorus, magnesium, zinc, manganese, copper and iron, as well as on egg quality in laying hens. A total of 192 hens (Lohmann Brown) aged 19 wk, were assigned using a randomized design with a 2 × 2 factorial arrangement. Four experimental diets were offered ad libitum. Eggs were analyzed for weight, shape index, area, shell weight per unit surface area, yolk color, air cell, blood spot, Haugh unit, albumen and yolk measures (index, weight, height, width and length), shell measures (surface area, stability, density, thickness and membrane weight), as well as percent contents of albumen, yolk, shell, and shell membrane. The ATD for phosphorus, manganese, and copper was higher in WSD compared with D treatment (P = 0.028, P = 0.028 and P = 0.016, respectively). The interaction between milling methods and thermal treatment influenced ATD of copper (P = 0.033), which was higher in WSD+M group (41.0 ± 20.2) compared with D+E group (-3.21 ± 25.1), whereas no differences were observed for D+M (1.90 ± 37.8) and WSD+E (8.02 ± 36.2) groups. Egg stability tended to be higher in E compared with M treatment (P = 0.055). Albumen weight, percentage albumen weight, and albumen: yolk were higher and percentage yolk weight was lower in D compared with WSD treatment (P = 0.043, P = 0.027, P = 0.024, and P = 0.041, respectively). Number of blood spots was higher in E than M treatment (P = 0.053). In conclusion, use of a wedge-shaped disc mill resulted in higher ATD for phosphorus, manganese, and copper than use of a disc mill however, digestibility for majority of minerals as well as egg quality parameters was comparable. Therefore, feed produced by either disc mill or wedge-shaped disc mill as mash or expandate may be used for laying hens without negative effects on egg quality.
Publisher: Public Library of Science (PLoS)
Date: 29-03-2021
DOI: 10.1371/JOURNAL.PONE.0248931
Abstract: While there is clear evidence that high levels of pollution are associated with increased all-cause mortality and cardiovascular mortality and morbidity, the biological mechanisms that would explain this association are less understood. We examined the association between long-term exposure to air pollutants and risk factors associated with cardiovascular disease. Air pollutant concentrations were estimated at place of residence for cohort members in the Western Australian Centre for Health and Ageing Health in Men Study. Blood s les and blood pressure measures were taken for a cohort of 4249 men aged 70 years and above between 2001 and 2004. We examined the association between 1-year average pollutant concentrations with blood pressure, cholesterol, triglycerides, C-reactive protein, and total homocysteine. Linear regression analyses were carried out, with adjustment for confounding, as well as an assessment of potential effect modification. The four pollutants examined were fine particulate matter, black carbon (BC), nitrogen dioxide, and nitrogen oxides. We found that a 2.25 μg/m 3 higher exposure to fine particulate matter was associated with a 1.1 percent lower high-density cholesterol (95% confidence interval: -2.4 to 0.1) and 4.0 percent higher serum triglycerides (95% confidence interval: 1.5 to 6.6). Effect modification of these associations by diabetes history was apparent. We found no evidence of an association between any of the remaining risk factors or biomarkers with measures of outdoor air pollution. These findings indicate that long-term PM 2.5 exposure is associated with elevated serum triglycerides and decreased HDL cholesterol. This requires further investigation to determine the reasons for this association.
Publisher: Oxford University Press (OUP)
Date: 2005
Publisher: American College of Physicians
Date: 09-2023
DOI: 10.7326/M23-0342
Publisher: Wiley
Date: 26-01-2023
Publisher: Elsevier BV
Date: 10-2023
Publisher: S. Karger AG
Date: 2004
DOI: 10.1159/000075299
Abstract: Among high vascular risk patients, acetylsalicylic acid (ASA) reduces the relative risk of serious vascular events by about one fifth. However, because ASA fails to prevent four fifths of serious vascular events, more effective, yet equally safe and affordable, antiplatelet regimens are desired. Compared with ASA, clopidogrel alone reduces the odds of serious vascular events by about 10%, and the combination of dipyridamole and ASA reduces the odds of serious vascular events by about 6%. Combining ASA with an orally administered platelet glycoprotein (GP) IIb/IIIa blocker is not effective, and indeed more hazardous than ASA alone. Among patients with non-ST-segment acute coronary syndromes (ACS), the addition of an intravenously administered GP IIb/IIIa receptor antagonist to ASA reduces the risk of vascular events by about 10% compared with ASA, and the addition of clopidogrel to ASA reduces the risk of vascular events by 20% compared with ASA alone. Among patients undergoing percutaneous coronary intervention (PCI), both the addition of an intravenously administered GP IIb/IIIa receptor antagonist to ASA, and the addition of clopidogrel to ASA reduce the risk of vascular events by 30% compared with ASA alone. The greater efficacy of the combinations of ASA with clopidogrel, and ASA with an intravenously administered GP IIb/IIIa receptor antagonist, in patients with ACS and those undergoing PCI has fostered several ongoing and planned trials of these regimens in the acute and long-term management of patients with ischaemic brain syndromes. The combination of ASA and clopidogrel is being compared with ASA alone within 12 h of onset of symptoms of TIA in two trials (FASTER, ATARI), and the use of an intravenously administered GP IIb/IIIa receptor antagonist is being compared with placebo within 6 h of onset of acute ischaemic stroke in two trials (AbESST, AbESST-2). Six trials are assessing the combination of clopidogrel and ASA in the long-term management of patients with ischaemic brain syndromes due to atherothrombosis (MATCH, CHARISMA, ARCH, CARESS, SPS3) or atrial fibrillation (ACTIVE). The MATCH trial of clopidogrel and ASA versus clopidogrel alone in patients with recent TIA or ischaemic stroke is the first which is likely to report its results – in mid 2004. The combination of dipyridamole and ASA is being compared with ASA in the ESPRIT trial and with the combination of clopidogrel and ASA in the planned PRoFESS trial. These ongoing and planned clinical trials of antiplatelet therapy promise to further define the role of combination antiplatelet therapy in the acute and long-term management of patients with ischaemic brain syndromes.
Publisher: Elsevier BV
Date: 12-2014
Publisher: SAGE Publications
Date: 10-2018
Abstract: Limited evidence exists to support very early intensive aphasia rehabilitation after stroke. VERSE is a PROBE trial designed to determine whether two types of intensive aphasia therapy, beginning within 14 days of acute stroke, provide greater therapeutic and cost-effectiveness than usual care. To publish the detailed statistical analysis plan for the VERSE trial prior to unblinding. This statistical analysis plan was based on the published and registered VERSE trial protocol and was developed by the blinded steering committee and management team, led by the trial statistician. This plan was developed using outcome measures and trial data collection forms. The VERSE statistical analysis plan is consistent with reporting standards for clinical trials and provides for clear and open reporting. Publication of a statistical analysis plan serves to reduce potential trial reporting bias and outlines transparent pre-specified analyses. Australian New Zealand Clinical Trials Registry (ANZCTR) Registration number: ACTRN12613000776707 Universal Trial Number (UTN) is U1111-1145-4130.
Publisher: Elsevier BV
Date: 08-2011
Publisher: Frontiers Media SA
Date: 07-07-2023
DOI: 10.3389/FIMMU.2023.1192028
Abstract: The RNA-binding protein AU-rich-element factor-1 (AUF-1) participates to posttranscriptional regulation of genes involved in inflammation and cellular senescence, two pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). Decreased AUF-1 expression was described in bronchiolar epithelium of COPD patients versus controls and in vitro cytokine- and cigarette smoke-challenged human airway epithelial cells, prompting the identification of epithelial AUF-1-targeted transcripts and function, and investigation on the mechanism of its loss. RNA immunoprecipitation-sequencing (RIP-Seq) identified, in the human airway epithelial cell line BEAS-2B, 494 AUF-1-bound mRNAs enriched in their 3’-untranslated regions for a Guanine-Cytosine (GC)-rich binding motif. AUF-1 association with selected transcripts and with a synthetic GC-rich motif were validated by biotin pulldown. AUF-1-targets’ steady-state levels were equally affected by partial or near-total AUF-1 loss induced by cytomix (TNFα/IL1β/IFNγ/10 nM each) and siRNA, respectively, with differential transcript decay rates. Cytomix-mediated decrease in AUF-1 levels in BEAS-2B and primary human small-airways epithelium (HSAEC) was replicated by treatment with the senescence- inducer compound etoposide and associated with readouts of cell-cycle arrest, increase in lysosomal damage and senescence-associated secretory phenotype (SASP) factors, and with AUF-1 transfer in extracellular vesicles, detected by transmission electron microscopy and immunoblotting. Extensive in-silico and genome ontology analysis found, consistent with AUF-1 functions, enriched RIP-Seq-derived AUF-1-targets in COPD-related pathways involved in inflammation, senescence, gene regulation and also in the public SASP proteome atlas AUF-1 target signature was also significantly represented in multiple transcriptomic COPD databases generated from primary HSAEC, from lung tissue and from single-cell RNA-sequencing, displaying a predominant downregulation of expression. Loss of intracellular AUF-1 may alter posttranscriptional regulation of targets particularly relevant for protection of genomic integrity and gene regulation, thus concurring to airway epithelial inflammatory responses related to oxidative stress and accelerated aging. Exosomal-associated AUF-1 may in turn preserve bound RNA targets and sustain their function, participating to spreading of inflammation and senescence to neighbouring cells.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JAD.2022.04.133
Abstract: Sleep difficulties increase the risk of current and future depression, but it is unclear if this relationship is causal. Prospective cohort study of a community s le of men aged 70-89 years followed for up to 17 years. Initial assessments occurred between 2001 and 2004. Participants were followed until death or 31 December 2018. Patient Health Questionnaire (PHQ-9) ≥ 10 at subsequent waves of assessments (every 2-3 years) or the recorded diagnosis of a depressive disorder in the Western Australian Data Linkage System marked the onset of depression during follow up. We excluded from follow up men with prevalent depression. The systematic review of longitudinal studies examining the association between disrupted sleep and depression in later life followed PRISMA guidelines. 3441 of 5547 older men reported sleep difficulties at study entry. Current or past depression affected 437 of 5547 participants. Of the 4561 older men free of depression, 2693 reported sleep difficulties. The hazard ratio (HR) of incident depression among participants with sleep problems was 1.67 (95%CI = 1.39-2.00). Statistical adjustments for age, place of birth, education, smoking and physical frailty did not change the effect-size of this association. The systematic review identified another 14 studies, and the meta-analysis yielded an overall risk ratio of depression of 1.82 (95%CI = 1.69-1.97), although the overall quality of available evidence was sub-optimal. Disrupted sleep increases the risk of depression in later life and this seems unlikely to be due to reverse causality. Older adults with sleep difficulties are legitimate targets of interventions to prevent depression.
Publisher: American Medical Association (AMA)
Date: 10-01-2017
Abstract: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million] 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million] 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million] 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this s le suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2020
DOI: 10.1186/S13063-020-4124-7
Abstract: Studies have suggested that fluoxetine might improve neurological recovery after stroke, but the results remain inconclusive. The EFFECTS (Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke) reached its recruitment target of 1500 patients in June 2019. The purpose of this article is to present all amendments to the protocol and describe how we formed the EFFECTS trial collaboration in Sweden. In this investigator-led, multicentre, parallel-group, randomised, placebo-controlled trial, we enrolled non-depressed stroke patients aged 18 years or older between 2 and 15 days after stroke onset. The patients had a clinical diagnosis of stroke (ischaemic or intracerebral haemorrhage) with persisting focal neurological deficits. Patients were randomised to fluoxetine 20 mg or matching placebo capsules once daily for 6 months. Seven amendments were made and included clarification of drug interaction between fluoxetine and metoprolol and the use of metoprolol for severe heart failure as an exclusion criterion, inclusion of data from central Swedish registries and the Swedish Stroke Register, changes in informed consent from patients, and clarification of design of some sub-studies. EFFECTS recruited 1500 patients at 35 centres in Sweden between 20 October 2014 and 28 June 2019. We plan to unblind the data in January 2020 and report the primary outcome in May 2020. EFFECTS will provide data on the safety and efficacy of 6 months of treatment with fluoxetine after stroke in a Swedish health system setting. The data from EFFECTS will also contribute to an in idual patient data meta-analysis. EudraCT 2011-006130-16 . Registered on 8 August 2014. ISRCTN, ISRCTN13020412 . Registered on 19 December 2014. ClinicalTrials.gov: NCT02683213 . Retrospectively registered on 2 February 2016.
Publisher: Oxford University Press (OUP)
Date: 10-2013
DOI: 10.1530/EJE-13-0306
Abstract: Thyroid dysfunction predicts poorer health outcomes, but the relationship between thyroid hormone levels within the reference range and mortality in older adults remains unclear. In this study, we examined the associations between the concentrations of free thyroxine (FT 4 ) and TSH and all-cause mortality in older men without thyroid disease. We performed a longitudinal study in community-dwelling men aged 70–89 years. Men with thyroid disease or taking thyroid-related medications were excluded. Baseline FT 4 and TSH levels were assayed. Incident deaths were ascertained using data linkage. There were 3885 men without thyroid disease followed for (mean± s.d .) 6.4±1.5 years, during which time 837 had died (21.5%). Men who had died had higher baseline FT 4 levels (16.2±2.3 vs 15.8±2.1 pmol/l, P .001), but comparable TSH levels (2.4±1.5 vs 2.3±1.5 mIU/l, P =0.250). After accounting for age, smoking, physical factors and medical comorbidities, higher circulating FT 4 levels predicted all-cause mortality (quartile Q4 vs quartiles Q1–Q3: FT 4 levels ≥17.32 vs .32 pmol/l: adjusted hazard ratio (HR)=1.19, 95% CI=1.02–1.39, P =0.025). TSH levels did not predict mortality. After excluding men with subclinical hyperthyroidism or hypothyroidism, there were 3442 men and 737 who had died (21.4%). In these men, higher FT 4 levels remained independently associated with all-cause mortality (quartile Q4 vs quartiles Q1–Q3: adjusted HR=1.19, 95% CI=1.02–1.41, P =0.032). Higher FT 4 levels are associated with all-cause mortality in euthyroid older men, independently of conventional risk factors and medical comorbidities. Additional research is needed to determine whether or not this relationship is causal and to clarify the utility of thyroid function testing to stratify mortality risk in ageing men.
Publisher: American Medical Association (AMA)
Date: 2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2022
DOI: 10.1161/CIRCULATIONAHA.121.055018
Abstract: Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in in iduals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-11-2019
DOI: 10.1161/CIRCULATIONAHA.119.040267
Abstract: Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive rolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non–vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non–vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: Springer Berlin Heidelberg
Date: 1989
Publisher: S. Karger AG
Date: 1996
DOI: 10.1159/000108068
Publisher: American Medical Association (AMA)
Date: 07-2021
Publisher: Elsevier BV
Date: 07-2023
Publisher: BMJ
Date: 2004
DOI: 10.1136/EBM.9.1.29
Publisher: Wiley
Date: 08-2011
DOI: 10.5694/J.1326-5377.2011.TB03241.X
Abstract: The clinical usefulness of laboratory testing of adult patients with venous thromboembolism (VTE) for heritable thrombophilia needs to be critically evaluated. At present, some clinicians use testing to identify patients at higher risk of recurrence (who may benefit from an extended period of anticoagulation beyond the usual 3-6 months) and their relatives at risk of a first VTE episode. As prevalence of heritable thrombophilia is related to age and ethnic origin, the pretest probability of detecting heritable thrombophilia may be low in unselected populations. Interpretation of laboratory results may not be straightforward. Apparent deficiencies of a natural anticoagulant may be due to acute thrombosis and "consumption", concomitant therapy with heparin and/or warfarin and other clinical factors. The predictive value of recurrent VTE conferred by the most common types of heritable thrombophilia (factor V Leiden and the G20210A prothrombin mutation) is limited. Risk of recurrence associated with deficiencies of a natural anticoagulant is less certain due to their rarity. Clinical risk factors (eg, the presence or otherwise of provoking factor(s) and whether or not the risk factor for VTE is reversible or permanent) appear to be the most important predictors of VTE recurrence. Duration of anticoagulation should be determined by clinical risk factors rather than the presence, or otherwise, of heritable thrombophilia. The benefit of identifying relatives who are carriers of thrombophilia is uncertain, as VTE is a multifactorial disease resulting from the interaction of various risk factors, some well recognised and others as yet unknown.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2022
DOI: 10.1161/STROKEAHA.122.039203
Abstract: Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal models of stroke, as well as in observational and trial stroke studies in humans. This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Medline, Embase, and PsycINFO for preclinical and clinical studies published between January 2000 and September 2021. A random-effects meta-analysis was conducted from observational studies. From 1625 retrieved studies, 42 were included in the systematic review. Of those, we identified 36 rodent models of stroke using preinsult or postinsult treatment with lithium, and 6 studies were conducted in human s les, of which 4 could be meta-analyzed. The review of animal models was stratified according to the type of stroke and outcomes. Human data were sub ided into observational and intervention studies. Treatment of rodents with lithium was associated with smaller stroke volumes, decreased apoptosis, and improved poststroke function. In humans, exposure to lithium was associated with a lower risk of stroke among adults with bipolar disorder in 2 of 4 studies. Two small trials showed equivocal clinical benefits of lithium poststroke. Animal models of stroke show consistent biological and functional evidence of benefits associated with lithium treatment, whereas human evidence remains sparse and inconclusive. The potential role of lithium in poststroke recovery is yet to be adequately tested in humans.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2013
DOI: 10.1161/STROKEAHA.113.001886
Abstract: High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among in iduals with stroke or transient ischemic attack ≥6 months previously. A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg vitamin B6, 25 mg vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up. A total of 3089 participants (38%) voluntarily undertook the MMSE months after the qualifying stroke 2608 participants were cognitively unimpaired (MMSE ≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L P .001) but no change from baseline in the mean MMSE score (−0.22 points versus −0.25 points difference, 0.03 95% confidence interval, −0.13 to 0.19 P =0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47% risk ratio, 1.01 95% confidence interval, 0.69–1.48 P =0.976), cognitive decline (9.1% versus 10.3% risk ratio, 0.89 0.67–1.18 P =0.414), or cognitive impairment or decline (11.0% versus 11.3% risk ratio, 0.98 0.75–1.27 P =0.855). Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years. URL: www.controlled-trials.com . Unique identifier: ISRCTN74743444 URL: www.clinicaltrials.gov . Unique identifier: NCT00097669.
Publisher: Elsevier BV
Date: 05-2014
Abstract: Poultry feed is a potential vector for pathogens. Heat processing and organic acid treatments may decontaminate feed and can affect bird performance as well as feed digestibility. The present study was performed to investigate the effect of different thermal treatments including pelleting (P), long-term conditioning at 85°C for 3 min (L), or expanding at 110°C (E110) and 130°C for 3 to 5 s (E130) without or with 0.75 and 1.5% organic acid supplementation (63.75% formic acid, 25.00% propionic acid, and 11.25% water) on performance, nutrient digestibility, and organ weights of broilers. In total, 960 one-day-old broiler chicks were randomly assigned to 8 replicates using a 3 × 4 factorial arrangement. Performance variables were determined, and the relative organ weights and ileal and total amino acid (AA) digestibilities were measured at d 35. The organic acid inclusion linearly improved feed efficiency in the first week (P ≤ 0.05). The acid inclusion levels and thermal treatments had no significant effect on the performance variables at later intervals of the growing period of the birds. The L group showed the lowest ileal AA and CP digestibility. The inclusion of organic acids had a quadratic effect on total and ileal digestibility of isoleucine (P ≤ 0.05), whereas it had no significant effect on the ileal digestibility of other AA and nutrients. The relative weights of the jejunum and small intestine were significantly higher in the E130 group compared with P and L (P ≤ 0.05). In conclusion, our study demonstrated that long-term heat conditioning can decrease ileal nutrient digestibility, whereas pelleting and expansion, independently of organic acid addition, seemed to have no negative impact on broiler performance and nutrient digestibilities. Moreover, adding a blend of organic acids to broiler diets had neither positive nor negative effects on nutrient digestibility and final broiler performance. This indicates the feasibility of short-term thermal treatment and acid supplementation for hygienization of broiler feed without negatively influencing performance.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2010
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.MATURITAS.2016.01.003
Abstract: To examine if diabetes and duration of diabetes are direct or indirect causes of depression in later life. Cross-sectional study of a community-derived s le of 5462 men aged 70-89 years. Men with 'current depression' scored 7 or more on the abbreviated Geriatric Depression Scale (GDS-15), whereas men with 'ever depression' were either currently depressed or reported history or treatment for past depression. The presence of diabetes was established by self-reported history, fasting glucose ≥7 mmol/L (126 mg/dL), or use of insulin or hypoglycemic drugs. Duration of diabetes relied on self-report. Other measured factors included age, place of birth, education, smoking history, and the FRAIL scale. Diabetes was associated with increased odds ratio (OR) of ever (OR=1.49, 95%CI=1.25, 1.76) and current depression (OR=1.94, 95%CI=1.15, 2.48). The association between duration of diabetes and risk of current depression was 'J-shaped' with odds ratios of 1.92 (95%CI=1.44, 2.54), 1.56 (95%CI=0.89, 2.75), 2.49 (95%CI=1.16, 5.32) and 3.13 (95%CI=1.28, 7.63) for <10, 10-19.9, 20-29.9 and ≥30 years of diabetes history compared with older men without diabetes. The strength of these associations was attenuated after the analyses were adjusted for other measured factors, but the shape of the curve did not change. Structural equation modeling showed that frailty mediated some of the association between diabetes duration and depression (about 15%) and was a strong predictor of depression in the s le. In older men, the association between time lived with the diagnosis of diabetes and the risk of depression is 'J-shaped'. Frailty mediates some of the association between diabetes and depression, although other unmeasured factors are also likely to play a role. The introduction of strategies that are effective at decreasing diabetes-related complications may also contribute to decrease the risk of depression among older men.
Publisher: BMJ
Date: 06-05-2004
Publisher: Georg Thieme Verlag KG
Date: 28-10-2013
Abstract: The effects of very early aphasia therapy on recovery are equivocal. This article examines predictors of very early aphasia recovery through statistical modeling. This study involved a secondary analysis of merged data from two randomized, single-blind trials conducted in Australian acute and subacute hospitals. Study 1 (n = 59) compared daily therapy to usual ward care for up to 4 weeks poststroke in patients with moderate to severe aphasia. Study 2 (n = 20) compared daily group therapy to daily in idual therapy for 20 1-hour sessions over 5 weeks, in patients with mild to severe aphasia. The primary outcome measure was the Western Aphasia Battery Aphasia Quotient (AQ) at therapy completion. This analysis used regression modeling to examine the effects of age, baseline AQ and baseline modified Rankin Scale (mRS), average therapy amount, therapy intensity, and number of therapy sessions on aphasia recovery. Baseline AQ (p = 0.047), average therapy amount (p = 0.030), and baseline mRS (p = 0.043) were significant predictors in the final regression model, which explained 30% (p < 0.001) of variance in aphasia recovery. The amount of very early aphasia therapy could significantly affect communication outcomes at 4 to 5 weeks poststroke. Further studies should include amount of therapy provided to enhance reliability of prognostic modeling in aphasia recovery.
Publisher: Springer Science and Business Media LLC
Date: 20-08-2015
DOI: 10.1186/S13063-015-0864-1
Abstract: Several small trials have suggested that fluoxetine improves neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials that aim to determine whether routine administration of fluoxetine (20 mg daily) for 6 months after acute stroke improves patients’ functional outcome. The three trial investigator teams have collaboratively developed a core protocol. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned in idual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients. The trials include patients ≥18 years old with a clinical diagnosis of stroke, persisting focal neurological deficits at randomisation between 2 and 15 days after stroke onset. Patients are randomised centrally via web-based randomisation systems using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Our primary outcome measure is the modified Rankin scale (mRS) at 6 months. Secondary outcomes include the Stroke Impact Scale, EuroQol (EQ5D-5 L), the vitality subscale of the Short-Form 36, diagnosis of depression, adherence to medication, adverse events and resource use. Outcomes are collected at 6 and 12 months. The methods of collecting these data are tailored to the national setting. If FOCUS, AFFINITY and EFFECTS combined enrol 6000 participants as planned, they would have 90 % power (alpha 5 %) to detect a common odds ratio of 1.16, equivalent to a 3.7 % absolute difference in percentage with mRS 0–2 (44.0 % to 47.7 %). This is based on an ordinal analysis of mRS adjusted for baseline variables included in the minimisation algorithm. If fluoxetine is safe and effective in promoting functional recovery, it could be rapidly, widely and affordably implemented in routine clinical practice and reduce the burden of disability due to stroke. FOCUS: ISRCTN83290762 (23/05/2012), AFFINITY: ACTRN12611000774921 (22/07/2011). EFFECTS: ISRCTN13020412 (19/12/2014).
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.AHJ.2005.04.025
Abstract: Dietary supplementation with folic acid and vitamin B12 lowers blood homocysteine concentrations by about 25% to 30% in populations without routine folic acid fortification of food and by about 10% to 15% in populations with such fortification. In observational studies, 25% lower homocysteine has been associated with about 10% less coronary heart disease (CHD) and about 20% less stroke. We reviewed the design and statistical power of 12 randomized trials assessing the effects of lowering homocysteine with B-vitamin supplements on risk of cardiovascular disease. Seven of these trials are being conducted in populations without fortification (5 involving participants with prior CHD and 2 with prior stroke) and 5 in populations with fortification (2 with prior CHD, 2 with renal disease, and 1 with prior stroke). These trials may not involve sufficient number of vascular events or last long enough to have a good chance on their own to detect reliably plausible effects of homocysteine lowering on cardiovascular risk. But, taken together, these 12 trials involve about 52,000 participants: 32,000 with prior vascular disease in unfortified populations and 14,000 with vascular disease and 6000 with renal disease in fortified populations. Hence, a combined analysis of these trials should have adequate power to determine whether lowering homocysteine reduces the risk of cardiovascular events within just a few years. The strength of association of homocysteine with risk of cardiovascular disease may be weaker than had previously been believed. Extending the duration of treatment in these trials would allow any effects associated with prolonged differences in homocysteine concentrations to emerge. Establishing a prospective meta-analysis of the ongoing trials of homocysteine lowering should ensure that reliable information emerges about the effects of such interventions on cardiovascular disease outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2010
DOI: 10.1161/STROKEAHA.110.594317
Abstract: Background and Purpose— The relationship of cortical and subcortical cerebral atrophy to cerebral microvascular disease is unclear. We aimed to assess the associations of retinal vascular signs with cortical and subcortical atrophy in patients with acute stroke. Methods— In the Multi-Centre Retinal Stroke Study, 1360 patients with acute stroke admitted to 2 Australian and 1 Singaporean tertiary hospital during 2005 to 2007 underwent neuroimaging and retinal photography. Cortical and subcortical cerebral atrophy were graded based on standard CT scans. A masked assessment of retinal photographs identified focal retinal vascular signs, including retinopathy and retinal arteriolar wall signs (ie, focal arteriolar narrowing, arteriovenous nicking, arteriolar wall light reflex) and measured quantitative signs (retinal arteriolar and venular caliber). Results— After adjusting for age, gender, study site, hypertension, hypercholesterolemia, diabetes, and smoking status, none of the retinal vascular signs assessed were associated with cortical atrophy, whereas retinopathy (OR, 1.9 CI, 1.2 to 3.0) and enhanced arteriolar light reflex (OR, 2.0 CI, 1.2 to 3.2) were significantly associated with subcortical atrophy. Conclusion— Our finding that certain retinal vascular signs are associated with subcortical but not cortical atrophy, suggests a differential pathophysiology between these 2 cerebral atrophy subtypes and a potential role for small vessel disease underlying subcortical cerebral atrophy.
Publisher: Elsevier BV
Date: 11-2013
Publisher: Wiley
Date: 30-03-2012
DOI: 10.1002/ECE3.218
Publisher: SAGE Publications
Date: 19-08-2023
DOI: 10.1177/17474930231190745
Abstract: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0–50 unacceptable 51–68 poor 68–80.3 good .3 excellent) were used to determine usability of PreventS-MD. Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2 95% CI [77.0–84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7 95% CI [79.1–84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and in iduals at risk of stroke/CVD. In iduals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2000
Abstract: Background and Purpose —The goal of the present study was to identify risk factors for vascular disease in the elderly. Methods —We conducted a prospective study of control subjects from a population-based study of stroke in Perth, Western Australia, that was completed in 1989 to 1990 and used record linkage and a survey of survivors to identify deaths and nonfatal vascular events. Data validated through reference to medical records were analyzed with the use of Cox proportional hazards models. Results —Follow-up for the 931 subjects was 88% complete. By June 24, 1994, 198 (24%) of the subjects had died (96 from vascular disease), and there had been 45 nonfatal strokes or myocardial infarctions. The hazard ratio for diabetes exceeded 2.0 for all end points, whereas the consumption of meat times weekly was associated with a reduction in risk of ≤30%. In most models, female sex and consumption of alcohol were associated with reduced risks, whereas previous myocardial infarction was linked to an increase in risk. Conclusions —There are only limited associations between lifestyle and major vascular illness in old age. Effective health promotion activities in early and middle life may be the key to a longer and healthier old age.
Publisher: Elsevier BV
Date: 2015
Publisher: Oxford University Press (OUP)
Date: 05-2011
DOI: 10.1530/EJE-11-0059
Abstract: Circulating IGF1 declines with age while ill-health increases. Controversy remains whether differences in the levels of IGF1 and its binding proteins 1 and 3 (IGFBP1 and IGFBP3) determine health outcomes during ageing. We examined associations of IGF1, IGFBP1 and IGFBP3 with all-cause and cardiovascular mortality in older men. We conducted a prospective cohort study of community-dwelling men aged ≥70 years. Plasma collected at baseline (2001–2004) was assayed for total IGF1, IGFBP1 and IGFBP3. Incidence and causes of death from time of recruitment to 31 December 2008 were ascertained using the Western Australian Data Linkage System. Cox regression analyses were performed, adjusting for conventional cardiovascular risk factors. Among 3983 men followed for 5.2 years (median), 694 deaths occurred, 243 from cardiovascular disease (CVD). There was no difference in survival according to quintiles of IGF1. Increased IGFBP1 predicted increased all-cause mortality (highest versus lowest quintile: adjusted hazard ratio (HR)=1.98, 95% confidence interval (CI)=1.52–2.57, P .001 for trend) and increased cardiovascular mortality (HR=3.42 (2.03–5.77), P .001 for trend). Decreased IGFBP3 predicted increased all-cause mortality (lowest versus highest quintile: HR=1.57, 95% CI=1.23–2.01, P =0.007 for trend). Associations of IGFBP1 and IGFBP3 with all-cause mortality were not attenuated by adjustment for IGF1 levels. In older men, higher IGFBP1 and lower IGFBP3 levels predict overall and CVD-related mortality, while IGF1 levels are not associated with mortality. Further studies are needed to clarify the underlying mechanisms by which IGFBP1 and IGFBP3 levels are associated with mortality risk, and whether this occurs independently of IGF1.
Publisher: American Medical Association (AMA)
Date: 04-2016
Publisher: Wiley
Date: 18-10-2010
Publisher: Oxford University Press (OUP)
Date: 14-09-2019
Abstract: The management of anticoagulation therapy in patients with atrial fibrillation (AF) and cancer is challenging due to increased thrombotic and bleeding risks. We sought to determine the safety and efficacy of rivaroxaban in patients with AF and a history of cancer. ROCKET AF randomized 14 264 patients with AF to rivaroxaban or warfarin with a median follow-up of 1.9 years. Cox regression models were used to assess the association between cancer history and clinical outcomes, and the relative treatment effect of rivaroxaban vs. warfarin in these patients. A total of 640 patients enrolled in ROCKET AF had a history of cancer, with the most common types being prostate (28.6%), colorectal (16.1%), and breast (14.7%) cancer. Patients with a history of cancer were older, more frequently male, more likely to have prior vitamin K antagonist (VKA) use and had higher rates of overall bleeding [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.16-1.47 P < 0.0001] and non-cardiovascular death (HR 1.47, 95% CI 1.04-2.07 P = 0.031) compared with those with no cancer history. There were no significant associations between cancer history and stroke, venous thromboembolism, or myocardial infarction. The relative efficacy of rivaroxaban vs. warfarin for prevention of stroke/systemic embolism was similar in those with and without a history of cancer (interaction P-value = 0.21). In ROCKET AF, a history of cancer was associated with a higher risk of bleeding and non-cardiovascular death, but not ischaemic events. The relative efficacy and safety of rivaroxaban compared with warfarin were not significantly different in patients with and without a history of cancer. The results of this study are exploratory and should be taken in context of the study population, which may not be generalizable to those with advanced malignancy. Further investigation is needed to understand optimal anticoagulation strategies in patients with AF and cancer.Clinical trial registration: ClinicalTrials.gov: NCT00403767.
Publisher: Oxford University Press (OUP)
Date: 08-02-2023
Abstract: Older men on an average have lower testosterone concentrations, compared with younger men, and more age-related comorbidities. Whether lower testosterone concentrations contribute to biological ageing remains unclear. Shorter telomeres are a marker for biological age. We tested the hypothesis that testosterone concentrations are associated with leucocyte telomere length (LTL), in middle- to older-aged men. Cross-sectional analysis of the UK Biobank study, involving community-dwelling men aged 40-69 years. Serum testosterone and sex hormone–binding globulin (SHBG) were assayed. Free testosterone was calculated (cFT). Leucocyte telomere length was measured using polymerase chain reaction. Multivariable models were used to assess associations of hormones with standardised LTL. In 167 706 men, median age 58 years, adjusting for sociodemographic, lifestyle, and medical factors, total testosterone was inversely associated with standardised LTL, which was 0.09 longer (95% confidence interval [CI], 0.08-0.10, P & .001) in men with total testosterone at median of lowest quintile [Q1] vs highest [Q5]. This relationship was attenuated after additional adjustment for SHBG (0.03 longer, CI = 0.02-0.05, P = .003). The association between cFT and LTL was similar in direction but lower in magnitude. In multivariable analysis, SHBG was inversely associated with standardised LTL, which was 0.12 longer (CI = 0.10-0.13, P & .001) for SHBG at median Q1 vs Q5. Results were similar with testosterone included in the model (0.10 longer, CI = 0.08-0.12, P & .001). Total testosterone and SHBG were independently and inversely associated with LTL. Men with higher testosterone or SHBG had shorter telomeres, arguing against a role for testosterone to slow biological ageing in men.
Publisher: American College of Physicians
Date: 04-2015
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.IJCARD.2016.01.196
Abstract: Hospitalization for atrial fibrillation (AF) is a large and growing public health problem. We examined current trends in the incidence, prevalence, and associated mortality of first-ever hospitalization for AF. Linked hospital admission data were used to identify all Western Australia residents aged 35-84 years with prevalent AF and incident (first-ever) hospitalization for AF as a principal or secondary diagnosis during 1995-2010. There were 57,552 incident hospitalizations, mean age 69.8 years, with 41.4% women. Over the calendar periods, age- and sex-standardized incidence of hospitalization for AF as any diagnosis declined annually by 1.1% (95% CI 0.93, 1.29), while incident AF as a principal diagnosis increased annually by 1.2% (95% CI 0.84, 1.50). Incident AF hospitalization was higher among men than women, and 15-fold higher in the 75-84 compared with 35-64 year age group. The age- and sex-standardized prevalence of AF increased annually by 2.0% (95% CI 1.88, 2.03) over the same period. Comorbidity trends were mixed with diabetes and valvular heart disease increasing, and hypertension, coronary artery disease, heart failure, cerebrovascular disease, and chronic kidney disease decreasing. The 1-year all-cause mortality after incident AF hospitalization declined from 17.6% to 14.6% (trend P<0.001), with an adjusted hazard ratio of 0.86 (95% CI 0.81, 0.91). This contemporary study shows that incident AF hospitalization is not increasing except for AF as a principal diagnosis, while population prevalence of hospitalized AF has risen substantially. The high 1-year mortality following incident AF hospitalization has improved only modestly over the recent period.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2004
Publisher: Elsevier BV
Date: 08-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-04-2023
DOI: 10.1212/WNL.0000000000207093
Abstract: Depression has been reported to be a risk factor of acute stroke, based largely on studies in high-income countries. In the INTERSTROKE study, we explored the contribution of depressive symptoms to acute stroke risk and 1-month outcome across regions of the world, within subpopulations and by stroke type. The INTERSTROKE is an international case-control study of risk factors of first acute stroke, conducted in 32 countries. Cases were patients with CT- or MRI-confirmed incident acute hospitalized stroke, and controls were matched for age, sex, and within sites. Standardized questions asked about self-reported depressive symptoms during the previous 12 months and the use of prescribed antidepressant medications were recorded. Multivariable conditional logistic regression was used to determine the association of prestroke depressive symptoms with acute stroke risk. Adjusted ordinal logistic regression was used to explore the association of prestroke depressive symptoms with poststroke functional outcome, measured with the modified Rankin scale at 1 month after stroke. Of 26,877 participants, 40.4% were women, and the mean age was 61.7 ± 13.4 years. The prevalence of depressive symptoms within the last 12 months was higher in cases compared with that in controls (18.3% vs 14.1%, p 0.001) and differed by region ( p interaction .001), with lowest prevalence in China (6.9% in controls) and highest in South America (32.2% of controls). In multivariable analyses, prestroke depressive symptoms were associated with greater odds of acute stroke (odds ratio [OR] 1.46, 95% CI 1.34–1.58), which was significant for both intracerebral hemorrhage (OR 1.56, 95% CI 1.28–1.91) and ischemic stroke (OR 1.44, 95% CI 1.31–1.58). A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms. While preadmission depressive symptoms were not associated with a greater odds of worse baseline stroke severity (OR 1.02, 95% CI 0.94–1.10), they were associated with a greater odds of poor functional outcome at 1 month after acute stroke (OR 1.09, 95% CI 1.01–1.19). In this global study, we recorded that depressive symptoms are an important risk factor of acute stroke, including both ischemic and hemorrhagic stroke. Preadmission depressive symptoms were associated with poorer functional outcome, but not baseline stroke severity, suggesting an adverse role of depressive symptoms in poststroke recovery.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 04-2006
Publisher: American Chemical Society (ACS)
Date: 08-1987
DOI: 10.1021/IC00263A004
Publisher: Hindawi Limited
Date: 09-04-2015
DOI: 10.1111/IJCP.12631
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
DOI: 10.1161/STROKEAHA.113.000780
Abstract: Minocycline, in animal models and 2 small randomized controlled human trials, is a promising neuroprotective agent in acute stroke. We analyzed the efficacy and safety of intravenous minocycline in acute ischemic and hemorrhagic stroke. A multicenter prospective randomized open-label blinded end point evaluation pilot study of minocycline 100 mg administered intravenously, commenced within 24 hours of onset of stroke, and continued 12 hourly for a total of 5 doses, versus no minocycline. All participants received routine stroke care. Primary end point was survival free of handicap (modified Rankin Scale, ≤2) at day 90. Ninety-five participants were randomized 47 to minocycline and 48 to no minocycline. In the intention-to-treat population, 29 of 47 (65.9%) allocated minocycline survived free of handicap compared with 33 of 48 (70.2%) allocated no minocycline (rate ratio, 0.94 95% confidence interval, 0.71–1.25 and odds ratio, 0.73 95% CI, 0.31–1.71). A meta-analysis of the 3 human trials suggests minocycline may increase the odds of handicap-free survival by 3-fold (odds ratio, 2.99 95% CI, 1.74–5.16) but there was substantial heterogeneity among the trials. In this pilot study of a small s le of acute stroke patients, intravenous minocycline was safe but not efficacious. The study was not powered to identify reliably or exclude a modest but clinically important treatment effect of minocycline. Larger trials would improve the precision of the estimates of any treatment effect of minocycline. URL: www.anzctr.org.au . Unique identifier: ACTRN12612000237886.
