Greenness and its composition and configuration in association with allergic rhinitis in preschool children.

BACKGROUND: Few studies focus on the associations of green space composition and configuration with children's allergic rhinitis (AR). METHODS: A multi-center population-based cross-sectional study was performed in 7 cities in mainland of China between 2019 and 2020, recruiting 36,867 preschool children. Information on the current AR symptoms and demographics were collected by questionnaire. Exposure to residential greenness was estimated by Normalized Difference Vegetation Index (NDVI, 1000 m buffer) around the residences. Greenness composition was estimated in 3 main categories: forest, grassland, shrubland. Configuration of each category and total greenness (a spatial resolution of 10 m × 10 m) was estimated by 6 landscape pattern metrics to quantify their area, shape complexity, aggregation, connectivity, and patch density. Exposure to daily ambient particulate matter (PM1, PM2.5 and PM10, a spatial resolution of 1 km × 1 km) was estimated. Multilevel logistic regression models were applied to analyze the associations of greenness and its composition and configuration with AR, and mediation effects by PMs were examined by mediation analysis models. RESULTS: The prevalence of self-reported current AR in preschool children was 33.1%. Two indicators of forest, Aggregation Index of forest patches (AIforest) (odds ratio (OR):0.92, 95% Confidential Interval (CI): 0.88-0.97), and Patch Cohesion of forest (COHESIONforest) (OR: 0.93, 95% CI:0.89-0.98) showed significantly negative associations with AR symptoms. Mediation analyses found the associations were partially mediated by PMs. Age, exclusive breastfeed duration and season were the potential effect modifiers. The associations varied across seven cities. CONCLUSION: Our findings suggest the inverse associations of the aggregation and connectivity of forest patches surrounding residence addresses with AR symptoms. Since the cross-sectional study only provides associations rather than causation, further studies are needed to confirm our results as well as the underlying mechanisms.

High-dimensional generalized median adaptive lasso with application to omics data.

Recently, there has been a growing interest in variable selection for causal inference within the context of high-dimensional data. However, when the outcome exhibits a skewed distribution, ensuring the accuracy of variable selection and causal effect estimation might be challenging. Here, we introduce the generalized median adaptive lasso (GMAL) for covariate selection to achieve an accurate estimation of causal effect even when the outcome follows skewed distributions. A distinctive feature of our proposed method is that we utilize a linear median regression model for constructing penalty weights, thereby maintaining the accuracy of variable selection and causal effect estimation even when the outcome presents extremely skewed distributions. Simulation results showed that our proposed method performs comparably to existing methods in variable selection when the outcome follows a symmetric distribution. Besides, the proposed method exhibited obvious superiority over the existing methods when the outcome follows a skewed distribution. Meanwhile, our proposed method consistently outperformed the existing methods in causal estimation, as indicated by smaller root-mean-square error. We also utilized the GMAL method on a deoxyribonucleic acid methylation dataset from the Alzheimer's disease (AD) neuroimaging initiative database to investigate the association between cerebrospinal fluid tau protein levels and the severity of AD.

Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity.

BACKGROUND: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress. METHODS: This retrospective study included patients with coronary artery disease and without cancer who underwent resting 18F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. 18F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex. RESULTS: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P=0.036). High amygdalar 18F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (P<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P=0.030). CONCLUSIONS: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618.

Exposure to Chinese famine in early life and height across 2 generations: a longitudinal study based on the China Health and Nutrition Survey.

BACKGROUND: Poor nutrition early in life is associated with short stature, which is associated with increased risk of cardiovascular disease and mortality in later life. Less evidence is available about the impact of early-life nutrition on height growth in the subsequent generation. OBJECTIVES: This study investigated the associations of famine exposure in utero and early childhood with height across 2 generations. METHODS: We used longitudinal data from the China Health and Nutrition Survey. We included 5401 participants (F1) born in 1955-1966 (calendar year around the Chinese famine in 1959-1961) and their 3930 biological offspring (F2). We classified F1 participants into subgroups by famine exposure status (unexposed/exposed) and timing (fetal-/childhood-exposed) according to their birth year and grouped F2 by their parents' exposure. Linear regression models were applied to examine the associations of famine exposure with adult height of F1 and F2. Linear mixed effect models with fractional polynomial functions were performed to estimate the difference in height between exposure groups of F2 during childhood. RESULTS: Participants (F1) exposed to famine in utero or in childhood were shorter than those unexposed by 0.41 cm (95% CI: 0.03, 0.80) and 1.12 cm (95% CI: 0.75, 1.48), respectively. Offspring (F2) of exposed fathers were also shorter than those of unexposed parents by 1.07 cm (95% CI: 0.28, 1.86) during childhood (<18 y) and by 1.25 cm (95% CI: 0.07, 2.43) in adulthood (≥18 y), and those with exposed parents had a reduced height during childhood by 1.29 cm (95% CI: 0.68, 1.89) (all P values < 0.05). The associations were more pronounced among child offspring of highly-educated F1, particularly for paternal exposure and among female offspring (all P for interaction < 0.05). CONCLUSIONS: The findings support the intergenerational associations of famine exposure in early life with height in Chinese populations, indicating the public health significance of improving the nutritional status of mothers and children in the long run.

