EClinicalMedicine最新文献

{"title":"Adherence and efficacy outcomes in young Australians with suicidal ideation using a self-management app and digital engagement strategy compared with a sham app: a three-arm randomised controlled trial.","authors":"Michelle Torok, Lauren McGillivray, Daniel Z Q Gan, Jin Han, Sarah Hetrick, Quincy J J Wong","doi":"10.1016/j.eclinm.2024.102963","DOIUrl":"10.1016/j.eclinm.2024.102963","url":null,"abstract":"<p><strong>Background: </strong>Digital interventions are important treatment solutions for suicidal ideation, but premature disengagement is a significant threat to their effectiveness. We tested the adherence to, and efficacy of, two versions of an app-based intervention (app only, app + engagement strategy) for suicidal ideation, compared to a sham app.</p><p><strong>Methods: </strong>This was an online double-blind, three-arm parallel randomised controlled trial in Australia. Recruitment occurred between May 30 and August 8, 2023 and eligible participants were aged 17-24 years and had suicidal ideation in the prior 30 days. They were randomly assigned 1:1:1 to receive (i) LifeBuoy-an app which delivered third wave cognitive behavioural therapy (CBT) skills, (ii) the LifeBuoy app plus a digital engagement strategy, or (iii) a sham app to minimise expectancy bias. The primary efficacy outcome was change in suicidal ideation scores, measured by the Suicidal Ideation Attributes Scale (SIDAS), at 30-, 60- and 120- days post-baseline. The primary engagement outcome was the number of app modules completed at 60-days post-baseline. The final assessment occurred on December 6, 2023. All data was analysed using intention-to-treat. This trial was registered at anzctr.org.au, trial number: ACTRN12621001247864.</p><p><strong>Findings: </strong>692 participants were assigned (mean age: 19.9 [SD 2.5]; 70% female; intervention (combined): n-459, control: n-233). Significant reductions in ideation scores were observed in the combined intervention condition at 60- (d 0.48) and 120- (d 0.29) days after random assignment compared to the control condition. There were no differences in the number of modules completed between the intervention conditions (OR 1.10, 1.03, respectively) and no significant differences in their ideation scores at any time (ds -0.15 to 0.08). Serious adverse events (hospital presenting non-suicidal self-harm and/or suicide attempts) were reported by 6% of participants during the trial (control condition: 9%; combined intervention condition: 4%). No deaths were reported.</p><p><strong>Interpretation: </strong>A third wave CBT app helped to reduce ideation severity, however providing additional online resources to promote therapeutic engagement did not enhance these effects.</p><p><strong>Funding: </strong>This trial and MT was funded by the National Health & Medical Research Council, Matana Foundation for Young People, Alex Roth Foundation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102963"},"PeriodicalIF":9.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885206","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":"Treatable traits in idiopathic pulmonary fibrosis: focus on respiratory tract infections-a systematic review and a meta-analysis.","authors":"Zsombor Matics, Anna Bardóczi, Csongor Galkó, Bence Szabó, Noémi Gede, Zsolt Molnár, Gábor Duray, Caner Turan, Péter Hegyi, Gábor Horváth, Veronika Müller","doi":"10.1016/j.eclinm.2024.102966","DOIUrl":"10.1016/j.eclinm.2024.102966","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a progressive, deadly lung disease with several factors, including respiratory tract infections (RTI), for disease worsening. There's no comprehensive data on RTI incidence in IPF patients across different therapies, including antifibrotic (nintedanib or pirfenidone), investigative or placebo treatments.</p><p><strong>Methods: </strong>A systematic search of databases Medline, EMBASE, Cochrane Central, Web of Science and Scopus was conducted on September 30th 2024 (PROSPERO registration number: CRD42023484213). Only randomized controlled trials of drugs intended for IPF treatment in adults and reporting RTI incidence were included. Pooled risk ratio with 95% confidence interval (CI), risk of bias, GRADE and CINEMA assessments were conducted along with subgroup analyses for upper and lower RTI and for different antifibrotic doses.