Association of Regular Opioid Use With Incident Dementia and Neuroimaging Markers of Brain Health in Chronic Pain Patients: Analysis of UK Biobank.

OBJECTIVES: We aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients. DESIGN: The primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes. SETTING AND PARTICIPANTS: Dementia-free UK Biobank participants with chronic pain and regular analgesic use. MEASUREMENTS: Chronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively. RESULTS: Prospective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08-1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19-0.71] per 1000 person-years; Wald χ2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07-1.37, Wald χ2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08-1.50, Wald χ2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23-1.67, Wald χ2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes. CONCLUSION: Regular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.

Persistence and Variation of the Indirect Effects of COVID-19 Restrictions on the Spectrum of Notifiable Infectious Diseases in China: Analysis of National Surveillance Among Children and Adolescents From 2018 to 2021.

BACKGROUND: Beyond the direct effect of COVID-19 infection on young people, the wider impact of the pandemic on other infectious diseases remains unknown. OBJECTIVE: This study aims to assess changes in the incidence and mortality of 42 notifiable infectious diseases during the pandemic among children and adolescents in China, compared with prepandemic levels. METHODS: The Notifiable Infectious Disease Surveillance System of China was used to detect new cases and fatalities among individuals aged 5-22 years across 42 notifiable infectious diseases spanning from 2018 to 2021. These infectious diseases were categorized into 5 groups: respiratory, gastrointestinal and enterovirus, sexually transmitted and blood-borne, zoonotic, and vector-borne diseases. Each year (2018-2021) was segmented into 4 phases: phase 1 (January 1-22), phase 2 (January 23-April 7), phase 3 (April 8-August 31), and phase 4 (September 1-December 31) according to the varying intensities of pandemic restrictive measures in 2020. Generalized linear models were applied to assess the change in the incidence and mortality within each disease category, using 2018 and 2019 as the reference. RESULTS: A total of 4,898,260 incident cases and 3701 deaths were included. The overall incidence of notifiable infectious diseases decreased sharply during the first year of the COVID-19 pandemic (2020) compared with prepandemic levels (2018 and 2019), and then rebounded in 2021, particularly in South China. Across the past 4 years, the number of deaths steadily decreased. The incidence of diseases rebounded differentially by the pandemic phase. For instance, although seasonal influenza dominated respiratory diseases in 2019, it showed a substantial decline during the pandemic (percent change in phase 2 2020: 0.21, 95% CI 0.09-0.50), which persisted until 2021 (percent change in phase 4 2021: 1.02, 95% CI 0.74-1.41). The incidence of gastrointestinal and enterovirus diseases decreased by 33.6% during 2020 but rebounded by 56.9% in 2021, mainly driven by hand, foot, and mouth disease (percent change in phase 3 2021: 1.28, 95% CI 1.17-1.41) and infectious diarrhea (percent change in phase 3 2020: 1.22, 95% CI 1.17-1.28). Sexually transmitted and blood-borne diseases were restrained during the first year of 2021 but rebounded quickly in 2021, mainly driven by syphilis (percent change in phase 3 2020: 1.31, 95% CI 1.23-1.40) and gonorrhea (percent change in phase 3 2020: 1.10, 95% CI 1.05-1.16). Zoonotic diseases were not dampened by the pandemic but continued to increase across the study period, mainly due to brucellosis (percent change in phase 2 2020: 0.94, 95% CI 0.75-1.16). Vector-borne diseases showed a continuous decline during 2020, dominated by hemorrhagic fever (percent change in phase 2 2020: 0.68, 95% CI 0.53-0.87), but rebounded in 2021. CONCLUSIONS: The COVID-19 pandemic was associated with a marked decline in notifiable infectious diseases in Chinese children and adolescents. These effects were not sustained, with evidence of a rebound to prepandemic levels by late 2021. To effectively address the postpandemic resurgence of infectious diseases in children and adolescents, it will be essential to maintain disease surveillance and strengthen the implementation of various initiatives. These include extending immunization programs, prioritizing the management of sexually transmitted infections, continuing feasible nonpharmaceutical intervention projects, and effectively managing imported infections.

