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Publisher: Oxford University Press (OUP)
Date: 12-12-2012
DOI: 10.1093/IJE/DYS173
Abstract: The Chronic Kidney Disease Prognosis Consortium (CKD-PC) was established in 2009 to provide comprehensive evidence about the prognostic impact of two key kidney measures that are used to define and stage CKD, estimated glomerular filtration rate (eGFR) and albuminuria, on mortality and kidney outcomes. CKD-PC currently consists of 46 cohorts with data on these kidney measures and outcomes from >2 million participants spanning across 40 countries/regions all over the world. CKD-PC published four meta-analysis articles in 2010-11, providing key evidence for an international consensus on the definition and staging of CKD and an update for CKD clinical practice guidelines. The consortium continues to work on more detailed analysis (subgroups, different eGFR equations, other exposures and outcomes, and risk prediction). CKD-PC preferably collects in idual participant data but also applies a novel distributed analysis model, in which each cohort runs statistical analysis locally and shares only analysed outputs for meta-analyses. This distributed model allows inclusion of cohorts which cannot share in idual participant level data. According to agreement with cohorts, CKD-PC will not share data with third parties, but is open to including further eligible cohorts. Each cohort can opt in/out for each topic. CKD-PC has established a productive and effective collaboration, allowing flexible participation and complex meta-analyses for studying CKD.
Publisher: BMJ
Date: 29-01-2013
DOI: 10.1136/BMJ.F324
Publisher: Wiley
Date: 27-09-2014
DOI: 10.1111/NEP.12284
Abstract: Acute kidney injury (AKI) is associated with increased mortality. While angiotensin-converting enzyme inhibitors (ACEI) are known to slow progression of chronic kidney disease, their role in AKI remains unclear. The Randomised Evaluation of Normal vs. Augmented Level Replacement Therapy (RENAL) study data were analysed according to ACEI use over time. The primary outcome was all-cause mortality at 90 days following randomisation. Analyses used a multivariate Cox model adjusted for either baseline or for time-dependent covariates, and a sensitivity analysis of patients surviving to at least the median time to ACEI initiation. Of the 1463 participants with available data on ACE inhibitors usage, 142 (9.7%) received ACEI at least once during study data collection. Participants treated with ACEI were older (P = 0.02) and had less sepsis at baseline (P < 0.001). ACEI use was significantly associated with lower mortality at 90 days (HR 0.46, 95% CI 0.30-0.71, P < 0.001), and an increase in renal replacement therapy-free days (P < 0.001), intensive care unit-free days (P < 0.001) and hospital free-days (P < 0.001) after adjusting for baseline covariates. Using the time-dependent analysis, however, the effect of ACEI administration was not significant (HR 0.78, 95% CI 0.51-1.21, P = 0.3). The sensitivity analysis in day 8 survivors produced similar results. In the RENAL study cohort, the use of ACEI during the study was not common and, after adjustment for time-dependent covariates, was not significantly associated with reductions in mortality. Further assessment of the effect of ACEI use in AKI patients is needed.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-01-2021
Abstract: In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate.
Publisher: American Medical Association (AMA)
Date: 06-10-2020
Publisher: Elsevier BV
Date: 12-2007
Publisher: Public Library of Science (PLoS)
Date: 19-01-2012
Publisher: Elsevier BV
Date: 07-2014
Publisher: Elsevier BV
Date: 05-2018
Publisher: BMJ
Date: 16-09-2009
DOI: 10.1136/BMJ.B3513
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1038/KI.2010.550
Publisher: Massachusetts Medical Society
Date: 02-11-2017
Publisher: Elsevier BV
Date: 04-2015
Publisher: American Medical Association (AMA)
Date: 12-01-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Elsevier BV
Date: 07-2015
Publisher: Elsevier BV
Date: 2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2016
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 03-2016
Publisher: Elsevier BV
Date: 11-2012
Publisher: American Medical Association (AMA)
Date: 23-06-2010
Abstract: Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04 95% confidence interval [CI], 0.97-1.12 P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%] RR, 1.05 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%] RR, 1.02 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%] RR, 1.18 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. isrctn.org Identifier: ISRCTN74348595.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Elsevier BV
Date: 10-2015
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.AHJ.2010.08.012
Abstract: Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Patients with advanced CKD (blood creatinine ≥ 1.7 mg/dL [≥ 150 μmol/L] in men or ≥ 1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Elsevier BV
Date: 10-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1161/STROKEAHA.116.013644
Abstract: Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity. Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s). Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13–91 P =0.004). Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4) the earlier that treatment is initiated, the greater the benefit.
