EClinicalMedicine最新文献

{"title":"Machine learning-based mortality risk assessment in first-episode bipolar disorder: a transdiagnostic external validation study.","authors":"Johannes Lieslehto, Jari Tiihonen, Markku Lähteenvuo, Alexander Kautzky, Aemal Akhtar, Bergný Ármannsdóttir, Stefan Leucht, Christoph U Correll, Ellenor Mittendorfer-Rutz, Antti Tanskanen, Heidi Taipale","doi":"10.1016/j.eclinm.2025.103108","DOIUrl":"10.1016/j.eclinm.2025.103108","url":null,"abstract":"<p><strong>Background: </strong>Accurate mortality risk prediction could enhance treatment planning in bipolar disorder, where mortality rates rival those of many cancers. Such prognostic tools are lacking in psychiatry, where assessments typically emphasize immediate suicidality while neglecting long-term mortality risks, and their clinical use is debated. We evaluated the recently developed machine learning model MIRACLE-FEP, initially developed for first-episode psychosis, in predicting all-cause mortality in patients with first-episode bipolar disorder (FEBD), hypothesizing that it would provide accurate risk prediction and guide pharmacotherapy decisions.</p><p><strong>Methods: </strong>We utilized national register-based cohorts of FEBD patients from Sweden (N = 31,013, followed 2006-2021) and Finland (N = 13,956, followed 1996-2018). We assessed the MIRACLE-FEP model's performance in predicting all-cause mortality using the area under the receiver operating characteristic curve (AUROC), calibration, and decision curve analysis. Additionally, we conducted a pharmacoepidemiologic analysis to examine the relationship between predicted mortality risk and pharmacotherapy effectiveness.</p><p><strong>Findings: </strong>MIRACLE-FEP achieved an AUROC = 0.77 (95%CI = 0.73-0.80) for 2-year mortality prediction in Sweden and 0.71 (95%CI = 0.67-0.75) in Finland. For 10-year all-cause mortality prediction, the model demonstrated an AUROC of 0.71 in both cohorts. The model demonstrated relatively good calibration and indicated potential clinical utility in decision curve analysis. Among patients with predicted risk exceeding the observed two-year mortality rate in FEBD, the lowest mortality risk was observed with polytherapy regimens (compared to non-use of antipsychotics or mood stabilizers), including quetiapine and lamotrigine (HR = 0.42, 95%CI = 0.23-0.80) or mood stabilizer polytherapy (HR = 0.47, 95%CI = 0.27-0.82). Conversely, in patients with predicted risk below this threshold, complex pharmacotherapy was not associated with a significant reduction in mortality risk.</p><p><strong>Interpretation: </strong>MIRACLE-FEP offers a promising approach to predicting long-term mortality risk and could guide proactive treatment decisions, such as targeting combination pharmacotherapy, in FEBD.</p><p><strong>Funding: </strong>The Swedish Research Council for Health, Working Life and Welfare, FORTE (2021-01079).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103108"},"PeriodicalIF":9.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540571","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":"The prognostic value of peritoneal metastases in patients with gastric cancer: a nationwide population-based study.","authors":"Niels A D Guchelaar, Micha J de Neijs, Bo J Noordman, Heilida E C Graaf, Irene E G van Hellemond, Pieter C van der Sluis, Esther Oomen-de Hoop, Sjoerd M Lagarde, Rob H A Verhoeven, Stijn L W Koolen, Misha D P Luyer, Ignace H J T de Hingh, Hanneke W M van Laarhoven, Bianca Mostert, Bas P L Wijnhoven, Ron H J Mathijssen","doi":"10.1016/j.eclinm.2025.103109","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103109","url":null,"abstract":"<p><strong>Background: </strong>The peritoneum is a common metastatic site in gastric cancer. The prognosis of synchronous peritoneal metastases compared to other metastatic sites in gastric cancer remains understudied. This study aims to evaluate the impact of peritoneal metastases on survival in patients with metastatic gastric cancer.</p><p><strong>Methods: </strong>Patients with gastric cancer and synchronous metastases between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Patients were categorized based on the site of metastases. Median overall survival (OS) was calculated for each metastatic site group. Multivariable Cox regression analyses were performed to evaluate the association between patient, tumour, and treatment characteristics, including the impact of systemic therapy, on OS.