Early-life exposure to tobacco, genetic susceptibility, and accelerated biological aging in adulthood.

Early-life tobacco exposure serves as a non-negligible risk factor for aging-related diseases. To understand the underlying mechanisms, we explored the associations of early-life tobacco exposure with accelerated biological aging and further assessed the joint effects of tobacco exposure and genetic susceptibility. Compared with those without in utero exposure, participants with in utero tobacco exposure had an increase in Klemera-Doubal biological age (KDM-BA) and PhenoAge acceleration of 0.26 and 0.49 years, respectively, but a decrease in telomere length of 5.34% among 276,259 participants. We also found significant dose-response associations between the age of smoking initiation and accelerated biological aging. Furthermore, the joint effects revealed that high-polygenic risk score participants with in utero exposure and smoking initiation in childhood had the highest accelerated biological aging. There were interactions between early-life tobacco exposure and age, sex, deprivation, and diet on KDM-BA and PhenoAge acceleration. These findings highlight the importance of reducing early-life tobacco exposure to improve healthy aging.

Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes.

The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.

Long-term variations of urban-Rural disparities in infectious disease burden of over 8.44 million children, adolescents, and youth in China from 2013 to 2021: An observational study.

BACKGROUND: An accelerated epidemiological transition, spurred by economic development and urbanization, has led to a rapid transformation of the disease spectrum. However, this transition has resulted in a divergent change in the burden of infectious diseases between urban and rural areas. The objective of our study was to evaluate the long-term urban-rural disparities in infectious diseases among children, adolescents, and youths in China, while also examining the specific diseases driving these disparities. METHODS AND FINDINGS: This observational study examined data on 43 notifiable infectious diseases from 8,442,956 cases from individuals aged 4 to 24 years, with 4,487,043 cases in urban areas and 3,955,913 in rural areas. The data from 2013 to 2021 were obtained from China's Notifiable Infectious Disease Surveillance System. The 43 infectious diseases were categorized into 7 categories: vaccine-preventable, bacterial, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. The calculation of infectious disease incidence was stratified by urban and rural areas. We used the index of incidence rate ratio (IRR), calculated by dividing the urban incidence rate by the rural incidence rate for each disease category, to assess the urban-rural disparity. During the nine-year study period, most notifiable infectious diseases in both urban and rural areas exhibited either a decreased or stable pattern. However, a significant and progressively widening urban-rural disparity in notifiable infectious diseases was observed. Children, adolescents, and youths in urban areas experienced a higher average yearly incidence compared to their rural counterparts, with rates of 439 per 100,000 compared to 211 per 100,000, respectively (IRR: 2.078, 95% CI [2.075, 2.081]; p < 0.001). From 2013 to 2021, this disparity was primarily driven by higher incidences of pertussis (IRR: 1.782, 95% CI [1.705, 1.862]; p < 0.001) and seasonal influenza (IRR: 3.213, 95% CI [3.205, 3.220]; p < 0.001) among vaccine-preventable diseases, tuberculosis (IRR: 1.011, 95% CI [1.006, 1.015]; p < 0.001), and scarlet fever (IRR: 2.942, 95% CI [2.918, 2.966]; p < 0.001) among bacterial diseases, infectious diarrhea (IRR: 1.932, 95% CI [1.924, 1.939]; p < 0.001), and hand, foot, and mouth disease (IRR: 2.501, 95% CI [2.491, 2.510]; p < 0.001) among gastrointestinal and enterovirus diseases, dengue (IRR: 11.952, 95% CI [11.313, 12.628]; p < 0.001) among vectorborne diseases, and 4 sexually transmitted and bloodborne diseases (syphilis: IRR 1.743, 95% CI [1.731, 1.755], p < 0.001; gonorrhea: IRR 2.658, 95% CI [2.635, 2.682], p < 0.001; HIV/AIDS: IRR 2.269, 95% CI [2.239, 2.299], p < 0.001; hepatitis C: IRR 1.540, 95% CI [1.506, 1.575], p < 0.001), but was partially offset by lower incidences of most zoonotic and quarantinable diseases in urban areas (for example, brucellosis among zoonotic: IRR 0.516, 95% CI [0.498, 0.534], p < 0.001; hemorrhagic fever among quarantinable: IRR 0.930, 95% CI [0.881, 0.981], p = 0.008). Additionally, the overall urban-rural disparity was particularly pronounced in the middle (IRR: 1.704, 95% CI [1.699, 1.708]; p < 0.001) and northeastern regions (IRR: 1.713, 95% CI [1.700, 1.726]; p < 0.001) of China. A primary limitation of our study is that the incidence was calculated based on annual average population data without accounting for population mobility. CONCLUSIONS: A significant urban-rural disparity in notifiable infectious diseases among children, adolescents, and youths was evident from our study. The burden in urban areas exceeded that in rural areas by more than 2-fold, and this gap appears to be widening, particularly influenced by tuberculosis, scarlet fever, infectious diarrhea, and typhus. These findings underscore the urgent need for interventions to mitigate infectious diseases and address the growing urban-rural disparity.