</p><p><strong>Findings: </strong>A total of 27 trials of different drugs aimed for IPF therapy were pooled in a pairwise meta-analysis, 11,542 patients were analyzed with an overall number of 4156 RTI events, representing an average incidence of 38.4 ± 23.5%. Most therapies did not affect RTI risk in IPF, although single trials with everolimus and trimethoprim/sulfamethoxazole showed a significant decrease compared to placebo. For antifibrotics, RTI incidence was similar with pirfenidone treatment compared to nintedanib (RR: 0.98 CI: [0.71; 1.36]) and compared to placebo (RR: 0.88 CI: [0.69; 1.10]) and nintedanib compared to placebo (RR: 0.89 CI: [0.71; 1.12]).</p><p><strong>Interpretation: </strong>RTIs are frequently reported adverse events in IPF patients over a one-year period, with different investigated treatments showing no profound impact compared to placebo. Future clinical trials should focus on targeting treatable traits like RTIs.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102966"},"PeriodicalIF":9.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884791","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 vulnerability and adverse mental health outcomes following mild traumatic brain injury: a meta-analysis of CENTER-TBI and TRACK-TBI cohorts.","authors":"Mart Kals, Lindsay Wilson, Daniel F Levey, Livia Parodi, Ewout W Steyerberg, Sylvia Richardson, Feng He, Xiaoying Sun, Sonia Jain, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, Geoff T Manley, Andrew I R Maas, Murray B Stein, David K Menon","doi":"10.1016/j.eclinm.2024.102956","DOIUrl":"10.1016/j.eclinm.2024.102956","url":null,"abstract":"<p><strong>Background: </strong>Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes.</p><p><strong>Methods: </strong>Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014-December 2017) and the TRACK-TBI study in the US (March 2014-July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13-15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans.</p><p><strong>Findings: </strong>Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30-1.84, <i>p</i> < 0.001, <i>I</i> ^<i>2</i>  = 20.8%]. Although the MDD-PRS increased the risk of depression after TBI, it did not reach significance in the individual cohorts. However, in a combined analysis, the risk was significantly elevated with a pooled OR of 1.26 [95% CI 1.03-1.53, <i>p</i> = 0.02, <i>I</i> ^<i>2</i>  = 0%]. The addition of PRSs improved the proportion of outcome variance explained in the two study cohorts from 19.5% and 30.3% to 21.6% and 34.0% for PTSD; and from 11.0% and 22.5% to 12.8% and 22.6% for depression. Patients in the highest cognate PRS quintile had increased odds of 3.16 [95% CI 1.80-5.55] and 2.03 [95% CI 1.04-3.94] of developing PTSD or depression compared to the lowest quintile, respectively.</p><p><strong>Interpretation: </strong>Associations of PRSs with PTSD and depression following TBI are not disorder-specific. However, the overlap between MDD-PRS and depression following TBI is less robust compared to PTSD-PRS and PTSD. PRSs could improve risk prediction, and permit enrichment for interventional trials.</p><p><strong>Funding: </strong>This study was supported by funding by an FP7 grant from the European Union, Hannelore Kohl Stiftung, Integra LifeSciences Corporation, NeuroTrauma Sciences, US National Institutes of Health, US Department of Defense, National Football League Advisory Board, US Department of Energy, and One Mind.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102956"},"PeriodicalIF":9.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885204","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":"International consensus to define outcomes for trials of chemoradiotherapy for anal cancer (CORMAC-2): defining the outcomes from the CORMAC core outcome set.","authors":"Robert Samuel, Stephen R Knight, Richard Adams, Prajnan Das, Jennifer Dorth, David Finch, Marianne G Guren, Maria A Hawkins, Susan Moug, Lakshmi Rajdev, David Sebag-Montefiore, Andrew G Renehan, Rebecca Fish","doi":"10.1016/j.eclinm.2024.102939","DOIUrl":"10.1016/j.eclinm.2024.102939","url":null,"abstract":"<p><p>Variation in outcomes definitions and reporting limit the utility of clinical trial results. The Core Outcome Research Measures in Anal Cancer (CORMAC) project developed a core outcome set (COS) for chemoradiotherapy trials for anal squamous cell carcinoma (ASCC) through an international healthcare professional and patient consensus process. The CORMAC-COS comprises 19 outcomes across 4 domains (disease activity, survival, toxicity, life impact). In CORMAC-2 we have established standardised definitions for the 11 disease activity and survival outcomes in the CORMAC COS. Definitions were agreed through a 3 step process, initially identifying existing definitions through systematic review (registered with PROSPERO, CRD42016036540), using these to populate a two-round Delphi questionnaire completed by 51 experts from 13 countries, and finally ratification through an online consensus meeting. Standardising the definitions for these core outcomes facilitates real world utilisation of the CORMAC-COS, thereby increasing the quality of data available for clinical decision-making and ultimately enhancing patient care.