Sibling Death in Childhood and Early Adulthood and Risk of Early-Onset Cardiovascular Disease.

Importance: Sibling death is a highly traumatic event, but empirical evidence on the association of sibling death in childhood and early adulthood with subsequent risk of incident cardiovascular disease (CVD) remains limited. Objective: To evaluate the association between sibling death in the early decades of life and subsequent risk of incident early-onset CVD. Design, Setting, and Participants: This population-based cohort study included 2 098 659 individuals born in Denmark from 1978 to 2018. Follow-up started at age 1 year or the date of the first sibling's birth, whichever occurred later, and it ended at the first diagnosis of CVD, the date of death, emigration, or December 31, 2018, whichever came first. Data analyses were conducted from November 1, 2021, through January 10, 2022. Exposures: The death of a sibling. Main Outcomes and Measures: The outcome was early-onset CVD. Cox models were used to estimate hazard ratios (HRs) with 95% CIs. Results: This study included 2 098 659 individuals (1 076 669 [51.30%] male; median [IQR] age at death of sibling, 11.48 [4.68-21.32] years). During the median (IQR) follow-up of 17.52 (8.85-26.05) years, 1286 and 76 862 individuals in the bereaved and nonbereaved groups, respectively, were diagnosed with CVD. Sibling death in childhood and early adulthood was associated with a 17% increased risk of overall CVD (HR, 1.17; 95% CI, 1.10-1.23; cumulative incidence in bereaved individuals, 1.96% [1.61%-2.34%]; cumulative incidence in nonbereaved individuals at age 41 years, 1.35% [1.34%-1.37%]; cumulative incidence difference: 0.61% [95% CI, 0.24%-0.98%]). Increased risks were also observed for most type-specific CVDs, in particular for myocardial infarction (HR, 1.66; 95% CI, 1.12-2.46), ischemic heart disease (HR, 1.52; 95% CI, 1.22-1.90), and heart failure (HR, 1.50; 95% CI, 1.00-2.26). The association was observed whether the sibling died due to CVD (HR, 2.54; 95% CI, 2.04-3.17) or non-CVD (HR, 1.13; 95% CI, 1.06-1.19) causes. The increased risk of CVD was more pronounced for individuals who lost a twin or younger sibling (HR, 1.25; 95% CI, 1.15-1.36) than an elder sibling (HR, 1.11; 95% CI, 1.03-1.20). Conclusions and Relevance: In this cohort study of the Danish population, sibling death in childhood and early adulthood was associated with increased risks of overall and most type-specific early-onset CVDs, with the strength of associations varying by cause of death and age difference between sibling pairs. The findings highlight the need for extra attention and support to the bereaved siblings to reduce CVD risk later in life.

Association of Maternal Body Mass Index During Early Pregnancy With Offspring Lower Respiratory Infections: A Nationwide Cohort Study.

OBJECTIVE: To assess whether or to what extent maternal obesity during early pregnancy could increase the risk of offspring lower respiratory infections (LRI). STUDY DESIGN: This population-based cohort included 688,457 live singleton births born in Denmark between 2004 and 2016. The exposure was maternal body mass index (BMI) during early pregnancy, and the outcome was LRI in offspring. Cox regression models were used to estimate hazard ratios with their 95% confidence intervals (CI) for the association. We also performed subanalysis stratified by the LRI onset age, number of infection episodes before the age of 3, infection pathogens, infection sites, duration of hospital stay due to LRI and allergic constitution of children. RESULTS: A total of 64,725 LRIs in offspring were identified during follow-up. Maternal overweight (BMI 25.0-29.9 kg/m 2 ), moderate or severe obesity (BMI 30.0-39.9 kg/m 2 ) and very severe obesity (BMI ≥40 kg/m 2 ) were associated with a 7% (95% CI: 5%-9%), 16% (95% CI: 14%-19%) and 21% (95% CI: 13%-28%) increased risk of LRI in offspring, respectively. Higher maternal BMI was positively associated with earlier onset age, more episodes before the age of 3, and longer hospital stay of LRI in offspring. In addition, allergic constitution of offspring significantly enhanced the effect of maternal BMI on offspring LRI (44% increased risk, 95% CI: 5%-97% for very severe obesity). CONCLUSIONS: Maternal BMI during early pregnancy might be a risk factor for offspring LRI, especially in children with allergic constitution.

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.

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.

