EClinicalMedicine最新文献

{"title":"Two-year follow-up of neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases: longitudinal insights on depression, anxiety, memory and adaptation in the INSPIRE cohort.","authors":"Melanie Sloan, Avni Varshney, David D'Cruz, Guy Leschziner, Alice Tunks, Felix Naughton, James A Bourgeois, Martha Piper, Paige Hamilton-Conaty, Lucy Calderwood, Alessandra Bortoluzzi, Arjoon Arunasalam, Sharmilee Gnanapavan, Xiaofeng Yan, James Brimicombe, Max Yates, Ellie Dalby, Thomas A Pollak","doi":"10.1016/j.eclinm.2026.103818","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103818","url":null,"abstract":"<p><strong>Background: </strong>To date, studies of neuropsychiatric symptoms in systemic autoimmune rheumatic diseases (SARDs) have largely been cross-sectional. Our longitudinal study with patients with SARDs from the international INSPIRE cohort aimed to advance knowledge of changes in patient-reported neuropsychiatric symptoms and adapting over time.</p><p><strong>Methods: </strong>We conducted an observational cohort study analysing longitudinal data from the international INSPIRE (<b>I</b>nvestigating <b>N</b>europsychiatric <b>S</b>ymptom <b>P</b>revalence and <b>I</b>mpact in <b>R</b>heumatology Patient <b>E</b>xperiences) research project. Self-reported validated survey measures for anxiety (GAD-7), depression (PROMIS SF8), and memory (EMQ-R) were compared between baseline (2022) and follow-up surveys 2 years later (2024). We invited all participants who had provided their contact details and consented for the follow-up survey. Our co-produced \"ADAPT\" instrument was used to assess and compare changes in how people with SARDs adapt to living with their disease over time. T-tests, Kruskal-Wallis and Mann-Whitney U tests were used to assess differences across groups for changes in study measures. Sociodemographic and disease differences were controlled for by generalised linear modelling in adjusted analyses. Patients with polymyalgia rheumatica (PMR) made up the reference group because the Kruskal-Wallis test established no significant difference between the PMR and the control group for memory, depression and anxiety scores on the baseline dataset.</p><p><strong>Findings: </strong>The modal within-person change between baseline (BL) and follow-up (FU) for the N = 742 participants was zero for all 3 validated tools. Significant improvements at group level over two years were identified for memory scores (BL:16.14 to FU: 13.96, p = 0.002), and all four ADAPT measures (p < 0.05), whereas mean depression (BL:16.61 to FU:16.21, p = 0.303) and anxiety (BL:5.83 to FU:5.36, p = 0.073) scores were unchanged over time. Significant improvements in memory scores were observed in SLE (p = 0.022) and RA/IA (p = 0.009), and in those diagnosed (at baseline) > 10 years (p = 0.016) and between 6 and 9 years (p = 0.020).</p><p><strong>Interpretation: </strong>This study provides evidence against the expectation of progressive memory impairment in most cases in SARDs, including SLE. Lack of improvement in mean depression and anxiety scores over time suggests that many patients with SARDs may benefit from more proactive/assertive rheumatologic disease control, psychiatric intervention, and/or psychosocial support. Early and effective SARDs disease control is required, with timely psychiatric intervention and psychosocial support provided, particularly for the newly diagnosed.</p><p><strong>Funding: </strong>This study was funded by The Lupus Trust.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103818"},"PeriodicalIF":10.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once-daily oral ritlecitinib or brepocitinib versus placebo in patients with moderate-to-severely active Crohn's disease (PIZZICATO): an international, randomised, phase 2a trial.","authors":"Severine Vermeire, Jessica R Allegretti, Hyo Jong Kim, Millie D Long, Jaroslaw Leszczyszyn, Stefan Schreiber, Jaroslaw Kierkus, Paulette D Chandler, Jyoti Ramakrishna, Elena Peeva, Michael S Vincent, Negin Shojaee, Ping Mahling, Christopher Banfield, Anindita Banerjee, Jeremy D Gale, Kenneth E Hung","doi":"10.1016/j.eclinm.2026.103820","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103820","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Crohn's disease (CD) has a high unmet need for treatment. Ritlecitinib (Janus Kinase [JAK]3/tyrosine kinase expressed in hepatocellular carcinoma [TEC] family kinase inhibitor) or brepocitinib (tyrosine kinase 2 (TYK2)/JAK1 inhibitor) are promising therapeutic targets. We aimed to evaluate efficacy, safety, pharmacokinetics, and pharmacodynamics of ritlecitinib and brepocitinib versus placebo in patients with moderate-to-severely active CD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PIZZICATO was a multicentre, randomised, placebo-controlled, parallel-group, induction-maintenance, phase 2a study in patients with moderate-to-severely active CD. Eligible patients (18-75 years old) had an established diagnosis (endoscopic and histopathology) of ileal, ileocolonic, or colonic active CD at least 3 months before the study started and had documented treatment failure with at least one conventional CD therapy. This study was double-blind during the 12-week induction phase and was open label for the subsequent 52-week open-label extension (OLE) phase. Study participants were enrolled from 140 sites in 26 countries and were randomly assigned (1:1:1) to receive once-daily oral ritlecitinib (200 mg [8 weeks] followed by 50 mg [4 weeks]) or brepocitinib (60 mg [12 weeks]) or placebo in the induction phase, followed by a reduced dose of 50 mg ritlecitinib or 30 mg brepocitinib during the 52-week OLE phase. The primary efficacy endpoint was the proportion of patients who achieved Simple Endoscopic Score (SES) for CD (SES-CD 50; defined as ≥50% reduction from baseline) at Week 12 (ritlecitinib versus placebo; brepocitinib versus placebo), and was assessed in the full analysis set (FAS; all participants who received at least one dose of the study drug or placebo). The primary endpoint was changed from clinically-meaningful endoscopic improvement (CMEI) by protocol amendment during study execution. The safety profile of ritlecitinib and brepocitinib was assessed as a secondary endpoint during the induction phase and as a primary endpoint during the OLE phase. Safety was assessed in the safety analysis set (SAS; same as FAS). This trial was registered with ClinicalTrials.gov, NCT03395184, and EudraCT, 2017-003359-43.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Feb 2, 2018, and Oct 19, 2023, 244 patients (median age: 33.0 [18, 71]) were randomly allocated into study groups (ritlecitinib n = 93; brepocitinib n = 72; placebo n = 79) and included in the FAS and SAS. Of 244 participants dosed in the induction phase, 217 (88.9%) completed the induction phase and entered the OLE phase; 216 were dosed in the OLE phase. Disease activity was generally similar across groups and the majority of participants were tumour necrotizing factor (TNF) inhibitor experienced. For the primary outcome at Week 12, a significantly higher proportion of participants achieved SES-CD 50 with ritlecitinib (difference versus placebo: 14.3% [90% CI 4.0-24.5]; p = 0.012) or brepoc","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103820"},"PeriodicalIF":10.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term trends in Post-COVID severity: a machine learning analysis from the POP/COVIDOM cohort of the German NAPKON Cohort Network.","authors":"Julian Gutzeit, Martin Weiß, Thomas Bahmer, Wolfgang Lieb, Stefan Schreiber, J Janne Vehreschild, Carolin Nürnberger, Sina M Pütz, Ekaterina Heim, Anne-Kathrin Ruß, Astrid Dempfle, Michael Krawczak, Susanne Poick, Anna Schäfer, Caroline Morbach, Clara Lehmann, M Cristina Polidori, Jens-Peter Reese, Thomas Zoller, Lilian Krist, Jan Heyckendorf, Lennart Michel Reinke, Jürgen Deckert, Grit Hein","doi":"10.1016/j.eclinm.2026.103822","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103822","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Findings: </strong>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.</p><p><strong>Interpretation: </strong>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.</p><p><strong>Funding: </strong>The COVIDOM study is funded by the Network University Medicine as part of the NAPKON.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103822"},"PeriodicalIF":10.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leisure-time physical activity and risk of sudden cardiac death: a 28-year follow-up from the Copenhagen City Heart Study.","authors":"Shotaro Isozaki, Tobias Skjelbred, Peder Emil Warming, Eleonora Casarini, Eva Irene Bossano Prescott, Reza Jabbari, Jasmin Mujkanovic, Jacob Tfelt-Hansen","doi":"10.1016/j.eclinm.2026.103825","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103825","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Findings: </strong>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.