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1.  Childhood Passive Smoking Exposure and Age at Menarche in Chinese Women Who Had Never Smoked: The Guangzhou Biobank Cohort Study 
PLoS ONE  2015;10(7):e0130429.
We examined the associations between childhood passive smoking exposure and age at menarche in women who had never smoked in southern China.
Among 30,518 participants in Guangzhou Biobank Cohort Study (GBCS) from 2003-2008, 20,061 women who had never smoked and had complete outcome data were included. Childhood passive smoking exposure was defined as living with 1 or more smokers in the same household during childhood. Data on the number of smokers in the household and frequency of exposure (density and frequency) were also obtained. Age at menarche was measured as a continuous variable.
11,379 (56.7%) participants were exposed to passive smoking during childhood. Compared to those with no passive smoking exposure during childhood, those with exposure ≥5 days/week had menarche 0.19 year (95% confidence interval (CI): 0.13-0.25) earlier on average. Those exposed to more than two smokers had menarche 0.38 year earlier (95% CI: 0.29-0.47). Childhood exposure was associated with early age at menarche (≤13 vs. >13 years), with an adjusted odds ratio of 1.34 (95% CI: 1.21-1.48) for high density, and 1.17 (95% CI: 1.09-1.26) for high frequency of exposure.
Childhood passive smoking exposure was associated with earlier age at menarche, with a dose-response relationship in Chinese women who had never smoked. If causal, the results support the promotion of smoking cessation in families with children, particularly young girls.
PMCID: PMC4506068  PMID: 26186646
2.  The role of grandparents in childhood obesity in China - evidence from a mixed methods study 
The 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.
A 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 (n = 99) 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 10 years) classes from each school (n = 497).
Grandparents 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 OR = 2.03; 95 % CI = 1.19 to 3.47); and to consume more sugar-added drinks and unhealthy snacks (B = 2.13, 95 % CI = 0.87 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 OR = 1.72; 95 % CI = 1.00 to 2.94).
Involvement of grandparents in childcare is an important factor contributing to childhood obesity in China. Future preventive interventions should include strategies that target grandparents.
PMCID: PMC4507318  PMID: 26122955
Child care; Childhood obesity; Chinese children; Eating behavior; Health behavior; Body mass index
3.  A cluster-randomised controlled trial to assess the effectiveness and cost-effectiveness of a childhood obesity prevention programme delivered through schools, targeting 6–7 year old children: the WAVES study protocol 
BMC Public Health  2015;15:488.
There is some evidence that school-based interventions are effective in preventing childhood obesity. However, longer term outcomes, equity of effects and cost-effectiveness of interventions have not been assessed.
The aim of this trial is to assess the clinical and cost-effectiveness of a multi-component intervention programme targeting the school and family environment through primary schools, in preventing obesity in 6–7 year old children, compared to usual practice.
This cluster randomised controlled trial is set in 54 primary schools within the West Midlands, UK, including a multi-ethnic, socioeconomically diverse population of children aged 6–7 years.
The 12-month intervention consists of healthy diet and physical activity promotion. These include: activities to increase time spent doing physical activity within the school day, participation in the ‘Villa Vitality’ programme (a programme that is delivered by an iconic sporting institution (Aston Villa Football Club), which provides interactive learning opportunities for physical activity and healthy eating), healthy cooking skills workshops in school time for parents and children, and provision of information to families signposting local leisure opportunities. The primary (clinical) outcome is the difference in body mass index (BMI) z-scores between arms at 3 and 18 months post-intervention completion. Cost per Quality Adjusted Life Year (QALY) will also be assessed. The sample size estimate (1000 children split across 50 schools at follow-up) is based on 90% power to detect differences in BMI z-score of 0.25 (estimated ICC ≤ 0.04), assuming a correlation between baseline and follow-up BMI z-score of 0.9. Treatment effects will be examined using mixed model ANCOVA. Primary analysis will adjust for baseline BMI z-score, and secondary analysis will adjust for pre-specified baseline school and child level covariates.