Evaluation of Hypertensive Disorder of Pregnancy and High Refractive Error in Offspring During Childhood and Adolescence.

Importance: Growing evidence indicates that adverse prenatal or intrauterine environments might contribute to the development of high refractive error (RE) later in life. However, the association of maternal hypertensive disorder of pregnancy (HDP) with high RE in offspring during childhood and adolescence remains unknown. Objective: To investigate the association between maternal HDP and overall and type-specific high REs in offspring in childhood and adolescence. Design, Setting, and Participants: This nationwide population-based cohort study included live-born individuals born in Denmark from 1978 to 2018 in the Danish national health registers. Follow-up started at the date of birth and ended at the date of RE diagnosis, 18th birthday, death, emigration, or December 31, 2018, whichever came first. Data analyses were conducted from November 12, 2021, through June 30, 2022. Exposures: Maternal HDP (n = 104 952), including preeclampsia or eclampsia (n = 70 465) and hypertension (n = 34 487). Main Outcomes and Measures: The main outcomes were the first occurrence of high RE (hyperopia, myopia, and astigmatism) in offspring. A Cox proportional hazards regression model was used to examine the association between maternal HDP and risk of high RE in offspring from birth until age 18 years, adjusting for multiple potential confounders. Results: This study included 2 537 421 live-born individuals, 51.30% of whom were male. During the follow-up of up to 18 years, 946 offspring of 104 952 mothers with HDP (0.90%) and 15 559 offspring of 2 432 469 mothers without HDP (0.64%) were diagnosed with high RE. The cumulative incidence of high RE was higher in the exposed cohort (1.12%; 95% CI, 1.05%-1.19%) than in the unexposed cohort (0.80%; 95% CI, 0.78%-0.81%) at 18 years of age (difference: 0.32%; 95% CI, 0.25%-0.40%). Offspring born to mothers with HDP had a 39% increased risk of overall high RE (hazard ratio [HR], 1.39; 95% CI, 1.31-1.49). Sibling-matched analysis revealed an increased risk of overall high RE in half siblings (HR, 1.21; 95% CI, 1.05-1.39) and full siblings (HR, 1.15; 95% CI, 0.99-1.34), but the difference was not significant for the latter. The elevated risks were observed for hypermetropia (HR, 1.41; 95% CI, 1.30-1.52), myopia (HR, 1.30; 95% CI, 1.10-1.53), and astigmatism (HR, 1.45; 95% CI, 1.22-1.71). The increased risk of high RE persisted among offspring aged 0 to 6 years (HR, 1.51, 95% CI, 1.38-1.65), 7 to 12 years (HR, 1.28; 95% CI, 1.11-1.47), and 13 to 18 years (HR, 1.16; 95% CI, 0.95-1.41), but the difference was not significant for the oldest group. When considering both timing of diagnosis and severity of maternal preeclampsia, the highest risk was observed in offspring prenatally exposed to early-onset and severe preeclampsia (HR, 2.59; 95% CI, 2.17-3.08). Conclusions and Relevance: In this cohort study of the Danish population, maternal HDP, especially early-onset and severe preeclampsia, was associated with an increased risk of high RE in offspring during childhood and adolescence. These findings suggest that early and regular RE screening should be recommended for children of mothers with HDP.

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.

Association of intellectual disability with overall and type-specific cardiovascular diseases: a population-based cohort study in Denmark.