Publisher: American Chemical Society (ACS)
Date: 08-1987
DOI: 10.1021/IC00263A005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2021
DOI: 10.1161/STROKEAHA.121.034705
Abstract: The EFFECTS (Efficacy of Fluoxetine—a Randomised Controlled Trial in Stroke) recently reported that 20 mg fluoxetine once daily for 6 months after acute stroke did not improve functional outcome but reduced depression and increased fractures and hyponatremia at 6 months. The purpose of this predefined secondary analysis was to identify if any effects of fluoxetine were maintained or delayed over 12 months. EFFECTS was an investigator-led, randomized, placebo-controlled, double-blind, parallel group trial in Sweden that enrolled adult patients with stroke. Patients were randomized to 20 mg oral fluoxetine or matching placebo for 6 months and followed for another 6 months. The primary outcome was functional outcome (modified Rankin Scale), at 6 months. Predefined secondary outcomes for these analyses included the modified Rankin Scale, health status, quality of life, fatigue, mood, and depression at 12 months. One thousand five hundred patients were recruited from 35 centers in Sweden between 2014 and 2019 750 were allocated fluoxetine and 750 placebo. At 12 months, modified Rankin Scale data were available in 715 (95%) patients allocated fluoxetine and 712 (95%) placebo. The distribution of modified Rankin Scale categories was similar in the 2 groups (adjusted common odds ratio, 0.92 [95% CI, 0.76–1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (interquartile range, 75–100) versus 93 (interquartile range, 82–100) P =0.0021 and communication 93 (interquartile range, 82–100) versus 96 (interquartile range, 86–100) P =0.024 domains of the Stroke Impact Scale compared with placebo. There were no other differences in secondary outcomes. Fluoxetine after acute stroke had no effect on functional outcome at 12 months. Patients allocated fluoxetine scored worse on memory and communication on the Stroke Impact Scale compared with placebo, but this is likely to be due to chance. URL: www.clinicaltrials.gov Unique identifier: NCT02683213.
Publisher: Cambridge University Press (CUP)
Date: 08-1992
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Elsevier BV
Date: 02-2011
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.JAD.2012.06.043
Abstract: The concept of 'vascular depression' implies that cardiovascular disease facilitates the onset or persistence of depression in later life, and that the natural course of depression should differ according to whether or not vascular pathology is present. Population-based cohort of 431 older men were diagnosed with depression (prevalent cases) and followed for up to 6 years. We used the Western Australian Data Linkage System to establish the presence of cardiovascular disease (CVD, documented history of coronary heart disease or stroke) and subsequent persistence or recurrence of depression during follow up (ICD-10 codes). Other measures recorded: age, place of birth, education, social support and disadvantage, smoking history, sensory impairment, medical morbidity burden and use of antidepressants. The age of participants ranged from 69 to 86 years and CVD was present in 212 (49.2%) of them. Depressed men with and without CVD had a similar distribution of demographic, lifestyle, social and clinical factors as men without CVD, but higher medical morbidity. One hundred and twenty six (29.2%) men died and another 43 had a recorded diagnosis of depressive disorder between the baseline assessment and the 31st December 2007. Compared with participants without CVD, the adjusted hazard ratio of recurrent or persistent depression during follow up for participants with CVD was 0.78 (95% confidence interval, 95% CI=0.43-1.42). An additional 30 men were identified with depression during a new clinical assessment in 2008-09. Logistic regression showed that the adjusted odds of depression for men with compared to those without CVD was 0.98 (95% CI=0.61-1.59). Persistence or recurrence of symptoms over 6 years in older men with depression is not influenced by the presence of CVD, which raises doubts about the usefulness and validity of the concept of vascular depression.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: American Chemical Society (ACS)
Date: 07-1970
DOI: 10.1021/IC00263A006
Publisher: Springer Science and Business Media LLC
Date: 2004
DOI: 10.2165/00129784-200404010-00006
Abstract: Aspirin (acetylsalicylic acid) reduces the odds of serious atherothrombotic vascular events and death in a broad category of high risk patients by about one-quarter. The mechanism is believed to be inhibition of thromboxane biosynthesis by inactivation of platelet cyclo-oxygenase-1 enzyme. However, aspirin is not that effective it still fails to prevent the majority of serious vascular events. Mechanisms that may account for the failure of aspirin to prevent vascular events include non-atherothrombotic causes of vascular disease, non-adherence to aspirin therapy, an inadequate dosage, alternative "upstream" pathways of platelet activation (e.g. via stimulation of the ADP, collagen or thrombin receptors on platelets), aspirin-insensitive thromboxane biosynthesis (e.g. via monocyte cyclo-oxygenase-2), or drugs that interfere with the antiplatelet effects of aspirin. Genetic or acquired factors may further modify the inhibitory effects of aspirin on platelets (e.g. polymorphisms involving platelet-associated proteins, increased platelet turnover states). Identification and treatment of the potential causes of aspirin failure could prevent at least another 20% of serious vascular events (i.e. over and above those that are currently prevented by aspirin). There is currently no role for routine laboratory testing to measure the antiplatelet effects of aspirin. Clinicians should ensure that patients at high risk of atherothrombosis (>3% risk over 5 years) are compliant with aspirin therapy and are taking the correct dosage (75-150 mg/day). Patients who cannot tolerate aspirin, are allergic to aspirin, or have experienced recurrent serious atherothrombotic events whilst taking aspirin, should be treated with clopidogrel, and patients with acute coronary syndromes benefit from the combination of clopidogrel plus aspirin. Future research is required to standardize and validate laboratory testing of the antiplatelet effects of aspirin and to identify treatments that can both improve these laboratory measures and reduce the risk of future atherothrombotic events.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2002
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.ENVINT.2019.01.075
Abstract: Natural outdoor environments may mitigate harmful environmental factors associated with city living. We studied the longitudinal relationship between natural ('green and blue') outdoor environments and mortality in a cohort of older men residing in Perth, Western Australia. We studied a cohort of 9218 men aged 65 years and older from the Health In Men Study. Participants were recruited in 1996-99 and followed until 2014, during which 5889 deaths were observed. Time-varying residential surrounding greenness based on the Normalized Difference Vegetation Index, and the number and size of parks, natural space and waterbodies were defined to characterize the natural outdoor environment. All-cause non-accidental and cause-specific mortality was ascertained with the Western Australian Data Linkage System. The association of the natural outdoor environment with mortality was examined using Cox regression analysis. After adjusting for age, men living in the highest quartile of cumulative average surrounding greenness had a 9% lower rate of all-cause non-accidental mortality (95% confidence interval [CI] 0.84, 0.98 p = .013) compared with those in the lowest quartile. This association was no longer present after adjustment for other risk factors, especially level of education. Living within 500 m of one (vs. no) natural space was associated with decreased mortality risk (adjusted hazard ratio 0.93 95% CI 0.86, 1.00 p = .046), but no association with mortality was found for two or more natural spaces compared to none and for parks. Associations between waterbodies and mortality were inconsistent, showing non-linear beneficial and harmful associations. In this longitudinal study of older men residing in Perth, we observed evidence suggestive of an association between access to natural spaces and decreased mortality. Associations between surrounding greenness and mortality seemed to be confounded by level of education, and associations with waterbodies were complex and need to be studied further.
Publisher: Wiley
Date: 10-05-2023
DOI: 10.1111/CEN.14926
Abstract: Older people are more prone to vitamin D deficiency than younger populations. In idual lifestyle factors have been associated with vitamin D status. We examined the influence of a combination of lifestyle factors on vitamin D status in older men. In a population‐based cohort study of older men (age ≥65 years), a lifestyle score was calculated from eight prudent health‐related behaviours (smoking, exercise, alcohol, fish and meat consumption, adding salt, milk choices and obesity) collected via questionnaire at baseline. Blood s les were collected 5 years afterwards to measure plasma 25‐hydroxyvitamin D (25OHD) levels. Associations between lifestyles and the likelihood of having plasma 25OHD levels of ≥75 versus nmol/L and ≥50 versus nmol/L were tested using logistic regression models. Of the 2717 men analysed, mean plasma 25OHD was 69.0 ± 23.5 nmol/L, with 20.7% having plasma 25OHD nmol/L. Men engaging in ≥4 healthy lifestyle behaviours had 20% higher odds of plasma 25OHD ≥75 nmol/L (adjusted OR = 1.20, 95% CI: 1.01−1.45) compared to those with healthy behaviours. No association was found for 25OHD ≥50 nmol/L. Higher physical activity was the only in idual component significantly associated with vitamin D sufficiency (highest vs. lowest quintiles of physical activity, adjusted OR = 2.01, 95% CI: 1.47−2.74 for 25OHD ≥50 nmol/L, adjusted OR = 2.35, 95% CI: 1.81−3.06 for 25OHD ≥75 nmol/L). Multiple healthy lifestyle behaviours are associated with better vitamin D status in older men. Further work is needed to determine the effects of promoting healthy lifestyle behaviours, including physical activity, on vitamin D sufficiency.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Informa UK Limited
Date: 31-12-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-01-2013
DOI: 10.1161/CIRCULATIONAHA.112.107128
Abstract: We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non–central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R 2 CHADS 2 ) improved net reclassification index by 6.2% compared with CHA 2 DS 2 VASc (C statistic=0.578) and by 8.2% compared with CHADS 2 (C statistic=0.575). The inclusion of creatinine clearance mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R 2 CHADS 2 in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%–22.5%) relative to CHADS 2 . In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. URL: www.ClinicalTrials.gov . Unique identifier: NCT00403767.
Publisher: Elsevier BV
Date: 08-2014
Abstract: Several studies illustrated that the structure of feed, i.e., the particle size, particle-size distribution, and the physical form of the diet, affects the avian gastrointestinal function and health leading to changes in productive performance. However, investigations concerning the effects of feeding differently processed diets on laying hens are limited and primarily concentrated on bird performance. The current study examines the effect of feed processing on the gastrointestinal morphology and on the jejunal glucose transport of laying hens. In 8 replicates, a total of 384 hens (Lohmann Brown) aged 20 wk were randomly allocated to 8 different groups and fed over a period of 21 d in a 3-factorial design. Diets differed in 1) grinding method, either hammer or roller mill 2) physical form, either mash or expandate and 3) particle size, either coarsely or finely ground. During the experimental trial, the laying performance of each feeding group was recorded daily and the feed intake and BW determined weekly. After slaughtering, the weights of the pancreas, proventriculus, gizzard, and small intestine were measured. Villus lengths and crypt depths of the duodenum, jejunum, and ileum were determined. The jejunal electrogenic glucose transport was studied in Ussing chambers. Hens that received mash instead of expandate had higher proventriculus (P = 0.011), gizzard (P < 0.001), and pancreas (P = 0.019) weights, whereas the feeding of coarsely instead of finely ground diets led to higher gizzard weights (P < 0.001). Mash-fed hens showed longer duodenal (P < 0.001) and shorter ileal villi (P = 0.047) and increased duodenal villus height-to-crypt depth ratios (P < 0.001) than those given the expandate. Mash-fed hens had higher glucose transport rates than expandate-fed hens (P < 0.001). In conclusion, the feeding of coarsely ground as well as mash diets had stimulating effects on the development of the gastrointestinal organs. Moreover, the feeding of mash influenced the intestinal microstructure of the epithelium that was accompanied by higher glucose transport capacities.
Publisher: Springer Science and Business Media LLC
Date: 26-06-2007
DOI: 10.1007/S11883-007-0038-Z
Abstract: Recent trials of antiplatelet therapy for stroke prevention indicate that the combination of clopidogrel (75 mg/d) plus low-dose aspirin (75-162 mg/d) was not more effective than low-dose aspirin alone in the long-term prevention of major vascular events among patients at high risk of atherothrombotic events, nor was it more effective than oral anticoagulation in patients with atrial fibrillation. Furthermore, oral anticoagulation (International Normalized Ratio of 2.0-3.0) was not more effective than aspirin alone among patients with recent cerebral ischemia of presumed arterial origin. However, the addition of extended-release dipyridamole to aspirin was more effective than aspirin alone among patients with recent cerebral ischemia of presumed arterial origin. A large trial comparing clopidogrel with the combination of aspirin and extended-release dipyridamole in more than 20,000 patients with recent (< 120 days) atherothrombotic ischemic stroke is expected to report in 2008.
Publisher: Elsevier BV
Date: 03-2013
Publisher: SAGE Publications
Date: 02-06-2014
DOI: 10.1111/IJS.12295
Abstract: Each year, 1·0–2·0% of in iduals with atrial fibrillation and 0·1–0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2–0·5% of in iduals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offers practical approaches to the management of patients receiving novel oral anticoagulants who present with an ischemic or hemorrhagic stroke. Specifically, we discuss the role of thrombolysis in anticoagulated patients with acute ischemic stroke and factors to consider concerning restarting anticoagulation after acute ischemic and hemorrhagic stroke.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.WNEU.2018.04.042
Abstract: Successful recanalization (SR) of the occluded artery does not always translate into a good outcome for patients with acute anterior circulation large-vessel occlusion stroke. This study aimed to develop a scale to predict poor outcome early despite SR after endovascular treatment (EVT) for candidates identified using current guidelines. The eligible patients with SR were retrospectively enrolled between 2014 and 2016. Poor outcome was defined as modified Rankin Scale of 3 to 6 at 90 days. Multivariable logistic regression was used to derive a PooR outcomE of enDovascular treatment wIth suCcessful recanalizaTion (PREDICT) scale. The discrimination and calibration of the scale were assessed. A total of 332 patients were enrolled. The PREDICT scale consisted of 5 items (prior intravenous thrombolysis, collateral status, blood glucose, blood neutrophil-to-lymphocyte ratio, and baseline National Institutes of Health Stroke Scale score). The scale had good discrimination and calibration. The risk of poor outcome was stratified into very low (PREDICT scale score ≤5), low (6-8), moderate (9-11), and high (≥12). Compared with patients with a score of ≤5, patients with a score of ≥12 had an 18.33-fold (95% confidence interval [CI], 6.36-52.89) increased risk of poor outcome. The PREDICT scale is a practical tool for early prediction of poor outcome despite SR after EVT in our patients and, if validated in other patient populations, may serve as a scale for identifying which patients are most, and least, likely to benefit from EVT.
Publisher: BMJ
Date: 08-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2014
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: American College of Physicians
Date: 08-2015
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JAMDA.2016.09.002
Abstract: Older adults with depression have increased risk of frailty and death. To determine if history of depression hinders future physical and functional capacity. Prospective longitudinal cohort study of 1148 men aged 70-87 years who were living in the Perth metropolitan community in 2001-2004 and completed a follow-up assessment of physical and functional capacity in 2011-2012. Outcomes were collected in 2011-2012 and included 4 measures of physical function (timed up-and-go, timed sit-to-stand, functional reach, and step test) and the assessment of basic (activities of daily living) and instrumental activities of daily living. We also collected information on depression and frailty [using the FRAIL (fatigue resistance ambulation illness, and loss of weight) scale] in 2001-2004 and 2011-2012. Frail men at the 2001-2004 were excluded from the analyses. Men with history of depression at the 2001-2004 assessment showed significantly worse performance than their counterparts in the timed sit-to-stand and step tests 9 years later. They also had approximately twice the risk of attaining the lowest decile of performance in both tests (analyses adjusted for age, education, and prevalent depressive symptoms). In addition, the adjusted risk ratio of impaired instrumental activities of daily living was 58% (95% confidence interval 15%, 116%) greater for men with than without history of past depression. These associations were particularly robust for men with current depression at the 2001-2004 assessment. Nonfrail older men with history of current or past depression showed greater impairment of physical and functional capacity 9 years later. Older men with history of depression may benefit from regular monitoring of physical and occupational function and should be targeted by preventive trials designed to improve function and decrease frailty.
Publisher: Springer Science and Business Media LLC
Date: 20-09-2008
Publisher: Wiley
Date: 28-11-2019
DOI: 10.1002/GPS.5028
Abstract: To determine if hearing loss is associated with increased risk of incident psychosis in later life. Longitudinal cohort study of a community-representative s le of 38 173 men aged 65 to 85 years at the start of the follow-up period of 18 years. We used the Western Australian Data Linkage System to ascertain the presence of hearing loss and of psychotic disorders according to the International Classification of Diseases (ICD) (versions 8, 9, and 10). We also collected information on concurrent morbidities: cancer and diseases of the cardiovascular, respiratory, digestive, and renal systems. One thousand four hundred forty-two (3.8%) and 464 (1.2%) men had a recorded diagnosis of hearing loss and psychosis at the start of follow-up. After excluding the 464 participants with prevalent psychosis, 37 709 men were available for the longitudinal study, and of these, 252 (0.7%) developed a psychotic disorder. Competing risk regression showed that hearing loss was associated incident psychosis (subhazard ratio = 2.03, 95% CI, 1.24-3.32 after statistical adjustment for age and concurrent morbidities). Hearing loss is associated with double the risk of incident psychosis in older men. Available evidence suggests that this link could be causal, although conclusive evidence is still missing from randomized controlled trials designed to test the effect of correction of hearing loss on the prevalence and incidence of psychosis.
Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000315099
Publisher: Elsevier BV
Date: 10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: The Endocrine Society
Date: 07-2009
DOI: 10.1210/JC.2008-2416
Abstract: Lower circulating testosterone concentrations are associated with metabolic syndrome, type 2 diabetes, carotid intima-media thickness, and aortic and lower limb arterial disease in men. However, it is unclear whether lower testosterone levels predict major cardiovascular events. We examined whether lower serum testosterone was an independently significant risk factor for symptomatic cerebrovascular events in older men. This was a prospective observational study with median follow-up of 3.5 yr. Community-dwelling, stroke-free older men were studied. A total of 3443 men at least 70 yr of age participated in the study. Baseline serum total testosterone, SHBG, and LH were assayed. Free testosterone was calculated using mass action equations. Incident stroke or transient ischemic attack (TIA) was recorded. A first stroke or TIA occurred in 119 men (3.5%). Total and free testosterone concentrations in the lowest quartiles (<11.7 nmol/liter and <222 pmol/liter) were associated with reduced event-free survival (P = 0.014 and P = 0.01, respectively). After adjustment including age, waist-hip ratio, waist circumference, smoking, hypertension, dyslipidemia, and medical comorbidity, lower total testosterone predicted increased incidence of stroke or TIA (hazard ratio = 1.99 95% confidence interval, 1.33-2.99). Lower free testosterone was also associated (hazard ratio = 1.69 95% confidence interval, 1.15-2.48), whereas SHBG and LH were not independently associated with incident stroke or TIA. In older men, lower total testosterone levels predict increased incidence of stroke or TIA after adjusting for conventional risk factors for cardiovascular disease. Men with low-normal testosterone levels had increased risk. Further studies are warranted to determine whether interventions that raise circulating testosterone levels might prevent cerebrovascular disease in men.
Publisher: Elsevier BV
Date: 2019
Publisher: AMPCo
Date: 11-1987
DOI: 10.5694/J.1326-5377.1986.TB113877.X
Abstract: The intrathecal administration of baclofen by way of an implanted subcutaneous drug delivery system is described in a patient with a severe spastic paraparesis due to multiple sclerosis. Intrathecally-administered baclofen is proposed as another therapeutic dimension and adjunct to physical therapy in the management of patients with severe spasticity that is unresponsive to antispasticity agents administered by mouth.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Georg Thieme Verlag KG
Date: 2017
DOI: 10.1160/TH13-09-0741
Abstract: This review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and stroke prevention in atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In patients prescribed a NOAC, can the anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can “cut-off points” between which anticoagulation is therapeutic (i.e. the “therapeutic range”) be defined? 2. In patients who are taking a NOAC and bleeding (e.g. intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can NOAC-associated bleeding and complications be minimised and patient outcome improved? 3. In patients taking a NOAC who experience an acute ischaemic stroke, to what degree of anticoagulation or plasma concentration of NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a NOAC (or warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have atrial fibrillation and are at high risk of stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is there a dose or dosing regimen for each NOAC that is as effective and safe as adjusted-dose warfarin for patients with atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?
Publisher: SAGE Publications
Date: 14-06-2021
DOI: 10.1177/17474930211022678
Abstract: To address unmet needs, electronic messages to support person-centered goal attainment and secondary prevention may avoid hospital presentations/readmissions after stroke, but evidence is limited. Compared to control participants, there will be a 10% lower proportion of intervention participants who represent to hospital (emergency/admission) within 90 days of randomization. Multicenter, double-blind, randomized controlled trial with intention-to-treat analysis. The intervention group receives 12 weeks of personalized, goal-centered, and administrative electronic messages, while the control group only receive administrative messages. The trial includes a process evaluation, assessment of treatment fidelity, and an economic evaluation. Participants: Confirmed stroke (modified Rankin Score: 0-4), aged ≥18 years with internet/mobile phone access, discharged directly home from hospital. Randomization: 1:1 computer-generated, stratified by age and baseline disability. Outcomes assessments: Collected at 90 days and 12 months following randomization. Primary outcomes include hospital emergency presentations/admissions within 90 days of randomization. Secondary outcomes include goal attainment, self-efficacy, mood, unmet needs, disability, quality-of-life, recurrent stroke/cardiovascular events/deaths at 90 days and 12 months, and death and cost-effectiveness at 12 months. S le size: To test our primary hypothesis, we estimated a s le size of 890 participants (445 per group) with 80% power and two-tailed significance threshold of α = 0.05. Given uncertainty for the effect size of this novel intervention, the s le size will be adaptively re-estimated when outcomes for n = 668 are obtained, with maximum s le capped at 1100. We will provide new evidence on the potential effectiveness, implementation, and cost-effectiveness of a tailored eHealth intervention for survivors of stroke.
Publisher: Springer Science and Business Media LLC
Date: 02-09-2012
DOI: 10.1038/NG.2397
Publisher: Springer Science and Business Media LLC
Date: 12-2017
DOI: 10.1186/S13063-017-2385-6
Abstract: Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients’ functional outcome. The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2–15 days after stroke onset. Patients are randomised centrally via each trials’ web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances the Stroke Impact Scale EuroQol (EQ5D-5 L) the vitality subscale of the 36-Item Short Form Health Survey (SF36) diagnosis of depression adherence to medication serious adverse events including death and recurrent stroke and resource use at six and 12 months and the mRS at 12 months. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned in idual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the in idual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020. FOCUS: ISRCTN , ISRCTN83290762 . Registered on 23 May 2012. EudraCT, 2011-005616-29. Registered on 3 February 2012. AFFINITY: Australian New Zealand Clinical Trials Registry, ACTRN12611000774921 . Registered on 22 July 2011. EFFECTS: ISRCTN , ISRCTN13020412 . Registered on 19 December 2014. Clinicaltrials.gov, NCT02683213 . Registered on 2 February 2016. EudraCT, 2011-006130-16 . Registered on 8 August 2014.
Publisher: Wiley
Date: 05-2009
DOI: 10.1111/J.1445-5994.2009.01938.X
Abstract: Intravenous tissue plasminogen activator (tPA) has been licensed in Australia for thrombolysis in selected patients with acute ischaemic stroke since 2003. The use of tPA is low but is increasing across Australia and national audits indicate efficacy and safety outcomes equivalent to international benchmarks. Implementing tPA therapy in clinical practice is, however, challenging and requires a coordinated multidisciplinary approach to acute stroke care across prehospital, emergency department and inpatient care sectors. Stroke care units are an essential ingredient underpinning safe implementation of stroke thrombolysis. Support systems such as care pathways, therapy delivery protocols, and thrombolysis-experienced multidisciplinary care teams are also important enablers. Where delivery of stroke thrombolysis is being planned, health systems need to be re-configured to provide these important elements. This consensus statement provides a review of the evidence for, and implementation of, tPA in acute ischaemic stroke with specific reference to the Australian health-care system.
Publisher: International Scientific Information, Inc.
Date: 2011
DOI: 10.12659/MSM.881931
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.AHJ.2016.05.019
Abstract: We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in particular, those with known coronary artery disease (CAD). Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg) 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14% P<.001) and heart failure (68% vs 59% P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37 P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42 P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43 P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009). Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF.
Publisher: BMJ
Date: 02-2002
Publisher: American Medical Association (AMA)
Date: 03-2016
Publisher: SAGE Publications
Date: 18-09-2014
DOI: 10.1111/J.1747-4949.2012.00865.X
Abstract: White matter lesions (WML) and lacunar infarcts (LI) are believed to have microvascular etiologies but the exact microvascular changes occurring in each is unclear. Aim Using the retina as a proxy, we assessed retinal microvascular changes in WML and LI. We prospectively recruited 1211 acute stroke patients. Four subgroups were identified from neuroimaging: WML alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs identified retinopathy and retinal arteriolar wall signs and measured retinal vascular caliber. Compared with 448 controls with neither WML nor LI, 384 patients with only WML were more likely to have retinopathy [odds ratio (OR) 1·5, 95% confidence interval (CI) 1·1 to 2·1] and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·1 to 2·3) 200 patients with only LI were more likely to have arteriolar narrowing (OR 1·6, 95% CI 1·1 to 2·3) and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·0 to 2·4) and 179 patients with both WML and LI were more likely to have arteriovenous nicking (OR 1·7, 95% CI 1·1 to 2·6), enhanced arteriolar light reflex (OR 2·0, 95% CI 1·3 to 3·2) and wider venules (OR 2·3, 95% CI 1·4 to 3·6). All analyses were adjusted for age, gender, study site and cardiovascular risk factors. Both WML and LI were associated with retinal microvascular signs, supporting a microvascular etiology. Differing patterns of association suggest different mechanisms may predominate, e.g. greater endothelial permeability in WML, and ischemia associated with arteriolar wall disease in LI.
Publisher: S. Karger AG
Date: 1999
DOI: 10.1159/000016010
Abstract: Carotid endarterectomy is currently indicated for patients with severe symptomatic carotid stenosis because it halves the risk of stroke. However, it is expensive and potentially risky, and is performed unnecessarily in most of these patients. In order to improve the cost effectiveness of carotid endarterectomy, other predictors of stroke, in addition to the presence of recent focal neurological symptoms and the degree of carotid stenosis, need to be identified. Further research into the nature of the carotid atherosclerotic plaque and the clustering of systemic factors (infectious, inflammatory and vascular risk factors) that trigger inflammatory and morphological changes in the asymptomatic plaque and predispose it to rupture (with subsequent symptomatic thromboembolism) may yield powerful predictors of stroke which, when combined with the degree of stenosis and presence of focal neurological symptoms, may improve patient selection for carotid endarterectomy and its cost effectiveness.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2004
Publisher: Elsevier BV
Date: 06-2014
Abstract: Thermal treatments of feed and organic acids are known to affect the gastrointestinal microbiota in chickens. The present study evaluated the effect of different thermal processes including pelleting (P), long-term conditioning at 85°C for 3 min (L), expanding at 110°C (E110), and 130°C for 3 to 5 s (E130) as well as organic acid (63.75% formic acid, 25.00% propionic acid, and 11.25% water) inclusion levels (0, 0.75, and 1.5%) on gastrointestinal microbiota in broilers. In total, 960 one-day-old chicks were randomly assigned to 8 replicates using a 3 × 4 factorial arrangement. At d 35, bacterial cell numbers in the crop, ileum, and cecum, and bacterial metabolites in the crop, gizzard, ileum, and cecum were determined. The inclusion of 1.5% organic acids increased cell numbers of all clostridial clusters in the crop. The organic acid supplementation increased the propionic acid concentration in the crop and gizzard and there was a decrease in lactic acid concentration. In the ileum, the 0% organic acid group had the highest numbers of Lactobacillus spp. and enterobacteria. Inclusion of 1.5% organic acids increased ileal acetate concentration. Increasing the feed processing temperature led to an increase of lactobacilli in the crop and ileum, whereas clostridia and enterobacteria seemed unaffected. Similarly, lactate concentrations increased in the ileum, but short-chain fatty acids remained identical. In the crop, an increase for acetate was found for the E130 group compared with all other thermal treatments. In conclusion, our study demonstrated that thermal treatments and organic acid supplementation to broiler diets more markedly influenced the bacterial status of the crop compared with the downstream segments and their effects decreased along the length of gastrointestinal tract. Whereas organic acids markedly modified bacterial composition and activity in the crop, expansion increased lactobacilli and lactate in the crop and ileum.
Publisher: Elsevier BV
Date: 03-1988
Publisher: Elsevier BV
Date: 2008
Publisher: Elsevier BV
Date: 10-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2010
DOI: 10.1161/STROKEAHA.110.586727
Abstract: Background and Purpose— Disabling stroke is costly and considered by some patients a fate worse than death. We aimed to determine whether clopidogrel reduces the rate and functional severity of stroke among high vascular risk patients, including patients with previous transient ischemic attack or ischemic stroke, who were enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial. Methods— We randomly assigned 15 603 high vascular risk patients to receive clopidogrel (75 mg daily) or placebo in addition to background acetylsalicylic acid and followed them for a median of 28 months. The main outcome of this prespecified substudy was the functional severity of stroke outcome events as measured by the modified Rankin Scale (mRS) score at 3 months after the stroke outcome. Results— During follow-up, 436 (2.8%) patients had a definite adjudicated stroke and a follow-up assessment of the mRS at 3 months poststroke, of whom 202 had been randomly assigned clopidogrel and 234 placebo (relative risk reduction 14%, 95% CI: −4% to 29%, P =0.12). There was no significant difference between the mean mRS scores at 3 months after stroke among patients assigned clopidogrel compared with placebo (mean mRS 3.6 [SD 2.4] clopidogrel versus 3.3 [SD 2.1] placebo P =0.15). There was also no significant difference between the various categories of the mRS score at 3 months after stroke among patients assigned to clopidogrel compared with placebo. Among 4320 patients with a qualifying diagnosis of transient ischemic attack or ischemic stroke, 233 (5.4%) experienced a stroke during follow-up, of whom 103 were randomly assigned clopidogrel and 130 placebo (relative risk reduction 20%, 95% CI: −3% to 38%). There was no significant difference between the mean mRS scores at 3 months after stroke among patients with a qualifying transient ischemic attack or ischemic stroke who were assigned clopidogrel compared with placebo (3.4 [SD 2.1] clopidogrel versus 3.3 [SD 1.9] placebo P =0.48). Conclusion— The addition of clopidogrel to acetylsalicylic acid did not significantly alter the rate and functional severity of stroke outcome events among high vascular risk patients enrolled in the CHARISMA trial.
Publisher: Elsevier BV
Date: 2012
Publisher: BMJ
Date: 03-1993
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
DOI: 10.1161/STROKEAHA.114.006573
Abstract: Our aim was to identify whether particular subgroups of patients had an unacceptably high risk of symptomatic intracranial hemorrhage or low chance of benefit when treated with alteplase (recombinant tissue-type plasminogen activator). Third International Stroke Trial was an international randomized trial of the intravenous (IV) recombinant plasminogen activator alteplase (0.9 mg/kg) versus control in 3035 (1515 versus 1520) patients. We analyzed the effect of recombinant tissue-type plasminogen activator on 6-month functional outcome, early death, and symptomatic intracranial hemorrhage (both ≤7 days). We tested for any differences in treatment effect between subgroups by a test of interaction. Our 13 protocol prespecified subgroups were time to randomization, age, sex, stroke subtype, atrial fibrillation, early ischemic change (clinician and expert panel), prior antiplatelet use, stroke severity, diastolic and systolic blood pressure at randomization, center’s thrombolysis experience, and trial phase. Analyses were adjusted for key baseline prognostic factors. There were no significant interactions in the subgroups analyzed that were consistent across all 3 outcomes. Treatment with recombinant tissue-type plasminogen activator increased the odds of symptomatic intracranial hemorrhage by a greater amount in patients taking prior antiplatelets than those who were not ( P =0.019 for test of interaction), but had no clear detrimental effect on functional outcome at 6 months in this group ( P =0.781 for test of interaction). Among the types of patient in the Third International Stroke Trial, this secondary analysis did not identify any subgroups for whom treatment should be avoided. Given the limitations of the analysis, we found no clear evidence to avoid treatment in patients with prior ischemic stroke, diabetes mellitus, or hypertension. URL: www.controlled-trials.com . Unique identifier: ISRCTN25765518. www.controlled-trials.com/ISRCTN25765518 .
Publisher: SAGE Publications
Date: 25-07-2018
Abstract: Training family carers to provide evidence-based rehabilitation to stroke patients could address the recognized deficiency of access to stroke rehabilitation in low-resource settings. However, our randomized controlled trial in India (ATTEND) found that this model of care was not superior to usual care alone. This process evaluation aimed to better understand trial outcomes through assessing trial implementation and exploring patients’, carers’, and providers’ perspectives. Our mixed methods study included process, healthcare use data and patient demographics from all sites observations and semi-structured interviews with participants (22 patients, 22 carers, and 28 health providers) from six s led sites. Intervention fidelity and adherence to the trial protocol was high across the 14 sites however, early supported discharge (an intervention component) was not implemented. Within both randomized groups, some form of rehabilitation was widely accessed. ATTEND stroke coordinators provided counseling and perceived that sustaining patients’ motivation to continue with rehabilitation in the face of significant emotional and financial stress as a key challenge. The intervention was perceived as an acceptable community-based package with education as an important component in raising the poor awareness of stroke. Many participants viewed family-led rehabilitation as a necessary model of care for poor and rural populations who could not access rehabilitation. Difficulty in sustaining patient and carer motivation for rehabilitation without ongoing support, and greater than anticipated access to routine rehabilitation may explain the lack of benefit in the trial. Nonetheless, family-led rehabilitation was seen as a concept worthy of further development.
Publisher: Elsevier BV
Date: 06-2007
Publisher: Elsevier BV
Date: 07-1999
Publisher: AIP Publishing
Date: 17-09-2013
DOI: 10.1063/1.4821766
Abstract: A combined study utilizing anion photoelectron spectroscopy and density functional theory was conducted to search for four-atom, chiral, metal, and mostly metal clusters. The clusters considered were AuCoMnBi−/0, AlAuMnO−/0, AgMnOAl−/0, and AuAlPtAg−/0, where the superscripts, −/0, refer to anionic and neutral cluster species, respectively. Based on the agreement of experimentally and theoretically determined values of both electron affinities and vertical detachment energies, the calculated cluster geometries were validated and examined for chirality. Among both anionic and neutral clusters, five structures were identified as being chiral.
Publisher: Elsevier BV
Date: 12-2012
Publisher: Wiley
Date: 07-2018
Publisher: Elsevier BV
Date: 02-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-09-2017
DOI: 10.1212/WNL.0000000000004560
Abstract: To determine whether common variants in familial cerebral small vessel disease (SVD) genes confer risk of sporadic cerebral SVD. We meta-analyzed genotype data from in iduals of European ancestry to determine associations of common single nucleotide polymorphisms (SNPs) in 6 familial cerebral SVD genes ( COL4A1 , COL4A2 , NOTCH3 , HTRA1 , TREX1 , and CECR1 ) with intracerebral hemorrhage (ICH) (deep, lobar, all 1,878 cases, 2,830 controls) and ischemic stroke (IS) (lacunar, cardioembolic, large vessel disease, all 19,569 cases, 37,853 controls). We applied data quality filters and set statistical significance thresholds accounting for linkage disequilibrium and multiple testing. A locus in COL4A2 was associated (significance threshold p 3.5 × 10 −4 ) with both lacunar IS (lead SNP rs9515201: odds ratio [OR] 1.17, 95% confidence interval [CI] 1.11–1.24, p = 6.62 × 10 −8 ) and deep ICH (lead SNP rs4771674: OR 1.28, 95% CI 1.13–1.44, p = 5.76 × 10 −5 ). A SNP in HTRA1 was associated (significance threshold p 5.5 × 10 −4 ) with lacunar IS (rs79043147: OR 1.23, 95% CI 1.10–1.37, p = 1.90 × 10 −4 ) and less robustly with deep ICH. There was no clear evidence for association of common variants in either COL4A2 or HTRA1 with non-SVD strokes or in any of the other genes with any stroke phenotype. These results provide evidence of shared genetic determinants and suggest common pathophysiologic mechanisms of distinct ischemic and hemorrhagic cerebral SVD stroke phenotypes, offering new insights into the causal mechanisms of cerebral SVD.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.AHJ.2016.05.001
Abstract: We conducted a retrospective analysis examining the association between systolic blood pressure (SBP) or hypertension bracket and stroke risk in patients with atrial fibrillation (AF). The study included 14,256 anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models were used to compare the risk of adverse outcomes by European Society of Cardiology hypertension bracket and screening SBP. In total, 90.5% of patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted risk of stroke or systemic embolism (SE) increased significantly for every 10-mm Hg increase in screening SBP (hazard ratio [HR] 1.07, 95% CI 1.02-1.13). There was a trend toward an increased adjusted risk of stroke or SE in patients with controlled (HR 1.22, 95% CI 0.89-1.66) and uncontrolled hypertension (HR 1.42, 95% CI 1.03-1.95) (P = .06). In contrast, the adjusted risk of major bleeding was similar between hypertensive brackets and did not vary significantly by screening SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of SBP (P interaction = .69). In a trial of anticoagulated patients with AF, increasing screening SBP was independently associated with stroke and SE, and one-third of patients had uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban versus warfarin were consistent across all levels of screening SBP. A single SBP may be an important factor in reducing the overall risk of stroke and SE in anticoagulated patients with AF.
