Associations of perceived built environment characteristics using NEWS questionnaires with all-cause mortality and major cardiovascular diseases: The prospective urban rural epidemiology (PURE)-China study.

BACKGROUND: Despite increased literature focusing on the role of the built environment (BE) in health, few cohort studies have quantitatively analyzed neighborhood walkability environment in relation to the risk of death and cardiovascular disease (CVD). This longitudinal study aimed at evaluating the association between perceived BE attributeswith mortality and major CVD based on the Prospective Urban Rural Epidemiology study in China (PURE-China). METHODS: The PURE-China study recruited 47,931 participants aged 35-70 years from 12 provinces of China between 2005 and 2009. The perceived BE information, including land use, street, aesthetics, and safety, was collected using the neighborhood environment walkability scale (NEWS) questionnaire, with higher scores indicating a more favorable rating. Two primary outcomes are all-cause mortality and major CVD event. The Cox frailty model with random intercepts was used to assess the association between the perceived total BE/subscales score and outcomes. RESULTS: Of 32,163 participants included in this study, 19,253 (59.9 %) were women, and the mean (SD) age was 51.0 (9.5) years. After a median follow-up period of 11.7 years (IQR 9.4 - 12.2), we observed that one standard deviation higher of combined BE scores was related to a lower risk of all-cause mortality (HR = 0.85; 95 %CI, 0.80-0.90), and major CVD events (HR = 0.95; 95 %CI, 0.90-0.99). The subscales of perceived BE were related to a lower risk, although a few were not significant. Land use mix-diversity and safety from crime were the two most significant subscales. Stronger risks were observed among urban and female participants. CONCLUSION: Favorable perceived BE characteristics were linked with a lower risk of all-cause mortality and major CVD events in Chinese population, especially in urban areas and females. Our findings can be used by policymakers to take action to mitigate the adverse effect of poor community conditions on health, such as improving local amenities and transport connectivity, providing building paths for walking, running and cycling.

Assessing Neurobehavioral Alterations Among E-waste Recycling Workers in Hong Kong.

Background: E-waste workers in Hong Kong are handling an unprecedented amount of e-waste, which contains various neurotoxic chemicals. However, no study has been conducted to evaluate the neurological health status of e-waste workers in Hong Kong. This study aimed to evaluate the prevalence of neurobehavioral alterations and to identify the vulnerable groups among Hong Kong e-waste workers. Methods: We recruited 109 Hong Kong e-waste workers from June 2021 to September 2022. Participants completed standard questionnaires and wore a GENEActiv accelerometer for seven days. Pittsburgh Sleep Quality Index and Questionnaire 16/18 (Q16/18) were used to assess subjective neurobehavioral alterations. The GENEActiv data generated objective sleep and circadian rhythm variables. Workers were grouped based on job designation and entity type according to the presumed hazardous level. Unconditional logistic regression models measured the associations of occupational characteristics with neurobehavioral alterations after adjusting for confounders. Results: While dismantlers/repairers and the workers in entities not funded by the government were more likely to suffer from neurotoxic symptoms in Q18 (adjusted odds ratio: 3.18 [1.18-9.39] and 2.77 [1.10-7.46], respectively), the workers from self-sustained recycling facilities also have poor performances in circadian rhythm. Results also showed that the dismantlers/repairers working in entities not funded by the government had the highest risk of neurotoxic symptoms compared to the lowest-risk group (i.e., workers in government-funded companies with other job designations). Conclusion: This timely and valuable study emphasizes the importance of improving the working conditions for high-risk e-waste workers, especially the dismantlers or repairers working in facilities not funded by the government.

Associations of dietary copper intake with cardiovascular disease and mortality: findings from the Chinese Perspective Urban and Rural Epidemiology (PURE-China) Study.