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102939"},"PeriodicalIF":9.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885205","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":"When to stop immunotherapy for advanced melanoma: the emulated target trials.","authors":"Mathilde Amiot, Laurent Mortier, Stéphane Dalle, Olivier Dereure, Sophie Dalac, Caroline Dutriaux, Marie-Thérèse Leccia, Eve Maubec, Jean-Philippe Arnault, Florence Brunet-Possenti, Julie De Quatrebarbes, Florence Granel-Brocard, Caroline Gaudy-Marqueste, Cecile Pages, Pierre-Emmanuel Stoebner, Philippe Saiag, Thierry Lesimple, Alain Dupuy, Delphine Legoupil, Henri Montaudié, Bastien Oriano, Celeste Lebbe, Raphael Porcher","doi":"10.1016/j.eclinm.2024.102960","DOIUrl":"10.1016/j.eclinm.2024.102960","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years. Prolonged follow-up of responders after treatment cessation shows sustained response and a low risk of relapse in the months following cessation. To date, the optimal duration of anti-PD-1 therapy for metastatic melanoma remains unestablished. The objective of this work was to evaluate the optimal duration of ICI administration.</p><p><strong>Methods: </strong>We emulated target trials using the cloning, weighting and censoring approach. Each emulation trial aimed to compare the effect of discontinuing versus continuing ICIs at a specific timepoint, among patients still under treatment and with disease control at that time. Patients were from MelBase between 2015 and 2021.</p><p><strong>Findings: </strong>435 participants in the MelBase cohort were eligible and were included in the 6-month discontinuation emulated trial. The results showed significantly lower OS when treatment was discontinued, than when treatment was prolonged for at least three months. The 48-month survival difference was 37.8% (95% confidence interval [CI] 19.8-60.5), and the corresponding restricted mean survival time difference was 8.3 months (95% CI: 4.1-12.7). Neither the 12-month nor the 18-month discontinuation emulated trials showed evidence of benefit of either discontinuing or continuing ICIs at either of these timepoints. The 24-month discontinuation emulated trial results were more in favor of discontinuing than continuing treatment at that time point, with an absolute 48-month survival rate that was 10.5% higher (95% CI 4.4-18.1).</p><p><strong>Interpretation: </strong>These results suggest that a one-year course of immunotherapy is both necessary and sufficient for patients with advanced melanoma. Prolonged treatment beyond 2 years does not appear to be beneficial in terms of survival and could even be detrimental.</p><p><strong>Funding: </strong>This work was supported by a grant from Bristol Myers Squibb, Merck Sharp Dhome, Pierre Fabre, Novartis, Sun Pharm, Regeneron, Sanofi, Nektar, Therapeutics and Oncyte.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102960"},"PeriodicalIF":9.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881465","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":"Adverse events in clinically complex elderly patients with atrial fibrillation according to oral anticoagulation status.","authors":"Tommaso Bucci, Giulio Francesco Romiti, Hironori Ishiguchi, Luigi Gerra, Marta Mantovani, Bi Huang, Marco Proietti, Gregory Y H Lip","doi":"10.1016/j.eclinm.2024.102974","DOIUrl":"10.1016/j.eclinm.2024.102974","url":null,"abstract":"<p><strong>Background: </strong>Few data are available about the impact of oral anticoagulants (OAC) in patients with Atrial Fibrillation (AF) and clinical complexity (CC).</p><p><strong>Methods: </strong>We conducted a retrospective study utilising data from the TriNetX network. Based on ICD-10-CM codes entered between 2020 and 2022, AF patients aged ≥75 years on long-term OAC with CC were categorised into two groups based on OAC use in the year before entering the study (maintained vs discontinued). CC was defined as BMI ≤23 kg/m², and/or history of bleeding, and/or chronic kidney disease. The primary outcomes were the one-year risk of all-cause death, major cardiovascular events (MACE), and major bleeding. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs before and after 1:1 propensity score matching (PSM).