Publisher: Springer Science and Business Media LLC
Date: 1991
DOI: 10.1007/BF00598608
Publisher: Wiley
Date: 25-05-2017
Publisher: Elsevier BV
Date: 07-2014
Abstract: Minerals play an important role for growth and bone stability in broilers. Thermal treatment and inclusion of organic acids in feed may affect the mineral absorption and tibial quality in broilers. The study was conducted to investigate the effect of thermal processing of feed including pelleting (P), long-term conditioning at 85°C (L), and expanding at 130°C (E) without and with 1.5% of an acid mixture containing 64% formic and 25% propionic acid on the apparent ileal absorption (AIA) of calcium, phosphorus, magnesium, potassium, sodium, iron, copper, manganese, and zinc, their concentrations in liver and tibia, as well as various tibial quality parameters in broilers. In total, 480 one-day-old Cobb broiler chicks were assigned using a completely randomized design with a 3 × 2 factorial arrangement. The ileal digesta, liver, and tibia were collected at d 35. The AIA of calcium and sodium was improved in group E compared with L (P ≤ 0.02 and P ≤ 0.01). Group P and E showed higher AIA for potassium than L (P ≤ 0.01). Bone ash content was increased in group E compared with L (P ≤ 0.04). The BW to bone weight ratio was lower and tibial zinc content was higher in group P compared with E (P ≤ 0.05). Tibial iron content was higher in group L than E (P ≤ 0.03). Acid addition did not affect AIA, mineral content in tibia, or tibial quality parameters. Thermal and acid treatment did not affect mineral concentrations in the liver, except an inconsistent interaction effect for DM content and sodium (P ≤ 0.03 and P ≤ 0.04, respectively). In conclusion, long-term thermal treatment reduced AIA of some minerals compared with short-term thermal treatments, but had no impact on tibia composition. Acid inclusion had no effect on AIA of minerals and tibia quality. Thermal treatment and the use of organic acids can therefore be considered as safe with regard to their impact on bone development in broilers.
Publisher: Wiley
Date: 11-02-2009
DOI: 10.1111/J.1365-2265.2008.03372.X
Abstract: Circulating testosterone declines during male ageing, and low testosterone may predispose to ill health. We sought to determine whether greater participation in healthy behaviours predicted reduced risk of subsequent lower circulating testosterone in older men. Cross-sectional analysis of a population-based follow-up study. A total of 3453 men aged 65-83 years. Lifestyle score, a tally of eight prudent health-related behaviours, was determined during 1996-99. Early morning sera collected in 2001-04 were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Mean (+/- SD) time between collection of lifestyle data and blood s ling was 5.7 +/- 0.9 years. Lifestyle score correlated with subsequent total testosterone (r = 0.06, P < 0.001) and SHBG (r = 0.07, P or= 7), odds ratio (95% CI) for total testosterone and SHBG in the lowest quartile were 0.37 (0.18-0.77) and 0.26 (0.13-0.54), respectively. Lower lifestyle scores including and excluding body mass index predicted higher risk of total testosterone and SHBG in the lowest quartiles. In men > 65 years old, higher lifestyle score reflecting greater engagement in healthy behaviours predicts higher subsequent total testosterone and SHBG levels. This relationship appears cumulative and may reflect interaction between lifestyle and insulin sensitivity. Successfully promoting healthy behaviours in older men could ameliorate the age-related decline in circulating testosterone.
Publisher: Wiley
Date: 14-11-2017
DOI: 10.1111/ENE.13191
Abstract: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31 95% confidence interval 1.48-3.62). In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.JOCN.2010.05.014
Abstract: Prevention of stroke requires optimal control of causal risk factors. However, only three-quarters of all strokes can be attributable to known causal risk factors. We aimed to identify novel risk factors for acute stroke in 48 patients with acute (<1 week) stroke admitted to Royal Perth Hospital Stroke Unit and 47 controls matched for age and sex from the northeast Perth metropolitan area. Patients and controls were interviewed, and had physical measurements and blood taken. Multiple odds ratios (OR) for risk factors, with 95% confidence intervals (CI), were calculated by unconditional multiple logistic regression. Mediterranean diet (OR: 0.1 95% CI, 0.02-0.4), increased waist-to-hip ratio (OR 4.0, 95% CI, 1.5-11), physical activity during leisure time (OR 0.2 95% CI, 0.1-0.9), periodontal disease (OR 6.4 95% CI, 1.5-27), and acute febrile illness (OR 14 95% CI, 1.5-127) were associated significantly and independently with ischaemic stroke. These preliminary data suggest that certain dietary and lifestyle behaviours may play as important a role in the aetiology (and prevention) of stroke as other conventional causal risk factors for stroke. However, these associations need confirmation from larger randomised trials given the small s le size of the current study.
Publisher: Elsevier BV
Date: 2011
Publisher: SAGE Publications
Date: 29-07-2014
DOI: 10.1111/IJS.12084
Abstract: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting n = 213) or carotid endarterectomy ( n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ⩾50% during follow-up. Carotid stenosis longer than 0·65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2·79 (1·17–6·65), P = 0·02] and carotid endarterectomy [2·43 (1·03–5·73), P = 0·04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1·68 (1·12–2·53), P = 0·01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0·003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials.
Publisher: Elsevier BV
Date: 08-2014
Publisher: Springer Berlin Heidelberg
Date: 2004
Publisher: Elsevier BV
Date: 08-2017
Publisher: Wiley
Date: 03-2014
Abstract: Very early aphasia rehabilitation studies have shown mixed results. Differences in therapy intensity and therapy type contribute significantly to the equivocal results. To compare a standardized, prescribed very early aphasia therapy regimen with a historical usual care control group at therapy completion (4-5 weeks post-stroke) and again at follow-up (6 months). This study compared two cohorts from successive studies conducted in four Australian acute/sub-acute hospitals. The studies had near identical recruitment, blinded assessment and data-collection protocols. The Very Early Rehabilitation (VER) cohort (N = 20) had mild-severe aphasia and received up to 20 1-h sessions of impairment-based aphasia therapy, up to 5 weeks. The control cohort (n = 27) also had mild-severe aphasia and received usual care (UC) therapy for up to 4 weeks post-stroke. The primary outcome measure was the Aphasia Quotient (AQ) and a measure of communicative efficiency (DA) at therapy completion. Outcomes were measured at baseline, therapy completion and 6 months post-stroke and were compared using Generalised Estimating Equations (GEE) models. After controlling for initial aphasia and stroke disability, the GEE models demonstrated that at the primary end-point participants receiving VER achieved 18% greater recovery on the AQ and 1.5% higher DA scores than those in the control cohort. At 6 months, the VER participants maintained a 16% advantage in recovery on the AQ and 0.6% more on DA scores over the control cohort participants. A prescribed, impairment-based aphasia therapy regimen, provided daily in very early post-stroke recovery, resulted in significantly greater communication gains in people with mild-severe aphasia at completion of therapy and at 6 months, when compared with a historical control cohort. Further research is required to demonstrate large-scale and long-term efficacy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2009
DOI: 10.1161/STROKEAHA.108.542571
Abstract: Background and Purpose— The risk of intracranial aneurysm (IA) rupture in asymptomatic members of families who have multiple affected in iduals is not known. Methods— First-degree unaffected relatives of those with a familial history of IA who had a history of smoking or hypertension but no known IA were offered cerebral MR angiography (MRA) and followed yearly as part of a National Institute of Neurological Diseases and Stroke-funded study of familial IA (Familial Intracranial Aneurysm [FIA] Study). Results— A total of 2874 subjects from 542 FIA Study families were enrolled. After study enrollment, MRAs were performed in 548 FIA Study family members with no known history of IA. Of these 548 subjects, 113 subjects (20.6%) had 148 IAs by MRA of whom 5 subjects had IA ≥7 mm. Two subjects with an unruptured IA by MRA/CT angiography (3-mm and 4-mm anterior communicating artery) subsequently had rupture of their IA. This represents an annual rate of 1.2 ruptures per 100 subjects (1.2% per year 95% CI, 0.14% to 4.3% per year). None of the 435 subjects with a negative MRA have had a ruptured IA. Survival curves between the MRA-positive and -negative cohorts were significantly different ( P =0.004). This rupture rate of unruptured IA in the FIA Study cohort of 1.2% per year is approximately 17 times higher than the rupture rate for subjects with an unruptured IA in the International Study of Unruptured Aneurysm Study with a matched distribution of IA size and location 0.069% per year. Conclusions— Small unruptured IAs in patients from FIA Study families may have a higher risk of rupture than sporadic unruptured IAs of similar size, which should be considered in the management of these patients.
Publisher: Elsevier BV
Date: 2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2003
DOI: 10.1161/01.STR.0000097491.82104.F3
Abstract: Background and Purpose— Spontaneous intracerebral hemorrhage is a major cause of death and disability, yet there is no convincing evidence of the benefit of any medical treatment and the role of surgery remains controversial. The international randomized Surgical Trial in Intracerebral Hemorrhage (STICH) provided an opportunity to assess the role of surgery within the centers taking part. Methods— Screening logs were completed to record details of all patients assessed by the department, whether they were included in the trial, the reasons if they were not included, and whether they underwent surgery. Results— Logs were returned by 42 centers and cover 704 months. They include details on 1578 patients with characteristics comparable to STICH inclusion criteria. Neurosurgeons were more likely to express clinical certainty about treatment for older patients, patients with a higher Glasgow Coma Score scale, and patients in whom the hematoma was located on the right or in the basal ganglia or thalamus. Patients for whom the neurosurgeon was certain about treatment were more likely to have the hematoma removed if they were younger (62 versus 68 years of age), had a lower Glasgow Coma Scale score (10 versus 13), and had a lobar hematoma (49% versus 40%). The operation rate varied between 74% in Lithuania and 2% in Hungary. Conclusions— The difference in operation rates could not be explained by differences in patient characteristics alone. This finding demonstrates the need for further evidence to ensure that treatment for intracerebral hemorrhage is not governed by local custom.
Publisher: Elsevier BV
Date: 06-2020
Publisher: SAGE Publications
Date: 26-07-2023
DOI: 10.1177/10398562231191692
Abstract: To determine the prevalence of common mental disorders among older Australians included in the Health In Men Data Linkage Study and compare those with the results of the 2020–2021 National Study of Mental Health and Wellbeing (NSMHW). We used longitudinal record linkage to estimate the prevalence of mental disorders from age 65 years in a random s le of 38173 Australian men aged 65–85 years living in the Perth metropolitan region. Outcome was the proportion of participants affected by depressive episodes or dysthymia, bipolar disorder, anxiety disorder, psychotic disorder and alcohol use disorder. Prevalence estimates for participants aged 65–69, 70–74, 75–79, 80–84 and ≥85 years were 0.9%, 2.0%, 3.6%, 5.8% and 12.6% for depressive, 0.2%, 0.3%, 0.4%, 0.4% and 0.7% for bipolar, 0.1%, 0.5%, 1.3%, 2.2%, 6.9% for anxiety, 0.2%, 0.4%, 0.5%, 0.4% and 0.6% for psychotic and 1.2%, 1.7%, 2.1%, 2.2% and 4.2% for alcohol use disorders. In contrast to the NSMHW, our data indicate that the prevalence of depressive and anxiety disorders increases with age, particularly among the older old. We conclude that the NSMHW should not be relied upon to guide planning or policies to address the mental health needs of older Australians.
Publisher: Elsevier BV
Date: 02-2004
Publisher: Public Library of Science (PLoS)
Date: 31-10-2014
Publisher: Elsevier BV
Date: 09-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: American Chemical Society (ACS)
Date: 02-2019
Publisher: AMPCo
Date: 07-2003
DOI: 10.5694/J.1326-5377.2003.TB05436.X
Abstract: The recently released PREVENT trial provides some answers.
Publisher: Wiley
Date: 03-02-2021
DOI: 10.1111/CODI.15474
Publisher: Springer Science and Business Media LLC
Date: 26-02-2012
DOI: 10.1007/S00198-011-1586-1
Abstract: In older men, both lower and higher total osteocalcin levels predict increased all-cause mortality, with comparable associations for cardiovascular and non-cardiovascular deaths. Differences in osteocalcin levels might influence glucose metabolism and thereby cardiovascular risk, or reflect changes in bone turnover thus representing a marker for poorer health outcomes. Reduced levels of total osteocalcin (TOC) are associated with adiposity, insulin resistance and type 2 diabetes, implying this bone-derived peptide might modulate cardiovascular risk. However, there are few longitudinal data relating TOC levels to survival. We examined associations of TOC level with all-cause and cardiovascular mortality in older men. We conducted a prospective cohort study of community-dwelling men aged 70-89 years. Aliquots of plasma collected at baseline (2001-2004) were assayed for TOC. Incidence and causes of death to 31 December 2008 were ascertained using data linkage. Cox regression analyses were performed with adjustment for conventional cardiovascular risk factors. From 3,542 men followed for median 5.2 years there were 572 deaths (16.1%). Mortality was lowest in men with TOC levels in the second quintile (12.6%). In multivariate analyses, men with TOC in the lowest and highest quintiles of values had increased all-cause mortality (Q1 vs Q2: hazard ratio [HR], 1.36 95% confidence interval 1.02-1.80 and Q5 vs Q2: HR, 1.53, 95% CI 1.18-1.98). Men with low TOC levels had similar HR for cardiovascular and non-cardiovascular deaths (Q1 vs Q2: HR, 1.35 and 1.30 respectively). Higher TOC levels predicted cardiovascular disease (CVD)-related mortality (Q5 vs Q2, HR, 1.69, 95% CI 1.09-2.64). TOC predicts all-cause and CVD-related mortality in community-dwelling older men. However, the relationship is U shaped with men at both ends of the distribution at increased risk. Further investigation is required to clarify whether the underlying mechanisms involve altered bone turnover or relate specifically to the biological activity of osteocalcin.
Publisher: Elsevier BV
Date: 03-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-01-2023
DOI: 10.1212/WNL.0000000000201388
Abstract: There is uncertainty about the association between alcohol consumption and stroke, particularly for low-moderate intake. We explored these associations in a large international study. INTERSTROKE, a case-control study, is the largest international study of risk factors for acute stroke. Alcohol consumption was self-reported and categorized by drinks/week as low (1–7), moderate (7–14 for females and 7–21 for males), or high ( for females and for males). Heavy episodic drinking (HED) was defined as drinks on ≥1 day per month. Multivariable conditional logistic regression was used to determine associations. We included 12,913 cases and 12,935 controls 25.0% (n = 6,449) were current drinkers, 16.7% (n = 4,318) former drinkers, and 58.3% (n = 15,076) never drinkers. Current drinkers were younger, male, smokers, active, and with higher-paid occupations. Current drinking was associated with all stroke (OR 1.14 95% CI 1.04–1.26) and intracerebral hemorrhage (ICH) (OR 1.50, 95% CI 1.21–1.84) but not ischemic stroke (OR 1.06 95% CI 0.95–1.19). HED pattern was associated with all stroke (OR 1.39 95% CI 1.21–1.59), ischemic stroke (OR 1.29 95% CI 1.10–1.51), and ICH (OR 1.76 95% CI 1.31–2.36). High level of alcohol intake was consistently associated with all stroke, ischemic stroke, and ICH. Moderate intake was associated with all stroke and ICH but not ischemic stroke. Low alcohol intake was not associated with stroke overall, but there were regional differences low intake was associated with reduced odds of stroke in Western Europe/North America (OR 0.66 95% CI 0.45–0.96) and increased odds in India (OR 2.18 95% CI 1.42–3.36) (p-interaction 0.037). Wine consumption was associated with reduced odds of all stroke and ischemic stroke but not ICH. The magnitudes of association were greatest in those without hypertension and current smokers. High and moderate intake were associated with increased odds of stroke, whereas low intake was not associated with stroke. However, there were important regional variations, which may relate to differences in population characteristics of alcohol consumers, types or patterns of consumption.
Publisher: AMPCo
Date: 02-2017
DOI: 10.5694/MJA16.01132
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
Publisher: BMJ
Date: 09-1991
Abstract: A cohort of 469 hospital-referred patients with transient ischaemic attacks (TIA) of the brain (66%) or eye (34%) due to presumed atheromatous thromboembolism, lipohyalinosis or cardiogenic embolism, without prior stroke, was assembled between 1976-86. Follow up was prospective and complete until the patients death or the end of 1986. During a mean period of follow up of 4.1 years there were 82 deaths (58 vascular, 24 non-vascular), 63 first-ever strokes and 58 patients with coronary events. A coronary event accounted for 51% of deaths whilst stroke was the cause in 12%. The average risk of death over the first five years after TIA was 4.5% per year. The risk of stroke was 6.6% in the first year and 3.4% per year on average over the first five years. Stroke occurred in the same vascular territory as the initial TIA in about two-thirds of cases, and was of lacunar type in one fifth of these strokes. The average risk of a coronary event over the first five years after TIA was 3.1% per year, similar to that of stroke. However, the risk of a coronary event, and also death, was fairly constant each year after a TIA, in contrast to the risk of stroke which was highest in the first year. The average risk of stroke, myocardial infarction or vascular death over the first five years after TIA was 6.5% per year and the average risk of stroke, myocardial infarction or death from any cause was 7.5% per year. The prognosis of this cohort of hospital-referred TIA patients was better than that of TIA patients in the same community who presented to the Oxfordshire Community Stroke Project (OCSP), and reflected the impact of referral bias. The hospital-referred patients were younger, assessed at a later date after their last TIA, and comprised a greater proportion of patients who had had a TIA of the eye (amaurosis fugax), which had a better prognosis than TIA of the brain. Knowledge of the prognosis of different populations of TIA patients not only enhances understanding and interpretation of previous studies but is also required for optimal patient management and the planning of treatment trials.
Publisher: Public Library of Science (PLoS)
Date: 25-03-2011
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0140-6736(05)70338-X
Abstract: Based on promising effects seen in a pilot study evaluating a generic mindfulness-based program for migraine, we developed a migraine-specific adaptation of the Mindfulness-Based Cognitive Therapy (MBCT) program. The aim of this study was to evaluate this program for feasibility and effectiveness in a randomized controlled trial. Fifty-four patients suffering from migraine were randomly allocated to either waitlist or the adapted MBCT. Outcomes were migraine-related parameters as well as variables of psychological functioning and coping. Assessment took place at baseline and post-intervention, for the intervention group also at follow-up (7 months). The effects of the intervention were analyzed by the use of ANCOVAs and linear mixed models. With respect to migraine parameters we did not find a significant group difference in the primary outcome (headache-related impairment), but the intervention resulted in a significant reduction of headache frequency (p = .04). In the analysis of secondary outcomes, MBCT showed superiority in four out of eight psychological parameters (perceived stress, anxiety, rumination, catastrophizing) with small to medium effect sizes. The intervention proved to be feasible and participants reported high degrees of contentment and achievement of personal goals. The migraine-specific MBCT program did not result in improvements with regard to headache-related impairment but showed a reduction in headache frequency as well as improved psychological functioning in secondary outcomes. This trial was registered in the German Trial Registry "Deutsches Register Klinischer Studien" (ID: DRKS00007477), which is a WHO-listed primary trial register.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-03-2022
DOI: 10.1212/WNL.0000000000200058
Abstract: To determine the sociodemographic and clinical factors associated with early, late, and persistent clinically significant symptoms of depression during the first year after a stroke. This cohort study included 1,221 men and women recruited within 2 weeks of stroke onset in Australia, New Zealand, and Vietnam. The NIH Stroke Scale (NIHSS) was used to assess stroke severity. Other study measures included age, sex, marital status, living arrangements, function before the stroke, depression before the stroke, modified Rankin Scale (mRS) score, and treatment with fluoxetine or placebo for 26 weeks. Clinically significant symptoms of depression during the 52 weeks after baseline was the outcome of interest, and the presence of depression was defined by a total Patient Health Questionnaire (PHQ-9) score of ≥9 at week 4, 12, 26, or 52 a clinician diagnosis of depression between assessments or pharmacologic or psychological treatment of depression during follow-up. Participants were classified as not depressed or as having early (initial 12 weeks), late (12–52 weeks), or persistent (before and after 12 weeks) depression. We used multinomial logistic regression to assess depression risk, with all listed measures entered simultaneously into the model. The mean age of participants was 63.8 (SD 12.3) years, and 775 (63.5%) were male. At baseline, 48 (3.9%) participants had previous treated depression, and 228 (18.7%) had clinically significant symptoms of depression (PHQ-9 score ≥9). Seven hundred thirty-four (63.3%) participants showed no evidence of depression in the year after the stroke 208 (17.9%) had early, 86 (7.4%) had late, and 131 (11.3%) had persistent depression. Increased stroke severity, as measured by doubling of the NIHSS scores, was associated with an increased risk of early (risk ratio [RR] 2.08, 95% CI 1.65–2.62), late (RR 1.53, 95% CI 1.14–2.06), and persistent (RR = 2.50, 95% CI 1.89–3.32) clinically significant symptoms of depression. Similar findings were apparent for the mRS, a measure of functional disability. Past depression was associated with increased risk of persistent clinically significant symptoms of depression (RR = 6.28, 95% CI 2.88–13.71), as was being married or partnered (RR = 3.94, 95% CI 2.42–6.41). The risk of clinically significant symptoms of depression was higher in Australia and New Zealand than in Vietnam. The severity of neurologic and functional deficits increases the risk of poststroke clinically significant symptoms of depression early and persistently. Depression before stroke, personal relationships, and cultural context contribute to mediate depression risk. Interventions that minimize the severity of neurologic and functional deficits should decrease the risk of poststroke clinically significant symptoms of depression. Clinical trial registration number ACTRN12611000774921.
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.EJVS.2008.04.001
Abstract: Carotid endarterectomy (CEA) for carotid stenosis is effective in preventing ipsilateral carotid territory ischaemic stroke. Paradoxically however, it causes a stroke (the event it is trying to prevent) in about 5% or more of cases. If carotid angioplasty/stenting (CAS) is to have a place in the management of patients with carotid stenosis (beyond those who are not suitable for CEA), it has to demonstrate that it is also effective and safe. Limited data from 12 randomised trials comparing CAS with CEA (the current "gold standard") in a total of 3227 patients with carotid stenosis (90% symptomatic) question the safety of CAS and suggest that it may cause more non-fatal, procedural strokes than CEA despite similar mortality rates and a much lower immediate local complication rate (eg cranial neuropathy). However, the published trials are rather heterogeneous (clinically and methodologically), none is large enough to provide robust and convincing data and long-term follow-up is very limited. Accordingly, it remains unknown whether CAS is effective in preventing recurrent stroke among patients with carotid stenosis, or whether it is safe. More data (from at least another 3,000 patients) are needed from the ongoing randomised trials before it can reliably be concluded whether CAS is inferior to, non-inferior to, or more effective than, CEA. More importantly, it will be possible to determine which patients should be treated preferentially with CAS, which patients with CEA, and which patients should not undergo either revascularisation procedure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2003
DOI: 10.1161/01.STR.0000092124.52084.4B
Abstract: Background and Purpose— Protein Z is a vitamin K–dependent plasma protein whose significance in arterial thrombosis remains uncertain. The objectives of this study were to determine the association between protein Z, ischemic stroke, and etiologic subtypes of ischemic stroke. Methods— We conducted a case-control study of 173 hospital cases of first-ever ischemic stroke and 186 randomly selected community controls. Using established criteria, we classified cases of stroke by etiologic subtype. Protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event. Results— Blood levels of protein Z measured within 7 days of acute stroke were significantly higher in cases than in controls (geometric mean, 1.46 versus 1.16 μg/mL P .0001). Compared with the lowest tertile, the upper 2 tertiles of protein Z were associated with an adjusted odds ratio (OR) of ischemic stroke of 1.75 (95% CI, 1.00 to 3.07) for the second tertile and 3.07 (95% CI, 1.73 to 5.45) for the upper tertile. The adjusted odds of ischemic stroke caused by large-artery atherothrombosis was nearly 8-fold greater for those with protein Z concentrations in the upper tertile compared with the lower tertile (OR, 7.91 95% CI, 3.11 to 20.14). The adjusted odds of ischemic stroke due to small-artery disease (OR, 1.79 95% CI, 0.83 to 3.87) and cardioembolism (OR, 1.80 95% CI, 0.58 to 5.64) was also increased among in iduals with protein Z concentrations in the upper tertile compared with the lower tertile, but not significantly so. There was no significant difference between mean protein Z concentrations among cases in the convalescent phase (3 months) after stroke and age- and sex-matched controls. Conclusions— There is a strong, independent relationship between elevated blood levels of protein Z and ischemic stroke during the acute phase, particularly ischemic stroke due to large-artery atherothromboembolism, which is no longer evident during the convalescent phase. These results are consistent with the notion that protein Z is either an important factor in the pathogenesis of ischemic stroke due to large-artery atherothromboembolism or an acute phase reactant. Further studies are required to elucidate whether protein Z has a causative or prognostic role in acute arterial thrombosis.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.ENVRES.2022.114349
Abstract: In areas with moderate to severe air pollution, pollutant concentrations are associated with dementia risk. It is unclear whether the same relationship is present in regions with lower ambient air pollution. To determine whether exposure to air pollution is associated with risk of incident dementia in general, and Alzheimer's disease and vascular dementia in particular, in older men living in a relatively low ambient air pollution region. The cohort comprised 11,243 men residing in Perth, Australia. Participants were aged ≥65 years and free of a dementia diagnosis at time of recruitment in 1996-1999. Incident dementia was identified from recruitment to 2018 via ICD diagnosis codes and subsequent study waves. Concentrations for three air pollutants, nitrogen dioxide (NO Of 3053 (27.2%) incident cases of dementia, 1670 (54.7%) and 355 (11.6%) had documented Alzheimer's disease and vascular dementia. The average concentration of NO Exposure to air pollution is not associated with increased risk of incident dementia in older men living in a region with relatively low ambient air pollution.
Publisher: AMPCo
Date: 08-1987
DOI: 10.5694/J.1326-5377.1987.TB133356.X
Abstract: Sudden hearing loss is an important symptom which demands immediate evaluation. Although it may be attributed to a number of disorders, relatively few clinicopathological correlations have been described. The role of vascular disease in the aetiology of sudden hearing loss has been acknowledged in several case reports, but remains unclear and perhaps underemphasized, given the prevalence of vascular disease in other organ systems in Western communities. Five cases of sudden hearing loss due to presumed vascular disease are reported. It is postulated that vascular disease is an important factor in the pathogenesis, and one which may be overlooked in the management of sudden hearing loss.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.MATURITAS.2018.03.004
Abstract: Dementia is a major source of disability worldwide and there are currently no available disease-modifying treatments. Hearing loss may be associated with increased risk of dementia in later life and therefore could be a modifiable risk factor, given the availability of efficacious interventions. We investigated the association of hearing loss and dementia through two complementary approaches: a prospective, cohort study of 37,898 older men (mean age 72.5 ± 4.6 years) with a mean follow-up of 11.1 years, and a systematic review and meta-analysis of prospective studies. In our cohort, men with hearing loss were more likely to develop dementia (n = 6948, 18.3%) than men free of significant hearing impairment - adjusted hazard ratio 1.69, 95% CI = 1.54-1.85. In our review, the aggregated hazard of dementia was 1.49 (95% CI 1.30-1.67) in those with hearing impairment (14 included studies). Study quality, duration and dementia type did not alter the results considerably. We found an increased risk of incident dementia with hearing impairment in both our novel data and the meta-analysis. This is an important finding, particularly in light of recent suggestions that mid-life hearing loss may account for up to 9.1% of dementia cases worldwide, and efforts to reduce its impact should continue to be explored.
Publisher: Wiley
Date: 12-1997
Abstract: Aspirin is only modestly effective in the secondary prevention after cerebral ischemia. Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation (international normalized ratio [INR] 3.0-4.5). Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke (Rankin grade < or =3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event "death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or nonfatal major bleeding complication." The trial was stopped at the first interim analysis. A total of 1,316 patients participated their mean follow-up was 14 months. There was an excess of the primary outcome event in the anticoagulated group (81 of 651) versus 36 of 665 in the aspirin group (hazard ratio, 2.3 95% confidence interval [CI], 1.6-3.5). This excess could be attributed to 53 major bleeding complications (27 intracranial 17 fatal) during anticoagulant therapy versus 6 on aspirin (3 intracranial 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remains to be determined.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.AMJCARD.2017.05.026
Abstract: Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS
Publisher: Elsevier BV
Date: 09-2014
Publisher: Wiley
Date: 17-08-2016
DOI: 10.1002/GPS.4347
Abstract: Depression is an established risk factor for dementia in later life, but it is unclear if this relationship is causal. This study aimed to determine if clinically significant depressive symptoms are likely to be causally related to cognitive impairment in later life. Observational cohort study of 4568 men aged 70-89 years living in Perth, Western Australia, who were free of cognitive impairment at the beginning of follow-up. Current clinically significant depressive symptoms were defined by a score of 7 or more on the Geriatric Depression Scale 15 items. Past depression was ascertained via electronic medical records, by self-report or use of antidepressants. A score of 27 or less on the Telephone Interview for Cognitive Status modified or a recorded diagnosis of dementia in electronic medical records established the presence of cognitive impairment. During the 5-year follow-up, 534 men developed cognitive impairment, 811 died and 1455 were lost. The presence of clinically significant depressive symptoms at study entry was associated with increased risk rate (RR) of cognitive impairment (RR = 2.59, 95% confidence interval: 95%CI = 1.57-4.27), death (RR = 5.07, 95%CI = 3.32-7.75) and loss to follow-up (RR = 2.03, 95%CI = 1.32-3.13). These associations remained statistically significant after adjustment for age, country of birth, education, smoking history, and prevalence hypertension, diabetes, coronary heart disease and stroke. History of past clinically significant depressive symptoms was not associated with incident cognitive impairment (RR = 1.09, 95%CI = 0.78-1.52). The lack of association between past depression and cognitive impairment suggests that the link between depression and cognitive impairment is not causal and that the presence of clinically significant depressive symptoms in later life may herald the onset of cognitive impairment in at least some people.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-11-2017
Abstract: Although implantation of cardiac implantable electronic devices ( CIED s) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting. Using data from Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo CIED implantation or revision. In this post‐hoc, postrandomization, on‐treatment analysis, only the first intervention per patient was analyzed. During a median follow‐up of 2.2 years, 453 patients (242 rivaroxaban group 211 warfarin group) underwent de novo CIED implantation (64.2%) or revision procedures (35.8%). Patients who received CIED s were older, more likely to be male, and more likely to have past myocardial infarction, but had similar stroke risk compared to patients who did not receive CIED s. Most patients who received a device had study drug interrupted for the procedure and did not receive bridging anticoagulation. During the 30‐day postprocedural period, 11 patients (4.55%) in the rivaroxaban group experienced bleeding complications compared with 15 (7.13%) in the warfarin group. Thromboembolic complications occurred in 3 patients (1.26%) in the rivaroxaban group and 1 (0.48%) in the warfarin group. Event rates were too low for formal hypothesis testing. Bleeding and thromboembolic events were low in both rivaroxaban‐ and warfarin‐treated patients. Periprocedural use of oral factor Xa inhibitors in CIED implantation requires further study in prospective, randomized trials. URL : www.clinicaltrials.gov . Unique identifier: NCT 00403767.
Publisher: AMPCo
Date: 05-2017
DOI: 10.5694/MJA16.01383
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2005
DOI: 10.1161/01.STR.0000166058.49577.CA
Abstract: Background and Purpose— We aimed to determine whether A-13G or G79A polymorphisms of the protein Z gene that have been reported to be an important determinant of blood concentrations of protein Z are associated with risk of ischemic stroke in a broad range of stroke patients and controls. Methods— We conducted a case control study of 151 hospital cases of first-ever ischemic stroke and 164 randomly selected community controls. Protein Z genotype was determined for the A-13G promoter polymorphism and the G79A intron F polymorphism, and plasma protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event. Results— Geometric mean concentrations of protein Z measured within 7 days of acute stroke were significantly higher in cases compared with controls (1.51 μg/mL versus 1.13 μg/mL P ·0001). Protein Z concentrations were highest among subjects with the A-13G AA genotype, intermediate among those with the AG genotype, and lowest among those with the GG genotype (1.39 μg/mL versus 1.05 μg/mL versus 0.76 μg/mL P .0001) and highest among those with the G79A GG genotype, intermediate among those with the GA genotype, and lowest among those with the AA genotype (1.47 μg/mL versus 1.13 μg/mL versus 0.66 μg/mL P .0001). The prevalence of A-13G and G79A genotypes was not significantly different between cases of ischemic stroke and controls. However, compared with the G79A GG genotype (reference), the odds of ischemic stroke was progressively lower for the heterozygote GA (odds ratio [OR], 0.83 95% CI, 0.52 to 1.33) and the homozygote AA genotype (OR, 0.63 95% CI, 0.20 to 1.98). A pooled analysis showed that compared with the G79A GG genotype (reference), the odds of ischemic stroke was progressively lower for the heterozygote GA (OR, 0.78 95% CI, 0.57 to 1.07) and the homozygote AA genotype (OR, 0.31 95% CI, 0.14 to 0.69). Conclusion— The consistency of the association between protein Z genotypes, blood concentrations of protein Z, and ischemic stroke, determined using 2 different methods that have different sources of bias strengthens the evidence that increased blood concentrations of protein Z concentrations are associated causally with an increased risk of ischemic stroke.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.YPMED.2016.09.022
Abstract: Suicide rates are high in later life, particularly among older men. Mood disorders are known risk factors, but the risk of suicide associated with poor physical health remains unclear. We completed a cohort study of a community representative s le of 38,170 men aged 65-85 in 1996 who were followed for up to 16years. Data on suicide attempts and completion were obtained from the Western Australia Data Linkage System, as was information about medical and mental health diagnoses. 240 (0.6%) participants had a recorded history of past suicide attempt, most commonly by poisoning (85%). Sixty-nine men died by suicide during follow up (0.3% of all deaths), most often by hanging (50.7%). Age-adjusted competing risk regression showed that past suicide attempt was not a robust predictor of future suicide completion (sub-hazard ratio, SHR=1.58, 95% CI=0.39, 6.42), but bipolar (SHR=7.82, 95% CI=3.08, 19.90), depressive disorders (SHR=2.26, 95% CI=1.14, 4.51) and the number of health systems affected by disease (SHR for 3-4 health systems=6.02, 95% CI=2.69, 13.47 SHR for ≥5 health systems=11.18, 95% CI=4.89, 25.53) were. The population fraction of suicides attributable to having 5 or more health systems affected by disease was 79% (95% CI=57%, 90%), and for any mood disorder (bipolar or depression) it was 17% (95% CI=3%, 28%). Older Australian men with multiple health morbidities have the highest risk of death by suicide, even after taking into account the presence of mood disorders. Improving the overall health of the population may be the most effective way of decreasing the rates of suicide in later life.
Publisher: AMPCo
Date: 09-2004
DOI: 10.5694/J.1326-5377.2004.TB06296.X
Abstract: Raised plasma homocysteine (tHcy) concentrations are caused by genetic mutations, vitamin deficiencies, renal and other diseases, numerous drugs, and increasing age. Raised tHcy concentrations are associated with laboratory evidence of atherogenesis (eg, endothelial dysfunction) and thrombosis, and epidemiological evidence of an increased risk of atherothrombotic vascular disease. An association between raised tHcy concentration and an increased risk of atherothrombosis is independent of other vascular risk factors, strong, dose-related and biologically plausible, but has not been proven to be causal in randomised controlled trials. A recent trial identified no significant benefit from lowering tHcy concentration by folic-acid-based multivitamin therapy among 3680 patients with recent ischaemic stroke, but did not reliably exclude a modest but important reduction in the relative risk of stroke of up to 20% a difference of only 2 mmol/L in tHcy concentration between the two treatment groups was probably due to widespread vitamin use and fortification of grains and staple foods with folate in North America. There is currently insufficient evidence to recommend routine screening and treatment of high tHcy concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease.
Publisher: Massachusetts Medical Society
Date: 20-04-2006
DOI: 10.1056/NEJMOA060989
Publisher: Elsevier BV
Date: 07-2023
Publisher: BMJ
Date: 04-1998
Abstract: A two generation family of Greek origin with mild myotonia, predominantly proximal muscle weakness, and cataracts compatible with the syndrome of proximal myotonic myopathy, is reported. In addition, brain MRI showed a diffuse leukoencephalopathy in the propositus. Molecular genetic studies showed the R894X mutation in exon 23 of the muscle chloride channel gene in the propositus but in only one of her two clinically affected offspring, indicating that it is not the mutation causing disease in this family.