</p><p><strong>Findings: </strong>A total of 4072 patients were included, of whom 1835 (45.1%) had peritoneal metastases. Of these, 58.1% had isolated peritoneal metastases. For patients with metastatic gastric cancer treated with systemic therapy, the median OS was 9.0 months (95% confidence interval (CI): 8.6-9.5), compared to 1.7 months (95% CI: 1.7-1.9) for treatment-naïve patients, who received only palliative care. The survival for patients with isolated peritoneal metastases (4.4 months, 95% CI: 4.0-4.8 months) was similar to those with isolated non-peritoneal metastases (4.6 months, 95% CI: 4.2-5.1 months, adjusted HR: 0.94, 95% CI: 0.86-1.03, p = 0.185). Systemic therapy was associated with comparable survival in patients with peritoneal metastases and those with metastases at other sites.</p><p><strong>Interpretation: </strong>This study demonstrates that there is no statistically significant difference in survival between patients with isolated peritoneal metastases and those with isolated non-peritoneal metastases in gastric cancer. Our findings emphasize the unique prognostic landscape for peritoneal metastases in gastric cancer, underscoring the need for disease-specific evaluations, rather than relying on assumptions derived from other cancer types.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103109"},"PeriodicalIF":9.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540576","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":"Multicenter validation of a machine learning model to predict intensive care unit readmission within 48 hours after discharge.","authors":"Leerang Lim, Mincheol Kim, Kyungjae Cho, Dongjoon Yoo, Dayeon Sim, Ho Geol Ryu, Hyung-Chul Lee","doi":"10.1016/j.eclinm.2025.103112","DOIUrl":"10.1016/j.eclinm.2025.103112","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Intensive care unit (ICU) readmission is a crucial indicator of patient safety. However, discharge decisions often rely on subjective assessment due to a lack of standardized guidelines. We aimed to develop a machine-learning model to predict ICU readmission within 48 h and compare its performance to traditional scoring systems.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We developed an ensemble model, iREAD, that generates a probability score at ICU discharge, representing the likelihood of the patient being readmitted to the ICU within 48 h, using data from Seoul National University Hospital (SNUH) and validated it using the MIMIC-III and eICU-CRD datasets. From September 2007 to August 2021, a total of 70,842 patients were included from SNUH. The MIMIC-III datasets comprised 43,237 patients admitted to ICUs between 2001 and 2012 at Beth Israel Deaconess Medical Center, and the eICU-CRD datasets included 90,271 ICU admissions across 208 hospitals between 2014 and 2015. Patients younger than 18, those who died in ICUs, or who refused life-sustaining treatment were excluded from the final analysis. The model's performance was evaluated using the area under the receiver operating characteristic curve (AUROC) and compared to the traditional scores and conventional machine learning models. Kaplan-Meier analysis was performed to compare the outcome between the high-risk and low-risk groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;We developed the iREAD, that utilized 30 input features, encompassing demographics, length of stay, vital signs, GCS, and laboratory values. iREAD demonstrated superior performance compared with other models across all cohorts (all P &lt; 0.001). In the internal validation, iREAD achieved AUROCs of 0.771 (95% CI 0.743-0.798), 0.834 (0.821-0.846), and 0.820 (0.808-0.832) for early (≤48 h), late (&gt;48 h), and overall ICU readmissions, respectively. External validations with MIMIC-III and eICU-CRD also showed modest performance with AUROCs of 0.768 (0.748-0.787) and 0.725 (0.712-0.739) for overall readmission in MIMIC-III and eICU-CRD respectively, demonstrating superior performance compared to other models (All P &lt; 0.001; higher than other models). Kaplan-Meier analysis revealed that over 40% of high-risk patients predicted by iREAD were readmitted within 48 h, representing a more than four-fold increase in predictive performance compared to the traditional scores.