</p><p><strong>Findings: </strong>We identified 6554 AF CC patients who discontinued OAC (mean age 81.5 ± 6.0 years, 46.7% females) and 23,212 AF patients with CC who maintained OAC (81.3 ± 6.0 years, 49.4% females). Before PSM, AF CC patients who discontinued OAC had a higher prevalence of intracranial, gastrointestinal haemorrhages, and antiplatelet use, with no significant differences after PSM. OAC discontinuation was associated with a higher risk of all-cause death (HR 1.22, 95% CI 1.11-1.35) and MACE (HR 1.38, 95% CI 1.25-1.53). The one-year risk of major bleeding was similar in those who discontinued or maintained OAC (HR 1.05, 95% CI 0.94-1.18), although it was significantly higher during the early follow-up (HR 1.51, 95% CI 1.24-1.83). The risk of primary outcomes decreased over time, with the risk of bleeding becoming not significant.</p><p><strong>Interpretation: </strong>AF CC patients who discontinued OAC have a high risk of adverse events. New antithrombotic and integrated care approaches to reduce thrombotic risk without increasing bleeding risk are needed in these patients.</p><p><strong>Funding: </strong>This study received no funding.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102974"},"PeriodicalIF":9.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834647","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":"Type I spinal muscular atrophy and disease modifying treatments: a nationwide study in children born since 2016.","authors":"Maria Carmela Pera, Giorgia Coratti, Marika Pane, Riccardo Masson, Valeria Ada Sansone, Adele D'Amico, Michela Catteruccia, Caterina Agosto, Antonio Varone, Claudio Bruno, Sonia Messina, Federica Ricci, Irene Bruno, Elena Procopio, Antonella Pini, Sabrina Siliquini, Riccardo Zanin, Emilio Albamonte, Angela Berardinelli, Chiara Mastella, Giovanni Baranello, Stefano Carlo Previtali, Antonio Trabacca, Chiara Bravetti, Delio Gagliardi, Massimiliano Filosto, Roberto de Sanctis, Richard Finkel, Eugenio Mercuri","doi":"10.1016/j.eclinm.2024.102967","DOIUrl":"10.1016/j.eclinm.2024.102967","url":null,"abstract":"<p><strong>Background: </strong>The advent of disease-modifying treatments (DMT) has changed natural history in 5q Spinal muscular atrophy (SMA). The aim of this study was to report survival and functional aspects in all the Italian type I children born since 2016.</p><p><strong>Methods: </strong>The study included all symptomatic children with type I SMA born since January 1st, 2016, when DMTs became available in Italy. All the Italian SMA referral centers provided data on survival and motor, respiratory, and nutritional status. To compare survival rate pre and post DMTs approval, we also included similar data from SMA I patients born between January 1st, 2010, and December 31st, 2015. A two-proportion z-test was conducted to compare the two cohorts. The significance level was set at p < .05.</p><p><strong>Findings: </strong>241 infants (98%) had type I SMA. Mean follow-up was 3.48 years (SD 2.33). Among type I patients, 42/241 did not survive (25 untreated), while 199 were alive at last follow-up (all treated; mean treatment age 0.6 years), with 25 needing >16 h/day ventilation or tracheostomy with continuous invasive ventilation. 130 of the 199 survivors (65%) achieved independent sitting, and 175 (87.9%) did not require tube feeding.</p><p><strong>Interpretation: </strong>Our study provides a picture of the 'new natural history' of type I SMA, confirming the impact of the new therapies on the progression of type I with longer survival r and has better motor, respiratory and nutritional.</p><p><strong>Funding: </strong>This research was partially funded by grants from the Italian Ministry of Health.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102967"},"PeriodicalIF":9.6,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834421","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 telerehabilitation program to improve visual perception in children and adolescents with hemianopia consecutive to a brain tumor: a single-arm feasibility and proof-of-concept trial.","authors":"Mariana Misawa, Inci Yaman Bajin, Bill Zhang, Monica Daibert-Nido, Danielle Tchao, Eduardo Garcia-Giler, Kyle Cheung, Lora Appel, Pi Nasir, Arun Reginald, Uri Tabori, Ute Bartels, Vijay Ramaswamy, Samuel N Markowitz, Eric Bouffet, Michael Reber","doi":"10.1016/j.eclinm.2024.102955","DOIUrl":"10.1016/j.eclinm.2024.102955","url":null,"abstract":"<p><strong>Background: </strong>Brain tumor in children can induce hemianopia, a loss of conscious vision, profoundly impacting their development and quality of life, yet no effective intervention exists for this pediatric population. This study aimed to explore the feasibility, safety, and potential effectiveness of a home-based audiovisual stimulation in immersive virtual-reality (3D-MOT-IVR) to improve visual function and functional vision.