Publisher: Oxford University Press (OUP)
Date: 28-08-2011
Abstract: Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages. We randomized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day [15 mg/day if creatinine clearance (CrCl) 30-49 mL/min] or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). Compared with patients with CrCl >50 mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/min were older (79 years) and had higher event rates irrespective of study treatment. Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin [hazard ratio (HR) 0.84 95% confidence interval (CI) 0.57-1.23] in the per-protocol population. Intention-to-treat analysis yielded similar results (HR 0.86 95% CI 0.63-1.17) to the per-protocol results. Rates of the principal safety endpoint (major and clinically relevant non-major bleeding: 17.82 vs. 18.28 per 100 patient-years P = 0.76) and intracranial bleeding (0.71 vs. 0.88 per 100 patient-years P = 0.54) were similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100 patient-years P = 0.047) occurred less often with rivaroxaban. Patients with AF and moderate renal insufficiency have higher rates of stroke and bleeding than those with normal renal function. There was no evidence of heterogeneity in treatment effect across dosing groups. Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2003
DOI: 10.1161/01.STR.0000077015.90334.A7
Abstract: Background and Purpose— Unaccustomed strenuous physical exertion can trigger myocardial infarction, but little is known about the mechanisms precipitating subarachnoid hemorrhage (SAH). Methods— We identified all cases of first-ever SAH among the combined populations (2.8 million) of 4 urban centers in Australia and New Zealand. Information on the type, time, and intensity of exposures in the 26 hours before the onset of SAH was ascertained by structured interviews. We used the case-crossover technique to assess the risk of SAH associated with transient exposures of moderate to extreme physical exertion, heavy cigarette smoking, and binge alcohol consumption. Results— We registered 432 first-ever cases of SAH (62% women mean age, 56.5 years). A definite time of onset of SAH was established for 393 patients (91%), and information on the levels of physical activity in the preceding 26 hours was obtained in 338 (78%). Of these patients, 19% engaged in moderate to extreme exertion (≥5 metabolic equivalents) in the 2 hours before SAH, which was associated with a tripling in the risk of SAH (odds ratio [OR], 2.7 95% CI, 1.6 to 4.6). There was no evidence of any association between heavy cigarette smoking or binge drinking and risk of SAH in the subsequent 2 hours (OR, 1.1 95% CI, 0.4 to 3.7 and OR, 0.41 95% CI, −∞ to 5.3). Habitual exercise did not appear to alter the risk of SAH associated with moderate to extreme exertion. Conclusions— Moderate to extreme physical exertion tripled the risk of SAH, but there was no association between transient heavy smoking or binge drinking and risk of SAH. These data suggest that heavy physical activity may trigger SAH.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.BURNS.2010.03.001
Abstract: Outcome assessment after burn is complex. Determination of quality of life is often measured using the Burns Specific Health Scale (BSHS), a validated tool in the burn population. The SF-36 is a generic quality of life questionnaire that is validated for numerous populations, but not in burns. The aim of the study was to examine the validity of SF-36, using the BSHS as a reference. 280 burn patients were recruited at Royal Perth Hospital. Each completed SF-36 and BSHS-B at regular intervals to 2 years after burn. Regression modelling was used to assess the temporal validity and the relative sensitivity of the measures. SF-36 domains and BSHS-B demonstrated significant associations at all time points (r=0.37-0.76, p<0.002). In the months after burn, SF-36 domains: role physical bodily pain social function and role emotional outperformed BSHS-B total score and domain scores. Greater measurement sensitivity was demonstrated in all SF-36 summary and subscales measures (except General Health) when compared to BSHS-B and sub-domains. This study demonstrated SF-36 as a valid measure of recovery of quality of life in the burn patient population. The data suggests that SF-36 components were more sensitive to change than the BSHS-B from ∼1 month after injury.
Publisher: SAGE Publications
Date: 04-01-2011
DOI: 10.1111/J.1747-4949.2010.00535.X
Abstract: The Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilisation, Management and Avoidance (CHARISMA) trial reported no statistically significant benefit of adding clopidogrel to acetylsalicylic acid in the long-term management of a broad population of patients with stable vascular disease. However, a subanalysis raised the hypothesis that dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid may be more effective than aspirin in patients with prior ischaemic stroke, myocardial infarction of symptomatic peripheral arterial disease. We aimed to determine whether the possible benefits of clopidogrel plus acetylsalicylic acid in patients with transient ischaemic attack and ischaemic stroke may be ‘front-loaded’, and maximal within the first 30-days of randomisation, without being unduly hazardous. This was a subanalysis of a randomised, double-blind, placebo-controlled trial of clopidogrel vs. placebo, in addition to background therapy with low-dose acetylsalicylic acid (CHARISMA trial), restricted to all patients with transient ischaemic attack or ischaemic stroke. The primary efficacy outcome was stroke, and safety outcome severe bleeding, during the follow-up period. Among all transient ischaemic attack and ischaemic stroke patients randomised to placebo ( n=2163), 131 (6·1%) experienced a stroke during follow-up compared with 105 (4·9%) of 2157 patients assigned clopidogrel (hazard ratio: 0·80, 95% confidence intervals: 0·62–1·03). There was no significant difference in severe bleeding (1·7% placebo vs. 1·9% clopidogrel, hazard ratio: 1·11, 95% confidence intervals: 0·71–1·73). Among all patients randomised within 30-days of their qualifying transient ischaemic attack or ischaemic stroke to placebo ( n=667), 46 (6·9%) experienced a stroke compared with 34 (5·1%) of 664 patients assigned clopidogrel (hazard ratio: 0·74, 0·46–1·16). There was no significant difference in severe bleeding (1·6% placebo vs. 1·4% clopidogrel, hazard ratio: 0·83, 95% confidence intervals: 0·34–2·01). The data are consistent with, but do not prove the hypothesis that early addition of clopidogrel to acetylsalicylic acid in patients with transient ischaemic attack and ischaemic stroke of arterial origin may be more effective and acceptably safe compared with acetylsalicylic acid alone. Adequately powered clinical trials that are dedicated to exploring this hypothesis are needed.
Publisher: Springer Science and Business Media LLC
Date: 03-2012
DOI: 10.1038/MP.2011.18
Publisher: Wiley
Date: 16-02-2016
Publisher: Springer Science and Business Media LLC
Date: 24-09-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2005
DOI: 10.1161/01.STR.0000150494.91762.70
Abstract: Background and Purpose— Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability. Methods— We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B 12 0.5 mg, and vitamin B 6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability. Results— At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [ P =0.32] soluble CD40L [ P =0.33] IL-6 [ P =0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [ P =0.27] intercellular adhesion molecule-1 [ P =0.08] von Willebrand factor [ P =0.92]), and hypercoagulability (P-selectin [ P =0.33] prothrombin fragment 1 and 2 [ P =0.81] D-dimer [ P =0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-μmol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy). Conclusions— Lowering tHcy by 3.7 μmol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required) (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured or (3) elevated tHcy is a noncausal marker of increased vascular risk.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.JOCN.2015.04.023
Abstract: We present a young woman (with an identical twin sister) who arrived at the Emergency Department (ED) within 1hour of her initial stroke symptoms. Previous microarray studies have demonstrated differential expression of multiple genes between stroke patients and healthy controls. However, for many of these studies there is a significant delay between the initial symptoms and collection of blood s les, potentially leaving the important early activators/regulators of the inflammatory response unrecognised. Blood s les were collected from the patient for an analysis of differential gene expression over time during the evolution of a fatal stroke. The time points for blood collection were ED arrival (T0) and 1, 3 and 24hours post ED arrival (T1, T3 and T24). This was compared to her identical twin and an additional two age and sex-matched healthy controls. When compared to the controls, the patient had 12 mRNA that were significantly upregulated at T0, and no downregulated mRNA (with a cut off fold change value ±1.5). Of the 12 upregulated mRNA at T0, granzyme B demonstrated the most marked upregulation on arrival, with expression steadily declining over time, whereas S100 calcium-binding protein A12 (S100A12) gene expression increased from T0 to T24, remaining >two-fold above that in the healthy controls at T24. Other genes, such as matrix metalloproteinase 9, high mobility group box 2 and interleukin-18 receptor I were not upregulated at T0, but they demonstrated clear upregulation from T1-T3, with gene expression declining by T24. A greater understanding of the underlying immunopathological mechanisms that are involved during the evolution of ischaemic stroke may help to distinguish between patients with stroke and stroke mimics.
Publisher: Oxford University Press (OUP)
Date: 24-01-2020
DOI: 10.1002/BJS.11422
Abstract: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P & 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46 P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent major 3·3 versus 3·4 per cent P = 0·110). Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2003
DOI: 10.1161/01.STR.0000097301.50041.6E
Abstract: Background and Summary— Selective cyclooxygenase (COX)-2 inhibitors are increasingly being used in place of “conventional” nonsteroidal anti-inflammatory drugs (NSAIDs). This is because they are just as effective as NSAIDs in relieving arthritic pain and yet less gastrotoxic. However, the cardiovascular safety of selective COX-2 inhibitors has been questioned because they selectively reduce prostacyclin production, thus disrupting the normal homeostatic balance and promoting a prothrombotic state. These theoretical concerns appear to be supported by the results of clinical trials demonstrating an increased risk of myocardial infarction with COX-2 inhibitors compared with a conventional NSAID, and indirect comparisons of the rates of myocardial infarction among patients treated with a selective COX-2 inhibitor compared with aspirin in different trials. However, emerging data from animal, experimental and clinical studies suggest that COX-2 is atherogenic and thrombogenic, and that selective COX-2 inhibitors may be cardioprotective. Meta-analyses of randomized trials of selective COX-2 inhibitors compared with placebo have demonstrated no excess of cardiovascular events among patients allocated COX-2 inhibitors, and preliminary data from a randomized controlled trial of the selective COX-2 inhibitor meloxicam, in patients with acute coronary syndrome who were treated with aspirin, demonstrated a reduction in cardiovascular events among patients allocated the COX-2 inhibitor. Conclusions— Continuing uncertainty regarding the direction and magnitude of any cardiovascular effects of selective COX-2 inhibitors, coupled with their widespread and increasing use, mandates prospective randomized evaluation of their efficacy and safety in patients at increased risk of future cardiovascular events.
Publisher: Elsevier BV
Date: 2022
Publisher: Wiley
Date: 04-1990
Publisher: AMPCo
Date: 07-1989
DOI: 10.5694/J.1326-5377.1989.TB101170.X
Abstract: A 12-year-old boy with corticosteroid-responsive mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is described. His mother proved to have an asymptomatic mitochondrial myopathy on examination of a muscle biopsy specimen. Three weeks after the onset of vomiting, headache, ataxia and visual and speech impairment, he presented with a background of somatic growth retardation, deafness and school failure. Examination revealed disorientation, dysphasia, dyspraxia, optic atrophy, hemianopia, hemiparesis and sensory inattention. A cranial computed tomographic scan disclosed a large, low-density area, which was consistent with infarction, in the left posterior hemisphere and marked calcification of the basal ganglia bilaterally. Within two weeks of the commencement of corticosteroid treatment, the neurological dysfunction resolved. Attempts to decrease the dosage of dexamethasone caused an exacerbation of symptoms repeatedly. Two weeks after ceasing corticosteroid therapy, the patient developed a serious neurological relapse and a new, large, low-density area, which resembled an infarction, in the right posterior hemisphere on a computed tomographic scan. The reintroduction of corticosteroid therapy again resulted in the rapid resolution of all symptoms. It became evident that the patient had an exquisitely sensitive corticosteroid dependency, whereby a reduction in the dexamethasone dosage of even 0.25 mg a day caused confusion, headaches and increasing lactic acidaemia. Although it is difficult to assess the impact of various therapies in MELAS because of the episodic natural course of the disease, this remarkable corticosteroid responsiveness also has been noted in four previously reported patients with MELAS syndrome therefore, it would seem reasonable to suggest that corticosteroid therapy now should be considered as standard treatment for this condition. However, corticosteroid therapy in other forms of mitochondrial disorders still awaits careful evaluation.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2006
Publisher: Informa UK Limited
Date: 02-2013
DOI: 10.1080/01635581.2013.756528
Abstract: The tropical edible red seaweed (Eucheuma cottonii L.) is rich in nutrients and polyphenolic compounds that may suppress cancer through its antioxidant and antiproliferative properties. The study reports on rat mammary tumor suppression and tissue antioxidant status modulation by E. cottonii ethanol extract (ECE). The effect of orally administered ECE (100 mg/kg body-weight) was compared with that of tamoxifen (10 mg/kg body-weight). Rat was induced to develop mammary tumor with subcutaneous injection of LA-7 cells (6 × 10(6) cells/rat). The ECE was more effective than tamoxifen in suppressing tumor growth (27%), improving tissues (plasma, liver, and kidney) malondialdehyde concentrations, superoxide dismutase activity and erythrocyte glutathione concentrations (P < 0.05). Unlike tamoxifen, the ECE displayed little toxicity to the liver and kidneys. The ECE exhibited strong anticancer effect with enzyme modulating properties, suggesting its potential as a suppressing agent for mammary gland tumor.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
DOI: 10.1161/STROKEAHA.113.001238
Abstract: In 1960s, a stroke belt with high stroke mortality was discovered in the southeast United States. In China, where stroke is the leading cause of death, we aimed to determine whether a focal region of high stroke incidence (stroke belt) exits and, if so, the possible causal and modifiable factors. We systematically reviewed all studies of stroke incidence in China between 1980 and 2010, and included those which met our criteria for a high-quality study. Criteria for a provincial region of high stroke incidence were ranking in the top one third of all provinces for stroke incidence and ranking of more than one third of prefectural regions within the province in the top two sevenths of all prefectural regions for stroke incidence. We also reviewed regional distribution of major vascular risk factors, socioeconomic status, and demographic profiles in China. Nine eligible studies provided data on the incidence of stroke in 32 of 34 provincial regions of China (with Hong Kong and Macao as exceptions) and 52% of the 347 prefectural regions. Nine provincial regions (Heilongjiang, Tibet, Jilin, Liaoning, Xinjiang, Hebei, Inner Mongolia, Beijing, and Ningxia) met our criteria for a region of high stroke incidence and constitute a stroke belt in north and west China. The incidence of stroke in the stroke belt was 236.2 per 100 000 population compared with 109.7 in regions outside the belt (rate ratio, 2.16 95% confidence interval, 2.10–2.22). The mean population prevalence of hypertension and overweight (body mass index, ) was greater in the stroke belt than that in other regions (15.3% versus 10.3%, P .001 21.1% versus 12.3%, P =0.013, respectively). The prevalence of hypertension and overweight also correlated significantly with regional stroke incidence ( R =0.642, P .001 R =0.438, P =0.014, respectively, by Spearman rank correlation). A stroke belt of high stroke incidence exists in 9 provincial regions of north and west China. The stroke belt may be caused, at least in part, by a higher population prevalence of hypertension and excess body weight. Lowering blood pressure and body weight in the stroke belt may reduce the geographic disparity in stroke risk and incidence in China.
Publisher: Oxford University Press (OUP)
Date: 11-05-2009
DOI: 10.1093/IJE/DYP199
Publisher: Springer Science and Business Media LLC
Date: 22-10-2022
DOI: 10.1186/S13063-022-06800-0
Abstract: Aboriginal Australians are known to suffer high levels of acquired brain injury (stroke and traumatic brain injury) yet experience significant barriers in accessing rehabilitation services. The aim of the Healing Right Way trial is to evaluate a culturally secure intervention for Aboriginal people with newly acquired brain injury to improve their rehabilitation experience and quality of life. Following publication of the trial protocol, this paper outlines the statistical analysis plan prior to locking the database. The trial involves a stepped wedge design with four steps over 3 years. Participants were 108 adult Aboriginal Australians admitted to one of eight hospitals (four rural, four urban) in Western Australia within 6 weeks of onset of a new stroke or traumatic brain injury who consented to follow-up for 26 weeks. All hospital sites started in a control phase, with the intervention assigned to pairs of sites (one metropolitan, one rural) every 26 weeks until all sites received the intervention. The two-component intervention involves training in culturally safe care for hospital sites and enhanced support provided to participants by Aboriginal Brain Injury Coordinators during their hospital stay and after discharge. The primary outcome is quality of life as measured by the Euro QOL–5D-3L VAS. A mixed effects linear regression model will be used to assess the between-group difference at 26 weeks post-injury. The model will control for injury type and severity, age at recruitment and time since commencement of the trial, as fixed effects. Recruitment site and participant will be included as random effects. Secondary outcomes include measurements of function, independence, anxiety and depression, carer strain, allied health occasions of service received and hospital compliance with minimum processes of care based on clinical guidelines and best practice models of care. The trial will provide the first data surrounding the effectiveness of an intervention package for Aboriginal people with brain injury and inform future planning of rehabilitation services for this population. The statistical analysis plan outlines the analyses to be undertaken. Australia New Zealand Clinical Trials Registry ACTRN12618000139279. Registered 30 January, 2018.
Publisher: AMPCo
Date: 09-2004
Publisher: Elsevier BV
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 23-02-2017
DOI: 10.1007/S12672-017-0287-4
Abstract: Advancing age is associated with increased cancer incidence, but the role of sex hormones as risk predictors for common cancers in older men remains uncertain. This study was performed to assess associations of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), with incident prostate, lung and colorectal cancer in community-dwelling older men. Plasma T, DHT and E2 were assayed using liquid chromatography-mass spectrometry between 2001 and 2004 in 3690 men. Cancer outcomes until 20 June 2013 were ascertained using data linkage. Analyses were performed using proportional hazards competing-risks models, and adjustments were made for potential confounding factors including smoking status. Results are expressed as subhazard ratios (SHR). There were 348, 107 and 137 cases of prostate, lung and colorectal cancers respectively during a median of 9.1-year follow-up. Mean T was comparable in current and non-smokers, whilst mean DHT was lower in ex- and current smokers compared to non-smokers. After adjusting for confounders including smoking, higher T or DHT was associated with an increased incidence of lung cancer (SHR = 1.30, 95% CI 1.06-1.60 p = 0.012 per 1 SD increase in T and SHR = 1.29, 95% CI 1.08-1.54 p = 0.004 for DHT). Sex hormones were not associated with prostate or colorectal cancer. In older men, higher T or DHT predict increased incidence of lung cancer over the next decade. Sex hormones are not associated with incident prostate or colorectal cancer. Further studies are warranted to determine if similar associations of sex hormones with lung cancer are present in other populations and to investigate potential underlying mechanisms.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.JACC.2015.09.024
Abstract: Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years hazard ratio: 1.42 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years p = 0.39 0.01 events/100 patient-years vs. 0.04 events/100 patient-years p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
DOI: 10.1161/STROKEAHA.113.004506
Abstract: Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02 95% CI, 1.39–2.94 black: hazard ratio, 3.25 95% CI, 1.43–7.41), age (1.35 1.13–1.63 per 10-year increase), reduced serum albumin (1.39 1.12–1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10 9 /L (1.08 1.02–1.13 per 10×10 9 /L decrease), previous stroke or transient ischemic attack (1.42 1.02–1.96), and increased diastolic blood pressure (1.17 1.01–1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60 0.44–0.82) and history of congestive heart failure (0.65 0.47–0.89). The ability of the model to discriminate in iduals with and without ICH was good ( C -index, 0.69 95% CI, 0.64–0.73). Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2002
DOI: 10.1097/00004872-200212000-00032
Abstract: To determine the relative importance of recognised risk factors for non-haemorrhagic stroke, including serum cholesterol and the effect of cholesterol-lowering therapy, on the occurrence of non-haemorrhagic stroke in patients enrolled in the LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease) study. The LIPID study was a placebo-controlled, double-blind trial of the efficacy on coronary heart disease mortality of pravastatin therapy over 6 years in 9014 patients with previous acute coronary syndromes and baseline total cholesterol of 4-7 mmol/l. Following identification of patients who had suffered non-haemorrhagic stroke, a pre-specified secondary end point, multivariate Cox regression was used to determine risk in the total population. Time-to-event analysis was used to determine the effect of pravastatin therapy on the rate of non-haemorrhagic stroke. There were 388 non-haemorrhagic strokes in 350 patients. Factors conferring risk of future non-haemorrhagic stroke were age, atrial fibrillation, prior stroke, diabetes, hypertension, systolic blood pressure, cigarette smoking, body mass index, male sex and creatinine clearance. Baseline lipids did not predict non-haemorrhagic stroke. Treatment with pravastatin reduced non-haemorrhagic stroke by 23% (P = 0.016) when considered alone, and 21% (P = 0.024) after adjustment for other risk factors. The study confirmed the variety of risk factors for non-haemorrhagic stroke. From the risk predictors, a simple prognostic index was created for non-haemorrhagic stroke to identify a group of patients at high risk. Treatment with pravastatin resulted in significant additional benefit after allowance for risk factors.
Publisher: CMA Joule Inc.
Date: 05-2014
DOI: 10.1503/JPN.130158
Publisher: BMJ
Date: 06-2007
DOI: 10.1136/EBM.12.3.88
Publisher: Wiley
Date: 03-1988
DOI: 10.1111/J.1445-2197.1988.TB01046.X
Abstract: An elderly Caucasian woman presented with a cervical myelopathy due to cervical spinal cord compression posteriorly by calcified ligamentum flavum and anteriorly by cervical osteophytic bars. Although recognized in the Japanese population, calcification of the ligamentum flavum as a cause of cervical myelopathy is very rare in Caucasians, with only one case previously reported.
Publisher: Elsevier BV
Date: 09-2011
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: Massachusetts Medical Society
Date: 04-07-2013
DOI: 10.1056/NEJME1305127
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14177
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2006
DOI: 10.1161/01.STR.0000199845.27512.84
Abstract: Background and Purpose— Increased plasma total homocysteine (tHcy) levels are a risk factor for stroke and can be reduced with vitamin therapy. However, data on the tHcy-lowering effects of vitamins are limited largely to white populations. Thus, we aimed to determine in Singaporean patients with recent stroke: (1) the efficacy of vitamin therapy (folic acid, vitamin B 12 , and B 6 ) on lowering tHcy, and (2) whether efficacy is modified by Methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphism(s). Methods— A total of 443 eligible patients were recruited after presenting with ischemic stroke within the past 7 months. Patients were randomized to receive either placebo or vitamins. Fasting blood s les collected at baseline and at 1 year were assayed for levels of plasma tHcy. Patients were genotyped for MTHFR C677T and A1298C polymorphisms. Results— Mean baseline tHcy was similar in the 2 groups (placebo 13.7 μmol/L vitamins 14.0 μmol/L P =0.70). At 1 year, mean tHcy was 14.5 μmol/L in the placebo group compared with 10.7 μmol/L in the vitamin group (difference 3.8 μmol/L 95% CI, 2.8 to 4.8 μmol/L P .0001). MTHFR C677T genotype was an independent determinant of tHcy levels at baseline ( P =0.005), but A1298C was not ( P= 0.08). Neither polymorphism significantly influenced the effect of vitamin therapy on tHcy at 1 year. The magnitude of the reduction in tHcy levels at 1 year with vitamin therapy was similar, irrespective of MTHFR genotypes. Conclusions— Vitamin therapy reduces mean tHcy levels by 3.8 μmol/L in the Singaporean stroke population studied. MTHFR C677T but not A1298C is independently associated with tHcy levels at baseline, and neither impacts the tHcy-lowering effect of vitamins used in this study.
Publisher: Oxford University Press (OUP)
Date: 05-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2008
DOI: 10.1161/ATVBAHA.108.162743
Abstract: Objective— The purpose of this study was to determine whether adjustment for renal function eliminates the relationship between total plasma homocysteine (tHcy) and vascular risk, assessed by carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery. Methods and Results— We used cross-sectional data from 173 stroke patients treated with B-vitamins (folic acid 2 mg, vitamin B 6 25 mg, and vitamin B 12 0.5 mg) or placebo in a randomized double-blinded trial to test the relationships between posttreatment tHcy, cystatin C (a marker of glomerular filtration rate), estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease equation) creatinine, CIMT, and FMD in stepwise and multivariable regression models. The strong linear relationship between tHcy and cystatin C was not altered by long-term B-vitamin treatment. tHcy lost significance as a predictor of the vascular measurements after adjustment for any single marker of renal function. Cystatin C, but not tHcy, was a significant independent predictor of FMD after adjustment for age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol, and treatment group. Conclusions— Adjusting for renal function eliminates the relationship between tHcy and CIMT and FMD, supporting the hypothesis that elevated tHcy is a marker for renal impairment rather than an independent cardiovascular risk factor.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.THROMRES.2006.08.014
Abstract: Aspirin resistance refers to less than expected suppression of thromboxane A(2) production by aspirin and has been reported to be independently associated with an increased risk of adverse cardiovascular events. Possible causes of aspirin resistance include poor compliance, drug interaction, inadequate aspirin dose, increase turnover of platelets, genetic polymorphisms of cyclo-oxygenase-1, and upregulation of alternate (non-platelet) pathways of thromboxane production. Laboratory methods used to detect aspirin resistance include those that measure thromboxane A(2) production and thromboxane A(2)-dependent platelet function. However, since there is currently no standardised approach to the diagnosis and there are no proven effective treatments for aspirin resistance that improve outcome, patients with cardiovascular disease receiving aspirin should not be routinely tested for aspirin resistance. Instead physicians should be aware of the factors that may impair aspirin function, ensure that they use an appropriate dose of aspirin and optimise compliance with aspirin therapy. Further research exploring the mechanisms of aspirin resistance is needed in order to better define and develop a standardised test for aspirin resistance that is specific, reliable, can be readily applied in routine laboratories and correlate with an increased risk of cardiovascular events.
Publisher: SAGE Publications
Date: 06-10-2020
Abstract: Effectiveness of early intensive aphasia rehabilitation after stroke is unknown. The Very Early Rehabilitation for SpEech trial (VERSE) aimed to determine whether intensive aphasia therapy, beginning within 14 days after stroke, improved communication recovery compared to usual care. Prospective, randomized, single-blinded trial conducted at 17 acute-care hospitals across Australia/New Zealand from 2014 to 2018. Participants with aphasia following acute stroke were randomized to receive usual care (direct usual care aphasia therapy), or one of two higher intensity regimens (20 sessions of either non-prescribed (usual care-plus or prescribed (VERSE) direct aphasia therapy). The primary outcome was improvement of communication on the Western Aphasia Battery-Revised Aphasia Quotient (AQ) at 12 weeks after stroke. Our pre-planned intention to treat analysis combined high intensity groups for the primary outcome. Among 13,654 acute stroke patients screened, 25% (3477) had aphasia, of whom 25% (866) were eligible and 246 randomized to usual care ( n = 81 33%), usual care-plus ( n = 82 33%) or VERSE ( n = 83 34%). At 12 weeks after stroke, the primary outcome was assessed in 217 participants (88%) 14 had died, 9 had withdrawn, and 6 were too unwell for assessment. Communication recovery was 50.3% (95% CI 45.7–54.8) in the high intensity group ( n = 147) and 52.1% (95% CI 46.1–58.1) in the usual care group ( n = 70 difference −1.8, 95% CI −8.7–5.0). There was no difference between groups in non-fatal or fatal adverse events ( p = 0.72). Early, intensive aphasia therapy did not improve communication recovery within 12 weeks post stroke compared to usual care.
Publisher: Wiley
Date: 05-04-2012
DOI: 10.1111/J.1365-2265.2011.04290.X
Abstract: Frailty is common in the elderly and predisposes to ill-health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men. Cross-sectional epidemiological study. Community-dwelling men aged 70-89 years. Circulating thyrotropin (TSH) and free thyroxine (FT(4) ) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale's 5 domains: fatigue resistance (difficulty climbing flight of stairs) ambulation (difficulty walking 100 m) illness (>5) or weight loss (>5%), blinded to hormone results. Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log-linear association of TSH with FT(4). There was no association between TSH and frailty. After adjusting for covariates, men with FT(4) in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01-1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04-1·79, P = 0·010 for trend). Higher FT(4) was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT(4) and frailty remained significant when the analysis was restricted to euthyroid men. High-normal FT(4) level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men.
Publisher: Physicians Postgraduate Press, Inc
Date: 15-07-2006
DOI: 10.4088/JCP.V67N0713
Abstract: We designed this study to determine whether the daily treatment of nondepressed acute stroke patients with sertraline reduced the incidence of depression at follow-up. 111 patients with recent stroke (< 2 weeks International Classification of Diseases, Tenth Revision criteria) were randomly assigned to treatment with placebo (N = 56) and sertraline (N = 55, 50 mg once daily) in this double-blind, placebo-controlled 24-week clinical trial. Subjects were recruited from the 2 largest teaching hospitals of Western Australia between June 2002 and June 2004. The primary endpoint of interest was development of clinically significant depressive symptoms as assessed by a Hospital Anxiety and Depression Scale-depression subscale score of 8 or above, or as diagnosed by the treating physician during 24 weeks. There was no significant difference in the incidence of depressive symptoms during 24 weeks of treatment (16.7% [8/48] sertraline vs. 21.6% [11/51] placebo, rate ratio = 0.8, 95% CI = 0.3 to 2.1, p = .590). The trial medication was discontinued by 51.8% (29/56) of patients assigned placebo and 47.3% (26/55) assigned sertraline (p = .634), most often because of perceived side effects or because the treating physician introduced an antidepressant medication. Twenty-four-week treatment with 50 mg of sertraline once daily initiated within 2 weeks of onset of acute stroke is not a significantly more effective strategy to prevent 6-month depression than usual care plus placebo among nondepressed stroke patients. New pharmacologic and nonpharmacologic strategies need to be developed to reduce the health and financial burden associated with depression after stroke.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JAMDA.2015.02.003
Abstract: The objective of this study was to establish the extent to which frailty was associated with attrition and then compare estimates of frailty prevalence and progression estimated from the observed data to those estimated after imputation. Population-based cohort study. The Health in Men Study (HIMS) with frailty estimated at Wave 2 (2001/2004) and Wave 3 (2008) and mortality follow-up to 2010. Participants were 10,305 community-dwelling men aged 70 and older, followed for up to 10 years. Participants completed an extensive questionnaire covering functional activities and illnesses. Frailty was assessed using the FRAIL Scale and a 32-item Frailty Index. Nonresponders at Wave 3 were more likely to have been frail at Wave 2. Imputed estimates of frailty prevalence were 8% to 10% higher than those derived from the observed data. Epidemiological surveys may substantially underestimate the levels of frailty among older people in the general population. This selective nonresponse results in an overoptimistic view of aging populations, particularly for the very old.
Publisher: Springer Science and Business Media LLC
Date: 17-08-2012
Publisher: American College of Physicians
Date: 15-07-2008
Publisher: Elsevier BV
Date: 11-2018
Publisher: BMJ
Date: 21-08-2009
DOI: 10.1136/BMJ.B2874
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.AMJCARD.2017.07.095
Abstract: The safety of intravenous thrombolysis in patients taking rivaroxaban has not been well established. We retrospectively analyzed the outcomes of all patients who received thrombolytic therapy in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). A review of medical and adverse event records for patients receiving thrombolytic therapy while enrolled in ROCKET AF was performed to determine their baseline characteristics, indications for thrombolysis, and type of agent used. Safety end points were 30-day post-thrombolytic rates of stroke, bleeding, and mortality. A total of 28 patients in ROCKET AF received thrombolytic therapy, with 19 patients on rivaroxaban and 9 patients on warfarin. Ischemic stroke was the most common indication for thrombolysis (n = 10), and alteplase was the most commonly used fibrinolytic agent (n = 14). Of the 19 patients in the rivaroxaban group, there were 2 nonfatal bleeding events and 2 deaths, mostly occurring when thrombolytic therapy was administered within 48 hours of the last rivaroxaban dose. Of the 9 patients in the warfarin group, there was 1 nonfatal bleeding event and 3 deaths, most occurring when thrombolytic therapy was administered outside of 48 hours from the last warfarin dose. In conclusion, these observations suggest that careful assessment of the time since the last dose may be of clinical significance in patients on novel oral anticoagulants who require emergent thrombolysis.
Publisher: BMJ
Date: 06-12-2012
Publisher: American Medical Association (AMA)
Date: 25-09-1996
Publisher: Oxford University Press (OUP)
Date: 02-2012
DOI: 10.1530/EJE-11-0725
Abstract: Abdominal aortic aneurysm (AAA) is most prevalent in older men. GH secretion declines with age resulting in reduced IGF1 levels. IGF1 and its binding proteins (IGFBPs) are expressed in vasculature, and lower IGF1 levels have been associated with cardiovascular risk factors and disease. However, the relationship of the IGF1 system with aortic dilation and AAA is unclear. We tested the hypothesis that circulating IGF1 and IGFBPs are associated with AAA and aortic diameter in older men. A cross-sectional analysis involving 3981 community-dwelling men aged 70–89 years was performed. Abdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays. After adjustment for age, body mass index, waist:hip ratio, smoking, hypertension, dyslipidemia, diabetes, coronary heart disease and serum creatinine, a higher IGF1 level was associated with AAA (odds ratio (OR)/1 s.d . increase 1.18, 95% confidence interval (CI) 1.05–1.33, P =0.006), as was the ratio of IGF1/IGFBP3 (OR=1.22, 95% CI 1.10–1.35, P .001). Highest IGF1 concentrations compared with lowest quintile were significantly associated with AAA (quintile (Q) 5 vs Q1: OR=1.80, 95% CI 1.20–2.70, P =0.004) as were IGF1/IGFBP3 ratios (Q5 vs Q1: OR=2.52, 95% CI 1.59–4.02, P .001). IGF1 and IGFBP1 were independently associated with aortic diameter ( β =0.200, 95% CI 0.043–0.357, P =0.012 and β =0.274, 95% CI 0.098–0.449, P =0.002 respectively). In older men, higher IGF1 and an increased ratio of IGF1/IGFBP3 are associated with AAA, while IGFBP1 is independently associated with increased aortic diameter. Components of the IGF1 system may contribute to, or be a marker for, aortic dilation in ageing men.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.BPOBGYN.2013.07.007
Abstract: Neurological conditions during pregnancy can be pregnancy related or can be caused by exacerbation of pre-existing neurological disorders. Knowledge of pre-existing epilepsy or myasthenia gravis in women of childbearing age requires preconception counselling by neurologist and planned pregnancy. Possible adverse effects of medication on the foetus should be balanced with the risk of uncontrolled symptoms. Interdisciplinary management before, during and after pregnancy is recommended. New acute neurological symptoms in pregnant or postpartum women should lead to an urgent neurological review. Patients need a thorough diagnostic evaluation that targets a range of serious pathological conditions that are either unique to (e.g. ecl sia) or arise more frequently (e.g. cerebral venous thrombosis) in this population. Most of these conditions are infrequent and require a specialized and multidisciplinary management. Treatment is challenging due to risks to the unborn child.
Publisher: Wiley
Date: 10-1989
DOI: 10.1111/J.1445-5994.1989.TB00308.X
Abstract: Benign headaches related to sexual activity and exertion are being recognised with increasing frequency. We wish to report a case of benign sexual headache (Type 2) and benign exertional headache, occurring sequentially in the same patient. Multiple areas of cerebral arterial spasm were demonstrable on angiography. This observation would support the concept that benign sexual headache (Type 2) and benign exertional headache may have a similar pathophysiology.
Publisher: AMPCo
Date: 10-2002
Publisher: The Endocrine Society
Date: 2012
DOI: 10.1210/JC.2011-1617
Abstract: Low testosterone is associated with all-cause mortality, but the relationship with cause-specific mortality is uncertain. Our objective was to explore associations between testosterone and its related hormones and cause-specific mortality. This was a population-based cohort study. Demographic and clinical predictors of mortality, and testosterone, SHBG, and LH were measured from 2001-2004 in 3637 community-dwelling men aged 70-88 yr (mean, 77 yr). Cause of death was obtained via electronic record linkage until December 31, 2008. During a mean follow-up period of 5.1 yr, there were 605 deaths. Of these, 207 [34.2% 95% confidence interval (CI) = 30.4-38.1%] were due to cardiovascular disease (CVD), 231 to cancer (38.2% 95% CI = 34.3-42.1%), 130 to respiratory diseases (21.5% 95% CI = 18.2-24.8%), and 76 to other causes (12.6% 95% CI = 9.9-15.2%). There were 39 deaths attributable to both cancer and respiratory diseases. Lower free testosterone (hazard ratio = 1.62 95% CI = 1.20-2.19, for 100 vs. 280 pmol/liter), and higher SHBG and LH levels were associated with all-cause mortality. In cause-specific analyses, lower free testosterone (sub-hazard ratio = 1.71 95% CI = 1.12-2.62, for 100 vs. 280 pmol/liter) and higher LH predicted CVD mortality, while higher SHBG predicted non-CVD mortality. Higher total testosterone and free testosterone levels (sub-hazard ratio = 1.96 95% CI = 1.14-3.36, for 400 vs. 280 pmol/liter) were associated with mortality from lung cancer. Low testosterone predicts mortality from CVD but is not associated with death from other causes. Prevention of androgen deficiency might improve cardiovascular outcomes but is unlikely to affect longevity otherwise.
Publisher: American Chemical Society (ACS)
Date: 11-1984
DOI: 10.1021/IC00192A005
Publisher: Elsevier BV
Date: 03-2000
Publisher: American Chemical Society (ACS)
Date: 11-1984
DOI: 10.1021/IC00192A006
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000086121
Abstract: i Background: /i Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy. i Methods: /i Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion. i Results: /i Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group. i Conclusions: /i These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.
Publisher: AMPCo
Date: 04-2008
Publisher: Massachusetts Medical Society
Date: 05-11-1998
Publisher: S. Karger AG
Date: 2000
DOI: 10.1159/000016094
Abstract: We prospectively examined 128 patients with acute first-ever stroke to determine the prevalence of swallowing disorders, the diagnostic accuracy of our clinical assessment of swallowing function compared with videofluoroscopy, and interobserver agreement for the clinical and videofluoroscopic diagnosis of swallowing disorders and aspiration. We found clinical and videofluoroscopic evidence of a swallowing disorder in 51% [95% confidence interval (CI) 42–60%] and 64% (95% CI 55–72%) of patients, respectively, and aspiration in 49% (95% CI 40–58%) and 22% (95% CI 15–29%) of patients, respectively. The optimal clinical criteria for detecting videofluoroscopic evidence of a swallowing disorder and aspiration were i any /i clinical evidence of a swallowing disorder (sensitivity 73%, 95% CI 62–82% specificity 89%, 95% CI 76–96%), and i any /i clinical evidence of aspiration (sensitivity 93%, 95% CI 76–99% specificity 63%, 95% CI 53–72%). The interobserver agreement between two speech pathologists for the clinical diagnosis of a swallowing disorder (κ: 0.82 ± 0.09) and aspiration (κ: 0.75 ± 0.09) was good, and between a speech pathologist and radiologist for the videofluoroscopic diagnosis of a swallowing disorder (κ: 0.75 ± 0.09) and aspiration (κ: 0.41 ± 0.09), it was good and fair, respectively. Although clinical bedside examination underestimates the frequency of swallowing abnormalities and overestimates the frequency of aspiration compared with videofluoroscopy, it may still offer valuable information for the diagnosis of swallowing impairment. Long-term follow-up studies are required to determine the independent functional significance of the findings of the bedside and videofluoroscopic examinations in predicting the occurrence of important outcome events such as aspiration pneumonia.
Publisher: Elsevier BV
Date: 06-2005
Publisher: SAGE Publications
Date: 05-05-2016
Abstract: The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014–2017. Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. All participants receive UC—usual ward-based aphasia therapy. Arm 1: UC—no additional therapy Arm 2: UC-plus usual ward-based therapy Arm 3: VERSE therapy—a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45–60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. Incremental cost-effectiveness ratios at 26 weeks will be reported. This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population.
