Epidemiology and Psychiatric Sciences

ObjectiveThere is little longitudinal research investigating links between violence exposure and mental disorders among children in low- and middle-income countries (LMICs), despite high rates of violence. We examined cross-sectional and longitudinal violence-mental health associations among children in a large South African birth cohort, the Drakenstein Child Health Study, including direct clinical interviews capturing childrens mental disorders. MethodIn this birth cohort (N=974), we assessed lifetime violence exposure and four subtypes (witnessed community, community victimization, witnessed domestic, domestic victimization) at ages 4.5 and 8-years via caregiver reports. At 8-years, caregivers completed the Child Behaviour Checklist; and psychiatric disorders were assessed using the Mini-International Neuropsychiatric Interview for Children and Adolescents, a self-report measure. We tested for associations using linear/logistic regressions, adjusted for confounders. ResultsMost children (91%) had experienced violence by 8-years. Cross-sectionally, total violence exposure was associated with total (B =0.49 [95% CI 0.32, 0.66]), internalizing (0.32 [0.17, 0.47]), and externalizing problems (0.46 [0.31, 0.61]), and with increased odds of disorder at 8 years (aOR=1.09 [1.05, 1.13]). Longitudinally, total violence exposure up to 4.5-years was associated with total (B=0.27 [0.03, 0.52]), internalizing (0.24 [0.04. 0.44]), and externalizing scores (0.23 [0.008, 0.45]) at 8-years, but not with increased risk of psychiatric disorders. The strongest and most consistent associations were observed for domestic versus community violence subtypes. ConclusionOur strong cross-sectional but weaker longitudinal findings suggest that recent violence exposures may be more critical than early exposures for childrens mental health. Longitudinal exploration of other violence-affected LMIC populations is urgently needed.

Abstract Importance Stigma and discrimination against transgender and gender-diverse people are prevalent across many settings and may contribute to substantial health disparities. Objective To synthesize global evidence on the prevalence of stigma, discrimination, and resilience among transgender (trans) and gender-diverse adults. Data Sources A systematic search was conducted in PubMed, Embase, CINAHL, Cochrane Central, LILACS, and PsycInfo for articles published between January 1, 2010 and January 2, 2023. This database search was supplemented by grey literature and secondary reference searches. Article Selection Studies were eligible if they presented primary quantitative data on prevalence of stigma, discrimination, and/or resilience among trans and gender-diverse adults (aged 18 and over), with no restrictions on study design, language, or geographic region. Data Extraction and Synthesis Two independent reviewers extracted data using standardized forms, with discrepancies resolved by consensus. The JBI Critical Appraisal Checklist for Prevalence Articles was used to assess risk of bias. Random effects meta-analysis was conducted for dichotomous prevalence measures using inverse variance weighting and logit transformation; non-dichotomous prevalence data were summarized descriptively. Main Outcomes and Measures Outcomes included prevalence estimates for various forms of stigma (anticipated, perceived, internalized, and experienced), discrimination in legal/institutional settings (housing, healthcare, employment, police/prison), and resilience. Results A total of 97 articles, with data from 72,158 unique trans and gender-diverse participants across 26 countries, met inclusion criteria. Studies showed moderate levels of anticipated stigma, perceived stigma, and internalized stigma. Meta-analyses of 36 studies provided pooled estimates of discrimination prevalence across multiple domains: 21.4% in housing (e.g., eviction, rental denial), 24.6% in healthcare (e.g., denial of care, mistreatment), 32.8% in employment (e.g., hiring bias, workplace harassment), and 39.1% in police/prison settings (e.g., profiling, mistreatment). High heterogeneity was observed across studies, reflecting regional and methodological differences. Resilience scores ranged from moderate to high, indicating variation within trans and gender-diverse communities. Conclusions and Relevance This systematic review and meta-analysis found that stigma and discrimination against trans and gender-diverse adults are pervasive globally. Variation in stigma and discrimination across settings and regions underscores the need for targeted interventions and policy reforms. Funding World Health Organization through a grant from the Elton John AIDS Foundation and the Bill and Melinda Gates Foundation.

