EClinicalMedicine最新文献

{"title":"Safety, reactogenicity, and immunogenicity of Ad26.COV2.S co-administered with a quadrivalent standard-dose or high-dose seasonal influenza vaccine: a non-inferiority randomised controlled trial.","authors":"Gabriela Tapia-Calle, Gloria Aguilar, Nathalie Vaissiere, Carla Truyers, Pedro Ylisastigui, Erik Buntinx, Mathieu Le Gars, Frank Struyf, Gert Scheper, Macaya Douoguih, Javier Ruiz-Guiñazú","doi":"10.1016/j.eclinm.2024.103016","DOIUrl":"10.1016/j.eclinm.2024.103016","url":null,"abstract":"<p><strong>Background: </strong>Vaccine co-administration can increase vaccination coverage. We assessed the safety, reactogenicity, and immunogenicity of concomitant administration of Ad26.COV2.S COVID-19 vaccine with seasonal influenza vaccines.</p><p><strong>Methods: </strong>This non-inferiority, Phase 3, randomised, double-blind study enrolled 859 healthy adults and was conducted between 02 November 2021 and 28 November 2022. Participants aged ≥18-64 years were randomised to receive a seasonal quadrivalent standard dose (SD) influenza vaccine (<i>Afluria</i> Quadrivalent, Seqirus) concomitantly with Ad26.COV2.S (Coad_SD) or placebo (0.9% NaCl; Control_SD) on Day 1 and placebo or Ad26.COV2.S on Day 29. Participants aged ≥65-years were randomised to the Coad_SD or Control_SD groups, or to Coad_HD or Control_HD groups that received a seasonal quadrivalent HD (high-dose) influenza vaccine (<i>Fluzone</i> High-Dose Quadrivalent, Sanofi Pasteur Inc) in the same schedules. The primary outcomes were haemagglutinin inhibition titres against the four influenza vaccine strains at Day 29, and SARS-CoV-2 Spike-specific antibodies at Day 29 in the Coad_SD group and Day 57 in the Control-SD group, with a non-inferiority margin (Control-SD group/Coad_SD group) of 1.5. Reactogenicity and safety were assessed in all participants (NCT05091307).</p><p><strong>Findings: </strong>Non-inferiority criteria for concomitant administration in the SD groups were met for SARS-CoV-2 Spike-specific antibodies (ratio 1.11, 95% CI 0.97-1.26) and haemagglutinin inhibition titres for all influenza strains (A/H3N2 1.23, 95% CI 1.05-1.45; B/Victoria 0.99, 95% CI 0.84-1.19; B/Yamagata, 1.03, 95% CI 0.88-1.21) except A/H1N1 (1.28, 95% CI 1.09-1.53) for which the upper limit of the 95% CI was >1.5. Concomitant administration of Ad26.COV2.S and SD influenza vaccine induced robust immune responses in terms of SARS-CoV-2 Spike-specific antibodies and haemagglutinin inhibition to all four influenza strains. Seroconversion and seroprotection rates against all influenza vaccine strains were comparable in the Coad and Control groups. Anti-Spike antibodies 28 days after receiving Ad26.COV2.S were similar whether administered with influenza vaccine or alone. Antibody responses persisted at least 6 months post-vaccination in all groups. The reactogenicity and safety profile following co-administration was consistent with the known safety profiles of the study vaccines. No safety concerns were identified. Coadministration was immunogenic and well tolerated in adults aged ≥65 years who received HD influenza vaccine.</p><p><strong>Interpretation: </strong>Co-administration of seasonal influenza vaccine with Ad26.COV2.S was immunogenic with an acceptable safety profile, supporting co-administration of these vaccines.</p><p><strong>Funding: </strong>Janssen Vaccines & Prevention BV and Biomedical Advanced Research and Development Authority.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103016"},"PeriodicalIF":9.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045981","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":"Dynamic changes and future trend predictions of the global burden of anxiety disorders: analysis of 204 countries and regions from 1990 to 2021 and the impact of the COVID-19 pandemic.","authors":"Si Chen, Wei Huang, Min Zhang, Yan Song, Chunshan Zhao, Hongwei Sun, Yanyu Wang, Jihong Wang, Yali Sun, Lei Zhou, Yan Zhu, HongYuan Wang, ZhengYang Xu, YuRui Bai, Cheng Chang","doi":"10.1016/j.eclinm.2024.103014","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.103014","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Anxiety disorders is a significant contributor to the Global Burden of Diseases (GBD), particularly in the aftermath of the COVID-19 