Institution
Clinical Trial Service Unit
About: Clinical Trial Service Unit is a based out in . It is known for research contribution in the topics: Population & Stroke. The organization has 428 authors who have published 1387 publications receiving 181920 citations.
Papers published on a yearly basis
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Sage Bionetworks1, University of Chicago2, Duke University3, Children's Hospital Oakland Research Institute4, University of Washington5, University of Pennsylvania6, Brigham and Women's Hospital7, Vanderbilt University Medical Center8, Los Angeles Biomedical Research Institute9, Clinical Trial Service Unit10
TL;DR: GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility tostatin-induced myopathy.
Abstract: Statins are prescribed widely to lower plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk and have been shown to have beneficial effects in a broad range of patients However, statins are associated with an increased risk, albeit small, of clinical myopathy and type 2 diabetes Despite evidence for substantial genetic influence on LDL concentrations, pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy or toxicity, and have produced little information regarding mechanisms that modulate statin response Here we identify a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment This analysis identified six expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including rs9806699, a cis-eQTL for the gene glycine amidinotransferase (GATM) that encodes the rate-limiting enzyme in creatine synthesis We found this locus to be associated with incidence of statin-induced myotoxicity in two separate populations (meta-analysis odds ratio = 060) Furthermore, we found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy
209 citations
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TL;DR: The aim of PROSPER is to address deficiencies in methodological quality and size by comparing the relative merits of different procedures in rectal prolapse treatment.
Abstract: Aim
Rectal prolapse is a profoundly disabling condition, occurring mainly in elderly and parous women. There is no accepted standard surgical treatment, with previous studies limited in methodological quality and size. PROSPER aimed to address these deficiencies by comparing the relative merits of different procedures.
Method
In a pragmatic, factorial (2 × 2) design trial, patients could be randomised between abdominal and perineal surgery (i), and suture vs resection rectopexy for those receiving an abdominal procedure (ii) or Altemeier's vs Delorme's for those receiving a perineal procedure (iii). Primary outcome measures were recurrence of the prolapse, incontinence, bowel function and quality of life scores (Vaizey, bowel thermometer and EQ-5D) measured up to 3 years.
Results
Two hundred and ninety-three patients were recruited: 49 were randomised between surgical approaches (i); 78 between abdominal procedures (ii); and 213 between perineal procedures (iii). Recurrence rates were higher than anticipated, but not significantly different in any comparison: Altemeier's vs Delorme's 24/102 (24%) and 31/99 (31%) [hazard ratio (HR) 0.81; 95% CI 0.47, 1.38; P = 0.4]; resection vs suture rectopexy 4/32 (13%) and 9/35 (26%) (HR 0.45; 95% CI 0.14, 1.46; P = 0.2); perineal vs abdominal 5/25 (20%) and 5/19 (26%) (HR 0.83; 95% CI 0.24, 2.86; P = 0.8). Vaizey, bowel thermometer and EQ-5D scores were not significantly different in any of the comparisons.
Conclusion
No significant differences were seen in any of the randomised comparisons, although substantial improvements from baseline in quality of life were noted following all procedures.
208 citations
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The Catholic University of America1, Oslo University Hospital2, Carlos III Health Institute3, Clinical Trial Service Unit4, French Institute of Health and Medical Research5, University of Chieti-Pescara6, Aarhus University Hospital7, Uppsala University8, University of Sheffield9, Katholieke Universiteit Leuven10, Radboud University Nijmegen Medical Centre11
TL;DR: The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.
Abstract: The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.
205 citations
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TL;DR: A large number of patients with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower were offered atorvastatin 10 mg daily open label and noted no significant differences between statin users and non-users in the rates of AEs.
204 citations
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TL;DR: Women always fared better than men and this was independent of stage and age in the first Medical Research Council trial in chronic lymphocytic leukaemia, suggesting a major biological difference between the sexes which has not been widely recognized.
Abstract: Summary. We report the analysis of prognostic factors in a cohort of 660 patients entered in the first Medical Research Council trial in chronic lymphocytic leukaemia (CLL) between 1978 and 1984. The majority (94%) of patients were aged 50 or over and the number of men (M) was almost twice that of women (F) with an M: F ratio of 1·8: 1. The M: F ratio was lower, 1·5:1, in patients aged 70 or over. Stage A CLL was the most common, and stage C the least common, among women of all ages, in contrast to men for whom stage A only predominated in the older age group. As the majority of CLL patients are elderly we have examined the causes of death in great detail. 29% of deaths were unrelated to CLL, mainly other cancers (12%) and cardiovascular complications (16%). The majority of deaths in patients presenting with stages B and C were from CLL-related causes, whilst almost half of the deaths in patients presenting with stage A were not obviously related to CLL. Univariate analysis disclosed that the A, B, C staging system was the most important factor considered; stratified and multivariate analysis showed that age and response to treatment were the main prognostic factors after stage. Women always fared better than men and this was independent of stage and age. This and other features documented in the trial suggest a major biological difference between the sexes which has not been widely recognized. The significant influence of treatment response on patients’ survival suggests that the search for better treatments in CLL may be rewarding. The improved median survival of stage C patients recorded in this trial, 41 months, compares favourably with previous reports and may have resulted from better treatment.
204 citations
Authors
Showing all 428 results
Name | H-index | Papers | Citations |
---|---|---|---|
Salim Yusuf | 231 | 1439 | 252912 |
Richard Peto | 183 | 683 | 231434 |
Cornelia M. van Duijn | 183 | 1030 | 146009 |
Rory Collins | 162 | 489 | 193407 |
Naveed Sattar | 155 | 1326 | 116368 |
Timothy J. Key | 146 | 808 | 90810 |
John Danesh | 135 | 394 | 100132 |
Andrew J.S. Coats | 127 | 820 | 94490 |
Valerie Beral | 114 | 471 | 53729 |
Mike Clarke | 113 | 1037 | 164328 |
Robert Clarke | 111 | 512 | 90049 |
Robert U. Newton | 109 | 753 | 42527 |
Richard Gray | 109 | 808 | 78580 |
Braxton D. Mitchell | 102 | 558 | 49599 |
Naomi E. Allen | 101 | 364 | 37057 |