EClinicalMedicine最新文献

{"title":"Safety and effectiveness of the early-onset sepsis calculator to reduce antibiotic exposure in at-risk newborns: a cluster-randomised controlled trial.","authors":"Bo M van der Weijden, Sanne W C M Janssen, Marijke C van der Weide, Renske J P M Cornelisse-van Vugt, Gavin W Ten Tusscher, Claire A M Lutterman, Arvid W A Kamps, Carmen M Lorente Flores, Jeroen Hol, Henriëtte van Laerhoven, Maarten Rijpert, Nadia A Oeij, Irene A M Schiering, Sylvia A Obermann-Borst, Douwe H Visser, Lisanne M van Leeuwen, René F Kornelisse, Annemarie M C van Rossum, Merijn W Bijlsma, Frans B Plötz, Niek B Achten","doi":"10.1016/j.eclinm.2025.103419","DOIUrl":"10.1016/j.eclinm.2025.103419","url":null,"abstract":"<p><strong>Background: </strong>Newborns are at risk for early-onset sepsis (EOS), occurring 0.2-2.0 per 1000 live births, and for antibiotic overtreatment: approximately 5-15% receive antibiotics for suspected EOS under conventional guidelines with categorical risk factor assessment. Use of the multivariate neonatal EOS calculator prediction tool can reduce overtreatment, but no trials have been conducted to compare its safety to these categorical guidelines.</p><p><strong>Methods: </strong>Between April 12th, 2022, and March 19th, 2024, we conducted an open-label, two-armed, cluster-randomised controlled trial among newborns born at ≥34 weeks' gestational age with ≥1 EOS risk factor, comparing 10 hospitals randomised 1:1 to EOS calculator use versus categorical guideline use (ClinicalTrials.gov number: NCT05274776). The EOS calculator was slightly adapted for Dutch use. The co-primary non-inferiority outcome assessed safety using four predefined harm criteria (respiratory support, circulatory support, referral to intensive care unit, and culture-confirmed EOS). Non-inferiority was established if the upper limit of the 95% confidence interval (CI) for the relative risk did not exceed 1.5. The co-primary superiority outcome assessed the reduction of participants starting antibiotic therapy for suspected EOS within 24 h postpartum. Secondary endpoints were the duration of antibiotic therapy and the initiation of antibiotic therapy between 24 and 72 h after birth. Intention-to-treat and per-protocol analyses were performed.</p><p><strong>Findings: </strong>1830 newborns (183 per cluster) were included. At least one harm criterion was present in 64 (7.0%) of 915 in the EOS calculator arm and 134 (14.6%) of 915 in the categorical guideline arm (relative risk 0.48; 95% Cl 0.36-0.63). Antibiotics for suspected EOS were started in 66 (7.2%) of 915 in the EOS calculator arm, compared with 243 (26.6%) of 915 in the categorical guideline arm (absolute risk reduction: 19.0%, 95% CI 11.3-26.7). Median duration of antibiotics was longer in the EOS calculator arm (5.5 days, IQR 1.8-6.6) than in the categorical guideline arm (2.1 days, IQR 1.6-6.3) (P 0.0019). We found no difference in the proportion of newborns started on antibiotic therapy for suspected EOS between 24 and 72 h after birth. Adverse event rates were similar between arms. Readmission for suspected early-onset sepsis occurred three times in the EOS calculator and two times in the categorical guideline arm. Any cultures obtained at readmission remained negative, and any symptoms resolved completely.</p><p><strong>Interpretation: </strong>These trial data support safety and effectiveness of the EOS calculator for harm criteria and for the proportion of participants that started antibiotic therapy.</p><p><strong>Funding: </strong>This study was supported by SPIN, the General Paediatrics Research Network of the Dutch Association for Paediatrics, supported by het Cultuurfonds.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103419"},"PeriodicalIF":10.