ORCID Profile
0000-0002-1049-5129
Current Organisation
Monash University
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Epidemiology | Public Health and Health Services | Other Behavioural And Cognitive Sciences | Other Artificial Intelligence | Health Economics | Preventive Medicine | Other Psychology and Cognitive Sciences | Health Information Systems (Incl. Surveillance) | Artificial Intelligence and Image Processing | Expert Systems | Human Bioethics | Public Health And Health Services Not Elsewhere Classified | Population Trends And Policies | Social Policy And Planning
Preventive medicine | Information processing services | Bioethics | The aged | Health related to ageing | Cardiovascular system and diseases | Child health | Evaluation of health outcomes | Health policy economic outcomes | Productivity | Respiratory system and diseases (incl. asthma) |
Publisher: BMJ
Date: 02-2020
DOI: 10.1136/BMJOPEN-2018-026876
Abstract: This review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin. We conducted a systematic review and exploratory meta-analysis of observational studies. Electronic searches of MEDLINE and Embase, and a manual search of bibliographies was undertaken for studies published to 28 March 2018. Studies were included if: participants were men or women aged ≥18 years the exposure of interest was aspirin and relative risks, ORs and 95% CIs for the risk of fracture or difference (percentage or absolute) in BMD (measured by dual energy X-ray absorptiometry) between aspirin users and non-users were presented. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists for observational studies. Pooled ORs for any fracture and standardised mean differences (SMDs) for BMD outcomes were calculated using random-effects models. Twelve studies met the inclusion criteria and were included in the meta-analysis. Aspirin use was associated with a 17% lower odds for any fracture (OR 0.83, 95% CI 0.70 to 0.99 I 2 =71% six studies n=511 390). Aspirin was associated with a higher total hip BMD for women (SMD 0.03, 95% CI −0.02 to 0.07 I 2 =0% three studies n=9686) and men (SMD 0.06, 95% CI −0.02 to 0.13, I 2 =0% two studies n=4137) although these associations were not significant. Similar results were observed for lumbar spine BMD in women (SMD 0.03, 95% CI −0.03 to 0.09 I 2 =34% four studies n=11 330) and men (SMD 0.08 95% CI −0.01 to 0.18 one study n=432). While the benefits of reduced fracture risk and higher BMD from aspirin use may be modest for in iduals, if confirmed in prospective controlled trials, they may confer a large population benefit given the common use of aspirin in older people.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2009
Publisher: Springer Science and Business Media LLC
Date: 12-2016
Publisher: Elsevier BV
Date: 11-2013
Publisher: S. Karger AG
Date: 1980
DOI: 10.1159/000172986
Abstract: Fungal meningitis is most commonly causes by
Publisher: American Society of Hematology
Date: 20-02-2020
Abstract: In a population-based analysis including a large database restricted to patients over age 70, the authors demonstrate that the A91V polymorphism in the familial hemophagocytic lymphohistiocytosis–related gene is a nonpathological polymorphism that confers no increase in cancer, death, or immunopathology.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.C.6547486.V1
Abstract: Abstract Although aspirin has been considered a promising agent for prevention of colorectal cancer, recent data suggest a lack of benefit among older in iduals. Whether some in iduals with higher risk of colorectal cancer may benefit from aspirin remains unknown. We used a 95-variant colorectal cancer polygenic risk score (PRS) to explore the association between genetic susceptibility to colorectal cancer and aspirin use in a prospective study of 12,609 in iduals of European descent ages ≥70 years, enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) double-blinded, placebo-controlled randomized trial (randomized controlled trial RCT). Cox proportional hazards models were used to assess the association of aspirin use on colorectal cancer, as well as the interaction between the PRS and aspirin treatment on colorectal cancer. Over a median of 4.7 years follow-up, 143 participants were diagnosed with incident colorectal cancer. Aspirin assignment was not associated with incidence of colorectal cancer overall [HR = 0.94 95% confidence interval (CI), 0.68–1.30] or within strata of PRS ( i P /i for interaction = 0.97). However, the PRS was associated with an increased risk of colorectal cancer (HR = 1.28 per SD 95% CI, 1.09–1.51). In iduals in the top quintile of the PRS distribution had an 85% higher risk compared with in iduals in the bottom quintile (HR = 1.85 95% CI, 1.08–3.15). In a prospective RCT of older in iduals, a PRS is associated with incident colorectal cancer risk, but aspirin use was not associated with a reduction of incident colorectal cancer, regardless of baseline genetic risk. Prevention Relevance: There is strong evidence to support prophylactic aspirin use for the prevention of colorectal cancer. However recent recommendations suggest the risk of bleeding in older in iduals outweighs the benefit. We sought to determine whether some older in iduals might still benefit from aspirin based on their genetic susceptibility. /
Publisher: Wiley
Date: 08-2005
DOI: 10.1111/J.1445-2197.2005.03484.X
Abstract: The present study explored a range of variables to identify predictors of mortality and morbidity and to develop prediction models based on these variables. Tools for predicting mortality, hospital length of stay and a patient's destination post-hospital discharge were developed using logistic regression in one dataset (design) and evaluated for prediction performance in a separate dataset (validation). The performance of the mortality model was compared to the trauma and injury severity score (TRISS) and a severity characterization of trauma (ASCOT). The profile of variables contributing to the final prediction models developed from the design dataset varied across the different outcomes of interest although age, injury severity score, development of complications and triage category were common predictors of all three outcomes. The performance of the new mortality prediction model was superior to both TRISS and ASCOT in the validation dataset. Overall, the new models did not meet the prespecified performance criteria. The present study identified key predictors of mortality and morbidity (length of hospital stay and discharge destination). The newly developed mortality model out-performed published trauma scoring methods. However, further development and trial of the new prediction models is required before implementation as definitive audit and benchmarking tools could be recommended.
Publisher: Wiley
Date: 18-03-2014
DOI: 10.1002/CNCR.28641
Abstract: Myelodysplastic syndromes (MDS) appear to be underreported to cancer registries, with important implications for cancer and transfusion support service planning and delivery. Two population-based databases were linked to estimate MDS incidence more accurately. Data from the statewide Victorian Cancer Registry (VCR) and Victorian Admitted Episode Dataset (VAED, capturing all inpatient admissions), in Australia, were linked. Incidence rates were calculated based on VCR reported cases and using additional MDS cases identified in VAED. Differences between reported and nonreported cases were assessed. A multivariate capture-recapture method was used to estimate missed cases. Between 2003 and 2010, 2692 cases were reported to VCR and an additional 1562 cases were identified in VAED. Annual incidence rate for those aged 65 years and older based on VCR was 44 per 100,000 (95% confidence interval [CI] = 43-45 per 100,000) and 68 per 100,000 (95% CI = 67-70 per 100,000) using both data sets. Cases not reported to VCR were more likely to have had previous malignancies recorded in VAED (23% versus 19%, P = .003) and to require red cell transfusion (59% versus 54%, P = .003). Using the multivariate model, an estimated 1292 cases were missed by both data sources: the re-estimate was 5546 (95% CI = 5438-5655) MDS cases, with an annual incidence in those aged 65 or older of 103 per 100,000 (95% CI = 100-106). This study reports a higher incidence of MDS using 2 data sources from a large and well-defined population than reported using cancer registry notifications alone.
Publisher: Springer Science and Business Media LLC
Date: 27-01-2021
Publisher: Springer Science and Business Media LLC
Date: 08-06-2014
DOI: 10.1007/S00408-014-9603-8
Abstract: Lung cancer remains a major disease burden in Victoria (Australia) and requires a complex and multidisciplinary approach to ensure optimal care and outcomes. To date, no uniform mechanism is available to capture standardized population-based outcomes and thereby provide benchmarking. The establishment of such a data platform is, therefore, a primary requisite to enable description of process and outcome in lung cancer care and to drive improvement in the quality of care provided to in iduals with lung cancer. A disease quality registry pilot has been established to capture prospective data on all adult patients with clinical or tissue diagnoses of small cell and non-small cell lung cancer. Steering and management committees provide clinical governance and supervise quality indicator selection. Quality indicators were selected following extensive literature review and evaluation of established clinical practice guidelines. A minimum dataset has been established and training and data capture by data collectors is facilitated using a web-based portal. Case ascertainment is established by regular institutional reporting of ICD-10 discharge coding. Recruitment is optimized by provision of opt-out consent. The collection of a standardized minimum data set optimizes capacity for harmonized population-based data capture. Data collection has commenced in a variety of settings reflecting metropolitan and rural, and public, and private health care institutions. The data set provides scope for the construction of a risk-adjusted model for outcomes. A data access policy and a mechanism for escalation policy for outcome outliers has been established. The Victorian Lung Cancer Registry provides a unique capacity to provide and confirm quality assessment in lung cancer and to drive improvement in quality of care across multidisciplinary stakeholders.
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Springer Science and Business Media LLC
Date: 06-06-2017
DOI: 10.1038/PCAN.2017.28
Abstract: Radical prostatectomy is a common surgical procedure performed to treat prostate cancer. Patient-reported outcomes after surgery include urinary incontinence, erectile dysfunction, decreased quality of life and psychological effects. Predictive tools to assess the likelihood of an in idual experiencing various patient-reported outcomes have been developed to aid decision-making when selecting treatment. A systematic review was undertaken to identify all papers describing tools for the prediction of patient-reported outcome measures in men with prostate cancer treated with radical prostatectomy. To be eligible for inclusion, papers had to provide a summary measure of accuracy. PubMed and EMBASE were searched from July 2007. Title/abstract screening, and full-text review were undertaken by two reviewers, while data extraction and critical appraisal was performed by a single reviewer. The search strategy identified 3217 potential studies, of which 191 progressed to full-text review and 14 were included. From these studies, 27 tools in total were identified, of which 18 predicted urinary symptoms, six predicted erectile function and one predicted freedom from a group of three outcomes ('trifecta') (biochemical recurrence, incontinence and erectile dysfunction). On the basis of tool accuracy (>70%) and external validation, two tools predicting incontinence and two tools predicting erectile dysfunction are ready for implementation. A small number of tools for the prediction of patient-reported outcomes following radical prostatectomy have been developed. Four tools were found to have adequate accuracy and validation and are ready for implementation for the prediction of urinary incontinence and erectile dysfunction.
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/IMJ.13528
Abstract: When registries collect accurate clinical data over time, they can act as fundamental support structures for patients and their families and powerful cost-effective instruments to support clinical trials and translational research to improve quality of care, quality of life and survival. Registries are critical for rare diseases (RD) with low prevalence and propensity for variation in treatment and outcomes. Rare Voices Australia is leading a call for action to the research and clinical community to prioritise RD data collection and develop an integrated RD Registry strategy for Australia. Financial, operational and governance challenges exist for establishing and maintaining RD registries. As a multidisciplinary team whose interests converge on RD, we highlight the need for the establishment of an Australian RD Registry Alliance. This 'umbrella' organisation will: (i) bring together existing RD registries across Australia (ii) establish National RD Registry Standards to support interoperability and cohesion across registries (iii) develop strategies to attract sustainable funding from government and other sources to maximise the utility of existing RD registries and support the development of new RD registries. The most important role for the Alliance would be to use the RD registries for translational research to address current knowledge gaps about RD and to improve the care for the over 1.4 million Australians estimated to live with RD.
Publisher: Massachusetts Medical Society
Date: 02-05-2019
DOI: 10.1056/NEJMC1901774
Publisher: Elsevier BV
Date: 1988
DOI: 10.1016/S0168-8227(88)80008-1
Abstract: This study has investigated the relationship of glycaemic control, blood pressure and proteinuria to early renal dysfunction in a cohort of 50 type I and 65 type II diabetics, with renal function ranging from normal to mildly impaired (serum creatinine less than 0.2 mM). Repeated measurements were made over a mean interval of 7 years and mean data from each subject were analysed by stepwise multiple linear regression. This enabled associations to be determined independently of the confounding influence of age and duration of disease. In type I diabetics, mean creatinine clearance was inversely related to systolic blood pressure (P less than 0.001), glycosylated haemoglobin (P less than 0.05), fasting plasma glucose (P less than 0.05) and to the renal clearance of albumin (P less than 0.001), transferrin (P less than 0.01) and IgG (P less than 0.05). By contrast, in type II diabetics, none of these associations were significant. No significant relationships were found with the rate of decline of creatinine clearance in either type of diabetic. Further studies will be needed to determine whether the changes in blood pressure and glycaemic control precede or follow the development of renal disease. However, these findings raise the possibility of a difference in the pathogenesis of renal disease in type I and type II diabetes.
Publisher: MDPI AG
Date: 13-02-2023
Abstract: Background: Optimism is a disposition characterised by positive future expectancies, while pessimism is characterised by expecting the worst. High optimism and low pessimism promote the health of older adults and may potentiate full engagement in life. We identified socioeconomic, behavioural, and social factors associated with optimism and pessimism in older adults. Methods: Participants included 10,146 community-dwelling, apparently healthy Australian adults aged 70 years and over from the ASPREE Longitudinal Study of Older Persons (ALSOP). Optimism and pessimism were measured using the revised Life Orientation Test. Cross-sectional ordinal logistic regression was used to determine the socioeconomic, behavioural, and social health factors associated with optimism and pessimism. Results: Higher education, greater physical activity, lower loneliness, and volunteering were associated with higher optimism and lower pessimism. Low social support was associated with higher pessimism. Higher socioeconomic advantage, greater income, and living alone were associated with lower pessimism. Women were more optimistic and less pessimistic than men. The association of age, smoking status, and alcohol consumption with optimism and pessimism differed for men and women. Conclusions: Factors associated with higher optimism and lower pessimism were also those demonstrated to support healthy ageing. Health-promotion action at the in idual level (e.g., smoking cessation or regular physical activity), health professional level (e.g., social prescribing or improving access and quality of care for all older adults), and community level (e.g., opportunities for volunteer work or low-cost social activities for older adults) may improve optimism and reduce pessimism, possibly also promoting healthy ageing.
Publisher: Informa UK Limited
Date: 30-01-2023
Publisher: Springer Science and Business Media LLC
Date: 07-1993
Abstract: The adverse effects of low-dose aspirin (100 mg daily) in the elderly were studied over a 12-month period in a double-blind, randomized, placebo-controlled trial of 400 subjects who were 70 years of age or older and had no preexisting major vascular diseases at the time of entry. Subjects were randomized so that 200 subjects received low-dose enteric-coated aspirin (100 mg daily) and 200 subjects received placebo. Compliance with medication, assessed by pill count, was 86%. Gastrointestinal symptoms were reported by 18% (n = 36) of participants receiving aspirin and 13% (n = 26) of those receiving placebo. Clinically evident gastrointestinal bleeding occurred in 3% (n = 6) of subjects receiving aspirin and none receiving placebo. Aspirin-treated subjects had a significant decrease in mean hemoglobin levels of 0.33 gm/dl during the 12-month study period, which was significantly greater than the decrease in the placebo-treated group (0.11 gm/dl p < 0.05). These rates of unwanted symptoms are comparable with previous studies that used higher doses of aspirin. Until the risk-benefit trade-off from the use of low-dose aspirin in the elderly is established with an appropriate clinical trial, caution should be exercised when this compound is used for primary prevention of cardiovascular disease in this age group.
Publisher: Oxford University Press (OUP)
Date: 1995
DOI: 10.1093/OXFORDJOURNALS.EPIREV.A036199
Abstract: With both stenosis and aneurysm, repairing a severely tortuous and coarcted aorta can present certain difficulties. The advent of hybrid arch frozen elephant trunk techniques, as well as other endovascular solutions, has produced safer surgical repair methods for such cases. We present the reconstruction and repair of a Type-1 thoracoabdominal aortic aneurysm using a staged approach in less-than-optimal anatomy. Interventions included hybrid frozen elephant trunk, balloon dilation, and thoracic endovascular repair.
Publisher: Wiley
Date: 2009
Publisher: Wiley
Date: 12-1999
DOI: 10.1046/J.1440-1606.1999.00240.X
Abstract: To describe the methodology of eye examination and the baseline eye characteristics of the Vitamin E, Cataract and Age-Related Maculopathy (VECAT) study participants. A s le of volunteers from an urban area of Melbourne, Australia, were recruited to participate in a randomized, controlled trial investigating the effect of vitamin E on the development of cataract and age-related maculopathy Standardized eye examinations involved clinical assessment, which included Wilmer grading of the lens, digital photography of the lens with Nidek EAS-1000 lens camera and stereo photography of the macular area with the Nidek 3-DX fundus camera. All cases of ophthalmic findings were determined on the basis of pathology in the worse eye. Most eyes were free from abnormalities. The most frequent findings were cataract and age-related macular changes. Nuclear cataract (nuclear opacity grade >2) was present in 4.5%, cortical cataract (cortical opacity grade >2) in 14.3% and posterior subcapsular cataract in 3.0% of participants in addition, coronary cataract was observed in 13.6%. Soft drusen larger than 125 pm were found in 11.4%, retinal pigment epithelium changes in 9.5%, epiretinal membrane in 6.6% and age-related macular degeneration in 0.5% of participants. Due to the selection criteria, the majority of participants had clear or minor lens changes and/or minor retinal age-related changes. Precise instrumental documentation will allow an accurate assessment of the incidence and dynamics of these changes throughout 4 years of observation.
Publisher: Elsevier BV
Date: 02-2004
DOI: 10.1016/S0967-5868(03)00148-6
Abstract: Non-reimbursed 'out of pocket' costs to stroke patients have not been included in existing cost of illness studies. We aimed to determine the nature and magnitude of 'out of pocket' costs to stroke patients during the first year after stroke. 'Out of pocket' costs during the first year after stroke were documented for 165 persons registered in a community-based stroke incidence study during 1996/1997. Virtually all cases reported some 'out of pocket' costs. The average cost over 12 months was A$1110. The highest cost items were home modifications, aids and equipment. The most commonly incurred expense was for prescription medications. Total 'out of pocket' costs incurred by first-ever stroke patients in Australia in 1997 were estimated to be A$29 million or 5% of the total cost of stroke. The majority of 'out of pocket' costs relate to post-acute care aimed at minimising disability and handicap rather than to 'acute' healthcare.
Publisher: Oxford University Press (OUP)
Date: 06-04-2016
DOI: 10.1093/ASJ/SJW055
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.INJURY.2006.07.015
Abstract: Risk-adjusted survival rates have been the principle mode of comparison between trauma systems. In mature trauma systems, it is possible that there will be further improvements in survival but these are likely to be small. In the future, the largest gains will come from quality of life and improved function of the survivors. The issues related to measuring quality of survival for trauma systems are reviewed, including feasibility, ethical considerations, risk adjustment of outcomes of survivors, and challenges for selection of instruments and administration. In addition, the preliminary experiences of measuring outcomes in survivors through the Victorian State Trauma Registry are discussed. Although function and quality of life have been identified as important factors to measure in trauma populations, a standardised protocol has not been established. The experience in Victoria suggests that monitoring of population-based outcomes in survivors is feasible and may create the basis for benchmarking the level of morbidity in survivors.
Publisher: The Endocrine Society
Date: 13-08-2019
Abstract: There is a lack of understanding of what is normal in terms of sex steroid levels in older women. To determine whether sex steroid levels vary with age in and establish reference ranges for women years of age. Cross-sectional, community-based study. Included 6392 women ≥70 years of age. Sex steroids measured by liquid chromatography–tandem mass spectrometry. A reference group, to establish sex steroid age-specific reference ranges, excluded women using systemic or topical sex steroid, antiandrogen or glucocorticoid therapy, or an antiglycemic agent. The reference group of 5326 women had a mean age of 75.1 (±4.2) years, range of 70 to 94.7 years. Median values (range) were 181.2 pmol/L (3.7 to 5768.9) for estrone (E1), 0.38 nmol/L (0.035 to 8.56) for testosterone (T), 2.60 nmol/L (0.07 to 46.85) for dehydroepiandrosterone (DHEA), and 41.6 nmol/L (2.4 to 176.6) for SHBG. Estradiol and DHT were below method sensitivity in 66.1% and 72.7% of the s les, respectively. Compared with women aged 70 to 74 years, women aged ≥85 years had higher median levels of E1 (11.7%, P = 0.01), T (11.3%, P = 0.02), and SHBG (22.7%, P 0.001) and lower DHEA (30% less, P 0.001). Women with overweight and obesity had higher E1 (P 0.001) and T (P 0.03) and lower SHBG (P 0.001) than did women with normal body mass index. Smokers had 17.2% higher median T levels (P = 0.005). From the age of 70 years, T and E1 increase with age, despite a steady decline in DHEA. Whether E1 and T are biomarkers for longevity or contribute to healthy aging merits investigation.
Publisher: Public Library of Science (PLoS)
Date: 22-12-2017
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.AAP.2012.03.024
Abstract: To describe trends in transport mortality for a range of common transport types in Australia over a 30-year period (1975-1977 to 2005-2007). Mortality data on all-cause and transport-related causes of death were supplied by the Australian Institute of Health and Welfare (AIHW). Mortality rates, expected number of deaths and probabilities of death were compared for three time periods: 1975-1977, 1990-1992 and 2005-2007. There were significant decreasing trends between 1975-1977 and 2005-2007 in all-cause and most other transport mortality types for both men and women. There were significant reductions in the contribution of transport-related mortality to all-cause mortality however the difference in mortality between men and women (higher for men) changed little over the evaluated period. Between 1975-1977 and 2005-2007 there were marked reductions in key causes of transport-related mortality amongst Australian adults, and the reductions in transport-related mortality exceeded reductions in all-cause mortality. The reductions could be attributed to better preventive measures and improved medical treatment for people involved in transport crashes. Although there is scope for further improvement, the reductions are evidence of a success in the prevention of crashes and the medical treatment of crash victims.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1987
DOI: 10.1097/00005344-198708000-00006
Abstract: Prazosin and terazosin are two alpha 1-adrenoceptor blocking agents, their principal difference being the longer half-life of terazosin. The present study was carried out to determine if elderly subjects are different from the young in their pharmacokinetic handling of these two drugs and if age influences the blood pressure response to each drug. Ten young healthy subjects (aged 19-30 years) and five older healthy subjects (aged 54-62 years) received 1 or 2 mg terazosin, 1 or 2 mg prazosin, or placebo 1 week apart according to a 5 X 5 Latin square design. Concentrations of prazosin and terazosin were measured using a high-performance liquid chromatographic procedure with a detection limit of approximately 0.25 ng/ml. Pharmacokinetic parameters of prazosin were virtually the same in both groups, whereas mean terazosin plasma concentrations were higher in the older group and pharmacokinetic analysis revealed higher peak plasma concentrations and a longer terminal elimination half-life. There was no evidence of increased sensitivity to the hypotensive action of the drug, as peak upright blood pressure falls were similar in the two groups. Symptoms of dizziness in the upright position were also less common. In view of their lack of sedative effects and minimal metabolic disturbances, further studies should be conducted to assess the suitability of these drugs as monotherapy for hypertension in elderly patients.
Publisher: Elsevier BV
Date: 2018
Publisher: Wiley
Date: 2011
DOI: 10.1038/OBY.2010.149
Abstract: The nature of excess body weight may be changing over time to one of greater central adiposity. The aim of this study is to determine whether BMI and waist circumference (WC) are increasing proportionately among population subgroups and the range of bodyweight, and to examine the public health implications of the findings. Our data are from two cross-sectional surveys (the US National Health and Nutrition Examination Studies (NHANES) in 1988-1994 (NHANES III) and 2005-2006), from which we have used s les of 15,349 and 4,176 participants aged ≥20 years. Between 1988-1994 and 2005-2006 BMI increased by an average of 1.8 kg/m² and WC by 4.7 cm (adjusted for sex, age, race-ethnicity, and education). The increase in WC was more than could be attributed simply to increases in BMI. This independent increase in WC (of on average, 0.9 cm) was consistent across the different BMI categories, sexes, education levels, and race-ethnicity groups. It occurred in younger but not older age groups. Overall in each BMI category, the prevalence of low-risk WC decreased and the prevalence of increased-risk or substantially increased-risk WC increased. These results suggest that the adverse health consequences associated with obesity may be increasingly underestimated by trends in BMI alone. Since WC is closely linked to adverse cardiovascular outcomes, it is important to know the prevailing trends in both of these parameters.
Publisher: Informa UK Limited
Date: 26-02-2020
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.INJURY.2005.10.016
Abstract: Despite the vast number of traumatic injuries that are orthopaedic in nature, comprehensive epidemiological data that characterise orthopaedic trauma are limited. The aim of this study was to investigate the nature of orthopaedic trauma admitted to adult Level 1 Trauma Centres. Data were obtained from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), which includes all patients with orthopaedic trauma admitted to the two adult Level 1 Trauma Centres in Victoria (Australia). Information was collected from the medical record and hospital databases on patients' demographics and injury event, diagnoses and management. Data were analysed on 784 patients recruited between August 2003 and March 2004. Patients were mainly young (<65 years) (70.7%), male (59.1%) and injured in a transport collision (51.3%). Fractures of the femur (23.7%) and spine (23.5%) were the most common injuries and were predominately managed with operative (87.6%) and conservative (78.8%) methods, respectively. Differences in most parameters were evident between younger ( or =65 years) patients. This study presents epidemiological data on patients with orthopaedic trauma who were admitted to adult Level 1 Trauma Centres. This information is critical for the future monitoring and evaluation of the outcomes of orthopaedic trauma.
Publisher: BMJ
Date: 10-1996
Abstract: This study aimed to explore lived experience and risk reduction behaviors among sero-negative, discordant male partners living with HIV-positive women in Addis Ababa, Ethiopia, 2019. A phenomenological study was conducted to explore lived experience and risk reduction behaviors. The study participants were purposively selected 13 sero-negative male partners living with HIV-positive women. An in-depth interview was used to explore important information. A semi-structured interview guide was used to execute the in-depth interview. The in-depth interview was analyzed thematically through the support of ATLAS-ti 7 software. Scientific explanation of discordant result is not well understood rather, it is associated with religious, cultural, natural resistance, and passive carrier explanations. Sero-negative partners faced several challenges and lived dilemmatic life related to partner mood or behavioral change, maintaining the marital relationship, the desire of child, psychosocial, sexual life, and lack of support system. Risk reduction behaviors like condom use, safe sex practice, preventing sexually transmitted infection, avoiding substance use, continuous checkup and follow-up were not well reflected in their lived experience and were poorly understood. Personalized use of sharp materials to avoid blood contact and support of a partner in the proper use of ART drugs were positively reported risk reduction behaviors. Sero-negative partners need special attention just as HIV-positive partners in couples with the discordant result. Life suffering is not limited to HIV-positive partners, rather sero-negative partners also faced several challenges and dilemmatic life. HIV transmission risk reduction behavior is not well established and understood.
Publisher: Wiley
Date: 31-10-2003
DOI: 10.1046/J.1445-5994.2003.00420.X
Abstract: Plasma homocysteine is elevated in patients with end-stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient. To determine whether 1 mg vitamin B12 lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid. Twenty-eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals. Fasting plasma total homocysteine, folic acid, red-cell folate, vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months. Both the two groups were well matched with respect to total homocysteine levels, folic acid, red-cell folate and vitamin B12 levels. Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L 95% confidence interval (CI) 103.0-332.5 P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 micromol/L 95% CI -4.44-10.61 P= 0.406). The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High-dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined.
Publisher: Springer Science and Business Media LLC
Date: 06-1989
DOI: 10.2165/00003088-198916060-00004
Abstract: The pharmacokinetics of doxazosin were determined in hypertensive subjects after a single dose of 1 mg, and at steady-state while receiving doses of 1, 2, 4 and 8 mg of the drug daily. Chlorothiazide 500 mg once daily was administered as additional therapy throughout the study. After a single dose doxazosin was rapidly absorbed, with peak plasma drug concentrations (Cmax) occurring after 2.1 +/- 0.4 hours. The elimination half-life in plasma was 10.7 +/- 1.2 hours. These parameters remained essentially unchanged during maintenance administration of doxazosin at each of the dose levels. Calculations of Cmax and area under the concentration-time curve (AUC0----infinity) indicated that the pharmacokinetic disposition of the drug remained linear over the dose range 1 to 8 mg.
Publisher: Wiley
Date: 04-1982
DOI: 10.1111/J.1365-2125.1982.TB01935.X
Abstract: Polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE), which is a piezoelectric, biocompatible polymer, holds promise as a scaffold in combination with Schwann cells (SCs) for spinal cord repair. Piezoelectric materials can generate electrical activity in response to mechanical deformation, which could potentially stimulate spinal cord axon regeneration. Our goal in this study was to investigate PVDF-TrFE scaffolds consisting of aligned fibers in supporting SC growth and SC-supported neurite extension and myelination in vitro. Aligned fibers of PVDF-TrFE were fabricated using the electrospinning technique. SCs and dorsal root ganglion (DRG) explants were co-cultured to evaluate SC-supported neurite extension and myelination on PVDF-TrFE scaffolds. PVDF-TrFE scaffolds supported SC growth and neurite extension, which was further enhanced by coating the scaffolds with Matrigel. SCs were oriented and neurites extended along the length of the aligned fibers. SCs in co-culture with DRGs on PVDF-TrFE scaffolds promoted longer neurite extension as compared to scaffolds without SCs. In addition to promoting neurite extension, SCs also formed myelin around DRG neurites on PVDF-TrFE scaffolds. This study demonstrated PVDF-TrFE scaffolds containing aligned fibers supported SC-neurite extension and myelination. The combination of SCs and PVDF-TrFE scaffolds may be a promising tissue engineering strategy for spinal cord repair.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 12-11-2017
DOI: 10.1111/HEX.12636
Publisher: Elsevier BV
Date: 03-2018
Publisher: S. Karger AG
Date: 1999
DOI: 10.1159/000015893
Abstract: To determine whether smoking contributes to the risk of primary intracerebral haemorrhage (ICH) a case-control study was carried out on 331 consecutive cases of first-episode ICH as verified by computed tomography. Patients were age- and sex-matched to 331 community-based controls. Unlike other forms of stroke where smoking is an established risk factor, there was no increase in risk of ICH with smoking in this study (odds ratio, OR, 1.07, 95% confidence interval, CI, 0.63–1.81). Similar ratios were obtained for past and current smokers. Neither the amount smoked nor the duration of smoking were associated with ICH. Further investigation, however, revealed an interaction between smoking and hypertension on the risk of ICH that was similar regardless of the amount of cigarettes currently smoked and was largely seen to be a phenomenon in men (OR 8.13, 95% CI 2.04–32.42). This interaction is a new finding, but the post-hoc nature of this analysis requires that it be further tested, preferably in a large prospective study.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2001
Abstract: Background and Purpose — Population-based stroke incidence studies are the only accurate way to determine the number of strokes that occur in a given society. Because the major stroke subtypes have different patterns of incidence and outcome, information on the natural history of stroke subtypes is essential. The purpose of the present study was to determine the incidence and case-fatality rate of the major stroke subtypes in a geographically defined region of Melbourne, Australia. Methods — All suspected strokes that occurred among 133 816 residents of suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and assessed. Multiple overlapping sources were used to ascertain cases, and standard criteria for stroke and case-fatality were used. Stroke subtypes were defined by CT, MRI, and autopsy. Results — Three hundred eighty-one strokes occurred among 353 persons during the study period, with 276 (72%) being first-ever-in-a-lifetime strokes. Of these, 72.5% (95% CI 67.2% to 77.7%) were cerebral infarction, 14.5% (95% CI 10.3% to 18.6%) were intracerebral hemorrhage, 4.3% (95% CI 1.9% to 6.8%) were subarachnoid hemorrhage, and 8.7% (95% CI 5.4% to 12.0%) were stroke of undetermined type. The 28-day case-fatality rate was 12% (95% CI 7% to 16%) for cerebral infarction, 45% (95% CI 30% to 60%) for intracerebral hemorrhage, 50% (95% CI 22% to 78%) for subarachnoid hemorrhage, and 38% (95% CI 18% to 57%) for stroke of undetermined type. Conclusions — The overall distribution of stroke subtypes and 28-day case-fatality rates are not significantly different from those of most European countries or the United States. There may, however, be some differences in the incidence of subtypes within Australia.
