EClinicalMedicine最新文献

{"title":"Efficacy and safety of tiotropium in partial and uncontrolled preschool asthma (TIPP): a phase III, multicentre, randomised, double-blind, placebo-controlled trial.","authors":"Stefan Zielen, Nadine Wollscheid, Tanja Nickolay, Caroline Grimmel, David Scheele, Franziska Sattler, Freerk Prenzel, Michael Lorenz, Bianca Schaub, Christiane Lex, Franziska Stieglitz, Jordis Trischler, Helena Donath, Susanne Lau, Eckard Hamelmann, Christian Vogelberg, Michael Gerstlauer, Ruth Grychtol, Ralf Schubert, Monika Gappa, Lukas Schollenberger, Julia Wosniok","doi":"10.1016/j.eclinm.2026.104172","DOIUrl":"10.1016/j.eclinm.2026.104172","url":null,"abstract":"<p><strong>Background: </strong>Preschool children with asthma are more susceptible to develop acute life-threatening respiratory distress leading to hospital admissions compared to school children and treatment options are limited for this age group. We evaluated the safety and efficacy of tiotropium as add-on therapy to inhaled corticosteroids (ICS) in preschool children with high-risk, partly controlled or uncontrolled asthma.</p><p><strong>Methods: </strong>TIPP was a phase III, prospective, multicentre, randomised, double-blind, placebo-controlled, parallel-group (investigator-initiated) trial conducted at 13 German centres (12 hospitals, one specialised medical practice). Children aged 1-5 years with physician-diagnosed asthma, partly controlled or uncontrolled symptoms despite ICS, and a history of severe exacerbations were randomly assigned to receive once-daily tiotropium (two puffs of 1.25 μg) via Respimat® inhaler or placebo as add-on to ICS therapy over 52 weeks. The primary outcome was time to first severe asthma exacerbation requiring hospitalisation and/or systemic corticosteroid treatment. All randomised participants were included in the intention-to-treat analysis and analysed by treatment received for safety. No primary or safety data were missing; therefore, no imputation was required. The study was registered in the \"EU Clinical Trials Registry\" (EudraCT 2021-000190-81).</p><p><strong>Findings: </strong>Between February 2022 and March 2025, 100 of the planned 204 children were enrolled, of whom 86 were randomised to tiotropium + ICS (n = 44) or placebo + ICS (n = 42). Mean age was 3.3 years (Standard deviation (SD) 1.3). The primary outcome time to first severe asthma exacerbation did not differ between groups (Hazard ratio (HR): 0.99, 95% confidence interval (CI): 0.51-1.92; p = 0.98). At least one adverse event was reported in 41 (93%) of 44 children in the tiotropium + ICS group and 42 (100%) of 42 children in the placebo + ICS group. 397 adverse events were reported with tiotropium + ICS group and 450 with placebo + ICS group. Tiotropium was well tolerated, and no new safety signal was identified.</p><p><strong>Interpretation: </strong>Tiotropium did not reduce the risk of a severe asthma exacerbation, but was well tolerated as add-on therapy to ICS in preschool children with high-risk asthma.</p><p><strong>Funding: </strong>German Federal Ministry of Education and Research (01KG2030); study medication provided by Boehringer Ingelheim Pharma GmbH & Co. KG (0205-0546).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104172"},"PeriodicalIF":12.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963153","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":"Natural language processing-based model to predict radiation pneumonitis in patients with locally advanced non-small cell lung cancer undergoing chemoradiotherapy: a retrospective cohort study.","authors":"Julie R Bloom, Nicole Tignor, Tielman Van Vleck, Dexter P Mendoza, Sooyun Caroline Tavolacci, Olivia Fankuchen, Glen Chun, Stephanie Chang, Michael Chung, Stephanie Tuminello, Fred R Hirsch, Abraham Chachoua, Joshua K Sabari, Juan Wisnivesky, Ion Cotarla, Daniel Simmons, Kristin Hsieh, Chris Tackaberry, Kenneth E Rosenzweig, Robert M Samstein, Pei Wang, Rajwanth R Veluswamy","doi":"10.1016/j.eclinm.2026.104137","DOIUrl":"10.1016/j.eclinm.2026.104137","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Radiation pneumonitis (RP) remains a significant treatment-related toxicity in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) undergoing chemoradiotherapy (CRT). Most existing predictive models rely on static baseline demographic or dosimetry variables and lack real-time clinical applicability. We developed a novel predictive framework that integrates longitudinal symptom data extracted from clinical notes using natural language processing (NLP) with clinical and dosimetry features to improve early RP prediction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively identified 227 patients with