Background: Post-COVID syndrome (PCS) affects many survivors with varying symptom profiles driven by acute disease severity (PCS-S) or individual resilience (PCS-R). While cross-sectional studies have identified risk factors and gender differences, long-term trajectories remain unclear. This study investigates the stability and progression of PCS-S and PCS-R scores after 9, 24 and 36 months from initial diagnosis, identifying key predictive factors stratified by gender.
Methods: We analyzed data from 1526 participants of the German National Pandemic Cohort Network (NAPKON), modeling symptom-based PCS-score trajectories over time with linear mixed-effects models. Data were split into training (n = 944), test (n = 233), and two-site external validation (n = 349) sets. Gender-stratified elastic-net regression used nine-month clinical and psychosocial measures to predict PCS scores at 24 and 36 months. All data were collected between November 2020 and February 2024. The study is registered on ClinicalTrials.gov (NCT04679584) and in the German Registry for Clinical Studies (DRKS00023742).
Findings: PCS-S and PCS-R scores showed small but significant declines between 9 and 36 months (β = -0.054 and -0.065, respectively; p < 0.001), indicating persistent symptom burden despite gradual improvement. Predictive models explained 16.7-52.6% of variance in later PCS severity. Fatigue after 9 months and age predicted later PCS-S; quality of life and depression added predictive value in females. Fatigue and sleep issues predicted PCS-R, with living/employment status relevant in females and cognitive deficits in males.
Interpretation: The severity of PCS subtype manifest after 9 months remains relatively stable over time, with distinct gender-specific predictors shaping symptom progression. Tailored interventions are essential for long-term management of PCS pathways.
Funding: The COVIDOM study is funded by the Network University Medicine as part of the NAPKON.
Background: Sudden cardiac death (SCD) remains a major public health challenge, yet the long-term association of leisure-time physical activity with SCD risk is not well established. We examined whether self-reported leisure-time physical activity is associated with SCD incidence over 28 years, accounting for competing risks from non-SCD mortality and time-updated changes in leisure-time physical activity.
Methods: We included 10,100 participants from the Copenhagen City Heart Study, examined in 1991-1994 and followed until 31 December 2021. SCD events were identified from Danish death certificates using a standardized protocol. Leisure-time physical activity was self-reported at baseline and at 10-year follow-up and incorporated as a time-updated exposure, categorized as low, moderate, or high. Cause-specific Cox models estimated associations with SCD, adjusting for age, sex, smoking, alcohol, and socioeconomic factors. Cumulative incidence was standardized to the Danish population, and population attributable risk for low activity was calculated. This study is registered at ClinicalTrials.gov (NCT02993172).
Findings: During a median follow-up of 28.6 years, 897 SCD events occurred among 10,100 participants (mean age 60.8 years; 56% women). Twenty-year standardized cumulative incidence rose with lower activity. In time-updated analyses, moderate and high leisure-time physical activity were associated with lower SCD risk compared with low activity (hazard ratio (HR) of 0.60, 95% confidence interval (CI) 0.50-0.72; and HR 0.50, 95% CI 0.41-0.62, respectively). After 25 years, 33% (95% CI 21-46%) of SCD could be attributed to low activity.
Interpretation: Higher leisure-time physical activity is associated with lower long-term risk of SCD in this observational cohort. These findings support the potential public health relevance of promoting leisure-time physical activity, although causality cannot be established.
Funding: Research Fund of Tokai University Educational System, Asahikawa Medical University Alumni Fund, Danish Heart Foundation, Birthe and John Meyer Family Foundation, Novo Nordisk Foundation.
Background: This study aimed to improve cervical screening efficiency by developing and validating machine-learning models for predicting high-grade cervical lesions or worse (HCL) risk.
Methods: From Swedish nationwide registers, we included 474,072 women invited to cervical screening in 2016 (split into 80% training and 20% test sets) and 370,105 women invited in 2017 for validation. All women underwent index cytology and/or human papillomavirus (HPV) testing within the recommended interval after age 29. Predictors included screening results (cytology and/or HPV testing), other HPV-related factors, and demographic factors (including age). Four random forest models were trained via 5-fold cross-validation with different predictors: Model 1 (M1) (all predictors), M2 (cytology, HPV testing, age), M3 (HPV testing, other HPV-related factors, and demographic factors), and M4 (HPV testing and age). We computed area under the curves (AUCs) and created plots to depict positive predictive value (PPV) by the number of women intervened.