Objectives: In Latin America, up-to-date information to monitor UNAIDS 95-95-95 HIV targets in key populations, such as men who have sex with men, is limited. Elsewhere, structural homophobia restricts access to ART. Conceptual frameworks suggest that intersecting forms of violence and discrimination may negatively influence HIV care outcomes through psychosocial and structural pathways, although empirical evidence remains limited. The study aimed to assess whether sexual orientation outness and recent homophobic violence are associated with not being on ART among Latin American MSM living with HIV. Methods: This cross-sectional study is a secondary analysis of data from LAMIS-2018, including 7,609 MSM aged 18+ with an HIV diagnosis [≥]1 year prior from 18 Latin American countries. Participants self-reported ART status, sociodemographic characteristics, homophobic violence, and sexual orientation outness. Bivariate and multivariate logistic regressions identified those factors associated with not being on ART. Results: Nine percent of MSM with HIV were not on ART, 18% reported low sexual orientation outness, and 27% experienced homophobic violence, especially in Andean and Central American countries. Not being on ART was associated with recent homophobic violence (aPR=1.25), low outness (aPR=1.22), unemployment (aPR=1.27), and residence in the Andean subregion (aPR=1.87), Mexico (aPR=1.28), or the Southern Cone (aPR=1.45) versus Brazil. Protective factors included being older (25-39: aPR=0.72; >39: aPR=0.49), living in large cities (aPR=0.72), having a stable partner (aPR=0.78), and university education (aPR=0.74). Conclusions: Recent homophobic violence and low sexual orientation outness were associated with not being on ART among MSM in Latin America. While access varies across countries, structural factors such as stigma and violence may limit engagement in care. Addressing these barriers alongside strengthening health systems may be key to improving ART uptake and advancing progress toward the 95-95-95 targets.

Background: Opioid-related mortality in Texas has escalated dramatically, increasingly driven by illicitly manufactured fentanyl. To address local surges in mortality, the Galveston County Health District deployed the Galveston County Opioid Defense Effort (GCODE) in July 2023, leveraging digitally integrated surveillance data from emergency medical services (EMS) and the Medical Examiner to provide targeted naloxone distribution in identified overdose hot spots. Methods: Using a segmented interrupted time series (ITS) design and Poisson regression with robust standard errors, we evaluated the population-level impact of GCODE on opioid-involved mortality through the end of 2025. Data were sourced from the Galveston Area Ambulance Authority (GAAA) and vital statistics (ICD-10 codes). We assessed mortality trajectory changes, the observed fatality ratio among EMS-detected opioid events (the Survival Gap), and demographic and geographic covariates. Results: The Poisson ITS model included 519 weekly observations (N = 14,827 tract-weeks across 101 census tracts). Pre-intervention, opioid mortality increased by 0.16% weekly (IRR = 1.0016; 95% CI: 1.000-1.003; p = 0.011). Following GCODE deployment, the mortality trajectory reversed to a sustained 0.55% weekly decrease (IRR = 0.9945; 95% CI: 0.990-0.999; p = 0.021). The observed fatality ratio among EMS-detected events declined from 7.59% (preintervention mean; SD = 0.111) to 1.71% (post-intervention; SD = 0.042; Chi^2 = 19.824; p = 0.0001). Opioid decedents were significantly younger than the general mortality population (OR = 0.945 per year of age; p < 0.001), and were descriptively more likely to lack documented race/ethnicity data (41.23% vs. 8.27% Unknown; p < 0.001), limiting equity analysis. Conclusions: The findings are consistent with GCODE having meaningfully reduced opioid mortality by substantially lowering event-level lethality. These results suggest that targeted, digitally coordinated harm reduction can decouple overdose incidence from fatal outcomes, with implications for harm reduction program design in structurally constrained environments.