Publisher: Elsevier BV
Date: 03-1992
DOI: 10.1016/0140-6736(92)90837-S
Abstract: During the course of a urinary tract infection, substantial levels of nitric oxide and reactive nitrogen intermediates are generated. We have found that many uropathogenic strains of Escherichia coli display far greater resistance to nitrosative stress than the K-12 reference strain MG1655. By selecting and screening for uropathogenic E. coli transposon mutants that are unable to grow in the presence of acidified nitrite, the cadC gene product was identified as a key facilitator of nitrosative stress resistance. Mutation of cadC, or its transcriptional targets cadA and cadB, results in loss of significant production of the polyamine cadaverine and increased sensitivity to acidified nitrite. Exogenous addition of cadaverine or other polyamines rescues growth of cad mutants under nitrosative stress. In wild-type cells, the concentration of cadaverine produced per cell is substantially increased by exposure to acidified nitrite. The mechanism behind polyamine-mediated rescue from nitrosative stress is unclear, but it is not attributable solely to chemical quenching of reactive nitrogen species or reduction in mutation frequency.
Publisher: Wiley
Date: 06-2004
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.JCLINEPI.2011.06.017
Abstract: At the time of licensing by regulatory agencies, the full range of risks and possible adverse drug reactions associated with a medication is rarely fully realized. This commentary aims to describe the role of registries as useful components of postmarketing pharmacovigilance systems for monitoring highly specialized medications associated with significant financial costs. We consider the limitations of traditional pharmacovigilance programs and discuss the strengths, limitations, and uses of registries in postmarketing pharmacovigilance systems. Registries have become increasingly appealing in postmarketing surveillance of medications however, their exact role continues to evolve. Key registry projects, including the Prospective Immunogenicity Surveillance Registry, British Society for Rheumatology Biologics Register, Australian Rheumatology Association Database, the Haemostasis Registry, and the Bosentan Patient Registry highlight the value of registries for monitoring the incidence of rare adverse events. Although often limited by lack of a control group and the need for complete case ascertainment to maintain data integrity, registries are a useful component of postmarketing pharmacovigilance systems for monitoring highly specialized medications associated with significant financial costs.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JTCVS.2015.03.015
Abstract: To assess whether introduction of universal leukodepletion (ULD) of red blood cells (RBCs) for transfusion was associated with improvements in cardiac surgery patient outcomes. Retrospective study (2005-2010) conducted at 6 institutions. Associations between leukodepletion and outcomes of mortality, infection, and acute kidney injury (AKI) were modeled by logistic regression, and intensive care unit length of stay (LOS) in survivors was explored using linear regression. To examine trends over time, odds ratios (ORs) for outcomes of transfused were compared with nontransfused patients, including a comparison with nontransfused patients who were selected based on propensity score for RBC transfusion. We studied 14,980 patients, of whom 8857 (59%) had surgery pre-ULD. Transfusions of RBCs were made in 3799 (43%) pre-ULD, and 2525 (41%) post-ULD. Administration of exclusively leukodepleted, versus exclusively nonleukodepleted, RBCs was associated with lower incidence of AKI (adjusted OR 0.80, 95% confidence interval [CI] 0.65-0.98, P = .035), but no difference in mortality or infection. For post-ULD patients, no difference was found in mortality (OR 0.96, 95% CI 0.76-1.22, P = .76) or infection (OR 0.91, 95% CI 0.79-1.03, P = .161) however, AKI was reduced (OR 0.79 95% CI 0.68-0.92, P = .003). However, ORs for post-ULD outcomes were not significantly different in nontransfused, versus transfused, patients. Furthermore, those who received exclusively nonleukodepleted RBCs were more likely to have surgery post-ULD. Universal leukodepletion was not associated with reduced mortality or infection in transfused cardiac surgery patients. An association was found between ULD and reduced AKI however, this reduction was not significantly different from that seen in nontransfused patients, and other changes in care most likely explain such changes in renal outcomes.
Publisher: Springer Science and Business Media LLC
Date: 08-2010
DOI: 10.2165/11536350-000000000-00000
Abstract: in order to evaluate the cost effectiveness of preventive strategies for myocardial infarction (MI), direct cost estimates are required. However, Australian-specific cost estimates for MI are not available. the CosMIC (Cost of Myocardial Infarction to the Community) in Australia study was designed to determine the resource use and estimate the direct costs associated with MI in the Australian Health Care System. This information could subsequently be used in cost-effectiveness evaluations. a prospective, multicentre survey was undertaken to investigate the costs associated with the initial hospitalization and the 12-month sequelae for patients with a first-ever MI. During the recruitment period 312 patients with MI from ten hospitals met the eligibility criteria. Of the 141 who consented to participate and were enrolled, three were withdrawn and 138 were included in the final analysis. Detailed data were collected for 12 months after the index hospitalization from several overlapping sources. All costs were considered from the point of view of total direct cost of care, i.e. regardless of who generated or paid for the service. the mean length of hospital stay for the initial acute episode was 7.4 days and the mean cost was $A10 934 (95% confidence interval [CI] 9588, 12 280) based on 2005 Australian dollars. There were 127 cardiac-related readmissions for 55 (40%) patients and the mean length of stay was 2.6 days. The mean total direct cost of an MI per patient was $A20 502 (95% CI 18 428, 22 576). The majority of the costs were for hospitalizations (initial and readmissions), which accounted for 77% of the total 12-month costs, whilst hospitalization costs for the initial acute event accounted for 53% of all costs. During the 12-month follow-up period, out-of-hospital medical service costs (Medicare Benefits Schedule services) contributed to 7% of the total costs incurred, medications 6%, ambulance costs 3% and all other outpatient services and carer costs 7%. the CosMIC study addresses the significant uncertainty associated with MI cost-of-illness data in Australia by providing an estimation of direct costs associated with MI in an Australian population. These direct costs can be used to determine the cost effectiveness of prevention strategies.
Publisher: Springer Science and Business Media LLC
Date: 05-1988
DOI: 10.2165/00003088-198814050-00003
Abstract: We compared a least squares regression method, used prospectively to in idualise the intravenous aminophylline and oral theophylline dosage of 48 patients, with 3 other pharmacokinetic methods - Chiou's, the steady-state clearance and the Bayesian - used retrospectively to analyse the same patient data. Methods were compared on the basis of the similarity of their parameter estimates and the accuracy with which serum concentrations during subsequent intravenous and oral therapy could be forecast, assuming each method's parameter estimates. The least squares and Bayesian programs were able to fit data from all but 4 and 2 patients, respectively. Mean absolute prediction errors were of the order of 20% for serum concentrations during intravenous therapy, and of the order of 40% for serum concentrations during oral therapy. The accuracy of the least squares, Bayesian and steady-state clearance methods were similar, but the accuracy of Chiou's method was comparable only when the 2 serum concentrations needed for the method were measured between 11 and 17 hours apart an interval which corresponds to the 1.0 to 1.5 half-lives previously suggested as desirable for implementation of the Chiou method.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.AMJCARD.2017.04.049
Abstract: We estimated the inpatient resource use for a Fontan patient from birth to adulthood and explored factors that might induce cost differences (2014 US dollar). Inpatient costing records from 4 hospitals with greatest numbers of Fontan patients in Australia and New Zealand were linked with the Fontan registry database. Inpatient records between July 1995 and September 2014 for 420 Fontan patients were linked, and the most frequent primary diagnoses were hypoplastic left heart syndrome (20.7%), tricuspid atresia (19.7%), and double inlet left ventricle (17.1%). The mean hospital cost for a Fontan patient from birth to 18 years of age was estimated to be $390,601 (95% confidence interval [CI] $264,703 to $516,499), corresponding to 164 (95% CI 98 to 231) inpatient days. The cost incurred from birth through to Fontan completion (the staged procedures period) was $219,482 (95% CI $202,410 to $236,553) and the cost thereafter over 15 years was $146,820 (95% CI $44,409 to $249,231), corresponding to 82 (95% CI 72 to 92) and 65 (95% CI 18 to 112) inpatient days, respectively. Costs were higher in male and hypoplastic left heart syndrome patients in the staged procedures period (p <0.001). Having fenestration was associated with higher costs in the staged procedures period (p <0.001) and lower cost after Fontan over 15 years (p = 0.66). In conclusion, patients with single ventricle congenital heart disease continue to demand considerable inpatient resources after the staged procedures period. Over 40% of the pediatric hospital costs for Fontan patients were estimated to occur after the last planned surgery.
Publisher: Wiley
Date: 04-05-2018
DOI: 10.1111/ANS.13954
Abstract: The Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) score is a simple post-operative risk assessment tool predicting disease recurrence after radical prostatectomy, which is easily calculated using available clinical data. To be widely useful, risk tools require multiple external validations. We aimed to validate the CAPRA-S score in an Australian multi-institutional population, including private and public settings and reflecting community practice. The study population were all men on the South Australian Prostate Cancer Clinical Outcomes Collaborative Database with localized prostate cancer diagnosed during 1998-2013, who underwent radical prostatectomy without adjuvant therapy (n = 1664). Predictive performance was assessed via Kaplan-Meier and Cox proportional regression analyses, Harrell's Concordance index, calibration plots and decision curve analysis. Biochemical recurrence occurred in 342 (21%) cases. Five-year recurrence-free probabilities for CAPRA-S scores indicating low (0-2), intermediate (3-5) and high risk were 95, 79 and 46%, respectively. The hazard ratio for CAPRA-S score increments was 1.56 (95% confidence interval 1.49-1.64). The Concordance index for 5-year recurrence-free survival was 0.77. The calibration plot showed good correlation between predicted and observed recurrence-free survival across scores. Limitations include the retrospective nature and small numbers with higher CAPRA-S scores. The CAPRA-S score is an accurate predictor of recurrence after radical prostatectomy in our cohort, supporting its utility in the Australian setting. This simple tool can assist in post-surgical selection of patients who would benefit from adjuvant therapy while avoiding morbidity among those less likely to benefit.
Publisher: Wiley
Date: 11-1994
Abstract: In a population-based case-control study of 416 incident gliomas in adults carried out in Melbourne, Australia, between 1987 and 1991, 409 age-sex-matched case-control pairs (243 male and 166 female) had adequate data available to examine associations between the dietary intake of N-nitroso compounds, N-nitroso precursors, other nutrients including N-nitroso inhibitors, and the risk of glioma. Dietary intakes were based on the reported frequency of consumption of 59 food items. Increased odds ratio (OR) were observed in males who consumed high levels of bacon, corned meats, apples, melons and oil. OR less than unity were observed in men consuming cabbage and cola drinks, and in women who consumed wholegrain bread, pasta, corned meat, bananas, cauliflower, brocoli, cola drinks and nuts. Generally, N-nitroso associations were greater in men and micronutrient associations were greater in women. Elevated OR in men, but not women, were associated with the intake of N-nitroso dimethylamine (NDMA), retinol and vitamin E. The intake of nitrate (largely of vegetable origin) was protective in women but not in men. When analyzed using multiple logistic regression, the association with NDMA intake in males was not modified by dietary micronutrient intakes. In females, beta carotene alone, though not directly associated with risk, modified the effect of NDMA. On balance, this study added only limited support to the N-nitroso hypothesis of glial carcinogenesis.
Publisher: BMJ
Date: 20-10-2011
Abstract: Emergency departments (EDs) in many developed countries are experiencing increasing pressure due to rising numbers of patient presentations and emergency admissions. Reported increases range up to 7% annually. Together with limited inpatient bed capacity, this contributes to prolonged lengths of stay in the ED disrupting timely access to urgent care, posing a threat to patient safety. The aim of this review is to summarise the findings of studies that have investigated the extent of and the reasons for increasing emergency presentations. To do this, a systematic review and synthesis of published and unpublished reports describing trends and underlying drivers associated with the increase in ED presentations in developed countries was conducted. Most published studies provided evidence of increasing ED attendances within developed countries. A series of inter-related factors have been proposed to explain the increase in emergency demand. These include changes in demography and in the organisation and delivery of healthcare services, as well as improved health awareness and community expectations arising from health promotion c aigns. The factors associated with increasing ED presentations are complex and inter-related and include rising community expectations regarding access to emergency care in acute hospitals. A systematic investigation of the demographic, socioeconomic and health-related factors highlighted by this review is recommended. This would facilitate untangling the dynamics of the increase in emergency demand.
Publisher: Wiley
Date: 11-2013
Publisher: Swets & Zeitlinger Publishers
Date: 1999
DOI: 10.1076/OPEP.6.3.181.1502
Abstract: (1) To develop the methodology for the grading of macular one-frame stereoslides and to assess the reliability of the system. (2) To determine the prevalence of soft drusen (> 63 microm) and pigment abnormalities synonymous with age-related maculopathy (ARM) at baseline, in a clinical trial of volunteers aged between 55 and 80 years of age. (3) To ascertain the power of the study to detect the 4-year incidence and progression of ARM in vitamin E versus placebo treated participants, given the baseline prevalence. The 1204 participants enrolled in the Vitamin E, Cataract, and Age-related Maculopathy Study (VECAT) had colour stereoslides of their fundus taken using the Nidek 3-DX mydriatic fundus camera. The stereoslides were graded by two masked graders according to the "International Classification System for ARM and AMD". Assessment of inter- and intra-observer reliability was carried out on a regular basis on 15% of randomly selected slides. Anticipated rates of incidence and progression were based on results reported by the Beaver Dam Eye Study and the Chesapeake Bay Waterman Study. Power estimations were determined using the "nQuery Advisor" software program. Analyses were carried out on the worse affected eye. Inter-observer reliability was moderate to substantial (Kappa 0.5-0.88) whilst intra-observer agreement was high (0.6-1.0). The prevalence of any soft drusen was 32%. Significant associations were found between soft large indistinct drusen, hypopigmentation, hyperpigmentation and age (p = 0.0001, 0.024 and 0.0001, respectively). The study has at least 87% power to detect an odds ratio equal to two for the progression of soft distinct, soft indistinct, hyperpigmentation and hypopigmentation. The VECAT study methodology appears to be highly reliable and to have sufficient power to detect the differences in the four-year progression of soft distinct and indistinct drusen and pigment abnormalities between the treatment groups.
Publisher: Wiley
Date: 10-2011
DOI: 10.1111/J.1445-5994.2011.02534.X
Abstract: Patients with established coronary heart disease (CHD) are at the highest risk of further events. Despite proven therapies, secondary prevention is often suboptimal. General practitioners (GPs) are in an ideal position to improve secondary prevention. To contrast management of cardiovascular risk factors in patients with established CHD in primary care to those in clinical guidelines and according to gender. GPs throughout Australia were approached to participate in a programme incorporating a disease management software (mdCare) program. Participating practitioners (1258 GPs) recruited in idual patients whose cardiovascular risk factor levels were measured. The mdCare programme included 12,509 patients (58% male) diagnosed with CHD. Their mean age was 71.7years (intra-quartile range 66-78) for men and 74years (intra-quartile range 68-80) for women. Low-density-lipoprotein cholesterol was above target levels in 69% (2032) of women compared with 58% (2487) in men (P < 0.0001). There was also a higher proportion of women with total cholesterol above target levels (76%, 3592) compared with men (57%, 3787) (P < 0.0001). In patients who were prescribed lipid-lowering medication, 53% (2504) of men and 72% (2285) of women continued to have a total cholesterol higher than recommended target levels (P < 0.0001). Overall, over half (52%, 6538) had at least five cardiovascular risk factors (55% (2914) in women and 50% (3624) in men, P < 0.0001). This study found less intensive management of cardiovascular risk factors in CHD patients, particularly among women, despite equivalent cardiovascular risk. This study has shown that these patients have multiple risk factors where gender also plays a role.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2017
DOI: 10.1007/S13679-017-0286-3
Abstract: Clinical registries systematically collect prospective information about patients with a particular medical condition, who have had a medical device implanted or who have undergone a particular procedure. When these variables are collected with pre-defined quality indices included, the benched-marked risk-adjusted data may be a valuable resource for providing feedback on outcomes, including performance, to practitioners, patients, health services and device manufacturers. There are ex les of feedback from clinical registries positively influencing patient care. The Australian National Joint Registry identified a poorly performing hip prosthesis which was ultimately withdrawn from the market. Feedback from the Victorian State Prostate Cancer Registry has contributed to improved patient care and fewer positive surgical margins noted over a 5-year reporting period. There are several national and regional registries collecting information on patients undergoing bariatric surgery, however, few currently focus on quality outcome measures. Whilst, current bariatric registries have contributed to improved understanding of some of the clinical situations relating to bariatric surgery, as well as developing composite risk scores and measuring quality cultures, they have not as yet demonstrably directly influenced patient care. This may reflect the fact that many of the registries do not hold data that are mature enough for proper analysis, but may also reflect problems with systematic data collection, bias from missing results and lack of appropriate funding. It will be important in the future that bariatric surgery registries actively seek to measure and validate their contribution to patient outcomes.
Publisher: Wiley
Date: 17-09-2021
DOI: 10.1111/JGS.17435
Abstract: This study examined the risk of mortality in older adults with newly detected cognitive impairment or dementia. Data from the Australian cohort of the ASPirin in Reducing Events in the Elderly (ASPREE) trial were examined. The ASPREE clinical trial compared daily low‐dose aspirin to a placebo and involved 16,703 in iduals aged 70 years and over, who were without major cognitive impairment, physical disability, or cardiovascular disease at recruitment. During the trial, evidence of cognitive impairment, based on cognitive testing and medical record information, triggered dementia adjudication of participants using DSM‐IV criteria. Cox proportional hazard models were used to compare mortality rates across the dementia, trigger‐only, and no‐trigger groups. Over a median 4.7‐year follow‐up period, 806 participants triggered dementia adjudication, with 485 (60.2%) judged to have dementia. Following recruitment, mortality risks were 32.9, 33.6, and 10.8 events per 1000 person‐years in the dementia, trigger‐no‐dementia, and no‐trigger groups, respectively. In the fully adjusted model, mortality risks remained higher in the dementia and trigger‐no‐dementia groups, with hazard ratios of 1.7 (95% CI: 1.3–2.1) and 1.9 (95% CI: 1.5–2.6), respectively. There was no discernible difference between the dementia and trigger‐no‐dementia groups in mortality rates following recruitment, or following a dementia trigger. These two groups were more likely to die from sepsis, respiratory disease, and dementia, but less likely to die from cancer than the no‐trigger group, χ 2 = 161.5, p 0.001. ASPREE participants who triggered for a dementia evaluation experienced a substantially higher mortality rate than those who remained cognitively intact. The increase was indistinguishable among persons who met DSM‐IV criteria for dementia vs. those who triggered for a dementia evaluation but failed to meet DSM‐IV criteria. Future work should investigate whether earlier detection of cognitive decline can be used to identify and prevent early mortality.
Publisher: Wiley
Date: 13-05-2020
DOI: 10.1111/JGS.16468
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.YPMED.2012.11.002
Abstract: As population ages and treatment for cardiovascular disease improves the risk of all-cause mortality has become a more meaningful outcome. We develop all-cause mortality equations for predicting long term risk using cardiovascular risk factors. The 24-year risk of all-cause mortality was evaluated using Cox model for participants aged 40-81 years at the 10th or 11th examination of the Framingham original cohort and the first examination of the offspring cohort-all of whom were free of major chronic diseases. The predictors of all-cause mortality were age, sex, systolic blood pressure, total cholesterol/HDL ratio and smoking status. Risk prediction improved significantly when intensity of smoking and time since quitting were included into smoking status. A reduced model based on non-laboratory risk factors also demonstrated good predictive performance. All-cause mortality risk equations incorporating cardiovascular risk factors provide an improved tool to quantify risk and guide prevention of mortality. There are great potentials for prevention of the CVD epidemic and for increased longevity with health, through improved life-styles and consequent lower levels of blood pressure, cholesterol and smoking.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.C.6547022.V1
Abstract: Abstract i MUTYH /i carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. i MUTYH /i carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male i MUTYH /i carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66 95% confidence interval (CI), 1.03–2.68 i P /i = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55 95% CI, 1.42–8.78 i P /i = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40 95% CI, 0.81–2.44 i P /i = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of i MUTYH /i carriers revealed no significant contribution toward early mutagenesis from widespread G:C T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of erse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic i MUTYH /i mutations. Prevention Relevance: Despite absence of loss of heterozygosity in colorectal cancers, elderly male i MUTYH /i carriers appeared to be at increased of colorectal cancer. /
Publisher: Springer Science and Business Media LLC
Date: 1994
DOI: 10.1038/CLPT.1994.11
Abstract: Clonidine in doses of 150 to 450 micrograms per day has been reported to reduce symptoms of craving associated with tobacco withdrawal and, in some cases, to improve long-term abstinence rates of smoking cessation programs. However, subjects frequently experienced symptoms of dry mouth and drowsiness. This study investigated the lower end of the effective dose range of clonidine for smoking cessation to identify the lowest useful dose and thus minimize the adverse effects of the drug. A randomized, double-blind, four-way crossover design compared the effects of clonidine doses or placebo within in idual subjects for 4 consecutive weeks. Smokers who were highly nicotine dependent were randomly assigned to different sequences of placebo and 300, 200, and 100 micrograms clonidine per day. Subjects were treated for 4 days of each treatment week and began smoking cessation from the end of day 2. Smokers recorded withdrawal symptoms on multiple visual analog scales during days 3 and 4 before resuming normal smoking until the next period of smoking cessation. A statistically significant dose-response effect was found for craving scores (dose-response gradient, -3.8/100 micrograms 95% confidence interval [CI], -6.2 to -1.5 p = 0.002) but not for pooled tobacco withdrawal scores. The dose of 300 micrograms per day reduced mean craving scores significantly (-16% 95% CI, -31% to -1%). Dosing with 200 micrograms approached statistical significance (-14% 95% CI -30% to 1%) but dosing with 100 micrograms did not (-6% 95% CI, -22% to 9%). Troublesome adverse experiences were reported by more than 67% of subjects during 200 and 300 micrograms dosing. This study showed a statistically significant dose-response effect of clonidine on tobacco withdrawal craving and a reduction in mean craving scores of 16% during 300 micrograms dosing. However, its clinical usefulness is doubtful because of frequently reported adverse experiences.
Publisher: American Thoracic Society
Date: 05-2001
Publisher: Oxford University Press (OUP)
Date: 10-1994
Publisher: BMJ
Date: 03-2016
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22534390
Abstract: Supplementary Figure from Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older In iduals
Publisher: Springer Science and Business Media LLC
Date: 1997
Abstract: Interin idual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable during smoking and transdermal nicotine treatment, even among in iduals taking in nominally similar doses of nicotine. This report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict concentrations during transdermal nicotine treatment. Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to in idual characteristics such as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters. Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance (baseline plasma concentration ided by cigarettes per day) together with other factors could account for 18 to 33% of the variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study. Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable in idual pharmacokinetic parameters and absorbed dose of nicotine. Considering the interin idual variability of plasma nicotine and cotinine concentrations together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility of a therapeutic drug monitoring approach for transdermal nicotine treatment-particularly for high dose regimens (> 22 mg per 24 hours).
Publisher: Wiley
Date: 18-03-2011
DOI: 10.1111/J.1445-5994.2010.02226.X
Abstract: End-stage kidney disease registry data have reported increased mortality in patients with diabetes as compared with those without. Here we examine whether diabetes is independently associated with an increased risk of major cardiovascular events and death in patients with advanced chronic kidney disease (CKD). Data from 315 participants with CKD in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) were assessed. Primary end-points were fatal or non-fatal cardiovascular events, including myocardial infarction, stroke, unstable angina, coronary revascularisation and peripheral vascular events assessed both jointly and separately using Cox-proportional hazard models. Twenty-three per cent reported diabetes. Median follow up was 3.6 years. In those with diabetes, an increased risk for major cardiovascular events was observed, crude hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.11-3.90). After adjustment for age, gender, smoking, systolic blood pressure, body mass index, past ischaemic heart disease and use of preventive therapies, diabetes was associated with an HR of 1.83 (1.28-2.61) for major cardiovascular events. The risk for peripheral vascular events was also increased, adjusted HR 6.31 (2.61-15.25). For all-cause death, major coronary and stroke events, the risk in those with diabetes was not significantly increased (all-cause death, adjusted HR 1.31 (95% CI 0.80-2.14) major coronary events, adjusted HR 1.26 (95% CI 0.64-2.49) and major stroke events, adjusted HR 1.28 (95% CI 0.55-2.99)). Diabetes significantly increases the risk of major cardiovascular events, especially peripheral vascular events in patients with advanced CKD. Trials of multifactorial management of cardiovascular risk factors are required to determine if outcomes for this population may be improved.
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/AH09866
Abstract: Background. Increased ambulance utilisation is closely linked with Emergency Department (ED) attendances. Pressures on hospital systems are widely acknowledged with ED overcrowding reported regularly in the media and peer-reviewed literature. Strains on ambulance services are less well-documented or studied. Aims. To review the literature to determine the trends in utilisation of emergency ambulances throughout the developed world and to discuss the major underlying drivers perceived as contributing to this increase. Method. A search of online databases, search engines, peer-reviewed journals and audit reports was undertaken. Findings. Ambulance utilisation has increased in many developed countries over the past 20 years. Annual growth rates throughout Australia and the United Kingdom are similar. Population ageing, changes in social support, accessibility and pricing, and increasing community health awareness have been proposed as associated factors. As the extent of their contribution has not yet been established these factors were reviewed. Conclusion. The continued rise in utilisation of emergency ambulances is placing increasing demands on ambulance services and the wider health system, potentially compromising access, quality, safety and outcomes. A variety of factors may contribute to this increase and targeted strategies to reduce utilisation will require an accurate identification of the major drivers of demand. What is known about the topic? Ambulance utilisation is increasing annually throughout the developed world, with previous research suggesting numerous underlying factors. What does this paper add? These factors have not been previously synthesised in the international literature. This narrative review clearly articulates the underlying problems. What are the implications for practitioners? This paper outlines the need for further research of the causes of increased emergency ambulance utilisation, to enable the development of appropriate strategies to manage demand in the future.
Publisher: S. Karger AG
Date: 1979
DOI: 10.1159/000170654
Abstract: Eukaryotic chromosomes terminate with telomeres, nucleoprotein structures that are essential for chromosome stability. Vertebrate telomeres consist of terminal DNA tracts of sequence (TTAGGG)n, which in rat are predominantly organized into nucleosomes regularly spaced by 157 bp. To test the hypothesis that telomeres of other animals have nucleosomes, we compared telomeres from eight vertebrate tissues and cell cultures, as well as two tissues from an invertebrate. All telomeres have substantial tracts of (TTAGGG)n comprising 0.01-0.2% of the genome. All telomeres are long (20-100 kb), except for those of sea urchin, human, and some chicken chromosomes, which are 3-10 kb in length. All of the animal telomeres contained nucleosome arrays, consistent with the original hypothesis. The telomere repeat lengths vary from 151 to 205 bp, seemingly uncorrelated with telomere size, regularity of nucleosome spacing, species, or state of differentiation but surprisingly correlated with the repeat of bulk chromatin within the same cells. The telomere nucleosomes were consistently approximately 40 bp smaller than bulk nucleosomes. Thus, animal telomeres have highly conserved sequences and unusually short nucleosomes with cell-specific structure.
Publisher: American College of Physicians
Date: 07-2023
DOI: 10.7326/M23-0675
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1016/S0735-1097(99)00155-2
Abstract: The purpose of this study was to investigate the role of hormone replacement therapy (HRT) in postmenopausal women who smoke. Hormone replacement therapy appears to afford cardiovascular protection in postmenopausal women however, in high risk in iduals, specifically smokers, this has not been adequately studied. This question was addressed in a cross-sectional study of arterial structure, function and plasma lipids in postmenopausal smokers and nonsmokers. Vascular ultrasound was performed in two age-matched groups of postmenopausal women, 70 on HRT (35 smokers) and 70 control subjects not on HRT (35 smokers). Indexes of arterial structure (carotid intima-media thickness [IMT]) and vascular function (systemic arterial compliance [SAC]) and lipid profiles were measured. Participant characteristics were similar in the two groups. Smokers on HRT, compared with smoking control subjects, had lower cholesterol (6.0+/-0.2 vs. 6.8+/-0.3 mmol/liter, p = 0.03) and more favorable mean values for IMT (0.64+/-0.02 vs. 0.74+/-0.03 mm, p = 0.007) and SAC (0.41+/-0.03 vs. 0.32+/-0.03 U/mm Hg, p = 0.03). Nonsmokers on HRT compared with nonsmoking control subjects had lower total cholesterol (5.7+/-0.2 vs. 6.5+/-0.2 mmol/liter, p = 0.02) and low density lipoprotein cholesterol (3.4+/-0.2 vs. 4.4+/-0.3 mmol/liter, p = 0.01). Mean IMT and SAC values in nonsmokers on HRT and control subjects were not significantly different. Multiple regression demonstrated significant correlation between HRT status and both IMT and SAC, in smokers and in those with increased cholesterol. In nonsmokers and those with lower cholesterol, HRT status was not significantly correlated with vascular parameters. In postmenopausal women who smoke there may be a beneficial effect of long-term estrogen therapy on indexes of arterial structure and function as surrogate markers of cardiovascular disease. Long-term controlled studies are needed to confirm these findings.
Publisher: Elsevier BV
Date: 08-1996
DOI: 10.1016/S0002-9149(96)00331-1
Abstract: Nonrheumatic atrial fibrillation (AF) frequently coexists with other risk factors for cerebral ischemia. This study was originally designed to determine which combinations of clinical and echocardiographic abnormalities were most closely associated with the risk of cerebral ischemic events. Patients with cerebral ischemic events (n = 214) and community-based control subjects (n = 201) underwent transesophageal echocardiography and carotid artery imaging. Adjusted odds ratios (ORs) were determined using multiple logistic regression analysis. Independent risk factors for cerebral ischemia included diabetes, carotid stenosis, aortic sclerosis, left ventricular dysfunction, left ventricular hypertrophy, left atrial (LA) spontaneous contrast, and proximal aortic atheroma. Nonrheumatic AF in combination with LA spontaneous contrast and LA enlargement showed a strong association with cerebral ischemic events (OR 33.7 [95% confidence interval 4.53 to 251]). In subjects with sinus rhythm or nonrheumatic AF, LA enlargement was not associated with an increased risk of cerebral ischemic events in the absence of LA spontaneous contrast. However, only 2 patients and 1 control subject had nonrheumatic AF without LA spontaneous contrast or LA enlargement. Therefore, study of a larger number of subjects is required to address the issue of whether nonrheumatic AF itself carries increased risk. The combination of nonrheumatic AF with LA spontaneous contrast is a potent risk factor for cerebral ischemia. Ascertaining the risk factor in nonrheumatic AF requires adequate examination for underlying cardiac, aortic, and carotid vascular disease. Transesophageal echocardiography may contribute to this assessment.
Publisher: Oxford University Press (OUP)
Date: 02-02-2021
DOI: 10.1093/JNCI/DJAB010
Publisher: MDPI AG
Date: 07-04-2021
Abstract: Health registries are critical to understanding, benchmarking and improving quality of care for specific diseases and conditions, but face hurdles including funding, bias towards clinical rather than population s les, lack of pre-morbid and outcomes data, and absent cross-registry harmonisation and coordination. Children are particularly under-represented in registry research. This paper lays out novel principles, methods and governance to integrate erse registries within or alongside a planned children’s mega-cohort to rapidly generate translatable evidence. GenV (Generation Victoria) will approach for recruitment parents of all newborns (estimated 150,000) over two years from mid-2021 in the state of Victoria (population 6.5 million), Australia. Its s le size and population denominator mean it will contain almost all children with uncommon or co-morbid conditions as they emerge over time. By design, it will include linked datasets, bios les (including from pregnancy), phenotypes and participant-reported measures, all of which will span pre-morbid to long-term outcomes. We provide a vignette of a planned new registry for high-risk pregnancies to illustrate the possibilities. To our knowledge, this is the first paper to describe such a methodology designed prospectively to enhance both the clinical relevance of a large multipurpose cohort and the value and inclusivity of registries in a population.
