EClinicalMedicine最新文献

{"title":"Effect of automated insulin delivery systems on person-reported outcomes in people with diabetes: a systematic review and meta-analysis.","authors":"Timm Roos, Norbert Hermanns, Christopher Groß, Bernhard Kulzer, Thomas Haak, Dominic Ehrmann","doi":"10.1016/j.eclinm.2024.102852","DOIUrl":"10.1016/j.eclinm.2024.102852","url":null,"abstract":"<p><strong>Background: </strong>Conclusive evidence on the benefits of automated insulin delivery (AID) systems on person-reported outcomes (PROs) is missing.</p><p><strong>Methods: </strong>In this systematic review and meta-analysis, four databases (PubMed, PsycINFO, Cochrane, and GoogleScholar) were searched from inception up to August 7th, 2024. All types of studies were included if studies reported on PROs in people with diabetes using an AID system. All types of control groups in randomised controlled trials (RCT) were included. Summary data were extracted by three reviewers. Main outcomes focused on diabetes distress, fear of hypoglycaemia and quality of life. Meta-analyses were conducted for RCTs and observational studies separately. When five or more studies could be pooled, random-effects meta-analysis was used, otherwise common-effects meta-analysis was used. Risk of bias was evaluated with Cochrane tools. This study was registered with PROSPERO, CRD42022352502.</p><p><strong>Findings: </strong>A total of 62 studies (n = 9253) were included reporting on 45 different questionnaires. Twenty-seven studies were RCTs and 25 were observational studies. RCT meta-analyses showed reduced diabetes distress (standardised mean difference [95% CI]: -0.159 [-0.309, -0.010], I² = 23.0%), reduced fear of hypoglycaemia (-0.339 [-0.566, -0.111], I² = 42.6%), and improved hypoglycaemia unawareness (-0.231 [-0.424, -0.037], I² = 0.0%), quality of life in adults (0.347 [0.134, 0.560], I² = 0.0%) and children/adolescents (0.249 [0.050, 0.448], I² = 0.0%). Observational meta-analyses corroborated improvements in diabetes distress (-0.217 [-0.403, -0.031], I² = 68.5%), fear of hypoglycaemia (-0.445 [-0.540, -0.349], I² = 0.0%), hypoglycaemia unawareness (-0.212 [-0.419, -0.004], I² = 0.0%), and showed improved sleep quality (-0.158 [-0.255, -0.061], I² = 0.0%).</p><p><strong>Interpretation: </strong>We found low to moderate effect sizes indicating that AID therapy is associated with reduced burden and improved well-being in people with diabetes. Evidence comes from both RCTs and observational studies. However, for some PROs only a limited number of studies could be pooled with a large heterogeneity in questionnaires used. More research is needed with a more uniformed assessment of PROs to demonstrate the added value of AID therapy on psychosocial outcomes.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102852"},"PeriodicalIF":9.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371311","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":"Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial.","authors":"Min Yan, Quchang Ouyang, Tao Sun, Limin Niu, Jin Yang, Li Li, Yuhua Song, Chunfang Hao, Zhanhong Chen, Zhenzhen Liu, Huimin Lv, Mengwei Zhang, Liping Liu, Xiaohong Yang, Huawu Xiao, Zhichao Gao, Xiaorui Li, Fangyuan Dong, Lingxiao Zhang, Danfeng Dong, Xiuchun Chen, Jianghua Qiao, Guifang Zhang, Huiai Zeng, Jing Wang, Huihui Sun, Yajing Feng, Yuting Chen, Fangzhou Xia","doi":"10.1016/j.eclinm.2024.102837","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102837","url":null,"abstract":"<p><strong>Background: </strong>The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up.</p><p><strong>Methods: </strong>Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m² twice daily on days 1-14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051).</p><p><strong>Findings: </strong>As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1-39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6-14.6) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6-33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0-15.8) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy.</p><p><strong>Interpretation: </strong>These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases.</p><p><strong>Funding: </strong>National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102837"},"PeriodicalIF":9.