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;iREAD demonstrates superior performance in predicting ICU readmission within 48 h after discharge compared to traditional scoring systems or conventional machine learning models in both internal and external validations. While the performance degradation observed in the external validations suggests the need for further prospective validation on diverse patient populations, the robust performance and ability to identify high-risk patients have the potential to guide clinical decision-making.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/s","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103112"},"PeriodicalIF":9.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540573","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":"Quantitative vascular feature-based multimodality prediction model for multi-origin malignant cervical lymphadenopathy.","authors":"Chunyan Li, Rui Li, Jinjing Ou, Fang Li, Tingting Deng, Cuiju Yan, Qingguang Lin, Ruixia Hong, Feng Han, Huiling Xiang, Yao Lu, Xi Lin","doi":"10.1016/j.eclinm.2025.103085","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103085","url":null,"abstract":"<p><strong>Background: </strong>The precise prediction of multi-origin malignant cervical lymphadenopathy is limited by the low inter-reader reproducibility of imaging interpretation, and a quantitative method to improve this aspect is lacking. This study aimed to develop and validate an artificial intelligence framework integrating quantitative vascular features for assessing cervical lymphadenopathy and explore its utility among radiologists.</p><p><strong>Methods: </strong>For this retrospective study, a total of 21,298 ultrasound images of 10,649 cervical lymph nodes (LNs) from 10,386 patients and 2366 images of 1183 LNs from 1151 patients at the Sun Yat-sen University Cancer Center between January 2011 and July 2022 were used for model development and internal testing, respectively. For external model testing, we used 776 images of 388 LNs from 360 patients at the Chongqing University Cancer Hospital between January and December 2022. Quantitative features used to characterize the vascular distribution and degree of richness were fused with morphological and semantic features on B-mode and color Doppler ultrasound images to develop a dual-modality, multi-feature, fusion lymph node network (DMFLNN). Subsequently, the performance of DMFLNN was compared with that of six radiologists, and its auxiliary value was assessed in test cohorts.</p><p><strong>Findings: </strong>DMFLNN achieved an area under the receiver operating characteristic curve (AUC) of 0.937 for the internal test cohort and 0.875 for the external test cohort. Using the internal test cohort with assistance from DMFLNN, the average AUC improved from 0.814 to 0.836 for senior radiologists (<i>P</i> = 0.00018), and from 0.778 to 0.847 for junior radiologists (<i>P</i> < 0.0001). Additionally, the average inter-radiologist agreement improved from fair to moderate (improvement in kappa: from 0.590 to 0.696 for senior radiologists; from 0.571 to 0.750 for junior radiologists). Similar trends were observed for the external test cohort. Moreover, the radiologists' average false-positive rate decreased by 3.8% and 9.8% for the internal and external test cohorts, respectively.</p><p><strong>Interpretation: </strong>DMFLNN could improve radiologists' performance and potentially reduce unnecessary biopsies of cervical lymphadenopathy. However, further testing is warranted before its wide adoption in clinical practice.</p><p><strong>Funding: </strong>The National Natural Science Foundation of China (82171955; 62371476; 82441027); the China Department of Science and Technology (2023YFE0204300); and the R&D project of Pazhou Lab (HuangPu) (2023K0606).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103085"},"PeriodicalIF":9.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540308","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 food restrictions to prevent infections in paediatric patients with cancer and haematopoietic cell transplantation recipients: a systematic review and clinical practice guideline.","authors":"Robert Phillips, Brian T Fisher, Elena J Ladas, Priya Patel, Paula D Robinson, L Lee Dupuis, Roland A Ammann, Melissa P Beauchemin, Fabianne Carlesse, Elio Castagnola, Bonnie L Davis, Kirsten Efremov, Caitlin W Elgarten, Andreas H Groll, Gabrielle M Haeusler, Christa Koenig, Alisa Morris, Maria Elena Santolaya, Daniela Spinelli, Wim J E Tissing, Joshua Wolf, Lillian Sung, Thomas Lehrnbecher","doi":"10.1016/j.eclinm.2025.103093","DOIUrl":"10.1016/j.eclinm.2025.103093","url":null,"abstract":"<p><strong>Background: </strong>Food restrictions during periods of neutropenia have been widely used in oncology settings to prevent infections. As there is a lack of clearly demonstrated effectiveness, this strategy is being increasingly questioned.