locally advanced NSCLC treated with definitive CRT at a high-volume cancer center in the United States. We included all patients older than 18 years who were diagnosed between Jan 1, 2006, and Dec 31, 2022 with histologically or cytologically confirmed unresectable Stage 2 or 3 NSCLC and treated with conformal radiotherapy to a minimum dose of ≥45 Gy with or without chemotherapy. Of these, 31 RP events were identified through manual adjudication using radiologic criteria and chart review. NLP was used to extract the temporal relationship of 16 pre-specified symptoms with treatment from over 100,000 clinical notes spanning pre- and during-treatment intervals. We trained and validated machine learning models on combinations of baseline clinical data, radiation dosimetry, and NLP-derived symptom features. Model performance was evaluated using a nested cross-validation framework, with an outer cross-validation loop reserved for performance assessment and an inner cross-validation loop used for model training and integration, and summarized using area under the receiver operating characteristic curve (AUC) and partial AUC (pAUC) at high specificity thresholds. Clinical utility was evaluated using decision curve analysis (DCA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;The best-performing model incorporated longitudinal NLP features and achieved a median AUC of 0.759 (90% confidence interval 0.753-0.766), significantly outperforming baseline models using only dosimetry (AUC 0.613) or clinical variables (AUC 0.635). NLP-based features such as cough trajectory, shortness of breath, and wheezing were among the most important predictors. Inclusion of NLP-derived symptom data improved early identification of high-risk patients, particularly in the clinically relevant high-specificity range (pAUC 0.021 vs. 0.010 for dosimetry alone). DCA showed that the calibrated MLP model provided greater net benefit than default strategies of treating all or no patients across clinically relevant threshold possibilities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In this early work, NLP-based extraction of longitudinal symptoms from routine clinical documentation meaningfully enhances RP prediction in patients undergoing CRT for NSCLC. This approach leverages existing electronic health record infrastructure to deliver real-time, scal","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104137"},"PeriodicalIF":12.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963101","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":"Effects of hearing intervention on blood-based biomarkers of neuroinflammation and neurodegeneration: a secondary analysis of the ACHIEVE randomised controlled trial.","authors":"James Russell Pike, Alison R Huang, Nicholas Reed, Michelle L Arnold, Theresa H Chisolm, David Couper, Jennifer A Deal, Sarah Faucette, Adele M Goman, Rebecca F Gottesman, Timothy M Hughes, David Knopman, Christine Mitchell, Thomas H Mosley, Priya Palta, James S Pankow, Victoria A Sanchez, Elizabeth Selvin, Kevin J Sullivan, Bharat Thyagarajan, Lynne E Wagenknecht, Frank R Lin, Josef Coresh","doi":"10.1016/j.eclinm.2026.104164","DOIUrl":"10.1016/j.eclinm.2026.104164","url":null,"abstract":"<p><strong>Background: </strong>Research suggests that hearing loss in older adults is associated with elevated neuroinflammation and neurodegeneration, both of which are risk factors for dementia. In a secondary analysis of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomised controlled trial (ClinicalTrials.gov identifier: NCT03243422), we examined if hearing intervention slowed 3-year change in blood-based biomarkers of neuroinflammation (glial fibrillary acidic protein [GFAP]) and neurodegeneration (neurofilament light chain [NfL]).</p><p><strong>Methods: </strong>ACHIEVE, a clinical trial in the United States conducted between January 4, 2018 and November 30, 2022, tested the effects of hearing intervention (audiological counselling, provision of hearing aids) versus health education control (counselling on chronic disease prevention) on 3-year cognitive decline among older adults without substantial cognitive impairment and with untreated hearing loss. Plasma was collected at baseline and three years later among ACHIEVE participants recruited from the Atherosclerosis Risk in Communities cohort. Covariate-adjusted linear mixed effects models estimated intention-to-treat effects on 3-year change in inverse-normal transformed values of GFAP and NfL.