pandemic, which has exacerbated the issue. Previous studies have not examined the impact of the COVID-19 pandemic on anxiety disorders over the entire time series, nor have they offered predictions regarding future trends of global anxiety disorders in the aftermath of the pandemic. This study aims to present the Age-Standardized Prevalence Rates (ASPR), Age-Standardized Incidence Rates (ASIR), and disability-adjusted life years (DALYs) associated with anxiety disorders from 1990 to 2021 across 204 countries and regions, emphasizing the age structure and the disease burden following the pandemic. Additionally, it examines the relationship between the burden of anxiety disorders and the COVID-19 pandemic, as well as trend predictions for the incidence of anxiety disorders from 2022 to 2050.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analysed data from the GBD 2021 study, employed the GBD method to integrate epidemiological data on ASPR, ASIR, and DALYs to accurately assess the global burden of anxiety disorders across various regions, genders, and age groups. Additionally, joint point regression analysis was applied to rigorously examine the time trends of anxiety disorders from 1990 to 2021, calculating the annual percentage change (APC), annual average percentage change (AAPC), and their corresponding 95% confidence intervals (CIs). Furthermore, path analysis was utilized to investigate the impact pathways between the COVID-19 pandemic and anxiety disorders. Finally, a Bayesian age-period-cohort (BAPC) model was employed to predict the prevalence trends of anxiety disorders from 2022 to 2050.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;From 1990 to 2021, the ASPR, ASIR, and DALYs associated with anxiety disorders worldwide exhibited a significant upward trend, particularly evident from 2019 to 2021, during which all three metrics experienced a sharp increase. The most pronounced changes in the burden of anxiety disorders from 2019 to 2021 were observed in high socio-demographic index (SDI) regions, where the ASIR surpassed expected levels in tropical Latin America, high-income North America, and Australia in 2021. Bulgaria recorded the highest increase in anxiety disorders burden during this period, with a change rate of 0.32, while Bhutan experienced the smallest increase, with a total change rate of 0.02. Notably, the global anxiety disorders burden among women is greater than that among men. From 2019 to 2021, women aged 20-24 years were particularly impacted by the COVID-19 pandemic, with a change rate of 0.21. Additionally, the ASIR of COVID-19 pandemic in 2021 had a significant positive correlation with the prevalence of anxiety disorders, standardized path coefficient value of 0.224 (z = 2.708, P &lt; 0.01). Projections indicate that by 2050, the number of individuals affected by anxiety disorders ","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103014"},"PeriodicalIF":9.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002121","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":"Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study.","authors":"Safoora Gharibzadeh, Ash Routen, Cameron Razieh, Francesco Zaccardi, Claire Lawson, Clare Gillies, Simon Heller, Melanie Davies, Helen Atkins, Stephen C Bain, Nazir L Lone, Krisnah Poinasamy, Tunde Peto, Elizabeth Robertson, Bob Young, Desmond Johnston, Jennifer Quint, Jonathan Valabhji, Khalida Ismail, Michael Marks, Alex Horsley, Annemarie Docherty, Ewen Harrison, James Chalmers, Ling-Pei Ho, Betty Raman, Chris Brightling, Omer Elneima, Rachel Evans, Neil Greening, Victoria C Harris, Linzy Houchen-Wolloff, Marco Sereno, Aarti Shikotra, Amisha Singapuri, Louise Wain, Claudia Langenberg, John Dennis, John Petrie, Naveed Sattar, Olivia Leavy, Mattew Richardson, Ruth M Saunders, Anne McArdle, Hamish McASuley, Tom Yates, Kamlesh Khunti","doi":"10.1016/j.eclinm.2024.103005","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.103005","url":null,"abstract":"<p><strong>Background: </strong>People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes.</p><p><strong>Methods: </strong>The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions.</p><p><strong>Findings: </strong>People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions.</p><p><strong>Interpretation: </strong>People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes.</p><p><strong>Funding: </strong>UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103005"},"PeriodicalIF":9.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002125","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 effects of anti-obesity medications on weight loss, cardiometabolic, and psychological outcomes in people living with overweight or obesity: a systematic review and meta-analysis.","authors":"Leiling Liu, Zhiqi Li, Wenrui Ye, Pu Peng, Yurong Wang, Luqing Wan, Jiangnan Li, Mei Zhang, Yihua Wang, Runqi Liu, Danyan Xu, Jingjing Zhang","doi":"10.1016/j.eclinm.2024.103020","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.103020","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Overweight and obesity pose serious health challenges for individuals and societies. This study aims to facilitate personalised treatment of obesity by summarising recent research on weight-loss pharmacotherapies, with a focus on their effects on weight reduction, cardiometabolic health, psychological outcomes, and adverse events.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This systematic review and meta-analysis included searches of Web of Science, PubMed, and Cochrane Central Register of Controlled Trials from inception to June 8, 2024. Randomised controlled trials evaluating weight-loss pharmacotherapies approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA) for treating overweight or obesity were included. Primary outcomes included changes in body weight, cardiometabolic indicators, psychological outcomes, and adverse events. Summary data was extracted from published reports. Random-effects meta-analyses were used to calculate weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CI). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used to assess the certainty of evidence for each pooled analysis. PROSPERO registration: CRD42024547905.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;A total of 154 randomised controlled trials (n = 112,515 participants) were included. Tirzepatide had the greatest weight-loss effect (WMD -11.69, 95% CI -19.22 to -4.15; &lt;i&gt;P&lt;/i&gt; = 0.0024; I&lt;sup&gt;2&lt;/sup&gt; = 100.0%; moderate certainty), followed by semaglutide (-8.48, -12.68 to -4.27; &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; I&lt;sup&gt;2&lt;/sup&gt; = 100.0%; moderate certainty). Tirzepatide had the strongest antihypertensive effect on both systolic (WMD -5.74, -9.00 to -2.48; &lt;i&gt;P&lt;/i&gt; = 0.0006; I&lt;sup&gt;2&lt;/sup&gt; = 99.8%; moderate certainty) and diastolic blood pressure (WMD -2.91, -4.97 to -0.85; &lt;i&gt;P&lt;/i&gt; = 0.0056; I&lt;sup&gt;2&lt;/sup&gt; = 99.8%; moderate certainty) and best reduced triglycerides (WMD -0.77, -0.85 to -0.69; &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; I&lt;sup&gt;2&lt;/sup&gt; = 3.2%; high certainty), fasting glucose (WMD -3.06, -5.53 to -0.59; &lt;i&gt;P&lt;/i&gt; = 0.015; I&lt;sup&gt;2&lt;/sup&gt; = 100.0%; moderate certainty), insulin (WMD -4.91, -8.15 to -1.68; &lt;i&gt;P&lt;/i&gt; = 0.0029; I&lt;sup&gt;2&lt;/sup&gt; = 97.0%; moderate certainty), and glycated haemoglobin levels (WMD -1.27, -1.82 to -0.73; &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; I&lt;sup&gt;2&lt;/sup&gt; = 100.0%; moderate certainty). Semaglutide (RR 0.83, 0.74-0.92; &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%; high certainty) and liraglutide (0.87, 0.79-0.96; &lt;i&gt;P&lt;/i&gt; = 0.0059; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%; high certainty) reduced the risk of major adverse cardiovascular events (MACEs). However, all three medications were associated with adverse gastrointestinal effects. Naltrexone/bupropion increased the risk of elevated blood pressure (RR 1.72, 1.04-2.85; &lt;i&gt;P&lt;/i&gt; = 0.036; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%; high certainty). Topiramate increased depression risk (RR 1.62, 1.14 to 2.30; &lt;i&gt;P&lt;/i&gt; = 0.0077; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%; high certainty), and phentermin","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103020"},"PeriodicalIF":9.