</p><p><strong>Methods: </strong>A multi-national panel of 23 individuals was convened to develop a clinical practice guideline (CPG) on the use of food restrictions to prevent infections in paediatric patients with cancer and haematopoietic cell transplantation (HCT) recipients. It included representation from persons with lived experience and physicians, dieticians, nurses, pharmacists and guideline methodologists working in paediatric oncology/HCT or infectious diseases. Panel members (female n = 15; 65%) were from North America (12, 52%), Europe (8, 35%), South America (2, 9%) and Australia (1, 4%). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to formulate the CPG recommendations based on a systematic review of randomised controlled trials (RCTs). MEDLINE, MEDLINE in-Process and Embase databases were searched from January 1, 1980, to May 7, 2024, with a broad strategy which combined subject headings and text words relating to neutropenia, infection and diet.</p><p><strong>Findings: </strong>The systematic review, which provided the evidence base for the CPG recommendations, identified 4312 unique citations, of which 52 were retrieved for full-text evaluation. Eight RCTs met the eligibility criteria and informed panel deliberations. Although there was clinical heterogeneity in the food restrictions evaluated, data were consistent in suggesting that food restrictions lack clinically significant benefit in preventing infections. The panel made two conditional recommendations against the use of food restrictions in a) paediatric patients with cancer receiving chemotherapy and b) in the setting of allogeneic and autologous HCT. The panel developed a good practice statement to emphasise the importance of health care organisations and families adhering to local food safety practices.</p><p><strong>Interpretation: </strong>This CPG provides the first evidence-based recommendations on use of food restrictions to prevent infections in children and adolescents undergoing chemotherapy and paediatric haematopoietic cell transplant recipients.</p><p><strong>Funding: </strong>This CPG was funded and developed through the POGO Guidelines Program.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103093"},"PeriodicalIF":9.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540578","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":"Tuberculosis-associated respiratory impairment and disability in children and adolescents: a systematic review.","authors":"Kamila Romanowski, Silvia S Chiang, Sierra A Land, Marieke M van der Zalm, Jonathon R Campbell","doi":"10.1016/j.eclinm.2025.103107","DOIUrl":"10.1016/j.eclinm.2025.103107","url":null,"abstract":"<p><strong>Background: </strong>While the immediate effects of pulmonary tuberculosis are well-documented, respiratory impacts persisting beyond treatment, particularly in children and adolescents, are less understood. This systematic review aimed to evaluate the current evidence on tuberculosis-associated respiratory impairment and disability in children and adolescents following tuberculosis treatment.</p><p><strong>Methods: </strong>We searched MEDLINE, Embase, CENTRAL, Global Index Medicus, and preprints from January 1, 2004, to December 5, 2024, to identify studies enrolling children (0-9 years old) or adolescents (10-19 years old) who completed treatment for microbiologically confirmed or clinically diagnosed pulmonary tuberculosis. Eligible studies measured at least one tuberculosis-associated respiratory impairment or disability outcome. Data were analyzed descriptively and stratified into three age groups based on median age of tuberculosis diagnosis: <5 years, 5-10 years, and >10 years. This study was prospectively registered (PROSPERO CRD42024529906).