Given the inconsistent evidence regarding hearing aid use and reduced dementia risk, this study evaluates whether hearing aid use, particularly effective use, is associated with lower probable dementia risk among hearing-impaired older adults. Using harmonized longitudinal data from 61,089 hearing-impaired participants (aged 55+ years) from seven cohorts (CHARLS, KLOSA, SHARE, ELSA, TILDA, HRS, and MHAS), we employ IPTW-corrected Cox models stratified by country income. Over a 6.5-year average follow-up (8,911 events), hearing aid use is associated with reduced dementia risk (hazard ratio [HR] = 0.91, 95% confidence interval [CI] 0.88-0.94). This association is confined to participants reporting effective hearing improvement (HR = 0.86, 95% CI 0.80-0.93), whereas those reporting poor hearing improvement show no reduced risk (HR = 0.98, 95% CI 0.90-1.07). The association is stronger in middle-income countries (HR = 0.76) and among subgroup populations, including those aged <70 years, women, those who are unmarried, and those with lower education. Quality hearing rehabilitation is a potential public health priority for addressing the dementia burden.

BACKGROUND:Prior observational studies have reported conflicting results regarding whether antidepressant treatment reduces long-term dementia risk, likely due to confounding by indication and reverse causation. We aimed to investigate the association between baseline antidepressant use and incident dementia, incorporating cognitive and neuroimaging outcomes. METHODS:We conducted a prospective cohort study using UK Biobank participants free of dementia at baseline. Antidepressant use was self-reported at baseline (2006-2010). Incident dementia was identified through linked electronic health records until December 19, 2022. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD), adjusting for sociodemographic, lifestyle, health-related, antidepressant indication factors, and co-medication of other anticholinergics. In subsamples, cognitive performance (n = 57,330) and structural brain imaging (n = 42,276) were examined as intermediate outcomes. RESULTS:Among 461,464 participants, 33,721 (7.3%) reported baseline antidepressant use. Over a mean follow-up of 13.4 years, 7,922 (1.7%) developed incident dementia. Baseline antidepressant use was associated with higher risks of all-cause dementia (adjusted HR: 1.47, 95% CI 1.36-1.60), AD (1.53, 1.36-1.73), and VD (1.44, 1.23-1.70). Users performed worse on fluid intelligence and prospective memory tasks and showed lower total and gray matter volume, regional reductions in the hippocampal gray matter and basal nucleus, and greater white matter hyperintensity volume. CONCLUSIONS:Baseline antidepressant use was linked to a higher risk of dementia, poorer cognitive performance, and adverse brain structural changes. These findings underscore the importance of judicious prescribing, regular cognitive monitoring, and consideration of non-pharmacological approaches in clinical care.

Predicting small for gestational age (SGA) and large for gestational age (LGA) newborns is crucial for preventing adverse pregnancy outcomes and improving neonatal health. Existing purely data-driven methods have achieved promising performance in SGA-LGA newborn prediction, but most of them lack model interpretability, raising doubts in clinical auxiliary diagnosis and failing to provide targeted interventions. To address this challenge, this paper proposes an obstetric knowledge-driven large language model, termed Obstet-LLM. Specifically, Obstet-LLM is pre-trained on the content from professional knowledge bases in the field of obstetrics. This pre-training enables the model to understand and integrate domain-specific knowledge and clinical insights. Subsequently, the model undergoes prompt engineering and instruction fine-tuning to learn precise predictions of neonatal growth outcomes. To enhance model interpretability, a causal learning paradigm is designed, allowing Obstet-LLM to generate clear and understandable explanations. Experimental results show that Obstet-LLM achieves an accuracy rate of over 90% in predicting SGA-LGA newborns, outperforming existing data-driven models. Moreover, by integrating domain-specific knowledge, Obstet-LLM provides actionable insights for clinicians, thereby enhancing the quality of prenatal care and reducing the risk of adverse pregnancy outcomes.