Publisher: SAGE Publications
Date: 24-01-2018
Abstract: The sources of emboli in those with embolic stroke of undetermined source may differ in old and young. We assessed the frequency, features and potential embolic sources of younger vs. older embolic stroke of undetermined source patients in the embolic stroke of undetermined source Global Registry. Cross-sectional study of consecutive patients over age 18 years, with recent ischaemic strokes at 19 centres conducted in 2013–2014. Characteristics of embolic stroke of undetermined source patients who aged ≤50 years were analysed and compared with embolic stroke of undetermined source patients who aged years. Among 2144 patients with ischaemic stroke, 323 (15.1%, 95% confidence interval: 13.6–16.7%) were ≤50 years old and, 1821 years. 24% ( n = 78) of young vs. 15% ( n = 273) of older patients met embolic stroke of undetermined source criteria. The mean age of young embolic stroke of undetermined source patients was 40 years (standard deviation +/−9), 33% were women and the most prevalent vascular risk factor was hypertension (38%). Conventional vascular risk factors were less frequent in younger embolic stroke of undetermined source patients. Fewer young embolic stroke of undetermined source patients (63%) had potential minor risk embolic sources identified vs. older embolic stroke of undetermined source patients (77%) ( p = 0.02). Stroke severity on admission was similar in younger vs. older patients (National Institute of Health Stroke Scale (NIHSS) 3 vs. 4, p = 0.06). Young embolic stroke of undetermined source patients comprise an important subset of ischaemic stroke patients around the world. Severity of stroke on admission and 30-day mortality rates are similar among young and older patients. However, there are important differences between younger vs. older embolic stroke of undetermined source patients with respect to risk factors, and potential embolic sources that could affect response to anticoagulants vs. antiplatelet therapies. This study provides a benchmark for the global frequency and characteristics of young embolic stroke of undetermined source patients and shows consistent high frequency of embolic stroke of undetermined source in young adults.
Publisher: BMJ
Date: 29-07-2010
DOI: 10.1136/BMJ.C3784
Publisher: American College of Physicians
Date: 18-01-2011
Publisher: The Endocrine Society
Date: 11-2012
DOI: 10.1210/JC.2012-2265
Abstract: Testosterone (T) levels decline with increasing age. Controversy exists over the threshold for classifying T as low vs. normal in older men. The relevance of assessing dihydrotestosterone (DHT) and estradiol (E2) remains unclear. We assessed the associations of T, DHT, and E2 in men aged 70 yr or older and established reference ranges for these in healthy older men. Community-dwelling men aged 70–89 yr residing in Perth, Western Australia, Australia, participated in the study. Plasma T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning s les from 3690 men. Increasing age, higher body mass index and waist to hip ratio, dyslipidemia, diabetes, and higher LH were independently associated with lower levels of T and DHT. Increasing age, diabetes, and higher LH were associated with lower E2. In a reference group of 394 men aged 76.1 ± 3.2 yr reporting excellent or very good health with no history of smoking, diabetes, cardiovascular disease, cancer, depression, or dementia, the 2.5th percentile for T was 6.4 nmol/liter (184 ng/dl) DHT, 0.49 nmol/liter and E2, 28 pmol/liter. Applying these cutoffs to all 3690 men, those with low T or DHT had an increased odds ratio for frailty, diabetes, and cardiovascular disease. Men with both low T and DHT had a higher odds ratio for these outcomes. The 2.5th percentile in a reference group of healthy older men provides age-appropriate thresholds for defining low T, DHT, and E2. Additional studies are needed to test their potential applicability and clinical utility in older men.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.IJCARD.2017.06.110
Abstract: The aim of this study was to determine the net clinical benefit (NCB) of rivaroxaban compared with warfarin in patients with atrial fibrillation. This was a retrospective analysis of 14,236 patients included in ROCKET AF who received at least one dose of study drug. We analyzed NCB using four different methods: (1) composite of death, stroke, systemic embolism, myocardial infarction, and major bleeding (2) method 1 with fatal or critical organ bleeding substituted for major bleeding (3) difference between the rate of ischemic stroke or systemic embolism minus 1.5 times the difference between the rate of intracranial hemorrhage and (4) weighted sum of differences between rates of death, ischemic stroke or systemic embolism, intracranial hemorrhage, and major bleeding. Rivaroxaban was associated with a lower risk of the composite outcome of death, myocardial infarction, stroke, or systemic embolism (rate difference per 10,000 patient-years [RD]=-86.8 [95% CI -143.6 to -30.0]) and fatal or critical organ bleeding (-41.3 [-68 to -14.7]). However, rivaroxaban was associated with a higher risk of major bleeding other than fatal or critical organ bleeding (55.9 [14.7 to 97.2]). Method 1 showed no difference between treatments (-35.5 [-108.4 to 37.3]). Methods 2-4 favored treatment with rivaroxaban (2: -96.8 [-157.0 to -36.8] 3: -65.2 [-112.3 to -17.8] 4: -54.8 [-96.0 to -10.2]). Rivaroxaban was associated with favorable NCB compared with warfarin. The NCB was attributable to lower rates of ischemic events and fatal or critical organ bleeding.
Publisher: Informa UK Limited
Date: 12-09-2015
DOI: 10.3109/02699206.2014.956263
Abstract: Decline in linguistic function has been associated with decline in cognitive function in previous research. This research investigated the informativeness of written language s les of Australian men from the Health in Men's Study (HIMS) aged from 76 to 93 years using the Computerised Propositional Idea Density Rater (CPIDR 5.1). In total, 60,255 words in 1147 comments were analysed using a linear-mixed model for statistical analysis. Results indicated no relationship with education level (p = 0.79). Participants for whom English was not their first learnt language showed Propositional Idea Density (PD) scores slightly lower (0.018 per 1 word). Mean PD per 1 word for those for whom English was their first language for comments below 60 words was 0.494 and above 60 words 0.526. Text length was found to have an effect (p = <0.0001). The mean PD was higher than previously reported for men and lower than previously reported for a similar cohort for Australian women.
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.AHJ.2005.03.017
Abstract: The manifestations of atherothrombosis such as myocardial infarction, ischemic stroke, limb ischemia, or cardiovascular death pose a global health care burden. Additional therapies to decrease ischemic events in patients with established vascular disease or at risk for developing vascular disease are necessary. We sought to characterize the risk factors and treatments of a erse contemporary population of patients with atherothrombosis. The CHARISMA trial has enrolled 15,603 patients from around the world. Patients with established coronary, cerebrovascular, or peripheral arterial disease, or those at high risk of developing atherothrombosis due to multiple risk factors, have been randomized to receive either the adenosine diphosphate receptor antagonist clopidogrel or placebo, in addition to background therapy with low- to moderate-dose aspirin. A high percentage of enrolled patients are being treated with statins and angiotensin-converting enzyme inhibitors. In the CHARISMA population, a total of 75.6% of the population had an abnormal body mass index: 42.2% were overweight and 33.4% were obese, with particularly high rates in the United States, especially of morbid obesity. Correspondingly, the prevalence of diabetes was 42%. The CHARISMA trial will further characterize atherothrombosis and provide insight into the role of dual antiplatelet therapy in improving outcomes in patients with multiple risk factors or established vascular disease. Of note, the rates of obesity and diabetes in patients with atherothrombosis throughout the world are particularly alarming.
Publisher: Elsevier BV
Date: 05-2018
Publisher: BMJ
Date: 03-09-2014
DOI: 10.1136/BJSPORTS-2013-092814
Abstract: Physical activity has been associated with improved survival, but it is unclear whether this increase in longevity is accompanied by preserved mental and physical functioning, also known as healthy ageing. We designed this study to determine whether physical activity is associated with healthy ageing in later life. We recruited a community-representative s le of 12 201 men aged 65-83 years and followed them for 10-13 years. We assessed physical activity at the beginning and the end of the follow-up period. Participants who reported 150 min or more of vigorous physical activity per week were considered physically active. We monitored survival during the follow-up period and, at study exit, assessed the mood, cognition and functional status of survivors. Healthy ageing was defined as being alive at the end of follow-up and having a Patient Health Questionnaire score 27, and no major difficulty in any instrumental or basic activity of daily living. Cox regression and general linear models were used to estimate HR of death and risk ratio (RR) of healthy ageing. Analyses were adjusted for age, education, marital status, smoking, body mass index and history of hypertension, diabetes, coronary heart disease and stroke. Two thousand and fifty-eight (16.9%) participants were physically active at study entry. Active men had lower HR of death over 10-13 years than physically inactive men (HR=0.74, 95% CI=0.68 to 0.81). Among survivors, completion of the follow-up assessment was higher in the physically active than inactive group (risk ratio, RR=1.18, 95% CI=1.08 to 1.30). Physically active men had greater chance of fulfilling criteria for healthy ageing than inactive men (RR=1.35, 95% CI=1.19 to 1.53). Men who were physically active at the baseline and follow-up assessments had the highest chance of healthy ageing compared with inactive men (RR=1.59, 95% CI=1.36 to 1.86). Sustained physical activity is associated with improved survival and healthy ageing in older men. Vigorous physical activity seems to promote healthy ageing and should be encouraged when safe and feasible.
Publisher: SAGE Publications
Date: 05-2007
DOI: 10.1111/J.1747-4949.2007.00111.X
Abstract: Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke, dementia and depression. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B 12 and vitamin B 6 , it is not known whether lowering tHcy, by means of B vitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. To determine whether the addition of B-vitamin supplements (folic acid 2 mg, B 6 25 mg, B 12 500 μg) to best medical and surgical management will reduce the combined incidence of stroke, myocardial infarction (MI) and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. A prospective, international, multicentre, randomised, double blind, placebo-controlled clinical trial. One hundred and four medical centres in 20 countries on five continents. Eight thousand (6600 recruited as of 5 January, 2006) patients with recent (7 months) stroke (ischaemic or haemorrhagic) or TIA (brain or eye). Randomisation and data collection are performed by means of a central telephone service or secure internet site. One tablet daily of either placebo or B vitamins (folic acid 2mg, B 6 25 mg, B 12 500 μg). The composite of stroke, MI or death from any vascular cause, whichever occurs first. Outcome and serious adverse events are adjudicated blinded to treatment allocation. TIA, unstable angina, revascularisation procedures, dementia, depression. With 8000 patients followed up for a median of 2 years and an annual incidence of the primary outcome of 8% among patients assigned placebo, the study will have at least 80% power to detect a relative reduction of 15% in the incidence of the primary outcome among patients assigned B vitamins (to 6·8%/year), applying a two-tailed level of significance of 5%. VITATOPS aims to recruit and follow-up 8000 patients between 1998 and 2008, and provide a reliable estimate of the safety and effectiveness of folic acid, vitamin B 12 , and vitamin B 6 supplementation in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke throughout the world.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-11-2021
Publisher: BMJ
Date: 03-1989
Abstract: Classical beliefs about the functions of the dorsal columns of the spinal cord have been attacked following recent evidence that position and vibration sensations may be carried in the dorsal spinocerebellar tracts. There is evidence that the one specific function of the dorsal columns is for the transmission of information concerning the direction of tactile cutaneous movement. Thirty normal controls, 43 patients with spinal cord disorders and 10 patients with functional disorders were examined prospectively using an easily administered "direction of scratch" protocol. Interpretation of the direction of a 2 cm vertical tactile cutaneous movement over the lower limbs was found to be accurate in normal controls and grossly inaccurate in patients with functional disorders, exceeding the error rate of guessing. Detection of direction of 2 cm scratch was moderately impaired in 11 of 13 patients with spastic paraparesis and preserved sensation to all other modalities and 23 of 24 patients with spastic paraparesis and impaired proprioception and/or vibration sensations. Direction of 2 cm scratch, proprioception and vibration sensations were preserved in the three cases with anterior spinal cord syndromes. It is proposed that tactile perception of direction of 2 cm scratch over the lower limbs is a sensitive sign of posterior column function which can be usefully incorporated into the clinical sensory examination in the evaluation of spinal cord disorders.
Publisher: Oxford University Press (OUP)
Date: 06-2022
DOI: 10.1530/EJE-22-0104
Abstract: Men are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations and poorer COVID-19-related outcomes. We analysed the associations of premorbid serum testosterone concentrations, not confounded by the effects of acute SARS-CoV-2 infection, with COVID-19-related mortality risk in men. This study is a United Kingdom Biobank prospective cohort study of community-dwelling men aged 40–69 years. Serum total testosterone and sex hormone-binding globulin (SHBG) were measured at baseline (2006–2010). Free testosterone values were calculated (cFT). the incidence of SARS-CoV-2 infections and deaths related to COVID-19 were ascertained from 16 March 2020 to 31 January 2021 and modelled using time-stratified Cox regression. In 159 964 men, there were 5558 SARS-CoV-2 infections and 438 COVID-19 deaths. Younger age, higher BMI, non-White ethnicity, lower educational attainment, and socioeconomic deprivation were associated with incidence of SARS-CoV-2 infections but total testosterone, SHBG, and cFT were not. Adjusting for potential confounders, higher total testosterone was associated with COVID-19-related mortality risk (overall trend P = 0.008 hazard ratios (95% CIs) quintile 1, Q1 vs Q5 (reference), 0.84 (0.65–1.12) Q2:Q5, 0.82 (0.63–1.10) Q3:Q5, 0.80 (0.66–1.00) Q4:Q5, 0.82 (0.75–0.93)). Higher SHBG was also associated with COVID-19 mortality risk (P = 0.008), but cFT was not (P = 0.248). Middle-aged to older men with the highest premorbid serum total testosterone and SHBG concentrations are at greater risk of COVID-19-related mortality. Men could be advised that having relatively high serum testosterone concentrations does not protect against future COVID-19-related mortality. Further investigation of causality and potential underlying mechanisms is warranted.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2023
Publisher: National Institute for Health and Care Research
Date: 05-2020
DOI: 10.3310/HTA24220
Abstract: Our Cochrane review of selective serotonin inhibitors for stroke recovery indicated that fluoxetine may improve functional recovery, but the trials were small and most were at high risk of bias. The Fluoxetine Or Control Under Supervision (FOCUS) trial tested the hypothesis that fluoxetine improves recovery after stroke. The FOCUS trial was a pragmatic, multicentre, parallel-group, in idually randomised, placebo-controlled trial. This trial took place in 103 UK hospitals. Patients were eligible if they were aged ≥ 18 years, had a clinical stroke diagnosis, with focal neurological deficits, between 2 and 15 days after onset. Patients were randomly allocated 20 mg of fluoxetine once per day or the matching placebo for 6 months via a web-based system using a minimisation algorithm. The primary outcome was the modified Rankin Scale at 6 months. Patients, carers, health-care staff and the trial team were masked to treatment allocation. Outcome was assessed at 6 and 12 months after randomisation. Patients were analysed by their treatment allocation as specified in a published statistical analysis plan. Between 10 September 2012 and 31 March 2017, we recruited 3127 patients, 1564 of whom were allocated fluoxetine and 1563 of whom were allocated placebo. The modified Rankin Scale score at 6 months was available for 1553 out of 1564 (99.3%) of those allocated fluoxetine and 1553 out of 1563 (99.4%) of those allocated placebo. The distribution across modified Rankin Scale categories at 6 months was similar in the two groups (common odds ratio adjusted for minimisation variables 0.951, 95% confidence interval 0.839 to 1.079 p = 0.439). Compared with placebo, patients who were allocated fluoxetine were less likely to develop a new episode of depression by 6 months [210 (13.0%) vs. 269 (16.9%), difference –3.78%, 95% confidence interval –1.26% to –6.30% p = 0.003], but had more bone fractures [45 (2.9%) vs. 23 (1.5%), difference 1.41%, 95% confidence interval 0.38% to 2.43% p = 0.007]. There were no statistically significant differences in any other recorded events at 6 or 12 months. Health economic analyses showed no differences between groups in health-related quality of life, hospital bed usage or health-care costs. Some non-adherence to trial medication, lack of face-to-face assessment of neurological status at follow-up and lack of formal psychiatric diagnosis during follow-up. 20 mg of fluoxetine daily for 6 months after acute stroke did not improve patients’ functional outcome but decreased the occurrence of depression and increased the risk of fractures. These data inform decisions about using fluoxetine after stroke to improve functional outcome or to prevent or treat mood disorders. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) (Australasia/Vietnam) and Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke (EFFECTS) (Sweden) trials recruited an additional 2780 patients and will report their results in 2020. These three trials have an almost identical protocol, which was collaboratively developed. Our planned in idual patient data meta-analysis will provide more precise estimates of the effects of fluoxetine after stroke and indicate whether or not effects vary depending on patients’ characteristics and health-care setting. Current Controlled Trials ISRCTN83290762. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 24, No. 22. See the NIHR Journals Library website for further project information. The Stroke Association (reference TSA 2011101) funded the start-up phase.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14132
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2010
DOI: 10.1161/STROKEAHA.109.558809
Abstract: Background and Purpose— Differences in risk factor profiles between lacunar and other ischemic stroke subtypes may provide evidence for a distinct lacunar arteriopathy, but existing studies have limitations. We overcame these by pooling in idual data on 2875 patients with first-ever ischemic stroke from 5 collaborating prospective stroke registers that used similar, unbiased methods to define risk factors and classify stroke subtypes. Methods— We compared risk factors between lacunar and nonlacunar ischemic strokes, altering the comparison groups in sensitivity analyses, and incorporated these data into a meta-analysis of published studies. Results— Unadjusted and adjusted analyses gave similar results. We found a lower prevalence of cardioembolic source (adjusted odds ratio, 0.33 95% CI, 0.24 to 0.46), ipsilateral carotid stenosis (odds ratio, 0.21 95% CI, 0.14 to 0.30), and ischemic heart disease (odds ratio, 0.75 95% CI, 0.58 to 0.97) in lacunar compared with nonlacunar patients but no difference for hypertension, diabetes, or any other risk factor studied. Results were robust to sensitivity analyses and largely confirmed in our meta-analysis. Conclusions— Hypertension and diabetes appear equally common in lacunar and nonlacunar ischemic stroke, but lacunar stroke is less likely to be caused by embolism from the heart or proximal arteries, and the lower prevalence of ischemic heart disease in lacunar stroke provides additional support for a nonatherosclerotic arteriopathy causing many lacunar ischemic strokes. Our findings have implications for how clinicians classify ischemic stroke subtypes and highlight the need for additional research into the specific causes of and treatments for lacunar stroke.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2011
Publisher: SAGE Publications
Date: 04-06-2015
DOI: 10.1111/IJS.12537
Abstract: Infarct location has a critical effect on patient outcome after ischemic stroke, but the study of its role independent of overall lesion volume is challenging. We performed a retrospective, hypothesis-generating study of the effect of infarct location on three-month functional outcome in a pooled analysis of the EPITHET and DEFUSE studies. Posttreatment MRI diffusion lesions were manually segmented and transformed into standard-space. A novel composite brain atlas derived from three standard brain atlases and encompassing 132 cortical and sub-cortical structures was used to segment the transformed lesion into different brain regions, and calculate the percentage of each region infarcted. Classification and Regression Tree (CART) analysis was performed to determine the important regions in each hemisphere associated with nonfavorable outcome at day 90 (modified Rankin score [mRS] 1). Overall, 152 patients (82 left hemisphere) were included. Median diffusion lesion volume was 37·0 ml, and median baseline National Institutes of Health Stroke Score was 13. In the left hemisphere, the strongest determinants of nonfavorable outcome were infarction of the uncinate fasciculus, followed by precuneus, angular gyrus and total diffusion lesion volume. In the right hemisphere, the strongest determinants of nonfavorable outcome were infarction of the parietal lobe followed by the putamen. Assessment of infarct location using CART demonstrates regional characteristics associated with poor outcome. Prognostically important locations include limbic, default-mode and language areas in the left hemisphere, and visuospatial and motor regions in the right hemisphere.
Publisher: American Medical Association (AMA)
Date: 10-2010
Publisher: Elsevier BV
Date: 03-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
DOI: 10.1161/STROKEAHA.113.004339
Abstract: Studies in rodent models suggest that upregulating angiopoietin-1 (Angpt1) improves stroke outcomes. The aims of this study were to assess the association of plasma Angpt1 with stroke occurrence and outcome. Plasma Angpt1 was measured in 336 patients who had experienced a recent stroke and 321 healthy controls with no stroke history. Patients with stroke (n=285) were reassessed at 3 months and plasma Angpt1 concentration on admission compared between those with severe and minor disability as assessed by the modified Rankin scale. In a separate cohort of 4032 community-acquired older men prospectively followed for a minimum of 6 years, the association of plasma Angpt1 with stroke incidence was examined. Median plasma Angpt1 was 3-fold lower in patients who had experienced a recent stroke (6.42, interquartile range, 4.26–9.53 compared with 17.36 interquartile range, 14.01–22.46 ng/mL P .001) and remained associated with stroke after adjustment for other risk factors. Plasma Angpt1 concentrations on admission were lower in patients who had severe disability or died at 3 months (median, 5.52 interquartile range, 3.81–8.75 ng/mL for modified Rankin scale 3–6 n=91) compared with those with minor disability (median, 7.04 interquartile range, 4.75–9.92 ng/mL for modified Rankin scale 0–2 n=194), P =0.012, and remained negatively associated with severe disability or death after adjusting for other risk factors. Plasma Angpt1 was not predictive of stroke incidence in community-dwelling older men. Plasma Angpt1 concentrations are low after ischemic stroke particularly in patients with poor stroke outcomes at 3 months. Interventions effective at upregulating Angpt1 could potentially improve stroke outcomes.
Publisher: Elsevier BV
Date: 2017
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.BEHA.2013.07.007
Abstract: In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K antagonists (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26 percent. Vitamin-K antagonists have a number of well documented shortcomings. Recently the results of randomised trials for three new oral anticoagulants that do not exhibit the limitations of vitamin-K antagonists have been published. These include direct factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide promising results for the new agents, including higher efficacy and a significantly lower incidence of intracranial bleeds compared with warfarin or aspirin. The new drugs show similar results in secondary as well as in primary stroke prevention in patients with AF. Apixaban was demonstrated to be clearly superior to aspirin and had the same rate of major bleeding complications. Meta-analyses show that the novel anticoagulants are superior to warfarin for the reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants add to the therapeutic options for patients with AF, and offer a number of advantages over warfarin, for both the clinician and patient, including a favorable bleeding profile and convenience of use. Aspirin is no longer an option in secondary stroke prevention in patients with atrial fibrillation. Consideration of these new anticoagulants will improve clinical decision making.
Publisher: Elsevier BV
Date: 15-01-2005
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 08-11-2013
Publisher: Elsevier BV
Date: 07-2000
Publisher: Elsevier BV
Date: 03-2001
Publisher: Springer Science and Business Media LLC
Date: 14-08-2012
DOI: 10.1038/TP.2012.79
Publisher: The Endocrine Society
Date: 2014
DOI: 10.1210/JC.2013-3272
Abstract: Testosterone (T) levels decline with age and lower T has been associated with increased mortality in aging men. However, the associations of its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with mortality are poorly defined. We assessed associations of T, DHT, and E2 with all-cause and ischemic heart disease (IHD) mortality in older men. Participants were community-dwelling men aged 70 to 89 years who were residing in Perth, Western Australia. Plasma total T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning s les collected in 2001 to 2004 from 3690 men. Deaths to December 2010 were ascertained by data linkage. There were 974 deaths (26.4%), including 325 of IHD. Men who died had lower baseline T (12.8±5.1 vs 13.2±4.8 nmol/L [mean±SD], P=.013), DHT (1.4±0.7 vs 1.5±0.7 nmol/L, P=.002), and E2 (71.6±29.3 vs 74.0±29.0 pmol/L, P=.022). After allowance for other risk factors, T and DHT were associated with all-cause mortality (T: quartile [Q] Q2:Q1, adjusted hazard ratio [HR]=0.82, P=.033 Q3:Q1, HR=0.78, P=.010 Q4:Q1, HR=0.86, P>.05 DHT: Q3:Q1, HR=0.76, P=.003 Q4:Q1, HR=0.84, P>.05). Higher DHT was associated with lower IHD mortality (Q3:Q1, HR=0.58, P=.002 Q4:Q1, HR=0.69, P=.026). E2 was not associated with either all-cause or IHD mortality. Optimal androgen levels are a biomarker for survival because older men with midrange levels of T and DHT had the lowest death rates from any cause, whereas those with higher DHT had lower IHD mortality. Further investigations of the biological basis for these associations including randomized trials of T supplementation are needed.
Publisher: Elsevier BV
Date: 04-1999
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2004
DOI: 10.1161/01.STR.0000116183.50167.D9
Abstract: Background and Purpose— Limited information exists on the long-term prognosis after first-ever stroke. We aimed to determine the absolute frequency of first recurrent stroke and disability and the relative frequency of recurrent stroke over 10 years after first-ever stroke in Perth, Western Australia. Methods— For a 12-month period beginning February 1989, all in iduals with suspected acute stroke or transient ischemic attack who lived in a geographically defined and representative region of Perth were registered prospectively. Patients with a definite first-ever stroke were followed up 10 years after the index event. Results— Over 10 years of follow-up, the cumulative risk of a first recurrent stroke was 43% (95% confidence interval [CI], 34 to 51). After the first year after first-ever stroke, the average annual risk of recurrent stroke was ≈4%. Case fatality at 30 days after first recurrent stroke was 41%, which was significantly greater than the case fatality at 30 days after first-ever stroke (22%) ( P =0.003). For 30-day survivors of first-ever stroke, the 10-year cumulative risk of death or new institutionalization was 79% (95% CI, 73 to 85) and of death or new disability was 87% (95% CI, 81 to 92). Conclusions— Over 10 years of follow-up, the risk of first recurrent stroke is 6 times greater than the risk of first-ever stroke in the general population of the same age and sex, almost one half of survivors remain disabled, and one seventh require institutional care. Effective strategies for prevention of stroke need to be implemented early, monitored frequently, and maintained long term after first-ever stroke.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.AMJCARD.2017.03.028
Abstract: We investigated stroke outcomes in normal weight (body mass index [BMI] 18.50 to 24.99 kg/m
Publisher: American Medical Association (AMA)
Date: 02-2006
Abstract: Peripheral arterial disease (PAD) affects approximately 20% of adults older than 55 years and is a powerful predictor of myocardial infarction, stroke, and death due to vascular causes. The goals of treatment are to prevent future major coronary and cerebrovascular events and improve leg symptoms. To review the best evidence for medical treatment of PAD. MEDLINE and the Cochrane database were searched from 1990 to November 2005 for randomized trials and meta-analyses of medical treatments for PAD. References from these articles were also searched. Search terms included, singly and in combination: peripheral arterial disease, peripheral artery disease, PAD, randomized controlled trial, controlled trial, randomized, and meta-analysis. Particular attention was directed toward randomized controlled trials and meta-analyses of clinically relevant medical treatments for PAD. Outcome measures included leg symptoms (intermittent claudication and walking distance), death, and major coronary and cerebrovascular events. Symptoms of leg claudication, walking distance, and quality of life can be improved by smoking cessation (physician advice, nicotine replacement therapy, and bupropion), a structured exercise program, statin drugs, cilostazol, and angiotensin-converting enzyme inhibitors. The risk of major coronary and cerebrovascular events can be reduced through lowering blood pressure with angiotensin-converting enzyme inhibitors and other antihypertensive drugs, use of statin drugs, antiplatelet therapy with aspirin or clopidogrel, and probably by stopping smoking. The substantial and increasing burden of PAD, and its local and systemic complications, can be reduced by lifestyle modification (smoking cessation, exercise) and medical therapies (nicotine replacement therapy, bupropion, antihypertensive drugs, statins, and antiplatelet drugs).
Publisher: Wiley
Date: 14-09-2020
DOI: 10.1111/FAF.12506
Publisher: Elsevier BV
Date: 10-2009
Publisher: Elsevier BV
Date: 03-1998
Publisher: Elsevier BV
Date: 11-2018
Publisher: Oxford University Press (OUP)
Date: 22-08-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Elsevier BV
Date: 12-2008
Publisher: Springer Science and Business Media LLC
Date: 17-10-2021
DOI: 10.1186/S12874-021-01388-6
Abstract: Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them. Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared in idual participant data from their trials. Ordered categorical versions of vascular event outcomes (such as stroke and myocardial infarction) were analysed using 15 statistical techniques and their results then ranked, with the result with the smallest p -value given the smallest rank. Friedman and Duncan’s multiple range tests were performed to assess differences between tests by comparing the average ranks for each statistical test. Data from 35 trials (254,223 participants) were shared with the collaboration. 13 trials had more than two treatment arms, resulting in 59 comparisons. Analysis approaches (Mann Whitney U, ordinal logistic regression, multiple regression, bootstrapping) that used ordinal outcome data had a smaller average rank and therefore appeared to be more efficient statistically than those that analysed the original binary outcomes. Ordinal vascular outcome measures appear to be more efficient statistically than binary outcomes and provide information on the severity of event. We suggest a potential role for using ordinal outcomes in vascular prevention trials.
Publisher: American Chemical Society (ACS)
Date: 04-1986
DOI: 10.1021/IC00228A031
Publisher: Wiley
Date: 28-01-2019
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.YPMED.2013.09.021
Abstract: This study aimed to develop a simple risk table of modifiable factors prospectively associated with depression in later life that could be used to guide the assessment, management and introduction of preventive strategies in clinical practice. This retrospective cohort study included 4636 men aged 65 to 83 years living in the community who denied history of past diagnosis or treatment for depression. They self-reported information about their physical activity, weight and height, smoking history, alcohol consumption and dietary habits, as well as history of hypertension, diabetes, coronary heart disease and stroke. We calculated the body mass index (BMI) in kg/m(2). Three to 8 years later they were assessed with the Geriatric Depression Scale 15 (GDS-15) and those with a total score of 7 or greater were considered to display clinically significant symptoms of depression. We used binomial exponentiated log-linked general linear models to estimate the risk ratio (RR) and 95% confidence interval (95% CI) of incident depression after adjusting for age, education, marital status and prevalent medical illnesses. We calculated the probability of depression for each in idual combination of risk factors and displayed the results in a risk table. Two hundred and twenty-nine men (4.5%) showed evidence of incident depression 5.7±0.9 (mean±standard deviation) years later. Measured dietary factors showed no association with incident depression. The probability of depression was the highest for older men who were underweight, overweight or obese, physically inactive, risk drinkers and smokers (12.0%, 95% CI=7.0%, 17.1%), and the lowest for those who had all 4 healthy lifestyle markers: physically active, normal body mass, non-risk drinking and non-smoking (1.6%, 95% CI=0.6%, 2.5%). The probability of incident depression fell between these two extremes for different combinations of lifestyle practices. Four modifiable lifestyle factors can be used in combination to produce a risk table that predicts the probability of incident depression over a period of 3 to 8 years. The risk table is simple, informative and can be easily incorporated into clinical practice to guide assessment and risk reduction interventions.
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Portland Press Ltd.
Date: 09-08-2011
DOI: 10.1042/CS20110215
Abstract: CYP450AAM [arachidonic acid metabolites of the CYP450 (cytochrome P450) enzyme system] have a range of biological functions. CYP450AAM are involved in the pathogenesis of hypertension, renal function and vascular function, yet their role in stroke has not been clarified. We aimed at determining the levels of circulating CYP450 metabolites in patients with acute ischaemic stroke (& h) compared with healthy age- and gender-matched controls. This was a retrospective case-controlled study of 44 acute ischaemic stroke patients and 44 matched controls. A subset of acute ischaemic stroke patients was available for follow-up. Acute ischaemic stroke patients had elevated plasma CYP450AAM, including 20-HETE (20-hydroxyeicosatetraenoic acid) (1921±170 compared with 1108±170 pmol/l, P& .001), EETs (epoxyeicosatrienoic acids) (77.88±3.34 compared with 35.35±3.34 nmol/l, P& .0001) and DiHETEs (dihydroxyeicosatetraenoic acids) (92.87±4.61 compared with 68.17±4.61 nmol/l, P& .0001), as well as increased plasma F2-isoprostane levels (3754±538 compared with 1947±538 pmol/l, P& .02), the latter a marker of oxidative stress, compared with controls. In a subset analysis of the stroke patients, plasma 20-HETE, EETs and F2-isoprostanes were attenuated 30 days after the stroke. Baseline 20-HETE levels were also associated with lesion size and functional indices within the stroke patients. The present study highlights the elevation in CYP450AAM and oxidative stress in acute ischaemic stroke patients. Further investigation of the effect this has on long-term clinical outcome or whether this can be modified by treatment is warranted.
Publisher: Wiley
Date: 04-2008
DOI: 10.1111/J.1445-5994.1990.TB01297.X
Abstract: The recurrence of an isolated unilateral left abducens nerve palsy on five occasions over five years is described in an adult. No evidence of any systemic or intracranial disorder has been identified. The aetiology remains uncertain and the clinical course is benign. The diagnosis of 'benign' abducens nerve palsy is one of exclusion and is made retrospectively after an adequate period of serial evaluations.
Publisher: Elsevier BV
Date: 04-2008
Publisher: AMPCo
Date: 19-06-2019
DOI: 10.5694/MJA2.50233
Abstract: Pulmonary embolism (PE) is a potentially life-threatening condition, mandating urgent diagnosis and treatment. The symptoms of PE may be non-specific diagnosis therefore relies on a clinical assessment and objective diagnostic testing. A clinical decision rule can determine the pre-test probability of PE. If PE is "unlikely", refer for a D-dimer test. If the D-dimer result is normal, PE can be excluded. If D-dimer levels are increased, refer for chest imaging. If PE is "likely", refer for chest imaging. Imaging with computed tomography pulmonary angiogram is accurate and preferred for diagnosing PE, but may detect asymptomatic PE of uncertain clinical significance. Imaging with ventilation-perfusion (VQ) scan is associated with lower radiation exposure than computed tomography pulmonary angiogram, and may be preferred in younger patients and pregnancy. A low probability or high probability VQ scan is helpful for ruling out or confirming PE, respectively however, an intermediate probability VQ scan requires further investigation. The direct oral anticoagulants have expanded the anticoagulation options for PE. These are the preferred anticoagulant for most patients with PE because they are associated with a lower risk of bleeding, and have the practical advantages of fixed dosage, no need for routine monitoring, and fewer drug interactions compared with vitamin K antagonists. Initial parenteral treatment is required before dabigatran and edoxaban.
Publisher: Springer Science and Business Media LLC
Date: 13-04-2017
DOI: 10.1038/JHH.2017.10
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
DOI: 10.1161/STROKEAHA.120.032973
Abstract: Stroke survivors have an increased risk of depression and bone fractures. Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures in observational studies. Several randomized controlled trials (RCTs) reporting the effect of SSRIs on the risk of fractures in stroke survivors have been published recently but have not been subject to a meta-analysis. We aimed to determine the risk of fractures associated with the use of SSRIs, and the risk of falls, seizures, and recurrent strokes as possible mediators of fractures, in stroke survivors. We conducted a systematic review and meta-analysis of RCTs of SSRIs in stroke survivors according to a protocol registered in PROSPERO (CRD42020192632). Web of Science, EMBASE, PsycINFO, and Ovid Medline/PubMed bibliographic databases, clinical trial registers, and grey literature sources were searched. RCTs of SSRIs versus placebo or no intervention that report the risk of fractures in adult survivors of hemorrhagic or ischemic stroke were included. Two reviewers independently screened search results and extracted data. Meta-analyses were conducted for each outcome using the Mantel-Haenszel random-effects models. The searches yielded 683 records, of which 4 RCTs of 6 months duration with a total of 6549 participants were included in the meta-analysis: 3 studies of fluoxetine and 1 study of citalopram. Treatment with an SSRI for 6 months increased the risk of fractures with a risk ratio of 2.36 (95% CI, 1.64–3.39) compared with placebo. The risk of falls, seizures, and recurrent stroke was not statistically significantly increased. Only studies of fluoxetine and citalopram were available for inclusion in the review, and hence the generalizability of the findings to other SSRIs is uncertain. Based on available RCTs of fluoxetine and citalopram, SSRIs used for 6 months doubled the risk of fractures in stroke survivors. URL: www.crd.york.ac.uk rospero/ Unique identifier: CRD42020192632.
Publisher: Elsevier BV
Date: 10-2023
Publisher: BMJ
Date: 08-01-1994
Publisher: Elsevier BV
Date: 08-2012
Publisher: The Endocrine Society
Date: 06-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-08-2015
Publisher: Elsevier BV
Date: 06-2014
Publisher: American Medical Association (AMA)
Date: 10-2010
DOI: 10.1001/ARCHNEUROL.2010.249
Abstract: The vascular pathogenesis underlying lobar intracerebral hemorrhage (ICH) is unclear. To determine whether certain retinal microvascular signs are associated with lobar ICH to improve understanding of its underlying cerebral vasculopathy. Prospective cohort study. Royal Melbourne Hospital and Westmead Hospital. Of 655 patients with acute stroke, 25 had lobar ICH, 51 had deep ICH, 93 had lacunar infarction, and 486 had nonlacunar cerebral infarction. Retinal photographs were assessed for retinopathy lesions (microaneurysms, retinal hemorrhages, cotton-wool spots, and hard exudates) and retinal arteriolar wall signs (focal arteriolar narrowing, arteriovenous nicking, and enhanced arteriolar wall light reflex) masked to the cerebral pathologic abnormalities and the study hypothesis. In patients without diabetes mellitus, retinopathy lesions were more likely to be present in persons with lobar ICH than in those with either lacunar infarction (47.8% vs 30.4% adjusted odds ratio, 3.5 95% confidence interval, 1.1-10.9) or nonlacunar cerebral infarction (47.8% vs 24.6% 3.3 .4-8.1). Most retinal arteriolar wall signs were less frequent in lobar ICH than in deep ICH, although this difference was significant only for focal arteriolar narrowing. Patients with lobar ICH were more likely than patients with lacunar or nonlacunar cerebral infarction to have retinopathy lesions, suggesting breakdown of the blood-retina barrier in patients with lobar ICH. These findings support a distinct vasculopathy in lobar ICH compared with other acute stroke subtypes resulting from cerebral small vessel disease or ischemic infarction.
Publisher: Massachusetts Medical Society
Date: 03-08-2000
Publisher: Springer Science and Business Media LLC
Date: 17-06-2008
Publisher: Springer Japan
Date: 1995
Publisher: Elsevier BV
Date: 2019
Publisher: AMPCo
Date: 04-2013
DOI: 10.5694/MJA12.11642
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2018
DOI: 10.1161/STROKEAHA.117.016674
Abstract: A variant in the histone deacetylase 9 ( HDAC9 ) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530 log-rank survival analysis P =0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44 95% confidence interval: 0.3–0.7 P =0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47 95% confidence interval: 0.29–0.77 P =0.003). These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke.
