Publications by authors named "Derrick Bennett"

147 Publications

Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis.

Lancet 2021 Nov;398(10313):1803-1810

Deep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address:

Background: Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.

Methods: We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.

Findings: 145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84-0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76-0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76-0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27-1·72]) and thiazide diuretics (RR 1·20 [1·07-1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92-1·13]).

Interpretation: Blood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.

Funding: British Heart Foundation, National Institute for Health Research, and Oxford Martin School.
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http://dx.doi.org/10.1016/S0140-6736(21)01920-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585669PMC
November 2021

Publisher Correction: Utility of single versus sequential measurements of risk factors for prediction of stroke in Chinese adults.

Sci Rep 2021 Oct 18;11(1):20874. Epub 2021 Oct 18.

Clinical Trial Service Unit and Epidemiological Studies, Nuffield Department of Population Health, University of Oxford, Big Data Institute, Old Road Campus, Oxford, OX 7LF, UK.

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http://dx.doi.org/10.1038/s41598-021-00401-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523744PMC
October 2021

Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease.

Br J Sports Med 2021 Sep 6. Epub 2021 Sep 6.

Nuffield Department of Population Health, University of Oxford, Oxford, UK

Objective: To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.

Methods: Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence.

Results: In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk.

Conclusion: Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.
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http://dx.doi.org/10.1136/bjsports-2021-104050DOI Listing
September 2021

Utility of single versus sequential measurements of risk factors for prediction of stroke in Chinese adults.

Sci Rep 2021 09 2;11(1):17575. Epub 2021 Sep 2.

Clinical Trial Service Unit and Epidemiological Studies, Nuffield Department of Population Health, University of Oxford, Big Data Institute, Old Road Campus, Oxford, OX 7LF, UK.

Absolute risks of stroke are typically estimated using measurements of cardiovascular disease risk factors recorded at a single visit. However, the comparative utility of single versus sequential risk factor measurements for stroke prediction is unclear. Risk factors were recorded on three separate visits on 13,753 individuals in the prospective China Kadoorie Biobank. All participants were stroke-free at baseline (2004-2008), first resurvey (2008), and second resurvey (2013-2014), and were followed-up for incident cases of first stroke in the 3 years following the second resurvey. To reflect the models currently used in clinical practice, sex-specific Cox models were developed to estimate 3-year risks of stroke using single measurements recorded at second resurvey and were retrospectively applied to risk factor data from previous visits. Temporal trends in the Cox-generated risk estimates from 2004 to 2014 were analyzed using linear mixed effects models. To assess the value of more flexible machine learning approaches and the incorporation of longitudinal data, we developed gradient boosted tree (GBT) models for 3-year prediction of stroke using both single measurements and sequential measurements of risk factor inputs. Overall, Cox-generated estimates for 3-year stroke risk increased by 0.3% per annum in men and 0.2% per annum in women, but varied substantially between individuals. The risk estimates at second resurvey were highly correlated with the annual increase of risk for each individual (men: r = 0.91, women: r = 0.89), and performance of the longitudinal GBT models was comparable with both Cox and GBT models that considered measurements from only a single visit (AUCs: 0.779-0.811 in men, 0.724-0.756 in women). These results provide support for current clinical guidelines, which recommend using risk factor measurements recorded at a single visit for stroke prediction.
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http://dx.doi.org/10.1038/s41598-021-95244-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413314PMC
September 2021

Long-term solid fuel use and risks of major eye diseases in China: A population-based cohort study of 486,532 adults.

PLoS Med 2021 07 29;18(7):e1003716. Epub 2021 Jul 29.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom.

Background: Over 3.5 billion individuals worldwide are exposed to household air pollution from solid fuel use. There is limited evidence from cohort studies on associations of solid fuel use with risks of major eye diseases, which cause substantial disease and economic burden globally.