Background Physical activity (PA) is inversely associated with all-cause mortality, yet how frailty status shapes the accumulation and saturation of this benefit remains unclear. This study aimed to assess frailty-specific associations between physical activity and all-cause mortality, characterize marginal benefits and benefit saturation across frailty strata, and identify high-benefit accelerometer-derived activity ranges linked to lower mortality risk. Methods This prospective cohort study included 90,573 UK Biobank participants with valid 7-day wrist-worn accelerometer data. Light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were quantified, and participants were classified as frail (n = 1631), pre-frail (n = 30,280), or robust (n = 58,662). Restricted cubic spline models and Cox proportional hazards models were used to characterize frailty-specific dose-response associations with all-cause mortality. Results Frail individuals experienced steeper relative risk reductions at lower PA levels, accompanied by earlier saturation of benefit, whereas robust individuals required higher activity volumes to achieve more modest benefit. The high-benefit LPA range was 1700–2100 min/week in frail individuals (65%–70% lower mortality risk), 1600–2200 min/week in pre-frail individuals (50%–60% lower risk), and 1800–2300 min/week in robust individuals (40%-50% lower risk). Corresponding high-benefit MVPA ranges were 240–500, 220–700, and 260–770 min/week, associated with 70%-80%, 40%-70%, and 30%-60% lower mortality risk, respectively. Conclusions Frailty modifies how PA-related mortality benefits accumulate and plateau, while preserving the overall inverse association between PA and mortality. These findings highlight the importance of frailty-aware interpretation of accelerometer-derived PA metrics in physiologically vulnerable populations.

BACKGROUND:Adverse childhood experiences (ACEs) are linked to long-term health risks, yet their association with chronic liver diseases (CLDs) and mediating roles of mental health, lifestyles, and socioeconomic status remain undefined. We aimed to investigate these associations. METHODS:This prospective cohort study included 107,363 UK Biobank participants free from CLDs at baseline. CLD diagnoses were ascertained through linkage to multiple sources. The primary outcomes were any CLD and metabolic dysfunction-associated steatotic liver disease (MASLD). Physical and emotional neglect, sexual, emotional, and physical abuse were assessed in 2016. Cox regression and mediation analyses were used. RESULTS:We identified 1888 (1.8%) cases of any CLD over a mean 13.6-year follow-up. Physical neglect and sexual/physical abuse were associated with higher risks of any CLD and MASLD. Linear dose-response relationships were observed between the number and overall intensity of ACE and any CLD and MASLD (Poverall < 0.05, Pnon-linearity > 0.05). Participants with 4-5 ACEs exhibited twofold or greater risks of any CLD (HR = 2.06; 95% CI: 1.69-2.51) and MASLD (HR = 2.09; 95% CI: 1.66-2.63). High overall ACE intensity was associated with more than 60% higher risks of any CLD (HR = 1.67; 95% CI: 1.46-1.92) and MASLD (HR = 1.66; 95% CI: 1.41-1.95). Mental health, lifestyles, and socioeconomic status were significant mediators, among which overweight/obesity mediates the largest proportion (up to 43.66%). CONCLUSIONS:ACEs are independent risk factors for CLDs, mediated by mental disorders, lifestyles, and socioeconomic status. Reducing ACE exposure and addressing overweight/ obesity may be effective strategies to mitigate ACE-related CLD risks.

Supplementary Figure S4 shows subgroup analyses for the association between glucosamine use and incidence of breast cancer in female participants.

The correlation between the co-infection of human respiratory adenovirus (HAdV) and clinical severity has not been firmly established yet. We carried out a systematic review and meta-analysis. We scoured six databases for studies published up to 16 May 2024. A total of 66 cohort studies, which involved 16 251 participants, were incorporated. When compared with patients suffering from HAdV single infection, those with co-infection of viruses (risk ratios [RRs] = 1.40, 95% confidence interval [CI]: 1.05-1.86), bacteria (RR = 1.50, 95% CI: 1.05-2.16), or fungi (RR = 2.86, 95% CI: 2.17-3.76) were more prone to experience severe clinical outcomes. Co-infection with Mycoplasma pneumoniae had a tendency to elevate the risk of common pneumonia (RR = 1.81, 95% CI: 1.66-1.97), and bacterial co-infection was likely to extend the hospital stay (mean differences = 2.23 days, 95% CI: 0.44-4.03). In summary, the co-infection of HAdV with other viral, bacterial, fungal respiratory pathogens or Mycoplasma pneumoniae heightened the risk of severe clinical outcomes in pediatric patients, leading to an increased utilization of medical resources. This implied that the ecological and biological mechanisms underlying the potential interactions between HAdV and other microorganisms merited further investigation.

