Replacement of sedentary behavior with various physical activities and the risk of all-cause and cause-specific mortality.

BACKGROUND: Sedentary behavior (SB) has emerged as a significant health concern that deserves attention. This study aimed to examine the associations between prolonged sedentary behavior and the risk of all-cause and cause-specific mortality as well as to explore desirable alternatives to sitting in terms of physical activity (PA). METHODS: Two prospective cohort investigations were conducted using the UK Biobank and NHANES datasets, with a total of 490,659 and 33,534 participants, respectively. Cox proportional hazards regression models were used to estimate the associations between SB and the risk of all-cause and cause-specific mortality due to cancer, cardiovascular disease (CVD), respiratory diseases, and digestive diseases. In addition, we employed isotemporal substitution models to examine the protective effect of replacing sitting with various forms of PA. RESULTS: During the average follow-up times of 13.5 and 6.7 years, 36,109 and 3057 deaths were documented in the UK Biobank and NHANES, respectively. Both cohorts demonstrated that, compared with individuals sitting less than 5 h per day, individuals with longer periods of sitting had higher risks of all-cause and cause-specific mortality due to cancer, CVD, and respiratory diseases but not digestive diseases. Moreover, replacing SB per day with PA, even substituting 30 min of walking for pleasure, reduced the risk of all-cause mortality by 3.5% (hazard ratio [HR] 0.965, 95% confidence interval [CI] 0.954-0.977), whereas cause-specific mortality from cancer, CVD, and respiratory diseases was reduced by 1.6% (HR 0.984, 95% CI 0.968-1.000), 4.4% (HR 0.956, 95% CI 0.930-0.982), and 15.5% (HR 0.845, 95% CI 0.795-0.899), respectively. Furthermore, the protective effects of substitution became more pronounced as the intensity of exercise increased or the alternative duration was extended to 1 h. CONCLUSIONS: SB was significantly correlated with substantially increased risks of all-cause mortality and cause-specific mortality from cancer, CVD, and respiratory diseases. However, substituting sitting with various forms of PA, even for short periods involving relatively light and relaxing physical activity, effectively reduced the risk of both overall and cause-specific mortality.

Night Shift Work Associates with All-Cause and Cause-Specific Mortality: A Large Prospective Cohort Study.

BACKGROUND: Health problems associated with shift work and night shift work are gaining increasing public attention. OBJECTIVE: To investigate the association between night shift work and the hazard of mortality. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 283,579 individuals with paid employment or self-employment aged 37-73 years were included from the UK Biobank with a median follow-up period of 14.0 years. MAIN MEASURES: Participants were divided into day workers and shift workers, including the frequency of night shifts, to evaluate the association between baseline work schedules and all-cause and cause-specific mortality using the Cox proportional hazards model. Additionally, 75,760 participants with work histories were assessed for the association between average frequency and cumulative years of exposure to night shift work and all-cause and cause-specific mortality. KEY RESULTS: Compared with that of day workers, the adjusted hazard of all-cause mortality was increased by 12.0% (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.07-1.18) in shift workers, particularly in those with no or rare night shifts (approximately 16.1%; HR, 1.16; 95% CI, 1.08-1.25) and those with irregular night shifts (approximately 9.2%; HR, 1.09; 95% CI, 1.00-1.19). Moreover, a non-linear relationship was identified between cumulative night shift years and all-cause and cause-specific mortality. Only individuals who worked night shifts for 20-30 years exhibited a substantially increased hazard of all-cause (HR, 1.52; 95% CI, 1.15-2.00) and cardiovascular disease (CVD; HR, 2.08; 95% CI, 1.16-3.71) mortality. CONCLUSIONS: Shift workers, particularly those with rare or irregular night shifts, exhibited an increased hazard of mortality. Additionally, participants who worked night shifts for 20-30 years exhibited a substantially increased hazard of all-cause and CVD mortality.

Association Between Adverse Early Life Factors and Telomere Length in Middle and Late Life.