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 TESSELLATION DENSITY WITH PROGRESSION OF AXIAL LENGTH AND REFRACTION IN CHILDREN: An Artificial Intelligence-Assisted 4-Year Study.

PURPOSE: To investigate fundus tessellation density (TD) and its association with axial length (AL) elongation and spherical equivalent (SE) progression in children. METHODS: The school-based prospective cohort study enrolled 1,997 individuals aged 7 to 9 years in 11 elementary schools in Mojiang, China. Cycloplegic refraction and biometry were performed at baseline and 4-year visits. The baseline fundus photographs were taken, and TD, defined as the percentage of exposed choroidal vessel area in the photographs, was quantified using an artificial intelligence-assisted semiautomatic labeling approach. After the exclusion of 330 ineligible participants because of loss to follow-up or ineligible fundus photographs, logistic models were used to assess the association of TD with rapid AL elongation (>0.36 mm/year) and SE progression (>1.00 D/year). RESULTS: The prevalence of tessellation was 477 of 1,667 (28.6%) and mean TD was 0.008 ± 0.019. The mean AL elongation and SE progression in 4 years were 0.90 ± 0.58 mm and -1.09 ± 1.25 D. Higher TD was associated with longer baseline AL (ß, 0.030; 95% confidence interval: 0.015-0.046; P < 0.001) and more myopic baseline SE (ß, -0.017; 95% confidence interval: -0.032 to -0.002; P = 0.029). Higher TD was associated with rapid AL elongation (odds ratio, 1.128; 95% confidence interval: 1.055-1.207; P < 0.001) and SE progression (odds ratio, 1.123; 95% confidence interval: 1.020-1.237; P = 0.018). CONCLUSION: Tessellation density is a potential indicator of rapid AL elongation and refractive progression in children. TD measurement could be a routine to monitor AL elongation.

Multiply robust estimator for the difference in survival functions using pseudo-observations.

BACKGROUND: When estimating the causal effect on survival outcomes in observational studies, it is necessary to adjust confounding factors due to unbalanced covariates between treatment and control groups. There is no study on multiple robust method for estimating the difference in survival functions. In this study, we propose a multiply robust (MR) estimator, allowing multiple propensity score models and outcome regression models, to provide multiple protection. METHOD: Based on the previous MR estimator (Han 2014) and pseudo-observation approach, we proposed a new MR estimator for estimating the difference in survival functions. The proposed MR estimator based on the pseudo-observation approach has several advantages. First, the proposed estimator has a small bias when any PS and OR models were correctly specified. Second, the proposed estimator considers the advantage pf the pseudo-observation approach, which avoids proportional hazards assumption. A Monte Carlo simulation study was performed to evaluate the performance of the proposed estimator. And the proposed estimator was used to estimate the effect of chemotherapy on triple-negative breast cancer (TNBC) in real data. RESULTS: The simulation studies showed that the bias of the proposed estimator was small, and the coverage rate was close to 95% when any model for propensity score or outcome regression is correctly specified regardless of whether the proportional hazard assumption holds, finite sample size and censoring rate. And the simulation results also showed that even though the propensity score models are misspecified, the bias of the proposed estimator was still small when there is a correct model in candidate outcome regression models. And we applied the proposed estimator in real data, finding that chemotherapy could improve the prognosis of TNBC. CONCLUSIONS: The proposed estimator, allowing multiple propensity score and outcome regression models, provides multiple protection for estimating the difference in survival functions. The proposed estimator provided a new choice when researchers have a "difficult time" choosing only one model for their studies.

An improved multiply robust estimator for the average treatment effect.

