Association of accelerated aging with the incidence risk of Cardiometabolic diseases in people with severe mental illnesses: A prospective analysis in UK Biobank.

Cardiometabolic diseases (CMDs) comorbidities among people with severe mental illnesses (SMI) are associated with a high healthcare burden and premature mortality. This study aims to evaluate whether biological aging has an interaction with SMI on incident CMDs, and to examine the association of four biological aging indicators with CMDs incidence in this population. Data were sourced from the UK Biobank, a large prospective cohort study. Four indicators were used to assess biological aging including frailty phenotype, frailty index, KDM-biological age acceleration and phenotypic age acceleration. Cox proportional hazards regression models were used to examine the associations. We observed higher prevalence of frailty and accelerated biological age with SMI than those without SMI. Further analysis found significant interaction effect of pre-frailty and SMI (PPre-frail*SMI=0.005) as well as biological age acceleration and SMI (PQ3 (>P75)*SMI=0.038). 14.7 % of the participants with SMI developed CMDs during the follow-up. Compared with non-frail participants, those with frailty (frailty phenotype: HR=1.68, 95 % CI: 1.50, 1.88, P < 0.001; frailty index: HR=2.44, 95 % CI: 2.11-2.81, P < 0.001) and biological age acceleration (KDM-biological age acceleration (Q3): HR=1.91, 95 % CI: 1.74, 2.11, P < 0.001; phenotypic age acceleration (Q3): HR=2.07, 95 % CI: 1.86, 2.30, P < 0.001) had a significantly higher risk of CMDs in the adjusted model. A series of sensitivity analyses were conducted to illustrate the robustness of the findings. These findings highlight the important implications for concerning about the high incidence of CMDs comorbidities and intervention of aging in people with SMI.

Allergic Phenotypes and Sarcopenia: Evidence from Observational Studies and Mendelian Randomization Analysis.

Commonly affected in early-life population, the impact of allergic phenotypes on mid- or late-life health is less discussed. This study is to explore the association of allergic phenotypes including atopic dermatitis (AD), asthma, eosinophils count (EC), and sarcopenia. We conducted observational studies and mendelian randomization (MR) analysis based on UK Biobank (UKB), the China Health and Retirement Longitudinal Study (CHARLS) and data from genome-wide association study (GWAS). Based on the UKB data, AD, asthma and EC were positively correlated with pre-sarcopenia and decreased skeletal muscle mass index and hand grip in fully adjusted model. Asthma and EC were significantly associated with sarcopenia while AD was marginally associated (p = 0.095). Based on the CHARLS cohort, asthma significantly added 109.4% risk for pre-sarcopenia in adjusted model (relative risk = 2.094; p = 0.002), respectively. Both asthma (ß = 0.100, p = 0.006) and EC (ß = 0.023, p = 0.017) exerted significantly casual effects on pre-sarcopenia. However, as for sarcopenia, merely EC exhibited a significantly casual effect (ß = 0.005, p = 0.048). Significant casual effects of AD (ß = - 0.027, p = 0.003), asthma (ß = - 0.029, p = 0.027) and EC (ß = - 0.041, p < 0.001) on decreased appendicular lean mass (ALM) were observed using the inverse-variance weighted method and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method. Our results revealed a contributory role of AD, asthma and EC on sarcopenia, especially in terms of decreased ALM, an indicator for sarcopenia diagnosis. The findings of our study will raise the awareness of preventing aging-related disorders or geriatric syndromes among allergic populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00110-4.

Association of air pollution with incidence of elderly-onset seborrheic dermatitis: A prospective cohort study in UK Biobank.