Long-term risk of psychiatric disorder and psychotropic prescription after SARS-CoV-2 infection among UK general population.

Despite evidence indicating increased risk of psychiatric issues among COVID-19 survivors, questions persist about long-term mental health outcomes and the protective effect of vaccination. Using UK Biobank data, three cohorts were constructed: SARS-CoV-2 infection (n = 26,101), contemporary control with no evidence of infection (n = 380,337) and historical control predating the pandemic (n = 390,621). Compared with contemporary controls, infected participants had higher subsequent risks of incident mental health at 1 year (hazard ratio (HR): 1.54, 95% CI 1.42-1.67; P = 1.70 × 10-24; difference in incidence rate: 27.36, 95% CI 21.16-34.10 per 1,000 person-years), including psychotic, mood, anxiety, alcohol use and sleep disorders, and prescriptions for antipsychotics, antidepressants, benzodiazepines, mood stabilizers and opioids. Risks were higher for hospitalized individuals (2.17, 1.70-2.78; P = 5.80 × 10-10) than those not hospitalized (1.41, 1.30-1.53; P = 1.46 × 10-16), and were reduced in fully vaccinated people (0.97, 0.80-1.19; P = 0.799) compared with non-vaccinated or partially vaccinated individuals (1.64, 1.49-1.79; P = 4.95 × 10-26). Breakthrough infections showed similar risk of psychiatric diagnosis (0.91, 0.78-1.07; P = 0.278) but increased prescription risk (1.42, 1.00-2.02; P = 0.053) compared with uninfected controls. Early identification and treatment of psychiatric disorders in COVID-19 survivors, especially those severely affected or unvaccinated, should be a priority in the management of long COVID. With the accumulation of breakthrough infections in the post-pandemic era, the findings highlight the need for continued optimization of strategies to foster resilience and prevent escalation of subclinical mental health symptoms to severe disorders.

Global burden of early-onset osteoarthritis, 1990-2019: results from the Global Burden of Disease Study 2019.