BACKGROUND: Previous in vitro and animal experiments have shown that copper plays an important role in cardiovascular health. Dietary copper is the main source of copper in the human body and the association between dietary copper and cardiovascular disease remains unclear. Our study aimed to investigate the associations of dietary copper intake with the risk of major cardiovascular disease incidence, cardiovascular disease mortality, and all-cause mortality in Chinese adults. METHODS: Our study is based on Prospective Urban Rural Epidemiology China (PURE-China), a large prospective cohort study of 47 931 individuals aged 35-70 years from 12 provinces in China. Dietary intake was recorded using a validated semi-quantitative food frequency questionnaire designed specifically for the Chinese population. The daily intake of copper was obtained by multiplying the daily food intake with the nutrient content provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary copper intake with mortality, major cardiovascular disease events, and their composite. RESULTS: A total of 45 101 participants (mean age: 51.1 ± 9.7 years old) with complete information were included in the current study. The mean dietary copper intake was 2.6 ± 1.1 mg/d. During the 482 833 person-years of follow-up, 2 644(5.9%) participants died, 4 012(8.9%) developed new cardiovascular diseases, and 5 608(12.4%) participants experienced the composite endpoint. Compared with those in the first and second quartile of dietary copper intake, individuals in the third and fourth quantile had higher risk of composite outcomes, all-cause death, cardiovascular disease death, major cardiovascular disease and stroke occurrences. The associations remained similar in the subgroup and sensitivity analyses. CONCLUSIONS: Our findings demonstrated that excessive dietary copper intake was associated with higher risks of death and cardiovascular diseases in Chinese adults. Further studies in populations with different dietary characteristics are needed to obtain dose-response relationships and to refine global dietary recommendations.

Socioeconomic disparity in mortality and the burden of cardiovascular disease: analysis of the Prospective Urban Rural Epidemiology (PURE)-China cohort study.

BACKGROUND: Although socioeconomic inequality in cardiovascular health has long been a public health focus, the differences in cardiovascular-disease burden and mortality between people with different socioeconomic statuses has yet to be adequately addressed. We aimed to assess the effects of socioeconomic status, measured via three socioeconomic-status indicators (ie, education, occupation, and household wealth and a composite socioeconomic-status disparity index, on mortality and cardiovascular-disease burden (ie, incidence, mortality, and admission to hospital) in China. METHODS: For this analysis, we used data from the Prospective Urban Rural Epidemiology (PURE)-China cohort study, which enrolled adults aged 35-70 years from 115 urban and rural areas in 12 provinces in China between Jan 1, 2005, and Dec 31, 2009. Final follow-up was on Aug 30, 2021. Indicators of socioeconomic status were education, occupation, and household wealth; these individual indicators were also used to create an integrated socioeconomic-status index via latent class analysis. Standard questionnaires administered by trained researchers were used to obtain baseline data and were supplemeted by physical measurements. The primary outcomes were all-cause mortality, cardiovascular-disease mortality, non-cardiovascular-disease mortality, major cardiovascular disease, and cardiovascular-disease admission to hospital. Hazard ratios (HRs) and average marginal effects were used to assess the association between the primary outcomes and socioeconomic status. FINDINGS: Of 47 931 participants enrolled in the PURE-China study, 47 278 (98·6%) had complete information on sex and follow-up. After excluding 1189 (2·5%) participants with missing data on education, household wealth, and occupation at baseline, 46 089 participants were included in this analysis. Median follow-up was 11·9 years (IQR 9·5-12·6); 26 860 (58·3%) of 46 089 participants were female and 19 229 (41·7%) were male. Having no or primary education, unskilled occupation, or being in the lowest third of household wealth was associated with a higher risk of all-cause mortality, cardiovascular-disease mortality, non-cardiovascular-disease mortality, major cardiovascular disease, and cardiovascular-disease admission to hospital compared with having higher education, a professional or managerial occupation, or more household wealth. After adjustment for confounders, people categorised as having low integrated socioeconomic status based on the index had a higher risk of all-cause mortality (HR 1·65 [95% CI 1·42-1·92]), cardiovascular-disease mortality (2·19 [1·68-2·85]), non-cardiovascular disease mortality (1·43 [1·18-1·72]), major cardiovascular disease (1·43 [1·27-1·61]) and cardiovascular-disease admission to hospital (1·14 [1·01-1·28]) compared with people categorised as having high integrated socioeconomic status. INTERPRETATION: Socioeconomic-status inequalities in mortality and cardiovascular-disease outcomes exist in China. Targeted policies of equal health-care resource allocation should be promoted to equitably benefit people with fewer years of education and less household wealth. FUNDING: Funding sources are listed at the end of the Article.