BACKGROUND: In observational studies, double robust or multiply robust (MR) approaches provide more protection from model misspecification than the inverse probability weighting and g-computation for estimating the average treatment effect (ATE). However, the approaches are based on parametric models, leading to biased estimates when all models are incorrectly specified. Nonparametric methods, such as machine learning or nonparametric double robust approaches, are robust to model misspecification, but the efficiency of nonparametric methods is low. METHOD: In the study, we proposed an improved MR method combining parametric and nonparametric models based on the previous MR method (Han, JASA 109(507):1159-73, 2014) to improve the robustness to model misspecification and the efficiency. We performed comprehensive simulations to evaluate the performance of the proposed method. RESULTS: Our simulation study showed that the MR estimators with only outcome regression (OR) models, where one of the models was a nonparametric model, were the most recommended because of the robustness to model misspecification and the lowest root mean square error (RMSE) when including a correct parametric OR model. And the performance of the recommended estimators was comparative, even if all parametric models were misspecified. As an application, the proposed method was used to estimate the effect of social activity on depression levels in the China Health and Retirement Longitudinal Study dataset. CONCLUSIONS: The proposed estimator with nonparametric and parametric models is more robust to model misspecification.

Covariate balance-related propensity score weighting in estimating overall hazard ratio with distributed survival data.

BACKGROUND: When data is distributed across multiple sites, sharing information at the individual level among sites may be difficult. In these multi-site studies, propensity score model can be fitted with data within each site or data from all sites when using inverse probability-weighted Cox regression to estimate overall hazard ratio. However, when there is unknown heterogeneity of covariates in different sites, either approach may lead to potential bias or reduced efficiency. In this study, we proposed a method to estimate propensity score based on covariate balance-related criterion and estimate the overall hazard ratio while overcoming data sharing constraints across sites. METHODS: The proposed propensity score was generated by choosing between global and local propensity score based on covariate balance-related criterion, combining the global propensity score fitted in the entire population and the local propensity score fitted within each site. We used this proposed propensity score to estimate overall hazard ratio of distributed survival data with multiple sites, while requiring only the summary-level information across sites. We conducted simulation studies to evaluate the performance of the proposed method. Besides, we applied the proposed method to real-world data to examine the effect of radiation therapy on time to death among breast cancer patients. RESULTS: The simulation studies showed that the proposed method improved the performance in estimating overall hazard ratio comparing with global and local propensity score method, regardless of the number of sites and sample size in each site. Similar results were observed under both homogeneous and heterogeneous settings. Besides, the proposed method yielded identical results to the pooled individual-level data analysis. The real-world data analysis indicated that the proposed method was more likely to find a significant effect of radiation therapy on mortality compared to the global propensity score method and local propensity score method. CONCLUSIONS: The proposed covariate balance-related propensity score in multi-site distributed survival data outperformed the global propensity score estimated using data from the entire population or the local propensity score estimated within each site in estimating the overall hazard ratio. The proposed approach can be performed without individual-level data transfer between sites and would yield the same results as the corresponding pooled individual-level data analysis.

Association of nocturnal sleep duration and nocturnal sleep changes with instrumental activities of daily living disability among middle-aged and elderly Chinese.

OBJECTIVE: To investigate the association of baseline nocturnal sleep duration and sleep changes with functional disability in middle-aged and elderly Chinese. METHODS: Data for this study were collected from the China Health and Retirement Longitudinal Study (CHARLS) from baseline (2011) to the Wave 3 follow-up (2018). 8361 participants free of IADL disability in 2011 and aged ≥ 45 years old were recruited and prospectively followed till 2018 to analyze the association between baseline nocturnal sleep duration and IADL disability. Of these 8361 participants, a total of 6948 participants had no IADL disability at the first three follow-up visits and completed the 2018 follow-up to analyze the association between nocturnal sleep changes and IADL disability. Nocturnal sleep duration (hours) was self-reported at baseline. The coefficient of variation (CV) of nocturnal sleep duration at baseline and three follow-up visits was used to calculate sleep changes and classified into mild, moderate, and severe degrees by the quantiles. Cox proportional hazards regression model was used to analyze the association of baseline nocturnal sleep duration with IADL disability, and the binary logistic regression model was used to analyze the association of nocturnal sleep changes with IADL disability. RESULTS: Among the 8361 participants of 50237.5 person-years follow-up with a median follow-up of 7 years, 2158 (25.81%) participants developed IADL disabilities. Higher risks of IADL disability were observed among participants with sleep duration <7 h [HR(95%): 1.23(1.09-1.38)], 8∼<9 h [HR(95%): 1.05(1.00-1.32)] and ≥9 h [HR(95%): 1.21(1.01-1.45)] compared to those with 7∼<8 h. Among the 6948 participants, a total of 745 (10.72%) participants finally developed IADL disabilities. Compared with mild nocturnal sleep changes, moderate [OR(95%): 1.48(1.19-1.84)] and severe [OR(95%): 2.43(1.98-3.00)] sleep changes increased the probability of IADL disability. The restricted cubic spline model showed that a higher degree of nocturnal sleep changes was associated with a greater probability of IADL disability. CONCLUSION: Both insufficient and excessive nocturnal sleep duration were associated with higher risk of IADL disability in middle-aged and elderly adults, independent of the participants' gender, age, and napping habits. Higher nocturnal sleep changes were associated with a higher probability of disability in IADL. These findings highlight the importance of appropriate and stable nocturnal sleep, and the need to pay attention to population differences in the impact of nocturnal sleep duration on health.