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882462","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":"Circulating tumour cells & circulating tumour DNA in patients with resectable colorectal liver metastases (MIRACLE): a prospective, observational biomarker study.","authors":"Lissa Wullaert, Maurice P H M Jansen, Jaco Kraan, Yannick M Meyer, Kelly Voigt, Stavros Makrodimitris, Vanja de Weerd, Corine M Beaufort, Mai Van, Maarten Vermaas, Eric J T Belt, Paul D Gobardhan, Stefan Sleijfer, Henk M W Verheul, John W M Martens, Dirk J Grünhagen, Saskia M Wilting, Cornelis Verhoef","doi":"10.1016/j.eclinm.2025.103406","DOIUrl":"10.1016/j.eclinm.2025.103406","url":null,"abstract":"<p><strong>Background: </strong>Recurrence risk after curative surgery for colorectal liver metastases (CRLM) remains high, underlining the need to identify prognostic markers enabling more individualised treatment approaches.</p><p><strong>Methods: </strong>In the MIRACLE, a prospective, observational biomarker study, a total of 188 patients with isolated, resectable CRLM without (neo)adjuvant chemotherapy were included between October 2015 and December 2021. Blood samples were collected before surgery (baseline) and three weeks after surgery. The primary objective was to assess the potential association between postoperative circulating tumour DNA (ctDNA) detection and recurrence of disease for patients with resectable CRLM within one year after resection. The secondary objective was the association between recurrence of disease within one year and detection of circulating tumour cells (CTCs). Baseline ctDNA was measured by next generation sequencing using a targeted panel (Oncomine Colon cell-free DNA assay) and postoperatively by digital PCR on genetic variants found preoperatively with the Oncomine panel. CTCs were enumerated using the FDA-approved CellSearch system.</p><p><strong>Findings: </strong>ctDNA was detected in 117/187 patients (63%) at baseline, and 28/104 evaluable patients (27%) still had detectable ctDNA postoperatively. CTC enumeration resulted in positivity for 37/183 patients (20%) at baseline and 14/158 patients (9%) postoperatively. No association was found between 1-year recurrence-free survival (RFS) and the presence of CTCs or ctDNA at baseline. In contrast, patients with postoperative undetectable ctDNA had a significantly improved 1-year RFS compared to patients with postoperative ctDNA (54% [95% CI 44%-67%] vs. 25% [95% CI 13%-47%], log-rank p = 0.0011). Similarly, patients with postoperative detectable CTCs had a significantly shorter 1-year RFS compared to patients without postoperative CTCs (15% [95% CI 4%-55%] vs. 53% [95% CI 45%-62%], log-rank p 0.0004). Also in multivariable analysis, detectable ctDNA and CTCs after surgery remained independently associated with a shorter 1-year RFS (HR 2.35; 95% CI 1.34-4.11; p = 0.0028 and HR 2.98; 95% CI 1.56-5.71; p = 0.0010, respectively).</p><p><strong>Interpretation: </strong>This is the first study conducted in patients with resectable CRLM without (neo)adjuvant chemotherapy, which demonstrates the impact of postoperative detectable circulating tumour load on 1-year RFS. Postoperative ctDNA and CTC detection both represent strong, independent predictors for a shorter RFS after local treatment, as opposed to preoperative detection.</p><p><strong>Funding: </strong>This work was supported by KWF Kankerbestrijding (Dutch Cancer Society, EMCR 2014-6340).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103406"},"PeriodicalIF":10.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946968","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":"Safety of budesonide/glycopyrronium/formoterol fumarate dihydrate delivered by HFO-1234ze versus HFA-134a in chronic obstructive pulmonary disease: a phase 3, multi-site, randomised, double-blind, parallel-group, active-comparator study.","authors":"Omar S Usmani, Fernando J Martinez, Hitesh Pandya, Matthew Camiolo, Artur Bednarczyk, Kinga Kucz, Marek Kokot, Christer Gottfridsson, Magnus Aurivillius, Lars Pettersson, Jie Mei, Karin Skansen, Jennifer L Bell, David Petullo, Kathryn Collison, Patrik Bondarov, Mandeep Jassal, Mehul Patel","doi":"10.1016/j.eclinm.2025.103402","DOIUrl":"10.1016/j.eclinm.2025.103402","url":null,"abstract":"<p><strong>Background: </strong>Pressurised metered dose inhalers (pMDIs) contain a hydrofluorocarbon propellant, such as hydrofluoroalkane-134a (HFA-134a), which is known to have global warming potential (GWP). Transitioning pMDIs to propellants with lower GWP will reduce the environmental impact of pMDIs. This study assessed the safety of a near-zero GWP propellant, hydrofluoroolefin-1234ze (HFO-1234ze), compared with HFA-134a when used in the delivery of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) in participants with chronic obstructive pulmonary disease (COPD). The results of this study advance our understanding of the safety of HFO-1234ze compared with HFA-134a.