The West Midlands ActiVe lifestyle and healthy Eating in School children (WAVES) study is the first trial that will examine the cost-effectiveness and long term outcomes of a childhood obesity prevention programme in a multi-ethnic population, with a sufficient sample size to detect clinically important differences in adiposity. The intervention was developed using the Medical Research Council framework for complex interventions, and outcomes are measured objectively, together with a comprehensive process evaluation.
Trial registration
Current Controlled Trials ISRCTN97000586 (registered May 2010).
PMCID: PMC4457211  PMID: 25968599
Cluster randomised controlled trial; Complex intervention; Childhood obesity prevention; Physical activity; Healthy eating; Cost-effectiveness
4.  Genetically Predicted Testosterone and Systemic Inflammation in Men: A Separate-Sample Mendelian Randomization Analysis in Older Chinese Men 
PLoS ONE  2015;10(5):e0126442.
Observationally, testosterone is negatively associated with systemic inflammation, but this association is open to both residual confounding and reverse causality. Large-scale randomized controlled trials (RCTs), assessing exogenous effects, are presently unavailable. We examined the association of endogenous testosterone with well-established systemic inflammatory markers (white blood cell, granulocyte, lymphocyte and high-sensitivity C-reactive protein (hsCRP)) using a separate-sample Mendelian randomization analysis to minimize reverse causality.
A genetic prediction rule for serum testosterone was developed in 289 young Chinese men with mean age of 21.0, using selected testosterone-related SNPs (rs10046, rs1008805 and rs1256031). Multivariable linear regression was used to examine the association of genetically predicted serum testosterone with inflammatory markers among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study.
Genetically predicted testosterone was unrelated to white blood cell count (-0.01 109/L per nmol/L testosterone, 95% confidence interval (CI) -0.05 to 0.04), granulocyte count (-0.02 109/L, 95% CI -0.06 to 0.02), lymphocyte count (0.005 109/L, 95% CI -0.01 to 0.02) and hsCRP (-0.05 mg/L, 95% CI -0.15 to 0.06).
Our findings did not corroborate any anti-inflammatory effects of testosterone or corresponding potentially protective effects of testosterone on chronic diseases resulting from reduced low-grade systemic inflammation.
PMCID: PMC4423952  PMID: 25950910
5.  TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol 
BMC Pulmonary Medicine  2014;14:157.
Many 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.
In 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.
This 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 registration
Current controlled trials ISRCTN14930255
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2466-14-157) contains supplementary material, which is available to authorized users.
PMCID: PMC4271517  PMID: 25280869
COPD; Case-finding; Screening; Primary care; Respiratory questionnaire; Spirometry; Cluster RCT; Cost-effectiveness
6.  Adverse Lifestyle Leads to an Annual Excess of 2 Million Deaths in China 
PLoS ONE  2014;9(2):e89650.
Adverse lifestyle factors have been associated with increased mortality, but data are lacking on their combined effect in developing populations, which we address in the present study.
In a death registry-based, case-control study among Hong Kong Chinese aged 30+y, proxy-reported lifestyle factors 10 y ago were collected for 21,363 cases (81% of all deaths) and 12,048 living controls. Risks associated with poor diet, inactivity, heavy alcohol intake, and smoking for all-cause and cause-specific mortality, adjusting for potential confounders, were determined, and excess deaths for the Chinese population were calculated.
