Associations of soy product intake with all-cause, cardiovascular disease and cancer mortality: Guangzhou Biobank Cohort Study and updated meta-analyses.

PURPOSE: We examined the associations of soy product intake with all-cause, cardiovascular disease (CVD), and cancer mortality and mediations through CVD risk factors based on the Guangzhou Biobank Cohort Study (GBCS), and conducted updated meta-analyses. METHODS: A total of 29,825 participants aged 50 + years were included. Causes of death were identified through record linkage. Soy product intake was assessed by food frequency questionnaire. Cox proportional hazards regression was used to analyze the associations between soy product intake and mortality, yielding hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses with CVD risk factors as mediators, and updated meta-analyses were conducted. RESULTS: During 454,689 person-years of follow-up, 6899 deaths occurred, including 2694 CVD and 2236 cancer. Participants who consumed soy product of 1-6 portions/week, versus no consumption, had significantly lower risks of all-cause and CVD mortality (adjusted HR (95% CI) 0.91 (0.86, 0.97) and 0.87 (0.79, 0.96), respectively). In participants who consumed soy product of ≥ 7 portions/week, the association of higher intake with lower CVD mortality was modestly mediated by total cholesterol (4.2%, 95% CI 1.0-16.6%). Updated meta-analyses showed that the highest level of soy product intake, versus the lowest, was associated with lower risks of all-cause and CVD mortality (pooled HR (95% CI) 0.92 (0.88, 0.96) and 0.92 (0.87, 0.98), respectively). CONCLUSION: Moderate and high soy product intake were associated with lower risks of all-cause and CVD mortality. Our findings provide support for current dietary guidelines recommending moderate soy product intake, and contribute additional evidence regarding the potential protective effects of high soy product intake.

Quantity and Variety in Fruit and Vegetable Consumption and Mortality in Older Chinese: A 15-year Follow-Up of a Prospective Cohort Study.

BACKGROUND: Independent associations of quantity and variety of fruit and vegetables (FVs) with mortality in older people are still unclear. OBJECTIVES: This study aimed to explore the association between the quantity and variety in FV consumption and mortality in older Chinese. METHODS: A total of 19,597 participants of the Guangzhou Biobank Cohort Study aged >50 y were recruited from 2003 to 2006 and followed up until April 2021. The diet was assessed using a 300-item validated FFQ. Variety as a continuous variable was defined as the number of unique FV items (excluding potatoes, legumes, and fruit juices) intake per week over the past week. The associations of quantity and variety of FVs with mortality were analyzed, and analyses by the color of edible parts was performed. Multivariable Cox regression yielded HRs and 95% CIs. RESULTS: During 286,821 person-year of follow-up, 4385 deaths occurred, including 1678 cardiovascular diseases (CVD), 1450 cancer, and 1257 other causes. Compared with the lowest quintile of variety in FV, the highest quintile was associated with lower risks of all-cause (HR: 0.81; 95% CI: 0.73-0.89) and CVD mortality (HR: 0.79; 95% CI 0.67-0.92). A greater variety of green and white FV intake was associated with lower risks of all-cause and CVD morality, and a greater variety of red/purple FV intake was associated with lower risks of all-cause and cancer mortality. However, the quantity of FV intake showed no association with all-cause, CVD, and cancer mortality. CONCLUSION: Our findings have first showed that the variety, rather than quantity, in FV intake was associated with a lower risk of mortality in older Chinese. Dietary guidelines may recommend increasing the variety in FV intake, especially green, red/purple, and white FVs in older people.

Timing of infant formula introduction in relation to BMI and overweight at ages 1 and 3 years: the Born in Guangzhou Cohort Study (BIGCS).