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388874","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":"Comparative efficacy, safety and benefit/risk of alerting agents for excessive daytime sleepiness in patients with obstructive sleep apnoea: a network meta-analysis.","authors":"Jean-Louis Pépin, Philippe Lehert, Raoua Ben Messaoud, Marie Joyeux-Faure, Christian Caussé, Jerryll Asin, Ferran Barbé, Maria R Bonsignore, Winfried Randerath, Johan Verbraecken, Sonya Craig, Yves Dauvilliers","doi":"10.1016/j.eclinm.2024.102843","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102843","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA.</p><p><strong>Methods: </strong>In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640.</p><p><strong>Findings: </strong>Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150 mg; effect size [ES] = 0.66 [95% CI: 0.36, 0.96]), pitolisant (20 mg; ES = 0.66 [95% CI: 0.44, 0.88]), and modafinil (200 mg; ES = 0.54: [95% CI: 0.33, 0.74]); 400 mg; ES = 0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200 mg, modafinil 400 mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400 mg and modafinil 200 mg for benefit-risk ratio.</p><p><strong>Interpretation: </strong>Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities.</p><p><strong>Funding: </strong>Bioprojet.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102843"},"PeriodicalIF":9.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343754","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":"Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI.","authors":"D J Spaanderman, S N Hakkesteegt, D F Hanff, A R W Schut, L M Schiphouwer, M Vos, C Messiou, S J Doran, R L Jones, A J Hayes, L Nardo, Y G Abdelhafez, A W Moawad, K M Elsayes, S Lee, T M Link, W J Niessen, G J L H van Leenders, J J Visser, S Klein, D J Grünhagen, C Verhoef, M P A Starmans","doi":"10.1016/j.eclinm.2024.102802","DOIUrl":"10.1016/j.eclinm.2024.102802","url":null,"abstract":"<p><strong>Background: </strong>As differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility.</p><p><strong>Methods: </strong>Three study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists.</p><p><strong>Findings: </strong>The validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85).</p><p><strong>Interpretation: </strong>The radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics.</p><p><strong>Funding: </strong>Hanarth fonds.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102802"},"PeriodicalIF":9.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of the Florey Dementia Risk Score web-based tool to screen for Alzheimer's disease in primary care.","authors":"Yijun Pan, Chenyin Chu, Yifei Wang, Yihan Wang, Guangyan Ji, Colin L Masters, Benjamin Goudey, Liang Jin","doi":"10.1016/j.eclinm.2024.102834","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102834","url":null,"abstract":"<p><strong>Background: </strong>It is estimated that ∼60% of people with Alzheimer's disease (AD) are undetected or undiagnosed, with higher rates of underdiagnosis in low-to middle-income areas with limited medical resources. To promote health equity, we have developed a web-based tool that utilizes easy-to-collect clinical data to enhance AD detection rate in primary care settings.</p><p><strong>Methods: </strong>This study was leveraged on the data collected from participants of the Australian Imaging, Biomarker & Lifestyle (AIBL) study and the Religious Orders Study and Memory and Aging Project (ROSMAP). The study included three phases: (1) constructing and evaluating a model on retrospective cohort data (1407 AIBL participants), (2) performing simulated trials to assess model accuracy (30 AIBL participants) and missing data tolerability (30 AIBL participants), and (3) external evaluation using a non-Australian dataset (500 ROSMAP participants). The auto-score machine learning algorithm was employed to develop the Florey Dementia Risk Score (FDRS). All the simulated trials and evaluation were performed using a web-based FDRS tool.</p><p><strong>Findings: </strong>FDRS achieved an area under the curve (AUC) of approximately 0.82 [95% CI, 0.75-0.88], with a sensitivity of 0.74 [0.60-0.86] and a specificity of 0.73 [0.70-0.79]. The accuracy of the simulated pilot trial for 30 AIBL participants with complete record was 87% (26/30 correct), while it only slightly decreased (80.0-83.3%, depending on imputation methods) for another 30 AIBL participants with one or two missing data. FDRS achieved an AUC of 0.82 [0.77-0.86] of 500 ROSMAP participants.</p><p><strong>Interpretation: </strong>The FDRS tool offers a potential low-cost solution to AD screening in primary care. The present study warrants future trials of FDRS for optimization and to confirm its generalizability across a more diverse population, especially people in low-income countries.</p><p><strong>Funding: </strong>National Health and Medical Research Council, Australia (GNT2007912) and Alzheimer's Association, USA (23AARF-1020292).