</p><p><strong>Methods: </strong>In a phase 2a, open-labeled, nonrandomized, single-arm study, conducted from July 2022 to October 2023 (NCT05065268), 10 children and adolescents with stable hemianopia were enrolled to perform 20-min sessions of 3D-MOT-IVR every other day for six weeks from home. We assessed feasibility by monitoring adoption, adherence and completion rates, remote data transfer and qualitative feedback. Safety was evaluated using validated cybersickness questionnaires. Comprehensive vision assessments following standardized low-vision evaluation procedures were conducted pre- and post-intervention, with follow-ups at 1- and 6 months.</p><p><strong>Findings: </strong>The home-based 3D-MOT-IVR intervention proved both feasible and safe, with no reported adverse events. All participants completed the prescribed stimulations and the pre- and post-intervention assessment points, 90% completed the follow-ups. Nine out of ten participants showed clinically meaningful enhancement in visual function and/or functional vision, namely binocular visual field restoration and increased reading speed, but two showed concomitant deterioration in monocular visual field. These positive effects were sustained at the 6-month follow-up. Exploratory outcomes revealed a significant positive correlation between the performance at the 3D-MOT-IVR intervention and the visual perception at the binocular visual field test.</p><p><strong>Interpretation: </strong>Our findings underscore the feasibility and safety of home-based audiovisual stimulation in immersive virtual-reality as a potential intervention for improving visual perception in children/adolescents with hemianopia consecutive to a pediatric brain tumor. These promising results lay a strong foundation for a larger randomized controlled trial, offering hope for a meaningful breakthrough in visual rehabilitation for this vulnerable population.</p><p><strong>Funding: </strong>Meagan Bebenek Foundation and University Health Network Foundation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102955"},"PeriodicalIF":9.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834645","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":"Risk of intraoperative hemorrhage during cesarean scar ectopic pregnancy surgery: development and validation of an interpretable machine learning prediction model.","authors":"Xinli Chen, Huan Zhang, Dongxia Guo, Siyuan Yang, Bao Liu, Yiping Hao, Qingqing Liu, Teng Zhang, Fanrong Meng, Longyun Sun, Xinlin Jiao, Wenjing Zhang, Yanli Ban, Yugang Chi, Guowei Tao, Baoxia Cui","doi":"10.1016/j.eclinm.2024.102969","DOIUrl":"10.1016/j.eclinm.2024.102969","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Current models for predicting intraoperative hemorrhage in cesarean scar ectopic pregnancy (CSEP) are constrained by known risk factors and conventional statistical methods. Our objective is to develop an interpretable prediction model using machine learning (ML) techniques to assess the risk of intraoperative hemorrhage during CSEP in women, followed by external validation and clinical application.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicenter retrospective study utilized electronic medical record (EMR) data from four tertiary medical institutions. The model was developed using data from 1680 patients with CSEP diagnosed and treated at Qilu Hospital of Shandong University, Chongqing Health Center for Women and Children, and Dezhou Maternal and Child Health Care Hospital between January 1, 2008, and December 31, 2023. External validation data were obtained from Liao Cheng Dong Chang Fu District Maternal and Child Health Care Hospital between January 1, 2021, and December 31, 2023. Random forest (RF), Lasso, Boruta, and Extreme Gradient Boosting (XGBoost) were employed to identify the most influential variables in the model development data set; the best variables were selected based on reaching the λ&lt;sub&gt;min&lt;/sub&gt; value. Model development involved eight machine learning methods with ten-fold cross-validation. Accuracy and decision curve analysis (DCA) were used to assess model performance for selection of the optimal model. Internal validation of the model utilized area under the receiver operating characteristic curve (AUC), sensitivity, specificity, Matthews correlation coefficient, and F1 score. These same indicators were also applied to evaluate external validation performance of the