Mounting evidence suggests that the first few months of life are critical for the development of obesity. The relationships between the timing of solid food introduction and the risk of childhood obesity have been examined previously; however, evidence for the association of timing of infant formula introduction remains scarce. This study aimed to examine whether the timing of infant formula introduction is associated with growth z-scores and overweight at ages 1 and 3 years. This study included 5733 full-term (≥ 37 gestational weeks) and normal birth weight (≥ 2500 and < 4000 g) children in the Born in Guangzhou Cohort Study, a prospective cohort study with data collected at 6 weeks, 6, 12 and 36 months. Compared with infant formula introduction at 0-3 months, introduction at 4-6 months was associated with the lower BMI, weight-for-age and weight-for-length z-scores at 1 and 3 years old. Also, introduction at 4-6 months was associated with the lower odds of at-risk of overweight at age 1 (adjusted OR 0·72, 95 % CI 0·55, 0·94) and 3 years (adjusted OR 0·50, 95 % CI 0·30, 0·85). Introduction at 4-6 months also decreased the odds of overweight at age 1 year (adjusted OR 0·42, 95 % CI 0·21, 0·84) but not at age 3 years. Based on our findings, compared with introduction within the first 3 months, introduction at 4-6 months has a reduction on later high BMI risk and at-risk of overweight. However, these results need to be replicated in other well-designed studies before more firm recommendations can be made.

Cereal intake and mortality in older Chinese: a 15-year follow-up of a prospective cohort study.

PURPOSE: We examined the association between whole grain and refined grain intake with all-cause, cancer and cardiovascular disease (CVD) mortality using the data from the Guangzhou Biobank Cohort Study. METHODS: 19,597 participants aged 50+ years were recruited from 2003 to 2006 and followed-up until April 2021. Multivariable Cox regression was used to calculate hazard radios (HRs) and 95% confidence intervals (CIs). Substitution analysis was used to replace a serving (50 g/day) of whole grain with a serving of refined grain. RESULTS: During 286,821 person-years of follow-up, 4385 deaths occurred, including 1450 from cancer, 1678 from CVD and 1257 from other causes. Compared with never whole grain intake, the highest intake category of whole grain (> 300 g/week) was associated with lower risk of all-cause (HR 0.90, 95% CI 0.82-0.98) and CVD mortality (HR 0.85, 0.74-0.98). Compared with the low-intake category of refined grain (< 500 g/day), the highest intake category (> 900 g/week) was associated with a lower risk of cancer mortality (HR 0.76, 0.62-0.95), but a higher risk of CVD mortality (HR 1.25, 1.03-1.51). No significant associations were found between whole grain intake and cancer mortality nor refined grain and all-cause mortality. The HRs of all-cause, cancer and CVD mortality substituting a serving of whole grain for refined grain were 0.96 (0.94-0.99), 1.01 (0.99-1.02) and 0.95 (0.90-0.99), respectively. CONCLUSION: We have first shown that in older Chinese, whole grain intake was associated with lower risk of all-cause and CVD mortality. Our results suggest that intake of whole grain of at least 300 g/week and refined grain of ≤ 900 g/day might be suitable for older Asian. Substituting 50 g/day of whole grain for refined grain was associated with a 4-5% lower risk of all-cause and CVD mortality.

Association of Multi-Dimensional Factors with Accelerating Age and Constructing a Healthy Lifestyle Index: Guangzhou Biobank Cohort Study.

INTRODUCTION: Ageing process is influenced by multi-dimensional factors collectively. Previous studies examined association of one separate factor with mortality without considering different manifestations of ageing process. We investigated associations of multi-dimensional factors with accelerating age (AA), a proxy to quantify ageing, in older Chinese. METHODS: 9,831 participants from Guangzhou Biobank Cohort Study were included. Four exposure domains of 15 variables including demographic and socio-economic factors, lifestyle factors, stress across the life course, and common diseases were assessed. AA was calculated based on chronological age and eight biomarkers. Traditional multivariable linear and Bayesian Network (BN) models were used. RESULTS: In both traditional and BN models, male sex, smoking, alcohol use, physical inactivity, greater waist circumference, and body mass index (BMI) were associated with higher AA, with the adjusted ß (95% confidence intervals) being 2.75 (2.40-3.09), 1.31 (0.87-1.76), 1.35 (0.55-2.15), 0.64 (0.40-0.88), 0.09 (0.06-0.11), and 0.13 (0.07-0.19) years, respectively. A Healthy Lifestyle Index (HLI) was constructed including the above lifestyle factors (non-smoking, non-alcohol use, physically active, non-central, and non-general obesity) with a point assigned for each. A higher index indicates healthier lifestyle. Compared with participants with an HLI of 5, those with an HLI of 0-2 had 2.90 (2.48-3.32) years older AA. CONCLUSIONS: Male sex, smoking, alcohol use, physical inactivity, greater waist circumference, and BMI were associated with higher AA by 0.09-2.75 years, suggesting that adopting a healthy lifestyle may alleviate process of phenotypic ageing.