</p><p><strong>Interpretation: </strong>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.</p><p><strong>Funding: </strong>Research Fund of Tokai University Educational System, Asahikawa Medical University Alumni Fund, Danish Heart Foundation, Birthe and John Meyer Family Foundation, Novo Nordisk Foundation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103825"},"PeriodicalIF":10.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an early prediction model for endometriosis risk: the simplified adolescent factors for endometriosis (SAFE) score.","authors":"Gita D Mishra, Mohammad Reza Baneshi, Sally Mortlock, Grant W Montgomery, Jenny Doust, Annette J Dobson, Jason Abbott","doi":"10.1016/j.eclinm.2026.103806","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103806","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis affects 11% of women of reproductive age. Diagnosis is often delayed by 6-8 years due to nonspecific symptoms and lack of early detection tools. This study aimed to develop an early risk prediction model for endometriosis to support referral decisions in primary care.</p><p><strong>Methods: </strong>Data were from an endometriosis-focused sub-study of the Australian Longitudinal Study on Women's Health. Data were split into a training (75% of women born 1989-95, n = 4005), internal test (remaining 25%, n = 1335), and external test (women born 1973-78, n = 4077) samples. Stable risk factors were identified using a bootstrapping procedure with multivariable logistic regression. A logistic regression model based on these factors was used to develop the Simplified Adolescent Factors for Endometriosis (SAFE) score, calculated as a count of risk factors. Models were evaluated in all three samples.</p><p><strong>Findings: </strong>Six stable risk factors were identified; three factors related to severity of general pelvic pain, two with menstrual disorders, and one with a family history of endometriosis. For the final logistic regression model, the areas under the curves (AUCs) were 0.81, 0.78, and 0.72 for the training, internal, and external test samples, respectively. Using the SAFE score (values 0-6), the corresponding AUCs were 0.79 (95% CI: 0.77-0.82), 0.79 (95% CI: 0.75-0.83), and 0.71 (95% CI: 0.69-0.73). Using a cut-point of ≥2 for the SAFE score, the corresponding sensitivity was 59.6, 64.2, and 46.7, specificity was 83.4, 82.6, and 85.7, and negative predictive value was 94.6, 94.4, and 89.7.</p><p><strong>Interpretation: </strong>The SAFE score is an evidence-based tool to guide endometriosis referrals in primary care. It shows strong statistical performance and warrants clinical evaluation.</p><p><strong>Funding: </strong>The ALSWH study is funded by the Australian Government Department of Health, Disability, and Ageing. The GELLES study is supported by the Medical Research Future Fund (MRFF) (MRFF1199785). GDM and GWM are Australian National Health and Medical Research Council (NHMRC) Fellows (APP2009577; GNT1177194). SM is a National Endometriosis Clinical and Scientific Trials Network Fellow.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103806"},"PeriodicalIF":10.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction models for high-grade cervical lesions or worse using machine learning.","authors":"Yunyang Deng, Joakim Dillner, Nicholas Baltzer, Laila Sara Arroyo Mühr, Roxana Merino Martinez, Alexander Ploner, Jiayao Lei, Mark Clements","doi":"10.1016/j.eclinm.2026.103819","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103819","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Interpretation: </strong>The models demonstrated strong predictive performance. Evaluating PPVs over the number of invited women provides the potential for risk-stratified screening and clinical utility.</p><p><strong>Funding: </strong>Vetenskapsrådet, FORTE, Karolinska Institutet, Horizon 2020, and Cancerfonden.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103819"},"PeriodicalIF":10.