Improved ambient air quality is associated with decreased prevalence of childhood asthma and infancy shortly after weaning is a sensitive exposure window.

BACKGROUND: The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top-ranking city of Shanghai, whether the improved air quality is beneficial for children's asthma and what time window of exposure plays critical roles. METHODS: Using a repeat cross-sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai. RESULTS: A significantly lower prevalence of doctor-diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM2.5 ), coarse particles (PM2.5-10 ) and inhalable particles (PM10 ) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log-binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM2.5 , PM2.5-10 and PM10 exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24-1.56), 1.51 (95% CI:1.15-1.98) and 1.53 (95% CI:1.27-1.85) for DDA, respectively. The distributed lag non-linear model showed the sensitive exposure window (SEW) was 5.5-11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding. CONCLUSIONS: Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma.

Stress-Related Neural Activity Associates With Coronary Plaque Vulnerability and Subsequent Cardiovascular Events.

BACKGROUND: Stress-related neural activity (SNA) assessed by amygdalar activity can predict cardiovascular events. However, its mechanistic linkage with plaque vulnerability is not fully elucidated. OBJECTIVES: The authors aimed to investigate the association of SNA with coronary plaque morphologic and inflammatory features as well as their ability in predicting major adverse cardiovascular events (MACE). METHODS: A total of 299 patients with coronary artery disease (CAD) and without cancer underwent 18F-fluorodexoyglucose positron emission tomography/computed tomography (PET/CT) and available coronary computed tomographic angiography (CCTA) between January 1, 2013, and December 31, 2020. SNA and bone-marrow activity (BMA) were assessed with validated methods. Coronary inflammation (fat attenuation index [FAI]) and high-risk plaque (HRP) characteristics were assessed by CCTA. Relations between these features were analyzed. Relations between SNA and MACE were assessed with Cox models, log-rank tests, and mediation (path) analyses. RESULTS: SNA was significant correlated with BMA (r = 0.39; P < 0.001) and FAI (r = 0.49; P < 0.001). Patients with heightened SNA are more likely to have HRP (40.7% vs 23.5%; P = 0.002) and increase risk of MACE (17.2% vs 5.1%, adjusted HR 3.22; 95% CI: 1.31-7.93; P = 0.011). Mediation analysis suggested that higher SNA associates with MACE via a serial mechanism involving BMA, FAI, and HRP. CONCLUSIONS: SNA is significantly correlated with FAI and HRP in patients with CAD. Furthermore, such neural activity was associated with MACE, which was mediated in part by leukopoietic activity in the bone marrow, coronary inflammation, and plaque vulnerability.

Age-specific association of stage of hypertension at diagnosis with cardiovascular and all-cause mortality among elderly patients with hypertension: a cohort study.