</p><p><strong>Methods: </strong>This phase 3, double-blind, parallel-group study (ClinicalTrials.govNCT05573464) across 9 countries (Argentina, Bulgaria, Canada, Germany, Mexico, Poland, Turkey, the United Kingdom, the United States) included participants (aged 40-80 years) with physician-diagnosed COPD using dual or triple inhaled maintenance therapies, COPD Assessment Test score ≥10, ≥10 pack-years smoking history, and no comorbid diagnosis of asthma or other clinically significant diseases impacting study outcomes. Participants were randomised (1:1) to receive either BGF HFO-1234ze or BGF HFA-134a (two inhalations of 160/7·2/5·0 μg twice daily) for 12 weeks in the main safety analysis set (or 52 weeks [first 120 participants per treatment]). Safety endpoints included the incidence of adverse events (AEs), measures of vital signs, clinical laboratory tests, and electrocardiograms.</p><p><strong>Findings: </strong>Participants were recruited between 27 September 2022 and 19 May 2023. A total of 874 participants were screened. Of 558 treated participants (mean [standard deviation] age, 67·0 [7·4] years; male, 315 [56·5%]) in the 12-week safety analysis set, 280 received BGF HFO-1234ze, and 278 received BGF HFA-134a. The AE incidence was balanced between formulations in the 12-week (HFO-1234ze, 124 [44·3%]; HFA-134a, 114 [41·0%]) and 52-week (HFO-1234ze, 80 [66·7%]; HFA-134a, 94 [78·3%]) safety analysis sets.</p><p><strong>Interpretation: </strong>These findings support the potential for HFO-1234ze to replace HFA-134a in pMDIs containing BGF, which could be evaluated further in a real-world setting.</p><p><strong>Funding: </strong>The study was supported by AstraZeneca.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103402"},"PeriodicalIF":10.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882463","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":"A European Association for Palliative Care White Paper defining an integrative palliative, geriatric, and rehabilitative approach to care and support for older people living with frailty and their family carers: a 28-country Delphi study and recommendations.","authors":"Lieve Van den Block, Kim de Nooijer, Sophie Pautex, Lara Pivodic, Nele Van Den Noortgate, Caroline Nicholson, Katarzyna Szczerbińska, Sandra Martins Pereira, Rebecca Tiberini, Barbara Hanratty, Rose Miranda","doi":"10.1016/j.eclinm.2025.103403","DOIUrl":"10.1016/j.eclinm.2025.103403","url":null,"abstract":"<p><strong>Background: </strong>A fast-growing number of older people living with frailty experience complex needs throughout their illness trajectory. However, currently, there is no international consensus on optimal care and support to older people living with frailty and their family carers. The European Association for Palliative Care (EAPC) Reference Group on Aging and Palliative Care aimed to develop a White Paper defining an optimal integrative palliative, geriatric, and rehabilitative approach to care and support for this population.</p><p><strong>Methods: </strong>We conducted an international Delphi study, comprising an iterative preparatory phase using literature and input from international and interdisciplinary experts in research, practice, and policy, (between 2020 and 2022) and an online consensus-based survey (2023) with 63 professional experts and 19 older person's representatives from 28 countries in Asia, Australia, Europe, and North America.