Kar Keung Cheng

Sudden death in patients receiving drugs tending to prolong the QT interval

AIMSnTo examine risks of sudden death in the community associated with drugs grouped by their risk of causing torsades de pointes (TdP) and to explore the risks for individual drugs.nnnMETHODSnCase-control study comparing prior drug intakes and morbidities, using the Arizona classification of drugs causing TdP. Participants included 1010 patients dying suddenly where post-mortem examination did not identify a clear cause of death, and 3030 matched living controls from primary care.nnnRESULTSnNoncardiac drug risk was posed by antipsychotics and antidepressants. Significantly raised odds ratios (ORs) were found for takers of typical and atypical antipsychotics, ORs [95% confidence interval] 3.94 (2.05, 7.55) and 4.36 (2.54, 7.51), and of selective serotonin reuptake inhibitors [SSRIs] rather than tricyclic antidepressants, ORs 2.21 (1.61, 3.05) and 1.44 (0.96, 2.13). No significant risk was associated with other, noncardiac or psychiatric drugs, OR 1.09 (0.85, 1.41). Arizona classified drugs considered to raise risk of TdP were associated with raised risk of sudden death, as were those only weakly associated with TdP and not considered to pose a risk in normal use, ORs 2.08 (1.45, 3.00) and 1.74 (1.33, 2.28), respectively.nnnCONCLUSIONSnAtypical and typical antipsychotic drug use were both strongly associated with raised risks, as were SSRIs. Tricyclic antidepressants were not associated with raised risks. The Arizona classification of risk of TdP was a poor predictor of likelihood of noncardiac drug-associated sudden death.

NSAIDs and gastrointestinal cancer prevention.

Numerous studies report the relationship between aspirin and other nonsteroidal anti-inflammatories (NSAIDs) and cancer incidence, in particular for colorectal cancer. This paper systematically reviews the evidence of the effect of aspirin and other NSAIDs on the primary prevention of colorectal and other gastrointestinal cancers in the general population.In 25 investigations of NSAIDs and colorectal cancer, 23 observational studies reported a relative risk reduction but estimates vary widely. Cohort studies generally indicate lesser reductions than case-control studies suggesting possible biases in the latter. Clear evidence of a dose relationship generally appears lacking but data do not indicate useful effects of aspirin in cardioprophylactic doses. Differences have otherwise not been detected between aspirin and other NSAIDs, nor between non-aspirin NSAIDs. There is some evidence that the risk of colorectal cancer reduces with increased duration of NSAID use. The lower incidence of oesophageal and gastric cancers results in smaller numbers of cases in the studies reporting these cancers, particularly in the cohort studies. The trend is for a risk reduction for oesophageal and gastric cancers in people taking NSAIDs, which is more likely to be statistically significant in the case-control studies. A very small number of observational studies have reported the relationship between NSAIDs and the incidence of pancreatic, gallbladder and liver cancers. These show no consistent relationship.In view of the inadequate information about optimal dose and duration of NSAIDs for colorectal cancer reduction, and the adverse effects of NSAIDs, we are not yet in a position to recommend NSAIDs for the primary prevention of colorectal cancer in the general population.

The role of grandparents in childhood obesity in China - evidence from a mixed methods study

BackgroundThe current literature on the influences of family environment on childhood obesity is predominantly based on western populations and has focused on the role of parents. This study examined the influence of grandparents on the development of obesity among Chinese primary school aged children.MethodsA mixed methods study was conducted in four socioeconomically distinct primary school communities in two cities of southern China. The qualitative study (17 focus groups and four personal interviews) involved parents, grandparents, school staff, and food retailers in the vicinity of the schools (nu2009=u200999) and explored perceived causes of childhood obesity. The cross-sectional study examined the association between children’s objectively measured weight status and reported health behaviours, and the presence and role of grandparents in the household. It included children from three randomly selected third grade (8 to 10xa0years) classes from each school (nu2009=u2009497).ResultsGrandparents were commonly perceived to contribute to childhood obesity through inappropriate perception (e.g. fat children are healthy and well cared for), knowledge (e.g. obesity related diseases can only happen in adults; the higher the dietary energy/fat content, the more nutritious the food), and behaviour (e.g. overfeeding and indulging through excusing the children from household chores). Conflicting child care beliefs and practices between grandparents and parents, and between grandparents and school teachers, were felt to undermine efforts to promote healthy behaviours in children. In the cross-sectional study, children who were mainly cared for by their grandparents were more likely to be overweight/obese (adjusted ORu2009=u20092.03; 95xa0% CIu2009=u20091.19 to 3.47); and to consume more sugar-added drinks and unhealthy snacks (Bu2009=u20092.13, 95xa0% CIu2009=u20090.87 to 3.40), than children who were mainly cared for by their parents or other adult. Children who lived with two or more grandparents in the household were more likely to be overweight/obese than children who did not live with any grandparent (adjusted ORu2009=u20091.72; 95xa0% CIu2009=u20091.00 to 2.94).ConclusionsInvolvement of grandparents in childcare is an important factor contributing to childhood obesity in China. Future preventive interventions should include strategies that target grandparents.