Adjusted odds ratios for all-cause mortality were 1.15 (95% CI 1.09, 1.23), 1.34 (1.27, 1.43), 1.36 (1.21, 1.52), and 1.58 (1.46, 1.70) for poor diet, inactivity, heavy alcohol intake and smoking, respectively. Increasing numbers of adverse lifestyle factors were associated with a dose-dependent increase in adjusted odds ratios of 1.30 (1.20, 1.40), 1.67 (1.54, 1.81), 2.32 (2.08, 2.60), and 3.85 (3.12, 4.75) for 1, 2, 3, and 4 risk factors relative to those with none. The population attributable fraction for all-cause, all-CVD and all-cancer mortality were 26.6%, 15.0%, and 32.1%, resulting in an excess of 2,017,541; 489,884; and 607,517 deaths annually, respectively. Although smoking was associated with the greatest excess loss of life (867,530), heavy drinking (680,466), and physical inactivity (678,317) were similarly important.
Adverse lifestyle factors contribute to one quarter of all deaths in China. Improving lifestyle practices, particularly focussing on moderating alcohol intake and increasing activity, and smoking cessation are critical to reducing the lifestyle-associated health burden.
PMCID: PMC3935915  PMID: 24586936
7.  Milk Consumption and Cardiovascular Risk Factors in Older Chinese: The Guangzhou Biobank Cohort Study 
PLoS ONE  2014;9(1):e84813.
Dairy products consumption is increasingly common globally. Most of the evidence concerning dairy products comes from observational studies in western populations which are inevitably open to confounding. To triangulate the evidence concerning dairy products, we examined the associations of whole cow's milk consumption with cardiovascular risk factors in a non-Western setting with a different pattern of milk consumption and cardiovascular diseases from Western populations.
We used multivariable censored linear or logistic regression to examine cross-sectionally the adjusted associations of whole cow's milk consumption (none (n = 14892), 1–3/week (n = 2689) and 3+/week (n = 2754)) with cardiovascular risk factors in Chinese (≥50 years) in the Guangzhou Biobank Cohort Study.
Whole cow's milk consumption was negatively associated with systolic blood pressure (3+/week compared to none −2.56 mmHg, 95% confidence interval (CI) −3.63 to −1.49), diastolic blood pressure (−1.32 mmHg, 95% CI −1.87 to −0.77) and triglycerides (−0.06 mmol/L, 95% CI −0.11 to −0.002), but was positively associated with HDL-cholesterol (0.02 mmol/L,95% CI 0.01 to 0.04) and fasting glucose (0.08 mmol/L, 95% CI 0.01 to 0.16) adjusted for age, sex, phase of study, socio-economic position, lifestyle (smoking, alcohol use and physical activity) and adiposity, but had no obvious association with LDL-cholesterol or the presence of diabetes.
Whole cow's milk consumption had heterogeneous associations with cardiovascular risk factors. Higher whole cow's milk consumption was associated with lower levels of specific cardiovascular risk factors which might suggest risk factor specific biological pathways with different relations to blood pressure and lipids than glucose.
PMCID: PMC3885601  PMID: 24416290
8.  Moderate Alcohol Use and Cardiovascular Disease from Mendelian Randomization 
PLoS ONE  2013;8(7):e68054.
Observational studies show moderate alcohol use negatively associated with ischemic heart disease (IHD) and cardiovascular disease (CVD). However, healthier attributes among moderate users compared to never users may confound the apparent association. A potentially less biased way to examine the association is Mendelian randomization, using alcohol metabolizing genes which influence alcohol use.
We used instrumental variable analysis with aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables for alcohol use to examine the association of alcohol use (10 g ethanol/day) with CVD risk factors (blood pressure, lipids and glucose) and morbidity (self-reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study.
ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6). Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg, 95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds ratio (OR) 0.98, 95% CI 0.76 to 1.27) or self-reported IHD (OR 1.10, 95% CI 0.83 to 1.45).
Low to moderate alcohol use among men had the expected effects on most CVD risk factors but not fasting glucose. Larger studies are needed to confirm the null associations with IHD, CVD and fasting glucose.
PMCID: PMC3712994  PMID: 23874492
9.  Study protocol for “Moving Bright, Eating Smart”– A phase 2 clinical trial on the acceptability and feasibility of a diet and physical activity intervention to prevent recurrence in colorectal cancer survivors 
BMC Public Health  2013;13:487.