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102834"},"PeriodicalIF":9.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343756","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 therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial.","authors":"Alexander Zarbock, Tobias E Larsson, Nicolas Noiseux, C David Mazer, Johannes Böhm, Maxime Laflamme, Klaus Matschke, Jan Burkert, Benoit de Varennes, Andrej Myjavec, Andreas Böning, Jay L Koyner, Dan Engelman, Michael Reusch, Matthias Thielmann","doi":"10.1016/j.eclinm.2024.102830","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102830","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65 mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] &lt;30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72 h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n = 45) and 39.8% (n = 35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p = 0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, 90% CI 0.51-8.12, p = 0.06; and MAKE 6.7% (n = 6) vs 15.9% (n = 14); RR: 0.41, 90% CI: 0.19, 0.88, p = 0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In this proof-of-concept study, RMC-035 did not reduce AKI 72 h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results m","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102830"},"PeriodicalIF":9.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343758","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":"Associations of socioeconomic status and healthy lifestyle with incident dementia and cognitive decline: two prospective cohort studies.","authors":"Kan Wang, Yuan Fang, Ruizhi Zheng, Xuan Zhao, Siyu Wang, Jieli Lu, Weiqing Wang, Guang Ning, Yu Xu, Yufang Bi","doi":"10.1016/j.eclinm.2024.102831","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102831","url":null,"abstract":"<p><strong>Background: </strong>Little is known about the complex associations of socioeconomic status (SES) and healthy lifestyle with cognitive dysfunction.</p><p><strong>Methods: </strong>Using data from the Health and Retirement Study (HRS) [2008-2020] and the English Longitudinal Study of Ageing (ELSA) [2004-2018], SES was constructed by latent class analysis using education level, total household income and wealth. Overall healthy lifestyle was derived using information on never smoking, low to moderate alcohol consumption (drinks/day: (0, 1] for women and (0, 2] for men), top tertile of physical activity, and active social contact.</p><p><strong>Findings: </strong>A total of 12,437 and 6565 participants from the HRS and ELSA were included (40.8% and 46.0% men and mean age 69.3 years and 65.1 years, respectively). Compared with participants of high SES, those of low SES had higher risk of incident dementia (hazard ratio 3.17, 95% confidence interval 2.72-3.69 in the HRS; 1.43, 1.09-1.86 in the ELSA), and the proportions mediated by overall lifestyle were 10.4% (7.3%-14.6%) and 2.7% (0.5%-14.0%), respectively. Compared with participants of high SES and favorable lifestyle, those with low SES and unfavorable lifestyle had a higher risk of incident dementia (4.27, 3.40-5.38 in the HRS; 2.02, 1.25-3.27 in the ELSA) and accelerated rate of global cognitive decline (<i>β</i> = -0.058 SD/year; 95% CI: -0.073, -0.043 in the HRS; <i>β</i> = -0.049 SD/year; 95% CI: -0.063, -0.035 in the ELSA).</p><p><strong>Interpretation: </strong>Unhealthy lifestyle only mediated a small proportion of the socioeconomic inequality in dementia risk in both US and UK older adults.</p><p><strong>Funding: </strong>This work was supported by grants from the National Natural Science Foundation of China (82088102 and 82370819), the National Key R&D Program of China (2023YFC2506700), the Shanghai Municipal Government (22Y31900300), the Shanghai Clinical Research Center for Metabolic Diseases (19MC1910100), the Innovative Research Team of High-Level Local Universities in Shanghai, the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission (202340084), and Ruijin Hospital Youth Incubation Project (KY20240805). Y.X. is supported by the National Top Young Talents program.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102831"},"PeriodicalIF":9.