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.

Menopause Characteristics, Total Reproductive Years, and Risk of Cardiovascular Disease Among Chinese Women

Abstract: Background— Previous studies, mostly of Western women, have reported inconsistent findings on the association of menopause characteristics (status, age, and time since menopause) and total reproductive years with risk of cardiovascular disease (CVD). Methods and Results— The China Kadoorie Biobank recruited 302 632 women in 2004 to 2008 from 10 regions across China. During 9-year follow-up, 19 393 incident cases of stroke, 18 611 of ischemic heart disease, and 4978 CVD deaths occurred. Cox regression yielded adjusted hazard ratios relating each menopause characteristic and total reproductive years to CVD risk. Among 274 233 women with no prior CVD at baseline, 134 010 were naturally postmenopausal women (mean [SD] age at menopause of 48.6 [4.0] years and total reproductive years 32.7 [4.4]). Compared with premenopausal women, naturally peri- or postmenopausal women were at a higher risk of either fatal or nonfatal CVD. Among women who had had menopause, inverse associations were observed between age at menopause and risks of CVD mortality, incident ischemic heart disease, stroke, and subtypes of stroke, with 1.5% higher risk of CVD death ( P P =0.002), and 0.5% for incident stroke ( P =0.02) for every 1 year lower age at menopause. Compared with women who had menopause at age 48 to 50 years, lower age at menopause (ie, 20 years since menopause compared with P Conclusions— Women with younger age at menopause, longer time since menopause, or fewer total reproductive years had a higher risk of CVD.

Measurement error in the explanatory variable of a binary regression: regression calibration and integrated conditional likelihood in studies of residential radon and lung cancer.

Abstract: In epidemiology, one approach to investigating the dependence of disease risk on an explanatory variable in the presence of several confounding variables is by fitting a binary regression using a conditional likelihood, thus eliminating the nuisance parameters When the explanatory variable is measured with error, the estimated regression coefficient is biased usually towards zero Motivated by the need to correct for this bias in analyses that combine data from a number of case-control studies of lung cancer risk associated with exposure to residential radon, two approaches are investigated Both employ the conditional distribution of the true explanatory variable given the measured one The method of regression calibration uses the expected value of the true given measured variable as the covariate The second approach integrates the conditional likelihood numerically by sampling from the distribution of the true given measured explanatory variable The two approaches give very similar point estimates and confidence intervals not only for the motivating example but also for an artificial data set with known properties These results and some further simulations that demonstrate correct coverage for the confidence intervals suggest that for studies of residential radon and lung cancer the regression calibration approach will perform very well, so that nothing more sophisticated is needed to correct for measurement error

The retinoblastoma gene (rb1) in acute myeloid leukaemia: analysis of gene rearrangements, protein expression and comparison of disease outcome.

Abstract: The occurrence of retinoblastoma gene abnormalities in a large subset of various malignancies suggests an important role for this tumour suppressor gene in carcinogenesis, but this varies considerably from one tumour type to another and results in patients with acute myeloid leukaemia (AML) have been controversial. We analysed 106 AML patients and 18 normal controls for RB1 gene rearrangements and 86 AML patients for RB protein (pRB) expression. Southern blot analysis detected no gross gene rearrangements, but several restriction enzyme polymorphisms were observed. By Western blot analysis, 20 patients (23%) had no detectable pRB protein and seven (8%) had truncated pRB bands. Discordance between the DNA and protein data suggests that there may be minor deletions and point mutations in the RB1 gene or abnormalities in the proteins regulating the expression of pRB. No significant differences in the frequency of attainment of complete remission or length of survival were observed between patients with normal and abnormal pRB.

The Asymptomatic Carotid Surgery Trial-2 (ACST-2): an ongoing randomised controlled trial comparing carotid endarterectomy with carotid artery stenting to prevent stroke.

