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.

The influence of EDTA and citrate anticoagulant addition to human plasma on information recovery from NMR-based metabolic profiling studies.

Abstract: The widely-used blood anticoagulants citrate and EDTA give rise to prominent peaks in (1)H NMR spectra of plasma samples collected in epidemiological and clinical studies, and these cause varying levels of interference in recovering biochemical information on endogenous metabolites. To investigate both the potential metabolic information loss caused by these substances and any possible inter-molecular interactions between the anticoagulants and endogenous components, the (1)H NMR spectra of 40 split human plasma samples collected from 20 individuals into either citrate or EDTA have been analysed. Endogenous metabolite peaks were selectively obscured by large citrate peaks or those from free EDTA and its calcium and magnesium complexes. It is shown that the endogenous metabolites that give rise to peaks obscured by those from EDTA or citrate almost invariably also have other resonances that allow their identification and potential quantitation. Also, metabolic information recovery could be maximised by use of spectral editing techniques such as spin-echo, diffusion-editing and J-resolved experiments. The NMR spectral effects of any interactions between the added citrate or EDTA and endogenous components were found to be negligible. Finally, identification of split samples was feasible using simple multivariate statistical approaches such as principal components analysis. Thus even when legacy epidemiological plasma samples have been collected using the NMR-inappropriate citrate or EDTA anticoagulants, useful biochemical information can still be recovered effectively.

IGH@ Translocations Are Prevalent in Teenagers and Young Adults With Acute Lymphoblastic Leukemia and Are Associated With a Poor Outcome

Abstract: Purpose To determine the prevalence and prognostic association of immunoglobulin heavy chain (IGH@) translocations in acute lymphoblastic leukemia (ALL). Patients and Methods The cohort comprised 3,269 patients treated on either the UKALL2003 trial for children and adolescents (1 to 24 years old) or the UKALLXII trial for adolescents and adults (15 to 59 years old). High-throughput fluorescent in situ hybridization was used to detect IGH@ translocations. Results We identified IGH@ translocations in 5% of patients with ALL (159 of 3,269 patients), in patients with both B-cell (148 of 2,863 patients) and T-cell (11 of 408 patients) disease. Multiple partner genes were identified including CRLF2 (n = 35), five members of the CEPB gene family (n = 17), and ID4 (n = 11). The level of the IGH@-positive clone varied and indicated that some IGH@ translocations were primary events, whereas others were secondary aberrations often associated with other established aberrations. The age profile of patients with IGH@ t...

Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. The Oxford Cholesterol Study Group.

Abstract: The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously. At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo. Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12·10%±6·08 of standard; 2 P <0·05) and non-significantly lower factor VII coagulant activity (8·24%±4·99 of standard) and fibrinogen concentrations (0·10±0·08 g.l−1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2·62±1·03 IU; 2 P <0·01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1·2, factor XII and C$$$ inhibitor). Total free fatty acid concentration was marginally significantly reduced (2 P =0·02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1·74±0·15 mmol.1−1; 2 P <0·0001) but also in VLDL cholesterol (0·28±0·08 mmol.1−1; 2 P <0·001) and IDL cholesterol (0·17±0·03 mmol.1−1; 2 P <0·0001). There were also lower triglyceride levels associated with LDL (0·07±0·01 mmol.1−1; 2 P <0·0001), IDL (0·03±0·01 mmol.1−1; 2 P <0·01) and VLDL (0·27±0·14; 2 P =0·05). The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA re1ductase inhibitors (and of the newer fibrates, which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.

Genome-wide meta-analysis identifies 3 novel loci associated with stroke

Abstract: We conducted a European-only and trans-ancestral genome-wide association meta-analysis in 72,147 stroke patients and 823,869 controls using data from UK Biobank (UKB) and the MEGASTROKE consortium. We identified an exonic polymorphism in NOS3 (rs1799983, p.Glu298Asp; p=2.2E-8; OR=1.05[1.04-1.07]) and variants in an intron of COL4A1 (rs9521634, p-value=3.8E-8, OR=1.04[1.03-1.06]) and near DYRK1A (rs720470, p=6.1E-9; OR=1.05[1.03-1.07]) at genome-wide significance for stroke. Effect sizes of known stroke loci were highly correlated between UKB and MEGASTROKE. Using Mendelian Randomization we further show that genetic variation in the nitric oxide synthase (NOS) - nitric oxide (NO) pathway in part affects stroke risk via variation in blood pressure.

Chronic kidney disease and the risk of cancer: an individual patient data meta-analysis of 32,057 participants from six prospective studies.

Abstract: Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease but the relevance of reduced kidney function to cancer risk is uncertain. Individual patient data were collected from six studies (32,057 participants); including one population-based cohort and five randomized controlled trials. Participants were grouped into one of five CKD categories (estimated glomerular filtration rate [eGFR] ≥75 mL/min/1.73 m2; eGFR ≥60 to <75 mL/min/1.73 m2; eGFR ≥45 to <60 mL/min/1.73 m2; eGFR <45 mL/min/1.73 m2; on dialysis). Stratified Cox regression was used to assess the impact of CKD category on cancer incidence and cancer death. Over a follow-up period of 170,000 person-years (mean follow-up among survivors 5.6 years), 2626 participants developed cancer and 1095 participants died from cancer. Overall, there was no significant association between CKD category and cancer incidence or death. As compared with the reference group with eGFR ≥75 mL/min/1.73 m2, adjusted hazard ratio (HR) estimates for each category of renal function, in descending order, were: 0.98 (95 % CI 0.87–1.10), 0.99 (0.88–1.13), 1.01 (0.84–1.22) and 1.24 (0.97–1.58) for cancer incidence, and 1.03 (95 % CI 0.86–1.24), 0.95 (0.78–1.16), 1.00 (0.76–1.33), and 1.58 (1.09–2.30) for cancer mortality. Among dialysis patients, there was an excess risk of cancers of the urinary tract (adjusted HR: 2.34; 95 % CI 1.10–4.98) and endocrine cancers (11.65; 95 % CI: 1.30–104.12), and an excess risk of death from digestive tract cancers (2.11; 95 % CI: 1.13–3.99), but a reduced risk of prostate cancers (0.38; 95 % CI: 0.18–0.83). Whilst no association between reduced renal function and the overall risk of cancer was observed, there was evidence among dialysis patients that the risk of cancer was increased (urinary tract, endocrine and digestive tract) or decreased (prostate) at specific sites. Larger studies are needed to characterise these site-specific associations and to identify their pathogenesis.