OBJECTIVES: Early-onset osteoarthritis (OA) is an emerging health issue amidst the escalating prevalence of overweight and obesity. However, there are scant data on its disease, economic burden and attributable burden due to high body mass index (BMI). METHODS: Using data from the Global Burden of Diseases Study 2019, we examined the numbers of incident cases, prevalent cases, years lived with disability (YLDs) and corresponding age-standardised rates for early-onset OA (diagnosis before age 55) from 1990 to 2019. The case definition was symptomatic and radiographically confirmed OA in any joint. The average annual percentage changes (AAPCs) of the age-standardised rates were calculated to quantify changes. We estimated the economic burden of early-onset OA and attributable burden to high BMI. RESULTS: From 1990 to 2019, the global incident cases, prevalent cases and YLDs of early-onset OA were doubled. 52.31% of incident OA cases in 2019 were under 55 years. The age-standardised rates of incidence, prevalence and YLDs increased globally and for countries in all Sociodemographic Index (SDI) quintiles (all AAPCs>0, p<0.05), with the fastest increases in low-middle SDI countries. 98.04% of countries exhibited increasing trends in all age-standardised rates. Early-onset OA accounts for US$46.17 billion in healthcare expenditure and US$60.70 billion in productivity loss cost in 2019. The attributable proportion of high BMI for early-onset OA increased globally from 9.41% (1990) to 15.29% (2019). CONCLUSIONS: Early-onset OA is a developing global health problem, causing substantial economic costs in most countries. Targeted implementation of cost-effective policies and preventive intervention is required to address the growing health challenge.

Observational methods for COVID-19 vaccine effectiveness research: an empirical evaluation and target trial emulation.

BACKGROUND: There are scarce data on best practices to control for confounding in observational studies assessing vaccine effectiveness to prevent COVID-19. We compared the performance of three well-established methods [overlap weighting, inverse probability treatment weighting and propensity score (PS) matching] to minimize confounding when comparing vaccinated and unvaccinated people. Subsequently, we conducted a target trial emulation to study the ability of these methods to replicate COVID-19 vaccine trials. METHODS: We included all individuals aged ≥75 from primary care records from the UK [Clinical Practice Research Datalink (CPRD) AURUM], who were not infected with or vaccinated against SARS-CoV-2 as of 4 January 2021. Vaccination status was then defined based on first COVID-19 vaccine dose exposure between 4 January 2021 and 28 January 2021. Lasso regression was used to calculate PS. Location, age, prior observation time, regional vaccination rates, testing effort and COVID-19 incidence rates at index date were forced into the PS. Following PS weighting and matching, the three methods were compared for remaining covariate imbalance and residual confounding. Last, a target trial emulation comparing COVID-19 at 3 and 12 weeks after first vaccine dose vs unvaccinated was conducted. RESULTS: Vaccinated and unvaccinated cohorts comprised 583 813 and 332 315 individuals for weighting, respectively, and 459 000 individuals in the matched cohorts. Overlap weighting performed best in terms of minimizing confounding and systematic error. Overlap weighting successfully replicated estimates from clinical trials for vaccine effectiveness for ChAdOx1 (57%) and BNT162b2 (75%) at 12 weeks. CONCLUSION: Overlap weighting performed best in our setting. Our results based on overlap weighting replicate previous pivotal trials for the two first COVID-19 vaccines approved in Europe.

Use of Sex-Specific Body Mass Index to Optimize Low Correlation With Height and High Correlation With Fatness: A UK Biobank Study.

Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of -50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes.

Predicting recurrence and survival in patients with non-metastatic renal-cell carcinoma after nephrectomy: a prospective population-based study with multicenter validation.