Publisher: Wiley
Date: 10-04-2013
DOI: 10.1111/CEN.12052
Abstract: Ageing is associated with frailty and decreased anabolic hormones, insulin-like growth factor-I (IGF-I) and testosterone. We hypothesized that components of the IGF-I system, in conjunction with testosterone, modulate frailty risk in the elderly. We examined associations between IGF-I, its binding proteins IGFBP1 and IGFBP3 and testosterone with frailty in men. Observational study of 3 447 community-dwelling men aged 70-89 years assessed in 2001-04, with 1 654 reassessed in 2008-09. Baseline total IGF-I, IGFBP1, IGFBP3 and testosterone were assayed. Frailty was assessed using the FRAIL scale, comprising 5 domains: fatigue difficulty climbing stairs difficulty walking >100 m >5 illnesses weight loss >5%. Men with ≥ 3 domains were considered frail. At baseline, 527 men (15·3%) were frail. Frail men had lower IGFBP3 (3 630 ng/ml vs not frail: 3 800 ng/ml, P < 0·001) and comparable IGFBP1 (23·5 vs 21·5 ng/ml, P = 0·09). In multivariate analyses, higher IGFBP1 was associated with increased prevalence of frailty (highest vs lowest quartile Q4:Q1, adjusted odds ratio [OR] = 1·39, 95% CI = 1·03-1·88). New-onset frailty arose in 260 (17·5%) of 1 484 men. Lower baseline IGF-I predicted new-onset frailty (Q1:Q4 OR = 1·48, 95% CI = 1·00-2·20) as did higher IGFBP1 (Q4:Q1 OR = 1·59, 95% CI = 1·01-2·50). Men with both IGF-I and free testosterone in Q1 had greater odds of prevalent frailty (OR = 2·13, 95% CI = 1·54-2·95). Older men with higher IGFBP1 level, or both lower IGF-I and testosterone, are more likely to be frail, while those with lower IGF-I and higher IGFBP1 are more likely to become frail. Components of the IGF-I system may be biomarkers or independent predictors of frailty.
Publisher: Wiley
Date: 16-06-2021
Abstract: Patients with ischaemic stroke due to large vessel occlusion (LVO) can be treated successfully with mechanical thrombectomy (MT) and/or intravenous thrombolysis. In the landmark trials, MT was only performed for those with no functional disability prior to stroke (mRS 0–2). There are limited data available regarding clinical outcomes for patients with pre‐stroke moderate disability (mRS ≥ 3). The aims of this study were to analyse the clinical outcomes and financial implications in regard to accommodation costs of performing MT in patients with pre‐stroke mRS = 3. An observational cohort study was performed of 802 patients with anterior circulation LVO ischaemic stroke who underwent MT between October 2016 and January 2020 at three tertiary hospitals. Patient demographics, premorbid mRS, stroke and interventional data, 90‐day mRS and accommodation situation were recorded. Eighty‐two patients with anterior circulation LVO ischaemic stroke were pre‐stroke mRS 3. 38% had a good clinical outcome, as defined by mRS 3 at 90 days. Mortality rate was 38%. The majority of patients presented from home (83%) and greater than one third of those returned home during the 90 days post treatment. 81% of patients had no increase in accommodation cost at 90 days. Patients with pre‐stroke moderate disability may benefit from MT if they are appropriately selected. This may result in fewer patients requiring nursing home placement and less financial burden on the public health system, indicating significant savings are possible.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.ATHEROSCLEROSIS.2016.05.022
Abstract: Experimental studies using a rodent model have suggested that iron overload may contribute to abdominal aortic aneurysm (AAA) pathogenesis. We assessed the association of total body iron, as measured by plasma ferritin, with AAA diagnosis, size and growth in 4024 community-dwelling older men screened for AAA, using logistic regression and linear mixed effects models. Plasma ferritin concentrations were similar in men who did (n = 293) and did not (n = 3731) have an AAA (median [inter-quartile range] concentrations 115.4 [63.0-203.1] and 128.5 [66.1-229.1] ng/mL respectively, p = 0.124). There was no association between plasma ferritin concentration and AAA diagnosis in unadjusted logistic regression (odds ratio (OR) for a 1 standard deviation increase: 0.880 [95%CI: 0.764-1.015] p = 0.078), or when adjusting for AAA risk factors and factors known to influence circulating ferritin (OR for a 1 standard deviation increase: 0.898 [95% CI: 0.778-1.035] p = 0.138). Iron overload prevalence (plasma ferritin concentrations >200 ng/mL) was lower in men with an AAA (25.3%) than those without (30.8% p = 0.048), but was not associated with AAA diagnosis after adjusting as above (OR: 0.781 [95% CI:0.589-1.035] p = 0.086). The association of iron overload with AAA growth was investigated in 265 men with small AAAs who received at least 1 repeat ultrasound scan in the 3 years following screening. We saw no difference in AAA growth between men who did and did not have iron overload (n = 65 and 185 respectively, p = 0.164). Our data suggest that iron overload is unlikely to be important in AAA pathogenesis.
Publisher: BMJ
Date: 04-2008
Abstract: Models are used to adjust for case mix and to stratify treatment allocation in clinical trials and can, if accurate enough, be used to aid decision-making in in idual patients. We aimed to validate, in patients assessed within 6 hours of onset, a previously described six simple variable (SSV) model that was developed in stroke patients who were assessed sub-acutely. The explanatory variables in the model are age, living alone, independent pre-stroke, Glasgow Coma Scale verbal score, ability to lift arms and ability to walk. The six variables were collected at randomisation in the Third International Stroke Trial (IST3) trial of recombinant tissue plasminogen activator in ischaemic stroke. We assessed survival to 30 days and functional status at 6 months using the Oxford Handicap Scale. We constructed receiver operator characteristic (ROC) curves to establish the model's discriminatory performance and tested its calibration by charting predicted versus actual outcomes. 537 patients (mean age, 74 years) were included, of whom 422 (79%) survived 30 days and 179 (33%) were alive and independent at 6 months. The SSV model had an area under the ROC curve of 0.73 for 30-day survival and 0.82 for independent survival at 6 months. Calibration was satisfactory. This study confirms the external validity of the SSV model in an ischaemic stroke population assessed within 6 hours of symptom onset. The SSV model comprising easily collected variables can therefore be used to stratify patients in hyper-acute stroke trials, but probably is not accurate enough for decision-making in in idual patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2010
Publisher: Informa UK Limited
Date: 06-07-2023
Publisher: Oxford University Press (OUP)
Date: 03-03-2009
DOI: 10.1093/IJE/DYN041
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-09-2013
Publisher: American College of Physicians
Date: 18-06-2013
DOI: 10.7326/0003-4819-158-12-201306180-00003
Abstract: In ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), a large randomized, clinical trial, rivaroxaban was noninferior to warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation. To determine the efficacy and safety of rivaroxaban compared with warfarin among vitamin K antagonist (VKA)-naive and VKA-experienced patients. Prespecified subgroup analysis. (ClinicalTrials.gov: NCT00403767). Global. 14,264 persons with atrial fibrillation. Interaction of the relative treatment effect of rivaroxaban and warfarin on stroke or systemic embolism among VKA-naive and VKA-experienced patients. Overall, 7897 (55.4%) patients were VKA-experienced and 6367 (44.6%) were VKA-naive. The effect of rivaroxaban versus warfarin on stroke or systemic embolism was consistent: Rates per 100 patient-years of follow-up were 2.32 versus 2.87 for VKA-naive patients (hazard ratio [HR], 0.81 [95% CI, 0.64 to 1.03]) and 1.98 versus 2.09 for VKA-experienced patients (HR, 0.94 [CI, 0.75 to 1.18] interaction P = 0.36). During the first 7 days, rivaroxaban was associated with more bleeding than warfarin (HR in VKA-naive patients, 5.83 [CI, 3.25 to 10.44], and in VKA-experienced patients, 6.66 [CI, 3.83 to 11.58] interaction P = 0.53). After 30 days, rivaroxaban was associated with less bleeding than warfarin in VKA-naive patients (HR, 0.84 [CI, 0.74 to 0.95]) and similar bleeding in VKA-experienced patients (HR, 1.06 [CI, 0.96 to 1.17] interaction P = 0.003). The trial was not designed to detect differences in these subgroups. The efficacy of rivaroxaban in VKA-experienced and VKA-naive patients was similar to that of the overall trial. There were more bleeding events within 7 days of study drug initiation with rivaroxaban, but after 30 days, rivaroxaban was associated with less bleeding in VKA-naive patients and similar bleeding in VKA-experienced patients. This information may be useful to clinicians considering a transition to rivaroxaban for patients receiving VKA therapy. Johnson & Johnson and Bayer HealthCare.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.JACC.2012.09.057
Abstract: The purpose of this study was to understand the possible risk of discontinuation in the context of clinical care. Rivaroxaban is noninferior to warfarin for preventing stroke in atrial fibrillation patients. Concerns exist regarding possible increased risk of stroke and non-central nervous system (CNS) thromboembolic events early after discontinuation of rivaroxaban. We undertook a post-hoc analysis of data from the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation, n = 14,624) for stroke or non-CNS embolism within 30 days after temporary interruptions of 3 days or more, early permanent study drug discontinuation, and end-of-study transition to open-label therapy. Stroke and non-CNS embolism occurred at similar rates after temporary interruptions (rivaroxaban: n = 9, warfarin: n = 8, 6.20 vs. 5.05/100 patient-years, hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 0.49 to 3.31, p = 0.62) and after early permanent discontinuation (rivaroxaban: n = 42, warfarin: n = 36, 25.60 vs. 23.28/100 patient-years, HR: 1.10, 95% CI: 0.71 to 1.72, p = 0.66). Patients transitioning to open-label therapy at the end of the study had more strokes with rivaroxaban (n = 22) versus warfarin (n = 6, 6.42 vs. 1.73/100 patient-years, HR: 3.72, 95% CI: 1.51 to 9.16, p = 0.0044) and took longer to reach a therapeutic international normalized ratio with rivaroxaban versus warfarin. All thrombotic events within 30 days of any study drug cessation (including stroke, non-CNS embolism, myocardial infarction, and vascular death) were similar between groups (HR: 1.02, 95% CI: 0.83 to 1.26, p = 0.85). In atrial fibrillation patients who temporarily or permanently discontinued anticoagulation, the risk of stroke or non-CNS embolism was similar with rivaroxaban or warfarin. An increased risk of stroke and non-CNS embolism was observed in rivaroxaban-treated patients compared with warfarin-treated patients after the end of the study, underscoring the importance of therapeutic anticoagulation coverage during such a transition.
Publisher: Springer International Publishing
Date: 2023
Publisher: AMPCo
Date: 05-2005
DOI: 10.5694/J.1326-5377.2005.TB06791.X
Abstract: Venous thromboembolism (VTE) affects 1-2 per 1000 people in the general population each year. Clinical diagnosis of deep venous thrombosis (DVT) is unreliable, and must be confirmed by compression ultrasonography or venography. A low clinical pretest probability of DVT and negative D-dimer result reliably exclude the diagnosis, with no need for diagnostic imaging. Initial treatment of DVT is with low-molecular-weight heparin or unfractionated heparin for at least 5 days, followed by warfarin (target INR, 2.0-3.0) for at least 3 months. A vena cava filter is indicated in patients who are ineligible for anticoagulant therapy or who experience embolism despite therapeutic anticoagulation. Thrombolysis or surgical embolectomy may be used as a limb-saving measure in patients with extensive proximal DVT and circulatory compromise that threatens the viability of the leg. Decisions regarding the optimal duration of anticoagulation to prevent recurrent VTE should be in idualised and balance the risk of recurrence if warfarin is stopped against the risk of major bleeding and inconvenience of continuing treatment. The risk of recurrence is highest in people with recurrent unprovoked DVT or chronic predisposing factors (eg, cancer) who require indefinite anticoagulant treatment.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Oxford University Press (OUP)
Date: 15-10-2013
Publisher: Elsevier
Date: 2022
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1111/J.1538-7836.2005.01427.X
Abstract: Stroke is a major cause of death and disability in the world. The main causes of stroke are atherothromboembolism and cardiogenic embolism. The main causal and treatable risk factors for atherothromboembolic ischemic stroke are increasing blood pressure (BP), increasing cholesterol, cigarette smoking and diabetes and the main risk factors for cardiogenic ischemic stroke are atrial fibrillation (AF) and ischemic heart disease. Strategies to reduce the incidence of stroke include prevention of first-ever and recurrent stroke, and treatment of patients with acute stroke to reduce death and disability. The two main strategies of stroke prevention are the 'population' (or 'mass') approach and the 'high risk' approach. The 'population' approach aims to reduce stroke by lowering the prevalence and mean level of causal risk factors in the community, by means of public education and government legislation. The 'high risk' approach aims to reduce stroke by identifying in iduals at high risk of stroke, and lowering their risk by means of optimal medical therapies. Level 1 evidence from randomized controlled trials indicates that effective treatments for high risk patients include control of causal risk factors (lowering BP, lowering blood cholesterol), antithrombotic therapy (antiplatelet therapy with aspirin, clopidogrel, or the combination of aspirin and dipyridamole for patients in sinus rhythm, and anticoagulation with warfarin or ximelagatran for patients in AF) and, where appropriate, carotid revascularization for patients with severe carotid stenosis.
Publisher: Elsevier BV
Date: 10-2009
Publisher: Wiley
Date: 2021
DOI: 10.1002/TRC2.12200
Abstract: Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. We meta‐analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end‐stage disease to calculate the total number of deaths that could be attributed to dementia. We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41–4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27–2.71]) than men (0.56 million [0.14–1.51]), largely but not entirely due to the higher life expectancy in women (age‐standardized female‐to‐male ratio 1.19 [1.10–1.26]). Due to population aging, there was a large increase in all‐age mortality rates from dementia between 1990 and 2019 (100.1% [89.1–117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among in iduals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally.
Publisher: Elsevier BV
Date: 12-1999
Publisher: BMJ
Date: 11-07-2012
Abstract: Elevated total plasma homocysteine (tHcy) has been associated with increased risk of dementia. The C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) increases tHcy and provides a means of studying the association between tHcy and dementia while not being as susceptible to the common biases and confounding of observational studies. The authors designed this longitudinal study to determine if high tHcy and the MTHFR C677T polymorphism increase the risk of incident dementia among older men. The authors studied 4227 men aged 70-89 years from the Health in Men Study cohort and established the diagnosis of dementia (International Classification of Diseases-10th edition) using morbidity and mortality records. Information on tHcy, MTHFR gene status, lifestyle and clinical variables were obtained using postal and face-to-face assessments. 230 men (5.4%) developed dementia during the mean follow-up period of 5.8 ± 1.6 years (range 0.1-8.2 years). The hazard of dementia increased with a doubling of tHcy concentration (adjusted HR 1.48, 95% CI 1.10 to 2.00) and was higher in men with tHcy >15 μmol/l (adjusted HR 1.36 95% CI 1.03 to 1.81, p=0.032). Men with the TT genotype had a HR of dementia of 1.25 (95% CI 0.81 to 1.92). The results of this prospective study are consistent with a causal link between high tHcy and incident dementia, but the study lacked power to determine an effect of the MTHFR genotype.
Publisher: BMJ
Date: 10-03-2011
Abstract: This study investigated the effect of clopidogrel treatment on inflammatory activity as evidenced by the change in high-sensitivity C-reactive protein (hsCRP) levels in a broad population of patients who are at high risk of atherothrombotic events. The predictive value of hsCRP levels for a treatment benefit of clopidogrel was also explored. The study included 8021 patients with established atherosclerotic disease or multiple cardiovascular risk factors enrolled in the CHARISMA trial. Patients were randomly assigned either to clopidogrel plus aspirin or placebo plus aspirin. HsCRP was measured at study entry and at study termination (median 28&emsp14 months). The predefined primary composite endpoint was myocardial infarction, stroke, or death from cardiovascular causes. There was a stepwise increase in the event rate of the combined primary endpoint with increasing quartiles of hsCRP at baseline (4.0%, 6.1%, 7.4% and 8.7% for the highest quartile). In both treatment groups the changes in hsCRP levels over time were identical. In patients with low hsCRP levels (<3 mg/l) clopidogrel treatment was associated with a lower event rate compared with placebo (4.0% vs 6.0%, log rank p=0.005). In contrast no treatment effect was observed in patients with high hsCRP levels (8.1% vs 8.0%, ns). In this broad population, hsCRP is a powerful predictor of ischaemic events. Compared with placebo, clopidogrel was without effect on inflammatory markers. The reduction in cardiovascular events by antiplatelet treatment with clopidogrel was isolated to patients with low levels of hsCRP.
Publisher: Elsevier BV
Date: 09-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2020
Publisher: AMPCo
Date: 06-2019
DOI: 10.5694/MJA2.50201
Abstract: Diagnosis of deep vein thrombosis (DVT) requires a multifaceted approach that includes clinical assessment, evaluation of pre-test probability, and objective diagnostic testing. Common symptoms and signs of DVT are pain, swelling, erythema and dilated veins in the affected limb. The pre-test probability of DVT can be assessed using a clinical decision rule that stratifies DVT into "unlikely" or "likely". If DVT is "unlikely", refer for D-dimer test. If the D-dimer level is normal, DVT can be excluded if the D-dimer level is increased, refer for compression ultrasound. If DVT is "likely", refer for compression ultrasound. When DVT is confirmed, anticoagulation is indicated to control symptoms, prevent progression and reduce the risk of post-thrombotic syndrome and pulmonary embolism. Anticoagulation may consist of a parenteral anticoagulant overlapped by warfarin or followed by a direct oral anticoagulant (DOAC) (dabigatran or edoxaban), or of a DOAC (apixaban or rivaroxaban) without initial parenteral therapy. DOACs are the preferred treatment for DVT because they are at least as effective, safer and more convenient than warfarin. DOACs may require dose reduction or avoidance in patients with renal dysfunction, and should be avoided in pregnancy. Recent evidence shows that DVT in patients with cancer may be treated with edoxaban (after discontinuation of 5 days of initial heparin or low molecular weight heparin [LMWH]) or rivaroxaban if patients prefer not to have daily injections of LMWH, but the risk of gastrointestinal bleeding is higher with DOACs than with LMWH in patients with gastrointestinal cancer.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-02-2019
DOI: 10.1212/WNL.0000000000007138
Abstract: To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study. The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0–2 vs 3–6 and 0–1 vs 2–6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p 5 × 10 −8 . We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0–2 vs 3–6, p = 5.3 × 10 −9 ). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21 , which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome ( p 10 −5 ), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4 , TEK , and PTCH1 ). In this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
Publisher: BMJ
Date: 04-2008
Abstract: Most transient ischaemic attacks (TIAs) stop, with or without treatment, but some are followed by stroke within days or longer. But if the TIAs do not stop then the diagnosis must be reviewed (are they really TIAs or could they be migraine or epilepsy?), and if they are TIAs, what are they caused by (atherothromboembolism, embolism from the heart, etc)? With this information, both the medical and any surgical treatment can be optimised, even though one must accept that the randomised controlled trials mostly have not addressed the particular issue of continuing TIAs.
Publisher: Informa UK Limited
Date: 03-2008
DOI: 10.2147/CIA.S1735
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2015
Publisher: BMJ
Date: 07-1990
Abstract: It is essential to image the carotid bifurcation adequately in patients with symptomatic carotid territory ischaemia if they are being considered for carotid endarterectomy. Optimal resolution is achieved by selective intraarterial contrast angiography which is an invasive procedure carrying some risk. The overall risk-benefit of carotid endarterectomy is currently being investigated in several large randomised trials in Europe and North America. Because cerebral angiography is a prerequisite for carotid endarterectomy, the risks of cerebral angiography will need to be added to those of surgery when considering whether carotid endarterectomy is effective in the management of these patients. This study evaluated prospectively 382 patients with symptomatically mild carotid ischaemia who had cerebral angiography to visualise a potentially resectable lesion at the carotid bifurcation. Complications followed 14 cerebral angiograms in 13 patients (3.4%) two complications were local (0.5%), two systemic (0.5%) and 10 were neurological (2.6%). The neurological complications were transient (TIA 1, generalised seizure 1) in two patients (0.5%), reversible (stroke) in three (0.8%) and permanent (stroke) in five patients (1.3%). There were no deaths. The significant risk factors for post angiographic stroke were (1) stroke before angiography compared with transient ischaemic attacks of the eye or brain and (2) the presence of greater than or equal to 50% diameter stenosis of the symptomatic internal carotid artery unfortunately it may be the latter patients who are most at risk of stroke as part of the natural history of their disease and therefore most in need of prophylactic carotid endarterectomy (which requires cerebral angiography). The absolute risk of post-angiographic stroke of patients for cerebral angiography using clinical evaluation and Duplex carotid ultrasound screening.
Publisher: American College of Physicians
Date: 21-05-2013
Publisher: American Medical Association (AMA)
Date: 03-11-2008
DOI: 10.1001/ARCHPSYC.65.11.1286
Abstract: The prevalence of depression in later life increases with plasma total homocysteine concentration (tHcy). High tHcy accounts for about 15% of prevalent cases, but observational studies are prone to confounding and bias. Genetic association studies are not prone to the same sources of error and offer an opportunity to explore the consistency and external validity of this association. To determine if tHcy is causally related to depression in later life. Cross-sectional study (Health in Men Study), systematic review, and meta-analysis. Patients Community s le of 3752 men aged 70 years or older (Health in Men Study). Fifteen-Item Geriatric Depression Scale and self-reported past or current treatment for depression (Health in Men Study). In the Health in Men Study, the odds ratio (OR) of prevalent depression increased 4% (OR, 1.04 95% confidence interval [CI], 1.02-1.05) with every unit increase of tHcy (micromoles per liter). The tHcy was 0.19 mg/L higher among participants with the MTHFR C677T TT genotype compared with the CC genotype. The meta-analysis showed that older adults with high tHcy had increased risk of depression (OR, 1.70 95% CI, 1.38-2.08) and TT carriers were 22% more likely than CC carriers to have current depression or a history of depression (OR, 1.22 95% CI, 1.01-1.47). The triangular association between the MTHFR genotype, tHcy, and depression implies that higher concentrations of tHcy increase the risk of depression and that lowering tHcy by 0.19 mg/L could reduce the odds of depression by about 20%. Confirmatory data from sufficiently powered randomized trials of homocysteine-lowering therapy are now required to test if the relationship between tHcy and depression is truly causal.
Publisher: Wiley
Date: 10-2011
DOI: 10.1002/ANA.22444
Publisher: Elsevier BV
Date: 07-2015
Publisher: Elsevier BV
Date: 10-2020
Publisher: American Psychological Association (APA)
Date: 07-2021
DOI: 10.1037/PAS0000870
Publisher: Oxford University Press (OUP)
Date: 2019
DOI: 10.1530/EJE-19-0638
Abstract: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70–84 years. Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardio-metabolic risk factors, median splits defined low/high groups. Mean age was 76.7 ± 3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, P = 0.001 and 0.45, P = 0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1 s.d. increase in IGF1, P = 0.007, and 0.011 per 1 s.d. IGFBP3, P = 0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1 s.d. increase in estradiol, P = 0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 ( µg/L) and high estradiol ( pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, P = 0.018). Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological aging.
Publisher: Massachusetts Medical Society
Date: 05-11-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2019
Publisher: Informa UK Limited
Date: 02-09-2015
Publisher: Wiley
Date: 26-02-2013
DOI: 10.1111/DAR.12033
Abstract: The study aims to quantify trends in fentanyl prescribing and fentanyl mortality in Australia within the context of concern among health professionals concerning increasing accessibility of fentanyl, and the harms that may arise as a result. This paper presents data on prescribing patterns of fentanyl by 10 year age group adjusted by population rate, detailed analyses of fentanyl-related deaths from the National Coronial Information System and deaths adjusted for prescribing levels within Australia. Fentany prescriptions have increased and are most prevalent among Australians aged over 80 years. One hundred and thirty-six fentanyl-related deaths were recorded during 2000-2011 54% of decedents had a history of injecting drug use and, among this group, 95% had injected fentanyl at the time of death 62% of deaths recorded misuse (most notably injection) of fentanyl 50% recorded a history of drug dependence and 40% a mental health problem 37% recorded a history of chronic pain and 36% recorded fentanyl as being prescribed at the time of death. Deaths were primarily among Australians under 47 years of age. There have been significant increases in fentanyl prescribing in Australia. It is unclear what proportion of this increase represents legitimate treatment of pain. Fentanyl deaths have also increased, although mortality is currently low in Australia. A large proportion of the deaths involved the injection of erted fentanyl, highlighting the need for messages regarding safer injecting practices targeting people who inject drugs, and strategies to minimise the risks of ersion.
Publisher: AMPCo
Date: 08-2004
DOI: 10.5694/J.1326-5377.2004.TB06206.X
Abstract: The prevalence of peripheral arterial disease (PAD) in people aged over 55 years is 10%-25% and increases with age 70%-80% of affected in iduals are asymptomatic only a minority ever require revascularisation or utation. Patients with PAD alone have the same relative risk of death from cardiovascular causes as those with coronary or cerebrovascular disease, and are four times more likely to die within 10 years than patients without the disease. The ankle-brachial pressure index (ABPI) is a simple, non-invasive bedside tool for diagnosing PAD - an ABPI less than 0.9 is considered diagnostic of PAD. About half of patients with PAD (defined by an abnormal ABPI) have symptomatic coronary or cerebral vascular disease. The ABPI is an independent predictor of coronary and cerebrovascular morbidity and mortality. Patients with PAD require medical management to prevent future coronary and cerebral vascular events. There are currently insufficient data to recommend routine population screening for asymptomatic PAD using the ABPI.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2017
Publisher: Elsevier BV
Date: 08-2015
Publisher: Wiley
Date: 05-2010
Publisher: SAGE Publications
Date: 23-04-2015
DOI: 10.1111/IJS.12510
Abstract: The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. A prospective, Australian, multicentre, randomized controlled trial. Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. 1000 stroke survivors recruited as from March 2007 with a recent ( months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). Exposure to the ICARUSS model of integrated care or usual care. The composite of stroke, MI or death from any vascular cause, whichever occurs first. Risk factor management in the community, depression, quality of life, disability and dementia. With 1000 patients followed up for a median of one-year, with a recurrence rate of 7–10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
DOI: 10.1161/CIRCOUTCOMES.113.000132
Abstract: To evaluate the previously reported excess of thromboembolic events during the 30 days after the end of study (EOS) visit when participants transitioned from blinded therapy to open-label vitamin K antagonist. At the EOS visit, open-label vitamin K antagonist was recommended, and the international normalized ratio (INR) was not to be measured until 3 days later to preserve blinding. We analyzed transition strategies, clinical outcomes, and INR values. Event rates are per 100 patient-years. A total of 9248 (65%) participants were taking study drug at EOS, and, between days 3 and 30, an excess of stroke and systemic embolic events were observed in participants assigned to rivaroxaban (rivaroxaban 22 events, event rate 6.42 warfarin 6 events, event rate 1.73 hazard ratio, 3.72 95% confidence interval, 1.51–9.16 P =0.0044). No INR values were reported for ≈5% of participants transitioned to warfarin. By 30 days after EOS, 83% of the warfarin group and 52% of the rivaroxaban group had ≥1 therapeutic INR value. Median time to first therapeutic INR was 3 days in the warfarin group and 13 days in the rivaroxaban group. The excess of events at EOS was likely because of a period of inadequate anticoagulation in rivaroxaban participants switched to vitamin K antagonist therapy. If transition from rivaroxaban to vitamin K antagonist is needed, timely monitoring and careful dosing should be used to ensure consistent and adequate anticoagulation.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
DOI: 10.1161/STROKEAHA.119.026639
Abstract: The FOCUS trial (Fluoxetine or Control Under Supervision) showed that fluoxetine did not improve modified Rankin Scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk. A United Kingdom, multicenter, parallel-group, randomized, placebo-controlled trial. Patients ≥18 years with a clinical stroke and persisting deficit assessed 2 to 15 days after onset were eligible. Consenting patients were allocated fluoxetine 20 mg or matching placebo for 6 months. The primary outcome was the mRS at 6 months and secondary outcomes included fractures. Sixty-five of 3127 (2.1%) patients had 67 fractures within 6 months of randomization 43 assigned fluoxetine and 22 placebo. Fifty-nine (90.8%) had fallen and 26 (40%) had fractured their neck of femur. The effect of fluoxetine on mRS (common odds ratio =0.951) was not significantly altered by excluding fracture patients (common odds ratio =0.961). Cox proportional hazards modeling showed that only age year (hazard ratio =1.97 95% CI, 1.13–3.45 P =0.017), female sex (hazard ratio =2.13 95% CI, 1.29–3.51 P =0.003), and fluoxetine (hazard ratio =2.00 95% CI, 1.20–3.34 P =0.008) were independently associated with fractures. Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients’ function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex, and fluoxetine were independent predictors of fractures. URL: www.controlled-trials.com . Unique identifier: ISRCTN83290762.
Publisher: S. Karger AG
Date: 2001
DOI: 10.1159/000049139
Abstract: Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2–19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59–0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0–20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.
Publisher: BMJ
Date: 11-12-2015
DOI: 10.1136/BMJ.H6432
Abstract: To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Retrospective observational analysis. 56 acute stroke hospitals in eight countries. 1074 trial physiotherapists, nurses, and other clinicians. Number of babies born during trial recruitment per trial participant recruited. With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0) additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators' meetings and helped maintain a cohesive collaborative group. Australian New Zealand Clinical Trials Registry no 12606000185561. Participation in a rehabilitation trial does not guarantee successful reproductive activity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2009
DOI: 10.1161/STROKEAHA.108.535237
Abstract: Background and Purpose— Increased total homocysteine (tHcy) is a risk factor for stroke. This study examines whether the efficacy of B-vitamins in reducing tHcy is modified by ethnicity in a Singaporean ischemic stroke population. Methods— 505 patients (419 Chinese, 41 Malays and 45 Indians) with ischemic stroke were randomized to receive placebo or B-vitamins. Fasting blood s les collected at baseline and 1 year were assayed for tHcy. MTHFR polymorphisms were genotyped. Results— Ethnicity did not independently determine tHcy at baseline. The magnitude of tHcy reduction by B-vitamin treatment was consistent across ethnic groups (Chinese −3.8±4.5, Malay −4.9±4.2, and Indian −3.3±3.6μmol/L) despite ethnic differences in MTHFR genotype and baseline folic acid (FA) and vitamin B 12 (vitB 12 ) concentrations. Conclusions— Ethnicity does not appear to affect the tHcy-lowering effect of B-vitamins, despite differences in dietary intake and prevalence of MTHFR polymorphisms. This suggests that the effect of B-vitamins in lowering tHcy is generalizable across Asian populations. However, due to relatively small numbers of non-Chinese studied, confirmation in other populations is required.
Publisher: BMJ
Date: 11-2013
Publisher: BMJ
Date: 12-1988
Abstract: Two cyclists developed mononeuropathy of the deep palmar branch of the ulnar nerve due to ulnar nerve compression adjacent to the ulnar tunnel (of Guyon) by prolonged bicycle riding. A modification of hand grip on the bicycle handlebars resulted in rapid recovery in one patient.
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000083253
Abstract: i Background: /i Few studies provide information on trends in the long-term outcome of stroke. Weaimed to determine trends in survival and recurrent stroke, over 5 years after first-ever stroke, for 2 cohorts of patients enrolled in the Perth Community Stroke Study in 1989–90 and 1995–96. i Methods: /i For 12-month periods beginning February 1989 and February 1995, all in iduals with an acute stroke who were resident in a geographically-defined and representative region of Perth, Western Australia, were registered and followed-up prospectively 5 years after the index event. i Results: /i The 5-year cumulative risk of death was 59% (95% confidence interval (CI) 53%, 65%) and 58% (95% CI 52%, 65%) for the 1989–90 and 1995–96 cohorts, respectively (p = 0.94). The 5-year cumulative risk of first recurrent stroke was 32% (95% CI 25%, 40%) and 23% (95% CI 16%, 30%) for the 1989–90 and 1995–96 cohorts, respectively (p = 0.07). i Conclusions: /i Although no statistically significant improvement occurred in 5-year survival after first-ever stroke in Perth between 1989–90 and 1995–96, there was a statistically nonsignificant trend towards a smaller cumulative risk of recurrent stroke over 5 years after a first-ever stroke. Serial community-based studies of the incidence and outcome of stroke are an important means of monitoring the translation of proven preventive interventions to improvements in population health.
Publisher: Oxford University Press (OUP)
Date: 13-06-2020
DOI: 10.1002/BJS.11746
Publisher: SAGE Publications
Date: 11-08-2016
Abstract: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned s le size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.
Publisher: Oxford University Press (OUP)
Date: 17-07-2018
Abstract: Temporal trends in incidence and mortality of cardiovascular disease (CVD) have been well described, with recent data suggesting declining improvements in those aged under 55 years. However, little is known about the combined impact of incidence and mortality trends on disease prevalence, an important indicator of disease burden and cost. We analysed changes in age-specific and age-standardised temporal trends in prevalence and incidence of CVD subtypes. Annual prevalence and incidence rates of coronary heart disease, cerebrovascular disease and peripheral arterial disease for the Western Australian population for 1995–2010 were calculated using data from the Western Australian Data Linkage System. Joinpoint regression analyses were used to identify joinpoints in trends in age-specific and age-standardised annual prevalence and incidence rates for each CVD subtype. Between 1995 and 2010, age- and sex-specific incidence and prevalence of the CVD subtypes generally decreased among middle-aged and older adults, but were stable or increased among younger adults. In 55 year olds, increases in incidence tended to occur from 2003, while increases in prevalence were from 2007/2008. Declines in age-standardised incidence were greater than those in crude incidence, with changes in population structure having a greater impact among men than women. The majority of CVDs occurs in older adults. Our findings of generally worsening trends in prevalence in younger adults across most CVD subtypes were in contrast to generally declining trends in older age groups. These data highlight the importance of monitoring prevalence and incidence, particularly in younger adults.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2010
DOI: 10.1161/STROKEAHA.109.569764
Abstract: Background and Purpose— Deep intracerebral hemorrhage (ICH) and lacunar infarcts are the result of small vessel disease, whereas nonlacunar infarcts are often caused by large artery atherosclerosis or cardiac embolism. We hypothesized that patients with deep ICH and lacunar infarcts have similar retinal microvascular signs and that these differ from those seen in patients with nonlacunar infarcts. Methods— We studied patients with acute stroke and classified their stroke as deep ICH, lacunar infarction, or nonlacunar infarction. In a masked fashion we assessed retinal photographs for quantitative and qualitative evidence of microvascular damage. Results— We recruited 630 patients (51 had deep ICH, 93 had lacunar infarction, and 486 had nonlacunar infarction). Patients with deep ICH were more likely than those with nonlacunar infarcts to have severe focal narrowing of the retinal arterioles (OR, 3.7), severe arteriovenous nicking (OR, 2.6), and quantitatively narrower retinal arterioles and wider retinal venules. Retinal microvascular signs were similar in patients with deep ICH and lacunar infarction. Conclusions— Patients with deep ICH and lacunar infarcts are more likely than patients with nonlacunar infarcts to have signs indicating hypertensive damage in the retinal arteriolar wall.
Publisher: IEEE
Date: 03-2012
Publisher: Elsevier BV
Date: 10-2008
Publisher: The Endocrine Society
Date: 07-11-2020
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.JOCN.2004.09.009
Abstract: Evidence exists for an association between migraine and ischaemic stroke, but there is uncertainty about whether migraine is a risk factor for subarachnoid haemorrhage (SAH). A multi-centre, population-based, case-control study using cases of first-ever SAH during 1995-98 and matched controls in four study centres in Australia and New Zealand. Self- or proxy-reported history, frequency and characteristics of headaches, classified according to 1988 International Headache Society diagnostic criteria. 206 of 432 (48%) cases and 236 of 473 (50%) controls had a history of headaches. The frequency and characteristics of headaches were similar between the two groups. No association was found in logistic regression analyses for history or frequency of headaches, or migraine headaches. No evidence was found for an association between recurrent headaches and SAH. Such information is important for counselling patients and families about the significance of past and ongoing headaches in relation to this illness.
Publisher: Elsevier BV
Date: 10-2009
Publisher: Elsevier BV
Date: 10-2006
Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000306058
Abstract: Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 countries (29,972 participants), identified nine modifiable risk factors that accounted for % of population-attributable risk. However, traditional risk factors (e.g. hypertension, cholesterol) appear to exert contrasting risks for stroke compared with coronary heart disease, and the etiology of stroke is far more heterogeneous. In addition, our knowledge of risk factors for stroke in low-income countries is inadequate, where a very large burden of stroke occurs. Accordingly, a similar epidemiological study is required for stroke, to inform effective population-based strategies to reduce the risk of stroke. i Methods: /i INTERSTROKE is an international, multicenter case-control study. Cases are patients with a first stroke within 72 h of hospital presentation in whom CT or MRI is performed. Proxy respondents are used for cases unable to communicate. Etiological and topographical stroke subtype is documented for all cases. Controls are hospital- and community-based, matched for gender, ethnicity and age (±5 years). A questionnaire (cases and controls) is used to acquire information on known and proposed risk factors for stroke. Cardiovascular (e.g. blood pressure) and anthropometric (e.g. waist-to-hip ratio) measurements are obtained at the time of interview. Nonfasting blood s les and random urine s les are obtained from cases and controls. i Study Significance: /i An effective global strategy to reduce the risk of stroke mandates systematic measurement of the contribution of the major vascular risk factors within defined ethnic groups and geographical locations.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.MATURITAS.2021.10.008
Abstract: To determine if hearing loss is associated with increased risk of frailty in later life. Cross-sectional study of a community s le of 4,004 men aged 70 years and above living in the metropolitan region of Perth, Western Australia. Data were retrieved from the Health in Men Study (HIMS) and the Western Australian Data Linkage System (WADLS). Frailty was assessed using the FRAIL scale and the Frailty Index. Hearing loss was defined by self-report or by diagnosis recorded in the WADLS. We also collected demographic, lifestyle and social support information. Frailty was assessed using the FRAIL scale and the Frailty Index. The prevalence of frailty in the s le population was 16.1% and 25.4% when assessed using the FRAIL scale and the Frailty Index respectively. After adjusting for participant demographic, lifestyle and social factors, hearing loss was significantly associated with the prevalence of frailty when diagnosed by either measure (FRAIL scale: odds ratio [OR] 1.59, 95 CI% 1.32 to 1.91 Frailty Index: OR 1.76, 95 CI% 1.50 to 2.05). The proportion of men with hearing loss increased with increasing severity of frailty. Hearing loss is associated with increased prevalence of frailty in older men when assessed using the FRAIL scale and the Frailty Index. Future longitudinal studies using objective measures of hearing will be helpful in determining if this association is likely to be causal.
