EClinicalMedicine最新文献

{"title":"Treatment decision algorithms for tuberculosis screening and diagnosis in children below 5 years hospitalised with severe acute malnutrition: a cost-effectiveness analysis.","authors":"Marc d'Elbée, Nyashadzaishe Mafirakureva, Chishala Chabala, Minh Huyen Ton Nu Nguyet, Martin Harker, Clémentine Roucher, Gerald Businge, Perfect Shankalala, Bwendo Nduna, Veronica Mulenga, Maryline Bonnet, Eric Wobudeya, Olivier Marcy, Peter J Dodd","doi":"10.1016/j.eclinm.2025.103206","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103206","url":null,"abstract":"<p><strong>Background: </strong>Children with severe acute malnutrition (SAM) are an important risk group for underdiagnosis and death from tuberculosis. In 2022, the World Health Organization (WHO) recommended use of treatment decision algorithms (TDAs) for tuberculosis diagnosis in children. There is currently no cost-effectiveness evidence for TDA-based approaches compared to routine practice.</p><p><strong>Methods: </strong>The TB-Speed SAM study developed i) a one-step TDA including Xpert, clinical, radiological and echography features, and ii) a two-step TDA, which also included a screening phase, for children under 5 years hospitalised with SAM at three tertiary hospitals in Uganda and Zambia from 4th November 2019 to 20th June 2022. This study is registered with ClinicalTrials.gov, NCT04240990. We assessed the diagnostic accuracy and cost-effectiveness of deploying TB-Speed and WHO TDA-based approaches compared to the standard of care (SOC). Estimated outcomes included children started on tuberculosis treatment, false positive rates, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs).</p><p><strong>Findings: </strong>Per 100 children hospitalised with SAM, averaging 19 children with tuberculosis, the one-step TDA initiated 17 true positive children (95% uncertainty intervals [UI]: 12-23) on tuberculosis treatment, the two-step TDA 15 (95%UI: 10-22), the WHO TDA 14 (95%UI: 9-19), and SOC 4 (95%UI: 2-9). The WHO TDA generated the most false positives (35, 95%UI: 24-46), followed by the one-step TDA (18, 95%UI: 6-29), the two-step TDA (14, 95%UI: 1-25), and SOC (11, 95%UI: 3-17). All TDA-based approaches had ICERs below plausible country cost-effectiveness thresholds compared to SOC (one-step: $44-51/DALY averted, two-step: $34-39/DALY averted, WHO: $40-46/DALY averted).</p><p><strong>Interpretation: </strong>Our findings show that these TDA-based approaches are highly cost-effective for the vulnerable group of children hospitalised with SAM, compared to current practice.</p><p><strong>Funding: </strong>Unitaid Grant number: 2017-15-UBx-TB-SPEED.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"83 ","pages":"103206"},"PeriodicalIF":9.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977535","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":"Identification and characterisation of clinically distinct subgroups of adults hospitalised with influenza in the USA: a repeated cross-sectional study.","authors":"Catherine H Bozio, Svetlana Masalovich, Alissa O'Halloran, Pam Daily Kirley, Cora Hoover, Nisha B Alden, Elizabeth Austin, James Meek, Kimberly Yousey-Hindes, Kyle P Openo, Lucy S Witt, Maya L Monroe, Anna Falkowski, Lauren Leegwater, Ruth Lynfield, Melissa McMahon, Daniel M Sosin, Sarah A Khanlian, Bridget J Anderson, Nancy Spina, Christina B Felsen, Maria A Gaitan, Krista Lung, Eli Shiltz, Ann Thomas, William Schaffner, H Keipp Talbot, Emma Mendez, Holly Staten, Carrie Reed, Shikha Garg","doi":"10.1016/j.eclinm.2025.103207","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103207","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Patients hospitalised with influenza have heterogeneous clinical presentations and disease severity, which may complicate epidemiologic study design or interpretation. We applied latent class analysis to identify clinically distinct subgroups of adults hospitalised with influenza.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analysed cross-sectional study data on adults (≥18 years) hospitalised with laboratory-confirmed influenza from the population-based U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET) including 13 states during 2017-2018 and 2018-2019 influenza seasons (October 1 through April 30). Adults were included if they were residents of the FluSurv-NET catchment area, hospitalised with laboratory-confirmed influenza during these two seasons, and had both the main case report form and the supplemental disease severity case report form completed. We constructed a latent class model to identify subgroups from multiple observed variables including baseline characteristics (age and comorbidities) and clinical course (symptoms at admission, respiratory support requirement, and development of new complications and exacerbations of underlying conditions).