Background and Objectives: Telomere length (TL) has been acknowledged as biomarker of biological aging. Numerous investigations have examined associations between individual early life factors and leukocyte TL; however, the findings were far from consistent. Research Design and Methods: We evaluated the relationship between individual and combined early life factors and leukocytes TL in middle and late life using data from the UK Biobank. The early life factors (eg, maternal smoking, breastfeeding, birth weight, and comparative body size and height to peers at age 10) were measured. The regression coefficients (ß) and 95% confidence interval (CI) were applied to assess the link of the early life factors and TL in adulthood. Flexible parametric survival models incorporated age to calculate the relationship between early life factors and life expectancy. Results: Exposure to maternal smoking, lack of breastfeeding, low birth weight, and shorter height compared to peers at age 10 were identified to be associated with shorter TL in middle and older age according to the large population-based study with 197 504 participants. Individuals who experienced more than 3 adverse early life factors had the shortest TL in middle and late life (ß = -0.053; 95% CI = -0.069 to -0.038; p < .0001), as well as an average of 0.54 years of life loss at the age of 45 and 0.49 years of life loss at the age of 60, compared to those who were not exposed to any early life risk factors. Discussion and Implications: Early life factors including maternal smoking, non-breastfed, low birth weight, and shorter height compared to peers at age 10 were associated with shorter TL in later life. In addition, an increased number of the aforementioned factors was associated with a greater likelihood of shorter TL in adulthood, as well as a reduced life expectancy.

Ambient air pollution, lifestyle, and genetic predisposition on all-cause and cause-specific mortality: A prospective cohort study.

BACKGROUND: Although it is widely acknowledged that long-term exposure to ambient air pollution is closely related to the risk of mortality, there were inconsistencies in terms of cause-specific mortality and it is still unknown whether lifestyle and genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study involved 461,112 participants from the UK Biobank. The land-use regression model was used to estimate the concentrations of particulate matter (PM2.5, PMcoarse, PM10), and nitrogen oxides (NO2 and NOx). The association between air pollution and mortality was evaluated using Cox proportional hazard models. Furthermore, a lifestyle score incorporated with smoking status, physical activity, alcohol consumption, and diet behaviors, and polygenic risk score using 12 genetic variants, were developed to assess the modifying effect of air pollution on mortality outcomes. RESULTS: During a median follow-up of 14.0 years, 33,903 deaths were recorded, including 17,083 (2835; 14,248), 6970, 2429, and 1287 deaths due to cancer (lung cancer, non-lung cancer), cardiovascular disease (CVD), respiratory and digestive disease, respectively. Each interquartile range (IQR) increase in PM2.5, NO2 and NOx was associated with 7 %, 6 % and 5 % higher risk of all-cause mortality, respectively. Specifically, for cause-specific mortality, each IQR increase in PM2.5, NO2 and NOx was also linked to mortality due to cancer (lung cancer and non-lung cancer), CVD, respiratory and digestive disease. Furthermore, additive and multiplicative interactions were identified between high ambient air pollution and unhealthy lifestyle on mortality. In addition, associations between air pollution and mortality were modified by lifestyle behaviors. CONCLUSION: Long-term exposure to air pollutants increased the risk of all-cause and cause-specific mortality, which was modified by lifestyle behaviors. In addition, we also revealed a synergistically detrimental effect between air pollution and an unhealthy lifestyle, suggesting the significance of joint air pollution management and adherence to a healthy lifestyle on public health.

Vitamin D status, sleep patterns, genetic susceptibility, and the risk of incident adult-onset asthma: a large prospective cohort study.

Introduction: Vitamin D has been known to be associated with asthma, particularly in children, while the evidence among adults is limited and inconclusive. This study aimed to investigate the association between serum, vitamin D concentrations, and the incidence of adult-onset asthma and also the modified effect caused by sleep patterns and genetic risks. Methods: A prospective cohort study with 307,872 participants aged between 37 and 73 years was conducted based on the UK Biobank, with a median follow-up of 12 years. The Cox proportional hazard model was applied to evaluate the association between vitamin D status and incident adult-onset asthma, and the modified effect was investigated by conducting stratified analysis according to sleep pattern score and genetic risk score, and subgroup analyses were performed by sex, age, BMI, and smoking status as well. Results: Individuals with optimal vitamin D concentration were associated with 11.1% reduced risk of incident asthma compared to those participants with deficient vitamin D (HR = 0.889; 95% CI: 0.820-0.964; p = 0.005). Moreover, stratification analysis demonstrated that the protective effect of vitamin D on asthma risk was modified by sleep patterns or genetic susceptibility, with the strongest protective effect being observed in the subpopulation with a moderate sleep pattern (HR = 0.883; 95% CI: 0.797-0.977; p = 0.016) and a moderate genetic risk (HR = 0.817; 95% CI: 0.711-0.938; p = 0.004). In subgroup analyses, the protective effect of optimal vitamin D levels was only significant among men, individuals younger than 60 years of age, overweight individuals, and current or previous smokers. Conclusion: Increased serum vitamin D levels were associated with a lower risk of incident adult-onset asthma, and this association was modified by sleep patterns and genetic predisposition to some extent.