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002137","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":"Cost-effectiveness of targeted next-generation sequencing (tNGS) for detection of tuberculosis drug resistance in India, South Africa and Georgia: a modeling analysis.","authors":"Suvesh Shrestha, Angelina Addae, Cecily Miller, Nazir Ismail, Alice Zwerling","doi":"10.1016/j.eclinm.2024.103003","DOIUrl":"10.1016/j.eclinm.2024.103003","url":null,"abstract":"<p><strong>Background: </strong>Targeted next-generation sequencing (tNGS) is promising alternative to phenotypic drug susceptibility testing (pDST) for detecting drug-resistant tuberculosis (DRTB). This study explored the potential cost-effectiveness of tNGS for the diagnosis of DR-TB across 3 settings: India, South Africa and Georgia.</p><p><strong>Methods: </strong>To inform WHO guideline development group (GDG) on tNGS we developed a stochastic decision analysis model and assessed cost-effectiveness of tNGS for DST among rifampicin resistance individuals. We also assessed tNGS as initial test for TB drug resistance in bacteriologically confirmed TB. Diagnostic accuracy and cost data were sourced from a systematic review conducted for GDG, covering studies published until September 2022. The primary outcome was incremental cost (2021 US$) per disability-adjusted life year (DALY) averted.</p><p><strong>Findings: </strong>tNGS when compared with in-country DST, tNGS proved cost-effective in South Africa (ICER: $15,619/DALY averted, WTP: $21,165) but not in Georgia (ICER: $18,375/DALY averted, WTP: $15,069). In India, tNGS dominated in-country DST practice, providing greater health impact at lower cost. When comparing tNGS with universal pDST, tNGS was dominated by pDST in all three countries. In Georgia, using tNGS as initial test for TB drug-resistance compared to Xpert MTB/Rif followed by pDST appeared cost-effective. Scenario with 50% reduction in tNGS test kit costs made tNGS cost-effective across all three countries, while a high Bedaquiline resistance prevalence (30%) led to a worsening cost-effectiveness.</p><p><strong>Interpretation: </strong>tNGS may be cost-effective in India, South Africa and Georgia when comprehensive DST is not routinely performed. Thus, existing DST practice and healthcare infrastructure should be considered before implementation and scale-up of tNGS.</p><p><strong>Funding: </strong>Global Tuberculosis Program, World Health Organization (2022/1249364-0).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103003"},"PeriodicalIF":9.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of antiparasitic therapy on cardiovascular outcomes in chronic Chagas disease. A systematic review and meta-analysis.","authors":"Anis Rassi, Alyssa Grimshaw, Ashwin Sarwal, Ranjit Sah, Sangam Shah, Nelson I Agudelo Higuita, Fabio Mahamed Rassi, Michaele Francesco Corbisiero, Hannah M Kyllo, Jordan Stellern, Samantha Kaplan, Luis A Marcos, Edgar A Ramírez-García, Martin Casapia, Peter Hotez, Maria Elena Bottazzi, Shital Patel, Carlos Franco-Paredes, José Antonio Marin-Neto, Andrés F Henao-Martínez","doi":"10.1016/j.eclinm.2024.102972","DOIUrl":"10.1016/j.eclinm.2024.102972","url":null,"abstract":"<p><strong>Background: </strong>Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints. This study aims to evaluate the impact of antitrypanosomal therapy in preventing or reducing disease progression and mortality in chronic Chagas disease.</p><p><strong>Methods: </strong>We performed a systematic review and meta-analysis of studies reporting the cardiovascular outcomes of antitrypanosomal therapy in patients with chronic Chagas disease. We searched Ovid Embase, Ovid MEDLINE, Ovid Global Health, Scopus, Web of Science Core Collection, Cochrane Library, PubMed, Google Scholar, and Virtual Health Library databases from inception to May 18, 2024. We included aggregated data from randomized controlled studies and observational reports (full articles and abstracts) featuring antiparasitic interventions with benznidazole or nifurtimox compared to a control group. Primary outcomes were electrocardiogram (ECG) changes, disease progression, cardiovascular death, and overall mortality. A customized risk of bias scale assessed the methodological quality of studies, and a random-effects model estimated the pooled risk ratios. This investigation was registered in PROSPERO (CRD42023495755).