BACKGROUND: Elderly-onset seborrheic dermatitis (SD) seriously affects the quality of life. However, associations between air pollution exposures and elderly-onset SD incidence have not been elucidated. OBJECTIVES: Investigate air pollution's role in the incidence of elderly-onset SD. METHODS: We engaged a prospective cohort analysis utilizing the UK Biobank database. Exposure data for specific air pollutants (PM2.5, PM2.5-10, NOX, NO2, and PM10) spanning various years was incorporated. Through a composite air pollution score constructed from five pollutants and employing Cox proportional hazards models, the relationship between pollution and SD was delineated. RESULTS: Our examination of 193,995 participants identified 3,363 SD cases. Higher concentrations of specific pollutants, particularly in the upper quartile (Q4), were significantly linked to an elevated SD risk. Notably, PM2.5, PM10, NO2, and NOX exhibited hazard ratios of 1.11, 1.15, 1.22, and 1.15, respectively. The correlation was further solidified with a positive association between air pollution score increments and SD onset. Intriguingly, this association was accentuated in certain demographics, including younger males, the socioeconomically deprived, smokers, daily alcohol consumers, and those engaging in regular physical activity. CONCLUSIONS: Our findings revealed that air pollution exposures were associated with elderly-onset SD incidence. These results emphasize the importance of preventing environmental exposures to the risk of SD development.

Age at Natural Menopause, Reproductive Lifespan, and the Risk of Late-Onset Psoriasis and Psoriatic Arthritis in Women: A Prospective Cohort Study.

Although a peak incidence of psoriasis in women aged around 60 years has been observed, the link between reproductive lifespan and late-onset psoriatic diseases is underexplored. This study aims to elucidate the association between reproductive lifespan and the risk of late-onset psoriasis and psoriatic arthritis (PsA). Utilizing the UK Biobank data, we conducted a prospective cohort study in postmenopausal women without baseline psoriatic diseases. The exposure variables included age at natural menopause (ANM) and duration from menarche to menopause, termed reproductive years. The outcome variables were incident psoriasis and PsA. We employed Cox regression analysis, factoring in polygenic risk scores for psoriatic diseases and recognized risk factors. We found that later ANM and longer reproductive years were significantly associated with decreased risks of late-onset psoriasis and PsA in a dose-dependent manner (P<.05). ANM after age 55 years led to a 34 and 46% risk reduction in late-onset psoriasis and PsA, respectively, compared with ANM before age 45 years (P<.001). The population-attributable risks of ANM were 17.4% for late-onset psoriasis and 21.6% for PsA. In conclusion, reproductive lifespan, with its inherent homeostasis, plays a pivotal yet overlooked role in late-onset psoriatic diseases. Investigations into estrogen-centric causes and sex-specific interventions are imperative.

Characteristics and economic burden of hospitalized patients with herpes zoster in China, before vaccination.

Herpes zoster (HZ) brings a significant economic burden. The HZ vaccine was introduced in China for the first time in 2020, and there is a lack of up-to-date information on the hospitalization costs and characteristics prior to vaccination. This study aimed to describe the characteristics and economic burden of HZ inpatients in Hunan Province, China, and analyze the factors influencing the length of stay (LOS) and costs. This was a retrospective study and we extracted information from the Chinese National Health Statistics Network Reporting System on HZ inpatients in Hunan Province, China from 2017 to 2019. Spatial join tools and Global or Local Moran's Index were used for the geographic analysis of hospitalized HZ incidence. Multivariate linear regression models were used to analyze the factors influencing LOS and costs. There were 44,311 HZ inpatients included in this study, incurring a total of $31,857,734 medical costs. These patients had a median LOS of 8 days and a median expenditure of $573.47. Older age, more comorbidities, and the presence of complications with nervous system involved were all significantly associated with longer LOS and higher costs. HZ infection resulted in a large direct medical cost and heavy disease burden, especially in patients with advanced age or underlying medical conditions. The HZ vaccine has the potential to effectively reduce the disease burden and should be widely popularized especially among high-risk groups.

Association of exposure to artificial light at night during adolescence with blood pressure in early adulthood.