Preventing childhood obesity, phase II feasibility study focusing on South Asians: BEACHeS

Objective To assess feasibility and acceptability of a multifaceted, culturally appropriate intervention for preventing obesity in South Asian children, and to obtain data to inform sample size for a definitive trial. Design Phase II feasibility study of a complex intervention. Setting 8 primary schools in inner city Birmingham, UK, within populations that are predominantly South Asian. Participants 1090 children aged 6–8u2005years took part in the intervention. 571 (85.9% from South Asian background) underwent baseline measures. 85.5% (n=488) were followed up 2u2005years later. Interventions The 1-year intervention consisted of school-based and family-based activities, targeting dietary and physical activity behaviours. The intervention was modified and refined throughout the period of delivery. Main outcome measures Acceptability and feasibility of the intervention and of measurements required to assess outcomes in a definitive trial. The difference in body mass index (BMI) z-score between arms was used to inform sample size calculations for a definitive trial. Results Some intervention components (increasing school physical activity opportunities, family cooking skills workshops, signposting of local leisure facilities and attending day event at a football club) were feasible and acceptable. Other components were acceptable, but not feasible. Promoting walking groups was neither acceptable nor feasible. At follow-up, children in the intervention compared with the control group were less likely to be obese (OR 0.41; 0.19 to 0.89), and had lower adjusted BMI z-score (−0.15 kg/m2; 95% CI −0.27 to −0.03). Conclusions The feasibility study informed components for an intervention programme. The favourable direction of outcome for weight status in the intervention group supports the need for a definitive trial. A cluster randomised controlled trial is now underway to assess the clinical and cost-effectiveness of the intervention. Trial registration number ISRCTN51016370.

Socioeconomic determinants of childhood obesity among primary school children in Guangzhou, China.

BackgroundSocioeconomic inequalities in childhood obesity prevalence differ according to a country’s stage of nutrition transition. The aim of this study was to determine which socioeconomic factors influence inequalities in obesity prevalence in Chinese primary school children living in an urban setting.MethodsWe assessed obesity prevalence among 9917 children aged 5–12 years from a stratified random sample of 29 state-funded (residents) and private (migrants) schools in Guangzhou, China. Height and weight were objectively measured using standardised methods and overweight (+1 SDu2009<u2009BMI-for-age z-scoreu2009≤u2009+2 SD) and obesity (BMI-for-age z-scoreu2009>u2009+2 SD) were defined using the World Health Organisation reference 2007.xa0Socioeconomic characteristics were ascertained through parental questionnaires. Generalised Linear Mixed Models with schools as a random effect were used to compare likelihood of overweight/obesity among children in private, with public schools, adjusting for child age and sex, maternal and paternal BMI and education level, and household per-capita income.ResultsThe prevalence of overweight/obesity was 20.0xa0% (95xa0% CI 19.1xa0%–20.9xa0%) in resident compared with 14.3xa0% (95xa0% CI 13.0xa0%–15.4xa0%)xa0in migrant children. In the adjusted model, the odds of overweight/obesity remained higher among resident children (ORxa01.36; 1.16–1.59), was higher in boys compared with girls (ORxa02.56; 2.24–2.93), and increased with increasing age (OR 2.78; 1.95–3.97 in 11–12 vs 5–6 year olds), per-capita household income (ORxa01.27; 1.01–1.59 in highest vs lowest quartile)xa0and maternal educationxa0(OR 1.51; 1.16–1.97 in highest vs lowest). Socioeconomic differences were most marked in older boys, and were only statistically significant in resident children.ConclusionsThe socioeconomic gradient for childhood obesity in China is the reverse of the patterns seen in countries at more advanced stages of the obesity epidemic. This presents an opportunity to intervene and prevent the onset of social inequalities that are likely to ensue with further economic development. The marked gender inequality in obesity needs further exploration.

A comparison of patient and tumour characteristics in two UK bladder cancer cohorts separated by 20 years

To compare patient and tumour characteristics at presentation from two large bladder cancer cohorts, with recruitment separated by 15–20 years To identify significant differences in the West Midlands urothelial cancer of the bladder (UCB) population during this period.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol

BackgroundMany people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach.Methods/DesignIn this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach.DiscussionThis will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first.Trial registrationCurrent controlled trials ISRCTN14930255

Protocol for a nationwide survey of primary health care in China: the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) MPP (Million Persons Project) Primary Health Care Survey.

