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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TL;DR: Future trials need to adopt simple design, streamlined data collection, and use of the "uncertainty principle' to guide eligibility in order to detect any moderate improvements in major outcomes that may await discovery.
Abstract: The reliable detection of moderate differences in major health outcomes that arise as a result of treatment requires large-scale randomized evidence (and the appropriate interpretation of this evidence once it has been generated). This may take the form of a single mega-trial or, exceptionally, a meta-analysis of many smaller randomized trials may provide worthwhile information. Small or non-randomized studies cannot generally be trusted to distinguish reliably between a moderate benefit, a moderate hazard, and a negligible difference in major outcomes. Simple design, streamlined data collection, and use of the ‘uncertainty principle’ to guide eligibility would all encourage the recruitment of larger samples in randomized trials. Future trials need to adopt these methods in order to detect any moderate improvements in major outcomes that may await discovery.
23 citations
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University of Colorado Denver1, University of Toronto2, Baylor College of Medicine3, University of New South Wales4, Hebrew University of Jerusalem5, British Heart Foundation6, Monash University7, Linköping University8, Clinical Trial Service Unit9, Cedars-Sinai Medical Center10, Montreal Heart Institute11, Colorado School of Public Health12
TL;DR: In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib, and the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes.
Abstract: OBJECTIVE Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome. RESEARCH DESIGN AND METHODS In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4–12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A1c and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A1c ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L (fasting) or ≥11.1 mmol/L (random). RESULTS At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68–0.88; P CONCLUSIONS In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.
23 citations
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TL;DR: An improved test is described and its use with samples from the Leukaemia Research Fund CLL4 randomised clinical trial and previously treated patients is reported, providing further rationale for standard drug combinations and suggesting possible pentostatin salvage in fludarabine‐resistant patients.
Abstract: P>Previous results with individualised tumour response testing (ITRT) in vitro in chronic lymphocytic leukaemia (CLL) have consistently shown good correlation with patient response and survival. We describe here an improved test and report its use with samples from the Leukaemia Research Fund CLL4 randomised clinical trial and previously treated patients. ITRT was performed by the tumour response to anti-neoplastic compounds (TRAC) assay, a modification of the differential staining cytotoxicity (DiSC) assay. Improvements included drying drugs into wells before assay and using the Octospot system to cytocentrifuge eight spots of cells onto one microscope slide. We successfully tested 765/782 (98%) cellular blood samples received within 48 h of phlebotomy. Cross-resistance (Pearson's r > 0 center dot 7) in untreated CLL was found between similar drugs. Mitoxantrone (r = 0 center dot 31), cyclophosphamide (r = 0 center dot 35) and pentostatin (r = 0 center dot 29) had low cross-resistance with fludarabine. Treatment resulted in increased resistance to chlorambucil, cyclophosphamide, doxorubicin, mitoxantrone, corticosteroids, cladribine and fludarabine (P < 0 center dot 01) but not to pentostatin. These results provide further rationale for standard drug combinations such as fludarabine-mitoxantrone and fludarabine-mitoxantrone-cyclophosphamide and suggest possible pentostatin salvage in fludarabine-resistant patients. ITRT results could assist both in determining the best treatment for individual patients and in the design and rationale of future clinical trials.
23 citations
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TL;DR: More advanced CKD is associated with increased odds of falling into poverty, and kidney transplantation may have a role in reducing this risk.
23 citations
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TL;DR: The results indicate that IL6R haplotypes regulate the circulating levels of inflammatory biomarkers and associate with the risk of coronary heart disease and CHD in the three populations studied.
Abstract: Variants at the interleukin 6 receptor (IL6R) gene regulate inflammation and are associated with risk of coronary heart disease (CHD). The aim of the present study was to investigate the effects of IL6R haplotypes on circulating levels of inflammatory biomarkers and risk of CHD. We performed a discovery analysis in SHEEP, a myocardial infarction (MI) case control study (n = 2,774) and replicated our results in two large, independent European populations, PROCARDIS, a CHD case control study (n = 7,998), and IMPROVE (n = 3,711) a prospective cardiovascular cohort study. Two major haplotype blocks (rs12083537A/G and rs4075015A/T—block 1; and rs8192282G/A, rs4553185T/C, rs8192284A/C, rs4240872T/C and rs7514452T/C—block 2) were identified in the IL6R gene. IL6R haplotype associations with C-reactive protein (CRP), fibrinogen, IL6, soluble IL6R (sIL6R), IL6, IL8 and TNF-α in SHEEP, CRP and fibrinogen in PROCARDIS and CRP in IMPROVE as well as association with risk of MI and CHD, were analyzed by THESIAS. Haplotypes in block 1 were associated neither with circulating inflammatory biomarkers nor with the MI/CHD risk. Haplotypes in block 2 were associated with circulating levels of CRP, in all three study populations, with fibrinogen in SHEEP and PROCARDIS, with IL8 and sIL6Rin SHEEP and with a modest, non significant, increase (7%) in MI/CHD risk in the three populations studied. Our results indicate that IL6R haplotypes regulate the circulating levels of inflammatory biomarkers. Lack of association with the risk of CHD may be explained by the combined effect of SNPs with opposite effect on the CHD risk, the sample size as well as by structural changes affecting sIL6R stability in the circulation.
23 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 |