EClinicalMedicine最新文献

{"title":"Predictors of withdrawal of anticancer drug indications granted accelerated approval: a retrospective cohort study.","authors":"Ariadna Tibau, Edward R Scheffer Cliff, Alejandra Romano, Maria Borrell, Consolacion Molto, Aaron S Kesselheim","doi":"10.1016/j.eclinm.2025.103088","DOIUrl":"10.1016/j.eclinm.2025.103088","url":null,"abstract":"<p><strong>Background: </strong>The accelerated approval pathway allows the FDA to approve drugs for serious conditions based on promising surrogate measures, with confirmatory studies required later. If subsequent testing shows an unfavorable benefit-risk profile, the indication may be withdrawn. This study aimed to identify factors associated with the withdrawal of drug indications following accelerated approval.</p><p><strong>Methods: </strong>In this retrospective cohort study, we identified FDA-approved drugs for solid and hematologic cancers from 1992 to 2022 and extracted factors present at the time of accelerated approval, including pivotal trial characteristics, outcomes, and confirmatory study initiation timing from drug labels and published reports. Clinical benefit was assessed using the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS), with high benefit as A-B/4-5 and low as C/≤2. Multivariable logistic regression identified factors associated with drug indication withdrawal.</p><p><strong>Findings: </strong>Among 167 accelerated approval indications for 113 anticancer drugs, by August 2024, 102 (61%) had been converted to regular approval, 31 (19%) were withdrawn, and the remaining 34 (20%) were ongoing accelerated approvals. Of the 133 indications that were either converted or withdrawn, 52 (39%) were approvals for hematologic cancer drugs, and 41 (31%) supported genome-targeted drug approvals. Among 83 eligible indications, 46 (55%) were granted Breakthrough Therapy designation. In the 133 pivotal trials, 112 (84%) used response rate as the primary endpoint, and 66% (86/130) offered low clinical benefit on the ESMO-MCBS. In multivariable analysis, Breakthrough Therapy designations (OR 0.26; 95% CI, 0.10-0.75; p = 0.01) and indications for genome-targeted therapies (OR 0.26; 95% CI, 0.08-0.80; p = 0.02) were associated with lower withdrawal rates. Higher withdrawal rates were associated with low ESMO-MCBS scores (OR, 4.63; 95% CI, 1.50-14.33; p = 0.008).</p><p><strong>Interpretation: </strong>Accelerated approvals based on early data suggesting limited clinical benefit tend to have higher withdrawal rates, whereas therapies with Breakthrough Therapy designation and genome-targeted mechanisms are more likely to validate clinical benefits and achieve regular approval. Patients and healthcare providers should consider these factors when evaluating whether to use therapies granted accelerated approval.</p><p><strong>Funding: </strong>Alfonso Martín Escudero Foundation (to AT) and Arnold Ventures, the Commonwealth Fund, and Kaiser Permanente Institute for Health Policy Research (to ASK).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103088"},"PeriodicalIF":9.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674151","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":"No evidence of leukaemia (NEL) as a response criteria in paediatric AML: a multicentre analysis.","authors":"Evangelia Antoniou, Annika Puschnig, Naghmeh Niktoreh, Lina Marie Hoffmeister, Markus Schneider, Carolin Augsburg, Christel Katerkamp, Denise Kondryn, Tabea Ziedrich, Jan-Henning Klusmann, Michael Dworzak, Ursula Creutzig, Nora Mühlegger, Lux Melanie, Katharina Waack, Nils von Neuhoff, Dirk Reinhardt, Stephanie Sendker","doi":"10.1016/j.eclinm.2025.103272","DOIUrl":"10.1016/j.eclinm.2025.103272","url":null,"abstract":"<p><strong>Background: </strong>In AML, the assessment of response is one of the most important prognostic markers and is crucial for assessing clinical trials. Remission criteria for AML defined by Cheson et al. has remained virtually unchanged over the last two decades. Here we revised response criteria and provide a more precise standard for evaluating treatment outcomes in paediatric AML.</p><p><strong>Methods: </strong>A multicentre analysis of real-time data of 1094 paediatric patients diagnosed between 2004 and 2021 within the AML-BFM study group was conducted, categorising them into two alternative response groups \"evidence of leukaemia\" (EL, ≥5% blasts) and \"no evidence of leukaemia\" (NEL, <5% blasts) and comparing those with the previous CR versus no-CR classification across three different treatment timepoints.