Methods And Findings: The China Kadoorie Biobank recruited 512,715 adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Cooking frequency and primary fuel types in the 3 most recent residences were assessed by a questionnaire. During median (IQR) 10.1 (9.2 to 11.1) years of follow-up, electronic linkages to national health insurance databases identified 4,877 incident conjunctiva disorders, 13,408 cataracts, 1,583 disorders of sclera, cornea, iris, and ciliary body (DSCIC), and 1,534 cases of glaucoma. Logistic regression yielded odds ratios (ORs) for each disease associated with long-term use of solid fuels (i.e., coal or wood) compared to clean fuels (i.e., gas or electricity) for cooking, with adjustment for age at baseline, birth cohort, sex, study area, education, occupation, alcohol intake, smoking, environmental tobacco smoke, cookstove ventilation, heating fuel exposure, body mass index, prevalent diabetes, self-reported general health, and length of recall period. After excluding participants with missing or unreliable exposure data, 486,532 participants (mean baseline age 52.0 [SD 10.7] years; 59.1% women) were analysed. Overall, 71% of participants cooked regularly throughout the recall period, of whom 48% used solid fuels consistently. Compared with clean fuel users, solid fuel users had adjusted ORs of 1.32 (1.07 to 1.37, p < 0.001) for conjunctiva disorders, 1.17 (1.08 to 1.26, p < 0.001) for cataracts, 1.35 (1.10 to 1.66, p = 0.0046) for DSCIC, and 0.95 (0.76 to 1.18, p = 0.62) for glaucoma. Switching from solid to clean fuels was associated with smaller elevated risks (over long-term clean fuel users) than nonswitching, with adjusted ORs of 1.21 (1.07 to 1.37, p < 0.001), 1.05 (0.98 to 1.12, p = 0.17), and 1.21 (0.97 to 1.50, p = 0.088) for conjunctiva disorders, cataracts, and DSCIC, respectively. The adjusted ORs for the eye diseases were broadly similar in solid fuel users regardless of ventilation status. The main limitations of this study include the lack of baseline eye disease assessment, the use of self-reported cooking frequency and fuel types for exposure assessment, the risk of bias from delayed diagnosis (particularly for cataracts), and potential residual confounding from unmeasured factors (e.g., sunlight exposure).

Conclusions: Among Chinese adults, long-term solid fuel use for cooking was associated with higher risks of not only conjunctiva disorders but also cataracts and other more severe eye diseases. Switching to clean fuels appeared to mitigate the risks, underscoring the global health importance of promoting universal access to clean fuels.
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http://dx.doi.org/10.1371/journal.pmed.1003716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321372PMC
July 2021

Stroke risk prediction using machine learning: a prospective cohort study of 0.5 million Chinese adults.

J Am Med Inform Assoc 2021 07;28(8):1719-1727

Department of Engineering Science, University of Oxford, Oxford, UK.

Objective: To compare Cox models, machine learning (ML), and ensemble models combining both approaches, for prediction of stroke risk in a prospective study of Chinese adults.

Materials And Methods: We evaluated models for stroke risk at varying intervals of follow-up (<9 years, 0-3 years, 3-6 years, 6-9 years) in 503 842 adults without prior history of stroke recruited from 10 areas in China in 2004-2008. Inputs included sociodemographic factors, diet, medical history, physical activity, and physical measurements. We compared discrimination and calibration of Cox regression, logistic regression, support vector machines, random survival forests, gradient boosted trees (GBT), and multilayer perceptrons, benchmarking performance against the 2017 Framingham Stroke Risk Profile. We then developed an ensemble approach to identify individuals at high risk of stroke (>10% predicted 9-yr stroke risk) by selectively applying either a GBT or Cox model based on individual-level characteristics.

Results: For 9-yr stroke risk prediction, GBT provided the best discrimination (AUROC: 0.833 in men, 0.836 in women) and calibration, with consistent results in each interval of follow-up. The ensemble approach yielded incrementally higher accuracy (men: 76%, women: 80%), specificity (men: 76%, women: 81%), and positive predictive value (men: 26%, women: 24%) compared to any of the single-model approaches.

Discussion And Conclusion: Among several approaches, an ensemble model combining both GBT and Cox models achieved the best performance for identifying individuals at high risk of stroke in a contemporary study of Chinese adults. The results highlight the potential value of expanding the use of ML in clinical practice.
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http://dx.doi.org/10.1093/jamia/ocab068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324240PMC
July 2021

Associations of Skeletal Muscle Mass and Fat Mass With Incident Cardiovascular Disease and All-Cause Mortality: A Prospective Cohort Study of UK Biobank Participants.

J Am Heart Assoc 2021 05 19;10(9):e019337. Epub 2021 Apr 19.

Nuffield Department of Primary Care Health Sciences University of Oxford United Kingdom.