Associations of daytime napping and nighttime sleep quality with depressive symptoms in older Chinese: the Guangzhou biobank cohort study.

BACKGROUND: Poor sleep quality has been linked to depression in older adults, but results of the association between daytime napping and depression remains limited and conflicting. Moreover, whether the association of daytime napping with depression varies by nighttime sleep quality is unclear. Hence, we examined the associations of daytime napping and nighttime sleep quality with depressive symptoms in older Chinese. METHODS: A total of 16,786 participants aged ≥50 from the Guangzhou Biobank Cohort Study second-round examination (2008-2012) were included in this cross-sectional study. Geriatric Depression Scale (GDS-15), Pittsburgh Sleep Quality Index (PSQI), napping and demographic data were collected by face-to-face interview using a computerized questionnaire. Logistic regression was used to calculate odds ratio (OR) of depressive symptoms for napping and sleep quality. RESULTS: The prevalence of depressive symptoms (GDS score > 5) and poor global sleep quality (PSQI score ≥ 6) was 5.3 and 31.9%, respectively. Compared to non-nappers, nappers showed significantly higher odds of depressive symptoms, with OR (95% confidence interval (CI)) being 1.28 (1.11-1.49). The odds of depressive symptoms for daytime napping varied by nighttime sleep quality (P for interaction = 0.04). In good-quality sleepers, compared to non-nappers, nappers had significantly higher odds of depressive symptoms, with OR (95% CI) being 1.57 (1.23-2.01), whereas no association was found in poor-quality sleepers (OR = 1.13, 0.94-1.36). CONCLUSION: Napping was associated with higher odds of depressive symptoms in older people, and the association was stronger in good-quality sleepers.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

Polypill for prevention of cardiovascular diseases with focus on non-alcoholic steatohepatitis: the PolyIran-Liver trial.

AIMS: Individuals with non-alcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy for the prevention of major cardiovascular events (MCVE) among individuals with and without presumed non-alcoholic steatohepatitis (pNASH). METHODS AND RESULTS: Two thousand four hundred participants over 50 were randomized into the intervention and control groups. Consent was obtained post-randomization. Consenting participants in the intervention group were given a pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (polypill). Participants were followed for 5 years. Presumed non-alcoholic steatohepatitis was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov: NCT01245608. Among the originally randomized population, 138 of 1249 in the intervention group (11.0%) and 137 of 1017 controls (13.5%) had MCVE during the 5-year follow-up [unadjusted risk ratio (RR) 0.83, 95% confidence interval (CI) 0.66-1.03]. Of the 1508 participants who consented to additional measurements and treatment, 63 of 787 (8.0%) intervention group participants and 86 of 721 (11.9%) controls had MCVE (adjusted RR 0.61, 95% CI 0.44-0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95% CI 0.17-0.74) was under half that for participants without pNASH (0.73, 95% CI 0.49-1.00), the difference did not reach statistical significance. There was no change in liver enzymes in participants taking polypill but among those with pNASH, there was a significant decrease after 60 months of follow-up (intragroup -12.0 IU/L, 95% CI -14.2 to -9.6). CONCLUSION: Among patients consenting to receive fixed-dose combination therapy, polypill is safe and effective for the prevention of MCVE, even among participants with fatty liver and increased liver enzymes.

Associations of face-to-face and non-face-to-face social isolation with all-cause and cause-specific mortality: 13-year follow-up of the Guangzhou Biobank Cohort study.