Publisher: Public Library of Science (PLoS)
Date: 28-08-2012
Publisher: Massachusetts Medical Society
Date: 03-03-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-03-2021
DOI: 10.1212/WNL.0000000000011885
Abstract: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] −11.7 to −11.3, p 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI −13.8 to −12.7, p 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI −13.7 to −10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2–9.8, p 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
Publisher: Wiley
Date: 08-2016
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JAGP.2014.10.010
Abstract: A positive association between depression and diabetes has been reported, but the direction and nature of this association is unclear. Insulin resistance is a state of reduced responsiveness of target tissues to normal circulating levels of insulin and predisposes to diabetes in the presence of beta cell dysfunction. We conducted this cross-sectional and prospective study in a community representative s le of 3,140 older men free of diabetes to determine if insulin resistance was associated with prevalent and incident depressive symptoms. Men with insulin resistance had increased odds of depression cross-sectionally (odds ratio [OR]: 1.61 95% confidence interval [CI]: 1.08-2.40), although this was not significant after adjustment for possible confounding (OR: 1.32 95% CI: 0.85-2.03). In the longitudinal analysis, men with insulin resistance were more likely to develop clinically significant depressive symptoms (adjusted risk ratio [RR]: 2.33 95% CI: 1.17-4.62), and this risk was greatest for men in the highest quartile of insulin resistance compared with those in the lowest quartile (adjusted RR: 2.54 95% CI: 1.04-6.18). Older men with clinically significant depressive symptoms were more likely to have higher markers of insulin resistance. Additionally, the odds of depression increased with increasing levels of insulin resistance, and insulin resistance increased the risk of developing depression over 5 years later. Because depression is now a leading cause of disability worldwide, addressing the rising challenge of insulin resistance may prove important in improving the future health of our communities.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000118380
Abstract: i Background: /i Aspirin offers modest reduction in stroke in patients with atrial fibrillation. Whether combination of aspirin with clopidogrel offers additional protection is unclear. i Methods: /i Post-hoc subgroup analysis of 593 participants with a history of atrial fibrillation in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) randomized trial testing clopidogrel 75 mg per day plus aspirin (75–162 mg per day) vs. aspirin alone in patients with stable cardiovascular disease or multiple cardiovascular risk factors. i Results: /i Mean patient age was 70 years, 78% were men, and hypertension, heart failure and diabetes were present in 78, 20 and 44%, respectively. During a median follow-up of 2.3 years, stroke (ischemic and hemorrhagic) occurred in 15 of 298 assigned to clopidogrel plus aspirin and in 14 of 285 given aspirin alone (hazard ratio, HR, 1.03, 95% CI 0.49–2.1). There was no difference in all-cause mortality (HR 1.1, 95% CI 0.6–1.9) or in the composite of stroke, myocardial infarction, or vascular death (HR = 1.2, 95% CI 0.7–2.0). Severe/fatal extracranial hemorrhage occurred in 6 patients with combination vs. 3 with aspirin alone. i Conclusions: /i This post-hoc subgroup analysis does not support the use of this combination over aspirin alone in patients with a history of atrial fibrillation pending results of ongoing larger randomized trials.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2001
Abstract: Background and Purpose — One or more of the inherited thrombophilias may be causal risk factor for a proportion of ischemic strokes, but few studies have addressed this association or the association between thrombophilia and pathogenic subtypes of stroke. Methods — We conducted a case-control study of 219 hospital cases with a first-ever ischemic stroke and 205 randomly selected community control subjects stratified by age, sex, and postal code. With the use of established criteria, cases of stroke were classified by pathogenic subtype in a blinded fashion. The prevalence of conventional vascular risk factors fasting plasma levels of protein C, protein S, antithrombin III and genetic tests for the factor V Leiden and the prothrombin 20210A mutation were determined in cases and control subjects. Results — The prevalence of any thrombophilia was 14.7% (95% CI, 9.9% to 19.5%) among cases and 11.7% (95% CI, 7.4% to 17.0%) among control subjects (OR, 1.3 95% CI, 0.7% to 2.3%). The prevalence of in idual thrombophilias among cases ranged from 0.9% (95% CI, 0.1% to 3.4%) for protein S deficiency to 5.2% (95% CI, 0.3% to 9.1%) for antithrombin III deficiency among control subjects, the prevalence ranged from 1.0% (95% CI, 0.1% to 3.6%) for protein S deficiency to 4.1% (95% CI, 0.2% to 7.8%) for antithrombin III deficiency. There were no significant differences in the prevalence of thrombophilia between cases and control subjects or between pathogenic subtypes of ischemic stroke. Conclusions — One in 7 patients with first-ever acute ischemic stroke will test positive for one of the inherited thrombophilias, but the relation is likely to be coincidental rather than causal in almost all cases, irrespective of the pathogenic subtype of the ischemic stroke. These results suggest that routine testing for thrombophilia in most patients with acute ischemic stroke may be unnecessary. Whether the thrombophilias may still be important in younger patients with ischemic stroke or in predicting complications (eg, venous thrombosis) and stroke outcome remains uncertain.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.3382/PS/PEV030
Abstract: Various milling methods result in different particle size distributions and, in combination with mash and thermal treatment (expandate) of the feed, may have an impact on nutrient digestibility, pH of the digesta and subsequently the performance of an animal. Since this aspect has not been widely considered in laying hens, the objective of the present study was to investigate the effects of milling method, expansion, and particle size of feed on performance, apparent ileal nutrient digestibility, and pH of digesta in laying hens. Twelve variants of the same diet were produced. Four different milling techniques (hammer mill, roller mill, disc mill, and wedge-shaped disc mill) were used to grind the feed cereals. Coarse feed was obtained from all four mills. Additionally, fine feed was obtained from the hammer mill and the roller mill. Each of the six feed variants was offered as mash or expandate, resulting in a total of 12 treatments. The duration of the experimental period was 21 days. A total of 576 layers, each 19 weeks of age, were used in eight replicates. The statistical analysis for the four milling methods and two thermal treatments was performed using a 4×2 factorial arrangement. The effect of particle size was investigated using a 2×2×2 factorial arrangement including the coarse and fine particle sizes that were produced with the hammer mill and the roller mill as well as the mash and expandate. The animal performance and the pH of the digesta were not affected by the treatments. Ileal digestibility of starch was significantly improved by feeding mash compared to expandate (P=0.013) and by feeding coarse compared to fine feed (P=0.028). Based on this study, the tested milling methods can be used for the production of feed for laying hens without affecting performance and digestibility of nutrients.
Publisher: BMJ
Date: 10-2004
Publisher: Wiley
Date: 12-1998
Publisher: Cambridge University Press (CUP)
Date: 11-1994
Publisher: Elsevier BV
Date: 03-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-05-2023
DOI: 10.1212/WNL.0000000000207249
Abstract: Symptoms of sleep disturbance are common and may represent important modifiable risk factors of stroke. We evaluated the association between a spectrum of sleep disturbance symptoms and the risk of acute stroke in an international setting. The INTERSTROKE study is an international case-control study of patients presenting with first acute stroke and controls matched by age (±5 years) and sex. Sleep symptoms in the previous month were assessed through a questionnaire. Conditional logistic regression estimated the association between sleep disturbance symptoms and acute stroke, expressed as odds ratios (ORs) and 95% CIs. The primary model adjusted for age, occupation, marital status, and modified Rankin scale at baseline, with subsequent models adjusting for potential mediators (behavioral/disease risk factors). Overall, 4,496 matched participants were included, with 1,799 of them having experienced an ischemic stroke and 439 an intracerebral hemorrhage. Short sleep ( hours: OR 3.15, 95% CI 2.09–4.76), long sleep ( hours: OR 2.67, 95% CI 1.89–3.78), impaired quality (OR 1.52, 95% CI 1.32–1.75), difficulty getting to sleep (OR 1.32, 95% CI 1.13–1.55) or maintaining sleep (OR 1.33, 95% CI 1.15–1.53), unplanned napping (OR 1.48, 95% CI 1.20–1.84), prolonged napping ( hour: OR 1.88, 95% CI 1.49–2.38), snoring (OR 1.91, 95% CI 1.62–2.24), snorting (OR 2.64, 95% CI 2.17–3.20), and breathing cessation (OR 2.87, 95% CI 2.28–3.60) were all significantly associated with an increased odds of acute stroke in the primary model. A derived obstructive sleep apnea score of 2–3 (2.67, 2.25–3.15) and cumulative sleep symptoms ( : 5.38, 4.03–7.18 ) were also associated with a significantly increased odds of acute stroke, with the latter showing a graded association. After an extensive adjustment, significance was maintained for most of the symptoms (not difficulty getting to/maintaining sleep and unplanned napping), with similar findings for stroke subtypes. We found that sleep disturbance symptoms were common and associated with a graded increased risk of stroke. These symptoms may be a marker of increased in idual risk or represent independent risk factors. Future clinical trials are warranted to determine the efficacy of sleep interventions in stroke prevention.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.AHJ.2015.07.006
Abstract: The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial. We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding. The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09 interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72 interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients. The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF.
Publisher: CRC Press
Date: 15-01-2014
DOI: 10.1201/B16337-11
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2002
Publisher: SAGE Publications
Date: 12-2009
Publisher: Springer Science and Business Media LLC
Date: 25-02-2015
DOI: 10.1007/S12603-015-0483-2
Abstract: The effect of dietary salt intake on important population outcomes such as mortality is controversial. The aim of this study was to examine the association between the dietary habit of adding salt to food and mortality in older men. Design, participants, setting and measurements: A risk factor questionnaire which contained a question about the dietary habit of adding salt to food was completed by 11742 community recruited older men between 1996 and 1999. The men were followed by means of the Western Australia Data Linkage System until November 30th 2010. Deaths due to cardiovascular diseases and cancers were identified using ICD-10 codes in the ranges I00-I99 and C00-D48, respectively. The association between the frequencies of adding salt to food and mortality was assessed using Kaplan Meier estimates and Cox proportional hazard analysis. Median follow-up for survivors was 12.5 years (inter-quartile range 8.3-13.2 years). A total of 5399 deaths occurred of which the primary cause registered was cancer and cardiovascular disease in 1962 (36.3%) and 1835 (34.0%) men, respectively. The reported frequency of adding salt to food was strongly positively associated with all-cause (p<0.001), cancer-related (p<0.001) but not cardiovascular-related (p=0.649) mortality. Men reporting adding salt to their food always had a 1.12-fold (95% CI 1.05-1.20, p<0.001) and a 1.20-fold (95% CI 1.07-1.34, p=0.001) increased risk of all-cause and cancer-related mortality, respectively, after adjusting for other risk factors. Men reporting adding salt to their food sometimes had a 1.16-fold (95% CI 1.04-1.29, p=0.007) increased risk of cancer-related mortality after adjusting for other risk factors. A history of adding salt to food is associated with increased cancer-related mortality in older men.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2019
DOI: 10.1161/STROKEAHA.118.024181
Abstract: In idual markers of cerebral small vessel disease and cerebral atrophy explain a small proportion of variance in vascular risk factors and cognitive function. Combining these markers into a single measure of neurovascular and neurodegenerative disease may be more powerful. We assessed this using data contained in the Virtual International Stroke Trials Archive - Prevention sub-archive. We extracted white matter hyperintensities (WMH) and cerebrospinal fluid (CSF) volumes from 317 people with ischemic stroke or transient ischemic attack who had baseline magnetic resonance imaging. We assessed progression of volumes in 208 people who had 2-year follow-up magnetic resonance imaging. WMH and CSF volumes were segmented from fluid attenuated inversion recovery and T1 images. The combined neurovascular and neurodegenerative measure was the sum of WMH and CSF volume normalized by intracranial volume. We assessed (1) the relationship between baseline vascular risk factors and imaging markers and (2) the relationship between baseline imaging markers and Mini-Mental State Examination score at follow-up using multiple linear regression. We also assessed implications for s le size calculations using n=208 participants with follow-up magnetic resonance imaging. Vascular risk factors accounted for 7%, 11%, and 12% of the variance in WMH, CSF, and combined volume, respectively (all P .001). The association between baseline combined volume and 6-month follow-up Mini-Mental State Examination (β=−0.442 SE, 0.07 P .0001) was 32% greater than WMH (β=−0.302 SE, 0.06 P .0001) and 12% greater than CSF (β=−0.391 SE, 0.07 P .0001) alone. The combined volume required between 207 and 3305 (20%) fewer patients per arm than WMH alone to detect reductions of 10% to 40% in volume progression over 2 years. A combined neurovascular and neurodegenerative magnetic resonance imaging measure including WMH and CSF volume was more closely related to vascular risk factors and cognitive function than either WMH or CSF volume alone. The combined volume may be a more sensitive measurement for clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2020
DOI: 10.1186/S13063-020-04875-1
Abstract: Three large trials of fluoxetine for stroke recovery (FOCUS (fluoxetine or control under supervision), AFFINITY (the Assessment oF FluoxetINe In sTroke recovery) and EFFECTS (Efficacy oF Fluoxetine—a randomisEd Controlled Trial in Stroke)) have been collaboratively designed with the same basic protocol to facilitate an in idual patient data analysis (IPDM). The statistical analysis plan for the three in idual trials has already been reported in Trials , including a brief description of the IPDM. In this protocol, we describe in detail how we will perform the IPDM. Data from EFFECTS and AFFINITY will be transferred securely to the FOCUS statistician, who will perform a one-stage IPDM and a two-stage IPDM. For the one-stage IPDM, data will be combined into a single data set and the same analyses performed as described for the in idual trials. For the two-stage IPDM, the results for the three in idual trials will be combined using fixed effects meta-analyses. The primary and secondary outcome domains for the IPDM are the same as for in idual trials. We will also perform analyses according to several subgroups including country of recruitment, ethnicity and trial. We will also explore the effects of fluoxetine on our primary and secondary outcomes in subgroups defined by combinations of characteristics. We also describe additional research questions that will be addressed using the combined data set, and published subsequently, including predictors of important post-stroke problems such as seizures, low mood and bone fractures. An IPDM of our three large trials of fluoxetine for stroke recovery will allow us to provide the most precise estimates of any risks and benefits of fluoxetine vs placebo, to detect reliably a smaller overall effect size than those detectable by the in idual trials, to better determine the effects of fluoxetine vs placebo in subgroups of patients and outcomes and to broaden the generalisability of the results. Also, we may identify differences in treatment effects between studies. FOCUS: ISRCTN ISRCTN83290762 . Registered on 23 May 2012. EudraCT 2011-005616-29 . Registered on 3 February 2012. AFFINITY: Australian New Zealand Clinical Trials Registry ACTRN12611000774921 . Registered on 22 July 2011. EFFECTS: ISRCTN ISRCTN13020412 . Registered on 19 December 2014. ClinicalTrials.gov NCT02683213 . Registered on 2 February 2016. EudraCT 2011-006130-16 . Registered on 8 August 2014.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2000
Abstract: Background and Purpose —Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. Methods —We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. Results —In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0.98 2 P =0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for ≈2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by ≈2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. Conclusions —The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.
Publisher: BMJ
Date: 2008
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000515689
Abstract: b i Background: /i /b Increasing physical activity (PA) and improving diet quality are opportunities to improve secondary stroke prevention, but access to appropriate services is limited. Interventions co-designed with stroke survivors and delivered by telehealth are a potential solution. b i Aim: /i /b The aim of this study is to test the feasibility, safety, and potential efficacy of a 6-month, telehealth-delivered PA and/or dietary (DIET) intervention. b i Methods: /i /b Pilot randomized trial. 80 adults with previous stroke who are living at home with Internet access and able to exercise will be randomized in a 2 × 2 factorial (4-arm) pilot randomized, open-label, blinded outcome assessment trial to receive PA, DIET, PA + DIET, or control interventions via telehealth. The PA intervention aims to support participants to meet the minimum recommended levels of PA (150 min/week moderate exercise), and the DIET intervention aims to support participants to follow the AusMed (Mediterranean-style) diet. The control group receives usual care plus education about PA and healthy eating. The co-primary outcomes are feasibility (proportion and characteristics of eligible participants enrolled and proportion of scheduled intervention sessions attended) and safety (adverse events) at 6 months. The secondary outcomes include recurrent stroke risk factors (blood pressure, physical activity levels, and diet quality), fatigue, mood, and quality of life. Outcomes are measured at 3, 6, and 12 months. b i Conclusion: /i /b This trial will produce evidence for the feasibility, safety, and potential effect of telehealth-delivered PA and DIET interventions for people with stroke. Results will inform development of an appropriately powered trial to test effectiveness to reduce major risk factors for recurrent stroke. b i Trial registration: /i /b ACTRN12620000189921.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.MATURITAS.2011.05.006
Abstract: Vision and hearing decline with age. Loss of these senses is associated with increased risk of falls, injuries from falls, mortality and decreased health-related quality of life (HRQOL). Our objective was to determine if there are gender differences in the associations between visual and hearing impairment and these outcomes. 2340 men and 3014 women aged 76-81 years from the Health in Men Study and the Australian Longitudinal Study on Women's Health were followed for an average of 6.36 years. Dependent variables were self-reported vision and hearing impairment. Outcome variables were falls, injuries from falls, physical and mental components of HRQOL (SF-36 PCS and MCS) and all-cause mortality. Vision impairment was more common in women and hearing impairment was more common in men. Vision impairment was associated with increased falls risk (odds ratio (OR)=1.77, 95% CI=1.35-2.32 in men OR=1.82, 95% CI=1.44-2.30 in women), injuries from falls (OR=1.69, 95% CI=1.23-2.34 in men, OR=1.79, 95% CI=1.38-2.33 in women), and mortality (hazard ratio (HR)=1.44 95% CI=1.17-1.77 in men HR=1.50, 95% CI=1.24-1.82 in women) and declines in SF-36 PCS and MCS. Hearing impairment was associated with increased falls risk (OR=1.38, 95% CI=1.08-1.78 in men OR=1.45, 95% CI=1.08-1.93 in women) and declines in SF-36 PCS and MCS. Overall there were no gender differences in the association between vision and hearing impairment and the outcomes. In men and women aged 76-81 years, there were no gender differences in the association between self-reported vision and hearing impairment and the outcomes of falls, mortality and HRQOL.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2022
DOI: 10.1186/S12931-022-02125-3
Abstract: Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons. To determine the expression of markers of inflammation in COPD patients with rapid functional decline in comparison to slow or no decliners. In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the expression and localization of inflammatory markers was measured in bronchial biopsies of patients with no lung functional decline (FEV1% + 30 ± 43 ml/year, n = 21), slow (FEV1% ml/year, − 40 ± 19, n = 14) and rapid decline (FEV1% ml/year, − 112 ± 53, n = 15) using immunohistochemistry. ELISA test was used for polymeric immunoglobulin receptor (pIgR) quantitation “in vitro”. The expression of secretory IgA was significantly reduced in bronchial epithelium (p = 0.011) and plasma cell numbers was significantly reduced in the bronchial lamina propria (p = 0.017) of rapid decliners compared to no decliners. Bronchial inflammatory cell infiltration, CD4, CD8, CD68, CD20, NK, neutrophils, eosinophils, mast cells, pIgR, was not changed in epithelium and lamina propria of rapid decliners compared to other groups. Plasma cells/mm 2 correlated positively with scored total IgA in lamina propria of all patients. “In vitro” stimulation of 16HBE cells with LPS (10 μg/ml) and IL-8 (10 ng/ml) induced a significant increase while H 2 O 2 (100 μM) significantly decreased pIgR epithelial expression. These data show an impaired humoral immune response in rapid decliners with COPD, marked by reduced epithelial secretory IgA and plasma cell numbers in the bronchial lamina propria. These findings may help in the prognostic stratification and treatment of COPD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000082788
Abstract: i Background and Aims: /i It is uncertain what impact increasing voluntary folate fortification may be having on the statistical power of randomized trials testing the homocysteine hypothesis of atherothrombosis. The objective of this study was to determine whether there has been a change in folate status between 1998 and 2002 in stroke patients randomized into the VITAmins TO Prevent Stroke (VITATOPS) Study at a single center in Perth, Australia, and what impact this may have had on the magnitude of the homocysteine-lowering effect achieved over time with folic acid-based multivitamin therapy. i Methods: /i We conducted a randomized, double-blind, placebo-controlled study involving 285 patients with stroke or transient ischemic attack who were recruited between 1998 and 2002 and randomized to long-term folic acid 2.0 mg/day, pyridoxine 25 mg/day and cobalamin 0.5 mg/day (active VITATOPS medication) or placebo. Fasting plasma total homocysteine, red cell folate, serum cobalamin and serum pyridoxine levels were measured at baseline and 6 months, and the change in blood levels over 4 time quartiles and differences in levels between the two randomized treatments were examined. i Results: /i Between 1998 and 2002, there was a significant rise in baseline mean red cell folate levels over 4 time quartiles among the entire stroke cohort (723.3, 780.1, 922.6 and 1,023.7 nmol/l in the first, second, third and fourth quartiles, respectively p 0.0001), but this was not associated with a spontaneous reduction in mean baseline total homocysteine levels during the same time period (12.7, 14.3, 12.1 and 12.8 µmol/l in the first, second, third and fourth quartiles, respectively p = 0.55). The homocysteine-lowering effect of the active VITATOPS trial medication at 6 months after randomization also did not change significantly between 1998 and 2002 (difference between randomized groups: –4.1, –4.1, –3.1 and –3.6 µmol/l in the first, second, third and fourth quartiles, respectively p = 0.56). i Conclusions: /i The homocysteine-lowering effect of the active VITATOPS trial medication has not attenuated significantly in the past 5 years despite increasing voluntary fortification of foods with folic acid as reflected by a progressive rise in baseline folate status. These data suggest that in the continuing absence of a program of mandatory folate fortification of food in populations served by centers participating in the VITATOPS trial, the study will remain adequately powered to test the homocysteine-lowering hypothesis for which it was designed.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.AHJ.2009.06.027
Abstract: Thrombin potently activates platelets via interaction with the protease-activated receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin via antagonism of the protease-activated receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents. TRA 2 degrees P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment. TRA 2 degrees P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.
Publisher: Elsevier BV
Date: 03-2012
Publisher: Wiley
Date: 07-2014
DOI: 10.1111/JCH.12364
Publisher: Elsevier BV
Date: 10-2023
Publisher: American Physical Society (APS)
Date: 19-10-2020
Publisher: Springer Science and Business Media LLC
Date: 22-08-2005
Abstract: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of %, but nearly all had a 5-year stroke risk of %. Despite this, half of the cohort were obese (BMI 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
Publisher: Wiley
Date: 13-04-2013
DOI: 10.1111/CEN.12208
Abstract: In men, testosterone (T) levels decline with age, and lower T predicts all-cause and cardiovascular mortality. However, the associations of T and its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with symptomatic peripheral arterial disease remain unclear. We assessed associations of T, DHT and E2 with lower limb intermittent claudication in older men. Cross-sectional study. Community-dwelling men aged 70-89 years resident in Perth, Western Australia. Intermittent claudication was ascertained by the Edinburgh Claudication Questionnaire. Early morning, plasma T, DHT and E2 were assayed using liquid chromatography-tandem mass spectrometry. There were 268 men with intermittent claudication and 2435 without claudication or any leg pain. Men with nonspecific leg pain (n = 986) were excluded. After adjusting for age, smoking, BMI, waist/hip ratio, hypertension, dyslipidaemia, diabetes, creatinine and prevalent cardiovascular disease (CVD), higher T was associated with reduced risk of having claudication (per 1 SD increase, odds ratio [OR] = 0·80, 95% confidence interval [CI] = 0·69-0·94, P = 0·006 quartiles, Q4/Q1, OR = 0·54, 95% CI = 0·36-0·81). Higher DHT was associated with reduced risk of having claudication (per 1 SD increase, OR = 0·86, 95% CI = 0·73-1·00, P = 0·048 Q4/Q1, OR = 0·64, 95% CI = 0·43-0·95). E2 was not associated with claudication (per 1 SD increase, OR = 0·96, 95% CI = 0·83-1·11, P = 0·565 Q4/Q1, OR = 0·88, 95% CI = 0·60-1·29). Lower T or DHT levels, but not E2, are associated with symptoms of intermittent claudication in older men. Reduced exposure to androgens may represent a causal factor or biomarker for symptomatic peripheral arterial disease. Further studies are needed to examine underlying mechanisms and evaluate therapeutic options in ageing men.
Publisher: AMPCo
Date: 2007
Publisher: European Respiratory Society
Date: 04-09-2022
Publisher: Elsevier BV
Date: 04-2014
Publisher: Public Library of Science (PLoS)
Date: 23-12-2015
Publisher: Elsevier BV
Date: 11-2005
Publisher: Wiley
Date: 12-1987
DOI: 10.1111/J.1445-5994.1987.TB01264.X
Abstract: Orbital myositis implies orbital inflammation confined to one or more of the extraocular muscles. Orbital computerised tomography (CT) demonstrates irregular extraocular muscle enlargement which extends anteriorly to involve the tendon (muscle insertion). Six cases of presumed orbital myositis are reported, in each of whom the diagnosis was suspected clinically and confirmed by the orbital CT scan appearances. The mean age of the patients was 33 years (range 8-45 years). All presented with painful ophthalmoplegia and the majority manifested proptosis (five cases), conjunctival congestion (five cases) and periorbital and eyelid edema (two cases). Systemic corticosteroid therapy was used in two patients initially and also in another patient who relapsed, with rapid and dramatic responses. Extraocular muscle biopsy was performed in one case, disclosing features of non-specific muscle inflammation and no evidence of vasculitis. It is considered that orbital myositis is a discrete, identifiable subgroup within the spectrum of the nonspecific idiopathic orbital inflammatory syndromes termed previously orbital 'pseudotumours'. Although the clinical features are frequently suggestive, they are nonspecific, and non-invasive investigations such as orbital ultra-sonography and CT scanning are required for precise anatomical tissue localisation and diagnosis. The role of ocular muscle biopsy is probably limited to atypical cases, or those unresponsive to steroid therapy, particularly to exclude neoplasia. Orbital myositis may be acute, subacute or recurrent. The acute form responds well to high doses of oral corticosteroids tapered gradually, but it may recur or become chronic. The subacute form of the disease responds less well.
Publisher: Hindawi Limited
Date: 19-09-2012
Publisher: FapUNIFESP (SciELO)
Date: 2013
Publisher: Elsevier
Date: 2009
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12615
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.POP.2005.09.003
Abstract: Our understanding of the pathophysiology and clinical consequences of atrial fibrillation has led to an evidence-based revolution in the management of atrial fibrillation over the last decade. As we improve in our ability to detect recurrent atrial fibrillation and treat it definitively, the patients who benefit from long-term anticoagulation may change. We can expect, however,that stroke prevention through systemic anticoagulation will be a cornerstone of atrial fibrillation management for decades to come. Innovations in anticoagulation therapy will make the use of these medications safer. Finally, as we further understand the underlying mechanisms of the development of atrial fibrillation, the pursuit of preventative therapy will be an investigational focus of great import.
Publisher: Elsevier BV
Date: 08-2009
Publisher: Springer Science and Business Media LLC
Date: 07-2015
DOI: 10.1038/NATURE14618
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2013
Publisher: Public Library of Science (PLoS)
Date: 2010
Publisher: Wiley
Date: 02-1986
DOI: 10.1111/J.1445-5994.1986.TB01122.X
Abstract: The first reported case of disseminated histoplasmosis in Western Australia is described. The diagnosis was delayed because the clinical presentation closely resembled that of tuberculosis, the initial histoplasma serology was negative, and constant severe thrombocytopenia delayed efforts to obtain tissue required for culture and histology. Despite adequate therapy, relapse occurred on one occasion.
Publisher: Public Library of Science (PLoS)
Date: 2013
Publisher: Elsevier BV
Date: 11-2003
DOI: 10.1016/S1474-4422(03)00558-1
Abstract: Ischaemic stroke is an important cause of death and dependency in industrialised countries it has a high incidence (affecting up to 0.2% of the population each year) and is commonly lethal or disabling. One in six patients die in the first month after ischaemic stroke, and half of survivors are permanently disabled despite best efforts to rehabilitate them and to prevent complications, recurrent stroke, and other serious vascular events. Optimisation of the early, and ongoing, management of patients with acute ischaemic stroke is pivotal to the reduction of both case fatality and long-term disability. Guidelines for the early management of patients with ischaemic stroke have recently been published by the Stroke Council of the American Stroke Association (ASA Adams and co-workers, Stroke 2003 34: 1056-83) and the European Stroke Initiative (EUSI European Stroke Initiative Executive Committee and Writing Committee, Cerebrovasc Dis 2003 16: 311-38). Although transatlantic differences might create different interpretations, priorities, and views, the guidelines are remarkably similar, even regarding controversial issues. We believe this is not only because both groups have had the opportunity to discuss many of the controversial issues at international meetings, but also because both groups have endorsed the concept of evidence-based medicine and have based their recommendations on similar classifications of the levels of evidence for the effectiveness of interventions. This is a triumph for evidence-based medicine and a major step towards unification of acute stroke management worldwide. WHERE NEXT?: There are three main challenges in stroke management. To increase the body of reliable evidence from large randomised controlled trials (RCTs) of the safety, effectiveness, and cost of promising treatments (eg, thrombolysis, antithrombotic therapy, neuroprotection, and interventional recanalisation, alone and in combination) in a wide range of patients around the world. To facilitate the widespread development of stroke units, delivery of organised stroke care, and emergency transport of patients with stroke to appropriate stroke centres. And finally, to improve the uptake of effective therapies into clinical practice (eg, by widely disseminating the ASA and EUSI guidelines).
Publisher: Proceedings of the National Academy of Sciences
Date: 17-07-2017
Abstract: Bottom trawling is the most widespread source of physical disturbance to the world’s seabed. Predictions of trawling impacts are needed to underpin risk assessment, and they are relevant for the fishing industry, conservation, management, and certification bodies. We estimate depletion and recovery of seabed biota after trawling by fitting models to data from a global data compilation. Trawl gears removed 6–41% of faunal biomass per pass, and recovery times posttrawling were 1.9–6.4 y depending on fisheries and environmental context. These results allow the estimation of trawling impacts on unprecedented spatial scales and for data poor fisheries and enable an objective analysis of tradeoffs between harvesting fish and the wider ecosystem effects of such activities.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2000
Abstract: Background and Purpose —Few community-based studies have examined the long-term survival and prognostic factors for death within 5 years after an acute first-ever stroke. This study aimed to determine the absolute and relative survival and the independent baseline prognostic factors for death over the next 5 years among all in iduals and among 30-day survivors after a first-ever stroke in a population of Perth, Western Australia. Methods —Between February 1989 and August 1990, all in iduals with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. Results —Three hundred seventy patients with first-ever stroke were registered, and 362 (98%) were followed up at 5 years, by which time 210 (58%) had died. In the first year after stroke the risk of death was 36.5% (95% CI, 31.5% to 41.4%), which was 10-fold (95% CI, 8.3% to 11.7%) higher than that expected among the general population of the same age and sex. The most common cause of death was the index stroke (64%). Between 1 and 5 years after stroke, the annual risk of death was approximately 10% per year, which was approximately 2-fold greater than expected, and the most common cause of death was cardiovascular disease (41%). The independent baseline factors among 30-day survivors that predicted death over 5 years were intermittent claudication (hazard ratio [HR], 1.9 95% CI, 1.2 to 2.9), urinary incontinence (HR, 2.0 95% CI, 1.3 to 3.0), previous transient ischemic attack (HR, 2.4 95% CI, 1.4 to 4.1), and prestroke Barthel Index /20 (HR, 2.0 95% CI, 1.2 to 3.2). Conclusions —One-year survivors of first-ever stroke continue to die over the next 4 years at a rate of approximately 10% per year, which is twice the rate expected among the general population of the same age and sex. The most common cause of death is cardiovascular disease. Long-term survival after stroke may be improved by early, active, and sustained implementation of effective strategies for preventing subsequent cardiovascular events.
Publisher: Public Library of Science (PLoS)
Date: 2013
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1111/JTH.12546
Abstract: Idrabiotaparinux, a long-acting inhibitor of factor Xa, was shown to be effective in the treatment of patients with venous thromboembolism. To assess non-inferiority for the efficacy of idrabiotaparinux versus warfarin in patients with atrial fibrillation (AF) at risk of stroke and systemic embolism. Bleeding was also assessed. This randomized, double-blind trial enrolled patients with electrocardiogram-documented AF. Idrabiotaparinux was administered weekly via subcutaneous injection, and warfarin was administered daily with dose adjustment to maintain the international normalized ratio between 2.0 and 3.0. Each idrabiotaparinux injection was 3 mg for the first 7 weeks, followed by 2 mg thereafter, except in patients with a creatinine clearance of 30-50 mL min(-1) or aged ≥ 75 years. The patients received 1.5 mg after the first 7 weeks. The efficacy outcome was the composite of all fatal or non-fatal strokes and systemic embolism. The safety outcome was clinically relevant bleeding (major and clinically relevant non-major bleeding). The study was terminated prematurely by the sponsor for strategic/commercial, not scientific, reasons, with 39% of the planned number of patients included and an average duration of treatment of 240 days. Of the 1886 idrabiotaparinux recipients, 20 developed stroke or systemic embolism (1.5% per year), whereas this occurred in 22 of the 1887 warfarin patients (1.6% per year, hazard ratio 0.98, 95% confidence interval 0.49-1.66). The annual incidence of bleeding was 6.1% in the idrabiotaparinux and 10.0% in the warfarin group (hazard ratio 0.61, 95% confidence interval 0.46-0.81). If anything, despite its early termination, the idrabiotaparinux regimen studied suggested a comparable efficacy to dose-adjusted warfarin, with a lower bleeding risk.
Publisher: Public Library of Science (PLoS)
Date: 2015
Publisher: Public Library of Science (PLoS)
Date: 2015
Publisher: Wiley
Date: 11-03-2011
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.MATURITAS.2022.02.008
Abstract: To investigate whether diabetes and obesity are associated with frailty independently, and to determine the proportion of frailty cases attributable to each factor. Prospective cohort study of 4219 older men assessed in 2001-04 (time-point 1, T1), of whom 1939 were reassessed in 2008-09 (time-point 2, T2). Frailty was defined as positive responses on three or more of the five domains on the FRAIL scale: fatigue, difficulty climbing a flight of stairs (resistance), difficulty walking 100 m (ambulation), >5 illnesses, or >5% weight loss. We explored associations of diabetes and obesity with frailty using binary logistic regression, and estimated population attributable fractions for diabetes and obesity as risk factors for frailty. Associations of obesity and diabetes with frailty. At T1, 15.5% of participants (n = 652) were frail, 15.4% (n = 651) had diabetes, and 15.1% (n = 636) were obese (BMI ≥ 30 kg/m Diabetes and obesity are modifiable risk factors which independently carry equal risk for the development of frailty in older men. Interventions targeting these risk factors may have the potential to reduce frailty risk.
Publisher: AMPCo
Date: 09-1999
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2017
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-05-2015
Abstract: Human genomes show extensive genetic variation across in iduals, but we have only just started documenting the effects of this variation on the regulation of gene expression. Furthermore, only a few tissues have been examined per genetic variant. In order to examine how genetic expression varies among tissues within in iduals, the Genotype-Tissue Expression (GTEx) Consortium collected 1641 postmortem s les covering 54 body sites from 175 in iduals. They identified quantitative genetic traits that affect gene expression and determined which of these exhibit tissue-specific expression patterns. Melé et al. measured how transcription varies among tissues, and Rivas et al. looked at how truncated protein variants affect expression across tissues. Science , this issue p. 648 , p. 660 , p. 666 see also p. 640
Publisher: Elsevier BV
Date: 03-1995
Publisher: AMPCo
Date: 11-2004
Publisher: CMA Joule Inc.
Date: 27-03-2015
DOI: 10.1503/CMAJ.121171
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/362961
Abstract: Haemorrhagic transformation (HT) of recently ischaemic brain is a feared complication of thrombolytic therapy that may be caused or compounded by ischaemia-induced activation of matrix metalloproteinases (MMPs). The tetracycline antibiotic minocycline inhibits matrix MMPs and reduces macroscopic HT in rodents with stroke treated with tissue plasminogen activator (tPA). The West Australian Intravenous Minocycline and TPA Stroke Study (WAIMATSS) aims to determine the safety and efficacy of adding minocycline to tPA in acute ischaemic stroke. The WAIMATSS is a multicentre, prospective, and randomised pilot study of intravenous minocycline, 200 mg 12 hourly for 5 doses, compared with standard care, in patients with ischaemic stroke treated with intravenous tPA. The primary endpoint is HT diagnosed by brain CT and MRI. Secondary endpoints include clinical outcome measures. Some illustrative cases from the early recruitment phase of this study will be presented, and future perspectives will be discussed.
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000517679
Abstract: The introduction and evolution of evidence-based stroke medicine has realized major advances in our knowledge about stroke, methods of medical research, and patient outcomes that continue to complement traditional in idual patient care. It is humbling to recall the state of knowledge and scientific endeavour of our forebears who were unaware of what we know now and yet pursued the highest standards for evaluating and delivering effective stroke care. The science of stroke medicine has evolved from pathophysiological theory to empirical testing. Progress has been steady, despite inevitable disappointments and cul-de-sacs, and has occasionally been punctuated by sensational breakthroughs, such as the advent of reperfusion therapies guided by imaging.