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Among the 43,811 influenza-associated hospitalizations reported during the 2017-2018 and 2018-2019 influenza seasons, 15,873 (36.2%) were included in our analytic population: among them, 7069 (44.5%) were male and 8804 (55.5%) were female. We identified five subgroups. Subgroup A included persons of all ages with few comorbidities and 87.9% (255/290) of pregnant women. Subgroup B included older adults with comorbidities (cardiovascular disease (79.7% [3650/4581]) and diabetes (50.6% [2320/4581])). Almost all patients in subgroups C and D had asthma or chronic lung disease and high proportions with exacerbations of underlying conditions (59.7% [889/1489] and 65.1% [2274/3496], respectively). Subgroup E had the highest proportion with new complications (90.3% [1383/1531]). Subgroups D and E had the highest proportions with severe disease indicators: 21.0% (733/3496) and 50.4% (771/1531) required ICU admission, 7.2% (253/3496) and 28.0% (428/1531) required invasive mechanical ventilation, and 3.3% (116/3496) and 11.4% (174/1531) died in-hospital, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The five identified subgroups of adults hospitalised with influenza had varying distributions of age, comorbid conditions, and clinical courses characterized by new complications versus exacerbations of existing conditions. Stratifying by these subgroups may strengthen analyses that assess the impact of influenza vaccination and antiviral treatment on risk of severe disease. Limitations included that results were based on a convenience sample within FluSurv-NET sites and were likely not representative of all adults hospitalised with influenza in the United States. Influenza testing was also clinician-driven, likely leading to under","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"83 ","pages":"103207"},"PeriodicalIF":9.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964344","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":"Genetic predisposition in sarcomas: clinical implications and management.","authors":"Elizabeth A Connolly, Kjetil Boye, Sylvie Bonvalot, Christian P Kratz, Andreas Leithner, David Malkin, Christina Messiou, Aisha B Miah, Pan Pantziarka, Beate Timmermann, Winette T A van der Graaf, David M Thomas, Silvia Stacchiotti","doi":"10.1016/j.eclinm.2025.103203","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103203","url":null,"abstract":"<p><p>Recent studies indicate up to 20% of sarcomas may be associated with predisposition genes, and this number will probably increase as genetic testing becomes more available. Evidence on the management of patients with sarcoma and genetic predisposition remains, however, scarce. This review compiles available research on genetic predisposition syndromes associated with sarcoma and sarcoma treatment within such syndromes, addressing key gaps in knowledge. We explore the current evidence on how genetic predisposition may influence treatment decisions and clinical management, focusing on surgery, radiotherapy, systemic treatment, and surveillance. Evidence-based recommendations are currently not available for most syndromes, and we have therefore included pragmatic advice for clinicians. Unanswered questions and unmet needs are also identified, underscoring the importance of multidisciplinary input from specialists such as geneticists, radiologists, surgeons and oncologists. The review stresses the need for future research to improve clinical outcomes for patients with sarcoma and genetic predisposition.</p><p><strong>Funding: </strong>No funding has been provided for this work.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"83 ","pages":"103203"},"PeriodicalIF":9.