model. Finally, visualization techniques were used to present the optimal model which was then deployed for clinical application via network applications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Setting λ&lt;sub&gt;min&lt;/sub&gt; at the value of 0.003, the optimal variable combination containing 9 variables was selected for model development. The optimal prediction model (Bayes) had an accuracy of 0.879 (95% CI: 0.857-0.901) an AUC of 0.882 (95% CI: 0.860-0.904), a DCA curve maximum threshold probability of 0.41, and a maximum return of 7.86%. The internal validation accuracy was 0.869 (95% CI: 0.847-0.891), an AUC of 0.822 (95% CI: 0.801-0.843), a sensitivity of 0.938, a specificity of 0.422, a Matthews correlation coefficient of 0.392, and an F1 score of 0.925. In the external validation, the accuracy was 0.936 (95% CI: 0.913-0.959), an AUC of 0.853 (95% CI: 0.832-0.874), a sensitivity of 0.954, a specificity of 0.5, a Matthews correlation coefficient of 0.365, and an F1 score of 0.966. This indicates that the prediction model performed well in both internal and external validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The developed prediction model, deployed in the network application, is capable of forecasting the risk of intraoperative hem","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102969"},"PeriodicalIF":9.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834471","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":"Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial.","authors":"Ewa Koscielniak, Gustaf Ljungman, Bernarda Kazanowska, Felix Niggli, Monika Sparber-Sauer, Rupert Handgretinger, Martin Zimmermann, Joachim Boos, Bernd Blank, Erika Hallmen, Irene Teichert von Lüttichau, Irene Schmid, Birgit Fröhlich, Hermann L Müller, Wolfgang Behnisch, Ruth Ladenstein, Monika Scheer, Christian Vokuhl, Thekla von Kalle, Claudia Blattmann, Stefan Bielack, Thomas Klingebiel","doi":"10.1016/j.eclinm.2024.102957","DOIUrl":"10.1016/j.eclinm.2024.102957","url":null,"abstract":"<p><strong>Background: </strong>Rhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.</p><p><strong>Methods: </strong>CWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries. Eligible patients were those aged 6 months to 21 years with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring in unfavourable sites with unfavourable age (≥10 years) and/or tumour size (>5 cm); all non-metastatic alveolar rhabdomyosarcoma and those with any non-metastatic rhabdomyosarcoma with nodal involvement. A further group was also eligible: patients with non-metastatic undifferentiated sarcoma, extraskeletal Ewing sarcoma and primary unresected synovial sarcoma. Patients in complete remission at the end of standard therapy (nine cycles of ifosfamide, vincristine with doxorubicine or dactinomycin, and surgery or radiotherapy, or both) were randomised to either stop treatment (S-arm) or to receive oral maintenance therapy (M-arm) with eight 10-day courses (25 weeks) of trofosfamide (2 × 75 mg/m²/day) and idarubicin (1 × 5 mg/m²/day 1,4,7,10) alternating with trofosfamide and etoposide (2 × 25 mg/m²/day). The primary outcome was event-free survival (EFS) and the secondary outcome was overall survival (OS) in the intent-to treat population. This trial is registered at ClinicalTrials.gov, NCT00876031, and, EudraCT 2007-0001478-10.</p><p><strong>Findings: </strong>Between July 1st, 2009 and June 30th, 2019, 195 patients were randomly assigned to the M-arm (n = 96) or S-arm (n = 99). In the intent-to-treat population, with a median follow-up of 5.2 years (IQR 3.9-6.1) for surviving patients, the 3-year EFS in the M-arm was 66.9% (95% CI 58.1-77.2) versus 75.6% (67.6-84.6) in the S-arm (hazard ratio, (HR) 1.62, 95% CI 0.98-2.69, p = 0.06). 3-year OS was 82.8% (95% CI 75.4-90.8) in the M-arm versus 84.7% (95% CI 77.8-92.1) in the S-arm (HR 1.55, 95% CI 0.84-2.89, p = 0.17). Grade 3-4 adverse events were haematological in 66% of patients, febrile infections in 6%, gastrointestinal in 10%, and sensory neuropathy in 1%.</p><p><strong>Interpretation: </strong>The addition of 25 weeks of oral maintenance therapy with trofosfamide, etoposide and idarubicin after standard therapy does not improve EFS and OS in patients with high-risk rhabdomyosarcoma and other STS.</p><p><strong>Funding: </strong>Deutsche Kinderkrebsstiftung Grant No.DKS 2009.09, DKS 2012.06, DKS 2015.13, DKS 2018.10 and DKS 2021.04.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"78 ","pages":"102957"},"PeriodicalIF":9.6,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834663","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}