Background There is debate whether body mass index is a good predictor of health outcomes because different tissues, namely skeletal muscle mass (SMM) and fat mass (FM), may be differentially associated with risk. We investigated the association of appendicular SMM (aSMM) and FM with fatal and nonfatal cardiovascular disease (CVD) and all-cause mortality. We compared their prognostic value to that of body mass index. Methods and Results We studied 356 590 UK Biobank participants aged 40 to 69 years with bioimpedance analysis data for whole-body FM and predicted limb muscle mass (to calculate aSMM). Associations between aSMM and FM with CVD and all-cause mortality were examined using multivariable Cox proportional hazards models. Over 3 749 501 person-years of follow-up, there were 27 784 CVD events and 15 844 all-cause deaths. In men, aSMM was positively associated with CVD incidence (hazard ratio [HR] per 1 SD 1.07; 95% CI, 1.06-1.09) and there was a curvilinear association in women. There were stronger positive associations between FM and CVD with HRs per SD of 1.20 (95% CI, 1.19-1.22) and 1.25 (95% CI, 1.23-1.27) in men and women respectively. Within FM tertiles, the associations between aSMM and CVD risk largely persisted. There were J-shaped associations between aSMM and FM with all-cause mortality in both sexes. Body mass index was modestly better at discriminating CVD risk. Conclusions FM showed a strong positive association with CVD risk. The relationship of aSMM with CVD risk differed between sexes, and potential mechanisms need further investigation. Body fat and SMM bioimpedance measurements were not superior to body mass index in predicting population-level CVD incidence or all-cause mortality.
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http://dx.doi.org/10.1161/JAHA.120.019337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200765PMC
May 2021

Genetic susceptibility, elevated blood pressure, and risk of atrial fibrillation: a Mendelian randomization study.

Genome Med 2021 03 4;13(1):38. Epub 2021 Mar 4.

Deep Medicine, Oxford Martin School, University of Oxford, 1st Floor, Hayes House, 75 George Street, Oxford, OX1 2BQ, UK.

Background: Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual's genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk.

Methods: First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a population of one million Europeans in total. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists.

Results: The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mmHg [OR] 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease.

Conclusions: The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF.
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http://dx.doi.org/10.1186/s13073-021-00849-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934395PMC
March 2021

Improved prediction of fracture risk leveraging a genome-wide polygenic risk score.

Genome Med 2021 02 3;13(1):16. Epub 2021 Feb 3.

Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Room H-413, 3755 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec, H3T 1E2, Canada.

Background: Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction.

Methods: We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors.

Results: A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13-1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727-0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791-0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072.

Conclusions: We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.
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http://dx.doi.org/10.1186/s13073-021-00838-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860212PMC
February 2021

Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study.

PLoS Med 2021 01 12;18(1):e1003487. Epub 2021 Jan 12.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom.

Background: Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD.

Methods And Findings: We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013-2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose-response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies.

Conclusions: In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.
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http://dx.doi.org/10.1371/journal.pmed.1003487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802951PMC
January 2021

Regional and seasonal variations in household and personal exposures to air pollution in one urban and two rural Chinese communities: A pilot study to collect time-resolved data using static and wearable devices.

Environ Int 2021 01 28;146:106217. Epub 2020 Oct 28.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK; MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, UK.

Background: Previous studies of the health impact of ambient and household air pollution (AAP/HAP) have chiefly relied on self-reported and/or address-based exposure modelling data. We assessed the feasibility of collecting and integrating detailed personal exposure data in different settings and seasons.

Methods/design: We recruited 477 participants (mean age 58 years, 72% women) from three (two rural [Gansu/Henan] and one urban [Suzhou]) study areas in the China Kadoorie Biobank, based on their previously reported fuel use patterns. A time-resolved monitor (PATS+CO) was used to measure continuously for 120-hour the concentration of fine particulate matter (PM) at personal and household (kitchen and living room) levels in warm (May-September 2017) and cool (November 2017-January 2018) seasons, along with questionnaires on participants' characteristics (e.g. socio-demographic, and fuel use) and time-activity (48-hour). Parallel local ambient monitoring of particulate matter (PM, PM and PM) and gaseous pollutants (CO, ozone, nitrogen oxides) was conducted using regularly-calibrated devices. The air pollution exposure data were compared by study sites and seasons.

Findings: Overall 76% reported cooking at least weekly (regular-cooks), and 48% (urban 1%, rural 65%) used solid fuels (wood/coal) for cooking. Winter heating was more common in rural sites than in urban site (74-91% vs 17% daily), and mainly involved solid fuels. Mixed use of clean and solid fuels was common for cooking in rural areas (38%) but not for heating (0%). Overall, the measured mean PM levels were 2-3 fold higher in the cool than warm season, and in rural (e.g. kitchen: Gansu = 142.3 µg/m; Gansu = 508.1 µg/m; Henan = 77.5 µg/m; Henan = 222.3 µg/m) than urban sites (Suzhou = 41.6 µg/m; Suzhou = 81.6 µg/m). The levels recorded tended to be the highest in kitchens, followed by personal, living room and outdoor. Time-resolved data show prominent peaks consistently recorded in the kitchen at typical cooking times, and sustained elevated PM levels (> 100 µg/m) were observed in rural areas where use of solid fuels for heating was common.