IntroductionIn many Low- and Middle-Income countries (LMIC), access to psychological therapies for psychosis remains extremely limited, contributing to significant treatment gaps and persistent inequalities in care. Novel interventions that are effective, scalable, and culturally acceptable across diverse settings are urgently needed. AVATAR therapy is an innovative digital intervention for distressing voices in psychosis, developed in the UK. The therapy enables voice-hearers to engage in a series of facilitated dialogues with a customized computer-based representation of their main distressing voice. AVATAR3 represents the first initiative to contextually adapt AVATAR therapy and evaluate its acceptability in two LMIC settings (Ethiopia and India). Methods and analysisWe will establish Innovation and Implementation Hubs in Addis Ababa, Ethiopia (Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa) at Addis Ababa University (AAU) and Mental Health Service Users Association (MHSUA), Ethiopia) and New Delhi, India (All India Institute of Medical Sciences). Phase 1 employs formative work and diverse stakeholder engagement to inform context-specific adaptations. Reflexive thematic analysis will be used, with data synthesis informed by the Cultural Adaptation of Scalable Psychological Interventions (CASPI) framework and Ecological Validity Model (EVM). Phase 2 tests adapted AVATAR therapy through a parallel case series (n=15 per site, targeting 70% completion rate) measuring feasibility, acceptability, and safety indicators at baseline, 12-weeks, and 24-weeks. Qualitative research will explore the experiences of participants (n=10) and therapists (n=8) at each site. Ethics and disseminationEthical approval has been obtained from Addis Ababa University College of Health Science Institutional Review Board, All India Institute of Medical Sciences (AIIMS) Institutional Review Board and the Kings College London (study sponsor) Research Ethics Committee. Findings will be disseminated to inform the implementation of AVATAR therapy across diverse international settings. Strengths and limitations of this studyO_LIInterdisciplinary and participatory approach C_LIO_LIContextual adaptation of a digital innovation C_LIO_LIExpert by experience leadership and involvement from the conception of the study C_LIO_LIThe study will develop tools and share learning to support future digital mental health innovation across diverse international settings C_LIO_LIThe case-series at each site will not have a control group C_LI

Background: Depression is associated with an increased risk of subsequent Parkinson's disease. Neuroimaging studies suggest a neurobiological overlap in mechanisms underlying Parkinson's disease and psychomotor retardation in depression. Our aim was to investigate whether, among individuals with depression, the presence of psychomotor retardation was associated with the development of subsequent Parkinson's disease. Methods: In a retrospective cohort study, electronic healthcare records from individuals diagnosed with depression at age 40 or over in a large mental health service in London, UK were examined for the presence of psychomotor retardation. Linkage to general hospital records was used to ascertain diagnoses of Parkinson's disease between 2007 and 2023. Cox regression was used to compare the hazard of Parkinson's disease in individuals with depression with and without psychomotor retardation. Results: Among 6327 patients with depression, 2402 (38.0%) had psychomotor retardation. The adjusted hazard ratio for development of Parkinson's in those with psychomotor retardation was 1.43 (95% CI 1.02 - 2.01, p = 0.04). Secondary analyses demonstrated a significant difference in psychomotor retardation incidence at least 10 years before Parkinson's diagnosis. Conclusions: Psychomotor retardation in later-life depression is associated with increased risk of subsequent Parkinson's diagnosis over an extended period of time, suggesting that the relationship cannot solely be explained by misdiagnosis. Psychomotor retardation may therefore serve as a marker of prodromal Parkinson's disease.

BackgroundPractical alcohol risk-reduction strategies are widely recommended in public-facing alcohol guidance, but randomized evidence from socially interactive drinking episodes remains limited. We conducted a pilot cluster randomized trial to evaluate the feasibility and preliminary effects of a package intervention comprising practical drinking-strategy information, participant self-selection of same-day strategies, and a brief commitment declaration in a social drinking laboratory. MethodsThis single-center, parallel-group pilot trial was conducted in Japan. Pre-existing social groups participated. One or two groups scheduled in the same session slot were combined into a time-slot allocation unit, which was randomized 1:1 either to the package intervention or to alcohol-related knowledge only. The primary outcome was total pure alcohol intake during the first 120 min. Session satisfaction on a Visual Analog Scale (VAS) was a prespecified secondary participant-experience outcome. ResultsOf 83 interested individuals, 63 were randomized and 59 participants in 17 social groups and 12 allocation units were included in the modified intention-to-treat analysis. The mean paired intervention-control difference for 120-min alcohol intake was-8.84 g (95% confidence interval [CI]-27.92 to 10.23; exact sign-flip p = 0.281). The corresponding exploratory 0-30 min difference was-4.90 g (95% CI-10.48 to 0.68; exact sign-flip p = 0.094). In a genotype-adjusted participant-level sensitivity analysis, the intervention coefficient for 120-min intake was-16.0 g (95% CI-30.9 to-1.1; p = 0.036). Session satisfaction was high in both arms with no clear between-arm difference. Next-day follow-up was 100%, and no adverse-event-related discontinuations occurred. ConclusionsThe intervention was feasible to deliver in a socially interactive drinking setting, and session satisfaction was high in both arms. Primary allocation-unit estimates favored lower alcohol intake but were imprecise. Larger trials are needed to estimate effects more precisely, while considering the potential influence of genotype imbalance on effect estimation in East Asian samples. Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000060685. Registered 17 February 2026.