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967705","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":"COSMIN systematic review and meta-analysis of the measurement properties of the Positive and Negative Syndrome Scale (PANSS).","authors":"Simon Geck, Maximilian Roithmeier, Markus Bühner, Sophia Wehr, Lucia Weigel, Josef Priller, John M Davis, Stefan Leucht","doi":"10.1016/j.eclinm.2025.103155","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103155","url":null,"abstract":"<p><strong>Background: </strong>The Positive and Negative Syndrome Scale (PANSS) is the most widely used tool for assessing the symptoms of schizophrenia. Despite its widespread use, the psychometric properties of the PANSS have not been systematically reviewed. This study fills that gap in the scientific literature.</p><p><strong>Methods: </strong>We utilized the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews and meta-analytical procedures to assess the psychometric properties of the PANSS in its original three-subscale form as well as the quality level of the evidence available. On this basis we formulated recommendations for future research and use. A study protocol was registered under 10.17605/OSF.IO/5EGMD. The search period was until February 21, 2024.</p><p><strong>Findings: </strong>We included 119 publications. According to COSMIN, the PANSS demonstrated sufficient reliability, construct validity, and responsiveness; but had significant shortcomings in content validity and structural validity. The original three-factor model showed poor structural validity, leading to its COSMIN classification as \"not recommendable\". The subscales showed overall acceptable measurement properties. However, the lack of structural validity of the three-subscale model renders its subscales less useful. Moreover, the PANSS negative subscale does not cover all domains of the National Institute of Mental Health consensus. Due to the length of the instrument (30-50 min), it is barely useable in clinical practice.</p><p><strong>Interpretation: </strong>Although the PANSS is the standard scale for schizophrenia symptom severity, its shortcomings regarding fundamental psychometric domains and practical applicability warrant the development of new scales for which appropriate methods should be applied from the start.</p><p><strong>Funding: </strong>There was no specific funding source for this research.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"82 ","pages":"103155"},"PeriodicalIF":9.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982664","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 of automated insulin delivery systems in people with type 1 diabetes: a systematic review and network meta-analysis of outpatient randomised controlled trials.","authors":"Anna Stahl-Pehe, Nafiseh Shokri-Mashhadi, Marielle Wirth, Sabrina Schlesinger, Oliver Kuss, Reinhard W Holl, Christina Bächle, Klaus-D Warz, Jutta Bürger-Büsing, Olaf Spörkel, Joachim Rosenbauer","doi":"10.1016/j.eclinm.2025.103190","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103190","url":null,"abstract":"<p><strong>Background: </strong>The comparative efficacy of automated insulin delivery (AID) systems and other treatment options for type 1 diabetes, accounting for the certainty of evidence (CoE), is unknown.</p><p><strong>Methods: </strong>We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov and included outpatient randomised controlled trials (RCTs) published until January 8, 2025, in people with type 1 diabetes with a three-week or longer intervention of AID systems (PROSPERO registration number: CRD42023395492). We performed pairwise and network meta-analyses and used the Risk of Bias tool 2 and the Grading of Recommendations Assessment, Development and Evaluation methods to determine the CoE for each outcome.</p><p><strong>Findings: </strong>A total of 46 studies involving seven insulin treatment options and 4113 participants were included, of which 29 and 17 had low and moderate risks of bias, respectively. The intervention AID systems, including the hybrid closed-loop (HCL), advanced HCL (AHCL) and full closed-loop (FCL) systems, were evaluated in 20, 25 and 1 studies, respectively. The network meta-analysis did not indicate global inconsistencies but did indicate global publication bias for all glycaemic outcomes. The CoE varied between very low and high, depending on the treatment and outcome under consideration. Compared with pump therapy, the percentage of time in the range 70-180 mg/dl was greater with AID use (HCL: 19.7% [95% confidence interval 13.2%; 26.1%], moderate CoE; AHCL: 24.1% [18.2%; 29.9%], moderate CoE; FCL: 25.5% [11.1%; 39.9%], high CoE). Compared with pump therapy, the percentage of time above 180 mg/dl and 250 mg/dl was lower with AHCL, on average, by 19.6% (14.0%; 25.1%), moderate CoE, and 14.8% (8.8%; 20.8%), moderate CoE, respectively. The CoE was very uncertain regarding the overall effect of AID systems on the percentage of time below 70 mg/dl and 54 mg/dl and the HbA1c.