</p><p><strong>Findings: </strong>The EAPC White Paper comprises 11 key domains that capitalize on the strengths of palliative care, geriatrics, and rehabilitation; and 34 key recommendations that elucidate what is needed from clinical, health service, and public health perspectives to address the multidimensional needs of this population, support their capacities, and maintain their quality of life and well-being until the end of life, including bereavement of carers.</p><p><strong>Interpretation: </strong>This EAPC White Paper presents a gold standard for the care and support for older people living with frailty and their family carers. It calls for a radical shift in healthcare provision to effectively integrate palliative, geriatric, and rehabilitative approaches to care and support for this population and represents a first critical step in establishing how to achieve this.</p><p><strong>Funding: </strong>Research Foundation Flanders Belgium funded the postdoctoral mandates of RM (12D4523N) and KDN (12AEO24N).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103403"},"PeriodicalIF":10.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946866","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":"Efficacy and safety of neoadjuvant toripalimab plus chemotherapy in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma (NICE): a multicentre, single-arm, exploratory phase 2 study.","authors":"Liying Zhao, Hao Liu, Jiang Yu, Shuqiang Yuan, Huayuan Liang, Wei Wang, Junliang Jiang, Lina Yu, Li Liang, Zhao Chen, Xinhua Chen, Xuefeng Zhong, Yating Zheng, Fengping Li, Tian Lin, Mingli Zhao, Tao Chen, Hao Chen, Yanfeng Hu, Guoxin Li","doi":"10.1016/j.eclinm.2025.103421","DOIUrl":"10.1016/j.eclinm.2025.103421","url":null,"abstract":"<p><strong>Background: </strong>In locally advanced gastric or gastroesophageal junction adenocarcinoma (GC/EGJC), deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) tumors exhibit high responsiveness to immunotherapy. The synergistic efficacy of neoadjuvant immunotherapy combined with chemotherapy in dMMR/MSI-H GC/EGJC remains uncertain.</p><p><strong>Methods: </strong>The NICE trial is a multicentre, single-arm, exploratory phase 2 study conducted at six hospitals in China, evaluating the safety and efficacy of toripalimab in combination with CapeOX as perioperative therapy for locally advanced GC/EGJC across three biomarker-defined cohorts. This report presents findings from cohort C. Eligible patients were aged 18-75 years with histologically or cytologically confirmed GC/EGJC, confirmed dMMR/MSI-H status, and clinically staged as cT3-4aNxM0 or cT2N + M0 (AJCC 8th edition) based on contrast-enhanced CT or MRI, upper endoscopy, diagnostic laparoscopy, and peritoneal lavage cytology. Patients received four cycles of neoadjuvant toripalimab (240 mg IV every 3 weeks) plus CapeOX (capecitabine 1000 mg/m² orally twice daily on Days 1-14 and oxaliplatin 130 mg/m² IV on Day 1), followed by curative-intent surgery and up to four cycles of the same regimen as adjuvant therapy. The primary endpoint was the major pathological response (MPR) rate, defined as ≤10% residual viable tumor cells in the tumor specimen resected after neoadjuvant therapy. All patients who received at least one dose of treatment were included in the efficacy and safety analyses. The trial is registered with ClinicalTrials.gov, NCT04744649.</p><p><strong>Findings: </strong>Between March 12, 2021 and June 1, 2024, twenty-two patients were screened, with sixteen meeting the inclusion criteria and undergoing treatment. Tumor stages were cT2N1 (n = 1), cT3N0-3 (n = 3), and cT4aN1-3 (n = 12). Fifteen patients completed four cycles of therapy preoperatively, while one patient completed two cycles due to adverse events. None of patients experienced disease progression. One patient achieved a complete clinical response as indicated by radiology and endoscopy and consequently refused surgery, while the remaining fifteen patients underwent resection. The R0 resection rate was 100% (15/15). The MPR rate was 93.3% (14/15), and the pathological complete response (pCR) rate was 80% (12/15). Six patients (37.5%, 6/16) experienced grade 3/4 treatment-related adverse events. One patient died of COVID-19 287 days post-surgery without relapse. No disease relapse was observed in any patient.