Abstract: Background A successful open surgical operation to remove atheromatous carotid artery narrowing that has not yet caused a stroke (asymptomatic carotid stenosis) carries some procedural risk but, if completed successfully, halves patients' future annual stroke risk for at least 10 years. A newer, less invasive alternative is carotid stenting, which also carries some procedural risk, especially if the carotid lesion has recently given rise to a stroke (symptomatic carotid stenosis). For both surgery and stenting, improvements in technique (and in medication) have reduced risk. Early studies showed that treating carotid narrowing by stenting, particularly for symptomatic lesions, caused more procedural minor strokes than surgery, but more recent trials in symptomatic and in asymptomatic patients found that both procedures might now be equally safe and effective. However, low patient numbers, short follow-up of the long-term effects on stroke rates and wide confidence intervals mean that worldwide uncertainty persists between carotid surgery and carotid stenting, and national and international guidelines remain unclear as to which is generally better. Objectives The second Asymptomatic Carotid Surgery Trial (ACST-2) compares carotid endarterectomy (CEA) with carotid artery stenting (CAS) directly, randomising patients with asymptomatic carotid stenosis for whom a carotid procedure is considered definitely necessary; both procedures seem anatomically feasible, and there is substantial uncertainty as to which of the two would be better for such individuals. Although it will compare procedural risks, the trial's primary aim is to compare the long-term durability of protection against strokes occurring in the years post procedure due to any remaining or recurrent carotid disease. Design Randomised controlled trial comparing CEA with CAS. Setting Hospitals in the UK and worldwide, in which carotid procedures are common. Participants Men and women with severely stenotic atherosclerotic carotid artery disease, with or without previous stroke but with no recent symptoms from the randomised artery. Interventions CEA and CAS. Outcomes (1) Periprocedural risk defined as myocardial infarction, stroke or death within 30 days after the randomised procedure and (2) long-term rates of disabling or fatal stroke during follow-up of patients. Measurement of costs and outcomes Measurement of intervention costs and stroke costs (periprocedural and during follow-up) and of quality of life [EuroQol-5 Dimensions (EQ-5D®)] for patients in the top six recruiting countries (UK, Italy, Belgium, Germany, Serbia and Sweden), who currently constitute 85% of those randomised. Progress so far By the end of March 2016, ACST-2 had included 2125 patients, nearly two-thirds of the planned recruitment of 3600; 1061 were randomly allocated to CEA and 1064 to CAS. Conclusions Further funding has been secured and recruitment continues, with completion anticipated by the end of 2019. ACST-2 will report initial results in 2021. Trial registration Current Controlled Trials ISRCTN21144362. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 57. See the NIHR Journals Library website for further project information. Funding was also received from BUPA Foundation [BUPAF/33(a)/05].

Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases.

Abstract: Importance Obesity is associated with a higher risk of cardiovascular disease (CVD), but little is known about the role that circulating protein biomarkers play in this association. Objective To examine the observational and genetic associations of adiposity with circulating protein biomarkers and the observational associations of proteins with incident CVD. Design, setting, and participants This subcohort study included 628 participants from the prospective China Kadoorie Biobank who did not have a history of cancer at baseline. The Olink platform measured 92 protein markers in baseline plasma samples. Data were collected from June 2004 to January 2016 and analyzed from January 2019 to June 2020. Exposures Measured body mass index (BMI) obtained during the baseline survey and genetically instrumented BMI derived using 571 externally weighted single-nucleotide variants. Main outcomes and measures Cross-sectional associations of adiposity with biomarkers were examined using linear regression. Associations of biomarkers with CVD risk were assessed using Cox regression among those without prior cancer or CVD at baseline. Mendelian randomization was conducted to derive genetically estimated associations of BMI with biomarkers. Findings In observational analyses of 628 individuals (mean [SD] age, 52.2 [10.5] years; 385 women [61.3%]), BMI (mean [SD], 23.9 [3.6]) was positively associated with 27 proteins (per 1-SD higher BMI; eg, interleukin-6: 0.21 [95% CI, 0.12-0.29] SD; interleukin-18: 0.13 [95% CI, 0.05-0.21] SD; monocyte chemoattractant protein-1: 0.12 [95% CI, 0.04-0.20] SD; hepatocyte growth factor: 0.31 [95% CI, 0.24-0.39] SD), and inversely with 3 proteins (Fas ligand: -0.11 [95% CI, -0.19 to -0.03] SD; TNF-related weak inducer of apoptosis, -0.14 [95% CI, -0.23 to -0.06] SD; and carbonic anhydrase 9: (-0.14 [95% CI, -0.22 to -0.05] SD), with similar associations identified for other adiposity traits (eg, waist circumference [r = 0.96]). In mendelian randomization, the associations of genetically elevated BMI with specific proteins were directionally consistent with the observational associations. In meta-analyses of genetically elevated BMI with 8 proteins, combining present estimates with previous studies, the most robust associations were shown for interleukin-6 (per 1-SD higher BMI; 0.21 [95% CI, 0.13-0.29] SD), interleukin-18 (0.16 [95% CI, 0.06-0.26] SD), monocyte chemoattractant protein-1 (0.21 [95% CI, 0.11-0.30] SD), monocyte chemotactic protein-3 (0.12 [95% CI, 0.03-0.21] SD), TNF-related apoptosis-inducing ligand (0.23 [95% CI, 0.13-0.32] SD), and hepatocyte growth factor (0.14 [95% CI, 0.06-0.22] SD). Of the 30 BMI-associated biomarkers, 10 (including interleukin-6, interleukin-18, and hepatocyte growth factor) were nominally associated with incident CVD. Conclusions and relevance Mendelian randomization shows adiposity to be associated with a range of protein biomarkers, with some biomarkers also showing association with CVD risk. Future studies are warranted to validate these findings and assess whether proteins may be mediators between adiposity and CVD.