Publisher: Elsevier BV
Date: 03-2020
Publisher: BMJ
Date: 10-01-2019
DOI: 10.1136/BMJ.K5301
Abstract: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. In idual participant data meta-analysis. Cohorts from 40 countries with data collected between 1970 and 2017. Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference six cohorts with high cardiovascular risk (n=84 417) and 18 cohorts with chronic kidney disease (n=91 607). GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR mL/min/1.73 m 2 ) and all cause mortality. Over a mean follow-up of eight years, 246 607 (5.6%) in iduals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in in iduals who have normal or reduced levels of estimated GFR.
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier BV
Date: 11-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2012
Publisher: Elsevier BV
Date: 03-2009
Publisher: Oxford University Press (OUP)
Date: 14-03-2018
Publisher: Elsevier BV
Date: 02-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
DOI: 10.2215/CJN.10371013
Publisher: SAGE Publications
Date: 24-11-2017
Abstract: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. We assessed outcomes in an in idual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2015
Publisher: Elsevier BV
Date: 04-2018
Publisher: Springer Science and Business Media LLC
Date: 23-08-2022
DOI: 10.1038/S41467-022-32398-7
Abstract: Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 in iduals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution ( p = 1.8 × 10 −09 ), favorable metabolic profile and protection from type 2 diabetes (~28% lower odds p = 0.004) for heterozygous protein-truncating mutations in INHBE , which encodes a circulating growth factor of the activin family, highly and specifically expressed in hepatocytes. Our results suggest that inhibin βE is a liver-expressed negative regulator of adipose storage whose blockade may be beneficial in fat distribution-associated metabolic disease.
Publisher: S. Karger AG
Date: 20-10-2016
DOI: 10.1159/000439581
Abstract: b i Aims: /i /b The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy (CRRT) and to study the impact of femoral versus non-femoral access on CRRT dose. b i Methods: /i /b Statistical analysis and predictive modelling of data from the Randomized Evaluation of Normal vs. Augmented Level renal replacement therapy trial. b i Results: /i /b The femoral vein was the first access site in 937 (67%) of 1,399 patients. These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores (p = 0.009) and lower pH (p 0.001) but similar mortality to patients with non-femoral access (44 vs. 45% p = 0.63). Lower body weight was independently associated with femoral access placement (OR 0.97, 95% CI 0.96-0.98). Femoral access was associated with a 1.03% lower CRRT dose (p = 0.05), but a 4.20% higher dose was achieved with 13.5 Fr catheters (p = 0.03). b i Conclusions: /i /b Femoral access was preferred in lighter and sicker patients. Catheter gauge had greater impact than catheter site in CRRT dose delivery. Video Journal Club “Cappuccino with Claudio Ronco” at www.karger.com/?doi=439581.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2019
DOI: 10.1097/CCM.0000000000003762
Abstract: To examine long-term survival and quality of life of patients with early septic shock. Prospective, randomized, parallel-group trial. Fifty-one hospitals in Australia, New Zealand, Finland, Hong Kong, and the Republic of Ireland. One-thousand five-hundred ninety-one patients who presented to the emergency department with early septic shock between October 2008 and April 2014, and were enrolled in the Australasian Resuscitation in Sepsis Evaluation trial. Early goal-directed therapy versus usual care. Long-term survival was measured up to 12 months postrandomization. Health-related quality of life was measured using the EuroQoL-5D-3L, Short Form 36 and Assessment of Quality of Life 4D at baseline, and at 6 and 12 months following randomization. Mortality data were available for 1,548 patients (97.3%) and 1,515 patients (95.2%) at 6 and 12 months, respectively. Health-related quality of life data were available for 85.1% of survivors at 12 months. There were no significant differences in mortality between groups at either 6 months (early goal-directed therapy 21.8% vs usual care 22.6% p = 0.70) or 12 months (early goal-directed therapy 26.4% vs usual care 27.9% p = 0.50). There were no group differences in health-related quality of life at either 6 or 12 months (EuroQoL-5D-3L utility scores at 12 mo early goal-directed therapy 0.65 ± 0.33 vs usual care 0.64 ± 0.34 p = 0.50), with the health-related quality of life of both groups being significantly lower than population norms. In patients presenting to the emergency department with early septic shock, early goal-directed therapy compared with usual care did not reduce mortality nor improve health-related quality of life at either 6 or 12 months.