BACKGROUND: Accurate prognostication of oncological outcomes is crucial for the optimal management of patients with renal cell carcinoma (RCC) after surgery. Previous prediction models were developed mainly based on retrospective data in the Western populations, and their predicting accuracy remains limited in contemporary, prospective validation. We aimed to develop contemporary RCC prognostic models for recurrence and overall survival (OS) using prospective population-based patient cohorts and compare their performance with existing, mostly utilized ones. METHODS: In this prospective analysis and external validation study, the development set included 11  128 consecutive patients with non-metastatic RCC treated at a tertiary urology center in China between 2006 and 2022, and the validation set included 853 patients treated at 13 medical centers in the USA between 1996 and 2013. The primary outcome was progression-free survival (PFS), and the secondary outcome was OS. Multivariable Cox regression was used for variable selection and model development. Model performance was assessed by discrimination [Harrell's C-index and time-dependent areas under the curve (AUC)] and calibration (calibration plots). Models were validated internally by bootstrapping and externally by examining their performance in the validation set. The predictive accuracy of the models was compared with validated models commonly used in clinical trial designs and with recently developed models without extensive validation. RESULTS: Of the 11  128 patients included in the development set, 633 PFS and 588 OS events occurred over a median follow-up of 4.3 years [interquartile range (IQR) 1.7-7.8]. Six common clinicopathologic variables (tumor necrosis, size, grade, thrombus, nodal involvement, and perinephric or renal sinus fat invasion) were included in each model. The models demonstrated similar C-indices in the development set (0.790 [95% CI 0.773-0.806] for PFS and 0.793 [95% CI 0.773-0.811] for OS) and in the external validation set (0.773 [0.731-0.816] and 0.723 [0.731-0.816]). A relatively stable predictive ability of the models was observed in the development set (PFS: time-dependent AUC 0.832 at 1 year to 0.760 at 9 years; OS: 0.828 at 1 year to 0.794 at 9 years). The models were well calibrated and their predictions correlated with the observed outcome at 3, 5, and 7 years in both development and validation sets. In comparison to existing prognostic models, the present models showed superior performance, as indicated by C-indices ranging from 0.722 to 0.755 (all P <0.0001) for PFS and from 0.680 to 0.744 (all P <0.0001) for OS. The predictive accuracy of the current models was robust in patients with clear-cell and non-clear-cell RCC. CONCLUSIONS: Based on a prospective population-based patient cohort, the newly developed prognostic models were externally validated and outperformed the currently available models for predicting recurrence and survival in patients with non-metastatic RCC after surgery. The current models have the potential to aid in clinical trial design and facilitate clinical decision-making for both clear-cell and non-clear-cell RCC patients at varying risk of recurrence and survival.

Progress in the epidemiology of COVID-19 infections in children and adolescents / 中国学校卫生

Abstract@#The COVID-19 pandemic has posed a series of complex challenges. COVID-19 in children and adolescents is generally less severe than in adults and the elderly; however, some children and adolescents may experience severe complications and adverse health effects even after mild or asymptomatic COVID-19 infections. The article focuses on gathering the epidemic characteristics, health impact, risk factors, prevention and control measures, and vaccination status of children and adolescents with COVID-19 infection to provide recommendations for protecting children and adolescents in the post COVID-19 era.

Long-Term Exposure to Low Concentrations of Ambient Benzene and Mortality in a National English Cohort.

Background: Benzene affects human health through environmental exposure in addition to occupational contact. However, few studies have examined the associations between long-term exposure to low concentrations of ambient benzene and mortality risks in nonoccupational settings.Methods: This prospective cohort study consists of 393,042 participants without stroke, myocardial infarction, or cancer at baseline from the UK Biobank. Annual average concentrations of benzene for each year during follow-up were measured using air dispersion models. The main outcomes were all-cause mortality and mortality from specific causes. Cox proportional-hazards models with time-varying exposure measurements were used to estimate the hazard ratios and 95% confidence intervals (CIs) for mortality risks. Restricted cubic spline models were used to estimate exposure-response relationships.Measurements and Main Results: With each interquartile range increase in the average annual concentration of benzene, the adjusted hazard ratios of mortality risk from all causes, cardiovascular disease, cancer, and respiratory disease were 1.26 (95% CI, 1.24-1.27), 1.24 (95% CI, 1.21-1.28), 1.27 (95% CI, 1.25-1.29), and 1.25 (95% CI, 1.20-1.30), respectively. The monotonically increasing exposure-response curves showed no threshold and plateau within the observed concentration range. Furthermore, the effect of benzene exposure on mortality persisted across different subgroups and was somewhat stronger in younger and White people (P for interaction < 0.05).Conclusions: Long-term exposure to low concentrations of ambient benzene significantly increases mortality risk in the general population. Ambient benzene represents a potential threat to public health, and further investigations are needed to support timely pollution regulation and health protection.