Discussion: Personal air pollution exposure can be readily assessed using a low-cost time-resolved monitor in different settings, which, in combination with other personal and health outcome data, will enable reliable assessment of the long-term health effects of HAP/AAP exposures in general populations.
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http://dx.doi.org/10.1016/j.envint.2020.106217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786640PMC
January 2021

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

Inj Prev 2020 10 24;26(Supp 1):i125-i153. Epub 2020 Aug 24.

Department of Pharmacy, Adigrat University, Adigrat, Ethiopia.

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria.

Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced.

Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes.

Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.
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http://dx.doi.org/10.1136/injuryprev-2019-043531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571362PMC
October 2020

Association of physical activity with risk of hepatobiliary diseases in China: a prospective cohort study of 0.5 million people.

Br J Sports Med 2021 Sep 21;55(18):1024-1033. Epub 2020 Aug 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China

Objective: There is limited prospective evidence on the association of physical activity with hepatobiliary cancer subtypes and other major hepatobiliary diseases, especially in China. We aimed to quantify the associations with risk of these diseases.

Methods: The study population involved 460 937 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without history of cancer or hepatobiliary disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with self-reported total and domain-specific physical activity (occupational and non-occupational, ie, leisure time, household and commuting).

Results: During ~10 years of follow-up, 22 012 incident cases of hepatobiliary diseases were recorded. The overall mean (SD) total physical activity was 21.2 (13.9) metabolic equivalent of task (MET)-hours/day, with 62% from occupational activity. Total physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease (HR comparing top vs bottom quintile: 0.62, 95% confidence interval (CI) 0.53 to 0.72), viral hepatitis (0.73, 95% CI 0.62 to 0.87), cirrhosis (0.76, 95% CI 0.66 to 0.88) and liver cancer (0.81, 95% CI 0.71 to 0.93), as well as gallstone disease (0.86, 95% CI 0.81 to 0.90), gallbladder cancer (0.51, 95% CI 0.32 to 0.80) and biliary tract cancer (0.55, 95% CI 0.38 to 0.78). The associations for occupational physical activity were similar to those for total physical activity, but for non-occupational physical activity they differed by disease subtype. For leisure-time physical activity, there was an inverse association with liver cancer and an inverse trend for gallstone disease (HR comparing ≥7.5 MET-hours/day with none: 0.83, 95% CI 0.75 to 0.91 and 0.82, 95% CI 0.66 to 1.01).

Conclusion: Among Chinese adults, high total physical activity, particularly occupational physical activity, was inversely associated with risk of major hepatobiliary cancers and diseases, including non-alcoholic fatty liver disease, cirrhosis and certain types of cancer.
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http://dx.doi.org/10.1136/bjsports-2020-102174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408581PMC
September 2021

Publisher Correction: Systemic inflammation is associated with incident stroke and heart disease in East Asians.

Sci Rep 2020 May 12;10(1):8084. Epub 2020 May 12.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-64764-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217894PMC
May 2020

Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017.

Inj Prev 2020 10 24;26(Supp 1):i96-i114. Epub 2020 Apr 24.

Faculty of Health Sciences - Health Management and Policy, American University of Beirut, Beirut, Lebanon.

Background: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries.

Methods: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs).

Findings: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505).

Interpretation: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.
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http://dx.doi.org/10.1136/injuryprev-2019-043494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571366PMC
October 2020

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

Ann Neurol 2020 07 7;88(1):56-66. Epub 2020 May 7.

Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.

Objective: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.

Methods: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses.

Results: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively.

Interpretation: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.
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http://dx.doi.org/10.1002/ana.25740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523882PMC
July 2020

Systemic inflammation is associated with incident stroke and heart disease in East Asians.