BACKGROUND: Individuals with mental health problems have been shown to have an increased risk of cardiovascular disorder (CVD), but little is known about the risk of early-onset CVD among those with intellectual disability. We aimed to investigate the association between intellectual disability and subsequent CVD, taking into consideration the severity of intellectual disability and neurodevelopmental and neurologic comorbidity. METHODS: This population-based cohort study used individual-level linked data from Danish national health registries. Participants were all live-born singletons born in Denmark during 1978-2016 (n = 2,288,393). Follow-up began from birth and continued until the onset of CVD, death, emigration, or December 31, 2018, whichever came first. Clinical diagnosis of any CVD or type-specific CVDs was identified in the Danish National Patient Register. Time-varying Cox regression analyses were used to estimate the hazard ratio (HR) of intellectual disability associated with overall and type-specific CVDs. RESULTS: A total of 11,954 individuals received a diagnosis of intellectual disability (7434 males and 4520 females). During a median follow-up time of 18.5 years (interquartile range, 18.1 years), 652 individuals with intellectual disability (5.5%) received a diagnosis of CVD (incidence rate, 2.4 per 1000 person-years), compared with 78,088 (3.4%) CVD cases in individuals without intellectual disability (incidence rate, 1.9 per 1000 person-years), corresponding to a HR of 1.24 (95% CI, 1.15-1.34). Increased risks of CVD were similar in both childhood (HR, 1.24; 95% CI, 1.08-1.43) and early adulthood (HR, 1.25; 95% CI, 1.14-1.38). For type-specific CVDs, intellectual disability was significantly associated with cerebrovascular disease (HR, 2.50; 95% CI, 2.02-3.10), stroke (HR, 2.20; 95% CI, 1.69-2.86), heart failure (HR, 3.56; 95% CI, 2.37-5.35), hypertensive disease (HR, 1.30; 95% CI, 1.22-1.39), and deep vein thrombosis (HR, 2.10; 95% CI, 1.60-2.75). Stratified HRs of overall CVD were 1.14 (95% CI, 1.01-1.30) for borderline/mild intellectual disability, 1.25 (95% CI, 1.01-1.54) for moderate intellectual disability, and 1.91 (95% CI, 1.47-2.48) for severe/profound intellectual disability. After the exclusion of individuals with neurodevelopmental and neurologic comorbidity, intellectual disability remained significantly associated with increased risks of CVD. CONCLUSIONS: Individuals with intellectual disability had increased risks of early-onset CVD, in particular, for cerebrovascular disease, stroke, heart failure, and deep vein thrombosis, and the risks also increased with the severity of intellectual disability. Our findings highlight the awareness of increased risks of CVD in intellectual disability patients.

Familial clustering of intrahepatic cholestasis of pregnancy: A nationwide population-based study in Denmark.

BACKGROUND AND AIMS: Genetics plays a role in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP); however, empirical evidence on familial clustering of ICP is scarce. We aimed to assess the extent of familial recurrence of ICP. APPROACH AND RESULTS: This population-based cohort study included all 668,461 primiparous women who gave birth between 1995 and 2018 in Denmark. Women diagnosed with ICP were included to the index cohort. Kinship with index women was determined with the Danish Civil Registration System. Log-binomial regression was used to calculate the relative recurrence risk (RRR) of ICP in relatives of index women. A total of 6722 (1.0%) primiparous women were diagnosed with ICP. In co-twins (n=57), first-degree (n=2279), second-degree (n=1373), and third-degree (n=1758) relatives of the index women, the incidence of ICP reached 5.3%, 2.6%, 0.7%, and 1.4%, respectively, corresponding to adjusted RRRs of 4.82 (95% CI, 1.60-14.48), 2.54 (1.98-3.26), 0.81 (0.44-1.51), and 1.15 (0.77-1.71), respectively. The first-degree relatives of women who had recurrent ICP or first-trimester ICP seemed to be at higher risks [RRR, 4.30 (2.85-6.48), 3.04 (1.93-4.77), respectively]. A minor increased risk was observed in nonbiological relatives [RRR, 1.35 (1.05-1.73); n=4274, including women's full-brothers' partner and women's husbands' full sisters]. CONCLUSIONS: Co-twins and first-degree relatives of ICP patients were at ~5- and ~2.5-fold increased risk of ICP, respectively. No increased risk was observed in second-degree and third-degree relatives. Recurrent ICP and first-trimester ICP might indicate a higher degree of family clustering. Further investigation is needed to investigate the increased risk of ICP in nonbiological relatives.

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.