BACKGROUND: Hypertension affects 31.1% of adults worldwide, with higher prevalence of great than 60% in elderly. Advanced hypertension stage was associated with the higher risk of mortality. However, little is known about the age-specific association of stage of hypertension at diagnosis on cardiovascular mortality or all-cause mortality. Therefore, we aim to explore this age-specific association among the hypertensive elderly through stratified and interaction analyses. METHODS: This cohort study included 125,978 elderly hypertensive patients aged 60+ years from Shanghai of China. Cox regression was used to estimate the independent and joint effect of hypertension stage and age at diagnosis on cardiovascular and all-cause mortality. Interactions were evaluated both additively and multiplicatively. Multiplicative interaction was examined by the Wald test of the interaction term. Additive interaction was assessed by relative excess risk due to interaction (RERI). All analyses were performed stratified by sex. RESULTS: 28,250 patients died during the follow-up up to 8.85 years, and 13,164 died of cardiovascular events. Older age and advanced hypertension stage were risk factors of cardiovascular mortality and all-cause mortality. Besides, smoking, rarely exercise, BMI < 18.5 and diabetes were also the risk factors. When we compared stage 3 hypertension with stage 1 hypertension, hazard ratios (95% confidence interval) of cardiovascular mortality and all-cause mortality were 1.56(1.41-1.72) and 1.29(1.21-1.37) for males aged 60-69 years, 1.25(1.14-1.36) and 1.13(1.06-1.20) for males aged 70-85 years, 1.48(1.32-1.67) and 1.29(1.19-1.40) for females aged 60-69 years, and 1.19(1.10-1.29) and 1.08(1.01-1.15) for females aged 70-85 years, respectively. Negative multiplicative interaction and positive additive interaction between age at diagnosis and stage of hypertension at diagnosis on cardiovascular mortality were observed in males (HR: 0.81, 95% CI: 0.71-0.93 RERI: 0.59, 95% CI: 0.09-1.07) and females (HR: 0.81, 95% CI: 0.70-0.93 RERI: 0.66, 95% CI: 0.10-1.23). CONCLUSIONS: Diagnosed with stage 3 hypertension was associated with higher risks of cardiovascular mortality and all-cause mortality, which were stronger among patients with age at diagnosis of 60-69 years compared with those with age at diagnosis of 70-85 years. Therefore, for the younger part of the elderly, the Department of Health should pay more attention to treating patients with stage 3 hypertension.

Association of Self-Reported Nighttime Sleep Duration with Chronic Kidney Disease: China Health and Retirement Longitudinal Study.

INTRODUCTION: The cohort study aimed to assess the association of nighttime sleep duration and the change in nighttime sleep duration with chronic kidney disease (CKD) and whether the association between nighttime sleep duration and CKD differed by daytime napping. METHODS: This study included 11,677 individuals from the China Health and Retirement Longitudinal Study (CHARLS) and used data from the 2011 baseline survey and four follow-up waves. Nighttime sleep duration was divided into three groups: short (<7 h per night), optimal (7-9 h), and long nighttime sleep duration (>9 h). Daytime napping was divided into two groups: no nap and with a nap. We used Cox proportional hazards model to examine the effect of nighttime sleep duration at baseline and change in nighttime sleep duration on incident CKD and a joint effect of nighttime sleep duration and nap time on onset CKD. RESULTS: With a follow-up of 7 years, the incidence of CKD among those with short, optimal, and long nighttime sleep duration was 9.89, 6.75, and 9.05 per 1,000 person-years, respectively. Compared to individuals with optimal nighttime sleep duration, short nighttime sleepers had a 44% higher risk of onset CKD (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.21-1.72). Compared to participants with persistent optimal nighttime sleep duration, those with persistent short or long nighttime sleep duration had an increased risk of incident CKD (HR: 1.44, 95% CI: 1.15-1.80). We found a lower incidence of CKD in participants with short nighttime sleep duration and a nap (HR: 0.74, 95% CI: 0.60-0.93), compared to those with short nighttime sleep duration and no nap. CONCLUSION: Short nighttime sleep duration and persistent long or short nighttime sleep duration were associated with a higher risk of onset CKD. Keeping persistent optimal nighttime sleep duration may help reduce CKD risk later in life. Daytime napping may be protective against CKD incidence.

Association of nocturnal sleep duration and midday napping with subjective poor hearing among middle-aged and older adults in China.

