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.

Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non‐cirrhotic portal hypertension. RESULTS FROM MRC CML II TRIAL COMPARING BUSULPHAN WITH BUSULPHAN AND THIOGUANINE

Abstract: Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML.

Chronic kidney disease, heart failure and neprilysin inhibition.

Abstract: Patients with chronic kidney disease are at increased risk of cardiovascular disease and this often manifests clinically like heart failure. Conversely, patients with heart failure frequently have reduced kidney function. The links between the kidneys and cardiovascular system are being elucidated, with blood pressure being a key risk factor. Patients with heart failure have benefitted from many trials which have now established a strong evidence based on which to base management. However, patients with advanced kidney disease have often been excluded from these trials. Nevertheless, there is little evidence that the benefits of such treatments are modified by the presence or absence of kidney disease, but more direct evidence among patients with advanced kidney disease is required. Neprilysin inhibition is the most recent treatment to be shown to improve outcomes among patients with heart failure. The UK HARP-III trial assessed whether neprilysin inhibition improved kidney function in the short- to medium-term and its effects on cardiovascular biomarkers. Although no effect (compared to irbesartan control) was found on kidney function, allocation to neprilysin inhibition (sacubitril/valsartan) did reduce cardiac biomarkers more than irbesartan, suggesting that this treatment might improve cardiovascular outcomes in this population. Larger clinical outcomes trials are needed to test this hypothesis.

Fresh fruit consumption and all-cause and cause-specific mortality: findings from the China Kadoorie Biobank.

Abstract: Background Higher fruit consumption is associated with lower risk of cardiovascular disease (CVD). Substantial uncertainties remain, however, about the associations of fruit consumption with all-cause mortality and mortality from subtypes of CVD and major non-vascular diseases, especially in China. Methods In 2004-08, the nationwide China Kadoorie Biobank Study recruited > 0.5 million adults aged 30-79 years from 10 diverse localities in China. Fresh fruit consumption was estimated using an interviewer-administered electronic questionnaire, and mortality data were collected from death registries. Among the 462 342 participants who were free of major chronic diseases at baseline, 17 894 deaths were recorded during ∼ 7 years of follow-up. Cox regression yielded adjusted rate ratios (RRs) for all-cause and cause-specific mortality associated with fruit consumption. Results At baseline, 28% of participants reported consuming fruit ≥ 4 days/week (regular consumers) and 6% reported never/rarely consuming fruit (non-consumers). Compared with non-consumers, regular consumers had 27% [RR = 0.73, 95% confidence interval (CI) 0.70-0.76] lower all-cause mortality, 34% lower CVD mortality (n = 6166; RR = 0.66, 0.61-0.71), 17% lower cancer mortality (n = 6796; RR = 0.83, 0.78-0.89) and 42% lower mortality from chronic obstructive pulmonary disease (COPD) (n = 1119; RR = 0.58, 0.47-0.71). For each of the above, there was an approximately log-linear dose-response relationship with amount consumed. For mortality from site-specific cancers, fruit consumption was inversely associated with digestive tract cancer (n = 2265; RR = 0.72, 0.64-0.81), particularly oesophageal cancer (n = 801; RR = 0.65, 0.50-0.83), but not with cancer of lung or liver. Conclusions Among Chinese adults, higher fresh fruit consumption was associated with significantly lower mortality from several major vascular and non-vascular diseases. Given the current low population level of fruit consumption, substantial health benefits could be gained from increased fruit consumption in China.

Assessment of the Role of Carotid Atherosclerosis in the Association Between Major Cardiovascular Risk Factors and Ischemic Stroke Subtypes.

Abstract: Importance A better understanding of the role of atherosclerosis in the development of ischemic stroke subtypes could help to improve strategies for prevention of stroke worldwide. Objective To assess the role of carotid atherosclerosis in the association between major cardiovascular risk factors and ischemic stroke subtypes. Design, Setting, and Participants The prospective China Kadoorie Biobank cohort study was conducted in the general population of 5 urban and 5 rural areas in China, with a baseline survey obtained between June 2004 and July 2008. A random sample of 23 973 participants with no history of cardiovascular disease at enrollment who had carotid artery ultrasonographic measurements recorded at a resurvey from September 2013 to June 2014 were included. Data analysis was performed from July 1, 2016, to April 10, 2019. Exposures Major cardiovascular risk factors (ie, blood pressure [BP], blood lipid levels, smoking, and diabetes). Main Outcomes and Measures Carotid ultrasonographic measures of plaque burden (derived from number and maximum size of carotid artery plaques at resurvey) and first ischemic stroke during follow-up (n = 952), with subtyping (data release, August 2018) as lacunar (n = 263), probable large artery (n = 193), probable cardioembolic (n = 66), or unconfirmed (n = 430). Associations between cardiovascular risk factors, carotid plaque burden, and ischemic stroke subtypes were adjusted for age, sex, and geographic area. Results The 23 973 participants in the study had a mean (SD) age of 50.6 (10.0) years, and 14 833 (61.9%) were women. Systolic BP had a stronger association (odds ratio [OR] per SD, 1.51; 95% CI, 1.42-1.61) than plaque burden (OR per SD, 1.34; 95% CI, 1.26-1.44) with ischemic stroke, and the associations of systolic BP with each subtype of ischemic stroke were modestly attenuated by adjustment for plaque burden. After adjustment for BP, plaque burden had a stronger association with probable large artery stroke (OR, 1.43; 95% CI, 1.24-1.63) than with lacunar stroke (OR, 1.25; 95% CI, 1.10-1.43) but was not associated with probable cardioembolic stroke (OR, 1.06; 95% CI, 0.83-1.36). Conclusions and Relevance Although BP was an important risk factor for all ischemic stroke subtypes, carotid atherosclerosis was an important risk factor only for large artery and lacunar strokes, suggesting that drug treatments targeting atherosclerosis may reduce the risk of stroke subtypes to different extents.