Prenatal Carbamazepine Exposure and Academic Performance in Adolescents: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: To investigate whether children born to mothers who used carbamazepine during pregnancy had worse academic performance in adolescence. METHODS: This population-based cohort study included all live-born singletons in Denmark between 1996 and 2002 who participated in the national ninth-grade exit examination (n = 370,859). Those born to mothers with prescription of antiseizure medications other than carbamazepine during pregnancy were excluded. We examined the association of in utero exposure to maternal carbamazepine redeemed during pregnancy (n = 290) with academic performance of offspring, defined by the scores in Danish and mathematics in ninth-grade exit examination. We estimated mean z-score difference with linear regression adjusted for socioeconomic factors and potential indications, including epilepsy and medication for other psychiatric disorders. Additional analyses addressing confounding by indication included comparison between in utero exposed vs past exposed and between past exposed and never exposed. In utero exposure to valproate monotherapy was used as a positive control and in utero exposure to lamotrigine as a negative control. RESULTS: At the age of 16.1 (SD 0.4) years, adolescents in utero exposed to maternal carbamazepine monotherapy had lower scores both in Danish and mathematics in ninth-grade exit examination (adjusted z-score difference, -0.14 [95% CI -0.24 to -0.05] and -0.17 [95% CI -0.28 to -0.07], respectively). In utero exposure to carbamazepine monotherapy was associated with lower scores than past exposure only (adjusted z-score difference, -0.24 [95% CI -0.41 to -0.06] for Danish and -0.25 [95% CI -0.44 to -0.06] for mathematics), while past exposure to carbamazepine was associated with minor decrease in offspring's academic performance (adjusted z-score difference, -0.02 [95% CI -0.09 to 0.06] for Danish and -0.07 [95% CI -0.16 to 0.01] for mathematics). The association was also observed for in utero exposure to valproate monotherapy, but not for in utero exposure to lamotrigine. DISCUSSION: In utero exposure to carbamazepine was associated with poorer academic performance in adolescence, as represented by lower scores in ninth-grade exit examination in Danish and mathematics. Additional studies are needed to confirm these findings because of limitations in this study and variable findings in prior studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that academic performance, as reflected in ninth-grade exit examinations in Danish and mathematics, was worse among those exposed to carbamazepine monotherapy in utero, compared with those without in utero exposure to antiseizure medications.

Maternal hypertensive disorder of pregnancy and mortality in offspring from birth to young adulthood: national population based cohort study.

OBJECTIVE: To examine the association of maternal hypertensive disorder of pregnancy (HDP) with overall and cause specific mortality in offspring from birth to young adulthood. DESIGN: Nationwide population based cohort study. SETTING: Danish national health registers. PARTICIPANTS: All 2 437 718 individuals live born in Denmark, 1978-2018, with follow-up from date of birth until date of death, emigration, or 31 December 2018, whichever came first. MAIN OUTCOME MEASURES: The primary outcome was all cause mortality. Secondary outcomes were 13 specific causes of death in offspring from birth to young adulthood (age 41 years). Cox regression was used to assess the association, taking into consideration several potential confounders. The role of timing of onset and severity of pre-eclampsia, maternal history of diabetes, and maternal education were also studied. RESULTS: 102 095 mothers had HDP: 67 683 with pre-eclampsia, 679 with eclampsia, and 33 733 with hypertension. During follow-up to 41 years (median 19.4 (interquartile range 9.7-28.7) years), deaths occurred in 781 (58.94 per 100 000 person years) offspring born to mothers with pre-eclampsia, 17 (133.73 per 100 000 person years) born to mothers with eclampsia, 223 (44.38 per 100 000 person years) born to mothers with hypertension, and 19 119 (41.99 per 100 000 person years) born to mothers with no HDP. The difference in cumulative incidence in overall mortality between cohorts exposed and unexposed to maternal HDP was 0.37% (95% confidence interval 0.11% to 0.64%), and the population attributable fraction for maternal HDP was estimated as 1.09% (95% confidence interval 0.77% to 1.41%). Maternal HDP was associated with a 26% (hazard ratio 1.26, 95% confidence interval 1.18 to 1.34) higher risk of all cause mortality in offspring. The corresponding estimates for maternal pre-eclampsia, eclampsia, and hypertension were 1.29 (1.20 to 1.38), 2.88 (1.79 to 4.63), and 1.12 (0.98 to 1.28). Increased risks were also observed for several cause specific mortalities, such as deaths from conditions originating in the perinatal period (2.04, 1.81 to 2.30), cardiovascular diseases (1.52, 1.08 to 2.13), digestive system diseases (2.09, 1.27 to 3.43), and endocrine, nutritional, and metabolic diseases (1.56, 1.08 to 2.27). The increased risks were more pronounced among offspring of mothers with early onset and severe pre-eclampsia (6.06, 5.35 to 6.86) or with both HDP and diabetes history (1.57, 1.16 to 2.14) or HDP and low education level (1.49, 1.34 to 1.66). CONCLUSION: Maternal HDP, particularly eclampsia and severe pre-eclampsia, is associated with increased risks of overall mortality and various cause specific mortalities in offspring from birth to young adulthood.

Determinants of workplace safety towards SARS-Cov-2 and combating COVID-19 among non-healthcare workers in Hong Kong, Nanjing and Wuhan, China.