</p><p><strong>Findings: </strong>The survival of patients newly classified as NEL was comparable to that of patients with CR. The revised NEL/EL comparison showed better predictive power in terms of survival than the former CR/no-CR classification. The poorest outcome at the end of induction (EOI) was noticed in patients with EL, which could be improved by HSCT. Stratification by NEL/EL revealed the highest independent predictive effect on overall and event-free survival. The integration of measurable residual disease monitoring using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) further improved the predictive power of the revised definition.</p><p><strong>Interpretation: </strong>By simplifying the response criteria for morphological assessment of blast persistence (NEL/EL), we provide an improved and more precise definition of response for paediatric AML, which presents a new milestone with a high prognostic impact in daily clinical practice and in interpreting clinical trials.</p><p><strong>Funding: </strong>Deutsche Krebshilfe e.V., University of Duisburg-Essen.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103272"},"PeriodicalIF":9.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301371","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":"Community-based testing of migrants for infectious diseases (COMBAT-ID): observational cohort study measuring the effectiveness of routine testing for infectious diseases among migrants attending primary care.","authors":"Rebecca F Baggaley, Christopher A Martin, Helen C Eborall, Marjan Gohar, Kashif Aziz, Muhammad Fahad, George Hills, Mayur Patel, Iain Stephenson, Pranabashis Haldar, Ibrahim Abubakar, Oliver Toovey, Helena A White, William Jones, Mark Pierce, Rachna Vyas, Nilesh Sanganee, Caroline Trevithick, Chris Griffiths, Manish Pareek","doi":"10.1016/j.eclinm.2025.103253","DOIUrl":"10.1016/j.eclinm.2025.103253","url":null,"abstract":"<p><strong>Background: </strong>Migrants are at increased risk of chronic infections and have poorer outcomes, being more likely to present late. Early diagnosis and management can reduce morbidity, mortality and onward infection transmission.</p><p><strong>Methods: </strong>We evaluated the effectiveness of an integrated approach to screening migrants for exposure to tuberculosis (TB) with an interferon gamma release assay (IGRA) test, HIV, hepatitis B virus (HBV, using hepatitis B surface antigen testing) and hepatitis C virus (HCV, using antibody testing with confirmatory PCR test) infection when patients first registered with general practices (GPs) in Leicester, UK, using test yields (test positivity rates), numbers of new diagnoses and numbers linked to care.</p><p><strong>Findings: </strong>Of 4004 migrant GP patients referred for testing 2016-2019, test yields were 0.48% (17/3545, 95% CI 0.30-0.77%, HIV), 3.34% (117/3502, 95% CI 2.80-3.99%, HBV), 0.18% (6/3402, 95% CI 0.08-0.38%, HCV) and 19.38% (496/2560, 95% CI 17.89-20.95%, IGRA). Of IGRA-positive patients attending clinic, 7% (31/437) had active TB and 92% (403/437) had latent TB infection. Seventeen (55%) active TB, 397 (99%) latent TB, 71 (61%) HBV, six (35%) HIV and five (83%) HCV infections were new diagnoses. There were high rates of linkage to care for those newly diagnosed. 98% (390/397) of new latent TB patients were offered chemoprophylaxis, of whom 94% (366/390) started treatment and of these, 95% (346/366) completed the course. 100% (6/6), 97% (69/71) and 100% (5/5) of newly HIV-, HBV- and HCV-diagnosed patients attended follow-up, respectively.</p><p><strong>Interpretation: </strong>This first primary care-based combined infection testing programme for recent migrants found high test yields for latent/active TB, HBV and HIV, substantial numbers of new diagnoses for these infections and excellent linkage to care. To influence UK screening guidelines, its cost-effectiveness and acceptability to other primary care settings must be evaluated.</p><p><strong>Funding: </strong>NIHR, Gilead Sciences.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103253"},"PeriodicalIF":9.