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.

Body Mass Index, Blood Pressure, and Mortality From Stroke A Nationally Representative Prospective Study of 212 000 Chinese Men

Abstract: Background and Purpose— Despite previous investigations, substantial uncertainty remains about the relation between body mass index (BMI) and stroke, especially in populations with a relatively low BMI but a high stroke rate. Methods— A nationally representative prospective study of mortality included 212 000 Chinese men 40 to 79 years old without known cardiovascular disease in 1990 to 1991 who were followed up for 10 years. Standardized hazard ratios were calculated for stroke mortality by baseline systolic blood pressure (SBP) and BMI. Results— Mean SBP and BMI were 124 mm Hg and 21.7 kg/m2, respectively. During 10 years of follow-up, 5766 stroke deaths were recorded. There were strong, positive relations between BMI and SBP and between SBP and stroke mortality, with a 3-mm Hg higher baseline SBP associated with a 5.6% (95% CI, 5.3% to 6.0%; P<0.00001) higher stroke mortality. The association between BMI and stroke mortality was, however, not linear, with the hazard increasing substantially only for BM...

Proof of causality: deduction from epidemiological observation.

Abstract: 499 IT IS A PARTICULAR PLEASURE to have the honor of giving a Fisher memorial lecture, for it gives me the opportunity to acknowledge the formative influence that Sir Ronald’s book, Statistical Methods for Research Workers (1934) had on my career. I had, as a boy, developed a love for mathematics and when, in October 1931, I started to study medicine, I sought ways in which I could apply numerical methods in my work. Nothing productive emerged until, a few years later, I discovered his book and realized how relevant it was to medical research.About that time, one of the teaching staff drew our attention to a report of the use of pituitary gonadotropic hormone in the treatment of undescended testes in adolescent boys, which the authors said had a smaller percentage of failure than had been achieved by reliance on spontaneous descent (Spence and Scowen 1935). There were, of course, many difficulties in making such a comparison; but suffice it to say that even if the series were properly comparable, no consideration had been paid to the possibility that the difference observed might have been due to chance. Fisher’s book led me to Pearson’s 2 test, which showed that with the numbers observed as big or bigger differences would have been expected to

Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm : A Meta-analysis

Abstract: Importance Risk factors for abdominal aortic aneurysm (AAA) are largely unknown, which has hampered the development of nonsurgical treatments to alter the natural history of disease. Objective To investigate the association between lipid-associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting, and Participants Genetic risk scores, composed of lipid trait–associated SNPs, were constructed and tested for their association with AAA using conventional (inverse-variance weighted) mendelian randomization (MR) and data from international AAA genome-wide association studies. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR, and multivariable MR method was used to test the independent association of lipids with AAA risk. The association between AAA and SNPs in loci that can act as proxies for drug targets was also assessed. Data collection took place between January 9, 2015, and January 4, 2016. Data analysis was conducted between January 4, 2015, and December 31, 2016. Exposures Genetic elevation of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Main Outcomes and Measures The association between genetic risk scores of lipid-associated SNPs and AAA risk, as well as the association between SNPs in lipid drug targets (HMGCR,CETP, andPCSK9) and AAA risk. Results Up to 4914 cases and 48 002 controls were included in our analysis. A 1-SD genetic elevation of LDL-C was associated with increased AAA risk (odds ratio [OR], 1.66; 95% CI, 1.41-1.96;P = 1.1 × 10−9). For HDL-C, a 1-SD increase was associated with reduced AAA risk (OR, 0.67; 95% CI, 0.55-0.82;P = 8.3 × 10−5), whereas a 1-SD increase in triglycerides was associated with increased AAA risk (OR, 1.69; 95% CI, 1.38-2.07;P = 5.2 × 10−7). In multivariable MR analysis and both MR-Egger and weighted median MR methods, the association of each lipid fraction with AAA risk remained largely unchanged. The LDL-C–reducing allele ofrs12916inHMGCRwas associated with AAA risk (OR, 0.93; 95% CI, 0.89-0.98;P = .009). The HDL-C–raising allele ofrs3764261inCETPwas associated with lower AAA risk (OR, 0.89; 95% CI, 0.85-0.94;P = 3.7 × 10−7). Finally, the LDL-C–lowering allele ofrs11206510inPCSK9was weakly associated with a lower AAA risk (OR, 0.94; 95% CI, 0.88-1.00;P = .04), but a second independent LDL-C–lowering variant inPCSK9(rs2479409) was not associated with AAA risk (OR, 0.97; 95% CI, 0.92-1.02;P = .28). Conclusions and Relevance The MR analyses in this study lend support to the hypothesis that lipids play an important role in the etiology of AAA. Analyses of individual genetic variants used as proxies for drug targets support LDL-C lowering as a potential effective treatment strategy for preventing and managing AAA.

Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003

Abstract: Despite the substantial outcome improvements achieved in paediatric acute lymphoblastic leukaemia (ALL), survival in teenage and young adult (TYA) patients has remained inferior. We report the treatment outcomes and toxicity profiles observed in TYA patients treated on the UK paediatric ALL trial, UKALL2003. UKALL2003 was a multi-centre, prospective, randomized phase III trial, investigating treatment intensification or de-escalation according to minimal residual disease (MRD) kinetics at the end of induction. Of 3126 patients recruited to UKALL2003, 229 (7·3%) were aged 16-24 years. These patients were significantly more likely to have high risk MRD compared to 10-15 year olds (47·9% vs. 36·6%, P = 0·004). Nonetheless, 5-year event-free survival for the TYA cohort (aged 16-24 years) was 72·3% [95% confidence interval (CI): 66·2-78·4] overall and 92·6% (95% CI: 85·5-99·7) for MRD low risk patients. The risk of serious adverse events was higher in patients aged ≥10 years compared to those aged 9 or younger (P < 0·0001) and novel age-specific patterns of treatment-related toxicity were observed. TYA patients obtain excellent outcomes with a risk- and response-adapted paediatric chemotherapy protocol. Whilst those aged 10 years and older have excess toxicity compared with younger patients, the age association is specific to individual toxicities.

Adherence to a healthy lifestyle and the risk of type 2 diabetes in Chinese adults

Abstract: Background Simultaneously adhering to multiple healthy lifestyle factors has been related to up to 90% reduction in type 2 diabetes (T2DM) incidence in White populations; however, little is known about whether such protective effects persist in other non-White populations. Methods We examined the associations of six lifestyle factors with T2DM in the China Kadoorie Biobank of 461 211 participants aged 30-79 years without diabetes, cardiovascular diseases or cancer at baseline. We defined low-risk lifestyle factors as non-smoking or having stopped for reasons other than illness; alcohol consumption of <30 g/day; upper quarter of the physical activity level; diet rich in vegetables and fruits, low in red meat and with some degree of replacement of rice with wheat; body mass index (BMI) of 18.5-23.9 kg/m2; and waist-to-hip ratio (WHR) <0.90 (men)/<0.85 (women). Results During a median of 7.2 years of follow-up, we identified 8784 incident T2DM. In multivariable-adjusted analyses, two important risk factors for developing T2DM were higher BMI and WHR. Compared with participants without any low-risk factors, the hazard ratio [95% confidence interval (CI)] for those with at least three low-risk factors was 0.20 (0.19, 0.22). Approximately 72.6% (64.2%, 79.3%) of the incident diabetes were attributable to the combination of BMI, WHR, diet and physical activity. The population attributable risk percentage (PAR%) of diabetes appeared to be similar for men and women, and higher among urban, older and obese participants. Conclusions Our findings indicate that adherence to a healthy lifestyle may substantially lower the burden of T2DM in the Chinese population.