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 impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI

Abstract: The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS) directed therapies in childhood acute lymphoblastic leukaemia (ALL). To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1) all patients (n = 555) versus related controls (n = 311), (2) low-risk children (presenting white cell count (WCC) < 50 × 109/l) randomised to intrathecal methotrexate (n = 197) versus intrathecal and high-dose intravenous methotrexate (HDM) (n = 202), and (3) high-risk children (WCC ≥ 50 × 109/l, age ≥ 2 years) randomised to HDM (n = 79) versus cranial irradiation (n = 77). There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P < 0.002) with a higher proportion of children with IQs < 80 in the patient groups (13% vs. 5% at 3 years p = 0.003). Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes. ISRCTN: ISRCTN16757172

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol.

Abstract: Blood lipids are causally involved in the pathogenesis of atherosclerosis, but their role in cerebral small vessel disease remains largely elusive. Here, we explored associations of genetic determinants of blood lipid levels, lipoprotein particle components, and targets for lipid-modifying drugs with small vessel disease phenotypes. We selected genetic instruments for blood levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, for cholesterol and triglycerides components of size-defined lipoprotein particles, and for lipid-modifying drug targets based on published genome-wide association studies (up to 617 303 individuals). Applying two-sample Mendelian randomization approaches we investigated associations with ischaemic and haemorrhagic manifestations of small vessel disease [small vessel stroke: 11 710 cases, 287 067 controls; white matter hyperintensities (WMH): 10 597 individuals; intracerebral haemorrhage: 1545 cases, 1481 controls]. We applied the inverse-variance weighted method and multivariable Mendelian randomization as our main analytical approaches. Genetic predisposition to higher HDL-C levels was associated with lower risk of small vessel stroke [odds ratio (OR) per standard deviation = 0.85, 95% confidence interval (CI) = 0.78-0.92] and lower WMH volume (β = -0.07, 95% CI = -0.12 to -0.02), which in multivariable Mendelian randomization remained stable after adjustments for LDL-C and triglycerides. In analyses of lipoprotein particle components by size, we found these effects to be specific for cholesterol concentration in medium-sized high-density lipoprotein, and not large or extra-large high-density lipoprotein particles. Association estimates for intracerebral haemorrhage were negatively correlated with those for small vessel stroke and WMH volume across all lipid traits and lipoprotein particle components. HDL-C raising genetic variants in the gene locus of the target of CETP inhibitors were associated with lower risk of small vessel stroke (OR: 0.82, 95% CI = 0.75-0.89) and lower WMH volume (β = -0.08, 95% CI = -0.13 to -0.02), but a higher risk of intracerebral haemorrhage (OR: 1.64, 95% CI = 1.26-2.13). Genetic predisposition to higher HDL-C, specifically to cholesterol in medium-sized high-density lipoprotein particles, is associated with both a lower risk of small vessel stroke and lower WMH volume. These analyses indicate that HDL-C raising strategies could be considered for the prevention of ischaemic small vessel disease but the net benefit of such an approach would need to be tested in a randomized controlled trial.

Patterns and socio-demographic correlates of domain-specific physical activities and their associations with adiposity in the China Kadoorie Biobank study

Abstract: Domain-specific physical activities may have different correlates and health effects, but few large studies have examined these questions, especially their separate associations with adiposity. We analysed cross-sectional data of 466 605 adults without any prior chronic diseases, enrolled during 2004–8, from 10 diverse localities across China. Physical activity level in each of 4 domains (occupation, commuting, household, and active-recreation), calculated as metabolic equivalent (MET)-hr/day, was related to social-demographic factors and measures of adiposity (body mass index [BMI], waist circumference [WC], and bio-impedance derived percentage body fat), using multivariable linear and logistic regression models. The overall mean age was 50.8 years. The mean total physical activity was 21.7 MET-hr/day, mainly from occupation (62%) and household chores (26%), but little from active-recreation (4%), with women having a much higher household activity than men. Older participants had a lower level of occupational activity but a higher level of household and active-recreational activity, particularly after retirement. There was no linear association of occupational activity with adiposity, but working women tended to have a lower adiposity (e.g. 1.0 cm WC) than non-working women. In men, there was an inverse and apparently linear association between adiposity and levels of both commuting-related and household activities, with 3 MET-hr/day associated with -0.11 and -0.13 kg/m2 BMI, -0.42 and -0.62 cm WC, and -0.28 and -0.33 percentage points of body fat, respectively. In women, only household activity showed a linear, but weaker, association with adiposity. A higher adiposity was observed among men and women with higher levels of active-recreational activity. In Chinese adults, physical activity mainly involves occupation and housework, with little from active-recreational activity. Domain-specific physical activities varied by socio-demographic factors and had different associations with adiposity.

Age at natural menopause and associated factors in adult women: Findings from the China Kadoorie Biobank study in Zhejiang rural area.

Abstract: Objectives To investigate the factors associated with age at natural menopause in a large population of Chinese adult women. Methods This cross-sectional study was part of the baseline survey of China Kadoorie Biobank in Zhejiang Province. A total of 17,076 postmenopausal women were included in the present study. Relevant data of socio-demographic, lifestyle, dietary and reproductive characteristics were collected. Multinomial logistic regression models were used to examine the associated factors of age at natural menopause with adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were reported. Results The mean age at natural menopause was 48.94 years, with 3.40% of the women experienced premature menopause and 6.75% early menopause. Younger age, higher education, consumption of meat (1-3 days per week) and increased parity were associated with late menopause. Current smoking, underweight, higher physical activity, consumption of sea food (1-3 days per week), fresh eggs (≥4 days per week), fresh fruits (≥1 day per week), taking vitamins, experiencing severe food shortage, earlier age at menarche and older age at first birth were associated with earlier age at natural menopause. Conclusions These results suggest that certain factors involved with socio-demographic, lifestyle, dietary and reproductive characteristics are related to the age at natural menopause in Chinese women.