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674119","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":"Treatment-related adverse events of chimeric antigen receptor-T therapies for cancers in clinical trials: a systematic review and meta-analysis.","authors":"Youwen Zhu, Kun Liu, Steven T Rosen, Wei Liu, Hong Zhu","doi":"10.1016/j.eclinm.2025.103267","DOIUrl":"10.1016/j.eclinm.2025.103267","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chimeric antigen receptor (CAR)-T cell therapies are being tested in many ongoing trials against hematologic malignancies and solid tumors. The incidence and profile of treatment-related adverse events are necessary when moving to clinical practice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Published clinical trials on CAR-T cell therapies were collected from PubMed, Embase, Cochrane, and Web of Science databases between January 1, 2010, and August 27, 2024, with an updated search up to May 1, 2025, to extract tabular data on treatment-related adverse events. A logit-transformed random effects model was used to calculate the incidence and 95% CI of all-grade and grade 3 or higher treatment-related adverse events, with inter-study heterogeneity primarily assessed by &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; statistics. Differences between different antigen-binder, co-stimulation, cancer types, and specific subgroups were also explored in detail. The study was registered on PROSPERO (ID, CRD42024596383).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;This systematic review and meta-analysis included 163 clinical trials involving 6342 patients. Of 4395 patients from 107 trials, 4312 (98.11% [95% CI, 97.65%-98.46%], &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; = 0.0%) had at least one adverse event of all-grade, and of 4248 patients from 103 trials, 3512 (82.67% [95% CI, 81.50%-83.78%], &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; = 82.8%) had at least one adverse event of grade 3 or higher. The most common all-grade adverse events and grade 3 or higher adverse events in hematological malignancies were cytokine release syndrome (81.50% [77.04%-85.43%]) and neutropenia (72.30% [62.94%-80.39%]), respectively. The most common all-grade adverse events and grade 3 or higher adverse events in solid tumors was lymphopenia (89.21% [45.31%-99.38%] and 51.96% [8.98%-92.87%]). Ciltacabtagene autoleucel was associated with a lower mean incidence of all-grade adverse events (Risk ratio [RR], 1.00; 95% CI, 0.99-1.01; Rank-score, 0.6341; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; = 0.0%) and tisagenlecleucel were associated with lower grade 3 or higher adverse events (RR, 0.93; 95% CI, 0.86-1.02; Rank-score, 0.9738; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; = 78.4%) compared with standard care and CAR T-cell therapies. Anti-CD19 CAR-T cells were associated with a lower mean incidence of grade 3 or higher adverse events compared with anti-BCMA CAR-T cells (RR, 0.93; 95% CI, 0.87-0.99; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; = 78.4%). CAR-T cells containing 4-1BB costimulation had a lower incidence of grade 3 or higher adverse events than CAR-T cells containing CD28 costimulation (RR, 0.88; 95% CI, 0.81-0.95; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt; = 78.4%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our study provides comprehensive data on adverse events associated with different CAR-T cell treatments, maps a complete toxicity profile, and provides an important reference for clinicians to select and manage anti-cancer therapies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103267"},"PeriodicalIF":9.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-enabled prenatal ultrasound for the detection of fetal cardiac abnormalities: a systematic review and meta-analysis.","authors":"Elena D'Alberti, Olga Patey, Carolyn Smith, Bojana Šalović, Netzahualcoyotl Hernandez-Cruz, J Alison Noble, Aris T Papageorghiou","doi":"10.1016/j.eclinm.2025.103250","DOIUrl":"10.1016/j.eclinm.2025.103250","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Advances in artificial intelligence (AI) have triggered interest in using intelligent systems to improve prenatal detection of fetal congenital heart defects (CHDs). Our aim is to systematically examine the current literature on diagnostic performance of AI-enabled prenatal cardiac ultrasound.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This systematic review and meta-analysis was registered with PROSPERO (CRD42024549601). Embase, Medline, Cochrane Central Database of Controlled Trials, and CINAHL were searched from inception until February 2025. Studies evaluating AI performance in prenatal detection of fetal CHDs were eligible for inclusion, and studies focusing on the application of AI before 16 weeks of gestation, or using three- or four-dimensional ultrasound, were excluded. Pooled sensitivity and specificity were obtained using random-effect method, and pooled proportions using the Freeman-Tukey arcsine square root transformation. Heterogeneity was assessed with I&lt;sup&gt;2&lt;/sup&gt; statistics. Risk of bias and adherence to reporting standards were assessed using QUADAS-2 and TRIPOD+AI, respectively. Risk of publication bias was assessed with Deek's test and