Findings: In training and test sets, 1-, 3-, and 5-year HCL incidence proportions were 0.25%, 0.68%, and 1.05%, respectively. Cross-validated AUCs were 0.83-0.96 (M1), 0.83-0.96 (M2), 0.91-0.94 (M3), and 0.91-0.93 (M4), depending on the prediction intervals. Similar AUCs were found in the test set. Additionally, the AUCs in the validation set were 0.85-0.95 (M1), 0.85-0.95 (M2), 0.91-0.94 (M3), and 0.92-0.93 (M4). Across all intervals, M1 consistently demonstrated the highest PPV, followed by M2, M3, and M4. For each model, PPVs were lowest for 1-year predictions but comparable at 3 and 5 years.
Interpretation: The models demonstrated strong predictive performance. Evaluating PPVs over the number of invited women provides the potential for risk-stratified screening and clinical utility.
Funding: Vetenskapsrådet, FORTE, Karolinska Institutet, Horizon 2020, and Cancerfonden.
Background: Most individuals with psychosis live in low and middle-income countries (LMICs) where treatment delays and gaps are common. Little is known about the types of interventions for first-episode psychosis (FEP) and clinical high-risk (CHR) for psychosis in LMICs and their effectiveness. This systematic review aimed to identify treatment components delivered for FEP or CHR in LMICs and evaluate their effectiveness.
Methods: In this systematic review, we searched PsycINFO, Embase, and Medline for relevant studies published, without any language restrictions, between database inception and Jan 23, 2022. This search was updated on May 15, 2024 and on January 2, 2026. Records were included if they evaluated at least one more intervention beyond medication and assessment for FEP and beyond assessment for CHR, in LMICs with at least one follow-up. Included papers were classified as programmes (offering FEP/CHR services) or research studies of intervention(s)/outcomes in FEP/CHR. Treatment components were categorised as guideline-based or additional. Effectiveness was assessed across 15 outcomes defined a priori. Study quality was evaluated using the Mixed Methods Appraisal Tool, and findings were synthesised narratively. This study was pre-registered with PROSPERO, CRD42022308467.
Findings: Of 6046 screened records, 125 were included (average: 152 participants; range: 10-1268) across 20 countries and five languages (English, Spanish, Portuguese, Turkish, and Persian). These comprised 10 programmes and 30 studies for FEP in 16 countries (11.7% of LMICs), and eight programmes and eight studies for CHR across eight countries (5.8%). They delivered guideline-based and additional components; however, psychological and psychosocial components were scarce. For FEP, the addition of any psychological or psychosocial component was associated with improved outcomes relative to medication alone. Patient psychoeducation and family interventions were the most frequently implemented components. For CHR, limited data prevented conclusions about the effectiveness of treatment components in LMICs.
Interpretation: Despite limited and moderate-quality evidence, our findings suggest that early intervention can improve outcomes in FEP. However, coverage remains limited to few LMICs and even they struggle to provide comprehensive care. Further research is needed to strengthen, scale, and culturally adapt such services.
Funding: Canadian Institutes of Health Research, Canada Research Chairs program.
Background: Although the prevalence of physical abuse in childhood is well studied, the extent among infants-a period of high vulnerability-remains poorly characterized. We aimed to estimate the prevalence of physical abuse of infants (<24 months) by caregivers, using data from anonymous self-report studies.
Methods: A systematic review and meta-analysis were conducted following the Cochrane Handbook. We searched MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science (inception to Sep 3rd, 2025) for studies anonymously reporting the prevalence of physical abuse toward infants (0-24 months) by primary caregivers. Two reviewers independently screened studies and assessed risk of bias using the Joanna Briggs Critical Appraisal tool for prevalence studies. Prevalence estimates were aggregated using Bayesian multilevel logistic regression and heterogeneity quantified with 95% prediction intervals. The protocol was registered with PROSPERO (ID: CRD42023459469).
Findings: We identified 20 relevant studies (>220,000 caregivers) with prevalence estimates spread across 16 types of abuse, spanning North America, Europe, and East Asia. The pooled prevalence of reporting at least one form of abuse in a typical sample was 4·8%, 95% CI [2·6%, 7·5%] or 3·9%, 95% CI [1·9%, 6·4%] excluding "lesser" forms of abuse (e.g., spanking)-but with notable heterogeneity, 95% prediction interval [0·6%, 11·9%]. Aggregate estimates ranged from <3% for severe forms of abuse (e.g., shaking, hitting) to 9·5% for spanking or 20·5%-21·0% for slapping on the wrist (which might be culturally sanctioned in some areas).
Interpretation: Approximately one in twenty infants in a typical sample worldwide experience physical abuse by caregivers, though estimates vary and are likely underreported. Even in the first two years of life, many children face violent caregiving practices, pointing to an urgent need for prevention. The large gap between self-reports and official statistics highlights that most infant abuse remains hidden.
