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.

Plasma phospholipid fatty acids and CHD in older men: Whitehall study of London civil servants.

Abstract: Dietary fatty acids (FA) are the major determinants of blood lipids, and measurements of plasma phospholipid FA (PL-FA) composition that reflect the dietary intake of FA may provide insights into the relationships between diet and CHD. We assessed CHD mortality associations with PL-FA (SFA, PUFA and MUFA) levels measured in a nested case-control study of 116 cases of CHD death and 239 controls that were frequency-matched for age and employment grade. The participants had plasma levels of total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol, apo B and apo A1, C-reactive protein (CRP) and fibrinogen recorded. SFA levels were significantly positively correlated with total cholesterol, LDL-C, apo B, CRP protein and fibrinogen. By contrast, phospholipid-PUFA were inversely associated with CRP, but not with any of the lipids. A higher SFA content (top v. bottom quarter) was associated with a 2-fold higher risk of CHD (OR and 95 % CI: OR 2.12; 95 % CI: 1.13, 3.99), and an equivalent difference in PUFA was associated with a halving in CHD risk (OR 0.49; 95 % CI: 0.26, 0.94), but MUFA was unrelated to CHD risk. These associations were substantially attenuated, after additional adjustment for lipids and inflammatory markers. Higher levels of saturated fat and lower levels of polyunsaturated fats were each associated with a higher risk of CHD in elderly men, and these associations were partly explained by their effects on blood lipids and biomarkers of inflammation.

The prevalence of chronic diseases and major disease risk factors at different ages among 150,000 men and women living in Mexico City: cross-sectional analyses of a prospective study.

Abstract: While most of the global burden from chronic diseases, and especially vascular diseases, is now borne by low and middle-income countries, few large-scale epidemiological studies of chronic diseases in such countries have been performed. From 1998–2004, 52 584 men and 106 962 women aged ≥35 years were visited in their homes in Mexico City. Self reported diagnoses of chronic diseases and major disease risk factors were ascertained and physical measurements taken. Age- and sex-specific prevalences and means were analysed. After about age 50 years, diabetes was extremely common – for example, 23.8% of men and 26.9% of women aged 65–74 reported a diagnosis. By comparison, ischaemic heart disease was reported by 4.8% of men and 3.0% of women aged 65–74, a history of stroke by 2.8% and 2.3%, respectively, and a history of cancer by 1.3% and 2.1%. Cancer history was generally more common among women than men – the excess being largest in middle-age, due to breast and cervical cancer. At older ages, the gap narrowed because of an increasing prevalence of prostate cancer. 51% of men and 25% of women aged 35–54 smoked cigarettes, while 29% of men and 41% of women aged 35–54 were obese (i.e. BMI ≥30 kg/m2). The prevalence of treated hypertension or measured blood pressure ≥140/90 mmHg increased about 50% more steeply with age among women than men, to 66% of women and 58% of men aged 65–74. Physical inactivity was highly prevalent but daily alcohol drinking was relatively uncommon. Diabetes, obesity and tobacco smoking are highly prevalent among adults living in Mexico City. Long-term follow-up of this and other cohorts will establish the relevance of such factors to the major causes of death and disability in Mexico.

The impact of risk stratification by early bone-marrow response in childhood lymphoblastic leukaemia: results from the United Kingdom Medical Research Council trial ALL97 and ALL97/99.

Abstract: The 1997 acute lymphoblastic leukaemia (ALL) trial (ALL97) was a randomised comparison of prednisolone versus dexamethasone and of 6-mercaptopurine versus 6-thioguanine During the first 2 years of the trial, review of survival data showed the preceding trial, UKALL XI, was no better than its predecessor and that survival for childhood ALL in the UK had not improved in the fashion witnessed by other cooperative treatment groups The therapy template was therefore altered to an American Children's Cancer Group (CCG) style regimen, including stratification by age, white cell count and early response to therapy by assessment of the bone marrow This phase of the trial was designated ALL97/99 Comparison of the two phases showed that the event-free survival (EFS) for both ALL97 and ALL97/99 was better than previous UKALL trials, as was overall survival (OS) for ALL97/99 Both EFS and OS were significantly better in ALL97/99 than in ALL97 (at five years, 800% vs 740%, P = 0002; and 880% vs 835%, P = 0005, respectively) Isolated central nervous system (CNS) relapse for patients in ALL97/99 was half that in ALL97 (30% vs 49%), P = 003) and the overall CNS relapse rate was halved in ALL97/99 (44% vs 96%, P < 000005) There were no significant differences for non-CNS relapse, induction deaths or deaths in remission between the two phases of the trial

Uptake of systematic reviews and meta-analyses based on individual participant data in clinical practice guidelines: descriptive study

Abstract: Objective To establish the extent to which systematic reviews and meta-analyses of individual participant data (IPD) are being used to inform the recommendations included in published clinical guidelines. Design Descriptive study. Setting Database maintained by the Cochrane IPD Meta-analysis Methods Group, supplemented by records of published IPD meta-analyses held in a separate database. Population A test sample of systematic reviews of randomised controlled trials that included a meta-analysis of IPD, and a separate sample of clinical guidelines, matched to the IPD meta-analyses according to medical condition, interventions, populations, and dates of publication. Data extraction Descriptive information on each guideline was extracted along with evidence showing use or critical appraisal, or both, of the IPD meta-analysis within the guideline; recommendations based directly on its findings and the use of other systematic reviews in the guideline. Results Based on 33 IPD meta-analyses and 177 eligible, matched clinical guidelines there was evidence that IPD meta-analyses were being under-utilised. Only 66 guidelines (37%) cited a matched IPD meta-analysis. Around a third of these (n=22, 34%) had critically appraised the IPD meta-analysis. Recommendations based directly on the matched IPD meta-analyses were identified for only 18 of the 66 guidelines (27%). For the guidelines that did not cite a matched IPD meta-analysis (n=111, 63%), search dates had preceded the publication of the IPD meta-analysis in 23 cases (21%); however, for the remainder, there was no obvious reasons why the IPD meta-analysis had not been cited. Conclusions Our results indicate that systematic reviews and meta-analyses based on IPD are being under-utilised. Guideline developers should routinely seek good quality and up to date IPD meta-analyses to inform guidelines. Increased use of IPD meta-analyses could lead to improved guidelines ensuring that routine patient care is based on the most reliable evidence available.

Mendelian randomization with fine-mapped genetic data: choosing from large numbers of correlated instrumental variables

Abstract: Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be used to assess this causal relationship. However, using too many genetic variants in the analysis can lead to spurious estimates and inflated Type 1 error rates. But if only a few genetic variants are used, then the majority of the data is ignored and estimates are highly sensitive to the particular choice of variants. We propose an approach based on summarized data only (genetic association and correlation estimates) that uses principal components analysis to form instruments. This approach has desirable theoretical properties: it takes the totality of data into account and does not suffer from numerical instabilities. It also has good properties in simulation studies: it is not particularly sensitive to varying the genetic variants included in the analysis or the genetic correlation matrix, and it does not have greatly inflated Type 1 error rates. Overall, the method gives estimates that are not so precise as those from variable selection approaches (such as using a conditional analysis or pruning approach to select variants), but are more robust to seemingly arbitrary choices in the variable selection step. Methods are illustrated by an example using genetic associations with testosterone for 320 genetic variants to assess the effect of sex hormone-related pathways on coronary artery disease risk, in which variable selection approaches give inconsistent inferences.