Publisher: American Medical Association (AMA)
Date: 10-2021
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 11-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-11-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-12-2015
Abstract: A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an in idual–level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope −5 ml/min per 1.73 m 2 per year, whereas 7% and 4% had a slope ml/min per 1.73 m 2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m 2 per year, a slope of −6 ml/min per 1.73 m 2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m 2 per year also associated with higher all–cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-12-2015
Abstract: eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta–analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of −6 versus 0 ml/min per 1.73 m 2 per year over the previous 3 years (a decline of 18 ml/min per 1.73 m 2 versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m 2 (a difference of 20 ml/min per 1.73 m 2 ) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR ml/min per 1.73 m 2 .
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 05-2023
Publisher: Massachusetts Medical Society
Date: 05-09-2013
Publisher: American Medical Association (AMA)
Date: 12-12-2012
Publisher: Elsevier BV
Date: 02-2001
DOI: 10.1016/S0140-6736(00)04042-3
Abstract: Statins inhibit the same biochemical pathway as aminobisphosphonates, therefore these cholesterol-lowering agents may have a beneficial effect on osteoporosis. This possibility has been supported by the finding that some statins also stimulate bone formation, and by observational studies suggesting that patients using statins have higher bone densities and lower fracture rates than controls. To assess whether statins have clinically significant effects on bone, we studied the frequency of fractures in a large randomised controlled trial of these agents. 9014 patients (17% women, median age 62 years) with ischaemic heart disease were randomly assigned pravastatin 40 mg daily or placebo and followed up for a mean of 6.0 years. Fractures were ascertained from adverse-event reports. 101 patients in the placebo group were admitted to hospital for fracture compared with 107 in the pravastatin group (hazard ratio 1.05 [95% CI 0.80-1.37]). When patients with fractures not necessitating hospital admission were added, the total number of patients having a fracture was 183 in the placebo group and 175 in the pravastatin group (0.94 [0.77-1.16]). Separate analyses for women alone and for in iduals aged 65 years and over gave similar results. These findings offer no support for the hypothesis that statins have a significant effect on fracture risk. However, this study was not of an osteoporotic population, and fracture rate, although clinically important, is an insensitive index of effects on bone. Statins should not be used to prevent osteoporosis until there is evidence for their efficacy based on randomised controlled trials.
Publisher: BMJ
Date: 11-2020
DOI: 10.1136/BMJOPEN-2020-040492
Abstract: Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results. In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019. UK stroke services. 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms the remaining participants had died (380), withdrawn consent or did not respond. Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email. It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future. ISRCTN83290762 Post-results.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 05-2021
Publisher: Springer Science and Business Media LLC
Date: 16-07-2016
Publisher: American Medical Association (AMA)
Date: 25-06-2014
Publisher: Massachusetts Medical Society
Date: 22-10-2009
Publisher: Elsevier BV
Date: 11-2014
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 12-2000
DOI: 10.1016/S0140-6736(00)03257-8
Abstract: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction. 3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model. Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group 22.3% of the pravastatin group). Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin.