HLA-C*07:01 and HLA-DQB1*02:01 protect against white matter hyperintensities and deterioration of cognitive function: A population-based cohort study.

BACKGROUND: Neuroinflammation and aberrant immune regulation are increasingly implicated in the pathophysiology of white matter hyperintensities (WMH), an imaging marker of cerebrovascular pathologies and predictor of cognitive impairment. The role of human leukocyte antigen (HLA) genes, critical in immunoregulation and associated with susceptibility to neurodegenerative diseases, in WMH pathophysiology remains unexplored. METHODS: We performed association analyses between classical HLA alleles and WMH volume, derived from MRI scans of 38 302 participants in the UK Biobank. To identify independent functional alleles driving these associations, we conducted conditional forward stepwise regression and lasso regression. We further investigated whether these functional alleles showed consistent associations with WMH across subgroups characterized by varying levels of clinical determinants. Additionally, we validated the clinical relevance of the identified alleles by examining their association with cognitive function (n = 147 549) and dementia (n = 460 029) in a larger cohort. FINDINGS: Four HLA alleles (DQB1*02:01, DRB1*03:01, C*07:01, and B*08:01) showed an association with reduced WMH volume after Bonferroni correction for multiple comparisons. Among these alleles, DQB1*02:01 exhibited the most significant association (ß = -0.041, 95 % CI: -0.060 to -0.023, p = 1.04 × 10-5). Forward selection and lasso regression analyses indicated that DQB1*02:01 and C*07:01 primarily drove this association. The protective effect against WMH conferred by DQB1*02:01 and C*07:01 persisted in clinically relevant subgroups, with a stronger effect observed in older participants. Carrying DQB1*02:01 and C*07:01 was associated with higher cognitive function, but no association with dementia was found. INTERPRETATION: Our population-based findings support the involvement of immune-associated mechanisms, particularly both HLA class I and class II genes, in the pathogenesis of WMH and subsequent consequence of cognitive functions.

Urban-Rural Disparity in Mortality Patterns of Respiratory Diseases Among Older Adults - China, 1987-2021.

What is already known about this topic?: Respiratory diseases (RDs) are the primary cause of death in older adults in China. However, there is limited evidence regarding the disparity in mortality rates of RDs between urban and rural areas among the elderly population. What is added by this report?: The age-standardized mortality rate (ASMR) due to RDs in the elderly population in both urban and rural areas of China has shown a consistent decrease. This trend is observed in both males and females. However, there was no significant change in the average annual percentage of ASMR for pneumonia among the urban elderly population and rural elderly men throughout the study period. What are the implications for public health practice?: Efforts should be made in China to reduce mortality from chronic lower respiratory disease and pneumonia among the elderly, particularly in urban populations.

Disparity in spectrum of infectious diseases between in-school and out-of-school children, adolescents, and youths in China: findings from a successive national surveillance from 2013 to 2021.