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal exercise modalities for enhancing motor function recovery after stroke: a Bayesian systematic review with pairwise and network meta-analyses.","authors":"Liqun Jiang, Huimin Ding, Hyun Seo, Buongo Chun","doi":"10.1016/j.eclinm.2026.103815","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103815","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;This study aimed to compare the effectiveness of different exercise interventions in improving motor function recovery after stroke and to identify optimal rehabilitation strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A comprehensive search of five databases was conducted for randomized controlled trials (RCTs) up to March 13, 2025. Primary outcomes included the 6-min walk test (6MWT), 10-m walk test (10MWT), Berg Balance Scale (BBS), and FMA (total, UE, LE). Pairwise and Bayesian network meta-analyses were performed to compare the relative effects of different exercise modalities. Risk of bias was assessed using the RoB 2 tool, and evidence certainty was rated using CINeMA. This systematic review was prospectively registered in PROSPERO (CRD420251091242).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;A total of 317 RCTs involving 14,464 stroke patients were included. Network meta-analysis showed that, compared with routine care, electrical stimulation plus exercise (ESX) was associated with the largest improvement in walking endurance (MD = 53.4 m, 95% CI 14.27-92.58, p &lt; 0.05, I&lt;sup&gt;2&lt;/sup&gt; = 0%), while aerobic exercise (AE), functional training (FT), gait training (GT), and mind-body exercise (MBE) showed smaller effects. Lower limb training (LLT) demonstrated the greatest improvement in gait speed (MD = 0.18 m/s, 95% CI 0.14-0.23, p &lt; 0.05, I&lt;sup&gt;2&lt;/sup&gt; = 0%), with TCMEX, task-oriented training (TOT), and MBE also showing benefits. For balance (BBS), core stability training (CST) ranked highest (SMD = 0.77, 95% CI 0.30-1.24, p &lt; 0.05, I&lt;sup&gt;2&lt;/sup&gt; = 93.24%), followed by MBE and FT. FT showed the largest pooled effect for total FMA (SMD = 2.15, 95% CI 0.48-3.81, p &lt; 0.05, I&lt;sup&gt;2&lt;/sup&gt; = 93.86%), whereas MBE showed larger pooled effects for FMA-LE (SMD = 1.94, 95% CI 0.04-3.85, p &lt; 0.05, I&lt;sup&gt;2&lt;/sup&gt; = 97.54%) and FMA-UE (SMD = 1.85, 95% CI 1.08-2.63, p &lt; 0.05, I&lt;sup&gt;2&lt;/sup&gt; = 95.57%). Substantial heterogeneity was observed in several pooled comparisons. Meta-regression analyses identified multiple outcome-specific clinical and contextual factors (e.g., intervention duration, stroke phase, stroke severity, routine rehabilitation, age, sex distribution, and socioeconomic setting) that partially explained between-study variability, although no single factor accounted for heterogeneity across all outcomes. Importantly, global network diagnostics indicated acceptable overall model fit and consistency, supporting cautious interpretation of the comparative estimates at the network level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Several structured exercise interventions were associated with improved motor outcomes after stroke. High heterogeneity was observed in some comparisons; however, meta-regression analyses suggested several potential sources of variability, and global network assessments indicated generally acceptable heterogeneity. These findings should therefore be interpreted cautiously, particularly for outcomes with subst","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103815"},"PeriodicalIF":10.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemsex and uptake of HIV pre-exposure prophylaxis among adult cisgender gay, bisexual and other men who have sex with men worldwide: a systematic review with meta-analysis.","authors":"Joan Gil Miñana, Sonia Arias García, Elisa De Lazzari, Francisco José Montoya Conesa, Lorena De La Mora, Montserrat Laguno, Josep Mallolas, Maria Martínez Rebollar, Alexandra Calmy, Lucía González Fernández","doi":"10.1016/j.eclinm.2026.103804","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103804","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;There is a lack of summarized information regarding the uptake of pre-exposure prophylaxis (PrEP) among HIV negative gay, bisexual and other men who have sex with men (GBMSM) who engage in chemsex. This systematic review and meta-analysis aimed to summarize, assess the quality of existing evidence, estimate the prevalence of PrEP uptake among GBMSM who engage in chemsex, based on available global evidence; and evaluate whether engagement in chemsex is associated with increased odds of PrEP uptake in this population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched Medline, Embase, Cochrane Reviews and CENTRAL, APA PsycInfo, Scopus, and LILACS. We included studies reporting chemsex practices among adult cisgender GBMSM and PrEP uptake until July 1, 2025. Evidence quality was assessed using the Newcastle-Ottawa Scale tool. Chemsex exposure was analyzed using two timeframe groups: recent (past 6 months) and ever (any longer or unspecified timeframe). Prevalence and associations -odds ratio (OR)- were pooled in meta-analyses using a random-effect model. Inconsistency, sensitivity, and publication bias analyses were conducted. PROSPERO registration: CRD42024573871.