</p><p><strong>Findings: </strong>Out of 4666 reports screened, 23 met the pre-specified inclusion criteria (8972 participants). Compared to no treatment or placebo, antiparasitic treatment led to a reduction in i) ECG changes (17 studies, 4994 participants: risk ratio (RR): 0.48, 95% CI 0.36-0.66, p < 0.001; <i>I</i> ² = 76.4%) with a number needed to treat (NNT) of 5; ii) disease progression (12 studies, 5722 participants: RR: 0.35, 95% CI 0.23-0.51, p < 0.001; <i>I</i> ² = 72.4%) NNT of 6; iii) cardiovascular death (7 studies, 5662 participants: RR: 0.44, 95% CI 0.21-0.95, p = 0.04; <i>I</i> ² = 50.5%) NNT of 22; and iv) overall mortality (10 studies, 7694 participants: RR: 0.54, 95% CI 0.34-0.87, p < 0.001; <i>I</i> ² = 60%) NNT of 23.</p><p><strong>Interpretation: </strong>We found compelling evidence that antiparasitic treatment significantly reduces the risk of ECG changes, disease progression, cardiovascular death, and overall mortality in chronic Chagas disease. Although the quality of evidence ranges from low to intermediate, with considerable heterogeneity across studies, the potential benefits are substantial. These findings support the broader use of trypanocidal therapy in the management of Chagas disease, though further research remains necessary.</p><p><strong>Funding: </strong>This study had no funding source.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102972"},"PeriodicalIF":9.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982139","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":"Inorganic nitrates to prevent in-stent restenosis. Is nitric oxide the Philosopher's stone?","authors":"Fernando Alfonso, Alexander Marschall, David Del Val","doi":"10.1016/j.eclinm.2024.103015","DOIUrl":"10.1016/j.eclinm.2024.103015","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103015"},"PeriodicalIF":9.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982640","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":"Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the Netherlands.","authors":"Ellis L Eikenboom, Lotte van Leeuwen, Floris Groenendijk, Jorien M Woolderink, Anne M Van Altena, Monique E Van Leerdam, Manon C W Spaander, Helena C van Doorn, Anja Wagner","doi":"10.1016/j.eclinm.2024.103006","DOIUrl":"10.1016/j.eclinm.2024.103006","url":null,"abstract":"<p><strong>Background: </strong>Female Lynch syndrome carriers have an increased risk of developing endometrial cancer. Regardless, research on endometrial carcinoma tumorigenesis is scarce and no uniform, evidence-based gynaecological management guidelines exist. We therefore described gynaecological surveillance and surgery outcomes in a nation-wide Lynch syndrome cohort.</p><p><strong>Methods: </strong>For this retrospective cohort study, female Lynch syndrome carriers, prospectively registered in the Dutch Lynch syndrome database (StOET), were included up to February 28th 2022. Carriers were linked to the Dutch national pathology (PALGA) database. The number of carriers with/without gynaecological surveillance, number of index carriers with endometrial carcinoma before Lynch syndrome diagnosis were assessed, as well as uptake of risk-reducing surgery and characteristics of endometrial carcinomas including the requisite for adjuvant therapy according to current guidelines. Overall survival after endometrial carcinoma diagnosis was analyzed using Kaplan Meier time to event analyses, cumulative incidence was calculated after adjusting for competing risks (death and prophylactic hysterectomy).</p><p><strong>Findings: </strong>In total, 1046 registered female Lynch syndrome carriers were eligible for surveillance, of whom 313 (30.0%) did not have surveillance and 21.4% (n = 224 of 1046) opted for prophylactic hysterectomy. In carriers with surveillance, more cases of endometrial carcinoma and hyperplasia were found than in those without (37 endometrial carcinomas (7.3%) and 28 hyperplasias (5.5%) in 506 carriers with surveillance versus 14 (2.6%) and 4 (0.7%) in 540 carriers without surveillance, respectively); carriers with surveillance were generally younger than those without (median 56 years [IQR 48-65] versus median 65 years [IQR 49-75] at database assembly, respectively; p < 0.0001). Endometrial carcinomas were predominantly of endometrioid type and FIGO stage IA, regardless of surveillance. Adjuvant external beam radiotherapy was required in one patient in both groups. Overall survival after endometrial carcinoma diagnosis did not differ between carriers with or without surveillance or carriers with endometrial carcinoma before LS diagnosis (p = 0.51). For all endometrial carcinomas together, including index carriers, cumulative incidence was 22.7% at age 70.