Publisher: Elsevier BV
Date: 09-1989
DOI: 10.1016/S0140-6736(89)90894-5
Abstract: To assess whether a rigorous clinical classification, based on computerised tomography, of patients with cerebral ischaemia would identify subgroups at higher or lower risk with respect to cigarette smoking habits, a case-control study was carried out on 422 cases of first-episode cerebral ischaemia matched for age and sex with 422 community-based neighbourhood controls. Patients with ischaemic stroke due to extracranial or intracranial vascular disease were at higher risk from smoking than has previously been reported for stroke (relative risk 5.7, 95% confidence interval 2.8, 12.0) whereas those with stroke due to cardiac emboli had no excess risk associated with smoking (relative risk 0.4 [0.1, 1.8]). After cessation of smoking, the relative risk declined gradually over 10 years, at the end of which time a significant risk was still evident. This finding may imply that the risk incurred by smoking is due mainly to atheroma formation, rather than transient haematological effects. Exposure to smoking by a spouse was an independent risk factor for the whole group of cerebral ischaemia patients (relative risk 1.7 [1.1, 2.6]), but this was not so for smoking by either parent (relative risk 1.2 [0.8, 1.8]). These findings suggest that smoking is a more potent risk factor for the most common form of ischaemic stroke than has previously been appreciated. The persistent nature of the risk even after cessation of smoking and the possible risk associated with passive exposure strengthens public health arguments against smoking.
Publisher: AMPCo
Date: 02-2012
DOI: 10.5694/MJA11.10955
Abstract: To measure the increase in volume and age-specific rates of presentations to public hospital emergency departments (EDs), as well as any changes in ED length of stay (LOS) and to describe trends in ED utilisation. Population-based retrospective analysis of Department of Health public hospital ED data for metropolitan Melbourne for 1999-00 to 2008-09. Presentation numbers presentation rates per 1000 person-years ED LOS. ED presentations increased from 550,662 in 1999-00 to 853,940 in 2008-09. This corresponded to a 32% rise in rate of presentation (95% CI, 29%-35%), an average annual increase of 3.6% (95% CI, 3.4%-3.8%) after adjustment for population changes. Almost 40% of all patients remained in the ED for ≥4 hours in 2008-09, with LOS increasing over time for patients who were more acutely unwell. The likelihood of presentation rose with increasing age, with people aged≥85 years being 3.9 times as likely to present as those aged 35-59 years (95% CI, 3.8-4.0). The volume of older people presenting more than doubled over the decade. They were more likely to arrive by emergency ambulance and were more acutely unwell than 35-59 year olds, with 75% having an LOS≥4 hours and 61% requiring admission in 2008-09. The rise in presentation numbers and presentation rates per 1000 person-years over 10 years was beyond that expected from demographic changes. Current models of emergency and primary care are failing to meet community needs at times of acute illness. Given these trends, the proposed 4-hour targets in 2012 may be unachievable unless there is significant redesign of the whole system.
Publisher: Oxford University Press (OUP)
Date: 20-01-2017
Publisher: American Thoracic Society
Date: 04-2013
Publisher: Oxford University Press (OUP)
Date: 11-11-2021
DOI: 10.1093/EURHEARTJ/EHAB770
Abstract: The aim of this study was to assess the impact and cost-effectiveness of offering population genomic screening to all young adults in Australia to detect heterozygous familial hypercholesterolaemia (FH). We designed a decision analytic Markov model to compare the current standard of care for heterozygous FH diagnosis in Australia (opportunistic cholesterol screening and genetic cascade testing) with the alternate strategy of population genomic screening of adults aged 18–40 years to detect pathogenic variants in the LDLR/APOB/PCSK9 genes. We used a validated cost-adaptation method to adapt findings to eight high-income countries. The model captured coronary heart disease (CHD) morbidity/mortality over a lifetime horizon, from healthcare and societal perspectives. Risk of CHD, treatment effects, prevalence, and healthcare costs were estimated from published studies. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER), discounted 5% annually. Sensitivity analyses were undertaken to explore the impact of key input parameters on the robustness of the model. Over the lifetime of the population (4 167 768 men 4 129 961 women), the model estimated a gain of 33 488years of life lived and 51 790 QALYs due to CHD prevention. Population genomic screening for FH would be cost-effective from a healthcare perspective if the per-test cost was ≤AU$250, yielding an ICER of & AU$28 000 per QALY gained. From a societal perspective, population genomic screening would be cost-saving. ICERs from societal perspective remained cost-saving after adaptation to other countries. Based on our model, offering population genomic screening to all young adults for FH could be cost-effective, at testing costs that are feasible.
Publisher: Springer Science and Business Media LLC
Date: 12-2008
Publisher: Springer Science and Business Media LLC
Date: 20-02-2017
Publisher: Wiley
Date: 02-1978
Publisher: BMJ
Date: 2017
Publisher: Elsevier BV
Date: 1991
DOI: 10.1016/0895-4356(91)90013-Y
Abstract: Formal evaluation of recruitment strategies for clinical trials conducted in the community setting, rather than in hospitals, is limited despite recruitment rates and costs having significant implications for the planning of large trials. As part of the development of a large-scale primary prevention trial of low-dose aspirin in 15,000 elderly persons (aged 70 years and above) to be undertaken in a community setting, a pilot study involving 400 participants was carried out to evaluate different recruitment strategies. Three techniques were compared: recruiting from the electoral roll (by in idual invitation using direct mail), local community approach (through retirement villages, local media, elderly community groups), and using general/family practice (identifying persons over 70 within a practice and direct mail invitation to participate). Screening of potential participants was carried out by a trained trial nurse with limited involvement only of medical practitioners. The target recruitment figure was achieved in 4 months using the equivalent of 1.5 full-time nurses. General practice was the most effective method utilized, with a yield of one participant recruited per six approached at an estimated cost of A$48.36 per recruited participant. This compares with yield rates of 1 per 29 (for the local community approach) and 1 per 17 for the electoral roll, and costs per participant of A$42.54 and A$59.37 respectively. Other less tangible benefits of general practice include the greater cooperation of primary care practitioners in patient follow-up and end-point ascertainment.
Publisher: Oxford University Press (OUP)
Date: 1993
DOI: 10.1093/IJE/22.3.412
Abstract: The possible association between prior infection with the protozoan Toxoplasma gondii and development of brain tumours was investigated as part of two Australian population-based case-control studies of adult brain tumours. One study, based in Adelaide, South Australia, collected blood from 73 subjects with glioma, 53 subjects with meningioma and 348 controls. The other study, based in Melbourne, Victoria, collected blood from 44 subjects with glioma and 67 controls. All tumours had been verified histologically. IgG antibodies to T. gondii were measured using Enzyme Linked Immunosorbent Assay (ELISA) techniques. In both the centre-specific and combined analyses, there was no difference between subjects with glioma and controls in the prevalence of antibody test-positivity (35% test-positive in glioma versus 33% in controls, age-, sex- and centre-adjusted odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.64-1.56). In the Adelaide study, there was a statistically significant increased risk of meningioma associated with antibody test-positivity (47% test-positive in meningioma versus 31% in controls, P = 0.02, adjusted OR = 2.09, 95% CI: 1.14-3.83). Our results do not support the hypothesis that antibody positivity to T. gondii is a risk factor for glioma, but suggest that it might be associated with meningioma.
Publisher: Wiley
Date: 21-12-2018
DOI: 10.1111/IWJ.12879
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.SCHRES.2012.08.018
Abstract: Despite the implementation of cardiac monitoring guidelines, clozapine-induced myocarditis continues to cause deaths in Australia, and the risk is a barrier to prescription of this effective drug for the treatment of schizophrenia. This study was designed to identify clinical and phenotypic risk factors for clozapine-induced myocarditis. Possible cases of clozapine related myocarditis occurring between June 1993 and November 2009 and a comparative group of controls taking clozapine for at least 45days without cardiac disease were documented from the patients' medical records. 105 cases, with time to onset of 10-33days, and 296 controls were included in the study. In multivariate analysis, the risk of myocarditis increased by 26% for each additional 250mg of clozapine administered in the first nine days of clozapine titration (odds ratio 1.26 95% confidence interval 1.02-1.55 p=0.03) and concomitant sodium valproate more than doubled the risk (2.59 1.51-4.42 0.001). Further, each successive decade in age was associated with a 31% increase in risk (1.31 1.07-1.60 0.009). Nevertheless, 33 cases received less than 920mg of clozapine during the first nine days of dose titration, did not take sodium valproate and were aged less than 40years and nine control patients received sodium valproate and more than 920mg of clozapine in the first nine days without developing myocarditis. Clozapine should be initiated by slow dose titration and sodium valproate is best avoided, if clinically feasible, during this period. All patients commencing clozapine should be monitored for myocarditis up to Day 28.
Publisher: SAGE Publications
Date: 07-1998
DOI: 10.1177/153857449803200402
Abstract: The purpose of this study was to introduce carotid plication as a simpler alternative approach to internal carotid resection, reimplantation, graft replacement in the management of symptomatic carotid kink, carotid perforation, and unacceptable end point. Fifty-two carotid plications (internal carotid = 49, common carotid = three) were performed on 50 patients (29 men, 21 women) and followed up for 8-129 months (mean 67). Carotid plications were performed for kink (n: 43), carotid perforation from plaque erosion (n: three), and unacceptable end point of endarterectomy (n: six). The operation was performed with 100% shunting and vein patch angioplasty. There was no death, stroke, aneurysm, pseudoaneurysm, rupture, or stenosis in the 52 carotid plications. Symptomatic relief was successful in amaurosis fugax, transient ischemic attack, global ischemia, and vertebral-basilar symptoms. Only partial relief was achieved in carotid throbbing. Carotid plication is a simple, dependable, and durable procedure for symptomatic carotid kink, carotid perforation due to plaque erosion not amendable to lateral repair, and unacceptable distal end point in carotid endarterectomy.
Publisher: Springer Science and Business Media LLC
Date: 23-01-2020
DOI: 10.1038/S41467-019-14079-0
Abstract: Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly in iduals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB in iduals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.
Publisher: SAGE Publications
Date: 10-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2006
DOI: 10.1161/01.STR.0000202588.95876.A7
Abstract: Background and Purpose— Greater stroke mortality has been reported among lower socioeconomic groups. We aimed to determine whether fatal, nonfatal, and overall stroke incidence varied by socioeconomic status. Methods— All suspected strokes occurring in 22 postcodes (population of 306 631) of Melbourne, Australia, during a 24-month period between 1997 and 1999 were found and assessed. Multiple overlapping sources were used to ascertain cases with standard clinical definitions for stroke. Socioeconomic disadvantage was assigned in 4 bands from least to greatest using an area-based measure developed by the Australian Bureau of Statistics. Results— Overall stroke incidence (number per 100 000 population per year), adjusted to the European population 45 to 84 years of age, increased with increasing socioeconomic disadvantage: 200 (95% CI, 173 to 228) 251 (95% CI, 220 to 282) 309 (95% CI, 274 to 343) and 366 (95% CI, 329 to 403 χ 2 for ranks P .0001). Similar incidence patterns were observed for both fatal and nonfatal stroke. Nonfatal stroke contributed most to this incidence pattern: 146 (95% CI, 122 to 169) 181 (95% CI, 155 to 207) 223 (95% CI, 194 to 252) and 280 (95% CI, 247 to 313 χ 2 for ranks P .0001). Conclusions— In this population-based study, both fatal and nonfatal stroke incidence increased with increasing socioeconomic disadvantage. The greater contributor to this incidence pattern was nonfatal stroke incidence. This may have implications for service provision to those least able to afford it. Area-based identification of those most disadvantaged may provide a simple and effective way of targeting regions for stroke prevention strategies.
Publisher: Elsevier BV
Date: 11-1992
DOI: 10.1016/0002-9149(92)90765-Q
Abstract: The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program. However, there is little information about the relative effectiveness of different drug regimens in this condition. This study compared the efficacy and tolerability of 50 mg of atenolol, 10 mg of enalapril, 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension. After a 3-week placebo run-in phase, 24 subjects were randomized into a 4-period double-blind crossover study by use of an orthogonal latin square design. Treatment periods were of 6 weeks' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure (BP). Each active treatment was followed by a 3-week placebo washout. Casual clinic and 24-hour ambulatory BP (Accutracker II) were measured at the end of each treatment phase. Routine biochemistry was also performed after the placebo run-in, at the end of each active treatment phase, and after the placebo run-out. Of the 24 subjects entered (mean age 72.3 years, 38% men) 20 completed the whole study. Mean +/- standard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 +/- 21/9 mm Hg and 165/82 +/- 23/15 mm Hg, respectively. All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period. Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: Environmental Health Perspectives
Date: 11-1970
DOI: 10.1289/EHP.5726
Abstract: An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily ided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine s les were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interin idual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring.
Publisher: Wiley
Date: 11-09-2012
DOI: 10.1111/J.1742-6723.2012.01609.X
Abstract: To describe the trends in emergency admissions over 10 years in terms of volume, age-specific rates, hospital length of stay (LOS) and clinical reasons. A retrospective analysis of population-based linked Department of Health ED and hospital admission data for metropolitan Melbourne 1999/2000 to 2008/2009 was conducted. Outcome measures included: hospital admission numbers (total, single day/overnight, ≥2 days LOS) admission rates per 1000 person-years (total, single day/overnight, ≥2 days LOS) hospital LOS. The volume of patients admitted to hospital through EDs rose by 56% over the 10 years to June 2009. The number of same day/overnight admissions rose by 60%, equating to a 6.1% average annual increase beyond that accounted for by demographic change (95% CI 5.7-6.5%). The volume of patients admitted for ≥2 days also increased however, the admission rate per 1000 persons for these longer-stay patients declined over the decade by 9% (95% CI 5-12%). The most frequent discharge diagnoses were injury or poisoning, and disorders of the circulatory, respiratory or digestive systems. The numbers and mortality rate for ED admissions declined over the decade. Emergency hospital admissions have risen over the last decade even after adjustment for population changes. There was a disproportionate rise in same day/overnight admissions, with overrepresentation of the elderly. This is possibly related to changes in ED models of care, including introduction of short-stay units, improved diagnostic and therapeutic capability, and risk-averse management to optimise safe discharge, within the context of time-based performance targets.
Publisher: American Association for Cancer Research (AACR)
Date: 24-05-2022
DOI: 10.1158/1940-6207.CAPR-22-0080
Abstract: Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.
Publisher: Elsevier BV
Date: 05-1990
DOI: 10.1016/0002-9149(90)90341-W
Abstract: There is an increasing awareness of the need to manage multiple risk factors in hypertensive patients, and of possible adverse metabolic effects of antihypertensive drugs which may counteract their ability to reduce the risk of cardiovascular disease. Data collected from the Austin Hospital Hypertension Clinic support previous observations that the incidence of cardiovascular risk factors such as plasma lipid abnormalities are high in hypertensive patients, and although it is becoming easier to control blood pressure in these patients, modification of other risk factors is difficult. The use of diuretics in doses lower than those conventionally prescribed has been advocated as a means of reducing the adverse metabolic effects. However, data from this study suggest that although low-dose hydrochlorothiazide therapy (25 to 50 mg/day) may be as effective as conventional doses of captopril in reducing blood pressure, adverse metabolic effects on plasma potassium, glucose and uric acid levels remain a problem. Indapamide, a relatively new diuretic when used at a fixed dose (2.5 mg/day), appears to be devoid of significant adverse metabolic effects and is a useful alternative to thiazide diuretics. An integrated approach to the management of multiple cardiovascular risk factors is important in hypertensive patients and should include non-pharmacologic methods and the selection of antihypertensive drugs that do not have adverse metabolic effects.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2003
DOI: 10.1161/01.STR.0000091395.85357.09
Abstract: Background and Purpose— Little is known about any variations in resource use and costs of care between stroke subtypes, especially nonhospital costs. The purpose of this study was to describe the patterns of resource use and to estimate the first-year and lifetime costs for stroke subtypes. Methods— A cost-of-illness model was used to estimate the total first-year costs and lifetime costs of stroke subtypes for all strokes (subarachnoid hemorrhages excluded) that occurred in Australia during 1997. For each subtype, average cost per case during the first year and the present value of average cost per case over a lifetime were calculated. Resource use data obtained in the North East Melbourne Stroke Incidence Study (NEMESIS) were used. Results— The present value of total lifetime costs for all strokes was Aus $1.3 billion (US $985 million). Total lifetime costs were greatest for ischemic stroke (72% Aus $936.8 million US $709.7 million), followed by intracerebral hemorrhage (26% Aus $334.5 million US $253.4 million) and unclassified stroke (2% Aus $30 million US $22.7 million). The average cost per case during the first year was greatest for total anterior circulation infarction (Aus $28 266). Over a lifetime, the present value of average costs was greatest for intracerebral hemorrhage (Aus $73 542), followed by total anterior circulation infarction (Aus $53 020), partial anterior circulation infarction (Aus $50 692), posterior circulation infarction (Aus $37 270), lacunar infarction (Aus $34 470), and unclassified stroke (Aus $12 031). Conclusions— First-year and lifetime costs vary considerably between stroke subtypes. Variation in average length of total hospital stay is the main explanation for differences in first-year costs.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-07-2021
Abstract: Blood pressure variability (BPV) in midlife increases risk of late‐life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long‐term, visit‐to‐visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow‐up visits. Time‐to‐event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. In iduals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P =0.02), with increased risk in men (HR, 1.68 95% CI, 1.19–2.39) but not women (HR, 1.01 95% CI, 0.72–1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P =0.15 men: HR, 1.36 95% CI, 1.16–1.59 women: HR, 1.14 95% CI, 0.98–1.32). High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. URL: www.clinicaltrials.gov Unique identifier: NCT01038583 isrctn.com . Identifier: ISRCTN83772183.
Publisher: Wiley
Date: 12-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1996
DOI: 10.1161/01.STR.27.11.2020
Abstract: Background and Purpose Given that hypertension is now relatively well controlled and use of antiplatelet agents has increased, our primary aims were to investigate the risk of intracerebral hemorrhage (ICH) associated with hypertension and use of antiplatelet agents. Methods In this city-wide case-control study, 370 consecutive cases of primary ICH, verified by CT or autopsy, were identified from one of 13 Melbourne hospitals. Ten subjects (or their next of kin) could not be located and 29 refused to participate, resulting in 331 eventual cases. Patients were aged between 18 and 80 years and had no prior stroke. Population-based control subjects were in idually age- (±5 years), sex-, and geographically matched to subject cases. A questionnaire administered to participants (or next of kin) elicited information about prior exposure to various potential risk factors. Results Hypertension approximately doubled the risk of ICH (odds ratio, 2.55 95% confidence interval, 1.72 to 3.79). The use of aspirinlike drugs, in doses used for secondary prevention of ischemic stroke or cardiac disease, was not associated with an increased risk of ICH (odds ratio, 0.66 95% confidence interval, 0.20 to 2.21). Factors associated with a reduced risk of ICH were a history of cardiovascular disease, arthritis, or high cholesterol level being moderately overweight or using hormone replacement therapy and drinking coffee. Conclusions Hypertension was the most important risk factor for ICH but not as high as previously reported, nor was it higher than that reported for ischemic stroke. There was no evidence for any association between the use of aspirinlike drugs and ICH.
Publisher: Wiley
Date: 05-1992
DOI: 10.1111/J.1440-1681.1992.TB00454.X
Abstract: 1. Repeated clinic blood pressure measurement was compared with non-invasive ambulatory blood pressure (ABP) monitoring in 10 elderly subjects with isolated systolic hypertension (ISH) and 11 normotensive controls (NT). 2. Subjects were assessed on four occasions at weekly intervals. None was receiving antihypertensive or vasoactive medication. 3. Mean clinic blood pressure was consistently higher than mean daytime ABP in both clinical groups. This effect was greater for systolic (SBP) than diastolic blood pressure (DBP) and in the ISH group compared with the NT group. The reproducibility of the clinic minus ABP difference was high in both groups the mean +/- s.d. of the differences was 26 +/- 15/9 +/- 2 mmHg in the ISH group and 7 +/- 18/8 +/- 9 mmHg in the controls. 4. ABP readings were normally distributed for both SBP and DBP in both groups. In the ISH group, the frequency distribution of SBP readings was shifted to the right whilst the distribution of DBP readings overlapped that of the NT subjects. 5. These results suggest a pressor response may largely account for the elevated SBP seen in elderly subjects with sustained ISH based on casual readings.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.JTCVS.2013.10.051
Abstract: Evidence is accumulating of adverse outcomes associated with transfusion of blood components. If there are differences in perioperative transfusion rates in cardiac surgery, and what hospital factors may contribute, requires further investigation. Analysis of 42,743 adult patients who underwent 43,482 procedures from 2005 to 2011 at 25 Australian hospitals, according to the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database. Multiple logistic regression examined associations of patient and hospital characteristics with transfusion of ≥1 red blood cell (RBC) unit platelet (PLT), fresh frozen plasma (FFP), and cryoprecipitate (CRYO) doses and ≥5 RBC units, from surgery until hospital discharge. Procedures included 24,222 (55%) isolated coronary artery bypass grafts, 7299 (17%) isolated valve, 4714 (11%) coronary artery bypass graft and valve, and 7247 (17%) other procedures. After adjustment for various patient and procedure characteristics, transfusion rates varied across hospitals for ≥1 RBC unit from 22% to 67%, ≥5 RBC units from 5% to 25%, ≥1 PLT dose from 11% to 39%, ≥1 FFP dose from 11% to 48% and ≥1 CRYO dose from 1% to 20%. Hospital characteristics, including state or territory, private versus public, and teaching versus nonteaching, were not associated with variation in transfusion rates. Variation in transfusion of all components and large volume RBC was identified, even after adjustment for patient and procedural factors known to influence transfusion, and this was not explained by hospital characteristics.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Touch Medical Media, Ltd.
Date: 09-09-2010
DOI: 10.4081/HI.2010.E11
Publisher: Wiley
Date: 08-11-2017
Publisher: Springer Science and Business Media LLC
Date: 06-05-2019
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533314
Abstract: Supplementary Figure from Incident Cancer Risk and Signatures Among Older i MUTYH /i Carriers: Analysis of Population-Based and Genomic Cohorts
Publisher: Wiley
Date: 02-1982
DOI: 10.1111/J.1365-2125.1982.TB01892.X
Abstract: 1 During chronic treatment of hypertensive patients observed mean steady-state plasma labetalol levels in ten patients were consistently and significantly higher than predicted from initial acute pharmacokinetic analysis. 2 Mean steady-state levels varied from 36 to 183 ng/ml on a chronic dose of 200 mg twice daily. 3 Patients with lower steady-state levels on a fixed dose of labetalol usually required higher maintenance doses to control blood pressure.
Publisher: Elsevier BV
Date: 09-2018
Publisher: BMJ
Date: 12-10-2009
Abstract: While the relationship between socio-economic disadvantage and cardiovascular disease (CVD) is well established, the role that traditional cardiovascular risk factors play in this association remains unclear. The authors examined the association between education attainment and CVD mortality and the extent to which behavioural, social and physiological factors explained this relationship. Adults (n=38,355) aged 40-69 years living in Melbourne, Australia were recruited in 1990-1994. Subjects with baseline CVD risk factor data ascertained through questionnaire and physical measurement were followed for an average of 9.4 years with CVD deaths verified by review of medical records and autopsy reports. CVD mortality was higher for those with primary education only, compared with those who had completed tertiary education, with an HR of 1.66 (95% CI 1.10 to 2.49) after adjustment for age, country of birth and gender. Those from the lowest educated group had a more adverse cardiovascular risk factor profile compared with the highest educated group, and adjustment for these risk factors reduced the HR to 1.18 (95% CI 0.78 to 1.77). In analysis of in idual risk factors, smoking and waist circumference explained most of the difference in CVD mortality between the highest and lowest education groups. Most of the excess CVD mortality in lower socio-economic groups can be explained by known risk factors, particularly smoking and overweight. While targeting cardiovascular risk factors should not ert efforts from addressing the underlying determinants of health inequalities, it is essential that known risk factors are addressed effectively among lower socio-economic groups.
Publisher: Wiley
Date: 02-1984
DOI: 10.1111/J.1365-2125.1984.TB02427.X
Abstract: A study was made of the influence of hydralazine on the oral availability of a sustained release formulation of propranolol (Inderal LA). Sustained release propranolol 160 mg was given orally either alone or in combination with oral hydralazine 25 mg on separate occasions to six healthy volunteers. Blood and urine s les were collected post-dosing over 34 h. Peak concentrations of propranolol, time to peak and area under the plasma concentration-time curve (AUC) were not altered by co-administration of hydralazine with sustained release propranolol. Similarly, there was no change in recovery of 11C-labelled propranolol and metabolites in those in iduals to whom tracer label was given. These results contrast with previous reports of marked interaction between the conventional formulation of propranolol and hydralazine or food. Interactions were confirmed between hydralazine and conventional propranolol in three subjects who had been studied previously with sustained release propranolol. Analysis of metabolite profiles in one of these subjects established that the major metabolites do change under hydralazine stimulus. These results indicate that substrate delivery rates may determine presystemic drug interactions, suggesting capacity limitations of hydroxylation processes or short-term flow redistribution following hydralazine, resulting in functional shunting past the hydroxylation enzymes. These results exclude global or lasting enzyme inhibition by hydralazine or simple flow-sensitivity of presystemic clearance.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.SCHRES.2011.01.017
Abstract: Fatal clozapine-induced myocarditis has not been investigated systematically. We describe the clinical course of 10 fatal cases of myocarditis with clozapine and identify factors associated with fatality. Cases of myocarditis were documented from the patient's medical records and fatal cases also from autopsy reports. The fatal cases of myocarditis occurred 1996-2009 and were diagnosed at autopsy. Before death, three had no symptoms of illness and only three had cardiac-specific diagnostic results. None was investigated by cardiac imaging techniques, and in none was myocarditis suspected before death. Duration of clozapine for the fatal cases was 14-33 days with an outlier at 4.5 months. Only 3 cases had significant coronary artery disease at autopsy. Comparison of these ten cases with 66 non-fatal cases indicated no significant difference in gender, age, smoking status, dose at onset or concomitant sodium valproate. However, obesity (BMI > 30 kg/m2) was significantly more frequent among fatal than non-fatal cases (60% vs. 26% p < 0.03) and duration of clozapine was significantly longer for fatal cases (20.8 vs. 17.0 days p 1000 U/L was also associated with death (p = 0.0004). Routine monitoring for myocarditis for the first 4 weeks of clozapine, and discontinuation of clozapine in the presence of evidence consistent with myocarditis may assist to prevent fatalities occurring from early-onset myocarditis. Investigation by cardiac imaging will give a measure of severity and need for intervention. Obesity may increase the risk of mortality and CK > 1000 U/L may indicate life-threatening illness.
Publisher: Springer Science and Business Media LLC
Date: 09-1987
Abstract: Clopamide pharmacokinetics were determined after oral doses of 5, 10, and 20 mg in normal volunteers. Maximum plasma concentrations occurred within 2 hours and were followed by a monoexponential decline with an elimination half-life of approximately 10 hours. There was an approximately linear relationship between dose and the AUC. Urinary sodium, chloride, and potassium excretion rates indicated that the peak diuretic activity corresponded with peak plasma drug concentrations and probably continued for 12 to 24 hours. There was little difference between the total sodium and chloride output after each dose of clopamide, suggesting that 5 mg may have been close to the top of the dose-response curve. Chlorothiazide, 500 mg, caused less sodium and chloride output with similar potassium loss. During chronic administration to patients with hypertension, hypokalemia was more marked with clopamide, 10 mg daily, than with clopamide, 5 mg, or chlorothiazide, 500 mg daily.
Publisher: Springer Science and Business Media LLC
Date: 1991
DOI: 10.1007/BF00114219
Publisher: Wiley
Date: 06-1997
DOI: 10.1111/J.1440-1681.1997.TB01225.X
Abstract: 1. Hormone replacement therapy (HRT) with oestrogen or oestrogen plus progestin may have different effects on arterial structure and function. To examine this question, carotid artery intima-medial thickness (IMT) and indices of systemic and carotid arterial compliance were measured in groups of older men, postmenopausal women not on HRT (non-HRT) and those women on long-term HRT with oestrogen alone (HRT-E) or oestrogen plus progestin (HRT-EP). 2. Sixty men, 90 postmenopausal women taking HRT and 91 not taking HRT participated in the study. The groups were similar for age, body mass index, numbers of smokers, physical activity, alcohol intake and blood pressure. 3. Plasma total cholesterol was reduced and high-density lipoprotein-cholesterol was increased in the HRT group compared with the non-HRT group low-density lipoprotein-cholesterol, triglyceride and lipoprotein (a) values were similar in these two groups. Results for HRT-E and HRT-EP subgroups were similar. 4. Carotid IMT was significantly reduced in the HRT group compared with men and non-HRT groups. Results for HRT-E and HRT-EP subgroups were similar. 5. Mean systemic arterial compliance (SAC) was significantly greater in men than in women and was related to age SAC was higher in both HRT-E and HRT-EP groups compared with the non-HRT group. Indices of carotid stiffness were similar in men and in non-HRT groups. The HRT-EP group showed increased carotid stiffness compared with the HRT-E group. 6. There is an apparent protective effect of long-term oestrogen therapy on carotid IMT and age-related changes in arterial stiffness. Progestin does not alter the IMT effects but may adversely influence arterial stiffness.
Publisher: Springer Science and Business Media LLC
Date: 08-1993
DOI: 10.1007/BF03258458
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2022
DOI: 10.1161/CIRCGEN.121.003429
Abstract: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of in iduals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older in iduals without a history of cardiovascular events. We used data from 12 792 genotyped, healthy older in iduals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08–1.42], P =0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00–74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32–75.24, P =0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15–0.28). A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in in iduals aged 70 years and older. URL: www.clinicaltrials.gov Unique identifier: NCT01038583
Publisher: Springer Science and Business Media LLC
Date: 06-05-2020
DOI: 10.1186/S13643-020-01370-1
Abstract: With technological advances, there has been increasing interest in developing contactless and/or non-invasive wearable technologies that continuously monitor vital signs in the clinical setting, and in particular in the deteriorating patient. These devices as of yet have not been well validated in the clinical setting in the clinical ranges observed in a critically unwell patient. We will perform a systematic review of all novel wearable and contactless devices in the clinical setting with focus on degree of novelty and the range of vital signs captured. Ovid MEDLINE including Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) Health Technology Assessment (HTA) database (Ovid), CINAHL with Full Text, searches of the grey literature, cited references of eligible studies through Web of Science, and reference lists of eligible studies will be searched. Outcomes of interest will include the quality of studies in relation to reporting guidelines, limitations of non-invasive technology, and application in different clinical populations. We will perform a qualitative assessment of the novelty of the device and discuss its validation in deteriorating patients. While novel monitoring devices are often proposed as a solution to problems with infection, discomfort, and frequency of monitoring in the clinical setting it has not yet been established which devices have been validated in clinical settings in the pathological ranges of vital signs that reflect patient deterioration. It is equally unclear what additional value these devices might provide. This systematic review will synthesize published data regarding devices that have been tested and validated in patients AND in a clinical setting AND in reference ranges that reflect severe illness. PROSPERO CRD42019130091
Publisher: Wiley
Date: 08-05-2019
DOI: 10.1002/GPS.5119
Publisher: Elsevier BV
Date: 07-1995
Publisher: American Society of Hematology
Date: 05-08-2022
DOI: 10.1182/BLOODADVANCES.2022007505
Abstract: There have been no comprehensive studies of a full range of blood group polymorphisms within the Australian population. This problem is compounded by the absence of any databases carrying genomic information on chronically transfused patients and low frequency blood group antigens in Australia. Here, we use RBCeq, a web server–based blood group genotyping software, to identify unique blood group variants among Australians and compare the variation detected vs global data. Whole-genome sequencing data were analyzed for 2796 healthy older Australians from the Medical Genome Reference Bank and compared with data from 1000 Genomes phase 3 (1KGP3) databases comprising 661 African, 347 American, 503 European, 504 East Asian, and 489 South Asian participants. There were 661 rare variants detected in this Australian s le population, including 9 variants that had clinical associations. Notably, we identified 80 variants that were computationally predicted to be novel and deleterious. No clinically significant rare or novel variants were found associated with the genetically complex ABO blood group system. For the Rh blood group system, 2 novel and 15 rare variants were found. Our detailed blood group profiling results provide a starting point for the creation of an Australian blood group variant database.