</p><p><strong>Findings: </strong>Participants in the analytic sample (n = 164) were mean (SD) age 78.1 (2.9) years, 64.0% female, and 73.2% White. Over three years, hearing intervention was associated with a slower rise in GFAP (intervention: -0.026; 95% CI: -0.144, 0.093, control: 0.149; 95% CI: 0.039, 0.260; difference: -0.175; 95% CI: -0.322, -0.028; p-difference: 0.019) and NfL (intervention: 0.171; 95% CI: 0.022, 0.319, control: 0.330; 95 %CI: 0.185, 0.475, difference: -0.159; 95 %CI: -0.348, 0.029; p-difference: 0.098).</p><p><strong>Interpretation: </strong>Randomisation to hearing intervention was associated with a slower three-year rise in a blood-based biomarker of neuroinflammation. Comparable estimates were observed for neurodegeneration, although the effect was not statistically significant. Findings suggest that hearing intervention may reduce the rate of change in non-specific blood-based biomarkers associated with brain health and dementia progression.</p><p><strong>Funding: </strong>US National Institutes of Health.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104164"},"PeriodicalIF":12.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963143","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":"Artificial intelligence and machine learning in heart and lung transplantation.","authors":"Gaurav Sharma, Vineet Kumar Kamal, Lauren K Truby, Maryjane Farr, Irina Timofte, Vaidehi Kaza, Srdjan Lesaja, John S K Murala, Suresh Keshavamurthy, Matthias Peltz, Michael E Jessen","doi":"10.1016/j.eclinm.2026.104180","DOIUrl":"10.1016/j.eclinm.2026.104180","url":null,"abstract":"<p><p>Artificial intelligence (AI) and machine learning (ML) are increasingly applied across the heart and lung transplant continuum, from donor organ evaluation and waitlist prioritisation through peri-operative decision support to post-transplant rejection surveillance and personalised immunosuppression. Deep learning for endomyocardial biopsy interpretation has achieved an area under the curve (AUC) of 0.962, with performance comparable to expert pathologists, while ML-augmented ex-vivo lung perfusion platforms have demonstrated the potential to expand organ utilisation in real-world implementation studies. Noninvasive donor-derived cell-free DNA assays and electrocardiogram-based deep learning models are beginning to reduce dependence on invasive surveillance biopsies. Across published studies, models predicting 1-year post-transplant mortality have shown only moderate discrimination. Most published models remain retrospectively validated on single-centre datasets with limited external validation, inconsistent calibration reporting, and unresolved concerns about algorithmic bias and global health equity. This scoping review synthesises current evidence, critically appraises model performance, and identifies the regulatory, ethical, and methodological steps required for responsible clinical integration. Future research should prioritise prospective, multicentre external validation, transparent calibration reporting, and formal evaluation of clinical utility before these tools are adopted in routine transplant care.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104180"},"PeriodicalIF":12.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963054","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":"Bundibugyo virus disease evidence map: a rapid research needs appraisal.","authors":"Louise Sigfrid, Dijana Spasenoska, Sinead O'Dwyer, Marieke de Swart, Eli Harriss, Thomas Mendy, Gemma Villanueva, Nicholas Henschke, Alice Norton","doi":"10.1016/j.eclinm.2026.104179","DOIUrl":"10.1016/j.eclinm.2026.104179","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The 2026 Bundibugyo virus disease (BVD) outbreak in DRC and Uganda underscores that filoviruses remain an unpredictable global health threat, particularly in resource-limited settings. The sporadic occurrence of outbreaks has constrained evidence-generation. We implemented a Rapid Research Needs Appraisal (RRNA) to rapidly and systematically synthesise published research evidence and identify gaps in the evidence base to support management and research strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched Ovid Medline, Embase and Scopus for primary research studies published between Jan 1, 1999, and Feb 6, 2026 by combining keywords and thesaurus headings for Bundibugyo and humans. This search was supplemented by an updated search in PubMed and MedRxiv up to June 25, 2026. Searches were conducted in English, but without language restrictions. Eligible studies including humans or human samples focused on at least one of the RRNA domains (clinical characteristics, immune response, transmission, risk factors, medical countermeasures and associated social and behavioural factors). Two reviewers screened records for inclusion, one reviewer extracted data with a second reviewer checking a proportion of the data. Data were analysed