Objectives: The primary aim of this study was to assess the feasibility of delivering an adapted problem-solving skills (PSS) intervention by quantifying the recruitment, follow-up and completion rates using a brief problem-solving intervention for people with a mental health diagnosis in two Polish prisons. Design: IAPPS is an open, multi-centred, parallel group feasibility randomised controlled trial (RCT). Setting: Two prisons in Poland. Participants: Men in custody aged 18 years and older, having a mental illness and living within the prison therapeutic unit. Interventions: The intervention consisted of an adapted PSS skills intervention plus care as usual (CAU) or care as usual only. Delivered in groups of up to five people in 1.5-hour sessions over the course of two weeks. Main outcome measures: Primary outcomes - rate of recruitment, follow-up, and feasibility to deliver the intervention. Secondary outcomes included measures of depression, general mental health, and coping strategies. Results: 129 male prisoners were screened, 64 were randomly allocated, with a mean age of 53.5 years (SD 14, range 23-84). 59 (95%) prisoners were of Polish origin. Our recruitment rate was 48%. There was differential follow up with those in the intervention group less likely to complete the post-test battery versus those who received care as usual. Outcome measures were successfully collected at both time points. Conclusions We were able to recruit, retain and deliver the intervention within the prison setting; some logistical challenges limited our assessment of intervention engagement. Our data helps to demonstrate how use of the RCT study design can be implemented and delivered within the complex prison environment. Trial registration number ISRCTN 70138247, protocol registration date May 2021

Background Individuals experiencing or at risk of homelessness face substantial barriers to preventive eye care that are poorly addressed by standard service models. Interdisciplinary optometry-social work collaboration offers a rights-based approach to improving engagement and continuity of care. Methods A convergent mixed-methods study was conducted between February and August 2024 at a multidisciplinary community centre. Clients experiencing or at risk of homelessness received integrated optometry and social work assessment and were prioritised as high, medium, or low based on combined clinical and social risk. Social work follow-up was guided by the Triple Mandate and W-Questions framework. Quantitative data were summarised using mean (SD), median [IQR], or n (%). Qualitative case notes were analysed using content analysis with inductive coding and secondary review for consistency. Results A total of 165 clients had priority categories coded (high: 68; medium: 47; low: 154). Demographic data were available for 132 clients (60% male; mean age 49.5 years [SD 16]); 27% had not completed high school, 89% reported weekly income below AUD 1000, and 28% had vision impairment. Two hundred forty-five case-note entries were consolidated into 146 unique records. SMS (46%) and phone calls (38%) were the most documented contact methods, although only 21% of calls were answered; missed calls (13%) and disconnected numbers (7%) were common. Multi-modal contact was more frequently documented for higher-priority clients. Appointment assistance was the most recorded facilitator (71%), while rights-based supports, including interpreter and transport assistance, were infrequently documented (<=5%). Qualitative analysis identified unstable communication, reliance on informal supports, and service fragmentation as key influences on recall outcomes. Conclusion This study supports an interdisciplinary, rights-based optometry-social work model to address barriers to preventive eye care among people experiencing or at risk of homelessness. Embedding structured handovers and tiered recall processes within community-based services may strengthen continuity and accountability for high-priority clients. Future implementation should evaluate outcomes related to equity of reach, service integration, and sustained engagement in care.

IntroductionFamily Constellation Therapy (FCT) has been widely disseminated in clinical, public health, and judicial settings despite persistent concerns regarding its theoretical basis, safety, and the limited availability of rigorous randomised evidence supporting its clinical use. ObjectiveThe aim of this systematic review is to assess the effects of FCT across all clinical conditions, explicitly considering both benefits and harms; and summarise the characteristics of studies and intervention settings used in randomised controlled trials of FCT. MethodsFollowing a prospectively registered protocol (CRD420251136190), we conducted a systematic search of seven databases (PubMed, EMBASE, APA PsycInfo, CENTRAL, BVS, Web of Science, and CINAHL) and grey literature (ICTRP and ProQuest database) without language or date restrictions to identify published and unpublished randomised controlled trials of FCT. Study selection, data extraction, risk of bias (RoB 2), and certainty of evidence (GRADE) were performed in duplicate. Statistical analyses followed a prospectively registered analysis plan with prespecified criteria for data pooling and for handling analytical limitations. ResultsNo reliable evidence was found to support the use of FCT for any condition across both clinical and non-clinical samples. All trials included were judged to be at high risk of bias and all comparisons were rated as very low-certainty evidence. Concerns regarding potential adverse effects were identified, and the available data was insufficient to establish the effectiveness of the intervention, precluding any clinical recommendation. ConclusionClinicians, policymakers, and consumers should reconsider adopting FCT while reliable evidence is not available.