Publisher: Elsevier BV
Date: 06-2019
Publisher: American Medical Association (AMA)
Date: 09-05-2012
Publisher: Massachusetts Medical Society
Date: 13-02-2020
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1038/KI.2013.553
Publisher: Wiley
Date: 21-05-2005
DOI: 10.1111/J.1464-5491.2005.01516.X
Abstract: To estimate the prevalence of undiagnosed diabetes and impaired fasting glucose in older British men and women, using the 1999 World Health Organization (WHO) thresholds based on fasting glucose measurements. Participants in the British Regional Heart Study and the British Women's Heart and Health Study were selected from one socially representative general practice in 24 British towns. Included in this analysis were 3736 men and 3642 women aged 60-79 years (predominantly white), who provided a single fasting blood s le at a clinical examination between 1998 and 2001, and who had no previous diagnosis of diabetes. Two hundred and eleven men (5.7%) and 190 women (5.2%) had a fasting blood glucose level consistent with the WHO threshold for a diagnosis of diabetes (> or = 7.0 mmol/l), whilst a further 667 men (17.9%) and 642 women (17.6%) had impaired fasting glucose levels (6.1 < or = 7 mmol/l). When analyses were restricted to subjects who had fasted for at least 8 h, and whose blood s le was taken before 12.00 h, the predicted prevalence of undiagnosed diabetes (based on two separate measurements) was 6.7% in men and 6.0% in women. The predicted prevalence of impaired fasting glucose (based on two separate measurements) was approximately 20% in both sexes. More than one-fifth of older white British men and women have either undiagnosed diabetes or impaired fasting glucose according to new WHO criteria. Strategies for the primary and secondary prevention of Type 2 diabetes among older in iduals are urgently needed.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Elsevier BV
Date: 10-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-10-2020
Abstract: Conventional epidemiology associates increased body mass index (BMI) with higher risk of CKD. Diabetes and high BP explain half of the association. However, residual confounding factors preclude causal inferences and impede mediation assessments. A genetic approach (Mendelian randomization) may overcome these limitations. Analyses of 281,228 genotyped UK Biobank participants identified positive independent genetic associations between central and general adiposity with CKD, suggesting both are causal risk factors. Conventional approaches underestimate the role of known mediators. Diabetes and BP (and correlates) explain % of genetic associations between waist-to-hip ratio and CKD and two-thirds between BMI and CKD. In people without diabetes, obesity appeared to cause CKD. BP accounted for about half of the BMI-CKD associations. The size of any causal contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown. Data from 281,228 UK Biobank participants were used to estimate the relevance of waist-to-hip ratio and body mass index (BMI) to CKD prevalence. Conventional approaches used logistic regression. Genetic analyses used Mendelian randomization (MR) and data from 394 waist-to-hip ratio and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes mellitus and BP) by adjusting for measured values (conventional analyses) or genetic associations of the selected loci (multivariable MR). Evidence of CKD was found in 18,034 (6.4%) participants. Each 0.06 higher measured waist-to-hip ratio and each 5-kg/m 2 increase in BMI were associated with 69% (odds ratio, 1.69 95% CI, 1.64 to 1.74) and 58% (1.58 1.55 to 1.62) higher odds of CKD, respectively. In analogous MR analyses, each 0.06–genetically-predicted higher waist-to-hip ratio was associated with a 29% (1.29 1.20 to 1.38) increased odds of CKD, and each 5-kg/m 2 genetically-predicted higher BMI was associated with a 49% (1.49 1.39 to 1.59) increased odds. After adjusting for diabetes and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI fell by 56%. In contrast, mediator adjustment using multivariable MR found 83% and 69% reductions in chi-squared values for genetically-predicted waist-to-hip ratio and BMI models, respectively. Genetic analyses suggest that conventional associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate mediating roles of diabetes, BP, and their correlates. Genetic approaches suggest these mediators explain most of adiposity-CKD–associated risk.