Sci Rep 2020 03 27;10(1):5605. Epub 2020 Mar 27.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Moreover, evidence is limited in non-European populations. We investigated associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a cohort of Chinese adults. A nested case-control study within the prospective China Kadoorie Biobank included 1,508 incident MCE cases, 5,418 IS cases, 4,476 ICH cases, and 5,285 common controls, aged 30-79 years. High-sensitivity CRP and low-density lipoprotein cholesterol (LDL-C) were measured in baseline plasma samples from all participants, and fibrinogen in a subset (n = 9,380). Logistic regression yielded adjusted odds ratios (ORs) per SD higher usual levels of log-transformed CRP and fibrinogen. The overall mean (SD) baseline LDL-C was 91.6 mg/dL (24.0) and geometric mean (95% CI) CRP and fibrinogen were 0.90 mg/L (0.87-0.93) and 3.01 g/L (2.98-3.03), respectively. There were approximately log-linear positive associations of CRP with each outcome, which persisted after adjustment for LDL-C and other risk factors, with adjusted ORs (95% CI) per SD higher CRP of 1.67 (1.44-1.94) for MCE and 1.22 (1.10-1.36) for both IS and ICH. No associations of fibrinogen with MCE, IS, or ICH were identified. Adding CRP to prediction models based on established risk factors improved model fit for each of MCE, IS, and ICH, with small improvements in C-statistic and correct reclassification of controls to lower risk groups. Among Chinese adults, who have low mean LDL-C, CRP, but not fibrinogen, was independently associated with increased risks of MCE and stroke.
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http://dx.doi.org/10.1038/s41598-020-62391-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101367PMC
March 2020

Socioeconomic differences in health-care use and outcomes for stroke and ischaemic heart disease in China during 2009-16: a prospective cohort study of 0·5 million adults.

Lancet Glob Health 2020 04;8(4):e591-e602

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Institute of Population Health Sciences, Queen Mary University of London, London, UK.

Background: China initiated major health-care reforms in 2009 aiming to provide universal health care for all by 2020. However, little is known about trends in health-care use and health outcomes across different socioeconomic groups in the past decade.

Methods: We used data from the China Kadoorie Biobank (CKB), a nationwide prospective cohort study of adults aged 30-79 years in 2004-08, in ten regions (five urban, five rural) in China. Individuals who were alive in 2009 were included in the present study. Data for all admissions were obtained by linkage to electronic hospital records from the health insurance system, and to region-specific disease and death registers. Generalised linear models were used to estimate trends in annual hospital admission rates, 28-day case fatality rates, and mean length of stay for stroke, ischaemic heart disease, and any cause in all relevant individuals.

Findings: 512 715 participants were recruited to the CKB between June 25, 2004, and July 15, 2008, 505 995 of whom were still alive on Jan 1, 2009, and contributed to the present study. Among them, we recorded 794 824 hospital admissions (74 313 for stroke, 69 446 for ischaemic heart disease) between 2009 and 2016. After adjustment for demographic, socioeconomic, lifestyle, and morbidity factors, hospitalisation rates increased annually by 3·6% for stroke, 5·4% for ischaemic heart disease, and 4·2% for any cause, between 2009 and 2016. Higher socioeconomic groups had higher hospitalisation rates, but the annual proportional increases were higher in those with lower education or income levels, those enrolled in the urban or rural resident health insurance scheme, and for those in rural areas. Lower socioeconomic groups had higher case fatality rates for stroke and ischaemic heart disease, but greater reductions in case fatality rates than higher socioeconomic groups. By contrast, mean length of stay decreased by around 2% annually for stroke, ischaemic heart disease, and any cause, but decreased to a greater extent in higher than lower socioeconomic groups for stroke and ischaemic heart disease.

Interpretation: Between 2009 and 2016, lower socioeconomic groups in China had greater increases in hospital admission rates and greater reductions in case fatality rates for stroke and ischaemic heart disease. Additional strategies are needed to further reduce socioeconomic differences in health-care use and disease outcomes.

Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and Chinese National Natural Science Foundation.
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http://dx.doi.org/10.1016/S2214-109X(20)30078-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090927PMC
April 2020

Neuroepidemiology Special Issue: Population-Based Epidemiological Studies of Neurological Disorders.

Neuroepidemiology 2020 25;54(2):95. Epub 2020 Feb 25.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Big Data Institute Building, Oxford, United Kingdom,

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http://dx.doi.org/10.1159/000505127DOI Listing
February 2021

Red meat, poultry and fish consumption and risk of diabetes: a 9 year prospective cohort study of the China Kadoorie Biobank.

Diabetologia 2020 04 22;63(4):767-779. Epub 2020 Jan 22.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK.

Aims/hypothesis: Previous evidence linking red meat consumption with diabetes risk mainly came from western countries, with little evidence from China, where patterns of meat consumption are different. Moreover, global evidence remains inconclusive about the associations of poultry and fish consumption with diabetes. Therefore we investigated the associations of red meat, poultry and fish intake with incidence of diabetes in a Chinese population.