There has been no validated tool to assess workplace infection control towards SARS-Cov-2 in non-healthcare industries. In this first year survey during 07/2020-04/2021, 6684 workers were recruited from varied non-healthcare settings of Hong Kong, Nanjing and Wuhan of China and responded standard questionnaires containing information of prevention measures and policies implemented by companies and personal preventive behaviour towards infection control. All participants were randomly stratified into two sub-samples as training and validation sample. Workplace safety index towards SARS-Cov-2 (WSI-SC2) was developed and validated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We identified 14 manifest variables in WSI-SC2, with three sub-indices named "Workplace infection control measures and prevention", "Company occupational safety and health management and commitment" and "Worker's personal preventive behavior and awareness towards infectious control". WSI-SC2 obtained a good internal consistency reliability (Cronbach's alpha coefficients ranged: 0.76-0.91), good composite reliability (composite reliability ranged: 0.70-0.95) and satisfactory fit of the model (GFI = 0.95; SRMR = 0.05; RMSEA = 0.07). We further performed stratified analysis according to cities, and the index remained stable. Workers with higher scores of WSI-SC2 were more likely to uptake COVID-19 test. This multi-city large study developed a novel and validated tool that could horizontally measure the workplace safety towards SARS-Cov-2 in non-healthcare workers.

Association of current income and reduction in income during the COVID-19 pandemic with anxiety and depression among non-healthcare workers.

BACKGROUND: Many workers experienced income reduction during the coronavirus disease 2019 (COVID-19) pandemic, which may link to adverse mental health. AIMS: This study aimed to examine the association of current income and reduction in income during COVID-19 with anxiety and depression levels among non-healthcare workers. METHODS: This is a multi-city cross-sectional study. We used standardized questionnaires to collect information. We regrouped the current income and income reduction during COVID-19 according to the tertile and median value of each specific city. Depression, Anxiety and Stress Scales-21 item short version (DASS-21) was used to assess anxiety and depression levels. We performed multinomial logistic regression to examine the association of current and reduced income with anxiety and depression. Path models were developed to outline the potential modification/indirect effect of subsidies from government. RESULTS: Large income reduction and low current income were significantly associated with more anxiety/depression symptoms. Path analysis showed that government subsidies could not significantly alleviate the impact of reduced income on anxiety/depression. CONCLUSION: Our findings showed that large income reduction and low current income were independently associated with anxiety/depression, while these symptoms may not be ameliorated by one-off government funds. This study suggests the need for long-term policies (e.g. developing sustained economic growth policies) to mitigate negative impacts of the COVID-19.

Associations between Preserved Foods and Breast Cancer Risk in Hong Kong Chinese Women.

Preserved food such as cured foods may contain nitrate and nitrite that may contribute to the breast cancer development. Evidence on the associations between these preserved food intakes and risk of breast cancer is sparse. This study aimed to examine the associations between preserved foods (i.e., cured meat, pickled vegetables, canned meat, and canned fruit/vegetables) and breast cancer risk in Hong Kong Chinese women. A total of 1,307 breast cancer cases and 1,050 age-matched controls were recruited from three hospitals during November 2011 through January 2018. We used a standardized questionnaire to collect information on dietary factors, including preserved foods. Unconditional multiple logistic regression was performed to calculate the adjusted odds ratio (AOR) of breast cancer in relation to preserved food with adjustment of potential confounders. We further performed stratified analysis according to the breast cancer biology subtypes. We found that cured meat consumption was significantly associated with the risk of breast cancer [AOR, 1.32; 95% confidence interval 95% (CI), 1.06-1.64]. Compared with no cured meat consumption, cured meat intake ≥ once per week was associated with an AOR of 2.66 (95% CI, 1.38-5.35). Women with canned fruit/vegetable ≥ consumption once per week had a higher risk of breast cancer (OR, 1.19; 95% CI, 1.00-1.41), particularly for the HER2-positive subtypes, but it became borderline after adjustment of confounders. Our study reveals a positive association between consumption of cured meat and breast cancer risk in Chinese population. Cured meat intake might be a potential novel risk factor for breast cancer but this would have to be confirmed by large prospective cohort studies. PREVENTION RELEVANCE: The main finding of this case-control study, an association between cured meat intake and a higher risk of breast cancer in Hong Kong Chinese women, contributes to the growing evidence for population-level health benefits of reducing cured meat consumption.