Publisher: Wiley
Date: 15-07-2020
DOI: 10.1111/JCH.13934
Publisher: Oxford University Press (OUP)
Date: 06-1992
DOI: 10.1093/INFDIS/165.6.1103
Abstract: Assessment of human papillomavirus (HPV) infection usually requires a speculum examination to collect genital specimens. A technique using t ons as a patient-administered method for the collection of specimens was studied by dot blot hybridization (HPV types 6, 11, 16, 18, 31, and 33) and polymerase chain reaction (PCR). T ons and cervical scrapes were collected from 48 consecutive women attending a dysplasia clinic. T ons provided a significantly larger pellet volume (P less than .002) and more DNA (P less than .01) than scrapes. There was a close correlation when s les were analyzed for the presence of HPV DNA. Using dot blot hybridization, 8 cervical scrapes (17%) and 9 t ons (19%) were positive for HPV DNA (90% correlation). By PCR, 35 cervical scrapes (73%) and 33 t ons (69%) were positive for HPV DNA (88% correlation). Thus, t on specimens are an easy method for assessment of genital HPV infection.
Publisher: Wiley
Date: 05-1991
DOI: 10.1111/J.1532-5415.1991.TB02494.X
Abstract: The benefits of prophylactic aspirin therapy to prevent cardiovascular and cerebrovascular disease in asymptomatic in iduals remains unclear. The rationale for developing a multicentered, double-blind, placebo-controlled clinical trial to determine whether low-dose aspirin (100 mg daily) prevents cardiovascular and cerebrovascular morbidity and mortality in persons aged 70 years and over with no evidence of pre-existing cardiovascular or cerebrovascular disease is described. S le size calculations have indicated that 15,000 subjects would be required over a 4-year follow-up period in order to demonstrate a 20% reduction in overall cardiovascular mortality at the 0.01 level with a power of 0.8. Such a large-scale community-based clinical trial has never been conducted in Australia in this age group. Therefore the PACE (prevention by low-dose aspirin of cardiovascular disease in the elderly) pilot study has been developed to test recruitment strategies and methods and ascertaining disease end-points.
Publisher: AMPCo
Date: 05-2013
DOI: 10.5694/MJA13.10357
Publisher: American Society of Tropical Medicine and Hygiene
Date: 10-01-2018
Publisher: Oxford University Press (OUP)
Date: 04-2023
Abstract: Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. To evaluate disability-free survival (DFS) in older in iduals by glycaemic status. This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70 years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] & 5.6 mmol/l, 64%), prediabetes (FPG 5.6 to & .0 mmol/l, 26%) and diabetes (self-report or FPG ≥ 7.0 mmol/l or use of glucose-lowering agents, 11%). The primary outcome was loss of disability-free survival (DFS), a composite of all-cause mortality, persistent physical disability or dementia. Other outcomes included the three in idual components of the DFS loss, as well as cognitive impairment-no dementia (CIND), major adverse cardiovascular events (MACE) and any cardiovascular event. Cox models were used for outcome analyses, with covariate adjustment using inverse-probability weighting. We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21–1.60), all-cause mortality (1.45, 1.23–1.72), persistent physical disability (1.73, 1.35–2.22), CIND (1.22, 1.08–1.38), MACE (1.30, 1.04–1.63) and cardiovascular events (1.25, 1.02–1.54) but not dementia (1.13, 0.87–1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93–1.12) or other outcomes. Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.
Publisher: Wiley
Date: 06-07-2018
Abstract: The p75 splice variant of lens epithelium-derived growth factor (LEDGF) is a 75 kDa protein, which is recruited by the human immunodeficiency virus (HIV) to tether the pre-integration complex to the host chromatin and promote integration of proviral DNA into the host genome. We designed a series of small cyclic peptides that are structural mimics of the LEDGF binding domain, which interact with integrase as potential binding inhibitors. Herein we present the X-ray crystal structures, NMR studies, SPR analysis, and conformational studies of four cyclic peptides bound to the HIV-1 integrase core domain. Although the X-ray studies show that the peptides closely mimic the LEDGF binding loop, the measured affinities of the peptides are in the low millimolar range. Computational analysis using conformational searching and free energy calculations suggest that the low affinity of the peptides is due to mismatch between the low-energy solution and bound conformations.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2011
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/ANS.14562
Publisher: Wiley
Date: 20-07-2020
DOI: 10.1002/CPT.1959
Publisher: Oxford University Press (OUP)
Date: 06-2006
DOI: 10.1097/01.HJR.0000219108.10167.46
Abstract: Our aim was to evaluate whether vitamin E (500 IU) slowed the progression of carotid atherosclerosis in a population of chronic smokers over 4 years as measured by ultrasound determination of carotid intima-media thickness (IMT) and systemic arterial compliance (SAC). The Melbourne Atherosclerosis Vitamin E Trial (MAVET) was a randomized, double-blind, placebo-controlled trial in which 409 male and female smokers aged 55 years and over were randomized to receive 500 IU per day of natural vitamin E or placebo. The primary endpoint was progression of carotid atherosclerosis determined by intima-media thickness of the right common carotid artery. Secondary outcomes were change in systemic arterial compliance and low-density lipoprotein (LDL) oxidative susceptibility over time. The mean increase in intima-media thickness over time in the vitamin E group was 0.0041 mm/year faster than placebo (95% confidence interval -0.0021 to 0.0102 mm/year, P = 0.20). Similarly, a non-significant difference between vitamin E and placebo was found for rate of change in systemic arterial compliance (P = 0.11). Vitamin E supplementation did, however, significantly reduce LDL oxidative susceptibility (P < 0.001). Vitamin E supplementation is ineffective in reducing the progression of carotid atherosclerosis as measured by intima-media thickness in chronic smokers. This finding extends our knowledge of lack of effectiveness of vitamin E supplementation in populations with high oxidant stress.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.SOCSCIMED.2015.01.014
Abstract: Aboriginal and Torres Strait Islander adults in the Australian state of Victoria have a higher prevalence of psychological distress than their non-Aboriginal and Torres Strait Islander counterparts. We sought to explain this inequality, focussing on the social determinants of health. We used population-based survey data from the 2008 Victorian Population Health Survey a cross-sectional landline computer-assisted telephone survey of 34,168 randomly selected adults. We defined psychological distress as a score of 22 or more on the Kessler 10 Psychological Distress scale. We used logistic regression to identify socio-demographic characteristics and social capital indicators that were associated with psychological distress. We then created multivariable models to explore the association between psychological distress and Aboriginal and Torres Strait Islander status that incorporated all significant socioeconomic status (SES) and social capital variables, adjusting for all non-SES socio-demographic characteristics. Aboriginal and Torres Strait Islander Victorians (24.5%) were more than twice as likely than their non-Aboriginal and Torres Strait Islander counterparts (11.3%) to have psychological distress (odds ratio (OR) = 2.56, 95% confidence interval 1.67-3.93). Controlling for SES, negative perceptions of the residential neighbourhood, lack of social support from family, social and civic distrust, and all non-SES socio-demographic variables (age, sex, marital status, household composition, and rurality), rendered the previously statistically significant inequality in the prevalence of psychological distress, between Aboriginal and Torres Strait Islander Victorians and their non-Aboriginal and Torres Strait Islander counterparts, insignificant at the p = 0.05 level (OR = 1.50 0.97-2.32). Psychological distress is an important health risk factor for Aboriginal and Torres Strait Islander adults that has yet to be widely acknowledged and addressed. Addressing the underlying inequalities in SES and social capital may be the key to addressing the inequality in psychological distress.
Publisher: Oxford University Press (OUP)
Date: 03-02-2019
DOI: 10.1093/ASJ/SJZ023
Abstract: The Breast-Q Implant Surveillance module (BREAST-Q IS) is a patient-reported outcome measure (PROM) that asks 5 questions on satisfaction (shape, feel, and rippling) and symptoms (pain and tightness) derived from the BREAST-Q. We aimed to pilot BREAST-Q IS on patients within the Australian Breast Device Registry (ABDR), an opt-out clinical quality device registry, and explored Short Message Service (SMS) communication as a follow-up method. Patients with a breast device surgery in the previous 10 to 15 months, age ≥18 years, with a mobile phone number, were invited to complete the 5-question PROM via SMS initially, followed by 3 phone call attempts if no response, an e-mail, and then a letter by post as a final engagement strategy. The study included 197 participants [breast augmentation (BA) = 118 breast reconstruction (BR) = 79]. Mean ± SD age was 40 ± 12 years (BA) and 44 ± 11 years (BR). Mean ± SD time since surgery was 414 ± 36 days (BA) and 413 ± 51 days (BR). The total response rate, including opt-outs, was 76%. Responses indicated that & % of BA and & % of BR were very or somewhat satisfied with shape, feel, and wrinkling & % of BA and & % of BR reported no pain or tightness. Completion of survey via SMS was 51% (BA) and 55% (BR). Further responses were received by phone (25%, 26%), post (21%, 16%), and e-mail (3%, 3%). This pilot demonstrated high levels of satisfaction and low levels of pain and tightness in patients with breast augmentation and breast reconstruction 1 year postoperatively. It also showed the effectiveness of our engagement strategy, which achieved a 76% response rate. Over 50% of respondents used SMS to reply to a 5-question PROM assessing long-term surgical outcomes. This engagement strategy will be used as BREAST-Q IS is rolled out nationally.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1999
Publisher: Hindawi Limited
Date: 2011
DOI: 10.1155/2011/179674
Abstract: Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs.
Publisher: Elsevier BV
Date: 09-2019
Publisher: AMPCo
Date: 06-2018
DOI: 10.5694/MJA17.00852
Publisher: Elsevier BV
Date: 07-1996
DOI: 10.1016/S0741-5214(96)70178-7
Abstract: Contemporary guidelines on thoracic aortic repair provide inconsistent reporting standards for the definition of aortic arch classification in Types I, II and III. The different reported criteria cannot be used interchangeably, due to a very low level of concordance, and this finding has relevant implications for the comparisons between studies using different classifications, and between different datasets of multicentre trials, which are not consistently analyzed with the same criteria. Also, the reported definitions, which were originally proposed for predicting difficult carotid stenting and therefore were conceived for healthy aortic arches, can be influenced by the pathological derangements of the aortic wall, including aneurysms and dissections. In this respect, the Madhwal's classification, which is based on the diameter of the left common carotid artery, appears to be the more suitable one for aortic arch classification in patients with thoracic aortic disease because it provides relevant clinical information along with an adequate reproducibility.
Publisher: Oxford University Press (OUP)
Date: 10-11-2021
Abstract: Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. In the United States and Australia, 19 114 community-dwelling in iduals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data. Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96−1.13 frailty index HR: 1.03, 95% CI 0.97−1.09). The proportion of in iduals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups. Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty.
Publisher: Wiley
Date: 09-1981
DOI: 10.1111/J.1365-2125.1981.TB01236.X
Abstract: 1 Ranitidine pharmacokinetics were studied in six healthy volunteers. Following an overnight fast, doses of 20 mg intravenously 20, 40 and 100 mg orally and 100 mg orally with a standard meal, were administered to each subject on separate occasions. 2 Following intravenous administration there was a bioexponential decline in plasma levels from 576 +/- 56 ng/ml at 4 min to 10 +/- 2 ng/ml at 8 h. The distribution half-life (T 1/2 alpha) was 6.1 +/- 0.9 min, elimination half-life (T 1/2 beta) was 1.9 +/- 0.1 h, the volume of distribution (Vd beta) was 115 +/- 7 l and systemic plasma clearance (Cltp) was 709 +/- 62 ml/min. 3 Following 20 mg oral doses, peak levels were reached at 1.6 +/- 0.2 h and the systemic availability was 88 +/- 10%. Elimination half-life (T 1/2 beta) was unaffected by dose and the area under the curve increased linearly with dose and was unaffected by food. 4 Renal excretion (24 h) of unmetabolized ranitidine accounted for 50-70% of the dose with a further 1-3% appearing as desmethyl ranitidine.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2020
DOI: 10.1186/S12913-019-4814-6
Abstract: Composite measures combine data to provide a comprehensive view of patient outcomes. Despite composite measures being a valuable tool to assess post-intervention outcomes, the patient perspective is often missing. The purpose of this study was to develop a composite measure for an established cardiac outcome registry, by combining clinical outcomes following percutaneous coronary interventions (PCI) with a patient-reported outcome measure (PROM) developed specifically for this population (MC-PROM). Two studies were undertaken. Study 1: Patients who had undergone a PCI at one of the three participating registry hospital sites completed the 5-item MC-PROM. Clinical outcome data for the patients (e.g. death, myocardial infarction, repeat vascularisation, new bleeding event) were collected 30 days post-intervention as part of routine data collection for the cardiac registry. Exploratory factor analysis of clinical outcomes and MC-PROM data was conducted to determine the minimum number of constructs to be included in a composite measure. Study 2: Clinical experts participated in a Delphi technique, consisting of three rounds of online surveys, to determine the clinical outcomes to be included and the weighting of the clinical outcomes and MC-PROM score for the composite measure. Study 1: Routine clinical outcomes and the MC-PROM data were collected from 266 patients 30 days post PCI. The MC-PROM score was not significantly correlated with any clinical outcomes. Study 2: There was a relatively consistent approach to the weighting of the clinical outcomes and MC-PROM items by the expert panel ( n = 18) across the three surveys with the exception of the clinical outcome of ‘ deceased at 30 days’ . The final composite measure included five clinical outcomes within 30 days weighted at 90% (new heart failure, new myocardial infarction, new stent thrombosis, major bleeding event, new stroke, unplanned cardiac rehospitalisation) and the MC-PROM score (comprising 10% of the total weighting). A single patient level composite score, which incorporates weighted clinical outcomes and a PROM was developed. This composite score provides a more comprehensive reported measure of in idual patient wellbeing at 30 days post their PCI-procedure, and may assist clinicians to further assess and address patient level factors that potentially impact on clinical recovery.
Publisher: MDPI AG
Date: 29-06-2023
DOI: 10.3390/GERIATRICS8040071
Abstract: Objective: To identify the socio-demographic, lifestyle, and clinical characteristics associated with self-reported weight status in early (age 18 years) and late (age ≥ 70 years) adulthood. Methods: The number of participants was 11,288, who were relatively healthy community-dwelling Australian adults aged ≥70 years (mean age 75.1 ± 4.2 years) in the Aspirin in Reducing Events in the Elderly (ASPREE) Longitudinal Study of Older Persons (ALSOP) sub-study. Self-reported weight at the study baseline (age ≥ 70 years) and recalled weight at age 18 years were collected. Height measured at baseline was used to calculate the BMI at both time points. In iduals were categorised into one of five ‘lifetime’ weight status groups: healthy weight (at both age 18 year and ≥70 years), overweight (at either or both times), non-obese (age 18 year) to obesity (age ≥70 years), obesity (age 18 years) to non-obese (age ≥ 70 years), and early and later life obesity (at age 18 years and ≥70 years). Results: Participants who experienced obesity in early and/or late adulthood were at a higher risk of adverse clinical characteristics. Obesity in late adulthood (regardless of early adulthood weight status) was associated with high proportions of hypertension, diabetes, and dyslipidaemia, whereas obesity in early adulthood (regardless of late adulthood weight status) was associated with lower cognitive scores (on all four measures). Discussion/Conclusion: Healthy or overweight weight status in early and later adulthood was associated with more favourable socioeconomic, lifestyle, and clinical measures. Obesity in early adulthood was associated with lower cognitive function in later adulthood, whereas obesity in later adulthood was associated with hypertension, diabetes, and dyslipidaemia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2014
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.BJPS.2017.04.003
Abstract: An estimated 1-3% of all women in the Netherlands carry breast implants. Since the introduction five decades ago, problems with a variety of breast implants have emerged with direct consequences for the patients' health. Plastic surgeons worldwide reacted through c aigning for auditing on long-term implant quality, surgeon performance, and institutional outcomes in implant registries. Especially, the PIP implant scandal of 2010 demonstrated the paucity of epidemiological data and uncovered a weakness in our ability to even 'track and trace' patients. In addition, a recent report of the Dutch Institute of National Health showed a lack of compliance of 100% of breast implant producers to CE requirements. These arguments stress the need for an independent implant registry. Insufficient capture rates or dependence from the implant producers made the variety of national and international patient registries unreliable. The Dutch Breast Implant Registry (DBIR) is unique because it is an opt-out registry without the need for informed consent and thus a high capture rate. Furthermore, an estimated 95% of breast implants are implanted by board-certified plastic surgeons. Funding was received from a non-governmental organisation to increase the quality of health care in the Netherlands, and maintenance is gathered by 25 euros per implant inserted. This article describes the way the Dutch have set up their system, with special attention to the well-known hurdles of starting a patient registry. Ex les include: funding, medical ethical issues, opt out system, benchmarking, quality assurance as well as governance and collaboration. The Dutch consider their experience and data shareware for others to be used globally to the benefit of patient safety and quality improvement.
Publisher: Springer Science and Business Media LLC
Date: 29-01-2018
DOI: 10.1007/S11136-018-1795-6
Abstract: Patient-reported outcome measures (PROMs) capture health information from the patient's perspective that can be used when weighing up benefits, risks and costs of treatment. This is important for elective procedures such as those for coronary revascularisation. Patients should be involved in the development of PROMs to accurately capture outcomes that are important for the patient. The aims of this review are to identify if patients were involved in the development of cardiovascular-specific PROMs used for assessing outcomes from elective coronary revascularisation, and to explore what methods were used to capture patient perspectives. PROMs for evaluating outcomes from elective coronary revascularisation were identified from a previous review and an updated systematic search. The studies describing the development of the PROMs were reviewed for information on patient input in their conceptual and/or item development. 24 PROMs were identified from a previous review and three additional PROMs were identified from the updated search. Full texts were obtained for 26 of the 27 PROMs. The 26 studies (11 multidimensional, 15 unidimensional) were reviewed. Only nine studies reported developing PROMs using patient input. For eight PROMs, the inclusion of patient input could not be judged due to insufficient information in the full text. Only nine of the 26 reviewed PROMs used in elective coronary revascularisation reported involving patients in their conceptual and/or item development, while patient input was unclear for eight PROMs. These findings suggest that the patient's perspective is often overlooked or poorly described in the development of PROMs.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2020
DOI: 10.1186/S12877-020-01741-2
Abstract: Dementia was identified as a priority area for the development of a Clinical Quality Registry (CQR) in Australia in 2016. The Australian Dementia Network (ADNeT) Registry is being established as part of the ADNeT initiative, with the primary objective of collecting data to monitor and enhance the quality of care and patient outcomes for people diagnosed with either dementia or Mild Cognitive Impairment (MCI). A secondary aim is to facilitate the recruitment of participants into dementia research and trials. This paper describes the Registry protocol. The ADNeT Registry is a prospective CQR of patients newly diagnosed with either dementia or MCI. Eligible patients will be identified initially from memory clinics and in idual medical specialists (e.g., geriatricians, psychiatrists and neurologists) involved in the diagnosis of dementia. Participants will be recruited using either an opt-out approach or waiver of consent based on three key determinants (capacity, person responsible, and communication of diagnosis). Data will be collected from four sources: participating sites, registry participants, carers, and linkage with administrative datasets. It is anticipated that the Registry will recruit approximately 10,000 participants by the end of 2023. The ADNeT registry will be developed and implemented to comply with the national operating principles for CQRs and governed by the ADNeT Registry Steering Committee. The ADNeT Registry will provide important data on current clinical practice in the diagnosis, treatment and care of people with dementia and MCI in Australia as well as long-term outcomes among these people. These data will help to identify variations in clinical practice and patient outcomes and reasons underlying these variations, which in turn, will inform the development of interventions to improve care and outcomes for people with dementia and MCI.
Publisher: Oxford University Press (OUP)
Date: 25-03-2011
Abstract: Assessing the reliability of clinical registries is important for ensuring the availability of credible data. Therefore, this study aimed to investigate the reliability of data collected by the Australian and New Zealand Haemostasis Registry (the registry). Data from 5% of randomly selected registry cases were re-abstracted by an independent data auditor who was blinded to the results of the original data abstraction. Categorical data were investigated for agreement between original and re-abstracted data. The mean difference and standard deviations (SD) of differences were calculated for continuous variables. We estimated a 'prediction interval' as the mean difference ± twice the SD of differences. We computed a coefficient of variation as the SD of differences. The registry records all cases of off-licence use of recombinant activated factor VII (rFVIIa) at participating institutions (on-licence use of rFVIIa is not recorded). Data on 76 registry cases (6% of registry) were re-abstracted. Various parameters demonstrated high levels of inter-rater reliability, including age, gender and intensive care unit admission (88, 99 and 99% agreement, respectively). Other variables were highly unreliable, including crystalloid infusion volumes (coefficient of variation 123.01%), red blood cell units (92.05%) and time from bleeding onset to administration of rFVIIa (153.06%). Registry audits are useful for identifying variables with poor reliability. Repeated audits will not improve data reliability however, they can assist in identifying and evaluating the impact of modified data collection processes on improving data reliability.
Publisher: BMJ
Date: 05-1996
Publisher: Springer Science and Business Media LLC
Date: 04-1988
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2020
DOI: 10.1161/HYPERTENSIONAHA.120.16209
Abstract: High office blood pressure variability (OBPV) in midlife increases the risk of cardiovascular disease (CVD), but the impact of OBPV in older adults without previous CVD is unknown. We conducted a post hoc analysis of ASPREE trial (Aspirin in Reducing Events in the Elderly) participants aged 70-years and older (65 for US minorities) without history of CVD events at baseline, to examine risk of incident CVD associated with long-term, visit-to-visit OBPV. CVD was a prespecified, adjudicated secondary end point in ASPREE. We estimated OBPV using within-in idual SD of mean systolic BP from baseline and first 2 annual visits. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% CI for associations with CVD events. In 16 475 participants who survived to year 2 without events, those in the highest tertile of OBPV had increased risk of CVD events after adjustment for multiple covariates, when compared with participants in the lowest tertile (HR, 1.36 [95% CI, 1.08–1.70] P =0.01). Similar increased risk was observed for ischemic stroke (HR, 1.56 [95% CI, 1.04–2.33] P =0.03), heart failure hospitalization, or death (HR, 1.73 [95% CI, 1.07–2.79] P =0.02), and all-cause mortality (HR, 1.27 [95% CI, 1.04–1.54] P =0.02). Findings were consistent when stratifying participants by use of antihypertensive drugs, while sensitivity analyses suggested the increased risk was especially for in iduals whose BP was uncontrolled during the OBPV estimation period. Our findings support increased OBPV as a risk factor for CVD events in healthy older adults with, or without hypertension, who have not had such events previously. URL: www.clinicaltrials.gov Unique identifiers: NCT01038583 URL: www.isrctn.com Unique identifiers: ISRCTN83772183.
Publisher: Oxford University Press (OUP)
Date: 17-02-2018
Abstract: The onset of many illnesses is confounded with age and sex. Increasing age is a risk factor for the development of many illnesses, and sexual dimorphism influences brain anatomy, function, and cognition. Here, we examine frequency-specific connectivity in resting-state networks in a large s le (n = 406) of healthy aged adults. We quantify frequency-specific connectivity in three resting-state networks known to be implicated in age-related decline: the default mode, dorsal attention, and salience networks, using multiband functional magnetic resonance imaging. Frequency-specific connectivity was quantified in four bands: low (0.015–0.027 Hz), moderately low (0.027–0.073 Hz), moderately high (0.073–0.198 Hz), and high (0.198–0.5 Hz) frequency bands, using mean intensity and spatial extent. Differences in connectivity between the sexes in each of the three networks were examined. Each network showed the largest intensity and spatial extent at low frequencies and smallest extent at high frequencies. Males showed greater connectivity than females in the salience network. Females showed greater connectivity than males in the default mode network. Results in this healthy aged cohort are compatible with those obtained in young s les, suggesting that frequency-specific connectivity, and differences between the sexes, are maintained into older age. Our results indicate that sex should be considered as an influencing factor in studies of resting-state connectivity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2011
DOI: 10.1161/STROKEAHA.111.615674
Abstract: Warfarin is an effective drug for the prevention of thromboembolism in the elderly. The major risk for patients taking warfarin is bleeding. We aimed to assess the impact of psychosocial factors, including mood, cognition, social isolation, and health literacy on warfarin instability among community-based elderly patients. A case–control study was conducted between March 2008 and June 2009 in a community-based setting. Cases were patients previously stabilized on warfarin who recorded an international normalized ratio ≥6.0. Control subjects were patients whose international normalized ratio measurement was maintained within the therapeutic range. Patient interviews investigated potential predisposing factors to elevated International Normalized Ratio levels. A total of 486 patients were interviewed: 157 cases and 329 control subjects, with an approximate mean age of 75 years. Atrial fibrillation was the most common primary indication. Adjusted multivariate logistic regression revealed impaired cognition (OR, 1.9 95% CI, 1.0 to 3.6), depressed mood (OR, 2.2 95% CI, 1.2 to 3.9), and inadequate health literacy (OR, 4.0 % CI, 2.1 to 7.4) were associated with increased risk of an elevated International Normalized Ratio. This study identified impaired cognition, depressed mood, and inadequate health literacy as risk factors for warfarin instability. These had a similar impact to well-recognized demographic, clinical, and medication-related factors and are prevalent among the elderly. These findings suggest that elderly patients prescribed warfarin should be reviewed regularly for psychosocial deficits.
Publisher: Oxford University Press (OUP)
Date: 17-07-2019
DOI: 10.1093/ASJ/SJZ178
Publisher: American Diabetes Association
Date: 07-1987
Abstract: We prospectively investigated the evolution of proteinuria in 52 type I diabetics over 7.8 ± 0.3 (mean ± SE) yr and in 61 type II diabetics over 6.4 ± 0.3 yr. Measurements of renal protein clearance were performed serially, and the time course of proteinuria was classified in each subject based on a threshold albumin clearance of 11 nl/s, equivalent to a urinary albumin excretion rate of 30 μg/min. The classification based on this threshold yielded four distinct patterns of albuminuria: minimal, intermittent, progressing, and established. These patterns occurred in both type I and type II diabetics independently of the duration of follow-up. This study has identified a pattern of intermittent microalbuminuria that is also associated with transient elevations of transferrin and IgG clearances. The relationship of clinical and biochemical parameters to proteinuria patterns was evaluated. No relationship was detected between proteinuria patterns and glycemic control in either type I or type II diabetics. In type I but not type II diabetics, established proteinuria was associated with higher systolic blood pressure and decreased creatinine clearance. The phase of intermittent proteinuria detected in this study may represent a reversible stage in the development of diabetic nephropathy, but the factors that trigger the transition to progressing proteinuria remain obscure.
Publisher: Springer Science and Business Media LLC
Date: 27-01-2020
DOI: 10.1038/S41398-020-0722-0
Abstract: Clozapine is the most effective antipsychotic drug for schizophrenia, yet it can cause life-threatening adverse drug reactions, including myocarditis. The aim of this study was to determine whether schizophrenia patients with clozapine-induced myocarditis have a genetic predisposition compared with clozapine-tolerant controls. We measured different types of genetic variation, including genome-wide single-nucleotide polymorphisms (SNPs), coding variants that alter protein expression, and variable forms of human leucocyte antigen (HLA) genes, alongside traditional clinical risk factors in 42 cases and 67 controls. We calculated a polygenic risk score (PRS) based on variation at 96 different genetic sites, to estimate the genetic liability to clozapine-induced myocarditis. Our genome-wide association analysis identified four SNPs suggestive of increased myocarditis risk ( P 1 × 10 −6 ), with odds ratios ranging 5.5–13.7. The SNP with the lowest P value was rs74675399 (chr19p13.3, P = 1.21 × 10 −7 OR = 6.36), located in the GNA15 gene, previously associated with heart failure. The HLA-C*07:01 allele was identified as potentially predisposing to clozapine-induced myocarditis (OR = 2.89, 95% CI: 1.11–7.53), consistent with a previous report of association of the same allele with clozapine-induced agranulocytosis. Another seven HLA alleles, including HLA-B*07:02 (OR = 0.25, 95% CI: 0.05–1.2) were found to be putatively protective. Long-read DNA sequencing provided increased resolution of HLA typing and validated the HLA associations. The PRS explained 66% of liability ( P value = 9.7 × 10 −5 ). Combining clinical and genetic factors together increased the proportion of variability accounted for ( r 2 0.73, P = 9.8 × 10 −9 ). However, due to the limited s le size, in idual genetic associations were not statistically significant after correction for multiple testing. We report novel candidate genetic associations with clozapine-induced myocarditis, which may have potential clinical utility, but larger cohorts are required for replication.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.HLC.2017.07.013
Abstract: The Victorian Cardiac Outcomes Registry (VCOR) was established in 2012 to ensure the safety and quality of cardiac based therapies across Victoria. As a clinical quality registry, VCOR monitors the performance of health services in both the public and private sectors, by measuring and reporting on trends in the quality of patient care over time, within in idual hospitals, comparatively with other hospitals, and aggregated at the state level. The current paper describes the VCOR registry aims, methods, governance structure and progress to date. Primary management of the registry is undertaken at Monash University in association with the Victorian Cardiac Clinical Network, Department of Health and Human Services Victoria. The Victorian Cardiac Outcomes Registry has currently collected data on more than 33,000 cardiac patients across three separate areas of interest in 35 hospitals. These include percutaneous coronary intervention (PCI), the early treatment of acute myocardial infarction in rural and regional settings, and data relating to in-hospital management of heart failure. The Victorian Cardiac Outcomes Registry is a clinical cardiac registry that commenced data collection in 2013, providing a detailed description of selected aspects of contemporary cardiology clinical practice in a majority of Victorian hospitals. This information enables hospitals and cardiac units to benchmark their practice, clinical outcomes and quality of care to other similar units and hospitals across the state. If replicated by other states in Australia, there will be the potential for important national comparisons, with the goal to foster continuous improvement in patient care and outcomes across the entire Australian health system.
Publisher: Public Library of Science (PLoS)
Date: 27-12-2019
Publisher: Wiley
Date: 05-1999
DOI: 10.1002/(SICI)1097-0274(199905)35:5<491::AID-AJIM6>3.0.CO;2-H
Abstract: Respiratory symptoms are known to occur in some aluminum smelter employees working in the potroom department but little is known about the respiratory health of employees in other departments. This cross-sectional study examined the prevalence of work-related respiratory symptoms and levels of lung function in different departments of two aluminum smelters compared to administration employees. Multiple logistic regression was performed with each of four work-related symptoms as outcomes and multiple linear regressions were performed with FEV1 and FVC as outcomes. There were 1,529 male participants in the two smelters representing a response rate of 89.6%. After adjusting for age and smoking, work-related respiratory symptoms were reported significantly more often among the ingot mill, anode, and potroom groups in Smelter A. In Smelter B, ingot employees were more likely to report work-related wheeze and potroom employees were more likely to report work-related rhinitis. Symptoms tended to increase with increasing time in the potrooms but were more likely to occur in new employees in the ingot mill and anode process groups. After adjusting for age, height, and smoking, there were no significant differences between the process groups for either FEV1 or FVC at Smelter A, and at Smelter B potroom employees had slightly greater FEV1 and FVC than the administration employees. Work-related respiratory symptoms among aluminum smelter workers are not reported only by potroom employees but also by ingot mill and anode employees.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2017
Publisher: Frontiers Media SA
Date: 04-05-2017
Publisher: Elsevier BV
Date: 07-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1995
Publisher: Mary Ann Liebert Inc
Date: 11-2017
Publisher: Springer Science and Business Media LLC
Date: 07-11-2016
DOI: 10.1007/S40273-015-0343-2
Abstract: There is a growing appetite for large complex databases that integrate a range of personal, socio-demographic, health, genetic and financial information on in iduals. It has been argued that 'Big Data' will provide the necessary catalyst to advance both biomedical research and health economics and outcomes research. However, it is important that we do not succumb to being data rich but information poor. This paper discusses the benefits and challenges of building Big Data, analysing Big Data and making appropriate inferences in order to advance cancer care, using Cancer 2015 (a prospective, longitudinal, genomic cohort study in Victoria, Australia) as a case study. Cancer 2015 has been linked to State and Commonwealth reimbursement databases that have known limitations. This partly reflects the funding arrangements in Australia, a country with both public and private provision, including public funding of private healthcare, and partly the legislative frameworks that govern data linkage. Additionally, linkage is not without time delays and, as such, achieving a contemporaneous database is challenging. Despite these limitations, there is clear value in using linked data and creating Big Data. This paper describes the linked Cancer 2015 dataset, discusses estimation issues given the nature of the data and presents panel regression results that allow us to make possible inferences regarding which patient, disease, genomic and treatment characteristics explain variation in health expenditure.