Funding: No funding was received for this research.
Background: Tuberculosis (TB) remains a major public health challenge, with 10.8 million people developing TB in 2023. Diabetes mellitus (DM) is associated with an increased risk of TB and adverse TB outcomes. The prevalence of DM is rising, especially in regions of the world where TB is endemic. Early detection and proper management of DM in those with TB may improve outcomes.
Methods: We performed a systematic review and meta-analysis of the yield of screening and the prevalence of DM among people with TB. Databases searched included PubMed, Cochrane CENTRAL, CINAHL, Embase, Global Health, LILACS, and Web of Science between January 2000 and September 2025. We included studies on the yield and prevalence of DM determined through DM screening among people with TB, where TB was identified microbiologically. All records were independently screened by two reviewers and discrepancies resolved by discussion. Risk of bias (RoB) was assessed using the Hoy tool for prevalence studies. Studies were pooled using random-effects meta-analysis with inverse variance weighting and stratified by World Health Organization (WHO) region and age (over and under 40 years). This systematic review and meta-analysis is registered online on PROSPERO CRD42023425596.
Findings: Our search retrieved 7530 studies. After full-text screening we included 33 studies involving 19,581 individuals with TB from 21 countries. The overall pooled yield of DM screening in people with TB was 7.8% (95% CI: 5.1-11.1), ranging from 2.6% (95% CI: 1.5-4.0) in the Western Pacific region (3 studies from 1 country) to 31.6% (95% CI: 12.4-54.3) in the Eastern Mediterranean region (3 studies from 2 countries).
Interpretation: DM is common among people with TB. The yield of DM screening was greater in the Eastern Mediterranean and South-East Asia regions which had a higher prevalence of DM. Findings were limited by substantial heterogeneity across studies and lack of comparison groups without TB in included studies. Future studies are needed to optimize approaches to detect DM among people with TB.
Funding: The World Health Organization Department for HIV, Tuberculosis, Hepatitis and Sexually Transmitted Infections and the Department of Noncommunicable Diseases and Mental Health, and the Preventive Treatment of Latent Tuberculosis Infection in People with Diabetes Mellitus study.
Background: CNS disorders (CNSD) after haematopoietic stem cell transplantation (HSCT) are a significant complication, although there are few specific studies on it. The major objective of this prospective case-control observational study was to characterise infectious and non-infectious CNSD (iCNSD and niCNSD, respectively) after HSCT.
Methods: Patients were eligible for the CNSD group if they underwent HSCT between January 2021 and December 2022 at 20 centres in 11 countries and developed either an iCNSD or a niCNSD at any time after the start of conditioning prior to HSCT, up to the study termination (June 2023). Data were collected by local investigators and sent to the EBMT Leiden Study Unit, Leiden, Netherlands. For each case, two controls surviving the same period after HSCT without CNSD as the respective case were selected. Primary endpoints of this study were (1) percentage of iCNSD and niCNSD, including different causes, (2) characteristics of CNSD (e.g., percentage of patients with an abnormal brain imaging pattern), and (3) the course (e.g., mortality and overall survival [OS] = at different time points). This study is registered at ClinicalTrials.gov (NCT04737785).
Findings: 237 patients (84 cases and 153 controls) were included, of whom 98 (41%) were female and 139 (59%) were male. The frequency of CNSD after HSCT was estimated at 2.9% (84 of 2910 transplanted patients, 95% CI 2.3-3.6%). Among cases, 21 (25%) had a proven/probable iCNSD, 47 (56%) had a proven/probable niCNSD, and 16 (19%) had a possible or unclassified CNSD. Human herpes virus-6 (meningo-)encephalitis was the most frequent proven/probable iCNSD (n = 9, 43%). In patients with proven/probable niCNSD, vascular pathologies were dominant (n = 15, 32%). In a multivariable Cox regression analysis, CNSD at the inclusion time point (HR 2.96, 95% CI 1.13-7.74, p = 0.027) remained the only significant predictor of inferior OS. Causes of death in the CNSD group were the CNSD (n = 15/36, 42%, eight with proven/probable iCNSD, five with proven/probable niCNSD and two with possible/unspecified CNSD), other HSCT-related causes (n = 7, 19%), relapse/progression (n = 5, 14%), or other (including multifactorial reasons, n = 9, 25%). Relapse/progression was the most frequent cause of death among controls (n = 17/25, 68%).
Interpretation: CNSD represent a serious complication after HSCT with an estimated 2.9% frequency and non-infectious causes prevailing over CNS infections. Patients with a CNSD after HSCT have a reduced OS, with the CNSD itself being the main cause of death.
Funding: None.
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