Risk of malignancy following exposure to Epstein-Barr Virus associated infectious mononucleosis: A nationwide population-based cohort study.

Purpose: Epstein-Barr virus (EBV) infection has been shown to contribute to oncogenesis and often causes acute clinical manifestation of Infectious mononucleosis (IM). It is unknown whether IM could increase the risk of subsequent malignancies. We aimed to evaluate the association of IM caused by EBV (EBV-IM) with overall and subtypes of malignancy in a large population-based cohort study. Methods: This study included 1,419,407 individuals born in Denmark between 1973 and 2016 identified from national registers and 23,057 individuals had IM. The 5,394 of them had confirmed EBV-IM and they were birth date- and sex- matched (1:63) to 1,396,350 non-IM individuals. Cox regression was used to examine the associations of EBV-IM with malignancy. Results: Individuals with a history of confirmed EBV-IM had an 88% increased overall risk of malignancy (hazard ratio [HR]:1·88, 95% confidence interval [CI]: 1·42-2·49) and a five-fold risk of hematologic malignancies (HR 5·04, 95% CI: 3·07-8·25), compared to those without IM. Similar estimates were observed in the sibling analysis. The overall risk of malignancy was greater for EBV-IM with complications (HR 8·93, 95% CI: 3·35-23·81) than that for EBV-IM without complications (HR 1·35, 95% CI: 1·20-1·53). EBV-IM duration was related to increased risk of malignancy in a dose-response way. Notably, the significant elevated risk of overall malignancy was observed in the first two years after EBV-IM onset (rate ratio [RR] 4·44, 95% CI: 2·75-7·17) and attenuated thereafter. Conclusion: EBV-IM was associated with an increased risk in malignancy, particularly hematologic malignancies and in the first two years following IM exposure. Our findings suggest an important time-window for early screening of the EBV-attributed malignancy.

Changes in physical activity and rest-activity circadian rhythm among Hong Kong community aged population before and during COVID-19.

BACKGROUND: This study aims to determine the changes in physical activity and actigraphy-measured rest-activity circadian rhythm among Hong Kong community aged population before and during the outbreak of COVID-19. METHODS: This is a three repeated measure population-based cross-sectional study. We recruited community older men aged > 60 years in three periods of the COVID-19 outbreak in Hong Kong, i.e., before the COVID-19 outbreak (2 July 2019-8 January 2020), between the 2nd and 3rd waves of COVID-19 (23 June 2020-9 July 2020), and during the 3rd wave of COVID-19 (15 September 2020-29 September 2020). Participants reported detailed information on their physical activity habits using the International Physical Activity Questionnaire and wore actigraphs continuously for 7 days (168 h). The actigraph data were then transferred to four rest-activity circadian rhythm parameters: midline statistic of rhythm (MESOR), amplitude, acrophase and percent rhythm. Multivariate logistic regression was performed to estimate the association of period effect of COVID-19 on physical activity and rest-activity circadian rhythm parameters. RESULTS: Among the 242 community older men, 106 (43.8%) of them were recruited before the COVID-19 outbreak, 66 (27.3%) were recruited between the 2nd and 3rd waves of COVID-19, and 70 (28.9%) were recruited during the late phase of the 3rd wave of COVID-19. Compared with those recruited before COVID-19, participants recruited between the 2nd and 3rd waves of COVID-19 had lower physical activity (adjusted odds ratio (AOR) = 2.03, 95% confidence interval (95%CI) =1.05-3.93), MESOR (AOR = 2.05, 95%CI = 1.01-4.18), and amplitude (AOR = 1.91, 95%CI = 0.95-3.83). There was no difference in physical activity or circadian rhythm parameters between subjects recruited before and during the late phase of the 3rd wave. CONCLUSIONS: This study found that the effect of COVID-19 on physical activity and rest-activity circadian rhythm for the community people may be short-term, indicating strong resilience of the community population. Although maintaining physical activity are encouraged for the older adults to sustain good health, a rebound in their physical activity may be a sign for the next wave of outbreak if insufficient social distancing and population protection are facilitated.

Association of maternal body mass index with intellectual disability risk.