Publisher: BMJ
Date: 10-1994
Abstract: To assess the factors associated with cessation of smoking with transdermal nicotine and brief behavioural counselling. Interviews, treatment, and follow up for 26 weeks. 1481 subjects recruited by mass media publicity who smoked > or = 15 cigarettes a day and were motivated to stop smoking. Twelve weeks' treatment with transdermal nicotine and brief behavioural counselling at monthly visits. Sustained smoking cessation for the 28 days before the visit at week 26 verified by expired carbon monoxide concentrations. The logistic regression analysis included all subjects. Most subjects were dependent on nicotine, and the mean (SD) number of cigarettes smoked a day was 32 (12). Overall, 316/1481 subjects (21.3%) stopped smoking. Factors associated with stopping were being male (adjusted odds ratio 2.0 95% confidence interval 1.5 to 2.7), age > or = 40 years (1.5 1.1 to 2.0), living with a spouse or partner (1.5 1.1 to 2.1), motivation ("want to quit" 1.7 1.2 to 2.3), and concern about weight gain (1.7 1.3 to 2.2). Negative associations were smoking marijuana (0.4 0.2 to 0.8) and the presence of other smokers in the household (0.8 0.6 to 0.9). Almost all subjects who smoked three or more cigarettes in the first four weeks of treatment resumed smoking in the long term (525/547, 96%). Age, sex, marital status (living with a spouse or partner), motivation, concern about weight gain, recent marijuana smoking, and other smokers in the household were baseline factors associated with differences in outcome of smoking cessation attempts. Smoking three or more cigarettes in the first few weeks after stopping strongly predicted long term relapse.
Publisher: Elsevier BV
Date: 07-1990
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-10-2023
Publisher: Elsevier BV
Date: 09-1981
Abstract: An assay is described for the simultaneous determination of propranolol and its active metabolite, 4-hydroxypropranolol, in human plasma. Both compounds were separated from an ethereal extract by high-performance liquid chromatography employing a C18 bonded-phase column. Detection of the effluent was by fluorescence. Suitable fluorescent spectrometers and wavelength settings that allow optimum detection of both compounds have been described. The limit of sensitivity was 2 ng/ml for both propranolol and 4-hydroxypropranolol. Mean peak plasma levels of propranolol and 4-hydroxypropranolol in six patients receiving a single dose of a slow-release 160-mg formulation of propranolol were 28 and 6 ng/ml, respectively. These levels were about one-tenth the level obtained following a single conventionally prepared dose of propranolol (160 mg). Peak levels were delayed and plasma levels of propranolol persisted for a longer period with the slow-release formulation. Area under the curve estimates suggested that the bioavailability of the slow-release formulation following single-dose administration was about one-third that of the conventional preparation.
Publisher: Research Square Platform LLC
Date: 19-09-2023
Publisher: Springer Science and Business Media LLC
Date: 1984
DOI: 10.2165/00003495-198400282-00003
Abstract: Several compounds of the chemical class arylethanolamines have been shown to possess combined alpha- or vasodilator and beta-adrenoceptor blocking properties. The first drug was labetalol (AH5158)[5-(1-hydroxy-2)1-methyl-3-phenylpropyl(amino)-ethyl (salicylamide)]. Others include medroxalol, bucindolol and YM-09538, which differ from labetalol either by the nature of the substitution on the primary benzene ring and/or on the terminal nitrogen. All of these drugs are non-selective beta-blockers, except for bucindolol whose selectivity has not been carefully defined. The rationale for the development of this group of drugs was the knowledge that blockade of one adrenoceptor subtype causes reflex stimulation of the other, i.e. vasoconstriction after nonspecific beta-blockade and tachycardia after alpha-blockade. Since both of these compensatory responses act to prevent a fall in blood pressure, a relatively weak blockade of both receptor types should act synergistically to produce a lowering of blood pressure with minimal physiological disturbance. Haemodynamic studies have confirmed that the additional alpha-blocking properties of labetalol produce a pattern of haemodynamic changes unlike that of propranolol and other simple beta-adrenoceptor blocking agents. Peripheral vascular resistance, which falls acutely during the initial administration of the drug, tends to fall further during prolonged administration and the pulse rate tends to remain only slightly lower than pretreatment levels. In addition, at normal dose levels cardiac output is maintained by a compensatory increase in stroke volume. Thus, blood pressure is lowered largely by a reduction in vascular resistance, and although the heart rate falls significantly during exercise, the cardiac output is maintained by an increase in stroke volume. This pattern of events is different to that seen with beta-blocking agents which consistently reduce cardiac output during exercise. Currently labetalol is the only member of this group of drugs which is in established clinical use. Its antihypertensive efficacy has been confirmed in many studies and it has been shown to be effective in the management of both hypertensive emergencies and in the long term management of severe hypertension. It is particularly valuable in allowing a reduction in the number of drugs required for adequate blood pressure control. The early theoretical prediction that postural hypotension would occur with high doses is now acknowledged to be labetalol's major dose-limiting side effect. Most of the available pharmacokinetic data on labetalol were derived from studies which utilised a fluorimetric assay.(ABSTRACT TRUNCATED AT 400 WORDS)
Publisher: BMJ
Date: 04-2000
DOI: 10.1136/OEM.57.4.279
Abstract: Employees in alumina refineries are known to be exposed to a number of potential respiratory irritants, particularly caustic mist and bauxite and alumina dusts. To examine the prevalence of work related respiratory symptoms and lung function in alumina refinery employees and relate these to their jobs. 2964 current employees of three alumina refineries in Western Australia were invited to participate in a cross sectional study, and 89% responded. Subjects were given a questionnaire on respiratory symptoms, smoking, and occupations with additional questions on temporal relations between respiratory symptoms and work. Forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were measured with a rolling seal spirometer. Atopy was assessed with prick skin tests for common allergens. Associations between work and symptoms were assessed with Cox's regression to estimate prevalence ratios, and between work and lung function with linear regression. Work related wheeze, chest tightness, shortness of breath, and rhinitis were reported by 5.0%, 3.5%, 2.5%, and 9.5% of participants respectively. After adjustment for age, smoking, and atopy, most groups of production employees reported a greater prevalence of work related symptoms than did office employees. After adjustment for age, smoking, height, and atopy, subjects reporting work related wheeze, chest tightness, and shortness of breath had significantly lower mean levels of FEV(1) (186, 162, and 272 ml respectively) than subjects without these symptoms. Prevalence of most work related symptoms was higher at refinery 2 than at the other two refineries, but subjects at this refinery had an adjusted mean FEV(1) >60 ml higher than the others. Significant differences in FVC and FEV(1)/FVC ratio, but not FEV(1), were found between different process groups. There were significant differences in work related symptoms and lung function between process groups and refineries, but these were mostly not consistent. Undefined selection factors and underlying population differences may account for some of these findings but workplace exposures may also contribute. The differences identified between groups were unlikely to be clinically of note.
Publisher: Springer Science and Business Media LLC
Date: 12-06-2014
Publisher: Oxford University Press (OUP)
Date: 08-08-2023
DOI: 10.1093/AJE/KWAD168
Abstract: The ASPirin in Reducing Events in the Elderly (ASPREE) trial recruited 19,114 participants across Australia and the United States during 2010-14. Participants were randomized to receive either 100mg aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open label aspirin (OLA). In the placebo group, 35% and 11% ceased study medication and commenced OLA, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people along with an elevated risk of clinically significant bleeding.
Publisher: Wiley
Date: 04-1979
DOI: 10.1111/J.1365-2125.1979.TB04774.X
Abstract: 1 This study was designed to compare in a double-blind randomized crossover trial, atenolol, labetalol, metoprolol and pindolol. Considerable differences in dose (atenolol 138 +/- 13 mg daily labetalol 308 +/- 34 mg daily metoprolol 234 +/- 22 mg daily and pindolol 24 +/-2 mg daily were required to produce similar antihypertensive effects. 3 The overall incidence of side-effects was similar with atenolol, metoprolol and pindolol but was slightly less with labetalol. Sleep disturbances and abnormal dreaming patterns were most frequent with pindolol. 4 There was a significantly greater fall in pulse rate during atenolol and metoprolol treatment periods.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 02-1978
Publisher: Springer Science and Business Media LLC
Date: 18-10-2014
Publisher: Informa UK Limited
Date: 1986
Publisher: Wiley
Date: 05-1997
DOI: 10.1111/J.1440-1681.1997.TB01204.X
Abstract: 1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was > or = 160 mmHg systolic or > or = 90 mmHg diastolic if systolic BP was > or = 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82,000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP > or = 160/90 mmHg. Forty-seven per cent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2022
DOI: 10.1161/HYPERTENSIONAHA.122.19356
Abstract: Impaired cerebral blood flow has been associated with an increased risk of falls. Mean arterial pressure (MAP) and variability in MAP have been reported to affect cerebral blood flow but their relationships to the risk of falls have not previously been reported. Utilising data from the Aspirin in Reducing Events in the Elderly trial participants, we estimated MAP and variability in MAP, defined as within-in idual SD of MAP from baseline and first 2 annual visits. The relationship with MAP was studied in 16 703 participants amongst whom 1539 falls were recorded over 7.3 years. Variability in MAP was studied in 14 818 of these participants who experienced 974 falls over 4.1 years. Falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratio and 95% CI for associations with falls. Long-term variability in MAP was not associated with falls except amongst frail or prefrail participants using antihypertensive medications. Within this group each 5 mm Hg increase in long-term variability in MAP increased the risk of falls by 16% (hazard ratio, 1.16 [95% CI, 1.02–1.33]). Amongst the antihypertensive drugs studied, beta-blocker monotherapy (hazard ratio, 1.93 [95% CI, 1.17–3.18]) was associated with an increased risk of falls compared with calcium channel blockers. Higher levels of long-term variability in MAP increase the risk of serious falls in older frail and prefrail in iduals taking antihypertensive medications. The observation that the relationship was limited to frail and prefrail in iduals might explain some of the variability of previous studies linking blood pressure indices and falls.
Publisher: Wiley
Date: 11-1990
DOI: 10.1111/J.1365-2125.1990.TB03833.X
Abstract: 1. The antihypertensive effect of dilevalol, a compound which combines beta-adrenoceptor blocking and vasodilating properties due to beta 2-adrenoceptor agonism, was studied in nineteen patients with isolated systolic hypertension (ISH). A randomized, double-blind, placebo-controlled, cross-over trial with two 4 week treatment periods was used to compare the efficacy of once daily dosing with dilevalol (in the range of 100-400 mg daily) against placebo. Assessment of response involved both casual blood pressure readings (amongst all patients) and 24 h ambulatory blood pressure monitoring (in ten of the nineteen patients). 2. A mean fall of 12/5 mm Hg (s.e. mean 3/2, P less than 0.05) and 9/3 mm Hg (s.e. mean 3/2, P less than 0.05) in supine and standing blood pressure respectively was observed with dilevalol. Mean heart rate was unchanged. The ambulatory monitoring profile demonstrated a smaller reduction in mean blood pressure (7/8 mm Hg) over the 24 h period and a reduction of 10/11 mm Hg over the daytime period. A blunting of the early morning increase in systolic pressure was observed with dilevalol. 3. The drug was well tolerated with light headedness and lethargy being reported more commonly than with placebo. Biochemical parameters were unaffected. 4. It is concluded that dilevalol in the doses used has a small but measurable antihypertensive effect as monotherapy in the treatment of ISH.
Publisher: Informa UK Limited
Date: 24-01-2023
Publisher: SAGE Publications
Date: 07-2000
DOI: 10.1177/153857440003400414
Abstract: A 65-year-old man with right iliac artery occlusion, left iliofemoral stenosis, and bilateral superficial femoral arteries occlusion, instead of receiving the traditional aortofemoral bypass, underwent in sequence the following operations: left common iliac to femoral bypass, femorofemoral bypass, and bilateral femoropopliteal bypasses with use of polytetrafluoroethylene (PTFE) grafts. Occlusion of the femoropopliteal bypass and stenosis of the iliofemoral bypass at the distal anastomosis resulted in severe leg ischemia with nonhealing toes and leg ulcers. To minimize ischemia time to the lower extremities, pelvic organs, and kidney and avoid the need for multilevel revascularization, the patient received aortobipopliteal bypass via obturator foramina. The aortic anastomosis was intentionally constructed in and end-to-side fashion to avert the need for left accessory renal artery implantation and interruption of the pelvic arterial supply. The patient has palpable ankle pulses and progressed to heal the ischemic ulcers following the aortobipopliteal bypass operation.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2016
Publisher: Elsevier BV
Date: 04-2019
Publisher: Springer Science and Business Media LLC
Date: 12-2019
DOI: 10.1186/S13063-019-3789-2
Abstract: Large-scale studies risk generating inaccurate and missing data due to the complexity of data collection. Technology has the potential to improve data quality by providing operational support to data collectors. However, this potential is under-explored in community-based trials. The Aspirin in reducing events in the elderly (ASPREE) trial developed a data suite that was specifically designed to support data collectors: the ASPREE Web Accessible Relational Database ( AWARD ). This paper describes AWARD and the impact of system design on data quality. AWARD ’s operational requirements, conceptual design, key challenges and design solutions for data quality are presented. Impact of design features is assessed through comparison of baseline data collected prior to implementation of key functionality ( n = 1000) with data collected post implementation ( n = 18,114). Overall data quality is assessed according to data category. At baseline, implementation of user-driven functionality reduced staff error (from 0.3% to 0.01%), out-of-range data entry (from 0.14% to 0.04%) and protocol deviations (from 0.4% to 0.08%). In the longitudinal data set, which contained more than 39 million data values collected within AWARD , 96.6% of data values were entered within specified query range or found to be accurate upon querying. The remaining data were missing (3.4%). Participant non-attendance at scheduled study activity was the most common cause of missing data. Costs associated with cleaning data in ASPREE were lower than expected compared with reports from other trials. Clinical trials undertake complex operational activity in order to collect data, but technology rarely provides sufficient support. We find the AWARD suite provides proof of principle that designing technology to support data collectors can mitigate known causes of poor data quality and produce higher-quality data. Health information technology (IT) products that support the conduct of scheduled activity in addition to traditional data entry will enhance community-based clinical trials. A standardised framework for reporting data quality would aid comparisons across clinical trials. International Standard Randomized Controlled Trial Number Register, ISRCTN83772183 . Registered on 3 March 2005.
Publisher: MDPI AG
Date: 05-02-2023
Abstract: Introduction: Cancer treatment planning in older adults is complex and requires careful balancing of survival, quality of life benefits, and risk of treatment-related morbidity and toxicity. As a result, treatment selection in this cohort tends to differ from that for younger patients. However, there are very few studies describing cancer treatment patterns in older cohorts. Methods: We used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Cancer Treatment Substudy (ACTS) to describe cancer treatment patterns in older adults. We used a multivariate logistic regression model to identify factors affecting receipt of treatment. Results: Of 1893 eligible Australian and United States (US) participants with incident cancer, 1569 (81%) received some form of cancer treatment. Non-metastatic breast cancers most frequently received treatment (98%), while haematological malignancy received the lowest rates of treatment (60%). Factors associated with not receiving treatment were older age (OR 0.94, 95% CI 0.91–0.96), residence in the US (OR 0.34, 95% CI 0.22–0.54), smoking (OR 0.57, 95% CI 0.40–0.81), and diabetes (OR 0.56, 95% CI 0.39–0.80). After adjustment for treatment patterns in sex-specific cancers, sex did not impact receipt of treatment. Conclusions: This study is one of the first describing cancer treatment patterns and factors affecting receipt of treatment across common cancer types in older adults. We found that most older adults with cancer received some form of cancer treatment, typically surgery or systemic therapy, although this varied by factors such as cancer type, age, sex, and country of residence.
Publisher: Springer Science and Business Media LLC
Date: 02-12-2020
DOI: 10.1007/S10877-019-00437-2
Abstract: Respiratory rate (RR) is one of the most sensitive markers of a deteriorating patient. Despite this, there is significant inter-observer discrepancy when measured by clinical staff, and modalities used in clinical practice such as ECG bioimpedance are prone to error. This study utilized infrared thermography (IRT) to measure RR in a critically ill population in the Intensive Care Unit. This study was carried out in a Single Hospital Centre. Respiratory rate in 27 extubated ICU patients was counted by two observers and compared to ECG Bioimpedance and IRT-derived RR at distances of 0.4-0.6 m and > 1 m respectively. IRT-derived RR using two separate computer vision algorithms outperformed ECG derived RR at distances of 0.4-0.6 m. Using an Autocorrelation estimator, mean bias was - 0.667 breaths/min. Using a Fast Fourier Transform estimator, mean bias was - 1.000 breaths/min. At distances greater than 1 m no statistically significant signal could be obtained. Over all frequencies, there was a significant relationship between the RR estimated using IRT and via manual counting, with Pearson correlation coefficients between 0.796 and 0.943 (p 19 bpm (r = 0.562, p = 0.029). Overall agreement between IRT-derived RR at distances of 0.4-0.6 m and gold standard counting was satisfactory, and outperformed ECG derived bioimpedance. Contactless IRT derived RR may be feasible as a routine monitoring modality in wards and subacute inpatient settings.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2011
Publisher: SAGE Publications
Date: 26-11-2016
Abstract: The objective of our study was to describe spontaneously reported haemorrhagic adverse events associated with rivaroxaban and dabigatran in Australia. Data were sourced from the Australian Therapeutic Goods Administration (TGA) Database of Adverse Event Notifications between June 2009 and May 2014. Records of haemorrhagic adverse events in which rivaroxaban or dabigatran was considered as a potential cause were analysed. There were 240 haemorrhagic adverse events associated with rivaroxaban and 504 associated with dabigatran. Age was specified for 164 (68%) haemorrhages associated with rivaroxaban, of which 101 occurred in people aged ⩾75 years. Age was specified for 437 (87%) haemorrhages associated with dabigatran, of which 300 occurred in people aged ⩾75 years. Time from treatment initiation to haemorrhage was specified for 122 (51%) haemorrhages associated with rivaroxaban, with 69 (57%) haemorrhages occurring within 30 days of rivaroxaban initiation. Time from treatment initiation to haemorrhage was specified for 253 (50%) haemorrhages associated with dabigatran, with 123 (49%) haemorrhages occurring within 30 days of dabigatran initiation. Gastrointestinal (GI) haemorrhages were the most frequent type of haemorrhages associated with both rivaroxaban ( n = 105, 44%) and dabigatran ( n = 302, 60%). Data were available on the severity of haemorrhage for 101 (42%) haemorrhages associated with rivaroxaban, with haemorrhage leading to death in 17 people. The severity of haemorrhage was specified for 384 (76%) haemorrhages associated with dabigatran, with haemorrhage leading to death in 61 people. Our study highlights the need for research on the haemorrhagic complications of anticoagulation in clinical care. A considerable proportion of reported haemorrhagic events occurred within 30 days of rivaroxaban and dabigatran initiation. This highlights the importance of considering bleeding risk at the time of treatment initiation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1989
DOI: 10.1097/00004872-198908000-00008
Abstract: Two formulations of felodipine, conventional and extended release (ER) tablets, were compared in a double-blind, crossover study of patients whose blood pressure was not being controlled using metoprolol 100 mg once daily. Nineteen patients with a supine diastolic blood pressure greater than or equal to 95 mmHg after 4 weeks of taking metoprolol and placebo were randomly assigned to felodipine conventional (5 mg twice a day) or ER (10 mg once daily) for 4 weeks. A 2-week washout period was then followed by 4 weeks of treatment with the alternative formulation. Metoprolol once daily was taken concomitantly throughout the study. Clinic blood pressure was measured at 0 h (i.e. 12 h after the last dose of conventional, and 24 h after the last ER felodipine dose), and then 2 and 5 h after the following dose had been taken. Ambulatory blood pressure and the heart rate were monitored over 24 h using an Accutracker (Suntech Medical Instruments, Raleigh, North Carolina, USA). During the final treatment, both felodipine formulations caused similar substantial falls in supine blood pressure compared with pressures prior to randomized treatment. The falls in clinic blood pressures (systolic/diastolic) were similar with the conventional and ER formulations at all time points, i.e. 0 h (21/13 19/11 mmHg), 2 h (39/18 36/18 mmHg) and 5 h (30/12 35/11 mmHg) after the morning dose was taken. Both formulations also produced similar falls in blood pressures over 24 h and during the daytime (21/12 20/12 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 08-1982
DOI: 10.1016/0002-8703(82)90130-2
Abstract: The development of beta-adrenoreceptor-blocking drugs provided an important group of agents to treat the cardiovascular disorders hypertension, angina pectoris, and cardiac arrhythmias and to manage patients with thyrotoxicosis. For clinical purposes, these drugs can be ided into two groups, that is, those with intrinsic sympathomimetic activity (ISA) and those without (non-ISA). The non-ISA drugs include propranolol, which is noncardiac selective: labetalol, which is noncardiac selective with alpha blockade: and and metoprolol and atenolol, which are cardiac selective. The drugs with ISA include pindolol, oxprenolol, and alprenolol which are noncardiac selective, and practolol which is cardiac selective. These drugs resemble isoprenaline in chemical structure, but their interaction with the beta-adrenoreceptors causes no response or only a slight response if the drug has ISA. By occupying the receptors, they block excitation by noradrenaline released from the sympathetic nerves and by adrenaline from the adrenal medulla. Drugs with ISA appear to depress cardiac activity and to interfere with bronchodilator drive less than do non-ISA drugs. Beta-blocking drugs differ considerably in their bioavailability because of differences in the rate and extent of metabolism in the first past through the liver after absorption from the gut. The therapeutic dose range varies widely for those with low bioavailability but is more predictable for those with high bioavailability. The drugs also differ in plasma protein binding and in their receptor affinities. In addition to their usual adverse effects, which include exacerbation of cardiac failure, bronchospasm, sleep disturbances, and Raynaud's phenomenon, concern has arisen about possible ocular and mucocutaneous side effects with beta-blocking drugs. This is a recognized problem with practolol, and it is not certain whether it occurs with other beta-blocking drugs. A double-blind study reported here of 110 matched patients, 36 of whom were on pindolol for more than 2 years, did not reveal any evidence of oculomucocutaneous problems related to drug treatment.
Publisher: Wiley
Date: 14-02-2007
DOI: 10.1111/J.1445-2197.2006.03988.X
Abstract: The aim of this study was to develop a points-based approach to prioritize patients for elective transurethral resection of the prostate and to determine the relative contributions that clinical and psychosocial characteristics should make to a measurement of urgency for surgery. Another objective was to measure the agreement between urologists, other medical practitioners and laypersons in assessing the major determinants of priority. A focus group of urologists and epidemiologists developed a standard questionnaire identifying relevant clinical and psychosocial factors in men with benign prostatic hypertrophy. The questionnaire was used to interview 48 men with benign prostatic hypertrophy being placed on waiting lists for transurethral resection of the prostate at four Victorian public hospitals. In idual patient case vignettes were produced using the answers to the interview questions. Members of an assessor panel comprising six laypeople, six non-urologist medical practitioners, and five urologists in idually reviewed the vignettes and assigned urgency ratings and rankings to each patient. The urgency ratings and rankings were used to derive weightings for the clinical and psychosocial factors that were then incorporated into a prioritization tool framework. The assessor panel perceived a broad spread of urgency for surgery among the patients. Agreement on rankings and urgency ratings was moderate among assessors. Linear regression showed that the effect of clinical symptoms and psychosocial disturbance held approximately equal-strength independent associations with perceived urgency for all groups of assessors. Urologists, non-urologist medical practitioners and laypeople considered the severity of benign prostatic hypertrophy symptoms and any resulting psychosocial disturbance as equally important in establishing priority for transurethral resection of the prostate. New prioritization tools should take both into consideration and weight them equally.
Publisher: Wiley
Date: 14-02-2014
DOI: 10.1111/BJU.12509
Abstract: To describe the characteristics of patients with and without positive surgical margins (PSMs) and to analyse the impact of PSMs on secondary cancer treatment after radical prostatectomy (RP), with short-term follow-up. We analysed data from 2385 consecutive patients treated using RP, who were notified to the Prostate Cancer Registry by 37 hospitals in Victoria, Australia between August 2008 and February 2012. Independent and multivariate models were constructed to predict the likelihood of PSMs. Independent and multivariate predictors of secondary treatment after RP in the initial 12 months after diagnosis were also assessed. Data on PSM status were collected for 2219/2385 (93%) patients. In total 592/2175 (27.2%) RPs resulted in PSMs 102/534 (19.1%) in the low-risk group, 317/1218 (26.0%) in the intermediate-risk group, 153/387 (39.5%) in the high-risk group, and 9/11 (81.8%) in the very-high-risk disease group of patients. Patients having surgery in a hospital where <10 RPs occur each year were significantly more likely to have a PSM (incidence rate ratio [IRR] 1.44, 95% confidence interval [CI] 1.07-1.93) and those in the intermediate-, high- or very-high-risk groups (IRR 1.34, 95% CI 1.09-1.65, P = 0.007, IRR 1.96, 95% CI 1.57-2.45, P < 0.001 and IRR 3.81, 95% CI 2.60-5.60, P < 0.001, respectively) were significantly more likely to have a PSM than those in the low-risk group (IRR 2.50, 95% CI 1.23-5.11, P = 0.012). Patients with PSMs were significantly less likely to have been treated at a private hospital than a public hospital (IRR 0.76, 95% CI 0.63-0.93, P = 0.006) or to have undergone robot-assisted RP (IRR 0.69, 95% CI 0.55-0.87 P = 0.002) than open RP. Of the 2182 patients who underwent RP in the initial 12 months after diagnosis, 1987 (91.1%) received no subsequent treatment, 123 (5.6%) received radiotherapy, 47 (2.1%) received androgen deprivation therapy (ADT) and 23 (1.1%) received a combination of radiotherapy and ADT. Two patients (0.1%) received chemotherapy combined with another treatment. At a multivariate level, predictors of additional treatment after RP in the initial 12 months included having a PSM compared with a negative surgical margin (odds ratio [OR] 5.61, 95% CI 3.82-8.22, P < 0.001) pT3 compared with pT2 disease (OR 4.72, 95% CI 2.69-8.23, P < 0.001) and having high- or very-high-risk disease compared with low-risk disease (OR 4.36, 95% CI 2.24-8.50, P < 0.001 and OR 4.50, 95% CI 1.34-15.17, P = 0.015, respectively). Patient age, hospital location and hospital type were not associated with secondary treatment. Patients undergoing robot-assisted RP were significantly less likely to receive additional treatment than those receiving open RP (OR 0.59, 95% CI 0.39-0.88, P = 0.010). These data indicate an important association between hospital status and PSMs, with patients who underwent RP in private hospitals less likely than those in public hospitals to have a PSM. Patients treated in lower-volume hospitals were more likely to have a PSM and less likely to receive additional treatment after surgery in the initial 12 months, and robot-assisted RP was associated with fewer PSMs than was open RP in this non-randomized observational study. PSM status and pathological T3 disease are both important and independent predictors of secondary cancer treatment for patients undergoing RP. A robot-assisted RP approach appears to decrease the likelihood of subsequent treatment, when compared with the open approach.
Publisher: MDPI AG
Date: 30-08-2022
DOI: 10.3390/JCM11175117
Abstract: Uncertainty remains regarding the benefit of hip replacement in older adults in the context of age-related decline in physical function. This study aimed to examine the effect of hip replacement on functional outcomes and identify factors associated with clinically important improvement in physical function postoperatively in community-dwelling older adults. This cohort study was performed within the ASPREE trial, with 698 participants receiving hip replacement and 677 age- and sex-matched controls without knee or hip replacement during the trial drawn from 16,703 Australian participants aged ≥70 years. Health status (physical and mental component summary [PCS and MCS]) was assessed annually using the SF-12. Participants receiving hip replacement had significantly lower pre- and post-replacement PCS scores compared with controls (p 0.0001). There was significant improvement in PCS score following hip replacement (mean change 4.9, 95%CI 4.0–5.7) but no change in controls (0.01, 95%CI −0.7–0.7). Following hip replacement, 46.7% of participants experienced clinically important improvement in PCS score, while 15.5% experienced worsened PCS score. Participants experiencing improved postoperative PCS score had significantly lower PCS and higher MCS scores preoperatively. The degree of preoperative physical function impairment was a significant indicator of older people most likely to benefit from hip replacement surgery.
Publisher: Wiley
Date: 03-1990
DOI: 10.1111/J.1440-1681.1990.TB01306.X
Abstract: 1. The diagnosis of isolated systolic hypertension, diastolic hypertension and normotension in elderly subjects, as defined by casual office blood pressure measurement, was compared with 24 h ambulatory blood pressure monitoring using an Accutracker II. 2. Mean day-time ambulatory blood pressure monitoring underestimated the casual systolic blood pressure in all three clinical groups. Diastolic pressure was not underestimated to the same extent. 3. Ambulatory blood pressure monitoring best reflected casual blood pressure determination for normotensive subjects. In subjects with isolated systolic hypertension ambulatory blood pressures were only consistent with that diagnosis for 8% of the day time period. For 34% of the day time, their ambulatory blood pressures were consistent with diastolic/mixed hypertension. 4. It is concluded that isolated systolic hypertension may not be a sustained condition, but rather an isolated response to office measurement of blood pressure.
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/10641969309041648
Abstract: Repeated clinic blood pressure measurement was compared with non-invasive ambulatory blood pressure monitoring in 10 elderly subjects with persistent isolated systolic hypertension and 11 normotensive controls. Mean clinic blood pressures +/- Standard Deviation (SD), at visit 1 were 165/81 +/- 12/7 mmHg and 136/87 +/- 14/10 mmHg respectively. Subjects were assessed on three subsequent occasions at weekly intervals. None were receiving antihypertensive or vasoactive medication. Clinical systolic and diastolic blood pressures were consistently higher than the corresponding mean daytime ambulatory blood pressures in both clinical groups at each of the visits. The difference was greater between the systolic pressures than between the diastolic pressures and these differences in systolic pressures were greater in the isolated systolic hypertensives (26 +/- 5 mmHg) than in the normotensives (7 +/- 18 mmHg). Daytime ambulatory readings aggregated from all four visits were normally distributed for both blood pressure components in both clinical groups. In the isolated systolic hypertension group the clinic systolic and diastolic blood pressure measurements corresponded to the 93rd and 85th percentiles of the ambulatory pressures respectively whereas in the normotensives the equivalent percentiles were 69 and 78. These results suggest a pressor response may largely account for the elevated systolic blood pressure seen in elderly subjects with sustained isolated systolic hypertension based on clinic readings.