certainty of evidence for outcomes with GRADE approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Fifteen studies were included, of which fourteen developed and evaluated a model and one externally evaluated a previously trained model. Images and videos obtained during cardiac screening or fetal echocardiography of 30.121 fetuses were used for training, validation and testing. For the binary task of classifying heart as normal or abnormal, AI models achieved a pooled sensitivity of 0.89 (95% CI 0.83-0.93, I&lt;sup&gt;2&lt;/sup&gt; = 77.92%) and specificity of 0.91 (95% CI 0.84-0.95, I&lt;sup&gt;2&lt;/sup&gt; = 77.92%). The subgroup analysis showed that models tested on various CHDs exhibited lower sensitivity compared to those tested for a specific cardiac abnormality (0.85; 95% CI 0.75-0.91 vs 0.92; 95% CI 0.87-0.96), while specificity remained comparable (0.90; 95% CI 0.79-0.96 vs 0.91; 95% CI 0.81-0.97). Overall, AI models performed better than operators with lower expertise and were nearly comparable to experts; however, the human comparator group (median six clinicians, IQR 3-10) was usually small and non-blinded. Relevant sources of heterogeneity were the types of cardiac views collected, the prevalence of CHDs across different datasets, and the types of CHDs examined. The risk of bias was moderate-high and adherence to reporting standards low (&gt;70% in 18/51 TRIPOD+AI items). The risk of publication bias was not statistically significant (Deek's test p = 0.474).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;These findings suggest that AI models perform better than clinicians with lower expertise, but this must be interpreted with caution due to the high risk of bias and sources of heterogeneity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This study was partly supported by the InnoHK-funded Hong Kong Centre for Cerebro","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103250"},"PeriodicalIF":9.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674118","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":"Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysis.","authors":"Kevin Komakech, Derrick Semugenze, Moses Joloba, Frank Cobelens, Willy Ssengooba","doi":"10.1016/j.eclinm.2025.103257","DOIUrl":"10.1016/j.eclinm.2025.103257","url":null,"abstract":"<p><strong>Background: </strong>Limited access to accurate and accessible tuberculosis (TB) diagnostics remains a critical barrier to timely diagnosis and care in high burden low- and middle-income countries. Point-of-care (POC) TB Triage tests (POC-TTTs) defined as a test performed near to a patient or at the site of patient care without need for specialized expertise or infrastructure, may bridge this gap. We systematically reviewed and meta-analyzed studies on host blood protein biomarkers for POC-TTTs including C-reactive protein (CRP), 3-gene host response (3-gene HR), monocyte-to-lymphocyte ratio (MLR), interferon-γ induced protein 10 (IP-10), hemoglobin, neutrophil-to-lymphocyte ratio (NLR), tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) for their accuracy for screening of pulmonary TB (PTB).</p><p><strong>Methods: </strong>A literature search was conducted in PubMed, EMBASE and in Web of Science from 1990 to 31st January 2025. The review included studies that used unstimulated blood of presumptive TB patients who were screened with a POC device to quantify biomarkers for PTB diagnosis. Sputum mycobacterial culture or GeneXpert MTB/Rif or Ultra were used as a reference standard. Risk of bias was assessed using QUADAS-2 tool. Random effect analysis was performed using the Hartung-Knapp-Sidik-Jonkman (HKSJ) method to calculate summary estimates with their 95% confidence intervals (CI). Heterogeneity was tested and quantified using Cochran's Q and Higgin's I² test. Egger's linear regression test was used to assess small study effect. The systematic review protocol was registered in PROSPERO with an ID of CRD42023483281.</p><p><strong>Findings: </strong>We identified 282, 21, 28, 137, 132, 152, 100 and 77 studies from which 10, 6, 4, 2, 0, 0, 0 and 1 study(s) were included for CRP, 3-gene HR, MLR, hemoglobin, IP-10, TNF-a, IL-6 and NLR index tests respectively. The meta-analysis pooled sensitivity (95% CI) was 74% (58-85), 79% (59-90), 64% (15-95), 75% (18-98) and the pooled specificity was 68% (52-80), 85% (68-94), 69% (30-92) and 71% (18-100) for CRP, 3-gene HR, MLR, and hemoglobin respectively. Diagnostic odds ratios ranged from 3.70 (MLR) to 20.93 (3-gene HR) while higgin's I² value ranged from 87.4% (MLR) to 99.1% (hemoglobin). Meta-analysis was not performed on NLR.