Background: An accelerated epidemiological transition, economic development and urbanization have brought rapid reductions but a potential disparity in infectious diseases burdens in-school and out-of-school children, adolescents, and youths in China. This paper assesses the disparity in spectrum of infectious diseases between two groups, and described disparity's variation by age, year and province, and determined the priority diseases. Methods: A total of 7,912,274 new incident cases (6,159,021 in school and 1,753,253 out of school) aged 6-21 years across 43 notifiable infectious diseases have been collected based on China's Notifiable Infectious Disease Surveillance System from 2013 to 2021. All infectious diseases are categorized into seven categories: vaccine preventable, bacteria, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. We used the index of incidence rate ratio (IRR) of by specific disease, category, year, and age to assess the disparity between those out-of-school and in-school, and determine their separate priority diseases. Findings: From 2013 to 2021, a small disparity of notifiable infectious diseases existed with higher average yearly incidence for out-of-school children, adolescents, and youth than that in-school (327.601 v.s. 319.677 per 100,000, IRR = 1.025, 95%CI: 1.023-1.027, standardized IRR = 1.169, 95%CI: 1.155-1.183), and it gradually narrowed by surveillance years with IRR from 1.351 in 2013 to 1.015 in 2021 due to large decreased disparity in compulsory education stage group. Such disparity was mainly driven by sexually transmitted and bloodborne diseases, bacteria diseases, vectorborne diseases, quarantinable diseases and zoonotic diseases. However, vaccine preventable diseases, gastrointestinal and enterovirus diseases showed higher incidence of infectious diseases for those in-school than that out-of-school, particularly for seasonal influenza, mumps and hand-foot-and-mouth disease. Meanwhile, such disparity is obvious in most of ages and in eastern and coastal regions of China, and the narrowing trend is attributed to six categories diseases, except for sexually transmitted and bloodborne diseases with gradually widened disparity between two groups with surveillance years with IRR from 22.939 in 2013 to 23.291 in 2021 due to large disparity for those who have completed compulsory education. Interpretation: A huge achievement has been achieved in reducing the burden and disparity of infectious diseases between out-of-school and in-school children, adolescents, and youths in China, particularly for the compulsory education stage population. The priorities for the coming decades will be to extend successful strategies to a broad scope and promote education, particularly for the investment of social health resources and the improvement of personal health literacy in the non-compulsory education stage. This should involve extending the years of compulsory school, improving sex health education, strengthening monitoring, expanding immunization programs coverage and prioritizing the prevention and control of sexually transmitted diseases and tuberculosis among out-of-school population. Funding: National Natural Science Foundation of China and Beijing Natural Science Foundation.

Genetic risk, adherence to healthy lifestyle and acute cardiovascular and thromboembolic complications following SARS-COV-2 infection.

Current understanding of determinants for COVID-19-related cardiovascular and thromboembolic (CVE) complications primarily covers clinical aspects with limited knowledge on genetics and lifestyles. Here, we analysed a prospective cohort of 106,005 participants from UK Biobank with confirmed SARS-CoV-2 infection. We show that higher polygenic risk scores, indicating individual's hereditary risk, were linearly associated with increased risks of post-COVID-19 atrial fibrillation (adjusted HR 1.52 [95% CI 1.44 to 1.60] per standard deviation increase), coronary artery disease (1.57 [1.46 to 1.69]), venous thromboembolism (1.33 [1.18 to 1.50]), and ischaemic stroke (1.27 [1.05 to 1.55]). These genetic associations are robust across genders, key clinical subgroups, and during Omicron waves. However, a prior composite healthier lifestyle was consistently associated with a reduction in all outcomes. Our findings highlight that host genetics and lifestyle independently affect the occurrence of CVE complications in the acute infection phrase, which can guide tailored management of COVID-19 patients and inform population lifestyle interventions to offset the elevated cardiovascular burden post-pandemic.

Air pollution, alcohol consumption, and the risk of elevated liver enzyme levels: a cross-sectional study in the UK Biobank.

Evidences on the association between exposure to air pollution and liver enzymes was scarce in low pollution area. We aimed to investigate the association between air pollution and liver enzyme levels and further explore whether alcohol intake influence this association. This cross-sectional study included 425,773 participants aged 37 to 73 years from the UK Biobank. Land Use Regression was applied to assess levels of PM2.5, PM10, NO2, and NOx. Levels of liver enzymes including AST, ALT, GGT, and ALP were determined by enzymatic rate method. Long-term low-level exposure to PM2.5 (per 5-µg/m3 increase) was significantly associated with AST (0.596% increase, 95% CI, 0.414 to 0.778%), ALT (0.311% increase, 0.031 to 0.593%), and GGT (1.552% increase, 1.172 to 1.933%); The results were similar for PM10; NOX and NO2 were only significantly correlated with AST and GGT Significant modification effects by alcohol consumption were found (P-interaction < 0.05). The effects of pollutants on AST, ALT, and GGT levels gradually increased along with the weekly alcohol drinking frequency. In conclusion, long-term low-level air pollutants exposure was associated with elevated liver enzyme levels. And alcohol intake may exacerbate the effect of air pollution on liver enzymes.