Publisher: Massachusetts Medical Society
Date: 25-02-2016
Publisher: Elsevier BV
Date: 09-2004
Publisher: Cambridge University Press (CUP)
Date: 22-09-2009
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22534390.V1
Abstract: Supplementary Figure from Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older In iduals
Publisher: Springer Science and Business Media LLC
Date: 14-03-2019
Publisher: BMJ
Date: 05-08-1995
Abstract: To assess the efficacy and safety of a repeat course of treatment with transdermal nicotine for cessation of smoking in a brief intervention setting. Randomised, double blind, placebo controlled trial with follow up for 26 weeks. 629 smokers who had unsuccessfully attempted to stop smoking by using active transdermal nicotine and brief behavioural counselling. Smokers were motivated to quit smoking for a second time and smoked > or = 15 cigarettes a day. Twelve weeks' treatment with active transdermal nicotine patches or placebo and brief counselling at monthly visits. Sustained smoking cessation for the 28 days before the visit at week 12 verified by expired carbon monoxide concentrations. At 12 weeks 21/315 (6.7%) subjects allocated to active treatment had stopped smoking compared with 6/314 (1.9%) allocated to placebo (absolute difference 4.7% 95% confidence interval 1.6% to 7.9% P = 0.003). At 26 weeks the rates were 20/315 (6.4%) and 8/314 (2.6%) (3.8% 0.6% to 7.0% P = 0.021). Difficulty in sleeping was reported by 43/179 (24.0%) on active treatment and 19/143 (13.3%) on placebo (P = 0.015). Severe reactions at the site of application were rare (6/322 1.9%). Repeated treatment with transdermal nicotine together with brief counselling can improve the low success rates of smoking cessation in recently relapsed, moderate to heavy smokers. Questions remain about whether more intensive interventions or higher doses of nicotine could be more effective. The likelihood of severe reactions at the site of application with repeated treatment is low.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533314.V1
Abstract: Supplementary Figure from Incident Cancer Risk and Signatures Among Older i MUTYH /i Carriers: Analysis of Population-Based and Genomic Cohorts
Publisher: Oxford University Press (OUP)
Date: 06-2005
DOI: 10.1016/J.AMJHYPER.2004.12.018
Abstract: The identification of factors that contribute to noncompliance with trial drug initiation where virtually complete compliance might be expected, may help identify patients whose management is least likely to comply with clinical guidelines and study protocols. Examination of cross-sectional and longitudinal data arising from the Second Australian National Blood Pressure Study. Prevalence rate ratios (RR) and 95% confidence intervals (CI) estimated from log-binomial models were used to assess associations between subject characteristics and whether the randomized drug was prescribed at trial randomization. The study population consisted of 6083 hypertensive Australians aged 65 to 84 years. After adjusting for each variable in a multivariate model the following were significant predictors of failure to prescribe RR (95% CI): not previously prescribed antihypertensive drugs 2.89 (2.52-3.32) lower systolic blood pressure (BP) 1.51 (1.59-1.43) or diastolic BP 1.18 (1.22-1.13) younger age 80 to 84 v 65 to 79 years 0.75 (0.59-0.95) total cholesterol >or=6.6 v <or=5.0 mmol/L 1.27 (1.06-1.53) and not ever having had a raised cholesterol 1.20 (1.04-1.40). There was no difference in cardiovascular disease end points and death in those who were and were not initiated on drug therapy at randomization. Failure to initiate antihypertensive therapy for patients at the randomization visit was associated with lower BP measurements, previous drug therapy, younger age, and a historic or current raised cholesterol, but not with overt cardiovascular disease or other risk factors. There was no difference in cardiovascular disease end points and death in those who were and were not initiated on drug therapy at randomization.
Publisher: Wiley
Date: 12-10-2012
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.IJCARD.2017.04.056
Abstract: Patients undergoing palliative surgeries for single-ventricle conditions are affected by multiple comorbidities or non-cardiac conditions. The prevalence, costs and the cost implications of these conditions have not been assessed. Administrative costing records from four hospitals in Australia and New Zealand were linked with the Fontan registry database to analyze the inpatient resource use for co-morbid or non-cardiac conditions. Inpatient costing records from the birth year through to Fontan completion were available for 156 patients. The most frequent primary diagnoses were hypoplastic left heart syndrome (33%), double inlet left ventricle (13%), and tricuspid atresia (12%). During the staged surgical treatment period, children had a mean of 10±6 inpatient admissions and spent 85±64days in hospital. Among these admissions, 3±5 were for non-cardiac conditions, totaling 21±41 inpatient days. Whilst cardiac surgeries were the major reason for resource use (77% of the total cost), other cardiac care that is not surgical contributed 5% and non-cardiac admissions 18% of the total cost. The three most prevalent non-cardiac diagnostic admission categories were 'Respiratory system', 'Digestive system', and 'Ear, nose, mouth and throat', affecting 28%, 21% and 34% of the patients respectively. Multivariate regression estimated that admissions for each of these categories resulted in an increased cost of $34,563 (P=0.08), $52,438 (P=0.05) and $10,525 (P=0.53) per patient respectively for the staged surgical treatment period. Non-cardiac admissions for single-ventricle patients are common and have substantial resource implications. Further research assessing the causes of admission and extent to which admissions are preventable is warranted.
Publisher: Wiley
Date: 04-2017
DOI: 10.1111/IMJ.13384
Publisher: AMPCo
Date: 28-08-2017
DOI: 10.5694/MJA17.00005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1995
Abstract: Lacunar infarction is an important stroke subgroup with unique clinical and pathologic features, but its relative risks for associated risk factors have been rarely documented. To address this matter, we studied 203 consecutive patients with first-ever stroke due to lacunar infarction admitted to four general hospitals during the period 1985 to 1992. We obtained information concerning risk factor exposure status among the patients by interview using a structured questionnaire and by comparison with age- and sex-matched neighborhood controls. Odds ratios were estimated with adjustment for confounding variables by using multivariate logistic regression. Significantly increasing the risk of lacunar stroke were hypertension (with an odds ratio of 8.9 [95% confidence intervals 4.2, 18.8]), current smoking (6.6 [2.9, 14.8]), and diabetes (2.3 [1.0, 5.5]), whereas frequent physical exercise was associated with a significantly decreased risk (0.3 [0.1, 0.7]). There was no risk of lacunar stroke associated with heart disease (odds ratio 1.0 [0.5, 1.9]). Patients with hypertension or diabetes, and those who currently smoke, are at a higher risk of lacunar stroke, whereas those who undertake regular physical exercise may be at lower risk. The high risk associated with hypertension but absent risk with heart disease supports the "lacunar hypothesis" of a unique pathophysiologic mechanism for lacunar stroke.
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/10641969309041612
Abstract: Although lisinopril and enalapril are equipotent angiotensin converting enzyme (ACE) inhibitors lisinopril has been reported to produce greater inhibition of plasma ACE 24 hours after single doses. This study compared the antihypertensive effects of once daily 10mg doses of the drugs using a randomised, double-blind, two period cross-over design with ambulatory blood pressure monitoring. Lisinopril lowered mean 24 hour systolic blood pressure significantly more than enalapril after 4 weeks of treatment (14/7 +/- 2/1mmHg & 9/6 +/- 2/1mmHg, respectively, adjusted SBP difference 4.8mmHg, P < 0.01). This difference was confined to the second 12 hours of the daily dosage interval (adjusted SBP difference 13-24 hours after dosing 9.9mmHg, P < 0.001). The diastolic pressure showed a similar trend but this was not statistically significant. The side effects of each agent were minor. We conclude that chronic, once daily therapy with 10mg of lisinopril reduces systolic blood pressure more effectively than an equal dose of enalapril due to its greater effect in the latter half of the 24 hour dosage interval.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2010
Publisher: Springer Science and Business Media LLC
Date: 04-1990
DOI: 10.1038/CLPT.1990.58
Abstract: The present study was designed to compare the pharmacokinetic handling of a single oral dose of nicardipine in normal subjects and in patients with hepatic cirrhosis and to compare the sensitivity of the two groups to its hypotensive effect. Nicardipine plasma concentrations were substantially higher in the subjects with hepatic cirrhosis with impaired antipyrine clearance, as shown by a significantly higher average Cmax and AUC. The terminal elimination half-life in this group varied from 0.8 to 60.2 hours (median, 11.7 hours), compared with 0.6 to 4.1 hours (median, 1.4 hours) in the group of eight subjects with normal liver function. In the cirrhotic patients with impaired antipyrine clearance, the AUC of the pyridine metabolite averaged 10% of that of the parent drug, whereas in normal subjects the ratio averaged 48%. This finding suggests less conversion of nicardipine to this metabolite in subjects with impaired hepatic function. Peak blood pressure decreases were greater in the cirrhotic group, which was in keeping with the higher plasma levels in these subjects.
Publisher: MDPI AG
Date: 14-07-2021
Abstract: Genomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40–69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) in BC susceptibility genes (BRCA1/BRCA2/PALB2/CHEK2/ATM). The PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio (HR) per standard deviation (SD) = 1.4, 95% confidence interval (CI) 1.3–1.6) and hormone receptor (ER/PR)-positive disease (HR = 1.5 (CI 1.2–1.9)). Women in the top quintile of the PRS distribution had over two-fold higher risk of BC than women in the lowest quintile (HR = 2.2 (CI 1.2–3.9)). The concordance index of the model without the PRS was 0.62 (95% CI 0.56–0.68), which improved after addition of the PRS to 0.65 (95% CI 0.59–0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses. Our study demonstrates that a PRS predicts incident BC risk in women aged 70 years and older, suggesting potential clinical utility extends to this older age group.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-07-2020
Publisher: Springer Science and Business Media LLC
Date: 09-11-2016
Publisher: Oxford University Press (OUP)
Date: 06-12-2019
DOI: 10.1093/AJH/HPZ192
Abstract: Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both “untreated” and “treated but uncontrolled” high BP. We analyzed baseline data from 19,114 in iduals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. “Controlled hypertension” was defined if participants were receiving antihypertensive medication and BP & and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates logistic regression was used to investigate relationships with treatment and BP control. Overall, 74% (14,213/19,114) of participants were hypertensive and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to “treated but uncontrolled” BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US). High levels of “untreated” and “treated but uncontrolled” BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population. NCT01038583.
Publisher: Elsevier BV
Date: 2016
Publisher: Wiley
Date: 06-1994
DOI: 10.1111/J.1532-5415.1994.TB06864.X
Abstract: To document compliance with medication, drop-out and drop-in rates, and baseline cardiovascular event rates during the pilot phase of the PACE (Prevention with low-dose Aspirin of Cardiovascular disease in the Elderly) study. Randomized, double-blind, placebo-controlled trial of low-dose aspirin therapy. Community-based, in general practices and residential retirement villages, in Victoria, Australia. Four hundred persons aged 70 years and older (53% females), ambulatory and living independently, who volunteered to participate. None had significant vascular disease, peptic ulceration, hemorrhagic symptoms, or were currently taking non-steroidal anti-inflammatory drugs. Compliance with medication (assessed by pill count and platelet function tests), self-reported drop-out and drop-in rates, and incidence of cardiovascular events reported by participants and their general practitioners during a 12-month period. Two fatal cardiovascular events, three non-fatal coronary events, and eight non-fatal cerebrovascular events were observed during the 12-month period. These incidence figures were approximately 15%, 15%, and 40%, respectively, of those in the general population of the same age and sex, based on morbidity data available from the Australian Bureau of Statistics. Compliance to medication was excellent (87%), and premature withdrawal (other than for a study end point) was limited to 14.5%. Secondary 'softer' endpoints, such as transient ischaemic attack and unstable angina, necessitated patient withdrawal from randomized therapy and possibly contributed to the small number of primary 'hard' end points observed. The projected power of the main study to detect a 20% treatment effect on overall cardiovascular mortality in 15,000 subjects over a 4-year period may, therefore, be substantially reduced. These results suggest that any future primary prevention study of cardiovascular disease in the elderly examining the effect of low-dose aspirin on overall cardiovascular mortality will likely need to use much larger numbers of patients or use a combined end point of fatal and non-fatal ischemic events.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2020
Publisher: Oxford University Press (OUP)
Date: 22-01-2019
Publisher: American Medical Association (AMA)
Date: 10-2020
Publisher: Wiley
Date: 12-02-1988
DOI: 10.1111/J.1753-6405.1988.TB00575.X
Abstract: Our laboratory has demonstrated a clinical inverse association between H. pylori infection and inflammatory bowel disease (IBD). In our most recent work we described a possible mechanism by which H. pylori can reduce the risk of developing IBD. Specifically, we were able to demonstrate the immuno-regulatory properties of the H. pylori genome and its ability to downregulate inflammatory responses through interaction with mucosal dendritic cells both in an in vitro and in vivo model. Furthermore, we were able to demonstrate the ability of H. pylori DNA to downregulate dendritic cell production of IL-12 and type I interferon, two pro-inflammatory cytokines. In the present work, we conducted further studies to examine the unique properties of the H. pylori genome and the exact mechanism through which it interacts with dendritic cells. Our data highlight a specific immuno-regulatory sequence (IRS), TTTAGGG, which occurs significantly more frequently as compared with other IRS sequences and is unique to the H. pylori genome. Additionally, we illustrate that H. pylori DNA has no effect on modulating the TLR-4 dependent LPS-induction of dendritic cell IL-12 production. This indicates that the inhibitory effect of H. pylori genomic DNA is restricted to the TLR-9 signaling pathway that senses bacterial DNA. In conclusion, the findings of this addendum strengthen the evidence for unique immunoregulatory properties of the H. pylori genome and revealed the importance of TLR-9 mediated mechanism in the pathogenesis of IBD.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/107989
Abstract: Background. Increasing levels of obesity over recent decades have been expected to lead to an epidemic of diabetes and a subsequent reduction in life expectancy, but instead all-cause and cardiovascular-specific mortality rates have decreased steadily in most developed countries and life expectancy has increased. Methods. This paper suggests several factors that may be masking the effects of obesity on life expectancy. Results. It is possible that health and life expectancy gains could be even greater if it was not for the increasing prevalence of extreme obesity. It is also possible that the principal impact of obesity is on disability-free life expectancy rather than on life expectancy itself. Conclusion. If the principal impact of obesity were through disability-free life expectancy rather than on life expectancy itself, this would have substantial implications for the health of in iduals and the future burden on the health care system.
Publisher: Wiley
Date: 05-1992
DOI: 10.1111/J.1440-1681.1992.TB00455.X
Abstract: 1. This study investigated components of blood pressure variability in elderly subjects with isolated systolic hypertension (ISH) using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine s le size requirements for clinical trials of different designs. 2. Eleven elderly subjects not receiving antihypertensive medication were seen on four occasions at weekly intervals. On each occasion blood pressure was measured in the clinic and then for 24 h using a non-invasive ABPM device. Nested analysis of variance was used to calculate the 'between subject' and 'between subject within occasion' components of blood pressure variability. 3. Increasing the number of readings or occasions where measurement was performed in a parallel group trial only reduced the variability substantially when the number of subjects involved was less than 50. Use of a cross-over design substantially reduced the s le size required. 4. ABPM appears most useful as a strategy for reducing s le size in parallel group trials in ISH involving small numbers of subjects measured on one occasion.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
DOI: 10.1161/STROKEAHA.120.033670
Abstract: Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur. We predicted risk of incident IS events in a population of 12 792 healthy older in iduals enrolled in the ASPREE trial (Aspirin in Reducing Events in the Elderly). The PRS was calculated using 3.6 million genetic variants. Participants had no previous history of cardiovascular events, dementia, or persistent physical disability at enrollment. The primary outcome was IS over 5 years, with stroke subtypes as secondary outcomes. A multivariable model including conventional risk factors was applied and reevaluated after adding PRS. Area under the curve and net reclassification were evaluated. At baseline, mean population age was 75 years. In total, 173 incident IS events occurred over a median follow-up of 4.7 years. When PRS was added to the multivariable model as a continuous variable, it was independently associated with IS (hazard ratio, 1.41 [95% CI, 1.20–1.65] per SD of the PRS P .001). The PRS alone was a better discriminator for IS events than most conventional risk factors. PRS as a categorical variable was a significant predictor in the highest tertile (hazard ratio, 1.74 P =0.004) compared with the lowest. The area under the curve of the conventional model was 66.6% (95% CI, 62.2–71.1) and after inclusion of the PRS, improved to 68.5 ([95% CI, 64.0–73.0] P =0.095). In subgroup analysis, the continuous PRS remained an independent predictor for large vessel and cardioembolic stroke subtypes but not for small vessel stroke. Reclassification was improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.17–0.43). PRS predicts incident IS in a healthy older population but only moderately improves prediction over conventional risk factors. URL: www.clinicaltrials.gov Unique identifier: NCT01038583.
Publisher: BMJ
Date: 21-05-2015
Publisher: MDPI AG
Date: 19-11-2021
Abstract: Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70 years (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. The study endpoint was prostate cancer, including metastatic or non-metastatic disease, confirmed by an expert panel. After excluding participants with a history of prostate cancer at enrolment, we used a multivariable Cox proportional hazards model to assess the association between the PRS and incident prostate cancer risk, adjusting for covariates. Additionally, we examined the distribution of Gleason grade groups by PRS group to determine if a higher PRS was associated with higher grade disease. We tested for interaction between the PRS and aspirin treatment. Logistic regression was used to independently assess the association of the PRS with prevalent (pre-trial) prostate cancer, reported in medical histories. During a median follow-up time of 4.6 years, 218 of the 5701 participants (3.8%) were diagnosed with prostate cancer. The PRS predicted incident risk with a hazard ratio (HR) of 1.52 per standard deviation (SD) (95% confidence interval (CI) 1.33–1.74, p 0.001). Men in the top quintile of the PRS distribution had an almost three times higher risk of prostate cancer than men in the lowest quintile (HR = 2.99 (95% CI 1.90–4.27), p 0.001). However, a higher PRS was not associated with a higher Gleason grade groups. We found no interaction between aspirin treatment and the PRS for prostate cancer risk. The PRS was also associated with prevalent prostate cancer (odds ratio = 1.80 per SD (95% CI 1.65–1.96), p 0.001).While a PRS for prostate cancer is strongly associated with incident risk in men aged ≥70 years, the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease.
Publisher: Springer Science and Business Media LLC
Date: 09-11-2016
Publisher: AMPCo
Date: 06-2013
DOI: 10.5694/MJA12.11241
Abstract: To describe patterns of care for men diagnosed with prostate cancer in Victoria, Australia, between 2008 and 2011. Men who were diagnosed with prostate cancer at 11 public and six private hospitals in Victoria from August 2008 to February 2011, and for whom prostate cancer notifications were received by the Prostate Cancer Registry. Characteristics of men diagnosed with prostate cancer details of treatment provided within 12 months of diagnosis, according to National Comprehensive Cancer Network risk categories and characteristics of men who did not receive active treatment within 12 months of diagnosis. Treatment details were collected for 98.1% of men who were assessed as eligible to participate in the study (2724/2776) and were confirmed by telephone 12 months after diagnosis for 74.4% of them (2027/2724). Most patients (2531/2724 [92.9%]) were diagnosed with clinically localised disease, of whom 1201 (47.5%) were at intermediate risk of disease progression. Within 12 months of diagnosis, 299 of the 736 patients (40.6%) who had been diagnosed as having disease that was at low risk of progression had received no active treatment, and 72 of 594 patients (12.1%) who had been diagnosed as having disease that was at high risk of progression had received no active treatment. Of those diagnosed as having intermediate risk of disease progression, 54.5% (655/1201) had undergone radical prostatectomy. Those who received no active treatment were more likely than those who received active treatment to be older (odds ratio [95% CI], 2.96 [2.01-4.38], 10.94 [6.96-17.21] and 32.76 [15.84-67.89], respectively, for age 65-74 2013s, 75-84 2013s and ≥ 85 2013s, compared with < 55 2013s), to have less advanced disease (odds ratio [95% CI], 0.20 [0.16-0.26], 0.09 [0.06-0.12] and 0.05 [0.02-0.90], respectively, for intermediate, high and very high-risk [locally advanced] or metastatic disease, compared with low-risk disease) and to have had their prostate cancer notified by a private hospital (odds ratio [95% CI], 1.35 [1.10-1.66], compared with public hospital). Our data reveal a considerable "stage migration" towards earlier diagnosis of prostate cancer in Victoria and a large increase in the use of radical prostatectomy among men with clinically localised disease.
Publisher: SAGE Publications
Date: 06-2011
DOI: 10.3109/00048674.2011.572852
Abstract: Objective: To develop an evidence-based monitoring protocol for clozapine-induced myocarditis. Methods: Potential cases of clozapine-related myocarditis occurring between January 1994 and January 2009 and a comparative group of patients taking clozapine for at least 45 days without cardiac disease were documented from the patients’ medical records. Results: A total of 75 cases and 94 controls were included. Nine cases died. The time to onset was 10–33 days with 83% of cases developing between days 14 and 21 inclusive. At least twice the upper limit of normal troponin was found in 90% of cases, but 5 cases had C-reactive protein more than 100 mg/L and left ventricular impairment by echocardiography without a clinically significant rise in troponin. The proposed monitoring protocol recommends obtaining baseline troponin I/T, C-reactive protein and echocardiography, and monitoring troponin and C-reactive protein on days 7, 14, 21 and 28. Mild elevation in troponin or C-reactive protein, persistent abnormally high heart rate or signs or symptoms consistent with infective illness should be followed by daily troponin and C-reactive protein investigation until features resolve. Cessation of clozapine is advised if troponin is more than twice the upper limit of normal or C-reactive protein is over 100 mg/L. Combining these two parameters has an estimated sensitivity for symptomatic clozapine-induced myocarditis of 100%. The sensitivity for asymptomatic disease is unknown. Conclusion: This protocol recommends active monitoring for 4 weeks, relying predominantly on troponin and C-reactive protein results. It encourages continuation of clozapine in the presence of mild illness, but defines a threshold for cessation.
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2019-031434
Abstract: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia. It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. In iduals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public rivate hospital or private clinic in Australia and do not opt out of participation. The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile. The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2014
DOI: 10.1007/S10557-014-6560-7
Abstract: To evaluate the effect of oral vitamin E supplementation on all-cause mortality in apparently healthy people. A systematic review and meta-analysis was conducted on randomised controlled trials (RCTs) with ≥ 6 months of follow up investigating the effect of vitamin E supplementation on healthy adults in developed countries. Electronic databases (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) and reference lists of trial reports were searched for RCTs published between 1966 and June 2012. Three investigators assessed eligibility of identified trials. Disagreements were resolved by consensus. Two investigators independently extracted data according to the criteria. There were 18 RCTs identified with 142,219 apparently healthy participants (71,116 in vitamin E intervention groups and 71,103 in control groups) that were included in the final analysis. Fixed effect and random effects analysis of the 18 trials revealed that supplementation with vitamin E was not associated with all-cause mortality (relative risk 1.01, 95% confidence interval 0.97 - 1.05, p = 0.65). Subgroup analyses by type of vitamin E (natural or synthetic), dose or duration of exposure, study design or quality, and pre-specified mortality outcome showed no association with all-cause mortality. The evidence from pooled analysis of 18 randomised controlled trials undertaken in apparently healthy people shows no effect of vitamin E supplementation at a dose of 23-800 IU/day on all-cause mortality.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2022
Publisher: AMPCo
Date: 07-2013
DOI: 10.5694/MJA13.10381
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 03-1995
Publisher: Springer Science and Business Media LLC
Date: 25-06-2008
DOI: 10.1007/S10935-008-0143-Y
Abstract: It is well known that the current combination of aging populations and advances in health technology is resulting in burgeoning health costs in developed countries. Prevention is a potentially important way of containing health costs. In an environment of intense cost pressures, coupled with developments in disease prevention and health promotion, it is increasingly important for decision-makers to have a systematic, coordinated approach to the targeting and prioritization of preventive strategies. However, such a systematic approach is made difficult by the fact that preventive strategies need to be compared over the long term, in a variety of populations, and in real life settings not found in most trials. Information from epidemiological models can provide the required evidence base. In this review, we outline the role of epidemiological modeling in this context and detail its application using ex les. Editors' Strategic Implications: Policymakers and researchers will benefit from this description of the utility of epidemiological modeling as a means of generating translational evidence that helps to prioritize data-based prevention approaches and bridge the gap between clinical research and public health practice.
Publisher: Elsevier BV
Date: 1992
DOI: 10.1016/0002-9149(92)91307-P
Abstract: Isolated systolic hypertension represents an important public health issue in the 1990s because of its prevalence in the elderly and its importance as a risk factor for cardiovascular morbidity and mortality. Methodologic differences may account for the wide variation between prevalence rates in studies reported. With the advent of newer methods of blood pressure (BP) assessment, such as noninvasive ambulatory BP monitoring, it may be possible to define more accurately the true population at risk. Recent data from the Systolic Hypertension in the Elderly Program has indicated a clear benefit of treatment with a reduction in total stroke of 36%, and a reduction of 25 and 32% in the combined end points of coronary heart disease and cardiovascular disease, respectively. Further studies are now required to elucidate what treatment regimens are most effective in preferentially reducing both systolic BP, without producing undesirable effects such as diastolic hypotension, and fatal and nonfatal events. One such trial is underway in Europe using a drug regimen different from that in the Systolic Hypertension in the Elderly Program. The cost implications associated with treating the population at risk are potentially large but these are now based on firm scientific evidence.
Publisher: Wiley
Date: 27-04-2020
DOI: 10.1111/BJH.16660
Publisher: Elsevier BV
Date: 03-1984
DOI: 10.1016/0195-6701(84)90097-5
Abstract: A survey was undertaken of all isolations of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) at a large Australian teaching hospital over a 12 month period. All methicillin-resistant isolations obtained from the Casualty and Outpatient clinics were from staff members or patients with recent hospital contact. Twenty per cent of all methicillin-resistant isolations from in-patients were from specimens taken within 2 days of the patient's admission. Each of these patients had had hospital contact within the previous 4 months and it is assumed that the majority of them reintroduced the organism into the hospital. Such patients may provide an important means by which infection control procedures are bypassed. Patients who were relatively more likely to become infected or colonized with methicillin-resistant than with methicillin-sensitive strains included the elderly and those with postoperative wound infections (especially after orthopaedic or vascular surgery), spinal injuries, peripheral vascular disease, chronic skin ulcers or chronic diseases of the respiratory or urinary tracts. Eleven per cent of MRSA wound isolates and 15 per cent of sputum isolates were associated with serious infections requiring specific treatment, emphasizing the ability of these strains to produce serious illness. A small proportion of staff and asymptomatic patients were found to harbour MRSA and the importance of these in iduals in facilitating cross-infection requires further investigation.
Publisher: Oxford University Press (OUP)
Date: 06-07-2012
Abstract: Aortic valve stenosis (AS) and its precursor, aortic valve sclerosis (ASc), occur frequently in Western populations. Investigations to retard the progression of AS using statins have been unsuccessful. Development of ASc in humans is associated with increased aortic valve backscatter (AVBS) and poor tissue nitric oxide (NO) responsiveness. In an animal model, ramipril retarded AS/ASc development. We have now set out to identify factors associated with the progression of ASc in humans. At baseline and after 4 years, 204 randomly selected subjects (age 63 ± 6 years at study entry) underwent echocardiography with the determination of AVBS values, measurements of platelet NO responsiveness, plasma asymmetric dimethylarginine concentrations, lipid profile, high-sensitivity-C-reactive protein, routine biochemistry, and 25-hydroxy-vitamin D levels. During the study period, 68% of subjects had detectable AVBS progression. On multivariate analysis, higher calcium concentrations (β = 0.22 P = 0.004), poor platelet NO responsiveness (β = 0.18 P = 0.018), and increased arterial stiffness (β = 0.15 P = 0.044) were independent predictors of disease progression. The use of angiotensin-converting enzyme-inhibitors/angiotensin II receptor blockers (ACE-I/ARB) predicted the lack of disease progression (assessed categorically) in the overall cohort and in those without ASc at baseline (n = 159) (β = 0.8 P = 0.025 and β = 1.3 P = 0.001, respectively). No conventional coronary risk factors were associated with disease progression. This study of early aortic valve disease (i) demonstrates that disease progression occurs in the majority of the normal ageing population over a 4-year period (ii) provides evidence of the importance of the NO signalling cascade in disease development and progression and (iii) provides additional data linking ACE-I/ARB use with the retardation of ASc.
Publisher: Massachusetts Medical Society
Date: 12-01-2017
Publisher: MDPI AG
Date: 24-03-2021
Abstract: While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate cancer (PrCa) is limited by our current understanding of the genetic risk factors associated with predisposition to this potentially lethal disease phenotype. This study included 837 men diagnosed with aggressive PrCa and 7261 controls (unaffected men and men who did not meet criteria for aggressive PrCa). Rare germline pathogenic variants (including likely pathogenic variants) were identified by targeted sequencing of 26 known or putative cancer predisposition genes. We found that 85 (10%) men with aggressive PrCa and 265 (4%) controls carried a pathogenic variant (p 0.0001). Aggressive PrCa odds ratios (ORs) were estimated using unconditional logistic regression. Increased risk of aggressive PrCa (OR (95% confidence interval)) was identified for pathogenic variants in BRCA2 (5.8 (2.7–12.4)), BRCA1 (5.5 (1.8–16.6)), and ATM (3.8 (1.6–9.1)). Our study provides further evidence that rare germline pathogenic variants in these genes are associated with increased risk of this aggressive, clinically relevant subset of PrCa. These rare genetic variants could be incorporated into risk prediction models to improve their precision to identify men at highest risk of aggressive prostate cancer and be used to identify men with newly diagnosed prostate cancer who require urgent treatment.
Publisher: Swets & Zeitlinger Publishers
Date: 1999
DOI: 10.1076/OPEP.6.2.105.1561
Abstract: We examined the association between prior supplementation of vitamin E and early cataract changes in volunteers currently enrolled in the cross-sectional VECAT study. The Vitamin E and Cataract Prevention Study (VECAT) is a clinical trial currently in progress, designed to assess the affect of vitamin E supplementation on the development and progression of cataract and age-related macular degeneration. A history of vitamin E supplementation was ascertained through a self-administered questionnaire that was mailed to each of the 1,111 participants who were enrolled at the time in the prospective VECAT Study. With a 99% response rate, we found that 26% of participants reported prior supplementation of vitamin E. Only 8.8% of these participants took supplementation greater than the recommended daily intake (RDI) of 10 mg/day. Of these 26%, 57% took supplementation in the form of multivitamins as opposed to a vitamin E supplement on its own. The range of supplement intake ranged from as little as 0.1 mg/day to a maximum of 55 mg/day. A statistically significant association was found between prior supplementation and the absence of cortical opacity (OR = 0.47, 95%CI = 0.28-0.83), after adjusting for age. The levels of nuclear opacity (NO) were not statistically different between those who reported intake and those with no prior vitamin E supplementation. Prior vitamin E supplementation may protect VECAT participants from developing at least early cortical cataracts. No apparent protective role in terms of nuclear opacities and nuclear color was found regardless of the level, regularity or duration of intake.
Publisher: Wiley
Date: 05-1988
DOI: 10.1111/J.1442-9071.1988.TB01251.X
Abstract: The prognosis for death from metastatic choroidal melanoma following enucleation has been shown to be strongly correlated with a number of risk factors of which the most important are age of onset, aggressive cell types and tumour volume. The advantages of enucleation for the treatment of choroidal melanomas are put into question by the singular lack of a parallel increase in life expectancy following this treatment, and evidence that it may promote the development of metastatic disease. Alternative forms of treatment have been introduced including observation of small and asymptomatic tumours. We are using a computer-aided system for serial measurement and statistical analysis of area and volume of choroidal melanomas. A comparison of results using our method and the conventional method of estimating volume by the product of basal area and height for 51 measurements on 15 eyes over a 6-month period showed an overestimation of volume by conventional methods which could be corrected by applying a "shape constant" determined by linear regression. Calculation of tumour growth rates is also shape-dependent, and a slowing in growth rate or even a reduction in melanoma size is possible.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2006
DOI: 10.1161/01.HYP.0000209340.33592.50
Abstract: Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study (untreated blood pressure 169/88±12/8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival (hazard ratio [HR], 2.3 95% CI, 1.3 to 4.1 for pulse pressure ≥81 versus mm Hg P =0.01), no such relation was found for carotid augmentation index (HR, 0.80 95% CI, 0.44 to 1.44 P value not significant) or systemic arterial compliance (HR, 1.25 95% CI, 0.72 to 2.16 P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.