Colorectal cancer is the second most common cancer and cancer-killer in Hong Kong with an alarming increasing incidence in recent years. The latest World Cancer Research Fund report concluded that foods low in fibre, and high in red and processed meat cause colorectal cancer whereas physical activity protects against colon cancer. Yet, the influence of these lifestyle factors on cancer outcome is largely unknown even though cancer survivors are eager for lifestyle modifications. Observational studies suggested that low intake of a Western-pattern diet and high physical activity level reduced colorectal cancer mortality. The Theory of Planned Behaviour and the Health Action Process Approach have guided the design of intervention models targeting a wide range of health-related behaviours.
We aim to demonstrate the feasibility of two behavioural interventions intended to improve colorectal cancer outcome and which are designed to increase physical activity level and reduce consumption of a Western-pattern diet. This three year study will be a multicentre, randomised controlled trial in a 2x2 factorial design comparing the “Moving Bright, Eating Smart” (physical activity and diet) programme against usual care. Subjects will be recruited over a 12-month period, undertake intervention for 12 months and followed up for a further 12 months. Baseline, interim and three post-intervention assessments will be conducted.
Two hundred and twenty-two colorectal cancer patients who completed curative treatment without evidence of recurrence will be recruited into the study. Primary outcome measure will be whether physical activity and dietary targets are met at the end of the 12-month intervention. Secondary outcome measures include the magnitude and mechanism of behavioural change, the degree and determinants of compliance, and the additional health benefits and side effects of the intervention.
The results of this study will establish the feasibility of targeting the two behaviours (diet and physical activity) and demonstrate the magnitude of behaviour change. The information will facilitate the design of a further larger phase III randomised controlled trial with colorectal cancer outcome as the study endpoint to determine whether this intervention model would reduce colorectal cancer recurrence and mortality.
Trial registration No: NCT01708824
PMCID: PMC3716902  PMID: 23688320
Colorectal cancer; Cancer survivor; Diet; Meat; Grains; Physical activity; Behavioural intervention; Feasibility; Acceptability; Randomised
10.  Self-Reported Long Total Sleep Duration Is Associated With Metabolic Syndrome 
Diabetes Care  2011;34(10):2317-2319.
To examine the association between total sleep duration and the prevalence of metabolic syndrome (MetSyn) in older Chinese.
Cross-sectional analysis of baseline data from the Guangzhou Biobank Cohort Study (GBCS) was performed. Participants (n = 29,333) were aged ≥50 years. Risk of MetSyn and its components were identified for self-reported total sleep duration.
Participants reporting long (≥9 h) and short (<6 h) total sleep duration had increased odds ratio (OR) of 1.18 (95% CI 1.07–1.30) and 1.14 (1.05–1.24) for the presence of MetSyn, respectively. The relationship remained in long sleepers (OR 1.21 [1.10–1.34]) but diminished in short sleepers (0.97 [0.88–1.06]) after full adjustment.
Long sleep duration was associated with greater risk of MetSyn in older Chinese. Confirmation through longitudinal studies is needed. The mechanisms mediating the link between long sleep duration and MetSyn require further investigation.
PMCID: PMC3177714  PMID: 21873559
11.  Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study 
BMC Cancer  2012;12:255.
Most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients’ preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial.
Patients aged 60–74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared.
Two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population.
This study has confirmed and amplified recently published factors involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to individuals, the lack of knowledge about the aetiology of colon cancer and the lack of motivation to change behaviour are critical factors.
Trial registration
Current Controlled Trials ISRCTN03320951
PMCID: PMC3532076  PMID: 22708848
Adenomatous polyps; Feasibility studies; Prevention & control; Health behaviour; Attitude to health; Qualitative research; Colorectal neoplasms
12.  Physical activity for cancer survivors: meta-analysis of randomised controlled trials 
Objective To systematically evaluate the effects of physical activity in adult patients after completion of main treatment related to cancer.