descriptively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;29 primary studies were eligible for inclusion, accounting for 1593 probable or confirmed BVD cases. Of these 29 studies, most were observational (n = 28, 96.6%) and were most commonly conducted in Uganda (n = 15, 51.7%) and the DRC (n = 10, 34.5%). Only one interventional study was included, a non-randomized interventional study exploring EBOV, SUDV and BDBV cross-reactivity following EBOV vaccination. Among studies that reported age, most (58.6%, 17/29) included adults (18+ years), eight (27.6%) included children (0-18 years), and only two (6.9%) included pregnant women. Fever, vomiting, diarrhoea, headache, fatigue, dysphagia, anorexia, dyspnoea and abdominal pain were the most commonly reported symptoms. Haemorrhagic manifestations ranged from 10.4 to 54.0%, with a meta-analysis estimating a CFR of 32.8% (CI 25.8-40.2) based on past outbreaks. Evidence on cross-reactivity to previous Ebola exposure following natural infection of vaccination was sparse and conflicting. One study identified low levels of cross-reactivity in EBOV vaccinated participants, another among EBOV survivors, whereas a third did not detect cross-reactivity following EBOV vaccination. Long-term sequelae, persistent BVD survivor stigma and limited community awareness were also reported.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Whilst acknowledging the limitations of such a rapid appraisal, our findings show that urgent, coordinated investment is needed in countermeasure trials inclusive of pregnant women and children, supported by observational studies community engagement and co-production.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;The National Institute for Health Research (NIHR) a","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104179"},"PeriodicalIF":12.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962973","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-acting HIV pre-exposure prophylaxis adherence and discontinuation: a global systematic review and meta-analysis.","authors":"Xinyue Feng, Xinsheng Wu, Thomas S Fitzpatrick, Jason J Ong, Benjamin R Bavinton, Chien-Yu Cheng, Yingqing Chen, Nittaya Phanuphak, Hongbo Jiang, Xiaojie Huang, Linghua Li, Haiyan Min, Shu Liang, Rugang Wang, Xun Zhuang, Jun Zou, Lianguo Ruan, Sitong Luo, Xiaojun Meng, Hongxia Wei, Jin Zhao, Guochun Chen, Meiyin Zou, Jin Zhang, Zhen Ning, Feng Qian, Song Fan, Xiyu Liu, Maohe Yu, Jun Han, Yaokai Chen, Jianhua Yu, Yuxia Song, Yanhua Fu, Chengliang Chai, Hui Xue, Ping Ma, Yinzhong Shen, Bin Su, Huachun Zou","doi":"10.1016/j.eclinm.2026.104189","DOIUrl":"10.1016/j.eclinm.2026.104189","url":null,"abstract":"<p><strong>Background: </strong>Long-acting HIV pre-exposure prophylaxis (PrEP) may overcome adherence and discontinuation challenges facing oral PrEP, which remain unsystematically reviewed. This study aimed to synthesize the evidence on long-acting PrEP adherence and discontinuation.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of studies published from database inception to July 1, 2026 in PubMed, Web of Science, EMBASE, and Cochrane Library. Eligible studies reported adherence (on-time doses receipt at time points, e.g., at 2 months) or discontinuation (stopping doses or loss to follow-up within a time period, e.g., within 6 months) of long-acting PrEP, including long-acting injectable (LAI) and intravaginal ring (IVR) PrEP. Non-longitudinal designs and non-English publications were excluded. We used random-effects meta-analyses to pool estimates. Subgroup analyses were conducted by population, region, and study design.</p><p><strong>Findings: </strong>We identified 46 eligible studies (28 LAI and 18 IVR) including 22,945 individuals (14,190 and 8755). Adherence to six-monthly and two-monthly LAI-PrEP at 12 months was 93.0% (95% CI: 91.6-94.3) and 88.1% (84.7-90.8%); discontinuation for the six-monthly and two-monthly regimens within 12 months was 8.2% (4.9-13.4) and 16.0% (10.8-23.1). Discontinuation for two-monthly LAI-PrEP was higher in implementation studies than in clinical trials (14.6% vs. 1.8% within 6 months; 32.0% vs. 10.3% within 12 months, <i>P</i> < 0.0001). IVR-PrEP adherence was 66.1% (42.2-83.9%) at 6 months and discontinuation was 21.4% (12.6-33.8%) within 12 months. Compared with clinical trials, implementation studies showed lower adherence (32.0% vs. 73.8%) and higher discontinuation (41.1% vs. 7.7%) at 6 months (<i>P</i> < 0.0001).</p><p><strong>Interpretation: </strong>Adherence to LAI-PrEP remained high through 12 months, with the best adherence being observed in clinical trials, which serve as upper-bound benchmarks. Compared to LAI-PrEP, IVR-PrEP had lower adherence and higher discontinuation. Efforts facilitating longer-term adherence warrant research.