BACKGROUND: Although social isolation has been associated with a higher mortality risk, little is known about the potential different impacts of face-to-face and non-face-to-face isolation on mortality. We examined the prospective associations of four types of social isolation, including face-to-face isolation with co-inhabitants and non-co-inhabitants, non-face-to-face isolation, and club/organization isolation, with all-cause and cause-specific mortality separately. METHODS: This prospective cohort study included 30,430 adults in Guangzhou Biobank Cohort Study (GBCS), who were recruited during 2003-2008 and followed up till Dec 2019. RESULTS: During an average of 13.2 years of follow-up, 4933 deaths occurred during 396,466 person-years. Participants who lived alone had higher risks of all-cause (adjusted hazard ratio (AHR) 1.24; 95% confidence interval (CI) 1.04-1.49) and cardiovascular disease (CVD) (1.61; 1.20-2.03) mortality than those who had ≥ 3 co-habitant contact after adjustment for thirteen potential confounders. Compared with those who had ≥ 1 time/month non-co-inhabitant contact, those without such contact had higher risks of all-cause (1.60; 1.20-2.00) and CVD (1.91; 1.20-2.62) mortality. The corresponding AHR (95% CI) in participants without telephone/mail contact were 1.27 (1.14-1.42) for all-cause, 1.30 (1.08-1.56) for CVD, and 1.37 (1.12-1.67) for other-cause mortality. However, no association of club/organization contact with the above mortality and no association of all four types of isolation with cancer mortality were found. CONCLUSIONS: In this cohort study, face-to-face and non-face-to-face isolation were both positively associated with all-cause, CVD-, and other-cause (but not cancer) mortality. Our finding suggests a need to promote non-face-to-face contact among middle-aged and older adults.

Association of alcohol drinking with incident type 2 diabetes and pre-diabetes: The Guangzhou Biobank Cohort Study.

AIMS: We examined associations of baseline alcohol drinking with incident type 2 diabetes (T2D) or impaired fasting glucose (IFG), and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B). MATERIALS AND METHODS: All participants were aged 50+ (mean = 60.45; standard deviation = 6.88) years. Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident T2D was defined as fasting glucose ≥7.0 mmol/L or post-load glucose ≥11.1 mmol/L at follow-up examination (2008-2012), self-reported T2D and/or initiation of hypoglycaemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6 mmol/L and <7 mmol/L. RESULTS: Of 15,716 participants without diabetes and 11,232 participants without diabetes and IFG at baseline, 1624 (10.33%) developed incident T2D and 1004 (8.94%) developed incident IFG during an average 4 years of follow-up. After multivariable adjustments, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident hyperglycaemia (T2D + IFG) (odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.95-1.27, and 0.90 (0.69-1.18), respectively), whereas heavy alcohol drinking was associated with a higher risk of incident hyperglycaemia (T2D + IFG) (OR = 1.82, 95% CI 1.24-2.68). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B/ALDH2 genes with alcohol drinking on incident T2D and/or IFG were found (P for interaction from 0.12 to 0.85). CONCLUSIONS: Our results support a detrimental effect of heavy alcohol use on IFG and T2D. No protective effect was found for those carrying lower risk alleles for ADH1B/ALDH2 genes.

Association of alcohol use with memory decline in middle-aged and older Chinese: a longitudinal cohort study.

BACKGROUND: Previous studies on associations of alcohol use with memory decline showed inconclusive results. We examined these associations using longitudinal data from the Guangzhou Biobank Cohort Study (GBCS) and explored whether these associations varied by sex and age group. METHODS: Memory function was assessed by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT) at both baseline (2003-2008) and follow-up (2008-2012) examinations, expressed as the mean annual change and mean annual rate of change in scores. Memory cognitive impairment was defined by DWRT scores of less than 4. Multivariable linear regression models and restricted cubic spline were used for data analysis. RESULTS: Of 14,827 participants without memory cognitive impairment at baseline, 90.2% were never or occasional drinkers, 5% moderate drinkers, 1.5% excessive drinkers, and 3.3% former drinkers. The mean (standard deviation) age was 60.6 (6.6) years old. During an average of 4.1 years follow-up, 1000 (6.7%) participants developed memory cognitive impairment. After adjusting for confounders, compared with never or occasional drinkers, moderate and excessive drinkers had significant decline in DWRT scores (ß, 95% confidence interval (CI) = -0.04 (-0.08 to -0.01), and - 0.07 (-0.14 to 0.01), respectively), and IWRT scores (ß, 95% CI = -0.10 (-0.19 to -0.01), and - 0.15 (-0.30 to 0.01), respectively) annually. With respect to the mean annual rate of change, moderate and excessive drinkers also showed greater decline in DWRT scores (ß, 95% CI = -1.02% (-1.87% to -0.16%), and - 1.64% (-3.14% to -0.14%), respectively). The associations did not vary by sex and age group (all P values for interaction ≥ 0.10). CONCLUSION: Compared to never or occasional alcohol use, moderate and excessive alcohol users had greater memory decline and the associations did not vary by sex and age group.