BackgroundThe severity of positive psychotic symptoms largely defines emerging psychosis syndromes. However, depressive and negative symptoms are strongly psychologically and biologically interlinked. A transdiagnostic exploration of symptom severity across early illness syndromes could enhance the understanding of shared common factors and future trajectories of mental illness. We aimed to identify subgroups based on the severity of positive, negative, and depressive symptoms and assess relationships with: 1) premorbid functioning, 2) longitudinal illness course, 3) genetic risk, and 4) brain volume differences. MethodsWe analysed 749 participants from a multisite, naturalistic, longitudinal (18 months) cohort study of: clinical high risk for psychosis (n=147), recent onset psychosis (n=161), and healthy controls (n=286), and recent onset depression (n=155). Participants were stratified into subgroups based on severity of baseline positive, negative, and depression symptoms. Baseline and longitudinal differences between groups for clinical, functioning, and polygenic risk scores (schizophrenia, depression, cross-disorder) were assessed with ANOVAs and linear mixed models. Voxel-based morphometry was used to examine whole-brain grey matter volume differences. Discovery findings were replicated in a held-out sample (n=610). ResultsParticipants were stratified into no (n=241), mild (n=50), moderate (n=182), and severe symptom (n=254) subgroups. The mean (SD) age was 25.3 (6.0) and 344 (47.3%) were male. Symptom severity was associated with poorer premorbid functioning and illness trajectory, greater genetic risk, and lower brain volume. Findings were not confounded by the original study groups or symptoms and were largely replicated. Conclusions and relevanceTransdiagnostic symptom severity is linked to shared aetiologies, prognoses, and biological markers across diagnoses and illness stages. Such commonalities could guide therapeutic selection and future research aiming to detect unique contributions to specific psychopathologies.

ImportanceBlood-based biomarkers hold promise for psychiatric diagnosis and prognosis, yet clinical translation is constrained by poor reproducibility. Psychiatric biomarker studies are typically small, and demographic, behavioral, and temporal covariates often go undetected or cannot be adequately modeled. This may lead to residual confounding and unstable associations. ObservationsLeveraging UK Biobank data (N=~500,000), we systematically quantified how technical, demographic, behavioral, and temporal covariates influence 29 blood biomarkers commonly measured in research studies in psychiatry. Variance analyses showed substantial differences across biomarkers. Technical factors explained 1-6% and demographic factors explained 5-15% of the variance, with pronounced age-by-sex interactions for lipids and sex hormones. Behavioral covariates, particularly body mass index (BMI) and smoking, strongly influenced inflammatory markers. Temporal factors introduced systematic confounding. Chronotype was associated with blood collection time, multiple biomarkers exhibited marked diurnal rhythms (including testosterone, triglycerides, and immune markers), and inflammatory markers showed seasonal peaks in winter. In association analysis of biomarkers with major depression, bipolar disorder and schizophrenia, covariate adjustments attenuated or eliminated a substantial proportion of the biomarker-disorder associations, with BMI emerging as the dominant confounder. These findings demonstrate that such confounding structures exist and can be characterized in large cohorts, though specific biomarker-disorder relationships require validation in clinical samples. Conclusions and RelevancePoor reproducibility of biomarkers may not only stem from insufficient biological signal but also from inconsistent handling of confounders. We propose a systematic framework distinguishing technical factors (to be removed), demographic factors (addressed through adjustment or stratification), temporal factors (ideally controlled at design stages), and behavioral factors (requiring explicit causal reasoning). Associations robust to multiple adjustment strategies should be prioritized for clinical biomarker development. Standardized collection protocols, comprehensive covariate measurement, and transparent reporting across models are essential to improve reproducibility and identify biomarkers that reflect genuine illness-related pathophysiology.

