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.

Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

Abstract: BACKGROUND AND PURPOSE: Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. METHODS: Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype. RESULTS: Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4)). CONCLUSIONS: Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.

Risk prediction in patients with heart failure: a systematic review and analysis.

Abstract: Objectives This study sought to review the literature for risk prediction models in patients with heart failure and to identify the most consistently reported independent predictors of risk across models. Background Risk assessment provides information about patient prognosis, guides decision making about the type and intensity of care, and enables better understanding of provider performance. Methods MEDLINE and EMBASE were searched from January 1995 to March 2013, followed by hand searches of the retrieved reference lists. Studies were eligible if they reported at least 1 multivariable model for risk prediction of death, hospitalization, or both in patients with heart failure and reported model performance. We ranked reported individual risk predictors by their strength of association with the outcome and assessed the association of model performance with study characteristics. Results Sixty-four main models and 50 modifications from 48 studies met the inclusion criteria. Of the 64 main models, 43 models predicted death, 10 hospitalization, and 11 death or hospitalization. The discriminatory ability of the models for prediction of death appeared to be higher than that for prediction of death or hospitalization or prediction of hospitalization alone (p = 0.0003). A wide variation between studies in clinical settings, population characteristics, sample size, and variables used for model development was observed, but these features were not significantly associated with the discriminatory performance of the models. A few strong predictors emerged for prediction of death; the most consistently reported predictors were age, renal function, blood pressure, blood sodium level, left ventricular ejection fraction, sex, brain natriuretic peptide level, New York Heart Association functional class, diabetes, weight or body mass index, and exercise capacity. Conclusions There are several clinically useful and well-validated death prediction models in patients with heart failure. Although the studies differed in many respects, the models largely included a few common markers of risk.

Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial.

Abstract: Summary Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event-free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0·0007). Event-free survival was significantly improved with dexamethasone (84·2% vs. 75·6% at 5 years; P = 0·01), with no evidence of differing effects in any subgroup of patients. The use of 6·5 mg/m2 dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk-groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.