Publisher: Elsevier BV
Date: 08-2012
Publisher: American Diabetes Association
Date: 19-07-2018
DOI: 10.2337/DC18-1125
Abstract: Baseline data from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) indicated that tertiles of urinary albumin-to-creatinine ratios (ACRs) in the normal range at age 10–16 years are associated with risk markers for diabetic nephropathy (DN) and cardiovascular disease (CVD). We aimed to determine whether the top ACR tertile remained associated with DN and CVD risk over the 2–4-year AdDIT study. One hundred fifty adolescents (mean age 14.1 years [SD 1.6]) with baseline ACR in the upper tertile (high-ACR group) recruited to the AdDIT trial, who remained untreated, and 396 (age 14.3 years [1.6]) with ACR in the middle and lower tertiles (low-ACR group), who completed the parallel AdDIT observational study, were evaluated prospectively with assessments of ACR and renal and CVD markers, combined with carotid intima-media thickness (cIMT) at baseline and end of study. After a median follow-up of 3.9 years, the cumulative incidence of microalbuminuria was 16.3% in the high-ACR versus 5.5% in the low-ACR group (log-rank P & 0.001). Cox models showed independent contributions of the high-ACR group (hazard ratio 4.29 [95% CI 2.08–8.85]) and HbA1c (1.37 [1.10–1.72]) to microalbuminuria risk. cIMT change from baseline was significantly greater in the high- versus low-ACR group (mean difference 0.010 mm [0.079], P = 0.006). Changes in estimated glomerular filtration rate, systolic blood pressure, and hs-CRP were also significantly greater in the high-ACR group (P & 0.05). ACR at the higher end of the normal range at the age of 10–16 years is associated with an increased risk of progression to microalbuminuria and future CVD risk, independently of HbA1c.
Publisher: Massachusetts Medical Society
Date: 19-07-2100
Publisher: Elsevier BV
Date: 11-2010
Publisher: Elsevier BV
Date: 12-2004
DOI: 10.1016/J.JCLINEPI.2004.01.021
Abstract: We consider the number needed to treat (NNT) when the event of interest is defined by dichotomizing a continuous response at a threshold level. If the response is measured with error, the resulting NNT is biased. We consider methods to reduce this bias. Bias adjustment was studied using simulations in which we varied the distributions of the underlying response and measurement error, including both normal and nonnormal distributions. We studied a maximum likelihood estimate (MLE) based on normality assumptions, and also considered a simulation-extrapolation estimate (SIMEX) without such assumptions. The treatment effect across all potential thresholds was summarized using an NNT threshold curve. Crude NNT estimation was substantially biased due to measurement error. The MLE performed well under normality, and it continued to perform well with nonnormal measurement error, but when the underlying response was nonnormal the MLE was unacceptably biased and was outperformed by the SIMEX estimate. The simulation results were also reflected in empirical data from a randomized study of cholesterol-lowering therapy. Ignoring measurement error can lead to substantial bias in NNT, which can have an important practical effect on the interpretation of analyses. Analysis methods that adjust for measurement error bias can be used to assess the sensitivity of NNT estimates to this effect.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 07-2019
Publisher: Springer Science and Business Media LLC
Date: 05-2017
Publisher: Elsevier BV
Date: 07-2019
Publisher: Massachusetts Medical Society
Date: 21-08-2008
Publisher: Springer Science and Business Media LLC
Date: 16-07-2020
DOI: 10.1038/S41366-020-0642-3
Abstract: Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain. Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators. Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53–57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30–34%). Each 5 kg/m 2 higher BMI was associated with a 47% (46–49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33–37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure. Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity–albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.