BackgroundAccess to safe, equitable, and affordable surgical and anesthesia care is critical to reducing the burden of surgical diseases in Africa. To understand the state of access in South Sudan, we conducted a baseline assessment of surgical services in Central Equatoria State (CES) in May 2024. ObjectivesThis study aimed to survey public healthcare facilities in CES capable of providing essential surgical services. We used the capacity to perform cesarean section, laparotomy, and open fracture management--Bellwether procedures--as a proxy for assessing workforce, infrastructure, financing, information management, and service delivery. MethodsWe used a validated and contextualized Surgical Assessment Tool developed by the Harvard Program on Global Surgery and Social Change and the World Health Organization. Data were collected at the facility level and summarized descriptively using percentages, means (standard deviations), medians (minimum, maximum), and visualized in graphs, charts, and tables. ResultsAll three public health facilities assessed could perform Bellwether procedures for their catchment populations. However, workforce availability, financing, and surgical infrastructure were major constraints. The surgical workforce density was 2.27 surgical, anesthesia, and obstetric specialists per 100,000 population. Specialized procedures--such as repair of cleft lip and palate, clubfoot, and hydrocephalus shunt--were unavailable at all sites. None had magnetic resonance imaging (MRI) machines. The total average annual facility budget was $918,850, ranging from $3,960 to $800,000 at the teaching hospital--insufficient for proper operations. ConclusionWhile Bellwether procedures are routinely performed, access to quality and affordable care is compromised by deficits in workforce, financing, and infrastructure. We recommend that the Ministry of Health scale this survey nationally and develop a surgical policy and strategic plan focused on improving infrastructure, workforce, and financing for surgical and anesthesia care in South Sudan.

Progress in pharmacological treatment development for neurodevelopmental disorders is hindered by a misalignment between targeted mechanisms, outcome measures, and trial designs. This study was initiated as a post-trial access pathway for bumetanide and later expanded with treatment-naive participants. Within this framework, we implemented a parent-cocreated sensory outcome measure set (PROMset) in an unmasked, multiple-baseline single-case experimental design with randomized baseline periods of 2-12 weeks, followed by 6 months of bumetanide treatment (up to 1.5 mg twice daily). Participants (7-19 years) had atypical sensory reactivity and a diagnosis of ASD, ADHD, epilepsy, or TSC. The primary outcome was a PROMset comprising seven PROMIS item banks assessing anxiety, depressive symptoms, sleep disturbance, fatigue, sleep-related impairment, cognitive function, and peer relationships. Secondary outcomes included SSP, SRS-2, RBS-R, and ABC. Of 113 enrolled participants (mean age 13.2 [SD 2.7], 64% male), 102 completed the trial and 95 had analyzable PROMsets. At baseline, PROMset scores showed substantial impairment across domains (mean deviation =9.0 T-score points, p<.001) and correlated with sensory reactivity (SSP; r=-0.40, p<.001). Individual-level analyses showed improvement in 24-41% of participants per PROM domain, most frequently in anxiety and depressive symptoms (41% and 38%; mean across-case Cohen's d=-1). Overall, 83% improved on at least one domain. Group-level analyses showed improvement across all secondary outcomes (p<.001), with superiority over historic placebo for RBS-R and SSP. Integrating PROMsets with individualized trial designs can reveal clinically meaningful changes, supporting a more sensitive and patient-centered framework for treatment evaluation in heterogeneous populations.

ObjectiveTo examine whether menopausal women who initiate systemic menopausal hormone therapy (MHT) around menopause (45-60 years old) have a different risk of developing dementia than those not taking MHT. DesignSystematic review and meta-analysis of randomised controlled trials and longitudinal observational studies. Risk of bias was assessed using ROB-2 and ROBINS I-V2. Data sourcesMEDLINE, Web of Science, EMBASE, and Cochrane Library to 27 March 2026. Eligibility criteria for selecting studiesStudies which measured dementia or cognitive decline in women who initiated systemic MHT between ages 45-60 or within 5 years of menopause, compared with placebo or no MHT. Authors contacted for additional details if needed. Main outcome measuresDementia, Alzheimers disease (AD), cognitive decline. Results10 studies totalling 213,678 participants (189,525 in studies with the primary population). There was no significant increased risk in women with a uterus for all cause dementia (pooled hazard ratio (HR): 1.12; 95% CI 0.91-1.31, N=78,613, I2 = 96.9%), but increased AD risk (HR: 1.14; 95% CI 1.02, 1.29, N=134,865, I2 = 35.6%). Results were similar in sensitivity analyses including women with or without a uterus. Results for cognitive decline were variable. ConclusionsMHT initiated around the age of menopause should not be prescribed for cognition or dementia prevention. It is not protective against dementia and may increase risk slightly. The magnitude of risk was similar in AD and dementia, but the latter with larger confidence intervals. Studies which followed up individuals rather than on health records lost people to follow up. This may account for difference in cognitive decline outcomes between studies, as people with cognitive impairment and dementia are more likely not to attend. MHT prescribing should balance benefits against risks, including evidence of a small increased dementia risk. There are few high-quality studies, so further research would inform recommendations. Systematic review registration Prospero CRD420251010663 What is already known on this topic?O_LIMenopausal hormone therapy (MHT) is effective for alleviating vasomotor symptoms. Contemporary guidelines recommend treatment should be initiated for such symptoms under age 60 and or within 10 years of menopause onset. C_LIO_LIA large randomised trial on the topic found increased risk of dementia in women initiating MHT after the age of 65. C_LIO_LIIt is unknown whether initiating MHT around the age of menopause impacts the risk of dementia or cognitive decline. C_LI What this study addsO_LIThere was no evidence that taking MHT around the time of menopause decreases the risk of dementia or cognitive impairment. C_LIO_LIThey should not be prescribed for these indications. C_LIO_LIWe were able to find more studies which examine this question by contacting authors for additional data. C_LIO_LIInitiating MHT in women with a uterus around the age of menopause increased the risk of Alzheimers disease slightly, by over 10%, and there is a similar but not significant effect in the fewer studies of all cause dementia. Women with or without a uterus show similar results. C_LIO_LIWe found no significant difference shown in cognitive decline, possibly due to loss to follow up. This may be because most studies of cognitive decline follow up C_LI