Artificial light at night (ALAN) is related to various diseases, such as cancer, obesity, and coronary heart disease. However, its impact on blood pressure in adolescents is not well understood. To investigate this, we conducted a cross-sectional study with a nationwide sample of college students in China, who were freshmen from four disperse universities during Sep. and Oct. 2018. Mean levels of ALAN at participants' residential addresses during 2013-2018 were estimated using time-varying satellite data. The association of the 6-y average of ALAN with blood pressure was estimated by using generalized linear mixed models. A total of 17 046 participants (18.2 ± 0.7 y of age, 46.79% female) from 2,412 counties and cities were included in the final analysis. After a full adjustment for potential confounders, ALAN was positively associated with systolic blood pressure (ß = 0.20, p = 0.032) and pulse pressure (ß = 0.28, p = 0.001), but there was no association between ALAN and diastolic blood pressure (ß = -0.08, p = 0.213). In the sensitivity analysis, the results consistent with the main analysis were observed. The blood pressure of males and those with a BMI ≤24 kg/m2 were more susceptible to ALAN exposure. Our findings highlight the importance of ALAN management for blood pressure control, particularly among male and normal-weight individuals.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and the Risk of Incident Rosacea: Insights from Mendelian Randomization and Cohort Study in the UK Biobank.

BACKGROUND: Previous cross-sectional studies have failed to definitively establish a causal relationship between serum 25-hydroxyvitamin D (25OHD) concentrations and the onset of rosacea. OBJECTIVE: To investigate the potential association between serum 25OHD levels, vitamin D receptor (VDR) polymorphisms, and the risk of developing incident rosacea. METHODS: This cross-sectional population-based cohort study utilizing 370,209 individuals from the UK Biobank. Cox proportional hazard regression models and two-sample Mendelian randomization (MR) analyses were applied to explore the causative relationship between 25OHD and incident rosacea. RESULTS: Our findings revealed that elevated levels of serum 25OHD were inversely correlated with the risk of incident rosacea. Specifically, compared to participants with 25OHD levels below 25 nmol/L, the multivariate-adjusted HR for incident rosacea was 0.81 (95% CI: 0.70, 0.94) in those with 25OHD levels exceeding 50 nmol/L. Further, in comparison to individuals with serum 25OHD less than 25 nmol/L and the rs731236 (TaqI) AA allele, those with serum 25OHD higher than 75 nmol/L and the TaqI GG allele had a multivariate-adjusted HR of 0.51 (95% CI 0.32 to 0.81) for developing rosacea. Results from the MR study supported a significant association, with each standard deviation increase in serum 25OHD concentrations correlating to a 23% reduced risk of rosacea (HR = 0.77, 95% CI: 0.63, 0.93). CONCLUSIONS: The findings of this cohort study indicate an inverse association between increased concentrations of serum 25OHD and the risk of developing incident rosacea. While our results highlight the potential protective role of vitamin D, the definitive efficacy of vitamin D supplementation as a preventive strategy against rosacea requires further investigation.

Adenosine 5'monophosphate-activated protein kinase activation reduces the risks of psoriasis and its comorbidities: a mendelian randomisation study in the UK Biobank.

OBJECTIVE: Whether metformin and its adenosine 5'monophosphate-activated protein kinase (AMPK) activation protect from psoriasis risk is unconcluded. We investigated the effect of AMPK, a pharmacological target of metformin, on the risk of psoriasis and its comorbidities and mortality among participants in the UK Biobank(UKB). METHODS: To avoid immortal-time-biases in pharmacoepidemiologic studies, Mendelian randomisation was used to infer the AMPK pathway-dependent effects. The cut-off age for distinguishing early-onset/late-onset psoriasis (EOP/LOP) was set at 60 years, based on the incident psoriasis peak in UKB. A genetic instrument comprising 44 single-nucleotide polymorphisms associated with HbA1c, serving as a proxy for AMPK genetic risk score (negatively associated with AMPK activation), was employed as previously reported in the literature. Log-binomial models were used to estimate the effect size of AMPK regarding relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 407 159 participants were analyzed, including 9,126 EOP and 3,324 LOP. The AMPK-genetic-risk-score was associated with a 12.4% increase in the risk of LOP in men (RR = 1.124, 95% CI: 1.022-1.236). This association was not significant for EOP or women. AMPK genetic risk score exhibited an elevated risk of ischemic heart disease (RR = 1.217, 95% CI 1.062-1.395) in male psoriasis patients. CONCLUSIONS: AMPK activation may protect against LOPs and associated ischemic heart disease in men. A sex-specific, comorbidity-targeted intervention for psoriasis is needed.