</p><p><strong>Interpretation: </strong>AID systems improve glycaemic outcomes to varying degrees and with varying CoE.</p><p><strong>Funding: </strong>German Federal Ministry of Education and Research (BMBF; grant 01KG2203).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"82 ","pages":"103190"},"PeriodicalIF":9.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984494","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":"Qualitative and quantitative educational disparities and brain signatures in healthy aging and dementia across global settings.","authors":"Raul Gonzalez-Gomez, Josephine Cruzat, Hernán Hernández, Joaquín Migeot, Agustina Legaz, Hernando Santamaria-García, Sol Fittipaldi, Marcelo Adrián Maito, Vicente Medel, Enzo Tagliazucchi, Pablo Barttfeld, Daniel Franco-O'Byrne, Ana María Castro Laguardia, Patricio A Borquez, José Alberto Avila-Funes, María I Behrens, Nilton Custodio, Temitope Farombi, Adolfo M García, Indira Garcia-Cordero, Maria E Godoy, Cecilia Gonzalez Campo, Kun Hu, Brian Lawlor, Diana L Matallana, Bruce Miller, Maira Okada de Oliveira, Stefanie D Pina-Escudero, Elisa de Paula França Resende, Pablo Reyes, Andrea Slachevsky, Leonel T Takada, Görsev G Yener, Carlos Coronel-Oliveros, Agustin Ibañez","doi":"10.1016/j.eclinm.2025.103187","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103187","url":null,"abstract":"<p><strong>Background: </strong>While education is crucial for brain health, evidence mainly relies on individual measures of years of education (YoE), neglecting education quality (EQ). The effect of YoE and EQ on aging and dementia has not been compared.</p><p><strong>Methods: </strong>We conducted a cross-sectional assessment of the effect of EQ and YoE on brain health in 7533 subjects from 20 countries, including healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). EQ was based on country-level quality indicators provided by the programme for international student assessment (PISA). After applying neuroimage harmonization, we examined its effect, along with YoE, on gray matter volume and functional connectivity. Regression models were adjusted for age, sex, and cognition, controlling for multiple comparisons. The influence of image quality was assessed through sensitivity analysis. Data collection was conducted between June 1 and October 30, 2024.</p><p><strong>Findings: </strong>Less EQ and YoE were associated with brain alterations across groups. However, EQ had a stronger influence, mainly targeting the critical areas of each condition. At the whole-brain level, EQ influenced volume (HCs: Δmean = 2·0 [1·9-2·0] × 10^-2, <i>p</i> < 10^-5; AD: Δmean = 0·1 [-0·0 to 0·3] × 10^-2, <i>p</i> = 0·18; FTLD: Δmean = 3·5 [3·0-4·0] × 10^-2, <i>p</i> < 10^-5; all with 95% confidence intervals) and networks (HCs: Δmean = 13·5 [13·2-13·7] × 10^-2, <i>p</i> < 10^-5; AD: Δmean = 5·9 [5·2-6·7] × 10^-2, <i>p</i> < 10^-5; FTLD: Δmean = 13·2 [11·2-13·7] × 10^-2, <i>p</i> < 10^-5) 1·3 to 7·0 times more than YoE. These effects remain robust despite variations in income and socioeconomic factors at country and individual levels.</p><p><strong>Interpretation: </strong>The results support the need to incorporate education quality into studying and improving brain health, underscoring the importance of country-level measures.</p><p><strong>Funding: </strong>Multi-partner consortium to expand dementia research in Latin America (ReDLat).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"82 ","pages":"103187"},"PeriodicalIF":9.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964385","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":"Interaction between influenza vaccine and statins affecting the risk of rhabdomyolysis in Taiwan: a nationwide case-centred analysis.","authors":"Che-Yu Chen, Miyuki Hsing-Chun Hsieh, Wan-Ting Huang, Edward Chia-Cheng Lai","doi":"10.1016/j.eclinm.2025.103171","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103171","url":null,"abstract":"<p><strong>Background: </strong>Literature suggests a potential interaction between influenza vaccination, statin use and rhabdomyolysis, but evidence is limited to case reports.