Women living with HIV face about a six-fold higher risk of cervical cancer, yet screening uptake remains low in many sub-Saharan African settings. We explored factors influencing repeated decisions to decline cervical cancer screening during routine HIV care among women living with HIV at a large HIV clinic in Jos, Nigeria. Between September and December 2024, we conducted an exploratory qualitative study at the AIDS Prevention Initiative in Nigeria Clinic in Jos, Nigeria. We purposively recruited 27 women living with HIV aged 21 to 65 years who had never undergone cervical cancer screening and had repeatedly declined screening offers during routine HIV care, including at the current clinic visit. Semi-structured in-depth interviews were conducted in English or Hausa, audio-recorded, transcribed verbatim, and translated into English where needed. Data were analyzed thematically using theory-informed coding based on the Health Belief Model and Social Ecological Model. Among 27 women living with HIV who had repeatedly declined screening, perceived susceptibility was often low or uncertain despite recognition of cervical cancer severity. Perceived benefits were acknowledged but were frequently outweighed by overlapping barriers, including knowledge gaps and misinformation, indirect and downstream costs, emotional barriers, logistical constraints, clinic-flow and service-delivery barriers, and anticipated stigma. Education, reminders, and supportive clinic processes acted as cues to action, and most participants expressed willingness to screen in future. Among women living with HIV at this clinic who repeatedly declined screening when it was offered, perceived benefits were often outweighed by multilevel barriers. Screening programs may integrate fear-reduction and stigma-sensitive counseling with practical service delivery improvements, including shorter waiting times, reduced indirect costs, predictable and streamlined clinic flow, and consistent provider invitations and reminders, while addressing misinformation through community-embedded, culturally tailored messaging. These strategies may improve screening uptake and support more equitable cervical cancer prevention for women living with HIV in similar HIV-care settings.

Drug overdose deaths in the United States reached record levels during the fentanyl era before recently declining. A plausible hypothesis is that a sudden drop in fentanyl purity beginning in 2023 caused the downturn in overdose mortality. We evaluated this hypothesis by replicating a published analysis with regional overdose data, using models that account for time trends and autocorrelation, and negative control indicators to test for spurious correlation. When fentanyl purity was rising, the national purity series did not track overdose increases in most regions and showed only a modest association in the West. When both purity and mortality later declined, the observed associations were also seen with unrelated macroeconomic indicators that shared the same time pattern. National fentanyl purity alone does not provide a sufficient explanation for recent overdose declines.