Association of preserved ratio impaired spirometry with mortality: a systematic review and meta-analysis.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is prevalent within the general population. Increased mortality has been reported among subjects with PRISm, but the evidence has never been summarised. This systematic review aims to synthesise evidence on the association between PRISm and the risk of all-cause, cardiovascular and respiratory-related mortality. METHODS: We systematically searched MEDLINE, Embase and Web of Science for population-based cohort studies from inception to April 2023 using the terms related to impaired spirometry and mortality. Titles and abstracts were screened to identify eligible studies that reported mortality estimates for individuals with PRISm. We excluded studies that adopted other definitions of impaired spirometry, had a specific study setting (e.g. HIV patients), had an insufficient follow-up period (<1 year) or reported duplicated data. Random-effects meta-analysis was used to produce pooled hazard ratio (HR) with 95% confidence intervals. Between-study heterogeneity was assessed with I2. RESULTS: Eight studies met the inclusion criteria involving 40 699 individuals with PRISm. All included studies reported increased risk of all-cause mortality among adults with PRISm. Meta-analysis showed that PRISm was associated with an increased risk of all-cause mortality (pooled HR 1.71, 95% CI 1.51-1.93; I2=64%), cardiovascular mortality (pooled HR 1.57, 95% CI 1.44-1.72; I2=35%) and respiratory-related mortality (pooled HR 1.97, 95% CI 1.55-2.49; I2=0%). CONCLUSIONS: Individuals with PRISm have a significantly increased risk of mortality compared with those with normal spirometry.

Association Between Metabolic Syndrome and Mortality: Prospective Cohort Study.

BACKGROUND: Metabolic syndrome (MetS) is a common metabolic disorder that results from the increasing prevalence of obesity, which has been an increasing concern in recent years. Previous evidence indicated that MetS was associated with mortality; however, different definitions of MetS were used. In 2005, the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III updated the definition of MetS, which has since been widely adopted. Therefore, it is necessary to conduct a novel study among other populations and countries with a larger sample size using the updated definition of MetS and death code to examine the association of MetS with all-cause and cause-specific mortality. OBJECTIVE: We aimed to examine the associations of MetS with all-cause and cause-specific mortality. METHODS: A total of 36,414 adults were included in this study, using data from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and the continuous NHANES (1999-2014) in the United States. Death outcomes were ascertained by linkage to National Death Index records through December 31, 2015. MetS was defined by the NCEP ATP III-2005 criterion. Complex survey design factors including sample weights, clustering, and stratification were considered for all analyses with instructions for using NHANES data. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for mortality from all causes, heart disease, diabetes, and cancer. RESULTS: We observed 8494 deaths during the 16.71 years of follow-up. Compared with those without MetS, individuals with MetS were associated with a significantly elevated multiadjusted HR of 1.24 (95% CI 1.16-1.33), 1.44 (95% CI 1.25-1.66), and 5.15 (95% CI 3.15-8.43) for all cause, heart diseases, and diabetes mellitus, respectively, whereas no significant association was found for cancer mortality (HR 1.17, 95% CI 0.95-1.43). CONCLUSIONS: Our study provides additional evidence that MetS and its components are significantly associated with all-cause, heart disease, and diabetes mortality, but not with cancer mortality. Health care professionals should pay more attention to MetS and its individual component.

Association of spirometric restriction with mortality in the silicotics: a cohort study.

BACKGROUND: Restrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort. METHOD: This retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18-80 years and diagnosed with silicosis during 1981-2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV1/FVC ≥ 0.7, FVC < 80% predicted), AFO only (FEV1/FVC < 0.7, FVC ≥ 80% predicted), and RSP&AFO mixed (FEV1/FVC < 0.7, FVC < 80% predicted). The hazard ratio (HR) and 95% confidence intervals (95% CI) were computed using a Cox proportional hazards model adjusting for age, body mass index, history of tuberculosis, smoking status, pack-years, and radiographic characteristics of silicotic nodules. RESULTS: Among the 4315 patients enrolled in the study, the prevalence of RSP was 24.1% (n = 1038), including 11.0% (n = 473) with RSP only and 13.1% (n = 565) with mixed RSP and AFO. During the follow-up period, a total of 2399 (55.6%) deaths were observed. Compared with the silicotics with normal spirometry, those with RSP only had significantly increased risk of all-cause mortality (HR = 1.63, 95% CI 1.44-1.85) and respiratory-related mortality (HR = 1.56, 95% CI 1.31-1.85). Notably, a higher risk of mortality was observed in silicotics with mixed ventilatory defects of both RSP and AFO (all-cause mortality: HR = 2.22, 95% CI 1.95-2.52; respiratory-related mortality: HR = 2.59, 95% CI 2.18-3.07) than in those with RSP only. CONCLUSION: RSP is significantly associated with increased risk of all-cause and respiratory-related mortality in the silicotics, and patients with mixed restrictive and obstructive ventilatory defect have higher risk of mortality than those with single RSP or AFO. These findings emphasize the importance of recognizing RSP in the occupational settings, especially for the silicotic patients with mixed ventilatory defect.