</p><p><strong>Interpretation: </strong>None of the POC-TTT met the WHO target product profile minimum requirements for a TB triage test of 90% sensitivity and 70% specificity when a POC device was used for screening in a typical setting studied. Further research, specifically focusing on head-to-head comparisons and combination tests are recommended.</p><p><strong>Funding: </strong>Funding was received from the Mr. Willem Bakhuys Roozeboom Foundation. Additional support was given to KK through the EDCTP grant RIA2020I-3305.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103257"},"PeriodicalIF":9.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301368","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":"Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis.","authors":"Jacob Brain, Maha Alshahrani, Aysegul Humeyra Kafadar, Eugene Yh Tang, Elissa Burton, Leanne Greene, Deborah Turnbull, Bronwyn Myers, Aliya Naheed, Mario Siervo, Phillip J Tully, Blossom Cm Stephan","doi":"10.1016/j.eclinm.2025.103266","DOIUrl":"10.1016/j.eclinm.2025.103266","url":null,"abstract":"<p><strong>Background: </strong>Identifying modifiable risk factors is crucial for dementia prevention, a global health concern. Depression is considered a risk factor for dementia, but the temporal dynamics across the life course remain inconclusive. Therefore, we aimed to systematically assess the relationship between the timing of depression assessment and risk of all-cause late-life dementia.</p><p><strong>Methods: </strong>We conducted an umbrella review and meta-analysis to assess incident dementia in individuals with non-current history of depression. PubMed and Ovid Embase, MEDLINE, and PsycInfo were searched from inception up to February 17, 2025. Systematic reviews with meta-analyses investigating the association between depression and incident late-life dementia were included. From eligible reviews, we also extracted data from studies reporting dementia risk as hazard ratios (HRs), analysing the timing of depression measurement using random-effects models for meta-analysis. This study is registered with PROSPERO, CRD42021249706.</p><p><strong>Findings: </strong>Of the 7763 records identified, nine reviews were eligible for inclusion of the umbrella review. One review was judged to be of moderate quality, while the others were either low (<i>n</i> = 3) or critically low (<i>n</i> = 5). For our meta-analyses, 18 studies reporting depression onset in later life (<i>n</i> = 901,762 participants, <i>n</i> = 7595 incident dementia cases) and seven studies on depression assessed during midlife (<i>n</i> ≥ 2,501,269 participants, <i>n</i> ≥ 276,929 incident dementia cases) were included. All studies in the meta-analyses were deemed to be of good quality, with no strong evidence of publication bias. Pooled HRs indicated depression present in late-life (HR 1.95, 95% CI: 1.68-2.26; <i>I</i> ^<i>2</i> = 77.5%) and midlife (HR 1.56, 95% CI: 1.12-2.18; <i>I</i> ^<i>2</i> = 97.5%) significantly increased risk of all-cause dementia.</p><p><strong>Interpretation: </strong>The findings suggest that depression across the life course may increase dementia risk; however, substantial heterogeneity and review quality should be considered when interpreting the strength of this evidence. A life course approach to the treatment and prevention of depression may help reduce the burden of dementia, but this will require scaling up access to effective mental health care for vulnerable populations. Further research is needed to clarify if the stronger late-life association reflects depression as an immediate risk factor or an early manifestation of neurodegenerative processes.</p><p><strong>Funding: </strong>National Institute for Health and Care Research, UK Research and Innovation, and Saudi Arabian Cultural Mission.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103266"},"PeriodicalIF":9.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674152","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":"Polycystic ovary syndrome perspectives from patients and health professionals on clinical features, current name, and renaming: a longitudinal international online survey.","authors":"Helena J Teede, Lisa J Moran, Rachel Morman, Melanie Gibson, Anuja Dokras, Lorna Berry, Joop S E Laven, Anju Joham, Terhi T Piltonen, Michael F Costello, Robert J Norman, Mahnaz Bahri Khomami","doi":"10.1016/j.eclinm.2025.103287","DOIUrl":"10.1016/j.eclinm.2025.103287","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) has diverse features. However, the name reflects only ovarian aspects, overlooking broader features. This study aimed to investigate international stakeholder perspectives on PCOS.