</p><p><strong>Interpretation: </strong>Given the small sample size and limited population diversity, these findings should be interpreted with caution. Nonetheless, neoadjuvant toripalimab combined with the CapeOX regimen is feasible for localized advanced dMMR/MSI-H GC/EGJC, demonstrating high MPR and pCR rates without unexpected adverse events.</p><p><strong>Funding: </s","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103421"},"PeriodicalIF":10.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946894","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":"Dietary attribution to burden of chronic disease in Australia: a systematic analysis of the Australian Institute of health and welfare 2024 national burden of disease dataset.","authors":"Yuanxin Xu, Jing Sun","doi":"10.1016/j.eclinm.2025.103418","DOIUrl":"10.1016/j.eclinm.2025.103418","url":null,"abstract":"<p><strong>Background: </strong>Non-communicable chronic diseases (NCDs), including cardiovascular diseases, cancer, chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM), pose a significant burden on Australia's healthcare system. Despite advancements in disease prevention and management, NCDs remain the leading cause of morbidity and mortality. This study aimed to assess trends in the burden of NCDs and the impact of dietary risks in Australia from 2003 to 2024 using data from the Australian Institute of Health and Welfare (AIHW).</p><p><strong>Methods: </strong>Data were from the AIHW 2024 burden of disease dataset, which provided estimates for mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). Since the 2024 death counts were missing, total mortality attributable to dietary risks was expressed as the percentage change from 2003 to 2018. Joinpoint Regression was performed to assess DALYs, YLLs, and YLDs of NCDs from 2003 to 2024, analyze the contribution of various dietary risk factors to the disease burden and conduct subgroup comparisons based on sex.</p><p><strong>Findings: </strong>From 2003 to 2018, mortality attributed to dietary risks declined by 15.29%. From 2003 to 2024, dietary risks attributable to DALYs decreased by 16.93%. Atrial fibrillation showed the most significant decline in both mortality (-10.0%) and DALYs (-7.81%), driven by a reduction in high-sodium diets. In contrast, inflammatory heart disease experienced the highest increases in DALYs, rising by 18.18% percentage change, which is associated with diet high in sodium. Breast cancer showed the most significant growth driven by diet high in red meat in dietary attributable DALYs, with a percentage change of 6.45%; and in deaths, with a percentage change of 6.67%. T2DM also illustrated a slight increase in dietary attributable DALYs driven by a diet high in red meat, with a percentage change of 2.36%, and in deaths driven by a diet high in processed meat, with a percentage change of 4.10%. In contrast, CKD decreased due to reduction of high sodium in dietary attributable DALYs, with a percentage change of 1.49%, and deaths, with a percentage change of 3.13%. Males showed an increase in risks related to high sodium consumption, with inflammatory heart disease DALYs rising by 15.38%, and a rise in oesophageal cancer deaths linked to low vegetable intake, with a percentage change of 14.49%. Females experienced an increase in T2DM DALYs attributable to high red meat consumption, with a percentage change of 10.26%, and a significant rise in coronary heart disease deaths associated with high sodium intake, with a percentage change of 18.97%.</p><p><strong>Interpretation: </strong>These findings emphasize the ongoing impact of dietary risks on NCDs burden in Australia and underscore the need for sex-specific and targeted dietary interventions to reduce preventable NCDs. Strengthening public health pol","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103418"},"PeriodicalIF":10.