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.

Risks and Population Burden of Cardiovascular Diseases Associated with Diabetes in China: A Prospective Study of 0.5 Million Adults.

Abstract: Background In China, diabetes prevalence is rising rapidly, but little is known about the associated risks and population burden of cardiovascular diseases. We assess associations of diabetes with major cardiovascular diseases and the relevance of diabetes duration and other modifiable risk factors to these associations. Methods and Findings A nationwide prospective study recruited 512,891 men and women aged 30–79 y between 25 June 2004 and 15 July 2008 from ten diverse localities across China. During ~7 y of follow-up, 7,353 cardiovascular deaths and 25,451 non-fatal major cardiovascular events were recorded among 488,760 participants without prior cardiovascular disease at baseline. Cox regression yielded adjusted hazard ratios (HRs) comparing disease risks in individuals with diabetes to those without. Overall, 5.4% (n = 26,335) of participants had self-reported (2.7%) or screen-detected (2.7%) diabetes. Individuals with self-reported diabetes had an adjusted HR of 2.07 (95% CI 1.90–2.26) for cardiovascular mortality. There were significant excess risks of major coronary event (2.44, 95% CI 2.18–2.73), ischaemic stroke (1.68, 95% CI 1.60–1.77), and intracerebral haemorrhage (1.24, 95% CI 1.07–1.44). Screen-detected diabetes was also associated with significant, though more modest, excess cardiovascular risks, with corresponding HRs of 1.66 (95% CI 1.51–1.83), 1.62 (95% CI 1.40–1.86), 1.48 (95% CI 1.40–1.57), and 1.17 (95% CI 1.01–1.36), respectively. Misclassification of screen-detected diabetes may have caused these risk estimates to be underestimated, whilst lack of data on lipids may have resulted in residual confounding of diabetes-associated cardiovascular disease risks. Among individuals with diabetes, cardiovascular risk increased progressively with duration of diabetes and number of other presenting modifiable cardiovascular risk factors. Assuming a causal association, diabetes now accounts for ~0.5 million (489,676, 95% CI 335,777–681,202) cardiovascular deaths annually in China. Conclusions Among Chinese adults, diabetes is associated with significantly increased risks of major cardiovascular diseases. The increasing prevalence and younger age of onset of diabetes foreshadow greater diabetes-attributable disease burden in China.

Independent risk factors for simvastatin-related myopathy and relevance to different types of muscle symptom.

Abstract: Aims Statins are widely used to prevent cardiovascular events, but little is known about the impact of different risk factors for statin-related myopathy or their relevance to reports of other types of muscle symptom. Methods and results An observational analysis was undertaken of 171 clinically adjudicated cases of myopathy (defined as unexplained muscle pain or weakness with creatine kinase >10× upper limit of normal) and, separately, of 15 208 cases of other muscle symptoms among 58 390 individuals with vascular disease treated with simvastatin for a mean of 3.4 years. Cox proportional hazards models were used to identify independent predictors of myopathy. The rate of myopathy was low: 9 per 10 000 person-years of simvastatin therapy. Independent risk factors for myopathy included: simvastatin dose, ethnicity, sex, age, body mass index, medically treated diabetes, concomitant use of niacin-laropiprant, verapamil, beta-blockers, diltiazem and diuretics. In combination, these risk factors predicted more than a 30-fold risk difference between the top and bottom thirds of a myopathy risk score (hazard ratio : 34.35, 95% CI: 12.73-92.69, P across thirds = 9·1 × 10-48). However, despite the strong association with myopathy, this score was not associated with the other reported muscle symptoms (P across thirds = 0.93). Likewise, although SLCO1B1 genotype was associated with myopathy, it was not associated with other muscle symptoms. Conclusions The absolute risk of simvastatin-related myopathy is low, but individuals at higher risk can be identified to help guide patient management. The lack of association of the myopathy risk score with other muscle symptoms reinforces randomized placebo-controlled evidence that statins do not cause the vast majority of reported muscle symptoms.