</p><p><strong>Methods: </strong>Using out- and inpatient health records from Taiwan's National Health Insurance Research Database (NHIRD) between January 2016 and December 2021, we retrospectively constructed a nationwide cohort of patients aged 50 years and older, first-ever diagnosed with rhabdomyolysis, focusing on those who received an influenza vaccine within the preceding one year. We applied a case-centred analysis to evaluate the interaction between statin use and influenza vaccination within specific risk intervals: 1-7 days and 8-14 days post-vaccination, as well as 30-day and 60-day windows for statin use prior to rhabdomyolysis diagnosis. The main outcome measures were odds ratios (ORs) for statin-associated rhabdomyolysis, stratified by timing of influenza vaccination.</p><p><strong>Findings: </strong>Among the 5,602 rhabdomyolysis cases analysed, 1,765 patients were exposed to statins within 30 days, and 1,838 patients were exposed within 60 days. 74 individuals were vaccinated within 7 days prior to their diagnosis, 30 of which were taking statins inside the 30-day interval, these individuals were found to be at a significantly higher risk of statin-related rhabdomyolysis (OR: 1.67, 95% confidence interval: 1.04-2.69). A similar risk was observed when the statin risk interval was extended to 60 days, 74 vaccinated rhabdomyolysis patients with 32 within the 60 day window (OR: 1.79, 95% confidence interval: 1.12-2.87). However, this increased risk was not observed among the 97 individuals (24 patients in the 30 day window and 26 in the 60 day) who received vaccination 8-14 days before rhabdomyolysis onset (OR: 0.85, 95% confidence interval: 0.53-1.36), and not in those vaccinated outside these risk intervals.</p><p><strong>Interpretation: </strong>Our results suggest a significant temporal association between recent influenza vaccination and increased risk of statin-associated rhabdomyolysis within 7 days post-vaccination. These findings highlight the need for healthcare providers to monitor for rhabdomyolysis symptoms following influenza vaccination in patients receiving statin therapy. Further confirmation in larger prospective international studies is warranted to better understand this potential association.</p><p><strong>Funding: </strong>National Science and Technology Council of Taiwan (NSTC 112-2628-B-006-003-; NSTC 113-2628-B-006-009-) and the National Health Research Institutes of Taiwan (NHRI-11A1-CG-CO-04-2225-1; NHRI-12A1-CG-CO-04-2225-1; NHRI-13A1-CG-CO-04-2225-1; NHRI-14A1-CG-CO-04-2225-1).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"82 ","pages":"103171"},"PeriodicalIF":9.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957103","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":"Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trial.","authors":"Sean W X Ong, Ruxandra Pinto, Asgar Rishu, Steven Y C Tong, Robert J Commons, John M Conly, Gerald A Evans, Michael Fralick, Christopher Kandel, Philippe R S Lagacé-Wiens, Todd C Lee, Sylvain A Lother, Derek R MacFadden, John C Marshall, Valérie Martel-Laferrière, Michael Mayette, Emily G McDonald, John D Neary, Josef Prazak, Edward Raby, Adrian Regli, Benjamin A Rogers, Stephanie Smith, Linda R Taggart, Han Ting Wang, Terence Wuerz, Dafna Yahav, Paul J Young, Robert A Fowler, Nick Daneman","doi":"10.1016/j.eclinm.2025.103195","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103195","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The BALANCE trial demonstrated non-inferiority of 7 (vs 14) day antibiotic durations in patients with uncomplicated non-&lt;i&gt;S. aureus/lugdunensis&lt;/i&gt; bacterial bloodstream infections (BSI). However, there may be patient subgroups who benefit from longer durations. We aimed to evaluate if bedside clinical decision rules could identify these subgroups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this post-hoc analysis of the multicentre, randomised BALANCE trial (October 17, 2014-May 5, 2023), we applied three clinical decision rules to investigate heterogeneity of treatment effect in 7-day vs 14-day antibiotic durations on 90-day all-cause mortality. We used the rules to categorize patients in BALANCE into different risk groups and calculated the unadjusted absolute risk difference (RD) for 90-day mortality in patients receiving 7- vs 14-day antibiotics within each risk group. Statistical significance was tested using an interaction test. The BALANCE trial is registered with ClinicalTrials.gov (NCT03005145).