Effects of residential greenness and genetic predisposition on hemoglobin A1c and type 2 diabetes: Gene-environment interaction analysis from a nationwide study.

BACKGROUND: Current evidence on the relations of residential greenness with glucose homeostasis and type 2 diabetes (T2D) remained largely uncertain. Most importantly, no prior studies have investigated whether genetic predisposition modifies the above associations. METHODS: We leveraged data from the UK Biobank prospective cohort study, with participants enrolled between 2006 and 2010. Residential greenness was assessed by using the Normalized Difference Vegetation Index, and the weighting T2D-specific genetic risk score (GRS) was constructed based on previously published genome-wide association studies. Linear regression models and logistic regression models were used to investigate associations of residential greenness with glycated hemoglobin (HbA1c) and T2D prevalence, respectively. Interaction models explored whether genetic predisposition modifies greenness-HbA1c/T2D associations. RESULTS: Among 315,146 individuals (mean [SD] age, 56.59 [8.09] years), each one-unit increase in residential greenness was associated with reduction in HbA1c (ß: -0.87, 95% CI: -1.16 to -0.58) and a 12% decrease in odds of T2D (OR: 0.88, 95% CI: 0.79 to 0.98), respectively. Additionally, interaction analyses further demonstrated that residential greenness and genetic risk had cumulative effects on HbA1c and T2D. Compared with individuals who were exposed to low greenness and had high GRS, participants with low GRS and high greenness had a significant decline in HbA1c (ß: -2.96, 95% CI: -3.10 to -2.82, P for interaction = 0.04) and T2D (OR: 0.47, 95% CI: 0.45 to 0.50, P for interaction = 0.09). CONCLUSIONS: We add novel evidence that residential greenness has protective effects on glucose metabolism and T2D, and those beneficial effects can be amplified by low genetic risk. Our findings may facilitate the improvement of the living environment and the development of prevention strategies by considering genetic susceptibility to T2D.

Lifestyle, Genetic Susceptibility, and the Risk of Idiopathic Pulmonary Fibrosis: A Large Prospective Cohort Study.

BACKGROUND: Lifestyle is an important contributor of age-related chronic disease, but the association between lifestyle and the risk of idiopathic pulmonary fibrosis (IPF) remains unknown. The extent to which genetic susceptibility modifies the effects of lifestyle on IPF also remains unclear. RESEARCH QUESTION: Is there a joint effect or interaction of lifestyle and genetic susceptibility on the risk of developing IPF? STUDY DESIGN AND METHODS: This study included 407,615 participants from the UK Biobank study. A lifestyle score and a polygenic risk score were constructed separately for each participant. Participants were then classified into three lifestyle categories and three genetic risk categories based on the corresponding score. Cox models were fitted to assess the association of lifestyle and genetic risk with the risk of incident IPF. RESULTS: With favorable lifestyle as the reference group, intermediate lifestyle (hazard ratio, 1.384; 95% CI, 1.218-1.574) and unfavorable lifestyle (hazard ratio, 2.271; 95% CI, 1.852-2.785) were significantly associated with an increased risk of IPF. For the combined effect of lifestyle and polygenic risk score, participants with unfavorable lifestyle and high genetic risk had the highest risk of IPF (hazard ratio, 7.796; 95% CI, 5.482-11.086) compared with those with favorable lifestyle and low genetic risk. Moreover, approximately 32.7% (95% CI, 11.3-54.1) of IPF risk could be attributed to the interaction of an unfavorable lifestyle and high genetic risk. INTERPRETATION: Exposure to unfavorable lifestyle significantly increased the risk of IPF, particularly in those with high genetic risk.