Supplementary Figure S8 shows subgroup analyses for the association between glucosamine use and incidence of melanoma cancer.

Supplementary Table S5 shows sensitivity analyses for the association between glucosamine use and risk of overall cancer after censoring certain cancers by gender.

Supplementary Figure S6 shows subgroup analyses for the association between glucosamine use and incidence of esophageal cancer.

Supplementary Figure S9 shows subgroup analyses for the association between glucosamine use and incidence of ovary cancer in female participants.

Supplementary Figure S3 shows subgroup analyses for the association between glucosamine use and incidence of brain cancer.

Background The potential modifiable factors influencing irritable bowel syndrome (IBS) have not been thoroughly documented. We aimed to systematically investigate the modifiable factors associated with IBS, while accounting for the impact of unobserved confounders and coexisting disorders.Methods Genetic correlation and Mendelian randomisation (MR) analyses were integrated to identify potential modifiable factors and coexisting disorders linked to IBS. Subsequently, multiresponse MR (MR2) was employed to further examine these associations. Summary-level genome-wide association data were used. Modifiable factors and coexisting disorders (ie, gastrointestinal and psychiatric disorders) were identified based on evidence from cohort studies and meta-analysis. In all analyses, IBS was the primary outcome, while in the MR2 analysis, coexisting disorders were also treated as outcomes alongside IBS.Results Most identified modifiable factors and coexisting disorders exhibited genetic correlations with IBS. MR analyses revealed strong causation between IBS and multisite chronic pain (OR=2.20, 95% CI 1.82 to 2.66), gastro-oesophageal reflux disease (OR=1.31, 95% CI 1.23 to 1.39), well-being spectrum (OR=0.17, 95% CI 0.13 to 0.21), life satisfaction (OR=0.31, 95% CI 0.25 to 0.38), positive affect (OR=0.30, 95% CI 0.24 to 0.37), neuroticism score (OR=1.20, 95% CI 1.16 to 1.25) and depression (OR=1.50, 95% CI 1.37 to 1.66). Additionally, smoking, alcohol frequency, college or university degree, intelligence, childhood maltreatment, frailty index, diverticular disease of the intestine and schizophrenia were suggestively associated with IBS. Robust associations were found between multisite chronic pain and both IBS and coexisting disorders.Conclusions Our study identified a comprehensive array of potential modifiable factors and coexisting disorders associated with IBS, supported by genetic evidence, including genetic correlation and multiple MR analyses. The presence of multisite chronic pain may offer a promising avenue for the concurrent prevention of IBS and its coexisting disorders.

Supplementary Figure S14 shows subgroup analyses for the association between glucosamine use and incidence of hepatobiliary cancer.

Supplementary Figure S10 shows subgroup analyses for the association between glucosamine use and incidence of pancreas cancer.