Methods: The prospective China Kadoorie Biobank recruited ~512,000 adults (59% women, mean age 51 years) from ten rural and urban areas across China in 2004-2008. At the baseline survey, a validated interviewer-administered laptop-based questionnaire was used to collect information on the consumption frequency of major food groups including red meat, poultry, fish, fresh fruit and several others. During ~9 years of follow-up, 14,931 incidences of new-onset diabetes were recorded among 461,036 participants who had no prior diabetes, cardiovascular diseases or cancer at baseline. Cox regression analyses were performed to calculate adjusted HRs for incident diabetes associated with red meat, poultry and fish intake.

Results: At baseline, 47.0%, 1.3% and 8.9% of participants reported a regular consumption (i.e. ≥4 days/week) of red meat, poultry and fish, respectively. After adjusting for adiposity and other potential confounders, each 50 g/day increase in red meat and fish intake was associated with 11% (HR 1.11 [95% CI 1.04, 1.20]) and 6% (HR 1.06 [95% CI 1.00, 1.13]) higher risk of incident diabetes, respectively. For both, the associations were more pronounced among men and women from urban areas, with an HR (95% CI) of 1.42 (1.15, 1.74) and 1.18 (1.03, 1.36), respectively, per 50 g/day red meat intake and 1.15 (1.02, 1.30) and 1.11 (1.01, 1.23), respectively, per 50 g/day fish intake. There was no significant association between diabetes and poultry intake, either overall (HR 0.96 [95% CI 0.83, 1.12] per 50 g/day intake) or in specific population subgroups.

Conclusions/interpretation: In Chinese adults, both red meat and fish, but not poultry, intake were positively associated with diabetes risk, particularly among urban participants. Our findings add new evidence linking red meat and fish intake with cardiometabolic diseases.

Data Availability: Details of how to access the China Kadoorie Biobank data and rules of China Kadoorie Biobank data release are available from www.ckbiobank.org/site/Data+Access.
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http://dx.doi.org/10.1007/s00125-020-05091-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054352PMC
April 2020

Morbidity and mortality from road injuries: results from the Global Burden of Disease Study 2017.

Inj Prev 2020 10 8;26(Supp 1):i46-i56. Epub 2020 Jan 8.

Department of Public Health, Mizan-Tepi University, Teppi, Ethiopia.

Background: The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years.

Methods: We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury.

Results: Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change.

Conclusions: While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.
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http://dx.doi.org/10.1136/injuryprev-2019-043302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571357PMC
October 2020

Burden of injury along the development spectrum: associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017.

Inj Prev 2020 10 8;26(Supp 1):i12-i26. Epub 2020 Jan 8.

School of Public Health, Auckland University of Technology, Auckland, New Zealand.

Background: The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates.

Methods: Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate.

Results: For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced.

Conclusions: The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.
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http://dx.doi.org/10.1136/injuryprev-2019-043296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571356PMC
October 2020

Physical activity, sedentary leisure-time and risk of incident type 2 diabetes: a prospective study of 512 000 Chinese adults.

BMJ Open Diabetes Res Care 2019 18;7(1):e000835. Epub 2019 Dec 18.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: Aim to examine the independent and joint associations of physical activity (PA) and sedentary leisure-time (SLT) with risk of diabetes and assess the extent to which these associations were mediated by adiposity.

Research Design And Methods: The prospective China Kadoorie Biobank recruited ~512 000 adults from 10 diverse areas across China. Self-reported PA was estimated based on type, frequency and duration of specific types of PA, covering four domains (occupation, leisure, household and commuting). SLT was defined as hours per day spent watching television, reading or playing card games. Stratified Cox proportional hazards models were used to estimate adjusted HRs (aHRs) for PA and SLT associated with incident diabetes. Analyses were stratified by age-at-risk (5-year intervals), sex and region and adjusted for household income, education, alcohol consumption, smoking, fresh fruit intake, self-reported general health status, family history of diabetes and body mass index (BMI) status. Analyses of total PA, occupational and non-occupational PA and SLT were mutually adjusted for each other, as appropriate.

Results: After ~9 years of follow-up, there were 14 940 incident diabetes cases among 460 736 participants without prior diabetes or cardiovascular diseases at baseline. The mean (SD) age at baseline was 51 (10.6) years, 59% were women and 43% resided in urban areas. Overall, the mean BMI was 23.5 (3.3) kg/m, which differed by ~0.5 kg/m among individuals in the highest compared with the lowest PA and SLT groups. PA was inversely associated the risk of diabetes 16% (aHR: 0.84, 95% CI 0.81 to 0.88) lower in top than bottom fifth. After further adjustment for BMI this was attenuated to 0.99 (95% CI 0.98 to 1.00). SLT was positively associated with diabetes and each 1 hour per day higher usual level was associated with aHR of 1.13 (95% CI 1.09 to 1.17) for diabetes, attenuated to 1.05 (95% CI 1.01 to 1.09) after further adjustment for BMI.