</p><p><strong>Interpretation: </strong>In a nation-wide cohort of Lynch syndrome carriers, nearly one-third of eligible carriers did not undergo gynaecological surveillance. Endometrial carcinomas diagnosed during surveillance were slightly more often stage FIGO IA, but this did not seem to substantially decrease the requisite for adjuvant therapy or affect overall survival, questioning effectiveness of current gynaecological management. Prospective research should further assess this, as well as patient preferences.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103006"},"PeriodicalIF":9.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002132","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":"The effectiveness of community-wide screening for pulmonary tuberculosis: a systematic review.","authors":"Susanna S van Wyk, Ntombifuthi Blose, Lester Kapanda-Phiri, Mareli Claassens, Taryn Young","doi":"10.1016/j.eclinm.2024.103010","DOIUrl":"10.1016/j.eclinm.2024.103010","url":null,"abstract":"<p><p>This systematic review evaluated the effectiveness of community-wide screening for pulmonary tuberculosis (TB) in high-burden areas by analysing randomised controlled trials (RCTs). The review focused on interventions offering TB screening to entire communities, comparing them to standard care or alternative approaches. The main outcome assessed was microbiologically confirmed TB diagnoses, including rates and prevalence. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, Web of Science, and trial registries up to 27 May 2024, without language restrictions. Screening, data extraction, and risk of bias assessment were done in duplicate. Results were not pooled. Certainty of the evidence was assessed using GRADE. PROSPERO: CRD42023453356. We included six cluster-RCTs after screening 2460 titles/abstracts and 86 full-text articles. The evidence for symptom screening was very uncertain. We found that sputum smear microscopy screening may result in little to no difference in the prevalence of culture-confirmed TB (n = 962,655, RR 1.09; 95% CI: 0.86-1.38, 1 RCT, low certainty evidence). Community-wide nucleic acid amplification test (NAAT) screening probably reduces the prevalence of NAAT-positive TB (n = 105,108, RR 0.56; 95% CI: 0.40-0.78, 1 RCT, moderate certainty evidence). Community-wide screening for pulmonary TB may reduce TB prevalence if done annually with an accurate screening test and high coverage.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103010"},"PeriodicalIF":9.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982598","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":"Beyond bronchial thermoplasty - where to now?","authors":"Peter B Noble, David Langton, Chuan T Foo, Bruce R Thompson, Alvenia Cairncross, Michael J Hackmann, Francis Thien, Graham M Donovan","doi":"10.1016/j.eclinm.2024.103017","DOIUrl":"10.1016/j.eclinm.2024.103017","url":null,"abstract":"<p><p>With the impending 'retirement' of bronchial thermoplasty (BT) for the treatment of patients with asthma, there is much to learn from this real-world experiment that will help us develop more effective future therapies with the same primary target i.e., airway smooth muscle (ASM) remodelling. This viewpoint discusses initial controversy surrounding BT (lack of an effect on forced expiratory volume in 1 s), its underutilisation, and importantly how non-standard diagnostics successfully demonstrated therapeutic response which escaped traditional lung function metrics. It is anticipated that the next iteration of BT (likely in a drug form) will have an overall greater effect on the health care system by virtue of evoking ASM remodelling as a treatable trait, and after appropriately drawing on lessons learned from the ∼fifteen-year BT saga.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103017"},"PeriodicalIF":9.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983081","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}