</p><p><strong>Funding: </strong>This study was supported by the National Key R&D Program of China.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104189"},"PeriodicalIF":12.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963092","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":"Use of procalcitonin point-of-care testing to guide de-escalation of antibiotic therapy in adults with suspected bacterial sepsis in a tertiary hospital in Bangladesh: a randomised controlled open-label trial.","authors":"Forhad Uddin Hasan Chowdhury, Rabiul Alam Md Erfan Uddin, Mohammad Ali, Pranay Kumar Dutta, Durjoy Das, Abu Huraira Hanif, Stefano Di Gregorio, Moumita Kar, Faisal Bin Jahangir, Shafia Islam Khan, Karabi Chowdhury, Md Mohasin, Abdullah Abu Sayeed, Md Harunur Or Roshid, Naim Uddin Chy, Md Akram Hossain, Md Abdus Sattar, Marja Schilstra, Evelien de Jong, Constance Schultsz, Maarten Nijsten, Md Jashim Uddin, Aniruddha Ghose, Katherine Plewes, Luigi Pisani, Philippe Guerin, Mavuto Mukaka, Arjen M Dondorp","doi":"10.1016/j.eclinm.2026.104171","DOIUrl":"10.1016/j.eclinm.2026.104171","url":null,"abstract":"<p><strong>Background: </strong>Important drivers of antibiotic resistance in low- and middle-income countries (LMICs) include antibiotic overuse and scarcity of microbiological diagnostics. Procalcitonin point-of-care testing is a potential tool to guide antibiotic de-escalation in patients admitted with suspected bacterial sepsis.</p><p><strong>Methods: </strong>In an open-label randomised controlled clinical trial in Chittagong Medical College Hospital in Bangladesh, adult patients with suspected bacterial sepsis were randomised to procalcitonin (PCT)-guided de-escalation of antibiotic therapy or standard-of-care. In the intervention group, serum procalcitonin was assessed daily and clinicians received a non-binding advice to stop antibiotics after 72 h if procalcitonin dropped below pre-defined threshold concentrations (0.5 ng/mL or 80% from the peak value if baseline value > 2 ng/mL). The primary endpoint was length of antibiotic therapy analysed by intention-to-treat. The study is registered with ClinicalTrials.gov (NCT05955612) and was completed in July 2024.</p><p><strong>Findings: </strong>Between 26 July 2023 and 20 June 2024, 532 of the 1002 patients screened for eligibility were randomly assigned to procalcitonin-guided antibiotic therapy (n = 266) or standard-of-care (n = 266). Follow-up was completed on 30 July 2024. Median (interquartile range [IQR]) length of antibiotic therapy was 4.7 (2.8-8.0) days with procalcitonin-guided therapy compared to 9.0 (5.8-12.0) days in the control arm (p < 0.0001). Mortality was similar between the two groups. In the procalcitonin-guided arm, 23 of 265 participants died (8.7%; 95% confidence interval [CI], 5.6%-12.7%), compared with 21 of 265 participants (7.9%; 95% CI, 5.0%-11.9%) in the control arm. The absolute risk difference was 0.8 percentage points (95% CI, -3.9 to 5.5 percentage points) (p = 0.875). Following review, the Data Safety Monitoring Board did not identify any deaths as attributable to antibiotic discontinuation. The incidence of recurrent infections was 8/265 (3.0%) in procalcitonin-guided antibiotic therapy and 10/265 (3.8%) in the control arm (p = 0.811).</p><p><strong>Interpretation: </strong>In this single-centre trial in Bangladesh, procalcitonin-guided de-escalation reduced the duration of antibiotic therapy in adults with suspected bacterial sepsis. Mortality and recurrent infection were similar between the groups, although the trial was not powered to assess these outcomes formally. This promising approach of point-of-care procalcitonin-guided antibiotic discontinuation should be evaluated further in comparable resource-limited settings.</p><p><strong>Funding: </strong>Wellcome Trust of Great Britain.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104171"},"PeriodicalIF":12.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929276","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":"Pediatric yeast fungaemia species patterns, resistance profiles, and outcomes: a 20-year surveillance study in Paris, France.","authors":"Fanny Alby-Laurent, Thomas Obadia, Maud Gits-Muselli, Marie-Elisabeth Bougnoux, Benoit Brethon, Patricia Mariani, Juliette Guitard, Françoise Botterel, Elisabeth Chachaty, Karine Boukris-Sitbon, Olivier Lortholary, Marie Desnos-Ollivier, Fanny Lanternier","doi":"10.1016/j.eclinm.2026.104177","DOIUrl":"10.1016/j.eclinm.2026.104177","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The epidemiology of pediatric yeast bloodstream infections remains poorly characterized in high-income settings despite global shifts over the past two decades. As fungal species distribution varies geographically, national surveillance is essential. In France, recent reports have focused predominantly on adults, leaving a significant evidence gap for children.