</p><p><strong>Findings: </strong>We identified 117 studies reporting tuberculosis-associated respiratory impairment or disability outcomes. Of those, five met our inclusion criteria, as over 80% of the identified studies excluded children and adolescents. Following tuberculosis treatment, children and adolescents exhibited significant respiratory impairments. In children <5 years of age, impairment included reduced tidal volume and peak tidal expiratory flow. Among those 5-10 years, approximately 40% exhibited abnormal lung function post-treatment, increasing to 65% in adolescents >10 years. Disability was frequently reported, with 35-50% of children and adolescents experiencing respiratory symptoms and children <10 years showing reduced growth metrics and a diminished quality of life.</p><p><strong>Interpretation: </strong>Even after successful tuberculosis treatment, children and adolescents can experience respiratory impairments and disability that may reduce their quality of life, ability to participate in activities, and growth potential. The epidemiology and clinical manifestations of these impairments vary by age, reflecting distinct biological and behavioural differences. Future research should prioritize these younger populations to ensure their unique needs and challenges are adequately represented.</p><p><strong>Funding: </strong>The Robert E. Leet & Clara Guthrie Patterson Trust; Canadian Institutes of Health Research.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103107"},"PeriodicalIF":9.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540577","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":"Immunogenicity and reactogenicity of a booster dose of a typhoid conjugate vaccine (TCV) in Malawian pre-school children.","authors":"Nginache Nampota-Nkomba, Osward M Nyirenda, Shrimati Datta, Victoria Mapemba, Priyanka D Patel, Theresa Misiri, Felistas Mwakiseghile, John M Ndaferankhande, Bright Lipenga, Jennifer Oshinsky, Marcela F Pasetti, Leslie P Jamka, Melita A Gordon, Matthew B Laurens, Kathleen M Neuzil","doi":"10.1016/j.eclinm.2025.103100","DOIUrl":"10.1016/j.eclinm.2025.103100","url":null,"abstract":"<p><strong>Background: </strong>We assessed persistence of typhoid immunity conferred by Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (TCV) four years post-vaccination and immunogenicity of a booster dose of Vi-TT given at age five.</p><p><strong>Methods: </strong>In 2018, a phase 3 trial of Vi-TT in Malawi randomised children 1:1 to receive Vi-TT or meningococcal capsular group A conjugate vaccine (control). Subsequently, TCV was licensed and recommended in the region. In 2023, children vaccinated at 9-11 months in the original trial received a second (Booster- TCV) or first (1st-TCV) Vi-TT dose, at age five. Serum collected at days 0, 28, and 160-180 days after vaccination was tested for anti-Vi immunoglobulin (Ig)G and IgA, reported as enzyme-linked immunosorbent assay units (EU)/mL. Seroconversion was ≥4-fold rise in antibody titers from day 0 to day 28 post-vaccination. Safety outcomes included adverse events during follow-up.</p><p><strong>Findings: </strong>We enrolled 136 children: 72 Booster-TCV and 64 1st-TCV. At baseline, anti-Vi IgG geometric mean titers (GMT) were higher in Booster-TCV (18.8 EU/mL, 95% CI 15.2-23.2) than 1st-TCV (5.7 EU/mL, 4.6-7.2) arms. GMT increased significantly between days 0 and 28 in both arms, with higher levels in Booster-TCV (6867.9 EU/mL, 5794.1-8140.6) than 1st-TCV (2912.0 EU/mL, 2429.2-3490.7) arms, representing a 375.7 and 492.6 geometric mean fold rise, respectively. On day 28, all Booster-TCV children, and all but one 1st-TCV child, seroconverted. Similar trends were seen for IgA. Vi-TT reactogenicity was similar between vaccine arms.</p><p><strong>Interpretation: </strong>This study demonstrates sustained Vi-TT immunogenicity four years post-vaccination at 9-11 months old, and robust immune response following a booster dose at five years of age, informing policy decisions on TCV use in children.</p><p><strong>Funding: </strong>Bill & Melinda Gates Foundation (INV-030857).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103100"},"PeriodicalIF":9.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540569","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":"Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.","authors":"","doi":"10.1016/j.eclinm.2025.103080","DOIUrl":"10.1016/j.eclinm.2025.103080","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Low dose corticosteroids (e.g., 6 mg dexamethasone) have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with clinical hypoxia but not receiving ventilatory support (the combination of non-invasive mechanical ventilation, including high-flow nasal oxygen, continuous positive airway pressure and bilevel positive airway pressure ventilation, and invasive mechanical ventilation or extra-corporeal membrane oxygenation), but the balance of efficacy and safety in patients receiving ventilatory support is uncertain.