Corrigendum to 'Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study.' [EClinicalMedicine 59 (2023) 101981].

[This corrects the article DOI: 10.1016/j.eclinm.2023.101981.].

Association of joint exposure to various ambient air pollutants during adolescence with blood pressure in young adulthood.

The association of various air pollutants exposure during adolescence with blood pressure (BP) in young adulthood is uncertain. We intended to evaluate the long-term association of individual and joint air pollutants exposure during adolescence with BP in young adulthood. This cross-sectional study of incoming students was conducted in five geographically disperse universities in China during September and October 2018. Mean concentrations of particulate matter with diameters ≤2.5 µm (PM2.5 ), ≤10 µm (PM10 ), nitrogen dioxides (NO2 ), carbon monoxide (CO), sulfur dioxide (SO2 ), and ozone (O3 ) at participants' residential addresses during 2013-2018 were collected from the Chinese Air Quality Reanalysis dataset. Generalized linear mixed models (GLM) and quantile g-computation (QgC) models were utilized to estimate the association between individual and joint air pollutants exposure and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). A total of 16,242 participants were included in the analysis. The GLM analyses showed that PM2.5 , PM10 , NO2 , CO, and SO2 were significantly positively associated with SBP and PP, while O3 was positively associated with DBP. The QgC analyses indicated that long-term exposure to a mixture of the six air pollutants had a significant positive joint association with SBP and PP. In conclusion, air pollutant co-exposure during adolescence may influence BP in young adulthood. The findings of this study emphasized the impacts of multiple air pollutants interactions on potential health and the need of minimizing pollution exposures in the environment.

Exposure to ambient air pollutants is associated with an increased incidence of hyperuricemia: A longitudinal cohort study among Chinese government employees.

BACKGROUND: It is widely recognized that ambient air pollution can induce various detrimental health outcomes. However, evidence linking ambient air pollutants and hyperuricemia incidence is scarce. OBJECTIVES: To assess the association between long-term air pollution exposure and the risk of hyperuricemia. METHODS: In this study, a total of 5854 government employees without hyperuricemia were recruited and followed up from January 2018 to June 2021 in Hunan Province, China. Hyperuricemia was defined as serum uric acid (SUA) level of >420 µmol/L for men and >360 µmol/L for women or use of SUA-lowering medication or diagnosed as hyperuricemia during follow-up. Data from local air quality monitoring stations were used to calculate individual exposure levels of PM10, PM2.5, SO2 and NO2 by inverse distance weightingn (IDW) method. Cox proportional hazard model was applied to evaluate the causal relationships between air pollutant exposures and the risk of hyperuricemia occurrence after adjustment for potential confounders and meanwhile, restricted cubic spline was used to explore the dose-response relationships. RESULTS: The results indicated that exposures to PM10 (hazard ratio, HR = 1.042, 95% conficence interal, 95% CI: 1.028, 1.057), PM2.5 (HR = 1.204, 95% CI: 1.141, 1.271) and NO2 (HR = 1.178, 95% CI: 1.125,1.233) were associated with an increased HR of hyperuricemia. In addition, a nonlinear dose-response relationship was found between PM10 exposure level and the HR of hyperuricemia (p for nonlinearity = 0.158) with a potential threshold of 50.11 µg/m3. Subgroup analysis demonstrated that participants usually waking up at night and using natural ventilation were more vulnerable to the exposures of PM10, PM2.5, NO2, and SO2. CONCLUSION: Long-term exposures to ambient PM10, PM2.5 and NO2 are associated with an increased incidence of hyperuricemia among Chinese government employees.