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343753","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":"Comparing approaches for chemoprevention for school-based malaria control in Malawi: an open label, randomized, controlled clinical trial.","authors":"Alick Sixpence, Maclean Vokhiwa, Wangisani Kumalakwaanthu, Nicola J Pitchford, Karl B Seydel, Laurence S Magder, Miriam K Laufer, Don P Mathanga, Lauren M Cohee","doi":"10.1016/j.eclinm.2024.102832","DOIUrl":"10.1016/j.eclinm.2024.102832","url":null,"abstract":"<p><strong>Background: </strong>School-age children in sub-Saharan Africa suffer an underappreciated burden of malaria which threatens their health and education. To address this problem, we compared the efficacy of two school-based chemoprevention approaches: giving all students intermittent preventive treatment (IPT) or screening and treating only students with detected infections (IST).</p><p><strong>Methods: </strong>In a three-arm, open-label, randomized, controlled trial (NCT05244954) in Malawi, 746 primary school students, aged 5-19 years, were individually randomized within each grade-level to IPT (n = 249), IST with a high-sensitivity rapid diagnostic test (hs-RDT, n = 248), or control (n = 249). At six-week intervals three times within the peak malaria transmission season (February-June 2022) treatment with dihydroartemisinin-piperaquine (DP) was administered to girls <10 years and all boys, and chloroquine to older girls. The primary outcome was <i>Plasmodium falciparum</i> (<i>Pf)</i> infection detected by PCR 6-8 weeks after the final intervention. Secondary outcomes included anaemia, clinical malaria, and scores on tests of attention, literacy, and math. Analysis was by modified intention-to-treat.</p><p><strong>Findings: </strong>Outcomes analyses included 727 (97%) participants. At the end of the study, prevalence of <i>Pf</i> infection was 17% (41/243) in the IPT arm, 24% (58/244) in the IST arm, and 53% (127/240) in the control arm. Compared to controls, IPT and IST reduced the odds of <i>Pf</i> infection (IPT adjusted odds ratio [aOR]: 0.18 (95% CI: 0.11, 0.27); p < 0.0001; IST aOR: 0.27 (95% CI: 0.18, 0.40); p < 0.0001). However, only participants receiving IPT had a lower incidence of clinical malaria (0.19 cases per person per six months (95% CI: 0.14, 0.27) vs 0.56 (95% CI: 0.46, 0.68); incidence rate ratio: 0.38 (95% CI: 0.26, 0.55); p < 0.0001)) and prevalence of anaemia (8% [20/243] vs 15% [36/240]; aOR: 0.49 (95% CI: 0.27, 0.91); p = 0.023) compared to controls. Literacy scores were higher in both intervention arms. No between group differences in tests of attention or math or number of serious adverse events were found.</p><p><strong>Interpretation: </strong>Results support implementation of IST with hs-RDTs or IPT for reduction in the prevalence of infection. Based on reductions in clinical malaria, IPT may provide additional benefits warranting further consideration by school-based malaria chemoprevention programs.</p><p><strong>Funding: </strong>Doris Duke Charitable Foundation Clinical Scientist Development Award 2021191, U.S. NIH K24AI114996 & K23AI135076.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102832"},"PeriodicalIF":9.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343755","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":"Early, medium and long-term mental health in cancer survivors compared with cancer-free comparators: matched cohort study using linked UK electronic health records.","authors":"Harriet Forbes, Helena Carreira, Garth Funston, Kirsty Andresen, Urvita Bhatia, Helen Strongman, Esha Abrol, Liza Bowen, Ceinwen Giles, Krishnan Bhaskaran","doi":"10.1016/j.eclinm.2024.102826","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102826","url":null,"abstract":"<p><strong>Background: </strong>We aimed to compare the risk of incident depression, anxiety, non-fatal self-harm and completed suicide in survivors from a wide range of cancers versus cancer-free individuals.</p><p><strong>Methods: </strong>We used electronic health records from the United Kingdom Clinical Practice Research Datalink linked to cancer registry data, hospital admissions data and death records between 1998 and 2021. Adult survivors of the 20 most common cancers were matched (age, sex, general practice) 1:10 to cancer-free individuals. Cox regression models, adjusted for shared risk factors, were used to estimate associations between cancer survivorship and mental health outcomes.</p><p><strong>Findings: </strong>853,177 adults with cancer diagnosed in 1998-2018 were matched to 8,106,643 cancer-free individuals. Survivors of all 20 cancer types under study had a higher risk of experiencing a new episode of anxiety and depression during follow-up compared with cancer-free individuals; there was also evidence of raised risks of non-fatal self-harm in 17/20 cancers and completed suicide in 8/20 cancers. Effect sizes were greatest in cancers with poorer 5-year survival: hazard ratios (HRs) for anxiety and depression of 1.1-1.2 were seen for malignant melanoma survivors, while HRs for both outcomes were >2.5 for lung and oesophageal cancer survivors. HRs were highest in the first year from cancer diagnosis, reducing over time since diagnosis. However, 5-year cancer survivors still experienced elevated risks of a subsequent new episode of anxiety or depression, in 18/20 cancers.