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;3581 patients were included. All three rules predicted mortality risk, but none identified statistically significant effect modification: (a) static rule (low-risk: RD -0.58, 95% CI -8.91 to 7.73; moderate-risk: RD -.01, 95% CI -3.86 to 1.83; high-risk: RD -2.65, 95% CI -7.12 to 1.81; p = 0.74); (b) dynamic rule (met rule on day 7: RD -2.18, 95% CI -4.81 to 0.45; did not meet rule: RD 1.75, 95% CI -3.89 to 7.40; p = 0.16); and (c) early clinical failure criteria (score&lt;2: RD -2.38, 95% CI -5.0 to 0.23; score ≥2: RD -0.65, 95% CI -5.06 to 3.77; p = 0.24). Results were consistent across sensitivity analyses including imputation for missing data and restricting analyses to gram-negative BSI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The decision rules included in our analyses did not identify a subgroup of patients within BALANCE that would benefit from 14 (vs 7) days of treatment. 7-day treatment duration is sufficient for most patients with uncomplicated non-&lt;i&gt;S. aureus/lugdunensis&lt;/i&gt; BSI. Future research could explore data-driven machine-learning approaches to identify comprehensive combinations of patient characteristics that may guide individualised duration of antibiotic therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;The BALANCE trial was funded by the Canadian Institutes of Health Research, Health Research Council of New Zealand, Australian National Medical Research Council, Physicians Services Incorporated Ontario and Ontario Ministry of Health and Long-term Care Innovation Fund. SWXO conducted this study as part of his PhD studies, with funding from: the Emerging & Pandemic Infections Consortium (University of Toronto, Canada); Connaught International Scholarship (University of Toronto, Canada); the Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST; Government of Ontario, Canada); and the Melbourne Research Scholarship (University of Melbourne, Australia). VML is ","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"83 ","pages":"103195"},"PeriodicalIF":9.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970145","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 online adaptive magnetic resonance-guided fractionated stereotactic radiotherapy for brain metastases in non-small cell lung cancer (GASTO-1075): a single-arm, phase 2 trial.","authors":"Shiyang Zheng, Shouliang Ding, Biaoshui Liu, Yixin Xiong, Rui Zhou, Pengxin Zhang, Fangjie Liu, Yimei Liu, Meining Chen, Yu Situ, Mengru Wang, Xiaoyan Huang, Shaohan Yin, Wenfeng Fang, Yonggao Mou, Bo Qiu, Daquan Wang, Hui Liu","doi":"10.1016/j.eclinm.2025.103189","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103189","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases (BMs) in non-small cell lung cancer (NSCLC) are associated with poor prognosis and quality of life (QoL). This study aimed to evaluate the efficacy and safety of online adaptive MR-guided fractionated stereotactic radiotherapy (FSRT) using a 1.5 T MR-Linac in this subgroup of patients.</p><p><strong>Methods: </strong>This single-arm phase 2 trial was conducted at Sun Yat-sen University Cancer Centre. Patients aged 18-75 years with NSCLC, 1-10 BMs, and an ECOG status of 0-1 were included. Key exclusion criteria included inability to undergo contrast-enhanced MRI and contraindications to bevacizumab. Patients received 30 Gy adaptive FSRT in 5 daily fractions under real-time MR guidance, with bevacizumab before (day 1) and after (day 21) FSRT. The primary endpoint was 1-year intracranial progression-free survival (IPFS); secondary endpoints included objective response rate (ORR), 1-year progression-free survival (PFS), 1-year overall survival (OS), treatment-related toxicities, and QoL. All enrolled patients were included in primary and safety analyses. This trial is registered with Clinicaltrials.gov, NCT04946019.</p><p><strong>Findings: </strong>Between June 10th, 2021 and June 29th, 2023, 70 patients were assessed for eligibility and 55 patients were enrolled (median follow-up: 22.3 months). The median age was 58 years (IQR: 51-65), with 33% (18/55) female patients, and 82% (45/55) presenting with adenocarcinoma. The 1-year IPFS rate was 78.7% (95% CI, 68.2%-90.7%), with a median IPFS of 21.9 months (95% CI, 13.8-30.1 months). The 1-year PFS rate was 63.5% (95% CI: 51.8%-78.2%), and OS was 82.4% (95% CI: 72.6%-93.6%). The ORR reached 78% (95% CI: 65.0%-88.2%). Treatment-related toxicity was minimal, with only one case (2%) of grade 1 radiation necrosis. QoL improved steadily, with the Global Health Status score increasing from 65.67 ± 16.97 to 79.33 ± 8.79 at 6 months post FSRT (p < 0.0001).