Conclusions: Among Chinese adults, higher levels of PA and lower levels of SLT were associated with lower risks of diabetes with no evidence of effect modification by each other. These associations appeared to arise mainly through adiposity.
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http://dx.doi.org/10.1136/bmjdrc-2019-000835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936425PMC
September 2020

Menopause and risk of hip fracture in middle-aged Chinese women: a 10-year follow-up of China Kadoorie Biobank.

Menopause 2020 03;27(3):311-318

Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Old Road Campus, Oxford, United Kingdom.

Objective: Bone loss is accelerated after menopause in women, as is the risk of hip fracture, but little is known about the importance of age at menopause, time since menopause, and total reproductive years for risk of hip fracture.

Methods: Between 2004 and 2008, the China Kadoorie Biobank recruited 125,336 postmenopausal women who had a natural menopause and recorded 1,327 incident cases of hip fracture during the first 10 years of follow-up. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for incident hip fracture for age at menopause, time since menopause, and total reproductive years.

Results: The mean (SD) age at menopause was 48.8 (4.0) years. Compared with women who reached menopause before age 53 years, women with a later age at menopause had a 22% (95% CI, 11%-35%) lower risk of hip fracture. Compared with women who were <5 years since menopause, those who were 5 to 9, 10 to 14, 15 to 19, and ≥20 years since menopause had hazard ratios of hip fracture of 1.43 (95% CI, 1.01-2.04), 2.10 (95% CI, 1.71-2.57), 2.50 (95% CI, 2.21-2.83), and 2.33 (95% CI, 1.97-2.75), respectively. Women with a longer (≥36 y) versus shorter (<30 y) duration of total reproductive years had a 19% (95% CI, 9-28) lower risk of hip fracture.

Conclusions: Women with younger age at menopause, longer interval since menopause, or shorter duration of total reproductive years had the highest risks of hip fracture.
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http://dx.doi.org/10.1097/GME.0000000000001478DOI Listing
March 2020

Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis.

JAMA Netw Open 2019 12 2;2(12):e1917789. Epub 2019 Dec 2.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Importance: Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness.

Objective: To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs.

Data Sources: PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018.

Study Selection: Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control.

Data Extraction And Synthesis: Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019.

Main Outcomes And Measures: Any fracture and hip fracture.

Results: In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97).

Conclusions And Relevance: In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.17789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991219PMC
December 2019

Reproducibility of dietary intakes of macronutrients, specific food groups, and dietary patterns in 211 050 adults in the UK Biobank study.

J Nutr Sci 2019 29;8:e34. Epub 2019 Oct 29.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

To detect modest associations of dietary intake with disease risk, observational studies need to be large and control for moderate measurement errors. The reproducibility of dietary intakes of macronutrients, food groups and dietary patterns (vegetarian and Mediterranean) was assessed in adults in the UK Biobank study on up to five occasions using a web-based 24-h dietary assessment ( 211 050), and using short FFQ recorded at baseline ( 502 655) and after 4 years ( 20 346). When the means of two 24-h assessments were used, the intra-class correlation coefficients (ICC) for macronutrients varied from 0·63 for alcohol to 0·36 for polyunsaturated fat. The ICC for food groups also varied from 0·68 for fruit to 0·18 for fish. The ICC for the FFQ varied from 0·66 for meat and fruit to 0·48 for bread and cereals. The reproducibility was higher for vegetarian status (κ > 0·80) than for the Mediterranean dietary pattern (ICC = 0·45). Overall, the reproducibility of pairs of 24-h dietary assessments and single FFQ used in the UK Biobank were comparable with results of previous prospective studies using conventional methods. Analyses of diet-disease relationships need to correct for both measurement error and within-person variability in dietary intake in order to reliably assess any such associations with disease in the UK Biobank.
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http://dx.doi.org/10.1017/jns.2019.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842574PMC
July 2020

Solid fuels for cooking and tobacco use and risk of major chronic liver disease mortality: a prospective cohort study of 0.5 million Chinese adults.

Int J Epidemiol 2020 02;49(1):45-55

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Harmful substances in solid fuel and tobacco smoke are believed to enter the bloodstream via inhalation and to be metabolized in the liver, leading to chronic liver damage. However, little is known about the independent and joint effects of solid fuel use and smoking on risks of chronic liver disease (CLD) mortality.

Methods: During 2004-08, ∼0.5 million adults aged 30-79 years were recruited from 10 areas across China. During a 10-year median follow-up, 2461 CLD deaths were recorded. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the individual associations of self-reported long-term cooking fuel and tobacco use with major CLD death.