Young adulthood and adulthood adiposity in relation to incidence of pancreatic cancer: a prospective study of 0.5 million Chinese adults and a meta-analysis

Abstract: Background Adult adiposity is positively associated with pancreatic cancer in Western populations. Little is known, however, about the association in China where many have lower body mass index (BMI) or about the relevance of young adulthood adiposity for pancreatic cancer in both Western and East Asian populations. Methods The China Kadoorie Biobank (CKB) recruited 512 891 adults aged 30–79 years during 2004–2008, recording 595 incident cases of pancreatic cancer during 8-year follow-up. Cox regression yielded adjusted HRs for pancreatic cancer associated with self-reported young adulthood (mean ~25 years) BMI and with measured adulthood (mean ~52 years) BMI and other adiposity measures (eg, waist circumference (WC)). These were further meta-analysed with published prospective studies. Results Overall, the mean BMI (SD) was 21.9 (2.6) at age 25 years and 23.7 (3.3) kg/m 2 at age 52 years. Young adulthood BMI was strongly positively associated with pancreatic cancer in CKB (adjusted HR=1.36, 95% CI 1.16 to 1.61, per 5 kg/m 2 higher BMI) and in meta-analysis of CKB and four other studies (1.18, 1.12 to 1.24). In CKB, there was also a positive association of pancreatic cancer with adulthood BMI (1.11, 0.97 to 1.27, per 5 kg/m 2 ), similar in magnitude to that in meta-analyses of East Asian studies using measured BMI (n=2; 1.08, 0.99 to 1.19) and of Western studies (n=25; 1.10, 1.06 to 1.12). Likewise, meta-analysis of four studies, including CKB, showed a positive association of adulthood WC with pancreatic cancer (1.10, 1.06 to 1.14, per 10 cm). Conclusions In both East Asian and Western populations, adiposity was positively associated with risk of pancreatic cancer, with a somewhat stronger association for young than late-life adiposity.

Cerebral sinovenous thrombosis in children and young adults with acute lymphoblastic leukaemia - a cohort study from the United Kingdom