How People's COVID-19 Induced-Worries and Multiple Environmental Exposures Are Associated with Their Depression, Anxiety, and Stress during the Pandemic.

This study investigates how people's perceived COVID-19 risk, worries about financial hardship, job loss, and family conflicts, and exposures to greenspace, PM2.5, and noise (in people's residential neighborhoods and daily activity locations) are related to their depression, anxiety, and stress during the COVID-19 pandemic. Using a two-day activity-travel diary, a questionnaire, and real-time air pollutant and noise sensors, a survey was conducted to collect data from 221 participants living in two residential neighborhoods of Hong Kong during the COVID-19 pandemic. Linear regression was conducted to explore the relationships. Significant associations between people's COVID-19-related worries and exposures to grassland and PM2.5 with depression, anxiety, and stress were found in the results. These associations with depression, anxiety, and stress vary depending on people's demographic attributes. These results can help direct the public authorities' efforts in dealing with the public mental health crisis during the COVID-19 pandemic.

Bisphenol A substitutes and childhood obesity at 7 years: a cross-sectional study in Shandong, China.

Bisphenol A (BPA) substitutes, such as bisphenol S (BPS) and bisphenol AF (BPAF), are increasingly used due to restrictions on BPA usage, a known endocrine disrupting chemical and putative obesogen. However, little is known about the obesogenic effects of exposure to BPA substitutes in children. A total of 426 children aged 7 years old originally recruited from Laizhou Wan Birth Cohort in Shandong, China, during 2010-2013 participated in the 2019-2020 survey. Urinary BPA and its substitutes including BPS, BPAF, bisphenol B (BPB), bisphenol AP (BPAP), bisphenol Z (BPZ), and bisphenol P (BPP) were determined. Anthropometric measures including height, weight, waist circumference, and body fat percentage were assessed, and overweight/obesity was defined as BMI z-score ≥ 85th percentile. Linear and logistic regressions were used on continuous and binary obesity measures, respectively, and weighted quantile sum (WQS) regression was further used to estimate the mixture effects of exposure to diverse bisphenols, and sex-stratified analysis was performed. BPA substitutes were widely detected (> 75%) in children's urine samples. A positive association with obesity measures was consistently observed for urinary BPS and BPAF, i.e., BMI z-score, waist circumference, and overweight/obesity. Further analysis from the WQS regression model demonstrated a positive association between bisphenol mixtures and all measures of obesity, with BPAF contributing the greatest weighing to the observed associations. Sex difference might exist as the positive associations were only significant in boys. No significant association was found between obesity and BPA or other BPA substitutes. Our study adds to mounting evidence that BPA substitutes BPS and BPAF are linked to obesity in children, especially in boys. Further longitudinal studies with larger sample size with continued biomonitoring these chemicals and their obesogenic effects are necessary.

Association between matched chronotype and poor mental health among shift workers: a systematic review and meta-analysis.

BACKGROUND: Nearly 0.7 billion workers are involved in the shift work system, leading to concerns about its potential impacts on the large-scale population mental health. This study aimed to synthesise evidence of the associations between matched chronotype and the risk of poor mental health among shift workers. METHODS: Six computerised databases were searched from inception to September 2022. Observational studies were selected if they reported any association between common mental health parameters and chronotype scores/types of shift workers. The Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist was followed. We extracted adjusted risk estimates to calculate pooled effect sizes and explore sources of heterogeneity. The study was registered in PROSPERO: CRD42022357437. RESULTS: Fourteen studies including 49 909 workers were identified. Ever shift workers had a higher risk of poor mental health than the day workers (pooled OR 1.15, 95% CI 1.03 to 1.28; I2=14%, p=0.29), with the evening chronotype ever shift workers having a 1.47 times higher risk than those who worked during the day (pooled OR 1.47, 95% CI 1.13 to 1.91; I2=42%, p=0.16). Sensitivity analysis excluding studies with the highest risk of bias of each group demonstrated consistent findings. CONCLUSIONS: Evening chronotype ever shift workers have poorer mental health than shift workers with other chronotypes. Chronotype remains unrecognised in the contemporary rostering system, making it a hidden contributor to occupational mental health. Work-related physical and mental stresses may be prevented/mitigated with further investigation on optimising shift work schedule combined with individual chronotype preference.