Publisher: SAGE Publications
Date: 03-05-2013
DOI: 10.1111/IJS.12040
Abstract: Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. We describe the protocol for an updated in idual patient data meta-analysis of trials of intravenous alteplase, including results from the recently reported third International Stroke Trial, in which a wide range of patients enrolled up to six-hours after stroke onset were randomized to alteplase vs. control. This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third International Stroke Trial, as the proportion of patients having a ‘favorable’ stroke outcome, defined by modified Rankin Score 0–1 at final follow-up at three- to six-months. The primary analysis will be to estimate the extent to which the known benefit of alteplase on modified Rankin Score 0–1 diminishes with treatment delay, and the extent to which it is independently modified by age and stroke severity. Key secondary outcomes include effect of alteplase on death within 90 days analyses of modified Rankin Score using ordinal, rather than dichotomous, methods and effects of alteplase on symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, symptomatic ischemic brain edema and early edema, effacement and/or midline shift. This collaborative meta-analysis of in idual participant data from all randomized trials of intravenous alteplase vs. control will demonstrate how the known benefits of alteplase on ischemic stroke outcome vary across different types of patient.
Publisher: Massachusetts Medical Society
Date: 16-10-2014
Publisher: Springer Science and Business Media LLC
Date: 11-01-2013
DOI: 10.1007/S00134-012-2800-0
Abstract: In acute kidney injury patients, metabolic acidosis is common. Its severity, duration, and associated changes in mean arterial pressure (MAP) and vasopressor therapy may be affected by the intensity of continuous renal replacement therapy (CRRT). We aimed to compare key aspects of acidosis and MAP and vasopressor therapy in patients treated with two different CRRT intensities. We studied a nested cohort of 115 patients from two tertiary intensive care units (ICUs) within a large multicenter randomized controlled trial treated with lower intensity (LI) or higher intensity (HI) CRRT. Levels of metabolic acidosis at randomization were similar [base excess (BE) of -8 ± 8 vs. -8 ± 7 mEq/l p = 0.76]. Speed of BE correction did not differ between the two groups. However, the HI group had a greater increase in MAP from baseline to 24 h (7 ± 3 vs. 0 ± 3 mmHg p < 0.01) and a greater decrease in norepinephrine dose (from 12.5 to 3.5 vs. 5 to 2.5 μg/min p < 0.05). The correlation (r) coefficients between absolute change in MAP and norepinephrine (NE) dose versus change in BE were 0.05 and -0.37, respectively. Overall, LI and HI CRRT have similar acid-base effects in patients with acidosis. However, HI was associated with greater improvements in MAP and vasopressor requirements (clinical trial no. NCT00221013).
Publisher: Massachusetts Medical Society
Date: 28-09-2017
Publisher: Massachusetts Medical Society
Date: 25-02-2021
Publisher: Elsevier BV
Date: 09-2016
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 11-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2002
DOI: 10.1097/00007632-200209010-00004
Abstract: A multicenter, randomized controlled trial with unblinded treatment and blinded outcome assessment was conducted. The treatment period was 6 weeks with follow-up assessment after treatment, then at 3, 6, and 12 months. To determine the effectiveness of manipulative therapy and a low-load exercise program for cervicogenic headache when used alone and in combination, as compared with a control group. Headaches arising from cervical musculoskeletal disorders are common. Conservative therapies are recommended as the first treatment of choice. Evidence for the effectiveness of manipulative therapy is inconclusive and available only for the short term. There is no evidence for exercise, and no study has investigated the effect of combined therapies for cervicogenic headache. In this study, 200 participants who met the diagnostic criteria for cervicogenic headache were randomized into four groups: manipulative therapy group, exercise therapy group, combined therapy group, and a control group. The primary outcome was a change in headache frequency. Other outcomes included changes in headache intensity and duration, the Northwick Park Neck Pain Index, medication intake, and patient satisfaction. Physical outcomes included pain on neck movement, upper cervical joint tenderness, a craniocervical flexion muscle test, and a photographic measure of posture. There were no differences in headache-related and demographic characteristics between the groups at baseline. The loss to follow-up evaluation was 3.5%. At the 12-month follow-up assessment, both manipulative therapy and specific exercise had significantly reduced headache frequency and intensity, and the neck pain and effects were maintained (P < 0.05 for all). The combined therapies was not significantly superior to either therapy alone, but 10% more patients gained relief with the combination. Effect sizes were at least moderate and clinically relevant. Manipulative therapy and exercise can reduce the symptoms of cervicogenic headache, and the effects are maintained.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jonathan Emberson.