Design Meta-analysis of randomised controlled trials with data extraction and quality assessment performed independently by two researchers.
Data sources Pubmed, CINAHL, and Google Scholar from the earliest possible year to September 2011. References from meta-analyses and reviews.
Study selection Randomised controlled trials that assessed the effects of physical activity in adults who had completed their main cancer treatment, except hormonal treatment.
Results There were 34 randomised controlled trials, of which 22 (65%) focused on patients with breast cancer, and 48 outcomes in our meta-analysis. Twenty two studies assessed aerobic exercise, and four also included resistance or strength training. The median duration of physical activity was 13 weeks (range 3-60 weeks). Most control groups were considered sedentary or were assigned no exercise. Based on studies on patients with breast cancer, physical activity was associated with improvements in insulin-like growth factor-I, bench press, leg press, fatigue, depression, and quality of life. When we combined studies on different types of cancer, we found significant improvements in body mass index (BMI), body weight, peak oxygen consumption, peak power output, distance walked in six minutes, right handgrip strength, and quality of life. Sources of study heterogeneity included age, study quality, study size, and type and duration of physical activity. Publication bias did not alter our conclusions.
Conclusions Physical activity has positive effects on physiology, body composition, physical functions, psychological outcomes, and quality of life in patients after treatment for breast cancer. When patients with cancer other than breast cancer were also included, physical activity was associated with reduced BMI and body weight, increased peak oxygen consumption and peak power output, and improved quality of life.
PMCID: PMC3269661  PMID: 22294757
13.  Physical Activity, Adiposity, and Diabetes Risk in Middle-Aged and Older Chinese Population 
Diabetes Care  2010;33(11):2342-2348.
Physical activity may modify the association of adiposity with type 2 diabetes. We investigated the independent and joint association of adiposity and physical activity with fasting plasma glucose, impaired fasting glucose, and type 2 diabetes in a Chinese population.
Middle-aged and older Chinese (n = 28,946, ≥50 years, 72.4%women) from the Guangzhou Biobank Cohort Study were examined in 2003–2008. Multivariable regression was used in a cross-sectional analysis.
BMI, waist circumference, and waist-to-hip ratio (WHR) were positively associated with type 2 diabetes after multiple adjustment, most strongly for WHR with odds ratio (OR) of 3.99 (95% CI 3.60–4.42) for highest compared with lowest tertile. Lack of moderate-to-vigorous physical activity, but not walking, was associated with diabetes with an OR of 1.29 (1.17–1.41). The association of moderate-to-vigorous activity with fasting glucose varied with WHR tertiles (P = 0.01 for interaction). Within the high WHR tertile, participants who had a lack of moderate-to-vigorous activity had an OR of 3.87 (3.22–4.65) for diabetes, whereas those who were active had an OR of 2.94 (2.41–3.59).
In this population, WHR was a better measure of adiposity-related diabetes risk than BMI or waist circumference. Higher moderate-to-vigorous activity was associated with lower diabetes risk, especially in abdominally obese individuals.
PMCID: PMC2963492  PMID: 20713687
14.  Passive smoking and chronic obstructive pulmonary disease: cross-sectional analysis of data from the Health Survey for England 
BMJ Open  2011;1(2):e000153.
There is increasing evidence that passive smoking is associated with chronic respiratory diseases, but its association with chronic obstructive pulmonary disease (COPD) requires more study. In this cross-sectional analysis of data from 3 years of the Health Survey for England, the association between passive smoking exposure and risk of COPD is evaluated.