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analyzed data from the YEASTS program, a prospective multicentre hospital-based surveillance study conducted in 27 hospitals in the Paris area, France, between Oct 1, 2002, and Dec 31, 2022. All incident episodes of yeast bloodstream infection diagnosed during this period, were eligible. For the primary analysis, we included children and adolescents aged 6 months to 16 years; neonates and recurrent episodes were excluded. Adult cases (&gt;16 years) recorded during the same period were included for comparison. Species identification and antifungal susceptibility testing, using EUCAST standardized method, were performed at the National Reference Center of invasive Mycoses and Antifungals (NRCMA). The primary objective was to describe the epidemiology of yeast bloodstream infections in children and adolescents and compare findings with those observed in adults (&gt;16 years). The main outcomes assessed were species distribution, antifungal susceptibility patterns, treatment strategies, and 30-day all-cause mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Among 346 pediatric episodes, hematological malignancy was the main underlying condition (20.5%). &lt;i&gt;Candida albicans&lt;/i&gt; predominated (42%), although non-&lt;i&gt;albicans Candida&lt;/i&gt; species collectively accounted for a larger proportion of episodes, notably &lt;i&gt;Candida parapsilosis&lt;/i&gt; (23.5%) and &lt;i&gt;Candida tropicalis&lt;/i&gt; (10%). Species distribution varied by age: younger children had more &lt;i&gt;C. parapsilosis&lt;/i&gt;, older more &lt;i&gt;Pichia kudriavzevii&lt;/i&gt; (syn. &lt;i&gt;Candida krusei&lt;/i&gt;) and &lt;i&gt;Nakaseomyces glabratus&lt;/i&gt; (syn. &lt;i&gt;Candida glabrata&lt;/i&gt;). &lt;i&gt;Trichosporon asahii&lt;/i&gt; represented 2%. Resistance rates remained low (4% to caspofungin, 8.1% fluconazole) including 4 echinocandin-resistant isolates that harbored S645P mutations in the Fks coding region. 30-day mortality was 13.5%, independently associated with &lt;i&gt;C. tropicalis&lt;/i&gt;, &lt;i&gt;N. glabratus&lt;/i&gt;, &lt;i&gt;T. asahii&lt;/i&gt;, female sex, and ICU admission. Compared with 5889 adult cases, pediatric patients had a distinct species distribution, more frequent prior antifungal exposure, greater use of liposomal amphotericin B, and significantly lower adjusted 30-day mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Pediatric yeast bloodstream infections exhibit distinct epidemiological characteristics, species distribution, antifungal exposure patterns, and outcomes compared with adult infections. Future research should focus on prospective age-stratified studies to better define optimal antifungal treatment strategies, evaluate the clinical significanc","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104177"},"PeriodicalIF":12.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963075","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":"Intravenous ferric carboxymaltose and exercise capacity in iron-deficient kidney transplant recipients: a randomised, placebo-controlled trial in the Netherlands.","authors":"Joanna Sophia J Vinke, Michele F Eisenga, Amarens van der Vaart, Caspar J van Lieshout, Helma W G M Dolmans, Peter van der Meer, Jozine M Ter Maaten, Jacoba M Spikman, Aaltje L Ziengs, Jenny E Kootstra-Ros, Ilja M Nolte, Carlo G M Gaillard, Margriet F C de Jong, Stefan P Berger, Jan-Stephan F Sanders, Stephan J L Bakker, Arjan D van Zuilen, Martin H de Borst","doi":"10.1016/j.eclinm.2026.104169","DOIUrl":"10.1016/j.eclinm.2026.104169","url":null,"abstract":"<p><strong>Background: </strong>Whether correction of iron deficiency improves functional outcomes after kidney transplantation is unknown. We evaluated intravenous ferric carboxymaltose for improving exercise capacity in iron-deficient kidney transplant recipients.</p><p><strong>Methods: </strong>In this multicentre, double-blind, randomised, placebo-controlled trial, adult kidney transplant recipients with iron deficiency (ferritin <100 μg/L or 100-299 μg/L with transferrin saturation <20%) at least six months post-transplantation were recruited at two Dutch university hospitals between 7 October 2019 and 16 February 2024. Participants were assigned (1:1) to four intravenous doses of 500 mg ferric carboxymaltose or placebo at six-week intervals. The primary outcome was the between-group difference in 24-week change in 6-min walk test distance. Secondary outcomes included cardiac, kidney, muscle and cognitive function and quality of life. Efficacy was analysed by assigned treatment in 148 participants, with a per-protocol sensitivity analysis; safety analyses included 154 dosed participants. The trial was registered at ClinicalTrials.gov (NCT03769441).