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) assessed multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients receiving ventilatory support were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. Recruitment closed on 31 March 2024 when funding for the trial ended. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between 25 May 2021 and 9 January 2024, 477 COVID-19 patients receiving ventilatory support were randomly allocated to receive usual care plus higher dose corticosteroids vs. usual care alone (of whom 99% received corticosteroids during the follow-up period). Of those randomised, 221 (46%) were in Asia, 245 (51%) in the UK and 11 (2%) in Africa. 143 (30%) had diabetes mellitus. Overall, 86 (35%) of 246 patients allocated to higher dose corticosteroids vs. 86 (37%) of 231 patients allocated to usual care died within 28 days (rate ratio [RR] 0.87; 95% CI 0.64-1.18; p = 0.37). There was no significant difference in the proportion of patients discharged from hospital alive within 28 days (128 [52%] in the higher dose corticosteroids group vs. 120 [52%] in the usual care group; RR 1.04, 0.81-1.33]; p = 0.78). Among those not on invasive mechanical ventilation at baseline, there was no clear reduction in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (76 [37%] of 206 vs. 93 [45%] of 205; RR 0.79 [95% CI 0.63-1.00]; p = 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In patients hospitalised for COVID-19 receiving ventilatory support, we found no evidence that higher dose corticosteroids reduced the risk of death compared to usual care, which included low dose corticos","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103080"},"PeriodicalIF":9.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556148","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":"Weight gain among children under five with severe malnutrition in therapeutic feeding programmes: a systematic review and meta-analysis.","authors":"Grace O'Donovan, Daniel Allen, Thandile Nkosi-Gondwe, Kenneth Anujuo, Mubarek Abera, Amir Kirolos, Laurentya Olga, Debbie Thompson, Kimberley McKenzie, Elizabeth Wimborne, Tim J Cole, Albert Koulman, Natasha Lelijveld, Amelia C Crampin, Charles Opondo, Marko Kerac","doi":"10.1016/j.eclinm.2025.103083","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103083","url":null,"abstract":"<p><strong>Background: </strong>Globally, some 45 million children under five years of age are wasted (low weight-for-height). Although 2023 World Health Organisation guidelines on their care did not aim to identify optimal weight gain, they did mention 5-10 g/kg/day as a target, which is a change from prior guidelines that recommended 10-15 g/kg/day, when inpatient-only care was the norm. We aimed to inform future policy/programming on weight gain targets.</p><p><strong>Methods: </strong>For this systematic review and meta-analysis, we searched Embase, Global Health and Medline. The final search was on 23/02/2024. Papers were included if they reported weight gain of children aged 6-59 months with severe malnutrition during inpatient (facility-based), outpatient (home-based), and hybrid treatment (initially inpatient and progressing to outpatient treatment). Summary data were extracted, and quality was assessed using a NICE Quality Appraisal Checklist. Our primary outcome was mean rate of weight gain (g/kg/day) during treatment. We conducted random-effects meta-analysis to describe pooled mean weight gain by programme type. Meta-regression investigated potential associations of weight gain with length of stay and programme outcomes. We registered the study on PROSPERO (CRD42023266472).