Urinary neonicotinoid insecticides and adiposity measures among 7-year-old children in northern China: A cross-sectional study.

BACKGROUND: Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides used in various pest management regimens worldwide. Toxicology studies have indicated the obesogenic potential of NEOs, but their associations with adiposity measures are largely unknown. OBJECTIVES: We aimed to assess urinary levels of NEOs/metabolites and their associations with children's adiposity measures, and to further investigate the potential role of oxidative stress. METHODS: This study included 380 children who participated in the 7th year's follow-up of the Laizhou Wan Birth Cohort in northern China. Urinary levels of seven NEOs and two metabolites and a biomarker of lipid peroxidation named 8-iso-prostaglandin-F2α (8-iso-PGF2α) were detected. A total of nine indicators of adiposity were measured. Body mass index (BMI) z-score ≥85th percentile was defined as overweight/obesity, and waist-to-height ratio (WHtR) ≥0.5 was considered as abdominal obesity. Multiple linear regression, binary logistic regression and mediation analysis were performed. RESULTS: Six NEOs [imidacloprid (IMI, 99.7%), clothianidin (CLO, 98.9%), dinotefuran (DIN, 97.6%), thiamethoxam (THM, 95.5%), acetamiprid (ACE, 82.9%), thiacloprid (THD, 77.6%)] and two metabolites [N-desmethyl-acetamiprid (N-DMA, 100.0%), 6-chloronicotinic acid (6-CINA, 97.9%)] exhibited high detection rates. Multiple linear regressions showed positive associations of waist circumference with urinary levels of IMI and THM, of WHtR with IMI and THM levels, and of body fat percentage with 6-CINA levels. In contrast, exposure to N-DMA was negatively associated with body fat percentage and fat mass index. Binary logistic regressions further revealed that higher IMI levels were associated with overweight/obesity (OR = 1.556, 95% CI: 1.100, 2.201) and abdominal obesity (OR = 1.478, 95% CI: 1.078, 2.026) in children. 8-iso-PGF2α demonstrated 27.92%, 69.52% and 35.37% mediating effects in the positive associations of IMI, THD and THM with WHtR, respectively. Sex modified the associations of DIN with body fat mass (pint = 0.032), body fat percentage (pint = 0.009), fat mass index (pint = 0.037) and the overweight/obesity rate (pint = 0.046), with negative associations in girls and nonsignificant positive associations in boys. CONCLUSIONS: School-age children in northern China were widely exposed to NEOs/metabolites. Urinary levels of NEOs/metabolites were associated with adiposity measures through the mediating role of 8-iso-PGF2α. These associations were mixed, and a sex-specific effect might exist.

Household Air Pollution and Adult Lung Function Change, Respiratory Disease, and Mortality across Eleven Low- and Middle-Income Countries from the PURE Study.

BACKGROUND: Globally, household air pollution (HAP) is a major environmental hazard that affects respiratory health. However, few studies have examined associations between HAP and lung function decline and respiratory disease and mortality. METHODS: We used data from the Prospective Urban and Rural Epidemiology study and examined adults residing in 240 rural communities in 11 low- and middle-income countries where HAP from cooking with solid fuels is common. Spirometry was conducted for 28,574 individuals at baseline and 12,489 individuals during follow-up (mean of 8 y between spirometry measures). In cross-sectional analyses, we compared lung function measurements [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio] in those who used solid fuels for cooking in comparison with clean fuels. Using repeated measurements of lung function, we examined the percent change in lung function measures per year, comparing individuals by baseline fuel type and individuals who used solid fuels at baseline but switched to clean fuels during follow-up. We also examined associations with prospective health events (any respiratory diseases, respiratory disease hospitalizations, and all-cause mortality). RESULTS: In adjusted cross-sectional models, use of solid fuel in comparison with clean fuels was associated with lower FEV1 of -17.5mL (95% CI: -32.7, -2.3) and FVC of -14.4mL (95% CI: -32.0, 3.2), but not FEV1/FVC. In longitudinal analyses, individuals who switched from solid fuels to clean cooking fuels during follow-up (n=3,901, 46% of those using solid fuel at baseline), showed no differences in the annual rate of change in FEV1 or FVC, but had small improvements in FEV1/FVC change (0.2% per year, 95% CI: 0.03, 0.3). Individuals who switched from solid to clean fuels had a decreased hazard ratio for respiratory events of 0.76 (95% CI: 0.57, 1.00) in comparison with persistent solid fuel users, which was not attenuated by lung function measures. CONCLUSION: We observed modest associations between HAP exposure and lung function, lung function change, and respiratory disease and mortality. https://doi.org/10.1289/EHP11179.