</p><p><strong>Methods: </strong>We conducted international longitudinal anonymous online surveys and face-to-face workshops with individuals with PCOS and health professionals between 2015 and 2023, across six continents, seeking perspectives on clinical features of PCOS, the current name, the potential for renaming, the advantages and disadvantages of a name change, and possible alternative names.</p><p><strong>Findings: </strong>Results from 7708 survey respondents in 2015 and post publication of international guidelines in 2023, significantly improved recognition of the reproductive, cardiometabolic, hormonal, and psychological features of PCOS (p < 0·001). However, gaps remain, with ≥20% of patients and/or health professionals not recognising associations between PCOS and non-alcoholic fatty liver disease, pregnancy complications, cardiovascular risk factors, and endometrial cancer. Aligned to the breadth of PCOS, in the 2023 survey, a potential name change was explored with 85·6% of patients and 76·1% of health professionals agreeing that the name should be changed. Both groups agreed that a name change presents advantages with 59-90% agreeing with advantages and fewer than 27% agreeing with disadvantages. Terms such as 'endocrine' and 'metabolic' received the highest support in 2015 and 2023 for inclusion in a new name among both patients (78·5 and 86·2%) and health professionals (84·6 and 79·6%). Overall, 84% committed to a consensus-driven name change process on voting at a 2023 workshop.</p><p><strong>Interpretation: </strong>Widespread international engagement in 2015 showed major knowledge gaps on broad PCOS features, with follow-up in 2023 showing significant improvement after two international guidelines, widespread dissemination and advocacy group outreach. Stakeholders highlighted that the current name does not adequately reflect broad PCOS features and is confusing. They endorsed a name change, with perceived advantages outweighing potential disadvantages. This culminated in a commitment to a global consensus process to determine and implement a new name, alongside extensive education efforts, both of which are now underway.</p><p><strong>Funding: </strong>The Australian National Health and Medical Research Council (NHMRC) funded Centre for Research Excellence in Women's Health in Reproductive Life (CRE-WHiRL) [APP#1171592].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103287"},"PeriodicalIF":9.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674150","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":"Measure selection for an electronic patient-reported outcome (ePRO) system for CAR T-cell therapy patients: a modified Delphi consensus study.","authors":"Sarah E Hughes, Foram Khatsuria, Christel McMullan, Karen L Shaw, Anita Walker, Francesca Kinsella, David Burns, Olalekan L Aiyegbusi, Elin Haf Davies, John Ansell, Evelyn Chakera, Charles Craddock, Alastair Denniston, Rebecca Lloyd, Paul Ferguson, Ronjon Chakraverty, Melanie Calvert","doi":"10.1016/j.eclinm.2025.103256","DOIUrl":"10.1016/j.eclinm.2025.103256","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chimeric Antigen Receptor (CAR) T-cell therapies are effective for treating haematological cancers but carry risks of toxicity and substantial symptom burden. Patient-reported outcomes (PROs) could significantly enhance clinical management for patients undergoing these treatments. However, guidance on selection of PRO measures for monitoring adverse event and quality of life after CAR T-cell therapy is limited. This study aimed to achieve consensus among patients and healthcare professionals on the selection of PRO measures for an electronic PRO (ePRO) system for CAR T-cell therapy clinical settings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Two-round modified Delphi study (online survey and consensus meeting) conducted from December 2023 to January 2024 to select PRO measures for the ePRO system, guided by a conceptual framework with four measurement domains: symptom burden, impacts of cancer and CAR T-cell therapy, treatment tolerability, and health-related quality of life (HRQoL). Database searches (PubMed, ePROVIDE, COSMIN, and COMET) and licensing websites of cancer-specific PRO measures identified 113 PRO measures. Measures were pre-specified for treatment tolerability and HRQoL domains and concept mapping established conceptual coverage for the remaining domains. Seven PRO measures were shortlisted and prespecified inclusion thresholds and stopping criteria guided Delphi panel selection. Registration: ISRCTN11232653.