Obesity indicators as mediators of association between daytime napping and type 2 diabetes mellitus: the Guangzhou Biobank Cohort Study.

OBJECTIVE: To examine the mediating effect of obesity indicators on the association between daytime napping and type 2 diabetes mellitus (T2DM) qualitatively and quantitatively using baseline data from the Guangzhou Biobank Cohort Study. METHODS: Twenty-nine thousand three hundred fifty-five participants aged 50+ years were included in this cross-sectional study. Mediation analysis was used to assess the mediating effect of body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) on the association between daytime napping and T2DM after adjustment for sex, age, education, occupation, smoking status, alcohol use and physical activity. RESULTS: The mean (standard deviation) age of participants was 61.5 ( 7.1) years. The prevalence of T2DM and daytime napping was 12.5% and 65.2%, respectively. After adjustment for potential confounders, WC, WHR and WHtR showed partial mediating effects on the association between daytime napping and T2DM, with the proportion (95% confidence interval) of mediation effect being 10.17% (8.14-14.43%), 14.91% (11.95-21.24%) and 9.36% (7.49-13.29%), respectively. No mediating effect of BMI or HC on the association between daytime napping and T2DM was found. CONCLUSIONS: Our results showed significant mediating effects of WC, WHR and WHtR on the association between daytime napping and T2DM, suggesting that waist circumference management could be important in daytime nappers.

Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

BACKGROUND AND PURPOSE: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. METHODS: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. RESULTS: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]). CONCLUSIONS: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

Brain-derived neurotrophic factor gene variants and obesity in former smokers.

OBJECTIVE: From genome-wide association studies, brain-derived neurotrophic factor (BDNF) locus on chromosome 11 was the only SNP associated with both smoking and body mass index (BMI) in European, African and Asian population. This study aims to explore the unique genetic predisposition to obesity in former smokers by examining the effects of BDNF on BMI and waist circumference (WC). METHODS: The study design is case-control study with a cohort validation in supplementary. We included 15,072 ethnic Chinese participants in the Guangzhou Biobank Cohort Study (GBCS) with data of four BDNF SNPs related to both BMI and smoking behavior. We used baseline smoke exposure data in 2003-2007 and follow-up outcomes of general obesity (by BMI) and central obesity (WC) in 2008-2012. Odds ratios (ORs) and 95% confidence intervals (CIs) for general obesity and central obesity associated with these SNPs were derived from logistic regression. RESULTS: Of 15,072 participants (3169 men and 11,903 women), 1664 (11.0%) had general and 7868 (52.2%) had central obesity. In 1233 former smokers, the rs6265 GG, versus AA, genotype was associated with higher risks of general obesity (OR = 1.79, 95% CI = 1.06-3.01) and central obesity (OR = 2.08, 95% CI = 1.47-2.92) after adjustment. These associations were not significant in never or current smokers. In former heavy (≥20 cigarettes/day) smokers, the rs6265 GG genotype showed a higher odds for general obesity (OR = 2.15, 95% CI = 1.05-4.40), while no association was found in former light (1-9 cigarettes/day) smokers. Similar results were found for the association of rs6265 with central obesity and for the associations of other two BDNF SNPs (rs4923457 and rs11030104) with both general and central obesity. CONCLUSIONS: We firstly identified the genetic predisposition (BDNF SNPs) to general and central obesity in former smokers, particularly in former heavy smokers. The different associations of the SNPs for general/central obesity in different smoke exposure groups may be related to the competitive performance of the sites and epigenetic modification, which needs further study.

Quality of primary health care in China: challenges and recommendations.