Background: Hearing loss has occurred as a critical concern for aging and health. However, it remains unknown whether nocturnal sleep and midday napping duration are associated with hearing loss in middle-aged and older adults. Methods: The study comprised 9,573 adults from China Health and Retirement Longitudinal Study, who have completed the survey for sleep characteristics and subjective functional hearing. We collected self-reported nocturnal sleep duration (<5, 5 to <6, 6 to <7, 7 to <9, ≥9 h/night) and midday napping duration (≤5, 5 to ≤30, and >30 min). The sleep information was classified into different sleep patterns. The primary outcome was self-reported hearing loss events. Multivariate Cox regression models and restricted cubic splines were used to investigate the longitudinal association of sleep characteristics with hearing loss. We applied Cox generalized additive models and bivariate exposure-response surface diagrams to visualize the effects of different sleep patterns on hearing loss. Results: We confirmed 1,073 cases of hearing loss (55.1% female) during the follow-up. After adjusting for demographic characteristics, lifestyle factors and health condition, nocturnal sleep with < 5 h was positively associated with hearing loss [hazard ratio (HR): 1.45, 95% confidence interval [CI]: 1.20, 1.75]. Individuals with napping for 5 to ≤30 min had a 20% (HR: 0.80, 95%CI: 0.63, 1.00) lower risk of hearing loss compared with those with napping ≤ 5 min. Restrictive cubic splines showed the reverse J-shaped association between nocturnal sleep and hearing loss. Moreover, we found significant joint effects of sleeping < 7 h/night and midday napping ≤ 5 min (HR: 1.27, 95% CI: 1.06, 1.52) on hearing loss. Bivariate exposure-response surface diagrams also reflected the finding that short sleep without napping existed the highest risk of hearing loss. Compared with persistently sleeping moderately (7-9 h/night), those who persistently slept < 7 h/night or shifted from < 7 h/night to moderate or > 9 h/night had higher risks of hearing loss. Conclusion: Inadequate nocturnal sleep was associated with an elevated risk of poor subjective hearing in middle-aged and older adults, while moderate napping decreased the risk of hearing loss. Keeping sleep stable within recommendation duration may be a useful strategy for preventing poor hearing loss.

Association of dietary calcium with mortality from all causes, cardiovascular disease and cancer in people with hypertension.

Association between calcium intake and premature mortality in the general population has been well studied, but little is known about the association among specific populations. The authors aim to evaluate the association among people with hypertension and to provide a proper reference range of dietary calcium intake. This prospective cohort study included 8534 US adults with hypertension from National Health and Nutrition Examination Survey cycles 2003-2014. Dietary calcium intakes were self-reported and mortality status was ascertained by National Death Index records. During a median follow-up of 5.9 years, 1357 death occurred. Compared with participants of dietary calcium intake in quintile 1, participants in quintiles 2 and 4 had a 27% (HR: 0.73, 95% CI: 0.60-0.89) and a 29% lower risk (HR: 0.71, 95% CI: 0.57-0.88) of all-cause mortality respectively. The authors also observed a 34% lower risk (HR: 0.66, 95% CI: 0.45-0.97) of CVD death among participants in quintile 3 and a 37% lower risk (HR: 0.63, 95% CI: 0.40-0.99) of cancer-related death in participants in quintile 4 respectively. Restricted cubic spline (RCS) regression revealed a consistent protective effect of dietary calcium in participants with a daily intake of over 1000 mg, but a daily intake over 1200 mg fails to show further protective effect. Our findings suggest that elevated dietary calcium was associated with lower mortality risk from all-causes, cardiovascular disease (CVD) and cancer, and supplying sufficient dietary calcium intake, between 1000 and 1200 mg per day, in people with hypertension may be considered cost-effective to decrease risk of premature death.

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.

Machine learning to predict occult metastatic lymph nodes along the recurrent laryngeal nerves in thoracic esophageal squamous cell carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) metastasizes in an unpredictable fashion to adjacent lymph nodes, including those along the recurrent laryngeal nerves (RLNs). This study is to apply machine learning (ML) for prediction of RLN node metastasis in ESCC. METHODS: The dataset contained 3352 surgically treated ESCC patients whose RLN lymph nodes were removed and pathologically evaluated. Using their baseline and pathological features, ML models were established to predict RLN node metastasis on each side with or without the node status of the contralateral side. Models were trained to achieve at least 90% negative predictive value (NPV) in fivefold cross-validation. The importance of each feature was measured by the permutation score. RESULTS: Tumor metastases were found in 17.0% RLN lymph nodes on the right and 10.8% on the left. In both tasks, the performance of each model was comparable, with a mean area under the curve ranging from 0.731 to 0.739 (without contralateral RLN node status) and from 0.744 to 0.748 (with contralateral status). All models showed approximately 90% NPV scores, suggesting proper generalizability. The pathology status of chest paraesophgeal nodes and tumor depth had the highest impacts on the risk of RLN node metastasis in both models. CONCLUSION: This study demonstrated the feasibility of ML in predicting RLN node metastasis in ESCC. These models may potentially be used intraoperatively to spare RLN node dissection in low-risk patients, thereby minimizing adverse events associated with RLN injuries.