Publisher: BMJ
Date: 24-03-2017
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 12-03-2013
DOI: 10.1111/J.1365-2753.2012.01834.X
Abstract: Development of chronic disease risk prediction models has become a growing area of research in recent years. The internal validity of such models is sometimes lower than estimated from the development s le. Overfitting or overoptimism of the developed model and/or differences between the s les are likely causes for this. For modelling of an uncommon outcome, bootstrapping for overoptimism is the preferred method for afterwards shrinking of regression coefficients and the model's discrimination and calibration for overoptimism. However, computer programs for different types of bootstrap validation are not readily available. We developed two SAS macro programs--one for the simple bootstrap that compares the discriminatory performance of the Cox proportional hazards model from the original s le in bootstrap s les and another (which is more efficient), known as stepwise bootstrap validation, that makes the same comparison but from models developed by variable selection from bootstrap s les in the original s le. These are illustrated through an ex le from cardiovascular disease (CVD) risk prediction. Two SAS macro programs for Cox proportional hazards model using Proc PHREG were developed for estimating overoptimism in Harrell's C and Somers' D statistics. The computer programs were applied to data on CVD incidence for a Framingham cohort that combined both the original and offspring exams. The risk factors considered were current smoking, diabetes, age, sex, systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglycerides and body mass index. The degree of overoptimism in both Harrell's C and Somers' D statistics were low. Both these statistics were corrected for overoptimism by subtracting overoptimism from their observed values. Between the two bootstrap validation algorithms, the degree of overoptimism was estimated to be higher for stepwise bootstrap validation. The programs are very useful for evaluating the 'overoptimism corrected' predictive performance of Cox proportional hazards model.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1992
DOI: 10.1097/00005344-199209000-00024
Abstract: In a double-blind, placebo-controlled, parallel group study, 24 essential hypertensive subjects were randomised to receive either placebo or 2, 4, or 8 mg perindopril. Perindopril, its deesterified metabolite, perindoprilat, and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay (RIA). Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment. Perindopril peak levels were achieved in less than or equal to 2 h after dosing with an elimination t1/2 of 1-2 h. Peak levels of perindoprilat were achieved more slowly, reaching a maximum level 5-8 h after dosing, and had an elimination t1/2 of 40 h. Levels of the perindopril glucuronide peaked approximately 0.5 h later than perindopril, with an elimination t1/2 of approximately 2 h. Perindopril, perindoprilat, and its glucuronide conjugate followed linear kinetics in the dose range of 2-8 mg, and there was no evidence of accumulation with chronic dosing. Perindopril 4 and 8 mg produced significant decreases in predose blood pressure (BP) with chronic dosing, with maximal decreases occurring 5-7 h after dosing. Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme (ACE) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose.
Publisher: Wiley
Date: 10-2000
DOI: 10.1046/J.1442-9071.2000.00336.X
Abstract: To examine the sensitivity, specificity and overall agreement between photographic and clinical assessment in detecting age-related maculopathy (ARM) features in the context of an epidemiological study, the Vitamin E, Cataract and Age-related Maculopathy Study (VECAT). A total of 1204 volunteers aged between 55 and 80 years of age, who were enrolled in the VECAT Study, had both slit-l biomicroscopy examination and fundus photos taken as part of the baseline ophthalmic examination. The Nidek 3-DX fundus camera (Nidek, Gamagori, Japan) was used to produce paired, one-framed, coloured, 15 degrees stereoslides of the macular area at a fixed angle. An International Classification and Grading System for Age-related Maculopathy and Age-related Macular Degeneration was used to grade the stereoslides. Agreement in the detection of drusen, pigment abnormalities, and late stage ARM features was assessed using unweignted kappa statistic. Cases of disagreement were verified using clinical data records, grading documentation and the review of stereoslides. Macula status was available for 2386 eyes. For drusen of size or = 125 microm, sensitivity and specificity were > or =81%. Kappa values ranged from 0.56 to 0.71. Levels of agreement for pigment abnormalities and late ARM were in the substantial range (i.e. kappa values from 0.70 to 1.00). Slit-l biomicroscopy was found to be comparable to photograding (using the Nidek 3-DX fundus camera) for detecting features pertaining to ARM. However, given the objectivity and permanency of stereoslides, photograding is still the more reliable and the preferred system of assessing ARM in the context of an epidemiological study.
Publisher: Elsevier BV
Date: 07-2002
Abstract: To determine whether a relationship exists between high cholesterol levels and intracerebral haemorrhage (ICH) a case-control study was undertaken on 331 consecutive cases of first-episode primary ICH, verified by computed tomography, and 331 age- and sex-matched community controls. Using conditional logistic regression the adjusted odds ratio (OR) of ICH among in iduals reporting a high cholesterol level was 0.45 [95% confidence interval (CI), 0.28-0.73]. A similar finding was observed when the analysis was limited to those using cholesterol-lowering drugs (OR 0.25 95% CI, 0.08-0.80). These data provide support for an inverse relationship between high cholesterol levels and ICH. When considered together with previous findings, in which low cholesterol levels have been associated with an increased risk of haemorrhagic stroke, these data provide evidence that this inverse relationship may extend into a higher range of cholesterol values.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2013
Publisher: Massachusetts Medical Society
Date: 18-10-2018
Publisher: BMJ
Date: 15-12-1979
DOI: 10.1136/BMJ.2.6204.1555-A
Abstract: Forty-two different sense codons, coding for all 20 amino acids, were placed at the ribosomal E site location, two codons upstream of a UGA or UAG codon. The influence of these variable codons on readthrough of the stop codons was measured in Escherichia coli. A 30-fold difference in readthrough of the UGA codon was observed. Readthrough is not related to any property of the upstream codon, its cognate tRNA or the nature of its codon-anticodon interaction. Instead, it is the amino acid corresponding to the second upstream codon, in particular the acidic/basic property of this amino acid, which seems to be a major determinant. This amino acid effect is influenced by the identity of the A site stop codon and the efficiency of its decoding tRNA, which suggests a correlation with ribosomal pausing. The magnitude of the amino acid effect is in some cases different when UGA is decoded by a wildtype form of tRNA(Trp) as compared with a suppressor form of the same tRNA. This indicates that the structure of the A site decoding tRNA is also a determinant for the amino acid effect.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
DOI: 10.1097/ALN.0B013E3181A1093B
Abstract: Clinical indicators are increasingly developed and promoted by professional organizations, governmental agencies, and quality initiatives as measures of quality and performance. To clarify the number, characteristics, and validity of indicators available for anesthesia care, the authors performed a systematic review. They identified 108 anesthetic clinical indicators, of which 53 related also to surgical or postoperative ward care. Most were process (42%) or outcome (57%) measures assessing the safety and effectiveness of patient care. To identify possible quality issues, most clinical indicators were used as part of interhospital comparison or professional peer-review processes. For 60% of the clinical indicators identified, validity relied on expert opinion. The level of scientific evidence on which prescriptive indicators ("how things should be done") were based was high (1a-1b) for 38% and low (4-5) for 62% of indicators. Additional efforts should be placed into the development and validation of anesthesia-specific quality indicators.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.AMJMED.2009.09.024
Abstract: Vitamin D deficiency is associated with significant increases in the incidence of cardiovascular risk factors and mortality. However, the mechanisms underlying this association remain unclear. The current study evaluated the possible relationships among vitamin D status, endothelial dysfunction, and inflammation. Plasma concentrations of 25-hydroxyvitamin D(3) were determined by radioimmunoassay in a normal population cohort (n=253) aged 51 to 77 years (mean 63.4+/-6 years). Asymmetric dimethylarginine, a marker/mediator of endothelial dysfunction, was assayed by high-performance liquid chromatography. High-sensitivity C-reactive protein levels were used as a marker of inflammatory activation. On univariate analyses, low 25-hydroxyvitamin D(3) levels were inversely correlated with asymmetric dimethylarginine concentrations, high-sensitivity C-reactive protein levels, and body mass index. Seasonal fluctuations in 25-hydroxyvitamin D(3) levels were associated with reciprocal asymmetric dimethylarginine concentration fluctuations. Hypertension and treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker also were associated with low 25-hydroxyvitamin D(3) levels. On multiple linear analysis, both asymmetric dimethylarginine (beta=-0.19, P=.003) and high-sensitivity C-reactive protein (beta=-0.14, P=.03) concentrations were inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations other significant correlates were male gender (beta=0.19, P=.003), calcium levels (beta=0.14, P=.03), and use of angiotensin-converting enzyme inhibitor (beta=-0.17, P=.007). Low 25-hydroxyvitamin D(3) levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary risk.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2010
DOI: 10.1007/S10557-010-6246-8
Abstract: Smoking continues to be a major contributor to the burden of disease across the world although there has been a decrease in some developed countries such as USA and Australia. In countries of South-East Asia with a high prevalence of smoking, the incidence of tobacco-related diseases will continue to increase. We reviewed the literature in relation to the pharmacology of nicotine, the measures used to determine the efficacy of anti-smoking therapies, and the randomised controlled trials and systematic reviews of pharmacotherapies published between 2004 and 2010. We focused primarily on the three first line therapies that are currently available: nicotine replacement therapy (NRT), bupropion and varenicline. Randomised controlled trials and meta-analyses have demonstrated that single therapy with either NRT, bupropion or varenicline are all more effective than placebo for smoking cessation. Abstinence rates for monotherapies varies from 13.3% to 19% for NRT compared to 7.5% to 14% for placebo, 19% to 19.7% for bupropion versus 10.9% to 11% for placebo and 25.5% to 25.6% for varenicline versus 11.2% to 14.8% for placebo. Of current therapies varenicline appears to be more effective at achieving abstinence. Some combination therapies with one or two formulations of NRT or NRT plus bupropion have demonstrated superior results to monotherapy. To date there are no randomised controlled trials of varenicline in combination with NRT or bupropion. Further studies are required to address the uncertainty that exists on the most appropriate duration of therapy as well as the effectiveness and safety of combination pharmacotherapy. Post-marketing surveillance continues to play an important role in monitoring the adverse effects events associated with these therapies.
Publisher: S. Karger AG
Date: 1999
DOI: 10.1159/000055521
Abstract: To identify validity of the standardised Nidek EAS-1000 retroillumination image analysis, images of 450 consecutive patients were analysed for the standard 6.5 mm and for the maximal pupil size. The software allows for separation of cortical and posterior subcapsular opacities and defines threshold for cataract automatically at 12% below the brightest point of the histogram of pixel luminescence. The results were compared with clinical Wilmer cataract grading. Correlation between clinical and digital assessment was 0.48* for cortical opacities in maximal pupil size, 0.47* in 6.5 mm pupil size analyses, and 0.71* for posterior subcapsular opacities (*p 0.001). In 24.6% of maximal pupil size analyses and in 11.7% of standard pupil size analyses standardisation revealed confounding features, such as other opacities of media, refractive shadows etc., that masqueraded as cataract and interfered with the cortical opacity measurements. Automatic standardized analysis has reduced many sources of observer variation (level of illumination, pupil size and threshold adjustment), but the revealed range of confounding opacities and artifacts still requires observer interpretation.
Publisher: BMJ
Date: 03-08-2020
DOI: 10.1136/GUTJNL-2020-321585
Abstract: There is a lack of robust data on significant gastrointestinal bleeding in older people using aspirin. We calculated the incidence, risk factors and absolute risk using data from a large randomised, controlled trial. Data were extracted from an aspirin versus placebo primary prevention trial conducted throughout 2010–2017 (‘ASPirin in Reducing Events in the Elderly (ASPREE)’, n=19 114) in community-dwelling persons aged ≥70 years. Clinical characteristics were collected at baseline and annually. The endpoint was major GI bleeding that resulted in transfusion, hospitalisation, surgery or death, adjudicated independently by two physicians blinded to trial arm. Over a median follow-up of 4.7 years (88 389 person years), there were 137 upper GI bleeds (89 in aspirin arm and 48 in placebo arm, HR 1.87, 95% CI 1.32 to 2.66, p .01) and 127 lower GI bleeds (73 in aspirin and 54 in placebo arm, HR 1.36, 95% CI 0.96 to 1.94, p=0.08) reflecting a 60% increase in bleeding overall. There were two fatal bleeds in the placebo arm. Multivariable analyses indicated age, smoking, hypertension, chronic kidney disease and obesity increased bleeding risk. The absolute 5-year risk of bleeding was 0.25% (95% CI 0.16% to 0.37%) for a 70 year old not on aspirin and up to 5.03% (2.56% to 8.73%) for an 80 year old taking aspirin with additional risk factors. Aspirin increases overall GI bleeding risk by 60% however, the 5-year absolute risk of serious bleeding is modest in younger, well in iduals. These data may assist patients and their clinicians to make informed decisions about prophylactic use of aspirin. ASPREE. NCT01038583 .
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2005
DOI: 10.1097/01.TA.0000174840.35406.71
Abstract: The success of a trauma system relies on transfer of patients from the field to the most appropriate hospital for definitive care. However, no consensus has been reached regarding the best criteria or triage tool for identifying patients injured seriously enough to warrant transfer to a trauma center. Predictors of mortality and intensive care unit stay were identified and prediction models developed in a design data set. The performance of these models was evaluated in a test data set and compared with current trauma triage guidelines, derived from the American College of Surgeons model. The newly developed prediction models performed comparably with the current trauma triage guidelines. Although the performance of newly developed triage models was promising, their performance did not exceed that of the current trauma triage guidelines. In particular, the anatomic injury criteria appeared to be the key component of the current trauma triage guidelines.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2003
DOI: 10.1161/01.STR.0000077925.16041.6B
Abstract: Background and Purpose— Use of oral contraceptives has increased, and there is uncertainty about the stroke risk associated with their use. Our aim was to investigate this issue. Methods— Using case-control techniques, we identified consecutive women with ischemic stroke from 4 Melbourne hospitals. All patients were between 15 and 55 years of age and had no prior stroke. Neighborhood-based control subjects were in idually age-matched (±5 years) and geographically matched to subject cases. A questionnaire administered to participants elicited information about prior exposure to various potential risk factors, including the oral contraceptive pill (OCP). Results— We included 234 cases and 234 controls (mean age, 42 years). Compared with noncurrent use, current use of the OCP, in doses of ≤50 μg estrogen, was not associated with an increased risk of ischemic stroke (odds ratio [OR] 1.76 95% CI, 0.86 to 3.61 P =0.124). Factors associated with an increased risk of ischemic stroke were a history of hypertension (OR, 2.18 95% CI, 1.22 to 3.91), transient ischemic attack (OR, 8.17 95% CI, 1.69 to 39.6), previous myocardial infarction (OR, 5.64 95% CI, 1.04 to 30.61), and diabetes mellitus (OR, 5.42 95% CI, 1.42 to 20.75) family history of stroke (OR, 2.22 95% CI, 1.12 to 4.43) and smoking cigarettes per day (OR, 3.68 95% CI, 1.22 to 11.09). Conclusions— There was no evidence for an association between ischemic stroke and use of the OCP in low doses (≤50 μg estrogen) in young Australian women. Other modifiable risk factors such as hypertension, diabetes mellitus, and smoking are important.
Publisher: Wiley
Date: 02-1978
DOI: 10.1111/J.1440-1681.1978.TB00653.X
Abstract: 1. A precise and rapid gas chromatographic method for the measurement of plasma sodium valproate concentrations is presented. 2. The extraction is a single step procedure, and is reproducible and linear throughout the concentration range encountered. 3. Clinical evaluation of the drug is presented in eighteen epileptics on the basis of the percentage of days on which subjects had seizures before and after sodium valproate therapy. 4. A tentative therapeutic range for sodium valproate is presented on the basis of plasma levels and therapeutic effect.
Publisher: Wiley
Date: 09-1994
DOI: 10.1111/J.1445-2197.1994.TB02301.X
Abstract: Because of reduced health care funding it is becoming necessary for surgeons to take a greater interest in the costs of in idual operations. This study reports costs directly measurable to the patient, and also the indirect costs of hospital overheads, an operating suite and teaching, which were 37, 10 and 15%, respectively (62%), of hospital budget. A scheme has been developed which could give surgeons a standard to report direct costs. Pre-admission, ward, operating room, recovery, intensive care and post-admission are defined as cost periods and the modalities of staff, equipment (capital, maintenance and replacement), imaging, laboratory and consumables apply to each. This strategy was applied to assess open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) as an ex le. The direct costs for OC were $3706 and LC $2868, a difference of $838 the indirect and direct costs were OC $6004 and LC $4646, a difference of $1358. Thus indirect cost magnified the difference between the operations. Bed stay, density of nursing and use of disposable instruments were the major influence on direct costs. The in idual cost advantage of a shorter bed stay may be countervailed by an increased hospital activity. The main patient benefit of new operations may be improved quality of life and more rapid return to work with prevention of salary losses. A method has been developed to define costs of a particular surgical operation with the purpose of stimulating surgeons' interest in this topic and developing a common style of reporting.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-03-2020
DOI: 10.1212/WNL.0000000000009277
Abstract: To determine the effect of low-dose aspirin vs placebo on incident all-cause dementia, incident Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive decline in older in iduals. Aspirin in Reducing Events in the Elderly (ASPREE) was a double-blind, placebo-controlled trial of low-dose aspirin. In the United States and Australia, community-dwelling in iduals aged ≥70 years (US minorities ≥65 years) and free of cardiovascular disease, physical disability, and diagnosed dementia were enrolled. Participants were randomized 1:1–100 mg daily aspirin or placebo. The Modified Mini-Mental State Examination, Hopkins Verbal Learning Test–Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test assessed cognition at baseline and over follow-up. Additional cognitive testing was performed in participants with suspected dementia (“trigger”) based on within-study assessments or clinical history. Dementia was adjudicated according to DSM-IV criteria. National Institute on Aging–Alzheimer’s Association criteria were used for AD and MCI subclassification. A total of 19,114 participants were followed over a median 4.7 years and 964 triggered further dementia assessments. There were 575 adjudicated dementia cases, and 41% were classified as clinically probable AD. There was no substantial difference in the risk of all dementia triggers (hazard ratio [HR], 1.03 95% confidence interval [CI], 0.91–1.17), probable AD (HR, 0.96 95% CI, 0.74–1.24), or MCI (HR, 1.12 95% CI, 0.92–1.37) between aspirin and placebo. Cognitive change over time was similar in the aspirin and placebo groups. There was no evidence that aspirin was effective in reducing risk of dementia, MCI, or cognitive decline. Follow-up of these outcomes after initial exposure is ongoing. This study provides Class II evidence that for healthy older in iduals, low-dose aspirin does not significantly reduce the incidence of dementia, probable AD, MCI, or cognitive decline. NCT01038583.
Publisher: Wiley
Date: 02-2010
Publisher: S. Karger AG
Date: 2023
DOI: 10.1159/000528984
Abstract: b i Introduction: /i /b Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. b i Methods: /i /b This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the “ASPirin in Reducing Events in the Elderly (ASPREE)” clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). b i Results: /i /b At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67 95% CI: 1.50–1.86 and frail: HR: 2.80 95% CI: 2.27–3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. b i Conclusion: /i /b Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.
Publisher: Wiley
Date: 10-04-1997
DOI: 10.1002/(SICI)1097-0215(19970410)71:2<203::AID-IJC13>3.0.CO;2-I
Abstract: A population-based case-control study of 416 histologically diagnosed, incident gliomas in adults was carried out in Melbourne, Australia, to determine whether past medical, family or reproductive histories are risk factors for developing glioma. A total of 422 controls were selected from the Australian electoral roll and matched to cases for age, sex and post code of residence. An increased risk of developing glioma was observed among first-born in iduals OR (95% CI) 2.0 (1.4-2.9). It is possible that this effect is due to residual confounding by socio-economic status or that it is a chance finding. Alternatively, it may be that this is due to some other effect linked to the first pregnancy, such as maternal age, birth weight or circumstances of delivery. There was no apparent association between the development of glioma and other neuropsychiatric or general medical conditions or with family history or reproductive history. Allergies (asthma and eczema) were not associated with a decreased risk of glioma, as has previously been suggested.
Publisher: Wiley
Date: 05-2013
DOI: 10.1111/IMJ.12061
Abstract: Population ageing is projected to impact on health services utilisation including Emergency Departments (ED), with older patients reportedly having a high rate of return visits. We describe and compare patterns in ED utilisation between older and younger adults, and quantify the proportion and rate of return visits. Population-based retrospective analysis of metropolitan Melbourne public hospital ED data, 1999/2000 to 2008/2009. Numbers of patients, presentations, re-presentations and rates per 1000 population were calculated, with comparison of older (aged ≥ 70 years) and younger (15-69 years) attendances. Population growth in each age group was similar over the study period, yet ED presentations rose by 72% for older adults compared with a 59% increase for younger adults. Rates per 1000 population rose with increasing age. Of the population aged ≥ 70 years, 39% presented to ED compared with 17% of the population aged 15-69 years in 2008/2009. Twenty-seven per cent of the increase in older adult presentations was driven by a cohort who attended ≥ 4 times in 2008/2009. The number of older patients presenting ≥ 4 times doubled over the decade, contributing to 23% of all older presentations in 2008/2009. ED length of stay rose with increasing age 69% of older adults remained in ED for ≥ 4 h compared with 39% of younger adults in 2008/2009. The number of older adult ED hospital admissions doubled over the decade. Older patients are disproportionately represented among ED attendances. They also have an increasing propensity to re-present to ED, indicating a need to identify the clinical, social and health system-related risk factors for re-attendance by specific patients.
Publisher: Springer Science and Business Media LLC
Date: 04-2012
DOI: 10.2165/11599030-000000000-00000
Abstract: The role of aspirin in the secondary prevention of occlusive cardiovascular events has now been well established. Given this, aspirin in primary prevention has been the focus of several large trials and subsequent meta-analyses over the past 3 decades, and yet the issue remains controversial. Recent studies in populations with high baseline risk - such as diabetics and those with asymptomatic peripheral arterial disease - have not found the expected benefits of aspirin on cardiovascular endpoints, which contrasts with earlier studies that reported a reduced relative risk for outcomes such as myocardial infarction and ischaemic stroke, but not for mortality. Furthermore, in healthy populations, the absolute risk reduction conferred by aspirin is small and needs to be balanced against the risk of a major haemorrhage. Older adults have a higher risk for cardiovascular events and therefore might represent the group in which aspirin for primary prevention could deliver the greatest absolute benefit, yet at the same time, the elderly bear an increased vulnerability to major haemorrhage, including haemorrhagic stroke. It is also not known whether older adults experience the same risk reduction from aspirin as middle-aged in iduals. The current evidence base does not sufficiently clarify whether aspirin for primary prevention confers a meaningful net benefit in the elderly.
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Elsevier BV
Date: 11-2020
Publisher: BMJ
Date: 02-12-2009
Abstract: To establish the relationship between the history of hip and groin injuries in elite junior football players prior to elite club recruitment and the incidence of hip and groin injuries during their elite career. Retrospective cohort study. Analysis of existing data. 500 Australian Football League (AFL) players drafted from 1999 to 2006 with complete draft medical assessment data. Previous history of hip/groin injury, anthropometric and demographic information. The number of hip/groin injuries resulting in > or =1 missed AFL game. Data for 500 players were available for analysis. 86 (17%) players reported a hip/groin injury in their junior football years. 159 (32%) players sustained a hip/groin injury in the AFL. Players who reported a previous hip or groin injury at the draft medical assessment demonstrated a rate of hip/groin injury in the AFL >6 times higher (IRR 6.24, 95% CI 4.43 to 8.77) than players without a pre-AFL hip or groin injury history. This study demonstrated that a hip or groin injury sustained during junior football years is a significant predictor of missed game time at the elite level due to hip/groin injury. The elite junior football period should be targeted for research to investigate and identify modifiable risk factors for the development of hip/groin injuries.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1986
DOI: 10.1097/00005344-198611000-00016
Abstract: The pharmacokinetic handling of the beta 1 selective adrenoceptor blocking drug, bevantolol, was studied in 12 healthy volunteers. After intravenous (i.v.) administration of 50 mg of the drug, there was a biexponential decline in plasma levels with a terminal elimination half life (t1/2) of 1.9 h (range 1.4-2.3 h) and a total apparent volume of distribution at equilibrium of 62 L. After oral administration of the same dose, the bioavailability averaged 57% (range 26-98%) and peak plasma levels varied over a threefold range. On average, less than 1% of the dose was eliminated unchanged in the urine, indicating that the clearance of the drug was accounted for almost entirely by metabolism. Plasma levels after oral dosing with food showed an average 75-min delay in achievement of peak plasma levels and an average 14% increase in the extent of bioavailability of the drug. A positive correlation (r = 0.79) existed between the logarithm of the plasma bevantolol level and the percentage of reduction in postexercise heart rate. A plasma drug level of approximately 200 ng/ml produced a 10% reduction in postexercise heart rate. Pharmacological studies using guinea pig atrial and tracheal tissue demonstrated that the beta-blocking potency and beta-selectivity of bevantolol were intermediate between those of metoprolol and atenolol.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2010
Publisher: Japanese Society of Hypertension
Date: 1994
Publisher: American Medical Association (AMA)
Date: 25-09-1996
Publisher: Elsevier BV
Date: 07-1983
DOI: 10.1016/0002-9149(83)90185-6
Abstract: There is some evidence that partial agonism is an important property of beta-blocking drugs, and this property may be exploited to produce a new range of positive inotropic drugs. With the established beta-adrenoceptor-blocking drugs, the level of partial agonist activity is weak and the dose-response curve for this property is shallow. However, its absence appears to increase the likelihood of inducing bronchospasm and bradycardia, and drugs that lack intrinsic sympathomimetic activity appear more likely to be associated with rebound cardiac arrhythmias on cessation of treatment. The idea of a small level of hormone activity--in this case, catecholamine activity--being necessary to maintain normal cardiac and perhaps bronchial function is not new. Minimal doses of steroids are essential to maintaining the inotropic action of cardiac muscle. There is now enough accumulated evidence to suggest that a minimal degree of beta-adrenoceptor stimulation is also important for normal bronchial and cardiac function, and its absence increases the incidence of bradycardia and the risks of bronchospasm and rebound arrhythmias.
Publisher: No publisher found
Date: 2007
Publisher: Oxford University Press (OUP)
Date: 11-1993
DOI: 10.1093/EURHEARTJ/14.11.1465
Abstract: Aortic mechanical properties were assessed in a group of elderly subjects with untreated isolated systolic hypertension using two-dimensional echocardiography. Echocardiographic (two-dimensional and Doppler) assessment of left ventricular structure and function was also made. Ten subjects (mean age 71.7 +/- 1.9 years, 20% male, mean clinic blood pressure 163.6/79.2 +/- 1.2/2.0 mmHg) were compared with 16 normotensive subjects of similar age (69.4 +/- 1.6 years, 38% male, mean clinic blood pressure 129.8/78.2 +/- 3.2/2.9 mmHg). Aortic distensibility at the level of the transverse aortic arch was significantly reduced among subjects with isolated systolic hypertension. The thickness of the interventricular septum was approximately 20% greater in the hypertensive subjects (P < 0.01) and the average wall thickness to radius ratio was increased by 30%. Patterns of transmitral diastolic flow were also different in subjects with isolated systolic hypertension. Deceleration time was significantly greater (P < 0.01) and the ratio of early to late transmitral diastolic peak flow velocities was significantly less in the hypertensive (P < 0.05) than in the normotensive group. Left ventricular systolic function was well preserved. These findings are consistent with the suggestion that isolated systolic hypertension represents a state of increased aortic stiffness which may contribute to the development of left ventricular hypertrophy. Whether this increase in aortic stiffness is the cause or effect of the elevated systolic blood pressure remains unresolved.
Publisher: Elsevier BV
Date: 04-1996
DOI: 10.1016/S0260-6917(96)80063-3
Abstract: The provision of further education opportunities is generally known to be limited for enrolled nurses. With the phasing out of the enrolled nurse qualification, it appears that many of them have to compete for limited places on conversion courses. Such a situation which has been placed on them appears to create problems in their lives. This study was undertaken with a randomized s le of 30 enrolled nurses to find out what the psychosocial problems may be for them who have not yet been able to convert to registered nurse status. The findings reveal a sense of betrayal, frustration, anger and helplessness at being coerced into getting onto conversion courses. That is compounded by the fact that places on such courses are extremely limited. Superimposed on those, fears were also expressed for their jobs. That was particularly so in the case of nurses from the area of learning disabilities. Although there are suggestions that they need to get onto conversion courses, there is a sense of disillusionment as places on the courses are extremely limited. Whilst the intention to convert may be present, many feel prevented from doing so because of their family commitments. In many instances, those commitments were non-existent when they first embarked on their nurse education/training. At the very least, the findings suggest a moral responsibility on the part of the relevant authorities to undertake a coordinated effort to help this group of nurses. After all it may be suggested that their predicament is not of their own making.
Publisher: Springer Science and Business Media LLC
Date: 1989
DOI: 10.1007/BF00558139
Publisher: American Association for Cancer Research (AACR)
Date: 29-03-2022
DOI: 10.1158/1940-6207.CAPR-22-0011
Abstract: There is strong evidence to support prophylactic aspirin use for the prevention of colorectal cancer. However recent recommendations suggest the risk of bleeding in older in iduals outweighs the benefit. We sought to determine whether some older in iduals might still benefit from aspirin based on their genetic susceptibility.
Publisher: Cambridge University Press (CUP)
Date: 31-05-2016
DOI: 10.1017/S104161021600079X
Abstract: Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention. ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a s le size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression. This paper presents the rationale for the study and presents a summary of the study design. ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
Publisher: AMPCo
Date: 12-2011
DOI: 10.5694/MJA10.11052
Abstract: To assess which patient characteristics influence the assessments of urgency for surgery by orthopaedic surgeons and non-orthopaedic professionals. Cross-sectional study of 80 patients requiring elective hip or knee replacement attending a public hospital orthopaedic outpatient clinic or orthopaedic surgeon's private rooms. Patients were interviewed after being placed on the surgery waiting list. The interview asked about the severity of their joint disease and its effects on physical capability, psychological distress and social circumstances. Patient interviews were summarised and presented to assessors who ranked groups of eight patients in order of their perceived urgency for surgery. Eleven orthopaedic surgeon assessors completed 360 patient ratings and nine non-orthopaedic assessors from various professions, including physiotherapy, social work, research, management and engineering, completed 720 patient ratings. Visual analogue scale rating of patient urgency for surgery patient rankings for surgery scores for in idual domain contributions to urgency rating. A broad spread of perceived urgency was evident among the patients. For each group of eight patients, there was moderate agreement on overall urgency rankings between the two groups of assessors. Linear regression demonstrated that pain was the dominant determinant of urgency score for both assessor groups. Orthopaedic surgeons also took into account limitations to mobility and concurrent medical illness but gave less priority to psychological distress or social circumstances. For the non-orthopaedic assessors, limitations to mobility, social circumstances and psychological distress also contributed to urgency. Both orthopaedic surgeons and non-orthopaedic professionals considered pain the most important factor in establishing urgency and priority for joint replacement. Only the non-orthopaedic professionals considered psychosocial factors important when determining priority for surgery. Broader community discussion about prioritisation for elective surgery is needed to facilitate agreement about which patients factors should be considered.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2021
DOI: 10.1038/S41525-021-00211-X
Abstract: Genetic testing is used to optimise the management of inherited cardiovascular disorders that can cause sudden cardiac death. Yet more genotype–phenotype correlation studies from populations not ascertained on clinical symptoms or family history of disease are required to improve understanding of gene penetrance. We performed targeted sequencing of 25 genes used routinely in clinical genetic testing for inherited cardiovascular disorders in a population of 13,131 asymptomatic older in iduals (mean age 75 years) enrolled in the ASPREE trial. Participants had no prior history of cardiovascular disease events, dementia or physical disability at enrolment. Variants were classified following ACMG/AMP standards. Sudden and rapid cardiac deaths were clinically adjudicated as ASPREE trial endpoints, and assessed during mean 4.7 years of follow-up. In total, 119 participants had pathogenic/deleterious variants in one of the 25 genes analysed (carrier rate of 1 in 110 or 0.9%). Participants carried variants associated with hypertrophic cardiomyopathy ( N = 24), dilated cardiomyopathy (N = 29), arrhythmogenic right-ventricular cardiomyopathy ( N = 22), catecholaminergic polymorphic ventricular tachycardia ( N = 4), aortopathies ( N = 1), and long-QT syndrome ( N = 39). Among 119 carriers, two died from presumed sudden/rapid cardiac deaths during follow-up (1.7%) both with pathogenic variants in long-QT syndrome genes ( KCNQ1 , SCN5A ). Among non-carriers, the rate of sudden/rapid cardiac deaths was significantly lower (0.08%, 11/12936, p 0.001). Variants associated with inherited cardiovascular disorders are found in asymptomatic in iduals aged 70 years and older without a history of cardiovascular disease.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.IJROBP.2017.02.024
Abstract: To identify, through a systematic review, all validated tools used for the prediction of patient-reported outcome measures (PROMs) in patients being treated with radiation therapy for prostate cancer, and provide a comparative summary of accuracy and generalizability. PubMed and EMBASE were searched from July 2007. Title/abstract screening, full text review, and critical appraisal were undertaken by 2 reviewers, whereas data extraction was performed by a single reviewer. Eligible articles had to provide a summary measure of accuracy and undertake internal or external validation. Tools were recommended for clinical implementation if they had been externally validated and found to have accuracy ≥70%. The search strategy identified 3839 potential studies, of which 236 progressed to full text review and 22 were included. From these studies, 50 tools predicted gastrointestinal/rectal symptoms, 29 tools predicted genitourinary symptoms, 4 tools predicted erectile dysfunction, and no tools predicted quality of life. For patients treated with external beam radiation therapy, 3 tools could be recommended for the prediction of rectal toxicity, gastrointestinal toxicity, and erectile dysfunction. For patients treated with brachytherapy, 2 tools could be recommended for the prediction of urinary retention and erectile dysfunction. A large number of tools for the prediction of PROMs in prostate cancer patients treated with radiation therapy have been developed. Only a small minority are accurate and have been shown to be generalizable through external validation. This review provides an accessible catalogue of tools that are ready for clinical implementation as well as which should be prioritized for validation.