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882443","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":"Effectiveness of family-based behavioral intervention for smoking cessation in low-income households: a systematic review and meta-analysis.","authors":"Meng Yao Li, Tzu Tsun Luk, Derek Yee Tak Cheung, Zi Qiu Guo, Ka Ka Siu, Jia Guo, Sophia Siu Chee Chan, Tai Hing Lam, Sai Yin Ho, Sheng Zhi Zhao, Man Ping Wang","doi":"10.1016/j.eclinm.2025.103420","DOIUrl":"10.1016/j.eclinm.2025.103420","url":null,"abstract":"<p><strong>Background: </strong>Smoking-attributable harms are substantial in low-income households. The effectiveness of family-based behavioral interventions for smoking cessation in this population remains uncertain. This review aims to assess the effectiveness of family-based behavioral interventions on smoking cessation in low-income households.</p><p><strong>Methods: </strong>This systematic review and meta-analysis were conducted by searching six databases and one clinical trial registry for studies published from inception to 30 January 2024 (with an updated search conducted until 1st January 2025). Randomized controlled trials of family-based behavioral interventions for smoking parents from low-income households, co-living children aged ≤18 years, were included. Data extraction and analysis were independently performed by two investigators following the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Primary outcomes were self-reported 7-day point prevalence abstinence (PPA) or biochemically validated abstinence at 3 months or longer. The Mantel-Haenszel method was used to calculate the relative risk (RR) with random-effect model. The study was registered on PROSPERO (CRD42023466096).</p><p><strong>Findings: </strong>Among 22 trials (N = 5292) included in the review, 12 (N = 2782) were analyzed in the meta-analysis. Most of trials (17/22) were of moderate or high quality. Family-based behavioral interventions significantly increased self-reported 7-day PPA (RR:1.70, 95%CI: 1.16-2.48) compared with usual care at follow-ups of 3 months or longer. Behavioral counseling combined with nicotine replacement therapy (NRT) was most effective (RR: 2.45, 95% CI: 1.28-4.68) and for 12-month follow-up (RR: 1.96, 95% CI: 1.44-2.66). Further significant effects were observed in parents of non-asthmatic children (RR: 1.88, 95% CI: 1.39-2.53), parents both smoked (RR: 1.79, 95% CI: 1.23-2.60), and interventions including NRT provision (RR: 1.78, 95% CI: 1.15-2.74).</p><p><strong>Interpretation: </strong>Family-based behavioral interventions significantly increased abstinence in low-income households where both parents smoked and pharmacotherapy was included. Interventions that incorporated behavioral counseling with NRT and implemented with a long-term follow-up tended to be more effective.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103420"},"PeriodicalIF":10.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882444","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":"Impact of metabolic dysfunction on treatment responses to nucleos(t)ide analogues in chronic hepatitis B: a retrospective multi-center REAL-B cohort study.","authors":"Rui Huang, Dae Won Jun, Hidenori Toyoda, Yao-Chun Hsu, Huy Trinh, Akito Nozaki, Toru Ishikawa, Tsunamasa Watanabe, Haruki Uojima, Daniel Q Huang, Takashi Honda, Yasuhito Tanaka, Philip Vutien, Sebastián Marciano, Hiroshi Abe, Masaru Enomoto, Masanori Atsukawa, Hirokazu Takahashi, Kunihiko Tsuji, Ei Itobayashi, Koichi Takaguchi, Pei-Chien Tsai, Chia-Yen Dai, Jee-Fu Huang, Chung-Feng Huang, Ming-Lun Yeh, Eileen Yoon, Sung Eun Kim, Sang Bong Ahn, Gi-Ae Kim, Jang Han Jung, Soung Won Jeong, Hyunwoo Oh, Cheng-Hao Tseng, Masatoshi Ishigami, Angela Chau, Tiffany Hsiao, Mayumi Maeda, Satoshi Yasuda, Makoto Chuma, Takanori Ito, Keigo Kawashima, Joanne Kimiko Liu, Adrian Gadano, Ritsuzo Kozuka, Norio Itokawa, Kaori Inoue, Tomonori Senoh, Jie Li, Wan-Long Chuang, Ramsey Cheung, Chao Wu, Ming-Lung Yu, Mindie H Nguyen","doi":"10.1016/j.eclinm.2025.103407","DOIUrl":"10.1016/j.eclinm.2025.103407","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction is associated with liver disease but it is unclear if it would impact responses to antiviral treatment in chronic hepatitis B (CHB) patients.