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Chronic kidney disease (CKD) is suffered progressive loss of kidney function lasting more than 3 months and is classified according to the degree of kidney damage (level of proteinuria) and the decreased glomerular filtration rate (GFR). The most severe form of CKD is end-stage renal disease. The prevalence of CKD is high with fast growth rate and the disease burden has become increasingly serious. CKD has become an important public health problem threatening human health. The etiology of CKD is complex. In addition to genetic factors, environmental factors are an important cause of CKD. With the development of industrialization, environmental metal pollution has become increasingly severe, and its impact on human health has received widespread attention. A large number of studies have shown that metals such as lead, cadmium, and arsenic can accumulate in the kidney, which can cause damage to the structure and function of the kidney, and play an important role in the development of CKD. Therefore, summarizing the epidemiological research progress in the relationship between arsenic, cadmium, lead, and other metal exposures and kidney diseases can provide new ideas for the prevention and control of kidney diseases caused by metal exposure.

Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study.

Background: As the COVID-19 pandemic continues to spread, the number of associated deaths continues to increase, especially among those with pre-existing conditions. Azvudine is recommended as a priority treatment for patients with COVID-19, but its efficacy in patients with pre-existing conditions is unknown. Methods: This is a single-centre, retrospective cohort study between December 5, 2022 and January 31, 2023 in Xiangya Hospital of Central South University in China to evaluate the clinical efficacy of Azvudine in hospitalised patients with COVID-19 and pre-existing conditions. Patients with Azvudine and controls were propensity score-matched (1:1) for age, gender, vaccination status, time from symptom onset to treatment exposure, severity at admission, concomitant treatments initiated at admission. The primary outcome was a composite outcome of disease progression, and the secondary outcome was each of these individual disease progression outcomes. The univariate Cox regression model was used to estimate a hazard ratio (HR) with 95% confidence interval (CI) for each result between the groups. Findings: We identified 2118 hospitalised patients with COVID-19 during the study period, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 245 Azvudine recipients and 245 matched controls. Azvudine recipients had lower crude incidence rate of composite disease progression outcome compared with matched controls (7.125/1000 person-days vs. 16.004/1000 person-days, P = 0.018). There was no significant difference in all-cause death between these two groups (1.934/1000 person-days vs. 4.128/1000 person-days, P = 0.159). Azvudine treatment was associated with significantly lower risks of composite disease progression outcome compared with matched controls (HR: 0.49; 95% CI: 0.27-0.89, P = 0.016). A significant difference in all-cause death was not found (HR: 0.45; 95% CI: 0.15-1.36, P = 0.148). Interpretation: These findings indicate that Azvudine therapy showed substantial clinical benefits in hospitalised patients with COVID-19 and pre-existing conditions, and should be considered for this population of patients. Funding: This work was supported by the National Natural Science Foundation of China (Grant Nos. 82103183 to F. Z., 82102803, 82272849 to G. D.), National Natural Science Foundation of Hunan Province (Grant Nos. 2022JJ40767 to F. Z., 2021JJ40976 to G. D.), Huxiang Youth Talent Program (Grant Nos. 2022RC1014 to M.S.) and Ministry of Industry and Information Technology of China (Grant Nos. TC210804V to M.S.).

Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study.

Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID-19 patients compared with nirmatrelvir-ritonavir in terms of composite disease progression outcome.

Arsenic exposure and pruritus: Evidence from observational, interventional, and mendelian randomization studies.

BACKGROUND: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated. METHODS: A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen. RESULTS: Hair arsenic (µg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum ß-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of ß-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (ß = -0.98, p = 0.04). CONCLUSION: Arsenic exposure is associated with pruritus, and ß-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.