Cross-sectional analysis of the 1995, 1996 and 2001 Health Surveys for England including participants of white ethnicity, aged 40+ years with valid lung function data. COPD was defined using the lower limit of normal spirometric criteria for airflow obstruction. Standardised questions elicited self-reported information on demography, smoking history, ethnicity, occupation, asthma and respiratory symptoms (dyspnoea, chronic cough, chronic phlegm, wheeze). Passive smoking was measured by self-report of hours of exposure to cigarette smoke per week.
Increasing passive smoke exposure was independently associated with increased risk of COPD, with adjusted OR 1.05 (95% CI 0.93 to 1.18) for 1–19 h and OR 1.18 (95% CI 1.01 to 1.39) for 20 or more hours of exposure per week. Similar patterns (although attenuated and non-significant) were observed among never smokers. More marked dose–response relationships were observed between passive smoking exposure and respiratory symptoms, but the most marked effects were on the development of clinically significant COPD (airflow obstruction plus symptoms), where the risk among never smokers was doubled (OR 1.98 (95% CI 1.03 to 3.79)) if exposure exceeded 20 h/week.
This analysis adds weight to the evidence suggesting an association between passive smoking exposure and COPD.
Article summary
Article focus
Passive exposure to cigarette smoke is established as an important independent risk factor for the development of chronic conditions such as heart disease and lung cancer.
Although there is growing evidence implicating passive smoking in asthma and other respiratory diseases, the evidence for its effect on chronic obstructive pulmonary disease (COPD) is inconsistent.
Using cross-sectional data from the annual Health Survey for England, we examined the association between self-reported exposure to passive smoking and COPD.
Key messages
We have demonstrated a significant dose–response relationship between hours of exposure to passive smoking and increasing risk of COPD.
The most marked effects were observed on the development of clinically significant COPD (airflow obstruction plus symptoms), where the risk among never smokers was doubled (OR 1.98 (95% CI 1.03 to 3.79)) if exposure exceeded 20 h/week.
Passive smoking is prevalent worldwide, and even after the 2007 public smoking ban in the UK, 20% of the adult English population are still exposed to up to 20 h of passive smoking per week, with 5% exposed to more than 20 h/week; further measures are needed to investigate and reduce exposures in the home and elsewhere.
Strengths and limitations of this study
Our study has the advantage of being a large sample representative of the English population (>21 000 participants), conducted over 3 separate years, with a standardised protocol and objective measure of lung function.
However, due to the cross-sectional nature of the design, temporal associations cannot necessarily be inferred.
The Health Survey for England was not designed for the specific analyses presented in this paper, and thus some of the measures are crude.
Self-reported passive smoke exposure is only a proxy for true exposure levels, but is accepted as the most practical method of assessment.
PMCID: PMC3191589  PMID: 22021874
15.  Parental Death during Childhood and Adult Cardiovascular Risk in a Developing Country: The Guangzhou Biobank Cohort Study 
PLoS ONE  2011;6(5):e19675.
In observational studies from western countries childhood emotional adversity is usually associated with adult cardiovascular disease. These findings are open to contextual biases making evidence from other settings valuable. We examined the association of a potential marker of childhood emotional adversity with cardiovascular disease risk factors in a developing country.
We used multivariable regression in cross-sectional analysis of older (≥50 years) men (n = 7,885) and women (n = 20,886) from the Guangzhou Biobank Cohort Study (2003–8) to examine the adjusted association of early life (<18 years) parental death (none, one or two deaths) with blood pressure, fasting glucose, LDL-cholesterol, HDL-cholesterol, triglycerides, body mass index (BMI), waist-hip ratio (WHR) and white blood cell count (WBC). We used seated height and delayed 10-word recall to assess content validity of parental death as a measure of childhood emotional adversity. We also examined whether associations varied by sex.