</p><p><strong>Interpretation: </strong>Survivors of the 20 most common cancers were at increased risk of experiencing depression and anxiety, and these increased risks persisted in medium-to long-term cancer survivors. Substantially raised risks of non-fatal self-harm and completed suicide were also seen for several types of cancer. The risks of all mental health outcomes were generally higher in survivors of cancers with poorer prognosis. Our findings suggest a need for improved psychological support for all patients with cancer.</p><p><strong>Funding: </strong>Wellcome Trust.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102826"},"PeriodicalIF":9.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and procedural success of daycase-based endovascular procedures in lower extremity arteries of patients with peripheral artery disease: a systematic review and meta-analysis.","authors":"Lydia Hanna, Alexander D Rodway, Puneet Garcha, Luci Maynard, Janane Sivayogi, Oliver Schlager, Juraj Madaric, Vinko Boc, Lucas Busch, Martin B Whyte, Simon S Skene, Jenny Harris, Christian Heiss","doi":"10.1016/j.eclinm.2024.102788","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102788","url":null,"abstract":"<p><strong>Background: </strong>Timely and economic provision of revascularisation procedures is a major healthcare need. We aimed to examine the safety and efficacy of daycase-based lower extremity endovascular revascularisation procedures in patients with peripheral artery disease.</p><p><strong>Methods: </strong>In this systematic review and meta-analysis, we searched MEDLINE and Embase for studies from Jan 01, 2000 through Apr 01, 2024 reporting complications of lower limb endovascular revascularisation procedures with same-day discharge. Eligibility-criteria, complications, and patient characteristics were extracted, methodological quality assessed (adapted Newcastle-Ottawa Scale), and meta-analyses of complications and technical success performed to provide pooled estimates. This study is registered with PROSPERO, CRD42022316466.</p><p><strong>Findings: </strong>Thirty observational studies (17 retrospective, 13 prospective) and 1 RCT reported 2427 minor and 653 major complications after 99,600 daycase procedures (93,344 patients). Eighteen studies reported daycase eligibility-criteria including 'responsible adult companion' (78%), 'proximity to hospital', and 'telephone availability' and excluding unstable and severe co-morbidities, offset coagulation, and severe chronic kidney disease. Pooled incidences of minor (4.7% [95% CI 3.8-5.6%], <i>I</i> ² = 96%) and major (0.64% [95% CI 0.48-0.79%], <i>I</i> ^<i>2</i>  = 46%) complications were low and technical success high (93% [95% CI 91-96%], <i>I</i> ² = 97%). Most complications were related to the puncture site. Pooled conversion-to-hospitalisation rates and re-admission after discharge were 1.6% (95% CI 1.1-2.2%, <i>I</i> ² = 82%) and 0.11% (95% CI 0.095-0.23%, <i>I</i> ² = 97%), respectively. Meta-regression identified that minor complications decreased since 2000. Male sex and coronary artery disease were associated with more frequent, and higher age and closure device use with less minor complications. Diabetes mellitus and chronic kidney disease were associated with less major complications. Six studies reported complication rates both in daycases and inpatients and there was no significant difference (-0.8% [95% CI -1.9 to 0.3%]).</p><p><strong>Interpretation: </strong>After careful evaluation of eligibility, lower limb angioplasty can be performed safely with high technical success in a daycase setting. Most complications arise from the puncture site and not the procedure itself highlighting the importance of optimal access site management. The heterogeneity between studies warrants standardised monitoring of complications and outcomes.</p><p><strong>Funding: </strong>European Partnership on Metrology, co-financed from European Union's Horizon Europe Research and Innovation Programme and UK Research and Innovation, and Medical Research Council.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102788"},"PeriodicalIF":9.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282095","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}