China has substantially increased financial investment and introduced favourable policies for strengthening its primary health care system with core responsibilities in preventing and managing chronic diseases such as hypertension and emerging infectious diseases such as coronavirus disease 2019 (COVID-19). However, widespread gaps in the quality of primary health care still exist. In this Review, we aim to identify the causes for this poor quality, and provide policy recommendations. System challenges include: the suboptimal education and training of primary health-care practitioners, a fee-for-service payment system that incentivises testing and treatments over prevention, fragmentation of clinical care and public health service, and insufficient continuity of care throughout the entire health-care system. The following recommendations merit consideration: (1) enhancement of the quality of training for primary health-care physicians, (2) establishment of performance accountability to incentivise high-quality and high-value care; (3) integration of clinical care with the basic public health services, and (4) strengthening of the coordination between primary health-care institutions and hospitals. Additionally, China should consider modernising its primary health-care system through the establishment of a learning health system built on digital data and innovative technologies.

Prevalence of congenital microcephaly and its risk factors in an area at risk of Zika outbreaks.

BACKGROUND: Prevalence of neonatal microcephaly in populations without Zika-epidemics is sparse. The study aimed to report baseline prevalence of congenital microcephaly and its relationship with prenatal factors in an area at risk of Zika outbreak. METHODS: This study included singletons born after 24 gestational weeks in 2017-2018 at four hospitals in Guangzhou, China. Microcephaly was defined as a head circumference at birth >3SD below the mean for sex and gestational age. Prevalence of microcephaly was estimated by binomial exact method. Multivariable logistic regression was used to examine the associations of microcephaly with prenatal factors. The population attributable fraction (PAF) for associated risk factors was calculated. RESULTS: Of 46,610 live births included, 154 (3.3, 95% CI 2.8-3.9 per 1000 live births) microcephalies were identified. Maternal hepatitis B virus carriers (HBV, OR 1.80, 95% CI 1.05-3.10) and primipara (OR 2.68, 95% CI 1.89-3.81) had higher risk of having a microcephalic baby. Higher prevalence of microcephaly was observed in women who had premature labor (OR 1.98, 95% CI 1.17-3.34) and had a baby with fetal growth restriction (OR 16.38, 95% CI 11.81-22.71). Four identified factors (HBV, primiparity, preterm labor, and fetal growth restriction) contributed to 66.4% of the risk of microcephaly. CONCLUSIONS: The prevalence of microcephaly in Guangzhou was higher than expected. This study identified four prenatal risk factors that, together, contributed to two-thirds of the increased risk of microcephaly. This is the first reported association between maternal HBV carrier status and microcephaly.

The impact of training healthcare professionals' communication skills on the clinical care of diabetes and hypertension: a systematic review and meta-analysis.

BACKGROUND: Diabetes and hypertension care require effective communication between healthcare professionals and patients. Training programs may improve the communication skills of healthcare professionals but no systematic review has examined their effectiveness at improving clinical outcomes and patient experience in the context of diabetes and hypertension care. METHODS: We conducted a systematic review of randomized controlled trials to summarize the effectiveness of any type of communication skills training for healthcare professionals to improve diabetes and/or hypertension care compared to no training or usual care. We searched Medline, Embase, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform from inception to August 2020 without language restrictions. Data on the country, type of healthcare setting, type of healthcare professionals, population, intervention, comparison, primary outcomes of glycated hemoglobin (HbA1c) and blood pressure, and secondary outcomes of quality of life, patient experience and understanding, medication adherence and patient-doctor relationship were extracted for each included study. Risk of bias of included studies was assessed by Cochrane risk of bias tool. RESULTS: 7011 abstracts were identified, and 19 studies met the inclusion criteria. These included a total of 21,762 patients and 785 health professionals. 13 trials investigated the effect of communication skills training in diabetes management and 6 trials in hypertension. 10 trials were at a low risk and 9 trials were at a high risk of bias. Training included motivational interviewing, patient centred care communication, cardiovascular disease risk communication, shared decision making, cultural competency training and psychological skill training. The trials found no significant effects on HbA1c (n = 4501, pooled mean difference -0.02 mmol/mol, 95% CI -0.10 to 0.05), systolic blood pressure (n = 2505, pooled mean difference -2.61 mmHg, 95% CI -9.19 to 3.97), or diastolic blood pressure (n = 2440, pooled mean difference -0.06 mmHg, 95% CI -3.65 to 2.45). There was uncertainty in whether training was effective at improving secondary outcomes. CONCLUSION: The communication skills training interventions for healthcare professionals identified in this systematic review did not improve HbA1c, BP or other relevant outcomes in patients with diabetes and hypertension. Further research is needed to methodically co-produce and evaluate communication skills training for chronic disease management with healthcare professionals and patients.