Early life parental death was associated with shorter age- and sex-adjusted seated height. It was also associated with lower 10-word recall score adjusted for age, sex, socio-economic position, leg length and lifestyle. Similarly, adjusted early life parental death was not associated with blood pressure, fasting glucose, LDL-cholesterol or HDL-cholesterol but was associated with lower BMI (−0.40, 95% confidence interval (CI) −0.62 to −0.19 for 2 compared with no early life parental deaths) and triglycerides. Associations varied by sex for WHR and WBC. Among men only, early life parental death was associated with lower WHR (−0.008, 95% CI −0.015 to −0.001) and WBC (−0.35 109/L, 95% CI −0.56 to −0.13).
In a non-western population from a developing country, childhood emotional adversity was negatively associated with some cardiovascular risk factors, particularly among men. Our study suggests that some of the observed associations in western populations may be socially rather than biologically based or may be population specific.
PMCID: PMC3095611  PMID: 21603607
16.  Sudden death in patients receiving drugs tending to prolong the QT interval 
To 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.
Case–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.
Noncardiac 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.
Atypical 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.
PMCID: PMC2791981  PMID: 19916999
case–control studies; QT-prolonging drugs; sudden cardiac death
17.  Case finding for chronic obstructive pulmonary disease: a model for optimising a targeted approach 
Thorax  2010;65(6):492-498.
Case finding is proposed as an important component of the forthcoming English National Clinical Strategy for chronic obstructive pulmonary disease (COPD) because of accepted widespread underdiagnosis worldwide. However the best method of identification is not known. The extent of undiagnosed clinically significant COPD in England is described and the effectiveness of an active compared with an opportunistic approach to case finding is evaluated.
A cross-sectional analysis was carried out using using Health Survey for England (HSE) 1995–1996 data supplemented with published literature. A model comparing an active approach (mailed questionnaires plus opportunistic identification) with an opportunistic-only approach of case finding among ever smokers aged 40–79 years was evaluated. There were 20 496 participants aged ≥30 years with valid lung function measurements. The main outcome measure was undiagnosed clinically significant COPD (any respiratory symptom with both forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and FEV1 <80% predicted).
971 (4.7%) had clinically significant COPD, of whom 840 (86.5%) did not report a previous diagnosis. Undiagnosed cases were more likely to be female, and smoked less. 25.3% had severe disease (FEV1 <50% predicted), 38.5% Medical Research Council (MRC) grade 3 dyspnoea and 44.1% were current smokers. The active case-finding strategy can potentially identify 70% more new cases than opportunistic identification alone (3.8 vs 2.2 per 100 targeted). Treating these new cases could reduce hospitalisations by at least 3300 per year in England and deaths by 2885 over 3 years.
There is important undiagnosed clinically significant COPD in the population, and the addition of a systematic case-finding approach may be more effective in identifying these cases. The cost-effectiveness of this approach needs to be tested empirically in a prospective study.
PMCID: PMC2892752  PMID: 20522845
18.  Is childhood meat eating associated with better later adulthood cognition in a developing population? 
European Journal of Epidemiology  2010;25(7):507-516.
Inadequate childhood nutrition is associated with poor short-term academic and cognitive outcomes. Dietary supplementation with meat is associated with better cognitive outcome in children. Whether childhood nutrition has life long effects on cognitive function is unclear. We examined the association of childhood meat eating with adulthood cognitive function in southern China where the older population lived through significant hardship during their early years. Multivariable linear regression was used in a cross-sectional study of 20,086 Chinese men and women aged ≥ 50 years from the Guangzhou Biobank Cohort Study (phases 2 and 3) 2005–8. We assessed the association of childhood meat eating with delayed 10-word and immediate recall score. Adjusted for age, sex, education, childhood and adulthood socio-economic position and current physical activity, childhood meat eating almost daily, when compared to yearly or never childhood meat eating, was positively associated with delayed recall score (additional number of words recalled out of 10 = 0.22 [95% confidence interval = 0.11–0.31]). Similarly adjusted, childhood meat eating about once a month, about once a week and almost daily were positively associated with immediate recall score (additional number of words recalled out of 30 = 0.38 [0.23–0.54], 0.73 [0.56–0.89] and 0.76 [0.55–0.98] respectively). More frequent childhood meat eating was associated with better cognition through to old age. If confirmed, these results highlight the importance of adequate childhood nutrition and they also emphasise the childhood and adolescent antecedents of adult disease, with corresponding public health implications for healthy aging.