Publisher: American College of Physicians
Date: 17-03-2009
DOI: 10.7326/0003-4819-150-6-200903170-00006
Abstract: The optimal aspirin dose for the prevention of cardiovascular events remains controversial. To assess the incidence of and risk factors for adverse clinical outcomes by investigator-determined aspirin dose in a primary prevention trial. Post hoc observational analyses of data from a double-blind, placebo-controlled, randomized trial. Outpatient. 15 595 patients with cardiovascular disease or multiple risk factors. Clopidogrel, 75 mg/d, or placebo, with aspirin, 75 to 162 mg/d, as selected by the investigators. Incidence of the composite outcome of myocardial infarction, stroke, or cardiovascular death (efficacy end point), and incidence of severe or life-threatening bleeding (safety end point), at a median of 28 months (interquartile range, 23 to 31 months) of follow-up. Daily aspirin doses were categorized as less than 100 mg (75 or 81 mg) (n = 7180), 100 mg (n = 4961), and greater than 100 mg (150 or 162 mg) (n = 3454). The hazard of the primary efficacy end point was the same regardless of dose (adjusted hazard ratio, 0.95 [95% CI, 0.80 to 1.13] for 100 mg vs. less than 100 mg, and 1.0 [CI, 0.85 to 1.18] for greater than 100 mg vs. less than 100 mg). The hazard of the primary safety end point also did not depend on dose (adjusted hazard ratio, 0.85 [CI, 0.57 to 1.26] for 100 mg vs. less than 100 mg and 1.05 [CI, 0.74 to 1.48] for greater than 100 mg vs. less than 100 mg). In patients also receiving clopidogrel, daily aspirin doses greater than 100 mg seemed to be non-statistically significantly associated with reduced efficacy (adjusted hazard ratio, 1.16 [CI, 0.93 to 1.44]) and increased harm (adjusted hazard ratio, 1.30 [CI, 0.83 to 2.04]). The analysis was post hoc, and aspirin use was not randomized or blinded. Daily aspirin doses of 100 mg or greater were associated with no clear benefit in patients taking aspirin only and possibly with harm in patients taking clopidogrel. Daily doses of 75 to 81 mg may optimize efficacy and safety for patients requiring aspirin for long-term prevention, especially for those receiving dual antiplatelet therapy. None.
Publisher: Cambridge University Press (CUP)
Date: 14-11-2013
DOI: 10.1017/S1041610212001834
Abstract: Background: There is ongoing debate about whether a decline in body mass represents a true risk factor for dementia, whether it is a phenotypic marker of incipient dementia, or perhaps a marker of another process that increases dementia risk. This study was designed to determine if changes in body mass index (BMI) in later life are associated with hazard of incident dementia over a follow-up period of up to eight years. Methods: Method followed was a prospective cohort study of 4,181 men aged 65–84 years, resident in Perth, Australia. The exposure of interest was change in BMI measured between 1996–1998 and 2001–2004. The outcome was incident dementia, established using the Western Australia Data Linkage System until 2009. We used Cox regression models to establish crude and adjusted hazard of dementia for change in BMI. Results: Compared with men with a stable BMI, those with a decrease in BMI kg/m 2 had a higher adjusted hazard of dementia (hazard ratio (HR) = 1.89, 95% CI = 1.32–2.70). The cumulative hazard of dementia over follow-up for changes in BMI was greatest for men with a decrease in BMI kg/m 2 this trend was apparent for men in all BMI categories (underweight, normal, overweight, obese). A reverse “J-shaped” association between BMI change and incident dementia was observed, with the lowest dementia rate being for men whose BMI remained stable. Conclusions: Men who maintained a stable body mass had the lowest incidence of dementia. Further studies are needed to clarify causality and assess feasibility of interventional studies to preserve body mass in aging men.
Publisher: Frontiers Media SA
Date: 28-07-2020
Publisher: Wiley
Date: 06-12-2022
DOI: 10.1111/CEN.14648
Abstract: Testosterone and sex hormone‐binding globulin (SHBG) concentrations are reported to decline during male ageing, but whether these changes reflect physiological ageing or age‐related comorbidities remains uncertain. We examined longitudinal changes in serum testosterone and SHBG concentrations in middle‐aged to older men, concordance between baseline and follow‐up values and relationships with concomitant changes in lifestyle and medical factors. Population‐based longitudinal cohort study. Community‐dwelling men aged 40–69 years. Immunoassay serum total testosterone ( n = 7812) and SHBG ( n = 6491) at baseline (2006–2010) and follow‐up (2012–2013). Free testosterone (cFT) was calculated. Bland–Altman analyses and concordance correlation of repeated measurements were conducted. Associations of changes in hormone concentrations with lifestyle and medical factors were explored using Spearman's rank correlation. Over 4.3 years follow‐up, there was a negligible mean change (±SE) in serum total testosterone concentration (+0.06 ± 0.03 nmol/L), whereas mean SHBG concentration increased (+3.69 ± 0.12 nmol/L) and cFT decreased (−10.7 ± 0.7 pmol/L). Concordance estimates were 0.67 (95% confidence interval [CI]: 0.66–0.69) for total testosterone, 0.83 (CI = 0.82–0.84) for SHBG and 0.56 (CI = 0.54–0.58) for cFT. Changes in serum total testosterone correlated with changes in SHBG (Spearman's rank ρ = 0.33, CI = 0.30–0.35), and inversely with changes in body mass index (BMI) ( ρ = −0.18, CI = −0.20 to −0.16) and waist circumference ( ρ = −0.13, CI = −0.15 to −0.11) and in SHBG with changes in BMI ( ρ = −0.34, CI = −0.36 to −0.32) and waist circumference ( ρ = −0.21, CI = −0.24 to −0.19). In relatively healthy middle‐aged to older men, mean serum total testosterone concentration is stable with ageing, while mean SHBG concentration increases. Both total testosterone and SHBG concentrations were highly concordant over time.
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000479518
Abstract: b i Background: /i /b The burden of stroke in low- and middle-income countries (LMICs) is large and increasing, challenging the already stretched health-care services. b i Aims and Objectives: /i /b To determine the quality of existing stroke-care services in LMICs and to highlight indigenous, inexpensive, evidence-based implementable strategies being used in stroke-care. b i Methods: /i /b A detailed literature search was undertaken using PubMed and Google scholar from January 1966 to October 2015 using a range of search terms. Of 921 publications, 373 papers were shortlisted and 31 articles on existing stroke-services were included. b i Results: /i /b We identified efficient models of ambulance transport and pre-notification. Stroke Units (SU) are available in some countries, but are relatively sparse and mostly provided by the private sector. Very few patients were thrombolysed this could be increased with telemedicine and governmental subsidies. Adherence to secondary preventive drugs is affected by limited availability and affordability, emphasizing the importance of primary prevention. Training of paramedics, care-givers and nurses in post-stroke care is feasible. b i Conclusion: /i /b In this systematic review, we found several reports on evidence-based implementable stroke services in LMICs. Some strategies are economic, feasible and reproducible but remain untested. Data on their outcomes and sustainability is limited. Further research on implementation of locally and regionally adapted stroke-services and cost-effective secondary prevention programs should be a priority.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-03-2015
Publisher: Springer Science and Business Media LLC
Date: 16-11-2013
DOI: 10.1007/S00198-012-2218-0
Abstract: The aim of the present study was to assess whether peripheral arterial disease is associated with an increased risk of hip fracture in a cohort of 12,094 older men. There was no association between claudication and hip fracture, but there was a significant association with an ankle brachial index (ABI) <0.9. It is uncertain whether peripheral arterial disease (PAD) is associated with an increased risk of subsequent hip fracture. The aim of the present study was to assess this in a large cohort of men aged 65 years and over. Claudication was assessed by means of the Edinburgh Claudication Questionnaire in 12,094 men, and the ABI was measured in 4,321 of these men. Hospitalisations with hip fracture were identified by record linkage. The association between both claudication and an ABI <0.9 and subsequent hip fractures was assessed using survival curves and Cox regression models. Amongst the 12,094 men, the baseline prevalence of claudication according to the ECQ was 5.3 %. Amongst the 4,321 men with ABI results, the prevalence of an ABI <0.9 was 11.7 %. Of the 506 men with an ABI <0.9, 129 (25.5 %) also had claudication. Over a median (range) follow-up of 10.8 (0.3-12.7) years, 343 (2.8 %) of the 12,094 men were admitted to hospital with a hip fracture. There was no association between claudication and subsequent hip fractures (hazard ratio (HR) = 0.95 95 % confidence interval (CI), 0.60, 1.52). Over a median (range) follow-up of 11.1 (0.06-12.3) years 135 (3.1 %) of the 4,321 men with ABI data were admitted to hospital with hip fractures. There was a significant association between an ABI <0.9 and subsequent hip fracture (HR = 1.69 95 % CI, 1.08, 2.63). Older men with PAD defined as ABI < 0.9 are at increased risk of hip fracture, whereas the symptom of claudication is not an independent predictor of hip fracture.
Publisher: AMPCo
Date: 1997
DOI: 10.5694/J.1326-5377.1997.TB138714.X
Abstract: Although Brazil is currently the largest soybean producer in the world, only a small number of studies have analyzed the genetic ersity of Brazilian soybean. These studies have shown the existence of a narrow genetic base. The objectives of this work were to analyze the population structure and genetic ersity, and to identify selection signatures in the genome of soybean germplasms from different companies in Brazil. A panel consisting of 343 soybean lines from Brazil, North America, and Asia was genotyped using genotyping by sequencing (GBS). Population structure was assessed by Bayesian and multivariate approaches. Genetic ersity was analyzed using metrics such as the fixation index, nucleotide ersity, genetic dissimilarity, and linkage disequilibrium. The software BayeScan was used to detect selection signatures between Brazilian and Asian accessions as well as among Brazilian germplasms. Region of origin, company of origin, and relative maturity group (RMG) all had a significant influence on population structure. Varieties belonging to the same company and especially to the same RMG exhibited a high level of genetic similarity. This result was exacerbated among early maturing accessions. Brazilian soybean showed significantly lower genetic ersity when compared to Asian accessions. This was expected, because the crop's region of origin is its main genetic ersity reserve. We identified 7 genomic regions under selection between the Brazilian and Asian accessions, and 27 among Brazilian varieties developed by different companies. Associated with these genomic regions, we found 96 quantitative trait loci (QTLs) for important soybean breeding traits such as flowering, maturity, plant architecture, productivity components, pathogen resistance, and seed composition. Some of the QTLs associated with the markers under selection have genes of great importance to soybean's regional adaptation. The results reported herein allowed to expand the knowledge about the organization of the genetic variability of the Brazilian soybean germplasm. Furthermore, it was possible to identify genomic regions under selection possibly associated with the adaptation of soybean to Brazilian environments.
Publisher: Oxford University Press (OUP)
Date: 10-09-2015
Publisher: Elsevier BV
Date: 09-2021
Publisher: Informa Healthcare
Date: 03-2004
Abstract: Atherothrombotic coronary artery disease is the single most common cause of death worldwide and a growing public health problem. Platelets play a central role in the pathogenesis of atherothrombosis and are therefore commonly targeted by one or more antiplatelet drugs as part of primary and secondary atherothrombosis prevention strategies. Aspirin reduces the risk of serious vascular events (myocardial infarction, stroke or cardiovascular death) by approximately 20% in a broad range of high-risk patients and remains the first-line antiplatelet drug because of its relative safety, low cost and cost-effectiveness. Compared with aspirin alone, clopidogrel reduces the risk of serious vascular events by approximately 10% and the combination of aspirin and clopidogrel reduces the risk by approximately 20% in patients with non-ST-segment elevation acute coronary syndrome. Clopidogrel has a similar safety profile to aspirin but clopidogrel tablets are substantially more expensive. However, the incremental cost-effectiveness ratio of clopidogrel compared with aspirin is favourable, particularly in high-risk patients and is intermediate compared with a range of other effective therapeutic strategies for the treatment of coronary heart disease. Clopidogrel should be considered as a replacement for aspirin in patients who are allergic to aspirin, cannot tolerate aspirin, have experienced a recurrent atherothrombotic vascular event whilst taking aspirin and are at very high absolute risk of a serious vascular event (e.g., > 20%/year). The combination of clopidogrel and aspirin should be considered in patients with non-ST-segment elevation acute coronary syndrome or undergoing percutaneous coronary intervention.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.THROMRES.2017.04.010
Abstract: The ROCKET AF study evaluated once-daily rivaroxaban versus dose-adjusted warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). In this analysis, we compared rivaroxaban with warfarin in patients with AF from China, East Asia, and the rest of the world (ROW). We assessed baseline demographics and interaction of treatment effects of rivaroxaban versus warfarin among patients from mainland China, other East Asian countries, and ROW. Of the 14,236 patients enrolled in the per-protocol population, 495 were from mainland China, 433 from other East-Asian regions, and 13,308 from the rest of the world (ROW). At baseline, patients from China had significantly higher rates of previous stroke/transient ischemic attack (TIA) compared with patients from other East Asian regions and ROW (79.6%, 44.6%, 51.6% respectively p<0.0001) and lower rates of VKA use (33.7%, 66.7%, 63.4%, respectively p 0.12). Numerically higher rates of intracranial bleeding were seen in patients from China receiving warfarin versus rivaroxaban. In patients from China, rates of intracranial hemorrhage were numerically lower among those receiving rivaroxaban and consistent with the overall trial. URL: Unique identifier: NCT00403767.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-10-2021
Abstract: In event‐driven clinical trials, study termination is based on accrual of a target number of primary efficacy events. For noninferiority trials in which superiority is conditionally examined, the ideal cohort in which to track event accrual is unclear. We used data from the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial to determine the effect of primary efficacy‐event tracking in the per‐protocol cohort during the on‐treatment period versus the intention‐to‐treat (ITT) cohort during the ITT period. ROCKET AF was terminated after accruing 429 primary efficacy events (stroke or systemic embolism) in the per‐protocol cohort during the on‐treatment period for noninferiority. We identified the date on which 429 events occurred in the ITT cohort during the ITT period. We performed noninferiority and superiority analyses based on hypothetical study termination on this date. ROCKET AF would have terminated 226 days earlier if events were tracked during the ITT period. Similar to the main trial findings, rivaroxaban would have met noninferiority versus warfarin for the primary efficacy end point (hazard ratio [HR], 0.77 95% CI, 0.62–0.96 P .001). In contrast to the main trial findings, rivaroxaban would have met superiority for the primary efficacy end point (HR, 0.82 95% CI, 0.68–0.99 P =0.038). In both termination scenarios, rivaroxaban was associated with a lower risk of intracranial hemorrhage and similar risk of other safety end points. Clinical trial termination based on event accrual in the ITT cohort versus the per‐protocol cohort may have important implications on trial results depending on rates of study drug discontinuation and event rates off treatment.
Publisher: Public Library of Science (PLoS)
Date: 18-07-2014
Publisher: Elsevier BV
Date: 04-2014
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 10-2009
Publisher: Oxford University Press (OUP)
Date: 27-03-2012
Abstract: high levels of social support and engagement may help sustain good health and functional ability. However, the definition of social support in previous research has been inconsistent and findings are mixed. The aim of this analysis was to explore the effect of two aspects of social support on subsequent disability in a group of community dwelling older women and men. data were drawn from two concurrent prospective observational cohort studies of community-based older Australian women (N = 2,013) and men (N = 680). Baseline and follow-up data were drawn from the second (1999) and fifth (2008) surveys of the women and the second (2001) and third (2008) surveys of the men. At baseline, social support was measured by the two subscales (social network and subjective support) of the Duke Social Support Index (DSSI). The outcome measure was Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs). overall, social network size was not associated with subsequent disability in either women or men. After adjusting for health status at baseline, lack of satisfaction with social support was associated with greater difficulties in ADLs and IADLs for both women and men. our results suggest that the provision of social support is insufficient to limit subsequent disability: support provided must be subjectively perceived to be relevant and adequate.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.ARCHGER.2012.04.005
Abstract: The main purpose of this study was to determine the most robust predictor of mortality among global self-rated health (SRH), time-comparative SRH or a combination of both measures. We also sought to determine factors associated with global SRH and time-comparative SRH measures. A prospective cohort study of 5583 community-dwelling older men aged 70 years or over living in Perth, Western Australia, was used. Older age, depressive symptoms, low social support, sensory impairment, presence of pain, and high Charlson score index were associated with both SRH measures. Global and time-comparative SRH were independent predictors of all-cause mortality (adjusted hazard ratio, HR=1.24 vs. 1.41 respectively) and the risk of death was almost doubled in those with both negative global SRH and perception of worsening health over the preceding 12 months (adjusted HR 1.98, 95%CI 1.58-2.47). In this group, the rate of death was especially high during the initial four years of follow up. We concluded that the two measures of SRH are likely to reflect the same domains of health, and the simultaneous use of both measures is the best predictor of short to medium term mortality.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2012
DOI: 10.1158/1055-9965.EPI-12-0129
Abstract: Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer. Methods: This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010. Results: During a mean follow-up period of 6.7 ± 1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00–1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21–1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53–5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers. Conclusions: Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer. Impact: Further studies should investigate whether these risks apply to men receiving testosterone therapy. Cancer Epidemiol Biomarkers Prev 21(8) 1319–29. ©2012 AACR.
Publisher: BMJ
Date: 06-2018
Abstract: Supplementation with B vitamins (vitamin B 9 (folic acid), vitamin B 12 and vitamin B 6 ) lowers blood total homocysteine (tHcy) concentrations by about 25% and reduces the relative risk of stroke overall by about 10% (risk ratio (RR) 0.90, 95% CI 0.82 to 0.99) compared with placebo. Homocysteine-lowering interventions have no significant effect on myocardial infarction, death from any cause or adverse outcomes. Factors that appear to modify the effect of B vitamins on stroke risk include low folic acid status, high tHcy, high cyanocobalamin dose in patients with impaired renal function and concurrent antiplatelet therapy. In regions with increasing levels or established policies of population folate supplementation, evidence from observational genetic epidemiological studies and randomised controlled clinical trials is concordant in suggesting an absence of benefit from lowering of homocysteine with folic acid for prevention of stroke. Clinical trials indicate that in countries which mandate folic acid fortification of food, folic acid supplementation has no significant effect on reducing stroke risk (RR 1.05, 95% CI 0.90 to 1.23). However, in countries without mandatory folic acid food fortification, folic acid supplementation reduces the risk of stroke by about 15% (RR 0.85, 95% CI 0.77 to 0.94). Folic acid alone or in combination with minimal cyanocobalamin (≤0.05 mg/day) is associated with an even greater reduction in risk of future stroke by 25% (RR 0.75, 95% CI 0.66 to 0.86), whereas the combination of folic acid and a higher dose of cyanocobalamin (≥0.4 mg/day) is not associated with a reduced risk of future stroke (RR 0.95, 95% CI 0.86 to 1.05). The lack of benefit of folic acid plus higher doses of cyanocobalamin (≥0.4 mg/day) was observed in trials which all included participants with chronic kidney disease. Because metabolic B 12 deficiency is very common and usually not diagnosed, future randomised trials of homocysteine-lowering interventions for stroke prevention should probably test a combination of folic acid and methylcobalamin or hydroxocobalamin instead of cyanocobalamin, and perhaps vitamin B 6 .
Publisher: Oxford University Press (OUP)
Date: 02-12-2013
Abstract: Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, utation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02 interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11 interaction P = 0.037). Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
DOI: 10.1161/STROKEAHA.114.006609
Abstract: Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes. Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73 998), eGFR using cystatin C (eGFRcys: n=22 937), and urinary albumin to creatinine ratio (n=31 580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease. Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P .05 (peak P =0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P =0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio–based score also associated with small vessel disease ( P =0.03). The global pattern of results was unlikely to have occurred by chance ( P =0.02). This study suggests possible polygenic correlation between renal dysfunction and IS. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders seems merited.
Publisher: AMPCo
Date: 06-2005
DOI: 10.5694/J.1326-5377.2005.TB06816.X
Abstract: Pulmonary embolism (PE) affects 0.5-1 per 1000 people in the general population each year, and is one of the most common preventable causes of death among hospitalised patients. The clinical diagnosis of PE is unreliable and must be confirmed objectively with ventilation perfusion scanning or computed tomography pulmonary angiography. The diagnosis of PE can be reliably excluded, without the need for diagnostic imaging, if the clinical pretest probability for PE is low and the D-dimer assay result is negative. The initial treatment of PE is low-molecular-weight heparin or unfractionated heparin for at least 5 days, followed by warfarin (target international normalised ratio [INR], 2.0-3.0) for at least 3-6 months. Patients with a high clinical pretest probability of PE should commence treatment immediately while awaiting the results of the diagnostic work-up. Thrombolysis is indicated for patients with objectively confirmed PE who are haemodynamically unstable. Percutaneous transcatheter or surgical embolectomy may be life-saving in patients ineligible for, or unresponsive to, thrombolytic therapy. Unresolved issues in the management of venous thromboembolism include the roles of thrombophilia testing, thrombolysis for the treatment of stable PE patients who present with right ventricular dysfunction, and new anticoagulants and the duration of anticoagulation for first unprovoked venous thromboembolism.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2012
Abstract: Anticoagulant therapy for ischaemic stroke aims to prevent recurrent ischaemic stroke and venous thromboembolism. Several large clinical trials have provided insight into the safety and efficacy of anticoagulant therapies. Anticoagulant treatment provides no net benefit over placebo or antiplatelet therapy in patients with acute ischaemic stroke of arterial or cardiac origin, because reductions in early recurrent ischaemic events and venous thromboembolism are offset by increases in bleeding events. For patients with ischaemic stroke of cardiac origin due to atrial fibrillation, long-term warfarin treatment reduces the risk of recurrent stroke by two-thirds compared with control, and by half compared with antiplatelet therapy. New anticoagulants, such as dabigatran, rivaroxaban and apixaban, are as efficacious and safe as warfarin, and have a rapid onset of action, few drug interactions, and predictable anticoagulant effects that do not require routine monitoring. However, the anticoagulant effects of the new drugs cannot be reliably measured or rapidly reversed in the event of major non-compressible bleeding or urgent surgery. In addition, the new agents cannot be used in patients with severe renal impairment or active liver disease. Ongoing research aims to resolve these limitations, examine whether the promising results of clinical trials can be translated into clinical practice, and monitor the long-term safety of anticoagulant therapies.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.IJCARD.2012.03.120
Abstract: Angiopoietin-2 (Angpt2) has been implicated in the mediation and regulation of angiogenesis and inflammation which are believed to be critical mechanisms in the pathogenesis of both abdominal aortic aneurysm (AAA) and cardiovascular events. The aim of this study was to assess whether serum Angpt2 was associated with the prevalence of AAA and the occurrence of cardiovascular mortality in older men. A cohort of 997 elderly men was recruited in 1996-99. Aortic ultrasound identified an AAA in 308 (31%). In 2001-04, blood was collected and serum Angpt2 later measured by immunoassay. The association of Angpt2 with AAA was assessed using multiple regression analysis. All men were followed by means of the Western Australia Data Linkage System until July 31st 2009. The association of Angpt2 with cardiovascular mortality was assessed using Cox proportional hazard analysis. Median serum Angpt2 was significantly higher (3.16 ng/ml, inter-quartile range 2.51-4.54) in men with AAA compared with men without AAA (2.70 ng/ml, inter-quartile range 2.03-3.72 p 3.95 ng/ml) had a 2.57-fold (95% CI 1.66-3.97, p<0.001) increased odds of AAA and a 4.12-fold (95% CI 1.90-8.94, p<0.001) increased relative risk of cardiovascular mortality compared to men with serum Angpt2 in the lowest quartile (<2.13 ng/ml). Serum Angpt2 is elevated in men with AAA and associated with an increased risk of cardiovascular mortality in older men.
Publisher: BMJ
Date: 12-12-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-04-2011
Publisher: Oxford University Press (OUP)
Date: 06-08-2021
Abstract: Telomeres are essential DNA–protein complexes whose attrition results in cellular dysfunction and senescence. Leukocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However, its predictive value for mortality risk, and for cardiovascular versus cancer deaths, in older adults remains uncertain. We studied 3608 community-dwelling men aged 77.0 ± 3.6 years. Leukocyte telomere length was measured using multiplex quantitative PCR, expressed as amount of telomeric DNA relative to single-copy control gene (T/S ratio). Deaths from any cause, cardiovascular disease (CVD), and cancer were ascertained using data linkage. Curve fitting used restricted cubic splines and Cox regression analyses adjusted for age, cardiometabolic risk factors, and prevalent disease. There was a U-shaped association of LTL with all-cause mortality. Men with T/S ratio in the middle quartiles had lower mortality (quartiles, Q2 vs Q1, hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.77–0.97, p = .012 Q3 vs Q1 HR = 0.88, CI 0.79–0.99, p = .032). There was no association of LTL with CVD mortality. There was a U-shaped association of LTL with cancer mortality. Men with LTL in the middle quartiles had lower risk of cancer death (Q2 vs Q1, HR = 0.73, CI 0.59–0.90, p = .004 Q3 vs Q1, HR = 0.75, CI 0.61–0.92, p = .007). In older men, both shorter and longer LTL are associated with all-cause mortality. A similar U-shaped association was seen with cancer deaths, with no association found for cardiovascular deaths. Further research is warranted to explore the prognostic utility of LTL in ageing.
Publisher: Elsevier BV
Date: 09-2010
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.MAM.2021.100969
Abstract: Inhaled glucocorticoids (GCs) are drugs widely used as treatment for asthma patients. They prevent the recruitment and activation of lung immune and inflammatory cells and, moreover, have profound effects on airway structural cells to reverse the effects of disease on airway inflammation. GCs bind to a specific receptor, the glucocorticoid receptor (GR), which is a member of the nuclear receptor superfamily and modulates pro- and anti-inflammatory gene transcription through a number of distinct and complementary mechanisms. Targets genes include many pro-inflammatory mediators such as chemokines, cytokines, growth factors and their receptors. Inhaled GCs are very effective for most asthma patients with little, if any, systemic side effects depending upon the dose. However, some patients show poor asthma control even after the administration of high doses of topical or even systemic GCs. Several mechanisms relating to inflammation have been considered to be responsible for the onset of the relative GC resistance observed in these patients. In these patients, the side-effect profile of GCs prevent continued use of high doses and new drugs are needed. Targeting the defective pathways associated with GC function in these patients may also reactivate GC responsiveness.
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000514155
Abstract: b i Background: /i /b Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care inpatient intensive or stroke units posthospitalization rehabilitation follow-up including at-risk family and community and multispecialty departmental developments in the allied professions. b i Summary: /i /b The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. b i Key Messages: /i /b Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.
Publisher: SAGE Publications
Date: 19-08-2016
Abstract: Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24 p 0.001), hypertension (β = 0.09 p = 0.025), and deep white matter hyperintensities (β = 0.31 p 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22–2.42) and for clinical and imaging confounders (OR = 1.54 95% CI = 1.03–2.31). Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.
Publisher: SAGE Publications
Date: 17-10-2020
Abstract: To determine whether fluoxetine, at any dose, given within the first year after stroke to patients who did not have to have mood disorders at randomization reduced disability, dependency, neurological deficits and fatigue improved motor function, mood, and cognition at the end of treatment and follow-up, with the same number or fewer adverse effects. Searches (from 2012) in July 2018 included databases, trials registers, reference lists, and contact with experts. Co-primary outcomes were dependence and disability. Dichotomous data were synthesized using risk ratios (RR) and continuous data using standardized mean differences (SMD). Quality was appraised using Cochrane risk of bias methods. Sensitivity analyses explored influence of study quality. The searches identified 3414 references of which 499 full texts were assessed for eligibility. Six new completed RCTs (n = 3710) were eligible, and were added to the seven trials identified in a 2012 Cochrane review (total: 13 trials, n = 4145). There was no difference in the proportion independent (3 trials, n = 3249, 36.6% fluoxetine vs. 36.7% control RR 1.00, 95% confidence interval 0.91 to 1.09, p = 0.99, I This class I evidence demonstrates that fluoxetine does not reduce disability and dependency after stroke but improves depression.
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000515239
Abstract: b i Background: /i /b Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association. b i Aims: /i /b We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations. b i Methods: /i /b INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included in iduals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR & #x3c mL/min/1.73 m sup /sup . Multivariable conditional logistic regression was used to determine the association of renal function with stroke. b i Results: /i /b Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m sup /sup . The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, i /i & #x3c 0.001) and differed by region ( i /i & #x3c 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35 95% CI: 1.24–1.47), with higher odds for intracerebral hemorrhage (OR 1.60 95% CI: 1.35–1.89) than ischemic stroke (OR 1.29 95% CI: 1.17–1.42) ( i /i sub interaction /sub 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America ( i /i sub interaction /sub & #x3c 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97 95% CI: 2.50–3.54 for death within 1 month). b i Conclusion: /i /b Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2020
DOI: 10.1038/S41591-020-0807-6
Abstract: A double burden of malnutrition occurs when in iduals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of % in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Royal College of Psychiatrists
Date: 08-2016
DOI: 10.1192/BJP.BP.115.180059
Abstract: Bipolar disorder has been associated with cognitive decline, but confirmatory evidence from a community-derived s le of older people is lacking. To investigate the 13-year risk of dementia and death in older adults with bipolar disorder. Cohort study of 37 768 men aged 65–85 years. Dementia (primary) and death (secondary), as recorded by electronic record linkage, were the outcomes of interest. Bipolar disorder was associated with increased adjusted hazard ratio (HR) of dementia (HR = 2.30, 95% CI 1.80–2.94). The risk of dementia was greatest among those with years of history of bipolar disorder or who had had illness onset after 70 years of age. Bipolar disorder was also associated with increased mortality (HR = 1.51, 95% CI 1.28–1.77). Competing risk regression showed that bipolar disorder was associated with increased hazard of death by suicide, accidents, pneumonia or influenza, and diseases of the liver and digestive system. Bipolar disorder in later life is associated with increased risk of dementia and premature death.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
DOI: 10.1161/STROKEAHA.111.000433
Abstract: Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the protease-activated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7% hazard ratio, 1.03 95% confidence interval, 0.85–1.25), including recurrent ischemic stroke (hazard ratio, 0.99 95% confidence interval, 0.78–1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0% hazard ratio, 2.52 95% confidence interval, 1.46–4.36). In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke. www.clinicaltrials.gov . Unique identifier: NCT00526474.
Publisher: American College of Physicians
Date: 02-2022
DOI: 10.7326/M21-0551
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-1998
Abstract: This study was performed to explore the effect of childhood trauma on nonsuicidal self-injury (NSSI) in adolescents with bipolar II (BD II) depression. Based on the diagnostic criteria of the DSM-5 and structured interviews to assess the presence or absence of NSSI, 184 adolescent patients with BD II depression were ided into the NSSI (n = 112) and non-NSSI (n = 72) groups. The Adolescent Nonsuicidal Self-Injury Assessment Questionnaire (ANSAQ), Childhood Trauma Questionnaire-Short Form (CTQ-SF), Toronto Alexithymia Scale (TAS-20), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA) were used to assess the subjects. The CTQ-SF, HAMD, HAMA, and TAS-20 scores were significantly higher in the NSSI group than in the non-NSSI group (p .01). Logistic regression analysis showed emotional abuse (p = .028, OR = 1.14, 95% CI = 1.01-1.28) and age of onset (p = .009) as risk factors for NSSI. Adolescents with onset age 12-13 years (OR = 6.30, 95% CI = 1.72-23.10) and 14-15 years (OR = 2.24, 95% CI = 1.04-4.84) had a higher risk of self-injury relative to adolescents aged 16-18 years. Childhood trauma and alexithymia were important influencing factors in adolescent patients with BD II depression. Emotional abuse and age of onset as risk factors for NSSI, and difficulties in emotion recognition were positively associated with the patients' NSSI.
Publisher: SAGE Publications
Date: 11-2008
DOI: 10.1111/J.1747-4949.2008.00215.X
Abstract: The heterogeneity of the pathology of stroke has been a major difficulty in assessing new treatments for acute stroke, and contributes to the complexity of stroke medicine. Some underlying mechanisms are poorly understood, such as small vessel (lacunar) disease. New technology such as advanced brain imaging has transformed our knowledge of large vessel disease and we suggest that other new technology such as detailed analysis of retinal vessels may provide new insights into the pathology of small vessel (lacunar) stroke disease. We hypothesise that retinal microvascular signs differ by pathological stroke subtype, and we plan to test this hypothesis in over 1000 acute stroke patients. Eligible patients undergo a standardised neurological assessment followed by digital retinal photography. At a consensus meeting, an anatomical and aetiological classification is determined. Retinal photographs will be assessed qualitatively (e.g. retinal emboli, arteriovenous nicking) and quantitatively (arteriolar/venule ratio). Six-month vascular event rates together with disability and vital status are collected. Retinal vessel appearances may provide a ‘window’ to the brain and help determine the important underlying pathophysiological mechanisms of small vessel disease stroke.
Publisher: Public Library of Science (PLoS)
Date: 2008
Publisher: SAGE Publications
Date: 15-03-2010
Publisher: Public Library of Science (PLoS)
Date: 2008
Publisher: SAGE Publications
Date: 22-10-2016
Abstract: In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. India CTRI/2013/04/003557 Australian New Zealand Clinical Trials Registry ACTRN1261000078752 Universal Trial Number U1111-1138-6707.
Publisher: Public Library of Science (PLoS)
Date: 2008
Publisher: Public Library of Science (PLoS)
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 18-02-2020
DOI: 10.1038/S41467-020-14772-5
Abstract: Low thermal conductivity is favorable for preserving the temperature gradient between the two ends of a thermoelectric material, in order to ensure continuous electron current generation. In high-performance thermoelectric materials, there are two main low thermal conductivity mechanisms: the phonon anharmonic in PbTe and SnSe, and phonon scattering resulting from the dynamic disorder in AgCrSe 2 and CuCrSe 2 , which have been successfully revealed by inelastic neutron scattering. Using neutron scattering and ab initio calculations, we report here a mechanism of static local structure distortion combined with phonon-anharmonic-induced ultralow lattice thermal conductivity in α -MgAgSb. Since the transverse acoustic phonons are almost fully scattered by the compound’s intrinsic distorted rocksalt sublattice, the heat is mainly transported by the longitudinal acoustic phonons. The ultralow thermal conductivity in α -MgAgSb is attributed to its atomic dynamics being altered by the structure distortion, which presents a possible microscopic route to enhance the performance of similar thermoelectric materials.
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.AHJ.2018.02.013
Abstract: We investigated the impact of polyvascular disease in patients enrolled in ROCKET AF. Cox regression models were used to assess clinical outcomes and treatment effects of rivaroxaban compared with warfarin in patients with atrial fibrillation and coronary, peripheral, or carotid artery disease, or any combination of the 3. A total of 655 (4.6%) patients had polyvascular disease (≥2 disease locations), and 3,391 (23.8%) had single-arterial bed disease. Patients with polyvascular disease had similar rates of stroke/systemic embolism but higher rates of cardiovascular and bleeding events when compared with those without vascular disease. Use of rivaroxaban compared with warfarin was associated with higher rates of stroke in patients with polyvascular disease (hazard ratio [HR] 2.41, 95% CI 1.05-5.54) however, this was not seen in patients with single-bed (HR 0.90, 95% CI 0.64-1.28) or no vascular disease (HR 0.85, 95% CI 0.69-1.04 interaction P = .058). There was a significant interaction for major or nonmajor clinically relevant bleeding in patients with polyvascular (HR 1.23, 95% CI 0.91-1.65) and single-bed vascular disease (HR 1.30, 95% CI 1.13-1.49) treated with rivaroxaban compared with warfarin when compared with those without vascular disease (HR 0.95, 95% CI 0.87-1.04 interaction P = .0006). Additional antiplatelet therapy in this population did not improve stroke or cardiovascular outcomes. The use of rivaroxaban compared with warfarin was associated with a higher risk of stroke and bleeding in patients with polyvascular disease enrolled in ROCKET AF. Further studies are needed to understand the optimal management of this high-risk population.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-03-2019
Abstract: The Framingham Risk Score estimates the 10‐year risk of cardiovascular events. However, it performs poorly in older adults. We evaluated the incremental benefit of adding high‐sensitivity cardiac troponin I (hs‐cTnI) to the Framingham Risk Score. The HIMS (Health in Men Study) is a cohort study of community‐dwelling men aged 70 to 89 years in Western Australia. Participants were identified from the electoral roll, with a subset undergoing plasma analysis. Hs‐ cTnI (Abbott Architect i2000 SR ) was measured in 1151 men without prior cardiovascular disease. The Western Australia Data Linkage System was used to identify incident cardiovascular events. After 10 years of follow‐up, 252 men (22%) had a cardiovascular event ( CVE +) and 899 did not (CVE–). The Framingham Risk Score placed 148 (59%) CVE + and 415 (46%) CVE– in the high‐risk category. In CVE – men, adding hs‐ cTnI affected the risk categories of 244 (27.2%) men, with 64.8% appropriately reclassified to a lower and 35.2% to a higher category, which decreased the number of high‐risk men in the CVE– to 39%. In CVE + men, adding hs‐ cTnI affected the risk categories of 61 (24.2%), with 50.8% appropriately reclassified to a higher and 49.2% to a lower category and 82.5% remaining above the 15% risk treatment threshold. The net reclassification index was 0.305 ( P .001). Adding hs‐ cTnI increased the C‐statistic modestly from 0.588 (95% CI , 0.552–0.624) to 0.624 (95% CI , 0.589–0.659) and improved model fit (likelihood ratio test, P .001). Adding hs‐ cTnI to the Framingham Risk Score provided incremental prognostic benefit in older men, especially aiding reclassification of in iduals into a lower risk category.
Publisher: Научный центр неврологии
Date: 2020
Publisher: Royal Society of Chemistry (RSC)
Date: 1992
DOI: 10.1039/DT9920003453
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2001
DOI: 10.1097/00019052-200102000-00015
Abstract: During the past year epidemiological studies have linked elevated plasma total homocysteine concentrations with an increased risk of ischaemic stroke because of arterial disease. Laboratory studies have further explored the mitogenic effects of total homocysteine on vascular smooth muscle, and cytotoxic and thrombophilic effects on vascular endothelium. Also, a clinical trial has shown that lowering total homocysteine by means of multivitamin therapy decreases the rate of abnormal exercise electrocardiography tests. However, it remains to be determined whether lowering total homocysteine prevents hard clinical outcome events, such as stroke and other serious vascular events. An alternative explanation for the observed association between elevated total homocysteine and stroke is a confounding effect of factors associated with hyperhomocysteinaemia (e.g. cigarette smoking, renal impairment, an atherogenic diet, cystine deficiency, folate deficiency) or perhaps even the acute vascular events themselves, whereby the tissue damage temporarily increases total homocysteine levels. The results of ongoing clinical trials in stroke patients to determine the impact of multivitamin therapy on recurrent stroke and other serious vascular events are awaited.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2020
Publisher: BMJ
Date: 20-08-2013
Publisher: Public Library of Science (PLoS)
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 2014
Location: Australia
Location: Australia
Start Date: 2000
End Date: 2002
Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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