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.

Quantitative effects on cardiovascular risk factors and coronary heart disease risk of replacing partially hydrogenated vegetable oils with other fats and oils

Abstract: Background/objectives Reduced consumption of trans-fatty acids (TFA) is desirable to lower coronary heart disease (CHD) risk. In practice, partially hydrogenated vegetable oils (PHVO) that contain both TFAs and other fatty acids are the unit of replacement and could be replaced with diverse alternative fats and oils. We performed quantitative estimates of CHD effects if a person's PHVO consumption were to be replaced with alternative fats and oils based on (1) randomized dietary trials and (2) prospective observational studies. Subjects/methods We performed meta-analyses of (1) the effects of TFAs on blood lipids and lipoproteins in controlled dietary trials and (2) associations of habitual TFA consumption with CHD outcomes in prospective cohort studies. On the basis of these results and corresponding findings for saturated fatty acids (SFA), cis-monounsaturated fatty acids (MUFA) and cis-polyunsaturated fatty acids (PUFA), we calculated the effects on CHD risk for replacing 7.5% of energy from three different PHVO formulations (containing 20, 35 or 45% TFAs) with butter, lard, palm or vegetable oils. Results In controlled trials, each 1% energy replacement of TFAs with SFAs, MUFAs or PUFAs, respectively, decreased the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio by 0.31, 0.54 and 0.67; the apolipoprotein (Apo)-B/ApoAI ratio by 0.007, 0.010 and 0.011; and lipoprotein (Lp)(a) by 3.76, 1.39 and 1.11 mg/l (P Conclusions Effects on CHD risk of removing PHVO from a person's diet vary depending on the TFA content of the PHVO and the fatty acid composition of the replacement fat or oil, with direct implications for reformulation of individual food products. Accounting for the summed effects of TFAs on multiple CHD risk factors provides more accurate estimates of potential risk reduction than considering each risk factor in isolation, and approaches the estimated risk reduction derived from prospective cohort studies.

Residential radon and lung cancer – detailed results of a collaborative analysis of individual data on 7148 persons with lung cancer and 14 208 persons without lung cancer from 13 epidemiologic studies in Europe

Abstract: Objectives: Studies seeking direct estimates of the lung cancer risk associated with residential radon exposure lasting several decades have been conducted in many European countries. Individually these studies have not been large enough to assess moderate risks reliably. Therefore data from all 13 European studies of residential radon and lung cancer satisfying certain prespecified criteria have been brought together and analyzed. Methods: Data were available for 7148 persons with lung cancer and 14 208 controls, all with individual smoking histories and residential radon histories determined by long-term radon gas measurements. Results: The excess relative risk of lung cancer per 100 Bq/m3 increase in the observed radon concentration was 0.08 [95% confidence interval (95% CI) 0.03-0.16; P=0.0007] after control for confounding. The dose-response relationship was linear with no evidence of a threshold, and it remained significant when only persons with observed radon concentrations of <200 Bq/m3 were included. There was no evidence that the excess relative risk varied with age, sex, or smoking history. Removing the bias induced by random uncertainties related to radon exposure assessment increased the excess relative risk of lung cancer to 0.16 (95% CI 0.05-0.31) per 100 Bq/m3. With this correction, estimated risks at 0, 100, and 400 Bq/m3, relative to lifelong nonsmokers with no radon exposure, were 1.0, 1.2, and 1.6 for lifelong nonsmokers and 25.8, 29.9, and 42.3 for continuing smokers of 15-24 cigarettes/day. Conclusions: These data provide firm evidence that residential radon acts as a cause of lung cancer in the general population. They provide a solid basis for the formulation of policies with which to manage risk from radon and reduce deaths from the most common fatal cancer in Europe.

Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial.

Abstract: Summary Background Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia (ALL) during remission. We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. Methods Between Oct 1, 2003 and June 30, 2011, consecutive children and young adults (aged 1–24 years) with ALL from the UK and Ireland were recruited. Eligible patients were categorised into clinical standard, intermediate, and high risk groups on the basis of a combination of National Cancer Institute (NCI) criteria, cytogenetics, and early response to induction therapy, which was assessed by bone marrow blast counts taken at days 8 (NCI high-risk patients) and 15 (NCI standard-risk patients) after induction began. Clinical standard-risk and intermediate-risk patients were assessed for MRD. Those classified as MRD low risk (undetectable MRD at the end of induction [day 29] or detectable MRD [less than 0·01%] at day 29 that became undetectable by week 11) were randomly assigned to receive one or two delayed intensification courses. Patients had received induction, consolidation, and interim maintenance therapy before they began delayed intensification. Delayed intensification consisted of pegylated asparaginase on day 4; vincristine, dexamethasone (alternate weeks), and doxorubicin for 3 weeks; and 4 weeks of cyclophosphamide and cytarabine. Computer randomisation was done with stratification by MRD result and balancing for sex, age, and white blood cell count at diagnosis by method of minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcome was event-free survival (EFS), which was defined as time to relapse, secondary tumour, or death. Our aim was to rule out a 7% reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses. Analyses were by intention to treat. This trial is registered, number ISRCTN07355119. Findings Of 3207 patients registered in the trial overall, 521 MRD low-risk patients were randomly assigned to receive one (n=260) or two (n=261) delayed intensification courses. Median follow-up of these patients was 57 months (IQR 42–72). We recorded no significant difference in EFS between the group given one delayed intensification (94·4% at 5 years, 95% CI 91·1–97·7) and that given two delayed intensifications (95·5%, 92·8–98·2; unadjusted odds ratio 1·00, 95% CI 0·43–2·31; two-sided p=0·99). The difference in 5-year EFS between the two groups was 1·1% (95% CI −5·6 to 2·5). 11 patients (actuarial relapse at 5 years 5·6%, 95% CI 2·3–8·9) given one delayed intensification and six (2·4%, 0·2–4·6) given two delayed intensifications relapsed (p=0·23). Three patients (1·2%, 0–2·6) given two delayed intensifications died of treatment-related causes compared with none in the group given one delayed intensification (p=0·08). We recorded no significant difference between groups for serious adverse events and grade 3 or 4 toxic effects; however, the second delayed intensification course was associated with one ( Interpretation Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy. Funding Medical Research Council and Leukaemia and Lymphoma Research.