BACKGROUND:Previous research indicates that constipation may be an early symptom of Parkinson's disease (PD). However, it remains uncertain whether constipation is a unique symptom prior to PD or to other major neurological disorders as well. This study aimed to explore the association between premorbid constipation and three major neurological disorders: stroke, dementia and PD. METHODS:We conducted a retrospective cohort study using data from UK Biobank. Constipation was defined based on diagnosed cases in electronic health records, self-reported instances or regular laxative use. The primary outcome was defined as the first onset of any of three neurological disorders: stroke, dementia and PD. Cox regression was used to adjust for socio-demographic characteristics, lifestyle factors, medical conditions and regular medication use. RESULTS:Out of 462,327 eligible participants, those with constipation were associated with higher incidence of three outcome diseases (1415/20,263 [7.0%]) than those without (18,848/442,064 [4.3%]), with adjusted hazard ratio (HR) being 1.35 [1.27-1.42]. Specifically, those with constipation had a 20%, 50% and 56% higher risk of stroke, dementia and PD, respectively. Both self-reported and diagnosed constipation were associated with a higher risk of these conditions, with HR being 1.31 (1.23-1.40) and 1.44 (1.30-1.59), respectively. Interestingly, the association between constipation and neurological disorders was stronger within the first 2 years from baseline. DISCUSSION:These findings support the biological link between constipation and neurological disorders. Given its potential role as a prodromal symptom for these diseases, both diagnosed and self-reported constipation should be considered in risk prediction models.

Supplementary Table S1 shows ICD codes used for identification of cancer diagnosis in the UK Biobank.

Evidence suggests immune checkpoint inhibitor (ICI) can increase the risk of myocarditis. We investigated it in a large national cohort in China. Patients with stage IIIB-IV non-small cell lung cancer (NSCLC) using data from China's National Anti-Tumor Drug Surveillance System between January 2013 and December 2021. Exposure density sampling was applied to control for immortal time bias. Multivariate Cox regression with time-dependent exposures was used to examine the association between ICI therapy and the incidence of myocarditis while controlling for confounders. 55,219 patients were included. The median age was 61 years, and 62

Background: Hip or knee joint replacement (HJR or KJR) is linked to a short-term increased risk of venous thromboembolism (VTE), but evidence on long-term VTE risk beyond 1 year is limited. This study compared the 10-year VTE risk in HJR or KJR patients with the general population. Methods: We conducted a prospective matched cohort study using the UK Biobank. A total of 18,984 HJR and 16,709 KJR patients were matched with controls by age, sex, VTE history, and cancer history via exposure density sampling. Flexible parametric models and piecewise Cox models were used to estimate time-varying hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE over 10 years postsurgery. Results: A total of 211,190 participants were included in the HJR cohort and 192,440 in the KJR cohort. The 10-year VTE risk was 6.2% (95% CI, 5.7%-6.7%) for HJR and 7.5% (95% CI, 7.0%-8.0%) for KJR. VTE risk peaked immediately postsurgery, declined gradually, but remained elevated throughout the 10-year follow-up. For HJR, the HR decreased from 24.10 (95% CI, 16.93-34.30) in the first 30 days to 1.49 (95% CI, 1.17-1.90) in years 8 to 10. For KJR, it decreased from 27.31 (95% CI, 19.67-37.92) to 1.32 (95% CI, 1.04-1.68) over the same period. Conclusion: VTE risk rises sharply after HJR or KJR and remains elevated for 10 years. Further studies should extend follow-up and collect detailed covariates related to VTE events to validate and characterize the potential long-term risk associated with HJR or KJR.

This scoping review summarizes the current landscape of randomized controlled trials (RCTs) evaluating the use of large language models (LLMs) in digestive diseases. We conducted a systematic search of PubMed, Web of Science, Scopus, and CENTRAL for published RCTs, and of ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for ongoing trials. We included RCTs on digestive diseases in which LLMs were the primary intervention. A total of four published and ten ongoing RCTs were identified. Most trials were conducted in China and the United States, primarily as single-country, single-center studies. Gastrointestinal diseases were the main focus, followed by hepatobiliary conditions. The assessed LLM applications predominantly supported clinical decision-making and patient education, with question answering emerging as the most common natural language processing task. Notably, the trials were relatively balanced in their use of general-purpose versus domain-specific LLMs, reflecting diverse strategies in model deployment. The most common study design involved comparisons between LLM-assisted and unassisted approaches, with primary outcomes centered on various aspects of care management. The main limitation of this review is the relatively small number of available studies. Despite this, the identified trials highlight the promising potential of LLM applications in digestive diseases. Further international, multicenter, well-reported RCTs with a focus on real patient outcomes are urgently needed to confirm the usefulness of LLMs in clinical practice.