</p><p><strong>Findings: </strong>Of 155 participants randomised, seven were withdrawn under a prespecified COVID-19 amendment, leaving 148 participants for analysis (ferric carboxymaltose, n = 75; placebo, n = 73). Baseline 6-min walk test distance was 515 ± 91 m and 510 ± 114 m, respectively. Ferric carboxymaltose did not improve 6-min walk test distance versus placebo (adjusted mean difference +9 m [95% CI -10 to +28]). Ferric carboxymaltose corrected iron deficiency and increased haemoglobin, but did not improve cardiac function, muscle mass or strength, cognitive performance, or quality of life. Exploratory between-group differences occurred in estimated glomerular filtration rate and fibroblast growth factor 23. Infections and other clinically relevant adverse events did not differ between groups.</p><p><strong>Interpretation: </strong>Ferric carboxymaltose did not improve exercise capacity or most secondary outcomes, arguing against routine supplementation to improve functional capacity. Future studies should investigate observed differences in kidney function and fibroblast growth factor 23 concentrations and long-term clinical outcomes.</p><p><strong>Funding: </strong>Dutch Kidney Foundation, Dutch Heart Foundation, CSL Vifor.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104169"},"PeriodicalIF":12.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963087","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":"Women's leadership development programmes and gender equality: a systematic review in healthcare, academia and beyond.","authors":"Daisy Morris, Sana Rauf, Kathleen Riach, Helena Teede","doi":"10.1016/j.eclinm.2026.104185","DOIUrl":"10.1016/j.eclinm.2026.104185","url":null,"abstract":"<p><strong>Background: </strong>Women comprise 70% of the global health workforce yet hold only around 25% of leadership positions. Women's leadership development programmes (WLDPs) are widely implemented as organisational equity strategies; this review examined whether their reported outcomes extend beyond individual development to measurable organisational change.</p><p><strong>Methods: </strong>Systematic review without meta-analysis (PROSPERO: CRD42024554419), reported in accordance with PRISMA and SWiM. Nine databases were searched from 25 September 2015 to 5 July 2026. We included peer-reviewed studies evaluating structured WLDPs delivered to adult professionals in formal organisational roles that reported outcomes for women. Student-only populations and mentorship- or coaching-only interventions were excluded. Summary data were extracted from published reports by two independent reviewers using a standardised template incorporating TIDieR intervention-description items; quality was assessed using design-appropriate Joanna Briggs Institute critical appraisal tools. Outcomes were mapped using an extended Kirkpatrick framework spanning individual to organisational outcomes.</p><p><strong>Findings: </strong>From 2314 records, 57 studies evaluating 52 WLDPs across 23 countries were included. Most studies were from the United States (n = 36). Designs were predominantly mixed-methods or qualitative; none used randomisation, and four included comparison groups. All studies reported individual-level outcomes, most commonly self-reported improvements in confidence, knowledge, leadership capability, and behaviour. Thirty-two studies reported any organisational outcome, usually promotion or retention indicators. Subjective measures predominated over objective outcomes. Demographic reporting was limited: only 22 studies reported race or ethnicity, and very few reported sexual orientation, disability, or disaggregated advancement outcomes.</p><p><strong>Interpretation: </strong>WLDPs appear to support individual development, but current evidence cannot establish organisational transformation. Their broader equity potential depends on structural accountability: transparent and equitable recruitment pathways, institutional investment, and disaggregated outcome reporting, a reorientation of responsibility from individuals to organisations.</p><p><strong>Funding: </strong>The Australian National Health and Medical Research Council (NHMRC).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104185"},"PeriodicalIF":12.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963124","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}