</p><p><strong>Interpretation: </strong>Online adaptive FSRT using a 1.5 T MR-Linac has demonstrated effectiveness and good tolerability for BMs in patients with NSCLC. However, the relatively small sample size and short follow-up may affect result generalizability. Further randomised studies are warranted to confirm these findings and establish optimal treatment protocols.</p><p><strong>Funding: </strong>The National Natural Science Foundation of China (Grant Number 82073328).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"82 ","pages":"103189"},"PeriodicalIF":9.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996249","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":"Global landscape and trends in lifetime risks of haematologic malignancies in 185 countries: population-based estimates from GLOBOCAN 2022.","authors":"Kexin Sun, Hongliang Wu, Qian Zhu, Kai Gu, Hui Wei, Shaoming Wang, Li Li, Chunxiao Wu, Ru Chen, Yi Pang, Bingfeng Han, Hongmei Zeng, Meicen Liu, Rongshou Zheng, Wenqiang Wei","doi":"10.1016/j.eclinm.2025.103193","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103193","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Haematologic malignancies accounted for 6.6% of total cancer cases and 7.2% of total cancer-related deaths worldwide in 2022. We implemented a novel approach to estimate the lifetime risk of developing and dying from various types of haematologic malignancies at the global, regional and country-specific perspectives in 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrieved incidence and mortality rates for Hodgkin lymphoma (HL), Non-Hodgkin lymphoma (NHL), multiple myeloma (MM) and leukaemia from GLOBOCAN 2022 of 185 countries, along with the national population statistics and all-cause mortality data sourced from the United Nations. For trend analysis, we obtained consecutive cancer registry data spanning from 2003 to 2017 from the Cancer Incidence in Five Continents (CI5) Plus database. After quality control, datasets from 30 countries were included. We used the \"adjusted for multiple primaries (AMP)\" method to calculate the lifetime risk of incidence (LRI) and mortality (LRM) by cancer type, selected age interval, sex, country and geographic region.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;In 2022, the global lifetime risk of incidence (LRI) and mortality (LRM) for all haematologic malignancies was 1.67% and 0.98%, respectively. LRI was highest for NHL, whereas the LRM was highest for leukaemia. On a general level, males exhibited higher LRI and LRM compared to females. Both LRI and LRM increased with higher Human Development Index (HDI) levels. The LRI and LRM for haematologic malignancies were notably high in regions such as Australia/New Zealand, Northen America, as well as Northen, Western and Southern Europe, whereas they were comparatively low in Middle, Western and Eastern Africa. We observed about 5-fold regional disparity in the LRI/LRM ratio for HL, ranging from 1.50 in Middle Africa to 7.67 in Western Europe. Individuals aged 60 and above still faced 71.26% and 78.57% remaining risks for developing and dying from all haematologic malignancies. Among the 185 countries studied, NHL was the haematologic malignancy with the highest LRI in 68.65% of the countries. However, leukaemia had the highest LRM in 58.92% of these countries. MM exhibited the highest LRI and LRM particularly in islands surrounding the Caribbean Sea. Out of 30 countries with eligible consecutive cancer surveillance data, 24 exhibited significant upward trends in LRI of all haematologic malignancies, with AAPCs ranging from 0.5% in USA to 4.3% in Latvia. 25 countries showed significant upward trends in LRM, with AAPCs ranging from 1.0% in USA to 5.5% in Republic of Korea.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The global lifetime risks of haematologic malignancies exhibit considerable variations across different world regions, necessitating country-specific and targeted decision-making strategies. In contrast to traditional indicators, the compositive lifetime risks provide intuitive measures with profound public health implications, offering fres","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"83 ","pages":"103193"},"PeriodicalIF":9.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985468","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}