Publisher: Elsevier BV
Date: 2001
Abstract: The stroke classification developed for use in the Oxfordshire Community Stroke Project (OCSP) is simple, clinically meaningful and requires no investigations. However, its inter-rater reliability in a community setting is unknown. We aimed to assess the inter-rater reliability of this classification among neurologists and nurses within a community-based stroke incidence study. Fifty-four stroke patients with cerebral infarction who were registered in the North East Melbourne Stroke Incidence Study (NEMESIS) were assigned OCSP classifications by two neurologists and one of seven research nurses. There was moderate agreement between neurologists (kappa = 0.53), fair agreement between neurologist 1 and nurse (kappa = 0.31) and moderate agreement between neurologist 2 and nurse (kappa = 0.45). Disagreement about the neurological signs was an important reason for classification differences. The OCSP classification can be easily applied in a community setting with moderate inter-rater reliability and is thus a useful instrument for commun ity-based epidemiological studies.
Publisher: SAGE Publications
Date: 13-01-2015
Publisher: Oxford University Press (OUP)
Date: 11-08-2020
DOI: 10.1093/JNCI/DJAA114
Abstract: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger in iduals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.
Publisher: Informa UK Limited
Date: 07-2005
DOI: 10.1080/08037050510034194
Abstract: The characterization of blood pressure in treatment trials assessing the benefits of blood pressure lowering regimens is a critical factor for the appropriate interpretation of study results. With numerous operators involved in the measurement of blood pressure in many thousands of patients being screened for entry into clinical trials, it is essential that operators follow pre-defined measurement protocols involving multiple measurements and standardized techniques. Blood pressure measurement protocols have been developed by international societies and emphasize the importance of appropriate choice of cuff size, identification of Korotkoff sounds, and digit preference. Training of operators and auditing of blood pressure measurement may assist in reducing the operator-related errors in measurement. This paper describes the quality control activities adopted for the screening stage of the 2nd Australian National Blood Pressure Study (ANBP2). ANBP2 is cardiovascular outcome trial of the treatment of hypertension in the elderly that was conducted entirely in general practices in Australia. A total of 54 288 subjects were screened 3688 previously untreated subjects were identified as having blood pressure >140/90 mmHg at the initial screening visit, 898 (24%) were not eligible for study entry after two further visits due to the elevated reading not being sustained. For both systolic and diastolic blood pressure recording, observed digit preference fell within 7 percentage points of the expected frequency. Protocol adherence, in terms of the required minimum blood pressure difference between the last two successive recordings, was 99.8%. These data suggest that adherence to blood pressure recording protocols and elimination of digit preferences can be achieved through appropriate training programs and quality control activities in large multi-centre community-based trials in general practice. Repeated blood pressure measurement prior to initial diagnosis and study entry is essential to appropriately characterize hypertension in these elderly patients.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2018
DOI: 10.1007/S11356-018-2895-0
Abstract: Fruit shell residue from Xanthoceras sorbifolia was investigated as a potential biosorbent to remove crude oil from aqueous solution. The shell powder and its carbonized material were compared while assessing various factors that influenced oil removal capacity. The structure and sorption mechanism were characterized using scanning electron microscopy and Fourier-transform infrared spectroscopy. The oil removal capacity of the raw material (75.1 mg g
Publisher: Springer Science and Business Media LLC
Date: 22-10-2019
DOI: 10.1186/S41687-019-0152-Z
Abstract: To examine the acceptability of a Patient Reported Outcome Measure (PROM) that assesses perceptions and experiences of implants for breast reconstruction or augmentation, and the feasibility of implementing it in the Australian Breast Device Registry (ABDR). The BREAST-Q Implant Surveillance (BREAST-Q IS) is a 5-question PROM derived from the BREAST-Q questionnaire. It assesses perceptions of breast appearance and sensation, and experiences of pain. Breast implant recipients (recruited via community networks, social media and notices in surgeons’ rooms) and surgeons contributing to the ABDR were invited to review the BREAST-Q-IS. Participation was by in idual semi-structured interviews by telephone or email, or by completion of a paper questionnaire. Transcripts of audio recordings and emailed text were analysed thematically. Twenty one breast implant recipients (10 after reconstruction and 11 augmentation), 8 surgeons (five plastic, three breast) and 2 medical professionals performing cosmetic surgeries were interviewed. Six themes were identified: Overall impression , Emotional response to the BREAST-Q IS, Method of follow-up , S uggested improvements , Group variation, and Potential Clinical utility . Overall, breast implant recipients and surgeons found the BREAST-Q IS to be acceptable and unlikely to provoke strong emotional reactions. Email was the preferred mode of contact. Most suggested improvements were to add questions. Surgeons expressed concern that subjective responses to the PROM might not accurately reflect experiences and that the PROM would predict need for revision rather than device failure. This study supports the acceptability and feasibility of BREAST-Q IS as a PROM for recipients of breast implants. Further validation of the Breast-Q IS is required.
Publisher: Informa UK Limited
Date: 1989
DOI: 10.3109/10641968909035373
Abstract: Epidemiological studies of stroke have been consistent in identifying hypertension as the major single precursor of cerebrovascular disease. It is an equally important precursor of thromboembolic and major haemorrhagic stroke. Whereas young persons with mild hypertension are at increased risk of myocardial infarction, with increasing age and at higher blood pressure levels stroke becomes relatively more important. All the major intervention studies using antihypertensive drugs have shown a decline in fatal and non-fatal stroke in the treated group. In the five placebo-controlled studies where the average treatment placebo difference was 6 mmHg, the mean reduction in fatal stroke was 47% and non-fatal stroke was 51%. Evidence from the Mayo Clinic indicates a substantial decline in stroke incidence as well as stroke mortality. The period of this decline corresponds to the widespread introduction of antihypertensive therapy and it is tempting to speculate that the c aigns to reduce blood pressure are largely responsible for this decline.
Publisher: Wiley
Date: 2013
DOI: 10.1111/J.1445-5994.2012.02842.X
Abstract: To examine non-clinical factors associated with emergency department (ED) attendance by lower urgency older patients. An exploratory descriptive study comprising structured interviews with lower urgency community-dwelling patients aged ≥70 years presenting to a tertiary metropolitan Melbourne public hospital ED. Demographical and clinical characteristics, self-reported feelings of social connectedness, perceived accessibility to primary care, reason for attending ED were measured. One hundred patients were interviewed: mean age 82 years, 56% female, 57% lived alone 73% presented during business hours, 58% arrived by ambulance, 80% presented for illness, and 65% were discharged home within 48 h. Fifty-six per cent of patients reported feeling socially disconnected, comprising 49% living alone compared with 65% who lived with their spouse/family. All patients attended a regular general practitioner, 31% reporting regular review appointments. Thirty-five per cent reported waiting times >2-3 days for urgent problems 59% stated accessing care 'after hours' without attending ED as difficult, with 20% having attended ED 3-6 times in the previous 12 months. Reasons for attending ED were referral by a third party, difficulty with accessibility to primary care, patient preferences for timely care and fast-track access to specialist care. Most older patients of lower clinical urgency presented to ED because of perceived access block to primary or specialist services, alongside an expectation of more timely and specialised care. This suggests that EDs should be redesigned and/or integrated community-based models of care developed to meet the specific needs of this age group who have growing demand for acute care.
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: Massachusetts Medical Society
Date: 05-11-1998
Publisher: Springer Science and Business Media LLC
Date: 06-1992
DOI: 10.1038/SC.1992.87
Abstract: To establish whether the reported increased cardiovascular (CV) morbidity in spinal cord injury (SCI) patients is due to increased levels of established CV risk factors, we assessed overall CV risk in 102 consecutive patients aged 25-64 by calculation of a 'risk factor score' (RFS) derived from the MRFIT study (age, diastolic blood pressure (DBP), total cholesterol (TC) level, cigarettes/day, sex), obtaining a percentile position amongst an age and sex matched peer group from the 1983 Australian Risk Factor Prevalence Study. Chronic SCI patients had a very low overall percentile position of risk of 26.03 + 15.06 (mean +/- S.D.) and those patients with SCI for greater than 10 years had only a slightly higher risk position of 33.16 +/- 29.66. The low relative risk in SCI patients was due mainly to significantly lower DBP levels (67 +/- 13 mm hg), as TC levels (5.38 +/- 1.60 mmol/L) and cigarette consumption (31% smokers, mode 11-20/day) were similar to the control population (83 +/- 12 mmHg, 5.68 +/- 1.2 mmol/L, 28% smokers, mode 11-20/day, respectively). As other known risk factors such as lipoprotein cholesterol fractions were not included in the RFS index, these were measured in 327 consecutive SCI patients. HDL cholesterol levels, which are negatively correlated with CV risk, were significantly lower in SCI patients (1.12 +/- 0.30 mmol/L) compared to controls (1.35 +/- 0.35 mmol/L) and those patients more than 10 years post SCI had still lower levels (1.02 +/- 0.40). These data suggest that the reported increased incidence of CV disease in SCI patients is unexplained by increases in BP, TC or smoking. However, low HDL levels may contribute to CV risk and the role of other risk factors such as increased vascular reactivity remain to be established.
Publisher: Oxford University Press (OUP)
Date: 27-01-2018
Abstract: To investigate the attributes of Australian clinical quality registries (CQR). Survey of 40 CQRs between September 2015 and April 2016. CQR lead investigators roject managers. None. Registry organization, geographical coverage, data quality, management, characteristics, output and outcomes. Of those who responded (34/40 85.0%), 12 (34.3%) were binational (Australia and New Zealand) 22 (64.7%) were Australian-only registries and 13 (38.2%) had national coverage. CQRs covered critical care, infection control, cardiovascular diseases, cancer, chronic diseases, procedures and devices, and transplants. Overall, 24/34 CQRs (70.6%) were public sector funded. In total, 14 (41.2%) scored >75% on a composite score developed to assess data quality. Overall, 29/34 (85.3%) produced an annual multi-centred report only 15/34 (44.1%) produced provider-specific reports. Mortality/survival and quality of life were collected by 82.4 and 32.4% of CQRs, respectively. Most CQRs displayed data in bar/column charts (28/34, 82.4%) and funnel plots (17/34, 50%). Most CQRs adopted an opt-out consent process (n = 17/31 54.8%). Linear regression indicated that longer duration of CQR was associated with higher data quality (>20 vs 0-5 years coefficient = 4.76, 95% CI: 0.26, 9.26). Opt-in consent was associated with lower data quality (no active consent vs opt-in approval method, coefficient = -5.22, 95% CI: -8.71, -1.72). Six CQRs self-reported having undertaken an economic evaluation of their registry. CQRs varied in geographical coverage stage of development, approach to recruitment method and frequency of reporting their output and data quality assurance. An accreditation system for CQRs would likely assist in recognizing high-quality registries.
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.JACC.2005.10.064
Abstract: The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) aimed to establish whether high-dose folic acid would slow the progression of atherosclerosis and reduce cardiovascular events in patients with chronic renal failure (CRF). Hyperhomocysteinemia is a potential contributor to the high rates of cardiovascular morbidity and mortality in patients with CRF. A total of 315 subjects with CRF, mean age 57 years (range 24 to 79 years) were randomized to 15 mg folic acid daily or placebo and followed for a median of 3.6 years. The primary intima-media thickness (IMT) and clinical end points were: rate of progression of mean maximum carotid IMT and a composite of myocardial infarction (MI), stroke, and cardiovascular death. Secondary end points included all cardiovascular events and change in pulse wave velocity, systemic arterial compliance and augmentation index. Data were analyzed by intention-to-treat. Plasma total homocysteine was reduced by 19% in the folic acid group. There was no significant difference between the treatment groups in rate of change of IMT or any measure of artery function. Seventy-seven events occurred in the folic acid group (14.9 per 100 patient-years) as compared with 86 in the placebo group (16.3 per 100 patient-years). The rates of the primary and secondary clinical end points at five years were not significantly different after adjustment for baseline differences between the groups (adjusted hazard ratio for MI, stroke, and cardiovascular death: 0.98 [95% confidence interval: 0.66 to 1.47] p = 0.94 for all cardiovascular events: 0.95 [95% confidence interval: 0.69 to 1.30] p = 0.75). High-dose folic acid does not slow atheroma progression or improve cardiovascular morbidity or mortality in patients with CRF.
Publisher: BMJ
Date: 10-2018
DOI: 10.1136/BMJOPEN-2018-023141
Abstract: To inform the development of a patient-reported outcome measure, the aim of this study was to identify which symptoms and feelings following percutaneous coronary intervention (PCI) are most important to patients. Discrete-choice experiment consisting of two hypothetical scenarios of 10 symptoms and feelings (pain or discomfort shortness of breath concern/worry about heart problems tiredness confidence to do usual activities ability to do usual activities happiness sleep disturbance dizziness or light-headedness and bruising) experienced after PCI, described by three levels (never, some of the time, most of the time). Preference weights were estimated using a conditional logit model. Four Australian public hospitals that contribute to the Victorian Cardiac Outcomes Registry (VCOR) and a private insurer’s claim database. 138 people aged years who had undergone a PCI in the previous 6 months. Patient preferences via trade-offs between 10 feelings and symptoms. Of the 138 in iduals recruited, 129 (93%) completed all 16 choice sets. Conditional logit parameter estimates were mostly monotonic (eg, moving to worse levels for each in idual symptom and feeling made the option less attractive). When comparing the magnitude of the coefficients (based on the coefficient of the worst level relative to best level in each item), feeling unhappy was the symptom or feeling that most influenced perception of a least-preferred PCI outcome (OR 0.42, 95% CI 0.34 to 0.51, p .0001) and the least influential was bruising (OR 0.81, 95% CI 0.67 to 0.99, p=0.04). This study provides new insights into how patients value symptoms and feelings they experience following a PCI.
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.JCMG.2009.03.016
Abstract: We sought to identify clinical, physiological, and biochemical correlates, including markers of endothelial dysfunction and of tissue nitric oxide (NO) responsiveness, of the presence of aortic sclerosis (ASc) in an aging population. Aortic sclerosis has been regarded predominantly as a precursor of hemodynamically significant aortic stenosis. However, ASc also represents an independent correlate of increased risk of cardiovascular morbidity and mortality the basis of this association is incompletely understood. The assumption that the pathogenesis of aortic valve disease is similar to that of atherosclerosis has not been supported by recent studies rather there has been increasing evidence of a pathogenetic role of inflammation and endothelial dysfunction. Furthermore, we have recently developed methodology for echocardiographic quantitation of early aortic valve disease. Randomly selected subjects (n = 253) ages 51 to 77 years underwent transthoracic echocardiography aortic valve ultrasonic backscatter score (AV(BS)) was used to quantitate echogenicity of the aortic valve. Conventional coronary risk factors were identified. Integrity of NO generation/response was assessed via: 1) plasma asymmetric dimethylarginine concentrations, as a marker of endothelial dysfunction 2) inhibition of platelet aggregation by the NO donor sodium nitroprusside, as a measure of tissue NO responsiveness and also a coronary prognostic marker and 3) aortic augmentation index, as a measure of arterial stiffness/wave reflection. All putative correlations with AV(BS) were examined by univariate and multiple linear regression analyses. On the basis of AV(BS) scores, ASc was present in 19.4% of subjects. The AV(BS) directly correlated with patients' age but inversely correlated with high-sensitivity C-reactive protein, creatinine clearance, and platelet NO responsiveness. On multiple linear regression, ASc was associated with impaired platelet NO responsiveness (beta = -0.16, p = 0.02), advancing age (beta = 0.21, p = 0.003), and low body mass index (beta = -0.23, p = 0.001). Aortic sclerosis is associated with platelet NO resistance rather than conventional coronary risk factors: this might explain the increased thrombotic risk in ASc.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2011
Publisher: Wiley
Date: 02-07-2010
DOI: 10.1111/J.1468-1293.2009.00808.X
Abstract: Our aim was to compare three different definitions of treatment failure and discuss their use as quality outcome measures for a clinical service. Data for treatment-naïve patients who attended the Melbourne Sexual Health Centre (MSHC) between 1 January 2000 and 31 December 2008 were analysed. Definition 1 was the strict Food and Drug Administration (FDA) definition of treatment failure as determined using the time to loss of virological response (TLOVR) algorithm. Definition 2 defined treatment failure as occurring in those whose viral load never fell to or =400 copies/mL on any treatment (switching or stopping treatment with a viral load <400 copies/mL was permitted). Definition 3 was the same as definition 2 except that in iduals were also deemed to have failed if they stopped treatment for 6 months or longer. There were 310 antiretroviral-naïve patients who started treatment in the study period. Of these, 156 [50.3% 95% confidence interval (CI) 42.1-53.3%] experienced treatment failure under definition 1, 10 (3.2% 95% CI 1.5-5.8%) experienced treatment failure under definition 2, and 16 (4.5% 95% CI 2.5-7.4%) experienced treatment failure under definition 3 over the 108 months of follow-up. The probability of failing definition 1 was statistically different from the probability of failing definition 2 or 3 (P=0.01). There were significant differences in treatment failure for the three definitions. If definition 1 were used, the outcomes would be sufficiently common to enable clinics to be compared but would be less meaningful. If definition 2 or 3 were used, the events would be too rare to enable clinics to be compared, but it would be possible to set a benchmark level of success that clinics could aim to reach.
Publisher: BMJ
Date: 12-2017
DOI: 10.1136/BMJOPEN-2017-017778
Abstract: To establish a pilot clinical quality registry (CQR) to monitor the quality of care and device performance for breast device surgery in Australia. All patients having breast device surgery from contributing hospitals in Australia. A literature review was performed which identified quality indicators for breast device surgery. A pilot CQR was established in 2011 to capture prospective data on breast device surgery. An interim Steering Committee and Management Committee were established to provide clinical governance, and guide quality indicator selection. The registry’s minimum dataset was formulated in consultation with stakeholder groups potential quality indicators were assessed in terms of (1) importance and relevance, (2) usability, (3) feasibility to collect and (4) scientific validity. Data collection was by a two-sided paper-based form with manual data entry. Seven sites were recruited, including one public hospital, four private hospitals and two day surgeries. Patients were recruited and opt-out consent used. The pilot breast device registry provides high-quality population-based data. It provides a model for developing a national CQR for breast devices its minimum dataset and quality indicators reflect the opinions of the broad range of stakeholders. It is easily scalable, and has formed the basis for other international surgical groups establishing similar registries.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Wiley
Date: 04-1979
DOI: 10.1111/J.1365-2125.1979.TB04773.X
Abstract: 1 The pharmacokinetics of labetalol were studied in twelve hypertensive patients, ten of whom were not receiving other therapy. 2 Following intravenous administration there was a three- to fourfold variation in terminal elimination half-life, volume of distribution and total plasma clearance. The mean elimination half-life was 3.25 hours. 3 Following oral administration the drug was absorbed rapidly. Systemic availability varied from 11-86% (mean 33%). 4 Plasma levels correlated poorly with the acute effect on BP, raising the possibility of labetalol acting in a deep tissue compartment or alternatively an active metabolite contributing to its effect.
Publisher: Swets & Zeitlinger Publishers
Date: 1999
DOI: 10.1076/OPEP.6.3.195.1500
Abstract: Cataract is the leading cause of blindness in the world today, while age-related macular degeneration is responsible for the majority of new cases of visual impairment in the Western world. There is a growing body of evidence suggesting a role for antioxidant therapy to prevent the progression of these conditions. A 4-year prospective, randomised, controlled trial of an antioxidant versus placebo in a population of healthy volunteers aged 55-80 years at enrolment is described. This paper outlines the primary aims of the Vitamin E, Cataract and Age-related Macular Degeneration (VECAT) Study, the methodology, and the recruitment rates. Additional data on the toxicity and non-ocular effects of vitamin E will also be collected. Standardised clinical grading of macular and lens features, and comparison of serial macular photographs and digital lens photographs will form the basis for assessment of primary study outcomes. Information collected in this study will assist in the assessment of the potential value of antioxidants in preventing the enormous burden imposed on developed communities by age-related eye disease. In addition, important data on prevalence and progression rates of cataract and macular degeneration will be collected.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1996
Publisher: Oxford University Press (OUP)
Date: 07-1992
DOI: 10.1093/AJH/5.7.449
Abstract: This study investigated components of blood pressure variability in the elderly using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine s le size requirements for clinical trials of different design scenarios in the elderly. Twenty-six elderly subjects not receiving antihypertensive medication were recruited from general practices and seen on four occasions at weekly intervals. On each occasion of blood pressure was measured in the clinic using a standard mercury sphygmomanometer and then for 24 h using a noninvasive ambulatory monitoring device. The between subject and between subject/within occasion components of blood pressure variability were determined by analysis of variance and used to calculate to s le size requirements for parallel and crossover trials respectively. The between subject variance of mean blood pressure was 1/3 greater with clinic readings, except within a subgroup of subjects who had isolated systolic hypertension (ISH). Increasing the number of readings or occasions on which measurement was performed in a parallel group trial only reduced the variability substantially when the number of subjects involved was small. With crossover designs, the between subject component of variance is eliminated resulting in substantial reduction in s le size. Whereas 60 subjects with ISH would be required to detect a 10 mm Hg difference in systolic blood pressure between two treatments in a parallel design using casual readings, only 18 are required with a crossover trial. If ABPM is used the number of subjects required are 54 and 14, respectively. Reducing variability with ABPM involves a trade-off between the increased number of readings available with the technique against the highly uniform and standardized conditions used to determine clinic blood pressures. ABPM appears most useful as a strategy for reducing s le size in parallel group trials involving small numbers of subjects measured on one occasion.
Publisher: Oxford University Press (OUP)
Date: 2003
DOI: 10.1016/S0895-7061(02)03143-6
Abstract: Antihypertensive drug therapy is considered lifelong but in the family practice environment drug cessation may provide an opportunity to attempt nonpharmacologic strategies for blood pressure (BP) control with a clear outcome, maintaining drug-free status. The identification of simple predictors would assist the family physician to select who may or may not have their medication ceased. To monitor a drug cessation program in currently treated hypertensive patients in Australian family practice, 25,826 patients aged 65 to 84 years currently receiving antihypertensive medication, were offered drug withdrawal as part of the run-in phase of a large clinical trial. Outcomes investigated were the proportion of patients completing drug withdrawal and maintaining short-term BP control and factors that predicted these patients. A total of 18,993 patients did not enter the withdrawal program 6291 (92% of those who entered) completed drug withdrawal. In comparison to patients who did not complete drug withdrawal, they were younger and more likely male. A total of 1,228 (18% of those who entered) ceased medication and maintained adequate BP control for 0 to 76 weeks (median, 4 weeks). Cox regression analysis identified lower on therapy systolic and diastolic BP, younger age, type of agent, and monotherapy as predictors of successful drug withdrawal and maintenance of BP control. Cessation of antihypertensive drug therapy is possible in a substantial proportion (18%) of patients attending family practice who are willing to do so and is most successful in those who are younger with BP controlled on monotherapy. Where this strategy is initiated, use of such predictors, effective behavioral change, and systematic follow-up is recommended.
Publisher: S. Karger AG
Date: 1993
DOI: 10.1159/000108688
Publisher: Wiley
Date: 07-05-2019
DOI: 10.1111/NEP.13565
Publisher: Springer Science and Business Media LLC
Date: 25-01-2012
Publisher: Cambridge University Press (CUP)
Date: 29-10-2011
DOI: 10.1017/S1368980010002673
Abstract: To identify predictors of increasing waist circumference (WC) over a 5-year period in a contemporary population of Australian adults. Longitudinal national cohort of adults participating in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Australian adults in 2000 and 2005. A total of 2521 men and 2726 women aged ≥25 years at baseline who participated in AusDiab and provided anthropometric measurements at baseline (1999–2000) and follow-up (2005). A ≥5 % increase of baseline WC occurred in 27 % of men and 38 % of women over the 5-year period. In the multivariate analysis of the total population, there was a higher risk of ≥5 % gain in baseline WC in women, younger people, people with a lower baseline WC, people who never married compared with married/ de facto , current smokers compared with never smokers, people with a poorer diet quality and people with a low energy intake. However, there was no significant association with many expected predictors of waist gain such as physical activity. There were some associations between other lifestyle factors and change of WC by sex, age, level of education and across WC categories, but the associations differed across these groups. A ≥5 % increase of baseline WC occurred in a significant proportion of men and women over the 5-year period. Of the behavioural factors, poor diet quality was the key predictor of the ≥5 % increase of baseline WC in this cohort. The findings highlight the need to understand better the causal role of lifestyle in regard to increasing WC over time.
Publisher: Oxford University Press (OUP)
Date: 19-09-2014
DOI: 10.1093/NDT/GFU297
Publisher: BMJ
Date: 06-1997
Abstract: To determine by survey whether the frequency of use of performance enhancing drugs (drug doping) is significant in elite players of Australian Rules football, and to compare this frequency with that in other competitions. Randomised unannounced prospective urine testing during the period 1990-95 of players from the Australian Football League out of competition, in competition matches, and in finals matches testing was performed according to Olympic International Committee protocols and standards. The players' identities and clubs were unknown during testing. Of 900 random urine tests, no positive results were obtained for anabolic steroids, diuretics, caffeine, or peptide hormones. Five positive results (0.6%) were obtained-for pseudoephedrine in two instances, and for probenecid, methoxyphenamine, and dextropropoxyphene in one instance each. Each were inadvertent medical doping and declared before testing. Drug doping is not a problem in the Australian Football League. This is probably because no doping method is considered to be of value to Australian Rules football, because an educational programme is run by football authorities, and because random during season and out of season testing for drugs occurs.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1111/J.1753-6405.2011.00739.X
Abstract: This study investigated the sensitivity and specificity of the national mortality codes in identifying cardiovascular disease (CVD) deaths and documents methods of verification. A 12-year retrospective case ascertainment of all ICD-coded CVD deaths was performed for deaths between 1990 and 2002 in the Melbourne Collaborative Cohort Study, comprising 41,528 subjects. Categories of non-CVD codes were also examined. Stratified s les of 750 deaths were adjudicated from a total of 2,230 deaths. Expert panels of cardiologists and neurologists adjudicated deaths. Of the 750 deaths adjudicated, 582 were verified as CVD [392 coronary heart disease (CHD) and 92 stroke] and 168 non-CVD. Estimated sensitivity and specificity of national mortality codes for identifying specific causes of death were: CHD 74.2% (95% CI: 69.8-78.5%) and 97.6% (96.0-99.2%), respectively myocardial infarction 59.9% (50.9-69.0%) and 94.2% (92.4-96.0%), respectively haemorrhagic stroke 58.9% (46.0-71.7%) and 99.8% (99.4-100.0%), respectively and ischaemic stroke 38.7% (20.5-56.9%) and 99.9% (99.6-100.0%), respectively. Misclassification was most common for deaths with primary ICD codes for endocrine-metabolic and genito-urinary diseases. National mortality coding under-estimated the true proportion of CHD and stroke deaths in the cohort by 13.6% and 50.8%, respectively. Misclassification of cause of death may have implications for conclusions drawn from epidemiological research.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2014
DOI: 10.1038/CLPT.2014.86
Abstract: Dyslipidemia is common and is associated with the highest population-attributable risk for cardiovascular disease. Of various cardiovascular preventive therapies, the evidence from randomized controlled trials supporting the importance of aggressive lipid lowering is the most robust, particularly for statins. Despite the use of proven therapies, cardiovascular disease event rates remain relatively high, underpinning the development of novel therapies. In addition to testing new drugs to reduce low-density-lipoprotein cholesterol, there has been a major focus on treatments that can favorably influence high-density-lipoprotein cholesterol and triglyceride levels. This review provides an overview of the important relationship between lipids and cardiovascular disease, the lipid-modifying therapeutic approaches to reducing cardiovascular disease, new guidelines and recommendations, and the challenges ahead for the treatment of dyslipidemia, particularly whether statins will remain at the forefront of recommended therapies.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.C.6547022
Abstract: Abstract i MUTYH /i carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. i MUTYH /i carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male i MUTYH /i carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66 95% confidence interval (CI), 1.03–2.68 i P /i = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55 95% CI, 1.42–8.78 i P /i = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40 95% CI, 0.81–2.44 i P /i = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of i MUTYH /i carriers revealed no significant contribution toward early mutagenesis from widespread G:C T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of erse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic i MUTYH /i mutations. Prevention Relevance: Despite absence of loss of heterozygosity in colorectal cancers, elderly male i MUTYH /i carriers appeared to be at increased of colorectal cancer. /
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JTCVS.2018.09.113
Abstract: Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes. Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85 95% confidence interval, 0.64-1.13 P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87 95% CI, 0.76-1.00 P = .053). In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Springer Science and Business Media LLC
Date: 23-04-2022
DOI: 10.1038/S41397-022-00271-X
Abstract: One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p < 0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
Publisher: AMPCo
Date: 11-2016
DOI: 10.5694/MJA15.00921
Abstract: The provision of timely, relevant and reliable information on patient care to clinicians has been shown to drive improvements in health care quality. Well constructed clinical quality registries collect and report information on both the appropriateness of care (process) in keeping with clinical practice guidelines and the effectiveness of care (outcomes). Notwithstanding the successful establishment of several new registries and improvements in established registries, barriers persist for clinical groups wishing to improve the quality of information and level of participation in registries in Australia. To address these barriers, the Australian Commission on Safety and Quality in Health Care has developed the Framework for Australian Clinical Quality Registries. The Framework describes a mechanism by which government jurisdictions and private hospital groups can authorise and secure record-level data, within high priority clinical domains, to measure, monitor and report the appropriateness and effectiveness of health care. The provision of benchmarked information back to clinicians on the appropriateness and outcomes of care is expected to improve adherence to evidence-based practice and drive improvement in outcomes.
Publisher: Wiley
Date: 15-02-2016
DOI: 10.1111/BJU.13258
Abstract: To establish a Prostate Cancer Outcomes Registry-Australia and New Zealand (PCOR-ANZ) for monitoring outcomes of prostate cancer treatment and care, in a cost-effective manner. Stakeholders were recruited based on their interest, importance in achieving the monitoring and reporting of clinical practice and patient outcomes, and in amalgamation of existing registries. Each participating jurisdiction is responsible for local governance, site recruitment, data collection, and data transfer into the PCOR-ANZ. To establish each local registry, hospitals and clinicians within a jurisdiction were approached to voluntarily contribute to the registry following relevant ethical approval. Patient contact occurs following notification of prostate cancer through a hospital or pathology report, or from a cancer registry. Patient registration is based on an opt-out model. The PCOR-ANZ is a secure web-based registry adhering to ISO 27001 standards. Based on a standardised minimum data set, information on demographics, diagnosis, treatment, outcomes, and patient reported quality of life, are collected. Eight of nine jurisdictions have agreed to contribute to the PCOR-ANZ. Each jurisdiction has commenced implementation of necessary infrastructure to support rapid rollout. PCOR-ANZ has defined a minimum data set for collection, to enable analysis of key quality indicators that will aid in assessing clinical practice and patient focused outcomes. PCOR-ANZ will provide a useful resource of risk-adjusted evidence-based data to clinicians, hospitals, and decision makers on prostate cancer clinical practice.
Location: Hungary
Start Date: 2004
End Date: 10-2007
Amount: $150,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 09-2008
End Date: 12-2010
Amount: $306,977.00
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2008
End Date: 12-2013
Amount: $454,232.00
Funder: Australian Research Council
View Funded ActivityStart Date: 12-2004
End Date: 08-2010
Amount: $2,500,000.00
Funder: Australian Research Council
View Funded Activity