</p><p><strong>Methods: </strong>Using data from an international consortium of 4507 treatment-naïve CHB patients who initiated nucleos(t)ide analogues (NAs) between January 2004 and August 2024 from 32 centers and propensity-score matching (PSM) to balance the background of patients with and without metabolic disease (diabetes, obesity, dyslipidemia, or hypertension), we compared their biochemical (BR), virologic (VR), and complete (CR) response.</p><p><strong>Findings: </strong>More than half (54.8%) had at least one metabolic disease. Patients with metabolic disease (vs. no) were older and more likely male. In the PSM cohort of 893 pairs of patients, patients with metabolic disease had significantly lower 5-year cumulative BR (91.3% vs. 95.8%, <i>P</i> < 0.001) and CR rates (81.8% vs. 87.4%, <i>P</i> = 0.008), but similar VR (93.5% vs. 94.1%, <i>P</i> = 0.65) and HBeAg seroconversion rates (27.0% vs. 29.7%, <i>P</i> = 0.92). On multivariable Cox regression, metabolic disease was associated with lower BR (adjusted hazard ratio [aHR] 0.73, <i>P</i> < 0.001) and CR (aHR 0.79, <i>P</i> = 0.001), especially in those with ≥3 metabolic diseases (aHR 0.55 for BR; aHR 0.53 for CR, both <i>P</i> < 0.001).</p><p><strong>Interpretation: </strong>The presence and number of metabolic diseases were significantly and incrementally associated with lower BR. Metabolic disease should be taken into consideration in the management of CHB patients receiving NAs treatment.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103407"},"PeriodicalIF":10.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882445","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":"Trastuzumab deruxtecan in patients from China with previously treated human epidermal growth factor receptor 2-positive locally advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (DESTINY-Gastric06): results from a single-arm, multicenter, phase 2 trial.","authors":"Zhi Peng, Ping Chen, Jin Lu, Yiye Wan, Yulong Zheng, Feng Ye, Jianwei Yang, Ying Liu, Hongming Pan, Meili Sun, Qingxia Fan, Ying Yuan, Kai Chen, Zhuoer Sun, Han Tian, Ye Xia, Lin Shen","doi":"10.1016/j.eclinm.2025.103404","DOIUrl":"10.1016/j.eclinm.2025.103404","url":null,"abstract":"<p><strong>Background: </strong>Trastuzumab deruxtecan (T-DXd; 6·4 mg/kg) is approved for metastatic human epidermal growth factor receptor 2 (HER2)-positive (HER2+) gastric or gastroesophageal junction (GEJ) adenocarcinoma after a trastuzumab-based regimen. We report the final analysis of DESTINY-Gastric06, evaluating T-DXd in pretreated patients from China with advanced HER2+ gastric cancers (GC).</p><p><strong>Methods: </strong>The single-arm, multicenter, phase 2 DESTINY-Gastric06 trial (NCT04989816) enrolled patients from China with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+; locally documented) advanced gastric or GEJ adenocarcinoma with two or more prior treatments. Patients received T-DXd 6·4 mg/kg intravenous infusion every 3 weeks. The primary endpoint was confirmed objective response rate in HER2+ (IHC 3+ or IHC 2+/in situ hybridization-positive) tumors (full analysis set) by independent central review. Secondary endpoints included investigator-assessed confirmed objective response rate, progression-free survival by independent central review, overall survival, and safety.</p><p><strong>Findings: </strong>Of 126 patients screened between August 20, 2021, and December 7, 2022, 95 were enrolled (intent-to-treat; 73 patients had centrally confirmed HER2+ tumors). Median follow up was 10·2 months. Among the 73 patients, confirmed objective response rate (95% confidence interval) by independent central review was 28·8% (18·8-40·6%) and by investigator assessment was 37·0% (26·0-49·1%). Median progression-free survival by independent central review was 5·7 months. Median overall survival was 11·1 months. The most common Grade 1-2 adverse event was white blood cell count decreased (53·7%; 51/95).