Sex differences in the associations of sleep-wake characteristics and rest-activity circadian rhythm with specific obesity types among Hong Kong community-dwelling older adults.

BACKGROUND: Sex differences exist in sleep characteristics, circadian rhythm and body composition but the evidence on their associations with obesity risk remains unclear. We aimed to examine sex differences in the associations of sleep-wake cycle and rest-activity circadian rhythm with specific obesity types among aged Chinese population. METHODS: This report pooled data from 2 population-based surveys conducted during 4/2018-9/2018 and 7/2019-9/2020. All participants wore actigraphy on wrists for 7 days to measure their objective sleep patterns and rest-activity circadian rhythm. We measured participants' anthropometric data, and obtained their body weight, body fat percentage(fat%), visceral fat rating, muscle mass by calibrated bioelectrical impedance analysis device. Hand-grip strength was assessed by Jamar Hydraulic hand dynamometer. Multinomial logistic regression was performed to assess the odds ratio(OR) and 95% confidence intervals(95%CI). RESULTS: We recruited 206 male and 134 female older adults with complete actigraphy data, with obesity prevalence of 36.9% and 31.3%, respectively. Male participants who had delayed sleep-wake cycle(i.e.,sleep-onset-time and wake-up time) was associated with higher risk of obesity(late sleep-onset-time:OR=5.28, 95%CI=2.00-13.94), and the results remained consistent for different types of obesity. Males with late M10(i.e., most active 10-hours) onset had higher adipose outcomes with an adjusted OR of 2.92(fat%:95%CI=1.10-7.71; visceral fat:95%CI=1.12-7.61). Among female participants, those with lower relative amplitude were associated with higher BMI and lower hand-grip strength. CONCLUSIONS: This study revealed that circadian rhythm fragmentation was associated with obesity and muscle loss. Promoting good sleep quality and maintaining robust circadian rhythm and physical activity can prevent poor muscle strength among older adults.

Efficacy and safety of treatment regimens for patients with metastatic, locally advanced, or recurrent breast cancer carrying BRCA1/BRCA2 pathogenic variants: A network meta-analysis.

Objective: Patients with breast cancer carrying BRCA1 and BRCA2 genetic alterations show poor prognoses. However, the efficacy of pharmacotherapies for patients with advanced breast cancer carrying BRCA1/2 pathogenic variants remains unclear. This study aimed to conduct a network meta-analysis to assess the efficacy and safety of various pharmacotherapies for patients with metastatic, locally advanced, or recurrent breast cancer carrying BRCA1/BRCA2 pathogenic variants. Methods: A literature search was conducted using Embase, PubMed, and Cochrane Library (CENTRAL), from inception to 11th May 2022. The references of included articles were screened to identify relevant literature. This network meta-analysis included patients with metastatic locally advanced or recurrent breast cancer who received pharmacotherapy and carried deleterious variants of BRCA1/2. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed for conducting and reporting this systematic meta-analysis. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was employed to evaluate evidential certainty. Frequentist random-effect model was applied. Results of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and rates of any-grade adverse events were presented. Results: Nine randomized controlled trials were obtained comprising six treatment regimens, including 1912 patients with pathogenic variants of BRCA1 and BRCA2. The orchestration of PARP inhibitors with platinum-based chemotherapy was found to be the most effective with a pooled odds ratio (OR) of 3.52 (95% CI 2.14, 5.78) for ORR; 1.53 (1.34,1.76), 3.05 (1.79, 5.19), and 5.80 (1.42, 23.77) for 3-, 12-, and 24-month PFS, respectively, and 1.04 (1.00, 1.07), 1.76 (1.25, 2.49) and 2.31 (1.41, 3.77) for 3-, 12-, and 36-month OS, respectively compared to those receiving non-platinum-based chemotherapy. However, it posed an elevated risk of some adverse events. Platinum-based chemotherapy alone or PARP inhibitors markedly improved ORR, PFS, and OS compared to non-platinum-based chemotherapy. Interestingly, platinum-based chemotherapy surpassed PARP inhibitors in terms of efficacy. Evidence on programmed death-ligand 1(PD-L1) inhibitors and sacituzumab govitecan (SG) suggested low quality and insignificant results. Conclusions: Among all treatment regimens, PARP inhibitors with platinum exhibited the best efficacy, although with a trade-off of elevated risk of some types of adverse events. Future research on direct comparisons between different treatment regimens specifically targeting patients with breast cancer carrying BRCA1/2 pathogenic variants with a pre-specified adequate sample size is warranted.

DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.

BACKGROUND: Few studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and normal tissue, with less work done in non-European populations. In this study, we aimed to examine DNAm age and its associations with breast cancer risk factors, subtypes, somatic genomic profiles including mutation and copy number alterations and other aging markers in breast tissue of Chinese breast cancer (BC) patients from Hong Kong. METHODS: We performed genome-wide DNA methylation profiling of 196 tumor and 188 paired adjacent normal tissue collected from Chinese BC patients in Hong Kong (HKBC) using Illumina MethylationEPIC array. The DNAm age was calculated using Horvath's pan-tissue clock model. Somatic genomic features were based on data from RNA sequencing (RNASeq), whole-exome sequencing (WES), and whole-genome sequencing (WGS). Pearson's correlation (r), Kruskal-Wallis test, and regression models were used to estimate associations of DNAm AA with somatic features and breast cancer risk factors. RESULTS: DNAm age showed a stronger correlation with chronological age in normal (Pearson r = 0.78, P < 2.2e-16) than in tumor tissue (Pearson r = 0.31, P = 7.8e-06). Although overall DNAm age or AA did not vary significantly by tissue within the same individual, luminal A tumors exhibited increased DNAm AA (P = 0.004) while HER2-enriched/basal-like tumors exhibited markedly lower DNAm AA (P = < .0001) compared with paired normal tissue. Consistent with the subtype association, tumor DNAm AA was positively correlated with ESR1 (Pearson r = 0.39, P = 6.3e-06) and PGR (Pearson r = 0.36, P = 2.4e-05) gene expression. In line with this, we found that increasing DNAm AA was associated with higher body mass index (P = 0.039) and earlier age at menarche (P = 0.035), factors that are related to cumulative exposure to estrogen. In contrast, variables indicating extensive genomic instability, such as TP53 somatic mutations, high tumor mutation/copy number alteration burden, and homologous repair deficiency were associated with lower DNAm AA. CONCLUSIONS: Our findings provide additional insights into the complexity of breast tissue aging that is associated with the interaction of hormonal, genomic, and epigenetic mechanisms in an East Asian population.

Sleep behaviors and Parkinson's disease: A bidirectional Mendelian randomization analysis.

OBJECTIVE: Whether the quantity and quality of sleep are the risk factors for the development of Parkinson's disease remains unclear though it has now been confirmed that the quality of sleep among patients with Parkinson's disease is affected at the prodromal and clinical stages. Accordingly, this study aimed to examine the bidirectional causal relationships of multiple sleep-related phenotypes with Parkinson's disease using a two-sample Mendelian randomization (MR) method. METHODS: The summary-level data collected from the published genome-wide association studies was used for analysis. Besides, the genetic relationships between different sleep-related phenotypes, including self-reported and accelerometer measured traits, were estimated for the risk and age at the onset of Parkinson's disease. To conduct MR analysis, inverse variance weighted, weight median, MR-Egger, and MR-PRESSO method were mainly used. Moreover, sensitivity analyses were carried out to examine the pleiotropic effect. RESULTS: In general, there was insufficient evidence to support the causal effect of sleep-related phenotypes on risk (N cases/controls = 33,674/449,056) and age at the onset (N cases = 28,568) of Parkinson's disease. However, the results of this study indicated that the later onset age of Parkinson's disease was related to the frequent occurrence of insomnia (OR [95% CI] 1.007 [1.003, 1.011], P < 0.001) after the adjustment for multiple testing. CONCLUSIONS: The results of this study suggest that insomnia-associated single nucleotide polymorphisms are more frequent in later onset Parkinson's disease patients compared to earlier onset patients. However, given the limitations of statistical power and potential bias, further validation should be still conducted through larger population research.