Results: Overall, 49% reported solid fuel use and 26% smoked regularly. Long-term solid fuel use for cooking and current smoking were associated with higher risks of CLD deaths, with adjusted HRs of 1.26 (95% CI, 1.02-1.56) and 1.28 (1.13-1.44), respectively. Compared with never-smoking clean fuel users, the HRs were 1.41 (1.10-1.82) in never-smoking solid fuel users, 1.55 (1.17-2.06) in regular-smoking clean fuel users and 1.71 (1.32-2.20) in regular-smoking solid fuels users. Individuals who had switched from solid to clean fuels (1.07, 0.90-1.29; for median 14 years) and ex-regular smokers who stopped for non-medical reasons (1.16, 0.95-1.43; for median 10 years) had no evidence of excess risk of CLD deaths compared with clean fuel users and never-regular smokers, respectively.

Conclusions: Among Chinese adults, long-term solid fuel use for cooking and smoking were each independently associated with higher risks of CLD deaths. Individuals who had stopped using solid fuels or smoking had lower risks.
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http://dx.doi.org/10.1093/ije/dyz216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124491PMC
February 2020

Measuring stroke and transient ischemic attack burden in New Zealand: Protocol for the fifth Auckland Regional Community Stroke Study (ARCOS V).

Int J Stroke 2020 07 24;15(5):573-583. Epub 2019 Oct 24.

Centre for Public Health Research, Massey University, Wellington, New Zealand.

The goal of this paper is to provide a protocol for conducting a fifth population-based Auckland Regional Community Stroke study (ARCOS V) in New Zealand. : In this study, for the first time globally, (1) stroke and TIA burden will be determined using the currently used clinical and tissue-based definition of stroke, in addition to the WHO clinical classifications of stroke used in all previous ARCOS studies, as well as more advanced criteria recently suggested for an "ideal" population-based stroke incidence and outcomes study; and (2) age, sex, and ethnic-specific trends in stroke incidence and outcomes will be determined over the last four decades, including changes in the incidence of acute cerebrovascular events over the last decade. Furthermore, information at four time points over a 40-year period will allow the assessment of effects of recent changes such as implementation of the FAST campaign, ambulance pre-notification, and endovascular treatment. This will enable more accurate projections for health service planning and delivery. The methods of this study will provide a foundation for future similar population-based studies in other countries and populations.
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http://dx.doi.org/10.1177/1747493019884528DOI Listing
July 2020

Physical Activity, Sedentary Leisure Time, Circulating Metabolic Markers, and Risk of Major Vascular Diseases.

Circ Genom Precis Med 2019 09 28;12(9):386-396. Epub 2019 Aug 28.

Clinical Trial Service Unit and Epidemiological Studies Unit (Y.P., C.K., H.D., I.Y.M., Y.C., L.Y., R.W., F.B., R.P., R. Clarke, R. Collins, D.A.B., L.L., M.V.H., Z.C.), Nuffield Department of Population Health, University of Oxford, United Kingdom.

Background: Physical inactivity and sedentary behavior are associated with higher risk of cardiovascular disease (CVD). Little is known about the relevance of circulating metabolites for these associations.

Methods: A nested case-control study within the prospective China Kadoorie Biobank included 3195 incident CVD cases (2057 occlusive CVD and 1138 intracerebral hemorrhage) and 1465 controls aged 30 to 79 years without prior CVD or statin use at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers and derived traits in baseline plasma samples. Linear regression was used to relate self-reported physical activity and sedentary leisure time to biomarkers, adjusting for potential confounders. These were contrasted with associations of biomarkers with occlusive CVD risk.

Results: Physical activity and sedentary leisure time were associated with >100 metabolic markers, with patterns of associations generally mirroring each other. Physical activity was inversely associated with very low and low-density and positively with large and very large HDL (high-density lipoprotein) particle concentrations. Physical activity was also inversely associated with alanine, glucose, lactate, acetoacetate, and the inflammatory marker glycoprotein acetyls. In general, associations of physical activity and sedentary leisure time with specific metabolic markers were directionally consistent with the associations of these metabolic markers with occlusive CVD risk. Overall, metabolic markers potentially explained ≈70% of the protective associations of physical activity and ≈50% of the positive associations of sedentary leisure time with occlusive CVD.

Conclusions: Among Chinese adults, physical activity and sedentary behavior have opposing associations with a diverse range of circulating metabolites, which may partially explain their associations with CVD risk.
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http://dx.doi.org/10.1161/CIRCGEN.118.002527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752700PMC
September 2019
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