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.

Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements.

Abstract: Epidemiological studies have shown that higher blood homocysteine levels appear to be associated with higher risks of coronary, cerebral, and peripheral vascular disease and are inversely related to blood levels of folate and of vitamin B12 and vitamin B6. However, observational studies cannot exclude the possibility that elevated homocysteine levels may be associated with some other factor, rather than being causally related to vascular disease. Large-scale clinical trials of sufficient dose and duration of treatment are required to test this hypothesis, but there was substantial uncertainty about the optimal vitamin regimen to test in such trials. A meta-analysis of 12 randomized trials of vitamin supplements to lower homocysteine levels was carried out to determine the optimal dose of folic acid required to lower homocysteine levels and to assess whether vitamin B12 or vitamin B6 had additive effects. This meta-analysis demonstrated that reductions in blood homocysteine levels were greater at higher pretreatment blood homocysteine levels and at lower pretreatment folate concentrations. After standardization for a pretreatment homocysteine concentration of 12 micromol/L and folate concentration of 12 nmol/L (approximate average concentrations for western populations), dietary folic acid reduced homocysteine levels by 25% (95% confidence interval [CI]: 23 to 28%) with similar effects in a daily dosage range of 0.5 to 5 mg. Vitamin B12 (mean 0.5 mg) produced an additional reduction in blood homocysteine of 7%, whereas vitamin B6 (mean 16.5 mg) did not have any significant effect. Hence, in typical populations, daily supplementation with both 0.5 to 5 mg folic acid and about 0.5 mg vitamin B12 would be expected to reduce homocysteine levels by one quarter to one third (from about 12 micromol/L to about 8 to 9 micromol/L). Large-scale randomized trials of such regimens are now required to determine whether lowering homocysteine levels by folic acid and vitamin B12, with or without added vitamin B6, reduces the risk of vascular disease.

Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes A Pooled Analysis of 9 Trials

Abstract: Background— Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity. Methods— Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s). Results— Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13–91; P =0.004). Conclusions— Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4); the earlier that treatment is initiated, the greater the benefit.

Association of Solid Fuel Use With Risk of Cardiovascular and All-Cause Mortality in Rural China.

Abstract: Importance When combusted indoors, solid fuels generate a large amount of pollutants such as fine particulate matter. Objective To assess the associations of solid fuel use for cooking and heating with cardiovascular and all-cause mortality. Design, Setting, and Participants This nationwide prospective cohort study recruited participants from 5 rural areas across China between June 2004 and July 2008; mortality follow-up was until January 1, 2014. A total of 271 217 adults without a self-reported history of physician-diagnosed cardiovascular disease at baseline were included, with a random subset (n = 10 892) participating in a resurvey after a mean interval of 2.7 years. Exposures Self-reported primary cooking and heating fuels (solid: coal, wood, or charcoal; clean: gas, electricity, or central heating), switching of fuel type before baseline, and use of ventilated cookstoves. Main Outcomes and Measures Death from cardiovascular and all causes, collected through established death registries. Results Among the 271 217 participants, the mean (SD) age was 51.0 (10.2) years, and 59% (n = 158 914) were women. A total of 66% (n = 179 952) of the participants reported regular cooking (at least weekly) and 60% (n = 163 882) reported winter heating, of whom 84% (n = 150 992) and 90% (n = 147 272) used solid fuels, respectively. There were 15 468 deaths, including 5519 from cardiovascular causes, documented during a mean (SD) of 7.2 (1.4) years of follow-up. Use of solid fuels for cooking was associated with greater risk of cardiovascular mortality (absolute rate difference [ARD] per 100 000 person-years, 135 [95% CI, 77-193]; hazard ratio [HR], 1.20 [95% CI, 1.02-1.41]) and all-cause mortality (ARD, 338 [95% CI, 249-427]; HR, 1.11 [95% CI, 1.03-1.20]). Use of solid fuels for heating was also associated with greater risk of cardiovascular mortality (ARD, 175 [95% CI, 118-231]; HR, 1.29 [95% CI, 1.06-1.55]) and all-cause mortality (ARD, 392 [95% CI, 297-487]; HR, 1.14 [95% CI, 1.03-1.26]). Compared with persistent solid fuel users, participants who reported having previously switched from solid to clean fuels for cooking had a lower risk of cardiovascular mortality (ARD, 138 [95% CI, 71-205]; HR, 0.83 [95% CI, 0.69-0.99]) and all-cause mortality (ARD, 407 [95% CI, 317-497]; HR, 0.87 [95% CI, 0.79-0.95]), while for heating, the ARDs were 193 (95% CI, 128-258) and 492 (95% CI, 383-601), and the HRs were 0.57 (95% CI, 0.42-0.77) and 0.67 (95% CI, 0.57-0.79), respectively. Among solid fuel users, use of ventilated cookstoves was also associated with lower risk of cardiovascular mortality (ARD, 33 [95% CI, −9 to 75]; HR, 0.89 [95% CI, 0.80-0.99]) and all-cause mortality (ARD, 87 [95% CI, 20-153]; HR, 0.91 [95% CI, 0.85-0.96]). Conclusions and Relevance In rural China, solid fuel use for cooking and heating was associated with higher risks of cardiovascular and all-cause mortality. These risks may be lower among those who had previously switched to clean fuels and those who used ventilation.

WHO Scientific Update on trans fatty acids: summary and conclusions

Abstract: The purpose of the WHO scientific review on trans fatty acids (TFAs) was to examine the evidence generated since the 1993 Joint FAO/WHO Expert Consultation on Fats and Oils in Human Nutrition, and to inform member countries on the health consequences of TFAs consumption that have emerged since the last report was released. The new information was deemed sufficient to recommend the need to significantly reduce or to virtually eliminate industrially produced TFA from the food supply in agreement with the implementation of the 2004 WHO Global Strategy on Diet, Physical Activity and Health. This goal has been accomplished in some countries and cities, by the virtual elimination of partially hydrogenated vegetable oils in the human food supply, replacing them with healthy cis-unsaturated fatty acids. The document provides the evidence base to promote discussion between the international scientific community related to nutrition and health as well as between agriculturalists, food producers, relevant health professionals, national and international food regulatory agencies, civil society and the private sector to achieve the stated goal.

Association between Common Variation at the FTO Locus and Changes in Body Mass Index from Infancy to Late Childhood: The Complex Nature of Genetic Association through Growth and Development

Abstract: An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p = 10-20) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10-23). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p = 0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p = 0.01), and earlier AR (-4.72% (-5.81, -3.63), p = 10-17), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.