</p><p><strong>Findings: </strong>Our search yielded 3173 papers. We reviewed 321 full texts, identifying 126 eligible papers. Of these, 104 papers, including some 240,650 participants, reported weight gain as g/kg/day and were eligible for meta-analysis. Mean rate of weight gain was 8.8 g/kg/day (95% CI: 7.6, 9.9; I² = 97.8%) across 18 inpatient programmes, 3.4 g/kg/day (95% CI: 2.0, 4.7; I² = 99.4%) across 12 hybrid programmes, and 3.9 g/kg/day (95% CI: 3.4, 4.4; I² = 99.7%) across 60 outpatient programmes. We found inconsistent evidence of an association between slower weight gain and higher mortality: there was weak evidence of association after adjusting for programme type (coefficient = -0.4; 95% CI: -0.7, -0.02; p = 0.04; n = 118 programmes). There was high heterogeneity between studies. Details of weight gain calculation methods varied. We found no evidence for publication bias when accounting for programme type (Egger's test p-value = 0.2).</p><p><strong>Interpretation: </strong>Weight gain in outpatient programmes was markedly slower than in inpatient treatment. Clearer reporting of weight gain and a better understanding of the sequelae of faster/slower recovery is important to set future weight gain targets. Our results set an important baseline for current programmes to benchmark against.</p><p><strong>Funding: </strong>Medical Research Council/Global Challenges Research Fund, grant number: MR/V000802/1.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103083"},"PeriodicalIF":9.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540579","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":"Ensartinib for advanced or metastatic non-small-cell lung cancer with <i>MET</i> exon 14 skipping mutations (EMBRACE): a multi-center, single-arm, phase 2 trial.","authors":"Yang Xia, Panwen Tian, Mo Zhou, Jun Zhao, Yang Jin, Zhiyuan Guo, Xiuzhen Li, Weina Lu, Da Miao, Yuefei Lu, Wanting Xu, Yongchang Zhang, Xiuning Le, Wen Li","doi":"10.1016/j.eclinm.2025.103099","DOIUrl":"10.1016/j.eclinm.2025.103099","url":null,"abstract":"<p><strong>Background: </strong><i>MET</i> exon14 skipping mutations (<i>MET</i>ex14) is an established actionable driver oncogene of non-small-cell lung cancer (NSCLC). While ensartinib is a known second-generation tyrosine kinase inhibitor with primary activity against <i>ALK</i> translocation, it is also classified as a type Ia MET inhibitor. We have previously shown anti-tumor activity against <i>MET</i>ex14 positive NSCLC both <i>in vivo</i> and <i>in vitro</i>. The EMBRACE trial aims to evaluate the clinical efficacy and safety of ensartinib for treatment of <i>MET</i>ex14 positive NSCLC.</p><p><strong>Methods: </strong>This is a multicenter single arm phase II investigator-initiated study that enrolled <i>MET</i>ex14 positive lung cancer after failing first line chemotherapy and/or immunotherapy. Eligible patients received ensartinib 225 mg orally once daily in a continuous 28-day treatment cycle until disease progression, unacceptable side effect, or death. Primary endpoint was investigator-assessed objective response rate (ORR), and the secondary end point included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR) and safety profiles. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2100048767).</p><p><strong>Findings: </strong>From July 2021 to February 2024, a total of 31 patients were enrolled and received ensartinib. Median follow-up time of the 30 evaluable patients was 9.2 months (95% Confidence Interval [CI], 6.3-not estimable). The ORR was 53.3% (16/30; 95% CI, 35.5-71.2) and DCR was 86.7% (26/30; 95% CI, 74.5-98.8). Median PFS was 6.0 months (95% CI, 3.0-8.8) and median DoR was 7.9 months (95% CI, 4.8-8.7). Adverse events (AEs) were reported in 24 patients (80%), with 7 (23.3%) of grade 3. The most common AEs were rash (14/30, 46.7%), followed by anemia (7/30, 23.3%), increased ALT (7/30, 23.3%), increased AST (7/30, 23.3%), and pruritus (6/30, 20%). No serious adverse events or treatment-related deaths occurred. Importantly, the exploratory ctDNA analysis indicates that clearance of circulating tumor DNA (ctDNA) at four weeks treatment was associated with more favorable treatment outcomes comparing with patients having positive ctDNA.</p><p><strong>Interpretation: </strong>Ensartinib has a promising anti-tumor activity and manageable safety in previously treated patients with <i>MET</i>ex14 positive lung cancer.</p><p><strong>Funding: </strong>This work was supported by the National Natural Science Foundation of China [82370028, 82422001] and the CSCO-MET Aberrant Solid Tumor Research Grant [Y-2022METAZMS-0066].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"81 ","pages":"103099"},"PeriodicalIF":9.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540568","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}