Association of circadian rhythm with mild cognitive impairment among male pneumoconiosis workers in Hong Kong: a cross-sectional study.

Weakened circadian activity rhythms (CARs) were associated with mild cognitive impairment (MCI) in the general population. However, it remains unclear among pneumoconiosis patients. We aimed to address this knowledge gap. This cross-sectional study comprised 186 male pneumoconiosis patients (71.3 ± 7.8 years) and 208 healthy community men. Actigraphy was used to determine CARs parameters (percent rhythm, amplitude, MESOR, and acrophase). Values below the corresponding medians of the CARs parameters represented weakened CARs. The Cantonese version of Mini-Mental State Examination (CMMSE) was used to assess cognitive function, MCI, and the composite outcome of MCI plus cognitive impairment. Compared with the community referents, pneumoconiosis patients had worse cognition and dampened CARs. Compared with the community referents or pneumoconiosis patients with robust circadian rhythm, pneumoconiosis patients with weakened circadian rhythm were consistently associated with increased risk of MCI and the composite outcome. However, significant association was only observed between MESOR and the composite outcome (adjusted OR = 1.99, 95%: 1.04-3.81). A delayed phase of CARs was insignificantly associated with MCI and the composite outcome. Our findings showed that weakened CARs were associated with worse cognitive function among male pneumoconiosis workers. Intervention in improving CARs may mitigate cognitive deterioration in male pneumoconiosis workers.

Regional differences in the contribution of smoking, dietary and cooking behaviours to airflow obstruction in China: A population-based case-control study.

BACKGROUND AND OBJECTIVE: The major contributing risk factors to airflow obstruction (AO) in China remain largely unknown. We examined the environmental and lifestyle risk factors of unrecognized AO in the baseline of a population-based cohort drawn from 115 urban and rural communities across 12 provinces in China. METHODS: Amongst 46,285 adults recruited from 2005 to 2009, 3686 were identified with AO on spirometry (defined by the ratio of forced expiratory volume in the first second to forced vital capacity <0.7) and without known chronic lung disease. These cases were age- and sex-matched to 11,129 controls with normal spirometry and no chronic lung disease from the same community. Conditional multivariable adjusted OR and population attributable fraction (PAF) were calculated for each identified risk factor and their combined effect. RESULTS: Compared to controls, smoking initiation age <20 years (OR 1.22 [95% CI 1.01-1.48]), smoking duration ≥40 years (OR 1.82 [1.50-2.22]), low vegetables (OR 1.86 [1.67-2.07]) and fruits (OR 1.14 [1.02-1.29]) intake, cooking with biomass fuels (OR 2.54 [2.32-2.78]) and poor kitchen ventilation (OR 1.37 [1.19-1.58]) were significantly associated with elevated risks of unrecognized AO. The combined effect of these lifestyle factors significantly elevated the odds by 25 fold (18.6-34.3). The addition of prior tuberculosis and low socioeconomic status further increased the odds to 40.1 (28.2-57.0) and the PAF to 66.7% (51.1-78.1). CONCLUSION: Smoking, unhealthy diet, biomass cooking fuels and low socioeconomic status are strongly associated with AO. Addressing these risk factors could substantially reduce the burden of AO in China.

Association of Household Utility of Cleaner Fuel With Lower Hypertension Prevalence and Blood Pressure in Chinese Adults.

Objectives: To investigate whether lower hypertension prevalence or blood pressure was associated with cleaner household fuel usage for cooking and heating among Chinese adults. Methods: We enrolled 44,862 Chinese adults at the baseline of the prospective urban and rural epidemiology (PURE) study in China during 2005-2009, as a subset of the PURE-global China site. Multilevel logistic regression and generalized linear mixed models were conducted to estimate the adjusted odds ratio (AOR) and regression coefficient for hypertension and blood pressure respectively, while subgroup analysis by ambient PM2.5 concentration and location was also examined. Results: Compared with the least clean household solid fuel group, gas (AOR = 0.91, 95% CI: 0.83, 0.99) or electricity (AOR = 0.72, 95% CI: 0.60, 0.87) was associated with significantly lower levels of hypertension prevalence and blood pressure, and a similar pattern of the association was consistently observed among participants with high ambient PM2.5 exposure and those living in urban areas. Conclusion: Household utility of cleaner fuel type was associated with lower hypertension prevalence and blood pressure in Chinese adults. Our study urges the utilization of cleaner household energy to mitigate the burden of hypertension.