Introduction China has pioneered advances in primary health care (PHC) and public health for a large and diverse population. To date, the current state of PHC in China has not been subjected to systematic assessments. Understanding variations in primary care services could generate opportunities for improving the structure and function of PHC. Methods and analysis This paper describes a nationwide PHC study (PEACE MPP Primary Health Care Survey) conducted across 31 provinces in China. The study leverages an ongoing research project, the China Patient-centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project (MPP). It employs an observational design with document acquisition and abstraction and in-person interviews. The study will collect data and original documents on the structure and financing of PHC institutions and the adequacy of the essential medicines programme; the education, training and retention of the PHC workforce; the quality of care; and patient satisfaction with care. The study will provide a comprehensive assessment of current PHC services and help determine gaps in access and quality of care. All study instruments and documents will be deposited in the Document Bank as an open-access source for other researchers. Ethics and dissemination The central ethics committee at the China National Centre for Cardiovascular Disease (NCCD) approved the study. Written informed consent has been obtained from all patients. Findings will be disseminated in future peer reviewed papers, and will inform strategies aimed at improving the PHC in China. Trial registration number NCT02953926

Aldehyde dehydrogenase 2-a potential genetic risk factor for lung function among southern Chinese: evidence from the Guangzhou Biobank Cohort Study.

PURPOSEnIn Asia, moderate alcohol users have better lung function. Never users have more inactive aldehyde dehydrogenase 2 (ALDH2) alleles (A) potentially generating confounding because inactive alleles may increase acetaldehyde exposure and reduce lung function.nnnMETHODSnWe examined the association of ALDH2 genotypes with percentage predicted lung function (forced expiratory volume in 1xa0second; forced vital capacity) for age, sex, and height among 5641 older Chinese using multivariable linear regression.nnnRESULTSnALDH2 genotypes were associated with alcohol use and height but not other attributes. Inactive alleles were inversely associated with lung function (percentage predicted forced expiratory volume in 1xa0secondxa0-1.52%, 95% confidence interval [CI],xa0-2.52% toxa0-0.51% for one inactive allele andxa0-2.05%, 95% CI,xa0-3.85% toxa0-0.26% for two inactive alleles compared with two active alleles; and for percentage predicted forced vital capacityxa0-1.25%, 95% CIxa0-2.15% toxa0-0.35% andxa0-1.65%, 95% CI,xa0-3.25% toxa0-0.04%). The association of moderate use with lung function was attenuated after adjusting for ALDH2, in addition to other potential confounders.nnnCONCLUSIONSnPrevious findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease.

Early life vitamin D status and asthma and wheeze: a systematic review and meta-analysis.

BackgroundVitamin D deficiency has been linked to an increased risk of asthma. This study aimed to quantify the effect of early life vitamin D status on asthma and wheeze later in life.MethodsPubMed, Embase, CINAHL, and CNKI databases, the Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to July 2017. We included randomized controlled trials (RCTs) and cohort studies with vitamin D level in blood (maternal or cord or infant) or intake (maternal intake during pregnancy or infant intake) and asthma and/or wheeze. Two reviewers independently extracted data. Fixed- and random-effects models were used to summarize the risk estimates of comparisons between highest vs. lowest vitamin D categories.ResultsOf the 1485 studies identified, three RCTs and 33 cohort studies were included. We did not include the RCTs (1619 participants) in the meta-analysis as the comparators and outcome definitions were heterogenous. Three RCTs reported a non-statistically significant effect of vitamin D supplementation during pregnancy on offspring wheeze/asthma at 3xa0years of age. Pooled estimates of cohort studies suggest no association between antenatal blood vitamin D levels or vitamin D intake and offspring asthma assessed either >u20095xa0years oru2009≤u20095xa0years. The estimate for blood vitamin D remained unchanged when two studies assessing asthma in adulthood were excluded, but a significant inverse association emerged between vitamin D intake and childhood asthma. We found no association between antenatal vitamin D level and wheeze. On the other hand, vitamin D intake during pregnancy may have a protective effect against wheeze.ConclusionsThe pooled estimates from cohort studies show no association between antenatal blood vitamin D level and asthma/wheeze in later life. Whereas, the pooled estimates from cohort studies suggest that antenatal vitamin D intake may have an effect on childhood asthma >u20095xa0years or childhood wheeze. The inconsistent results from studies assessing vitamin D either in blood or intake may be explained by previously reported non-linear association between blood vitamin D3 and childhood asthma. Further trials with enough power and longer follow-up time should be conducted to confirm the results.