BackgroundHwa-byung (HB) is a Korean culture-bound syndrome characterised by prolonged suppression of anger and somatic complaints. No evidence-based digital therapeutic (DTx) has been developed for HB. We evaluated the feasibility, user experience (UX), and preliminary clinical effect of an acceptance and commitment therapy (ACT)-based DTx application, Hwa-free, for HB. MethodsAdults aged 19-80 years diagnosed with HB were enrolled in a four-week app-based intervention with assessment at baseline (Week 0), Week 2, Week 4, and Week 8 follow-up. The primary outcome was UX assessed via a 22-item survey at Week 4. Secondary outcomes included HB-related symptom and personality scales, depression, anxiety, anger expression, psychological flexibility, health-related quality of life, and heart rate variability. ResultsOf 45 screened, 30 were enrolled and 28 constituted the modified intention-to-treat population. Mean app use was 19.9 {+/-} 7.9 days (71.2% adherence over 28 days). Adverse events were infrequent and unrelated to the intervention. Positive response rates exceeded 80% for video content (items 2-4: 82.8-89.7%), HB self-assessment (86.2%), meditation therapy (86.2%), and in-app guidance (85.7%). Pre-post improvements from baseline to Week 4 were observed in 11 of 18 clinical scales, including HB Symptom Scale ({Delta} = -9.8, Cohens d = -0.92), Beck Depression Inventory-II ({Delta} = -13.3, d = -1.11), and state anger ({Delta} = -7.8, d = -0.96). The HB screening-positive rate declined from 100% at baseline to 55.6% at Week 8. ConclusionsHwa-free demonstrated adequate feasibility, acceptable UX, and preliminary evidence of clinically meaningful improvement in HB-related symptoms. Future randomised controlled trial is warranted. Trial registrationCRIS, KCT0011105

Background: Early adolescence is a common period of onset for depressive symptoms. In part, this may reflect a developmental manifestation of individual's genetic propensities as they undergo physiological and hormonal changes and interact with new environments. Many commonly proposed mechanisms assume direct effects of an individual's own genes on emerging variation in their depressive symptomatology. However, estimates of genetic influence based on analyses in unrelated individuals capture not only direct genetic effects but also genetic effects from parents and other biologically related family members. Aim: In data from the Norwegian Mother, Father and Child Cohort (MoBa), we used linear mixed models to distinguish developmentally-stable and adolescence-specific direct and parental indirect genetic effects. We examined effects of polygenic scores for major depressive disorder (MDD), ADHD, anxiety disorders, and educational attainment (EA) on depressive symptoms, which were assessed by maternal reports at ages 8 and 14. Results: Children's own MDD polygenic scores showed adolescence-specific effects on depressive symptoms ( b_PGS*wave=0.041, [95% CI: 0.017, 0.065]). Developmentally-stable direct effects from children's polygenic scores for MDD (b=0.016, [0.006, 0.039]), ADHD (b=0.024, [0.008, 0.041]) and EA (b=-0.02, [ -0.038, -0.002]) were also evident. The only evidence of indirect genetic effects was a stable effect of maternal EA polygenic scores (b=0.04, [0.024, 0.054]). Conclusion: Direct genetic effects linked to genetic liability to MDD accounted for emerging variation in depressive symptoms in adolescence. These results imply that specific etiological mechanisms related to MDD may become particularly relevant for depressive symptoms during early adolescence compared to at earlier ages.

BackgroundWomens autonomy in healthcare decision-making has become one of the most critical yet inequitably distributed determinants of health outcomes, gender equity, and sustainable development worldwide. In Northern Nigeria, the presence of ethnic and socio-cultural inequality is frequently concealed by the aggregated statistics of a region. MethodsThis cross-sectional secondary analysis utilized the 2024 Nigeria Demographic and Health Survey. The sample included 9,998 married women (15-49 years) identifying as Hausa, Fulani, or Kanuri in Northern Nigeria. Healthcare autonomy was categorized as husband/partner alone, respondent alone, or joint decision-making. Analysis included weighted descriptive statistics, Rao-Scott adjusted chi-square tests for residential associations, and complex sample multinomial logistic regression to identify multivariable correlates while adjusting for sampling weights, strata, and clusters. ResultsMean age was 30.38 years. Most participants lacked formal education (69.6%) and resided in rural areas (72.0%). Husband-only decision-making predominated (72.6%), while 22.5% reported joint and 4.9% independent autonomy. Joint decision-making was significantly higher in urban (33.3%) than rural areas (18.3%; Adjusted F=50.892, p<0.001). In adjusted models (Reference: Kanuri), Hausa and Fulani women had substantially lower odds of joint decision-making relative to husband-only outcomes. Rural residence correlated with lower odds of both independent and joint agency. Notably, wealth status was not a significant predictor after adjustment (p > 0.05). ConclusionsEthnicity and residence are robust determinants of healthcare autonomy among women in Northern Nigeria, persisting regardless of education or wealth. This "socio-cultural paradox" suggests that economic interventions alone are insufficient. Policies must complement socioeconomic approaches with culturally responsive strategies addressing household power dynamics and entrenched social norms.