Association of telomere length with risk of lung cancer: A large prospective cohort study from the UK Biobank.

OBJECTIVES: Leukocyte telomere length (LTL) is associated with a wide variety of diseases, including cancer. However, findings regarding the association between LTL and the risk for lung cancer have been inconclusive and inconsistent across previous observational studies. METHODS: This prospective cohort study included data from 425,146 participants 37-73 years of age housed in the UK Biobank. Quantitative polymerase chain reaction (qPCR) was used to measure LTL in baseline DNA samples. A multivariate Cox proportional hazards model was used to evaluate the relationship between LTL and the risk for lung cancer. RESULTS: An increase in LTL per interquartile range (IQR) was associated with a 9% increase in the risk for lung cancer (hazard ratio [HR] 1.09 [95% confidence interval (CI) 1.03-1.16]). Participants in the highest LTL quintile exhibited an approximately 25% elevated risk for developing lung cancer (HR 1.25 [95% CI 1.09-1.45]) compared with those in the lowest quintile. The relationship between per IQR increase in LTL and elevated risk for lung cancer was greater in the histological subtype of adenocarcinoma (HR 1.30 [95% CI 1.18-1.43]), female sex (HR 1.16 [95% CI 1.06-1.26]), non-smokers (HR 1.45 [95% CI 1.23-1.71]), and individuals with high genetic risk for lung cancer (HR 1.18 [95% CI 1.03-1.34]), respectively. Surprisingly, a per IQR increase in LTL was associated with increased risks for both lung adenocarcinoma (HR 1.56 [95% CI 1.24-1.96]) and squamous cell carcinoma (HR 2.01 [95% CI 1.13-3.56]) in never smokers. CONCLUSIONS: Longer LTL was associated with an elevated risk for lung cancer, particularly for adenocarcinoma and squamous cell carcinoma in never smokers. The results suggest the potential of telomeres as non-invasive biomarkers for the early screening of lung cancer, particularly in non-smokers, who are typically overlooked.

Associations Between Sex-Specific Reproductive Factors and Risk of New-Onset Lung Cancer Among Female Patients.

BACKGROUND: Several characteristics distinguish lung cancer in female patients from that in male patients, with adenocarcinoma being more prevalent in female patients and occurring more frequently in female patients who do not smoke. Uncertainty surrounds the relationship between female-specific reproductive factors and lung cancer risk. RESEARCH QUESTION: Are sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types? STUDY DESIGN AND METHODS: A Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of lung cancer developing in a prospective cohort study involving 273,190 female individuals from the UK Biobank. Subgroup analyses stratified by age, smoking status, BMI, genetic risk, and histologic subtype were conducted to emphasize the modification effects further. RESULTS: A total of 1,182 cases of lung cancer in female patients were recorded over a median follow-up period of 12.0 years in the cohort study. In multivariable-adjusted models, early menarche (age ≤ 11 years: hazard ratio [HR], 1.22; 95% CI, 1.03-1.46), early menopause (age ≤ 46 years: HR, 1.49; 95% CI, 1.19-1.86), a shorter reproductive span (≤ 32 years: HR, 1.42; 95% CI, 1.18-1.71; and 33-35 years: HR, 1.24; 95% CI, 1.00-1.53), and early age at first birth (age ≤ 20 years: HR, 1.63; 95% CI, 1.33-2.01) were associated with a higher risk of lung cancer. Stratified analysis revealed that several reproductive factors, including early age at menopause, shortened reproductive span, and early age at first birth, showed a substantially stronger relationship with an elevated risk of lung cancer, particularly of lung adenocarcinoma, in populations with high genetic risk and more detrimental behaviors. INTERPRETATION: Early age at menopause, a shortened reproductive life span, and early age at first birth were associated with higher risks of lung cancer, particularly of lung adenocarcinoma, in a subpopulation with higher genetic susceptibility and detrimental behaviors. The evidence provided by this study emphasizes the significance of screening for multiple reproductive factors to prevent lung cancer among female individuals.

Clinical Characteristics, Laboratory Findings, and Prognosis in Patients With Talaromyces marneffei Infection Across Various Immune Statuses.