OBJECTIVES: The study aimed to investigate the association between maternal body mass index (BMI) in early pregnancy and children's intellectual disability (ID) risk in the absence of chromosomal disorders, neurofibromatosis and tuberous sclerosis, taking adverse birth outcomes, maternal hypertension/diabetes and maternal socioeconomic status into consideration. METHODS: We conducted a cohort study of singletons without common genetic defects born in Sweden during 1992-2006, and followed them from birth until 31 December 2014 (n=1 186 836). Cox proportional hazards models were used to analyse the association between maternal BMI in early pregnancy and the risk of offspring's ID. RESULTS: The risk of ID was higher in children born to mothers who were underweight (HR=1.21, 95% CI=1.07 to 1.36), overweight (HR=1.28, 95% CI=1.21 to 1.34) or had obesity class I (HR=1.63, 95% CI=1.53 to 1.74), obesity class II (HR=2.08, 95% CI=1.88 to 2.30) and obesity class III (HR=2.31, 95% CI=1.46 to 3.65) than in children born to normal weight mothers. Results remained consistent after excluding children with adverse birth outcome or born to mothers with gestational hypertension/diabetes. Analysis stratified by maternal education and annual household income showed that the association between maternal underweight and children's ID risk was attenuated among children of mothers with tertiary education or with high income. CONCLUSIONS: Our findings suggest that maternal underweight or overweight/obesity in early pregnancy was associated with the development of ID in their offspring. This association was independent of the effect of adverse birth outcomes and maternal hypertension/diabetes. High socioeconomic status may attenuate the risk of ID among children of underweight mothers. This study highlights the importance of improving health education before conception to reduce children's ID risk.

Heterogeneous Associations Between Obesity and Reproductive-Related Factors and Specific Breast Cancer Subtypes Among Hong Kong Chinese Women.

Previous studies reported heterogeneous associations between obesity and reproductive-related breast cancer risk factors and breast cancer intrinsic subtypes; however, few studies have been conducted in Asian populations. Here, we aimed to examine whether risks associated with established breast cancer risk factors varied by breast cancer subtypes in Chinese women. We conducted a hospital-based case-control study in Hong Kong, including a total of 2169 Chinese women. Unconditional polytomous logistic regression models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals(95%CIs) to estimate relative risks associated with examined risk factors in case-control analyses and to test for heterogeneity across breast cancer subtypes in case-case analyses. In case-case analyses, compared with luminal A patients, luminal B (AOR = 1.76, 95% CI = 1.07-2.88), HER2 overexpressing (AOR = 3.40, 95% CI = 1.56-7.39), and triple negative (TNBC, AOR = 2.39, 95% CI = 1.18-4.82) patients were more likely to be postmenopausal. In case-control analyses, reduced risks associated with parity and younger age at first birth were only seen for luminal A and B cases especially among postmenopausal women, whereas having ≥ 3 children was associated with increased risk for HER2 overexpressing and TNBC among premenopausal women. Obesity was associated with increased risk for all subtypes. We found heterogeneous associations between parity-related risk factors by menopausal status and breast cancer subtypes among Chinese patients, which is similar to those observed in Western populations. Interestingly, obesity was associated with increased breast cancer risk regardless of menopausal status or subtypes, except for premenopausal luminal patients, which appears to be unique in Asian populations.

Associations between Coffee Products and Breast Cancer Risk: a Case-Control study in Hong Kong Chinese Women.

Coffee contains caffeine and diterpenes that were associated with decreased breast cancer risk, but results remained inconsistent. The study purpose was to investigate the associations between coffee products and breast cancer risk among Hong Kong Chinese women. We conducted a hospital-based case-control study in three public hospitals. 2169 Chinese women aged 24-84 years old were interviewed using a standardized questionnaire with questions asking types, cups and duration on coffee drinking. We used unconditional multivariate logistic regression to calculate the adjusted odds ratio (AOR) and 95% confidence interval (95% CI) for breast cancer risk with different coffee products. 238 (20.6%) cases and 179 (17.7%) controls are habitual coffee drinkers. No association was found between overall coffee drinking and breast cancer risk. Compared to the non-habitual coffee drinkers, women who consumed instant coffee (AOR = 1.50, 95% CI = 1.10-2.03) were significantly associated with an increased breast cancer risk. Women who drank brewed coffee (AOR = 0.48, 95% CI = 0.28-0.82) were negatively associated with breast cancer risk. A positive association between instant coffee and breast cancer risk was observed, contradicted to the outcomes of drinking brewed coffee. Larger studies are warranted to ascertain the role of different types of coffee products in breast cancer risk.