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Nineteen participants (5 CAR T-cell patients, 14 healthcare professionals/researchers) recruited from a UK National Health Service (NHS) cellular therapy centre and professional networks took part in Round One (Delphi online survey). Shortlisted measures were rated for relevance, comprehensiveness, and ease of understanding for the symptom burden and impacts of cancer and CAR T-cell treatment domains. Consensus was achieved after Round One, precluding the requirement for Round 2 (consensus meeting). The Symptom Burden Questionnaire™ (SBQ™) and the Quality of Life in Adult Cancer Survivors (QLACS) were selected to represent the Symptom Burden and Impacts domains, respectively. These measures, EQ5D-5L, measuring HRQoL, and Functional Assessment of Chronic Illness Therapy-Item GP5 (FACT-GP5), single-item global indicator of cancer treatment tolerability, will be included in the ePRO system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In the absence of guidance on PRO measure selection for CAR T-cell therapies, consensus-based methods represent an important step towards use of PROs with this clinical population. Modest sample size and representativeness of the patient subgroup are limitations of this study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;This study is funded by the National Institute for Health and Care Research (NIHR) Blood and Transplant Research Unit in Precision Cellular Therapeutics (NIHR203339). The views expressed are those of the authors and not necessarily those of the NI","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103256"},"PeriodicalIF":9.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282994","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":"Interventions to improve adherence to lipid-lowering drugs: a systematic review and meta-analysis.","authors":"Deborah Keng Wai Yow, Wei Jie Ang, Hao Jeun Yap, Sakura Ito, Jintana Liu, Junsuk Ko, Doreen Su-Yin Tan, Alberto Lorenzatti, Chin-Siang Ang","doi":"10.1016/j.eclinm.2025.103270","DOIUrl":"10.1016/j.eclinm.2025.103270","url":null,"abstract":"<p><strong>Background: </strong>Poor medication adherence to lipid-lowering medications (LLMs) remains a barrier in reducing the burden of cardiovascular disease (CVD). We sought to review interventions aimed at improving adherence to LLMs for the primary or secondary prevention of CVD, and evaluate their effectiveness on patient outcomes.</p><p><strong>Methods: </strong>A systematic review and meta-analysis was performed according to PRISMA guidelines. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, and CINAHL, were searched for studies published between January 1, 2016 and October 3, 2024, reporting randomised controlled trials on interventions to enhance adherence to LLMs. Cochrane's Risk-of-Bias (ROB-2) tool was utilised for quality appraisal. A narrative analysis and a random-effects meta-analysis was conducted, with adherence to LLMs as main outcomes. Pooled effects were calculated using Standardised Mean Difference (SMD) or Odds Ratios (OR). The review's protocol is available on Open Science Framework (https://osf.io/9gx5h).</p><p><strong>Findings: </strong>The systematic review and meta-analysis included 35 and 15 studies, respectively. Participants (n = 51,824) had a mean age ranging 50.2-74.4 years. 6 distinct interventions were employed; most were conducted in primary care settings and employed intensified patient care. Overall, interventions assessed with continuous (SMD 0.17, 95% CI [0.04, 0.31]) and dichotomous (OR 1.26, 95% CI [1.08, 1.47]) measures showed improvements in adherence. Participants who engaged in complex behavioural approaches exhibited improved adherence in dichotomous (OR 1.74, 95% CI [1.17, 2.58]) and continuous outcomes (SMD 0.35, 95% CI [0.15, 0.54]). Pooled estimates suggest no differences in physiological outcomes between the groups. A risk-of-bias assessment following worst-case scenario analysis assessed 3 studies as \"low risk\", 11 as \"high risk\", and 21 as \"unclear risk\".</p><p><strong>Interpretation: </strong>Current interventions bring about improvements in medication adherence, but such improvements are not sustained over the long-term. For real world and practice implications, interventions must be multipronged in nature, addressing a combination of at least two dimensions of medication adherence. Additional global studies, particularly long-term randomised controlled trials, are required to corroborate our findings.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"84 ","pages":"103270"},"PeriodicalIF":9.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274372","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}