PMCID: PMC2903695  PMID: 20526800
Aged; Childhood; China; Cognition; Cross-sectional studies; Dementia; Nutrition
19.  Effect of social factors on winter hospital admission for respiratory disease: a case–control study of older people in the UK 
Every winter, hospitals in the UK and other developed countries experience a surge in respiratory admissions. Ecological studies suggest that social circumstances may be an important determinant.
To establish the most important factors associated with winter hospital admissions among older people presenting with acute respiratory disease, especially the relative effect of social factors.
Design of study
case–control study.
Seventy-nine general practices in central England.
Of a cohort of patients consulting medical services with lower respiratory tract infection or exacerbation of chronic respiratory disease, 157 hospitalised cases were compared to 639 controls. Social, medical, and other factors were examined by interview and GP records.
Measures of material deprivation were not significant risk factors for admission at either individual or area level, although social isolation (odds ratio [OR] 4.5; 95% confidence interval [CI] = 1.3 to 15.8) resulted in an increased risk of admission. The most important independent risk factor was the presence of chronic obstructive pulmonary disease (COPD; OR 4.0; 95% CI = 1.4 to 11.4), other chronic disease (OR 2.9; 95% CI = 1.2 to 7.0), or both (OR 6.7; 95% CI = 2.4 to 18.4). Being housebound was also an independent risk factor (OR 2.2; 95% CI = 1.0 to 4.8).
Socioeconomic factors had little relative effect compared with medical and functional factors. The most important was the presence of long-term medical conditions (especially COPD), being housebound, and having received two or more courses of oral steroid treatment in the previous year. This combination of factors could be used by primary medical services to identify older patients most vulnerable to winter admissions. Clinicians should ensure that patients with COPD are better supported to manage their condition.
PMCID: PMC2419018  PMID: 18505611
elderly; hospitalisation; chronic obstructive pulmonary disease; respiratory tract infections; socioeconomic factors; winter pressures
20.  A practical method for monitoring general practice mortality in the UK: findings from a pilot study in a health board of Northern Ireland 
The Baker report into Dr Harold Shipman's murders recommended monitoring mortality in general practice, but there is currently no practical method available to implement this.
To monitor mortality rates in response to the Baker report and to use the data to improve quality of care.
Design of study
Prospective mortality monitoring study.
Eastern Health and Social Services Board, Northern Ireland.
Linked quarterly mortality data from 1994–2001 were compiled for 114 general practices in Eastern Health and Social Services Board in Northern Ireland. Cross-sectional control charts compared crude and adjusted mortality rates across all the practices. Longitudinal control charts analysed quarterly mortality rates over 28 quarters within each practice. Practices were sent their own control charts and invited to feedback workshops. Special cause variation in mortality was investigated as follows: checks on data, case-mix, practice structures, processes of care and finally individual carers.
Age, sex and deprivation adjusted cross-sectional control charts identified 18 practices as showing special cause variation in their mortality (11 high and 7 low). Assignable causes were found for all high special cause practices: large numbers of nursing home patients (six practices), very high levels of deprivation and high morbidity not captured by our case-mix adjustment (five practices). For three of seven low special cause practices, case-mix adjustment underestimated affluence and overestimated morbidity levels. Feedback indicated widespread support for the principle of monitoring, but concerns about the public disclosure of mortality data.
We have successfully developed and piloted a general practice mortality monitoring system with the support and participation of local stakeholders. This used control charts for analysis and followed a scientific strategy for investigating special cause variation.
PMCID: PMC1464080  PMID: 16176733
control charts; general practice; mortality; monitoring

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