Objective: Talaromyces marneffei (TM) is an opportunistic fungus that is predominantly prevalent among patients who are HIV-positive in South-East Asia. However, few studies focused on the clinical features, laboratory findings, and prognosis across varying immune states. Methods: A total of 54 patients with TM infection in Xiangya Hospital of Central South University from January 1, 2006 to October 31, 2021 were retrospectively analyzed. Clinical profiles were compared across the different immune statuses by HIV-positive (HIV group, n = 18), HIV negative but with immunocompromised conditions (Non-HIV with IC Group, n = 11), and immunocompetent patients (n = 25). Results: All the patients were diagnosed by pathogen culture or by metagenomic next-generation sequencing (mNGS). The median age was 50, and patients with HIV were much younger compared to the other two groups. The most common symptom at presentation was fever (79.6%), followed by cough (70.4%), weight loss (61.1%), and expectoration (53.7%). The patients with HIV were more likely to develop into a subtype of disseminated TM affecting multiple organs including lymph node, liver, skin, and spleen, thus, resulting in higher hospital mortality compared to the other two groups. Patients without HIV but with immunocompromised conditions presented similar hospital mortality rates compared to immunocompetent patients, while experiencing longer days of hospitalization to recover from the diseases. Additionally, in this study, the pathogen culture easily confirmed the patients with HIV. However, mNGS presented as a promising tool to confirm TM infection in those suspicious patients without HIV. Conclusions: In summary, patients with HIV were more likely to develop into disseminated TM, resulting in higher mortality compared to those patients without HIV. Additionally, mNGS presented as an important supplementary tool to confirm TM infection in patients without HIV, particularly in those with immunocompromised diseases.

Vitamin D status and asthma, lung function, and hospitalization among British adults.

Background: Vitamin D has been known to be associated with asthma. However, the association between vitamin D status and asthma, lung function as well as hospitalization among adults remains unclear. Objective: To investigate the role of serum vitamin D in asthma prevalence, lung function, and asthma control in adults. Methods: Multivariable logistic regression was applied to assess the relationship between serum vitamin D and asthma prevalence, lung function (FEV1, FVC, and FEV1/FVC), current wheeze, and asthma-linked hospitalizations in a cross-sectional study of 435,040 adults aged 37-73 years old from the UK Biobank. Results: Compared to vitamin D deficiency, the odds of asthma were decreased by 6.4% [adjusted odds ratio (aOR) = 0.936; 95% CI: 0.911-0.962; p < 0.001] and 9.8% (aOR = 0. 0.902; 95% CI: 0.877-0. 0.927; p < 0.001) in individuals with insufficient and optimal vitamin D concentration, respectively, in the fully adjusted model. In total asthmatic patients, serum vitamin D was obviously and positively related with FEV1 (ß = 1.328 ml, 95% CI = 0.575-2.080), FVC (ß = 2.018 ml, 95% CI = 1.127-2.908), and FEV1/FVC (ß = 0.006%, 95% CI = 0.002-0.010). Asthmatic patients whose vitamin D level was in the deficient category had 9.3-19.9% higher odds of current wheeze than insufficient categories (aOR = 0.907; 95% CI: 0.861-0.957; p < 0.001) and optimal categories (aOR = 0.801; 95% CI: 0.759-0.845; p < 0.001), but the relationship between vitamin D and asthma hospitalization was not significant. Conclusion: Vitamin D deficiency was related to higher odds of asthma and current wheeze, and lower lung function in a large sample size study of British adults. Our results indicate a potential positive impact of serum vitamin D on asthma occurrence and disease control in adults.

Clinical characteristics and prognosis of patient with leptospirosis: A multicenter retrospective analysis in south of China.

Purpose: Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. However, there is currently no consensual definition or diagnostic criteria for severe and different forms of leptospirosis. Therefore, more insight on clinical manifestations, risk factors, and outcomes of leptospirosis is warranted. The identification of leptospirosis with distinct clinical manifestations and prognosis in our population. Methods: Multiple correspondence analysis and hierarchical classification on principal components were presented to identify different clinical types of leptospirosis. The outcomes were clinical phenotypes, laboratory and imaging findings, and prognosis. Results: The 95 enrolled patients had median values of 54.0 years (39.0-65.0) for age, 9.0 (7.0-14.0) for total hospital stay lengths, of whom 86.3% was male and 40.0% was transferred to ICU. Three clinical types were distinguished: mild leptospirosis (n=43, 45.3%) with less organ dysfunction and shorter hospital stays; respiratory leptospirosis (n=28, 29.5%) with hemoptysis, and respiratory and circulatory failure; and hepato-renal leptospirosis (n=24, 25.3%) with worst liver and kidney dysfunction. Total hospital mortality was 15.8% and was associated with dyspnea and high levels of neutrophil counts. Conclusions: The identification of leptospirosis with distinct clinical manifestations and prognosis in our population may assist clinicians to distinguish leptospirosis-like disease. Moreover, dyspnea and neutrophil count were found to be independent risk factors for severe leptospirosis progression.