Abstract: Cerebral sinovenous thrombosis (CSVT) complicates therapy in 1–2% of children and young adults with acute lymphoblastic leukaemia (ALL) (Caruso et al, 2006; Qureshi et al, 2010; Ranta et al, 2015). In childhood, it has a mortality of 8–13% and can cause long-term neurological morbidity (deVeber et al, 2001; Wasay et al, 2008; Ranta et al, 2015). In addition, ALL therapy may be compromised by a reluctance to interrupt anticoagulation for intrathecal treatment and delayed/missed doses of L-asparaginase due to concern about thrombus progression or recurrence (Silverman et al, 2001). This retrospective study identified individuals who developed CSVT during ALL therapy on the Medical Research Council (MRC) UKALL 2003 trial (http://www.isrctn.com/ ISRCTN07355119) in order to characterize their thrombotic risk factors, presenting features, management and outcome. The UKALL 2003 trial recruited children and young adults aged 1–24 years from 45 UK centres between 2003 and 2011. This was a randomized study to investigate use of minimal residual disease monitoring to guide the intensity of ALL therapy (Vora et al, 2013, 2014). Pegylated (PEG) asparaginase (Oncaspar ; MEDAC GmBH, Germany) 1000 units/m intra-muscularly was administered twice during the induction phase. All participants received oral dexamethasone 6 mg/m/d throughout induction, interim maintenance and maintenance phases. CSVT cases were identified by screening adverse event reports for central nervous system (CNS) thrombosis and grade III/IV serious adverse events in the coagulation/thrombosis category. Reporting forms were sent to individual centres for collection of additional data. Ethical requirements were covered by overall consent for trial participation. Individuals with CSVT were compared to the remaining trial population, who did not have CSVT, using information from the study database. Statistical significance was measured for categorical variables using the Pearson chi-squared test. The overall effect of all variables was assessed using binary logistic regression. Forty-six cases of CSVT were identified amongst 3126 trial participants. Information was returned for 45 cases, 2 of which were excluded as arterial events. Forty-three cases of CSVT were included in the final analysis, giving an incidence of 1 4%. Table I compares the demographic features and disease characteristics between individuals who developed CSVT and those who did not. The CSVT cohort was significantly older. Individuals with CSVT were more likely to have high-risk cytogenetics, but this effect was not age-dependant. 33/43 (77%) of CSVT occurred during induction therapy. Median time from leukaemia diagnosis to thrombosis was 29 d (interquartile range [IQR]: 22–35). All cases had received L-asparaginase prior to CSVT; 32/43 (74%) received 2 doses. 77% of cases occurred within 3 weeks of the second dose of L-asparaginase (Fig 1). All cases were symptomatic. Frequent presenting features were neurological impairment (65%), seizures (56%) and headaches (47%). Concurrent intracranial haemorrhage (ICH) was present in 13 cases and cerebral infarction in 5. Additional risk factors for thrombosis included hospital stay (n = 22 cases), immobility for >3 d (n = 5), infection (n = 5), dehydration (n = 3) and use of an oestrogen-containing oral contraceptive pill (n = 2). Seventeen cases (40%) had no additional risk factor. A thrombophilia screen was performed in 11 cases (26%) and was normal in 8. Two had a reduced Protein S level and one was heterozygous for the F5 F506Q (Factor V Leiden) mutation. 21 individuals had an anti-thrombin (AT) level measured, of which 10 were below the reference range. Of the 10 cases that occurred postinduction, 8 were hospital in-patients at the time of presentation and 5 had >1 additional risk factor. Anticoagulant therapy was administered to 39/43 (91%), the majority of who received low molecular heparin (LMWH) (97%). Three did not receive anticoagulation due to the presence of ICH. AT concentrate was administered to 2 and fresh frozen plasma to 1. Median duration of anticoagulant therapy was 3 months (IQR: 3–6 months). ALL therapy was modified due to CSVT in 25 cases (58%). Systemic chemotherapy was delayed in 10 and doses missed in 4. Intrathecal chemotherapy was delayed in 6 and doses missed in 2. Sixteen of 42 cases (37%) scheduled to receive further doses of L-asparaginase, received no further doses. An additional 2 missed doses but had L-asparaginase re-introduced later. Of those re-exposed, the majority (22/26) received LMWH thromboprophylaxis during re-exposure. Four individuals with CSVT died, one due to their thrombotic event (in association with extensive ICH). Neurological morbidity was reported in 5 cases (12%) at a median of 41 months follow-up, 4 of who had ICH at presentation. There were no recurrent thrombotic events. correspondence

Family History and Stroke Risk in China: Evidence from a Large Cohort Study.

Abstract: BACKGROUND AND PURPOSE Large cohort studies on relationship between family history of stroke (FHS) and stroke risk are lacking in Asians We aimed to systematically evaluate the association of FHS with stroke risk in a cohort study of 05 million Chinese adults METHODS Information about FHS was self-reported The median follow-up time was 716 years and the end-point of follow-up was incident stroke, which was entered directly into the China Kadoorie Biobank system Multivariate analyses were performed with Cox proportional hazards model, and interaction analyses were carried using likelihood-ratio tests RESULTS Compared with participants without FHS, the hazard ratio (HR) (95% confidence interval, CI) of stroke for participants with FHS was 150 (146-155) The HRs increased with the number of first degree relatives with stroke (HRs=141, 198 and 247 for 1, 2 and ≥3 relatives, respectively, Ptrend <0001) The HRs were 157 (95% CI: 150-166) and 149 (95% CI: 145-154) for sibling history and parental history, respectively Similar associations with offspring stroke risk were observed between paternal history (HR=148, 95% CI: 143-154) and maternal history (HR=149, 95% CI: 143-155) Moreover, significant interactions were detected between FHS and health-risk behaviors (tobacco smoking and alcohol drinking) CONCLUSIONS FHS is an independent risk factor for stroke in Chinese The more first degree relatives are affected by stroke, the higher are individuals' risk of suffering from stroke The management of the health-risk behaviors for reducing stroke should be highlighted, especially for the individuals with FHS