</p><p><strong>Interpretation: </strong>Consistent with other GC trials, T-DXd showed durable benefit, with no new safety signals, in pretreated patients from China with HER2+ advanced GC; data support T-DXd as a third- or later-line therapeutic option in this population.</p><p><strong>Funding: </strong>AstraZeneca.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103404"},"PeriodicalIF":10.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882464","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 and validation of an interpretable machine learning model for retrospective identification of suspected infection for sepsis surveillance: a multicentre cohort study.","authors":"Renée A M Tuinte, Luuk P J Smolenaers, Bram T Knoop, Konstantin Föhse, Tamar J van der Aart, Hjalmar R Bouma, Mihai G Netea, Katrijn Van Deun, Jaap Ten Oever, Jacobien J Hoogerwerf","doi":"10.1016/j.eclinm.2025.103401","DOIUrl":"10.1016/j.eclinm.2025.103401","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;How to identify suspected infection for sepsis surveillance purposes remains a well-recognised challenge. This study aimed to operationalise suspected infection for sepsis surveillance by developing an interpretable machine learning (ML) model for retrospective identification of patients with sepsis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicentre cohort and machine learning study was conducted in two Dutch tertiary care hospitals. Adult patients with a quick Sequential Organ Failure assessment (qSOFA) ≥2 were included. Exclusion criteria included admission to the intensive care unit, transfer to or from another hospital, or patient refusal to reuse data. Cohort one consisted of patients admitted to the Emergency Department (ED) of hospital A between 01/01/2019 and 12/31/2019, to investigate community-onset sepsis. An external validation cohort of ED patients was obtained from hospital B between 01/01/2021 and 06/03/2022. Cohort two included hospitalised patients from hospital A between 01/01/2021 and 06/01/2022, to investigate hospital-onset sepsis. Objective data were extracted from electronic health records. Seven ML methods, including gradient boosting, random forest, logistic regression, decision trees, support vector machines, K nearest neighbours and stochastic gradient descent, were trained to identify sepsis with manual chart review as reference standard. The F1 score (harmonic mean of precision and recall), sensitivity and specificity were used as evaluation metrics. The best performing ML method was compared with other commonly used suspected infection proxies, including the Sepsis-3 definition, an adapted Adult Sepsis Event (ASE) definition and International Classification of Diseases (ICD) codes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;In the ED cohort, 655 patients were included (male: 355 (54.2%), female: 300 (45.8%)) and 240 (36.6%) had sepsis. For community-onset sepsis, gradient boosting performed best with an F1 score of 85.9%, a sensitivity of 91.1% (95%-CI 83.4-95.4%) and a specificity of 89.0% (95%-CI 83.4-92.8%). Most model features reflected either the inflammatory response (CRP, body temperature) or actions taken when an infection is suspected (antibiotic administration, microbial culture). In the external validation cohort, 185 patients were included (male: 94 (50.8%), female: 91 (49.2%)) and 54 (29.2%) had sepsis. External validation yielded an F1 score of 85.7%, a sensitivity of 87.5% (95%-CI 75.3-94.1%) and a specificity of 92.5% (95%-CI 85.9-96.2%). The gradient boosting model outperformed other commonly used proxies for suspected infection in terms of sensitivity, achieving 91.1% (95% CI: 83.4-95.4%), compared to Sepsis-3 with 78.9% (95% CI: 69.4-86.0%), the adapted ASE with 85.6% (95% CI: 76.8-91.4%), and ICD codes with 33.3% (95% CI: 24.5-43.6%). In the hospitalised cohort, 493 patients were included (male: 265 (53.8%), female: 228 (46.2%)) and 129 (26.2%) had sepsis. For hospital-onset s","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103401"},"PeriodicalIF":10.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871992","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}