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Among 3988 records screened, 28 studies comprising 36,339 participants across three world regions were included: Western and Central Europe and North America, Asia and the Pacific, and Latin America; all were rated low to moderate quality. The overall prevalence of PrEP use was 39% (95% CI: 29-49%) among GBMSM who engaged in chemsex, with no significant differences between &lt;i&gt;recent&lt;/i&gt; and &lt;i&gt;ever&lt;/i&gt; chemsex timeframe groups. Sensitivity analyses and meta-regressions showed no significant effect of study publication year, country income group or world region. Overall chemsex was associated with higher odds of PrEP use (OR = 3.44, 95% CI: 2.70-4.38), with a significantly stronger association for &lt;i&gt;ever&lt;/i&gt; chemsex (OR = 4.74, 95% CI: 3.48-6.46) than for &lt;i&gt;recent&lt;/i&gt; chemsex (OR = 2.84, 95% CI: 2.11-3.81p &lt; 0.05). Meta-regressions indicated significantly lower odds of PrEP use in studies from low- and middle-income countries for both &lt;i&gt;recent&lt;/i&gt; (OR = 0.54, 95% CI: 0.31-0.94; p = 0.031) and &lt;i&gt;ever&lt;/i&gt; (OR = 0.46, 95% CI: 0.21-0.99; p = 0.046) chemsex timeframes. Heterogeneity remained moderate to high across all analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our findings suggest that PrEP use is relatively common among GBMSM who engage in chemsex globally and chemsex is consistently and strongly associated with increased PrEP uptake in this population. The association between chemsex and PrEP use was significantly higher in studies from high-income settings, where chemsex practices are better described and PrEP is more widely available for this group. The lack of standardized definitions in the field contributes to the high heterogeneity and strongly influences the generation of global evidence. This first systematic review ","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103804"},"PeriodicalIF":10.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Availability and effectiveness of multicomponent interventions for early psychosis in 20 low-income and middle-income countries: a systematic review.","authors":"Ruben Valle, Nora Morrison, Vijaya Raghavan, Srividya N Iyer","doi":"10.1016/j.eclinm.2026.103795","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103795","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 <i>a priori</i>. Study quality was evaluated using the Mixed Methods Appraisal Tool, and findings were synthesised narratively. This study was pre-registered with PROSPERO, CRD42022308467.</p><p><strong>Findings: </strong>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.</p><p><strong>Interpretation: </strong>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.</p><p><strong>Funding: </strong>Canadian Institutes of Health Research, Canada Research Chairs program.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103795"},"PeriodicalIF":10.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of physical abuse by caregivers toward infants aged 0-24 months: a systematic review and meta-analysis.","authors":"Cora L Keeney, Nichole Fairbrother, Vanessa Kitchin, Bryn Stagg, Emily J Fawcett, Azadeh Vaziri, Catherine Xu, Chelsea A Lahey, Jonathan M Fawcett","doi":"10.1016/j.eclinm.2026.103812","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103812","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Findings: </strong>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).</p><p><strong>Interpretation: </strong>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.</p><p><strong>Funding: </strong>No funding was received for this research.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"93 ","pages":"103812"},"PeriodicalIF":10.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}