The experiences of Chinese general practitioners in communicating with people with type 2 diabetes-a focus group study.

BACKGROUND: China has more ascertained cases of diabetes than any other country. Much of the care of people with type 2 diabetes (T2DM) in China is managed by GPs and this will increase with the implementation of health care reforms aimed at strengthening China's primary health care system. Diabetes care requires effective communication between physicians and patients, yet little is known about this area in China. We aimed to explore the experiences of Chinese GPs in communicating with diabetes patients and how this may relate to communication skills training. METHODS: Focus groups with Chinese GPs were undertaken. Purposive sampling was used to recruit 15 GPs from Guangzhou city in China. All data were audio-recorded and transcribed. A thematic analysis using the Framework Method was applied to code the data and identify themes. RESULTS: Seven males and 8 females from 12 general practices attended 4 focus groups with a mean age of 37.6 years and 7.5 years' work experience. Four major themes were identified: diversity in diabetic patients, communication with patients, patient-doctor relationship, and communication skills training. GPs reported facing a wide variety of diabetes patients in their daily practice. They believed insufficient knowledge and misunderstanding of diabetes was common among patients. They highlighted several challenges in communicating with diabetes patients, such as insufficient consultation time, poor communication regarding blood glucose monitoring and misunderstanding the risk of complications. They used terms such as "blind spot" or "not on the same channel" to describe gaps in their patients' understanding of diabetes and its management, and cited this as a cause of ineffective patient-doctor communication. Mutual understanding of diabetes was perceived to be an important factor towards building positive patient-doctor relationships. Although GPs believed communication skills training was necessary, they reported rarely received this. CONCLUSIONS: Chinese GPs reported facing challenges in communicating with diabetes patients. Some of these were perceived as being due to the patients themselves, others were attributed to system constraints, and some were seen as related to a lack of clinician training. The study identified key issues for the development of primary care-based management of diabetes in China, and for developing appropriate communication skills training programs for the primary care workforce.

Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial.

BACKGROUND: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. METHODS: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle-eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome-occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)-was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985. FINDINGS: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study-3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5-92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55-0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49-0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51-1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33-0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up-ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. INTERPRETATION: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. FUNDING: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.

Glucose, Insulin, and Lipids in Cord Blood of Neonates and Their Association with Birthweight: Differential Metabolic Risk of Large for Gestational Age and Small for Gestational Age Babies.

OBJECTIVES: To investigate the association of birthweight percentile with cord blood glucose, lipids, and insulin levels. STUDY DESIGN: Data obtained from 1522 newborns were included in the Born in Guangzhou Cohort study. The generalized additive model and multivariable linear regression model were used to explore the nonlinear and linear relationships between birthweight and cord blood metabolic measures, and to evaluate the differences of metabolic measures Z-scores among small for gestational age, appropriate for gestational age, and large for gestational age babies. RESULTS: Birthweight Z-score was linearly associated with increased cord blood insulin Z-score (adjusted ß = 0.30; 95% CI, 0.22-0.37). Compared with appropriate for gestational age babies, neonates born small for gestational age had significantly higher cord blood triglycerides Z-score (adjusted mean difference [MDadj], 0.60; 95% CI, 0.40-0.79) and lower cord blood insulin (MDadj, -0.37; 95% CI, -0.57 to -0.16), high-density lipoprotein cholesterol (MDadj, -0.34; 95% CI, -0.55 to -0.13), total cholesterol (MDadj, -0.26; 95% CI, -0.47 to -0.05), and low-density lipoprotein (MDadj, -0.23; 95% CI, -0.43 to -0.02) Z-scores, and neonates born large for gestational age had higher cord blood insulin Z-score (MDadj, 0.31; 95% CI, 0.09 to 0.52). CONCLUSIONS: Our findings support the hypothesis that babies born small for gestational age and large for gestational age are exposed to different intrauterine environments, which may contribute to altered fat accumulation patterns with implications for the risk of metabolic dysfunction later in life. There is a need to consider the development of tailored intervention strategies to prevent metabolic dysfunction in adult life for these babies.