EClinicalMedicine最新文献

{"title":"Global, regional, and national burden of retinoblastoma in infants and young children: findings from the global burden of disease study 1990-2021.","authors":"Jianqi Chen, Xu Cao, Shengsong Xu, Xuhao Chen, Rui Xie, Guitong Ye, Yuan Zhang, Shaofen Huang, Xinyue Shen, Yue Xiao, Jinan Zhan, Yingting Zhu, Yehong Zhuo","doi":"10.1016/j.eclinm.2024.102860","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102860","url":null,"abstract":"<p><strong>Background: </strong>Retinoblastoma is considered a lethal but curable malignancy often presenting in childhood. We investigated its global, regional, and national burden among infants and young children from 1990 to 2021.</p><p><strong>Methods: </strong>We obtained data on retinoblastoma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Trends were analysed using joinpoint regression to calculate annual percentage changes. Spearman's rank correlation and locally estimated scatterplot smoothing regression were used to assess the relationship between retinoblastoma burden and sociodemographic index.</p><p><strong>Findings: </strong>In 2021, the global incidence, prevalence, mortality, and DALYs of retinoblastoma were 0.82 (95% uncertainty interval [UI], 0.48-1.10), 7.46 (95% UI, 4.42-10.08), 0.37 (95% UI, 0.22-0.51), and 32.81 (95% UI, 19.9-45.21), respectively. From 1990 to 2021, the global incidence and prevalence rates of retinoblastoma increased, with average annual percentage changes (AAPCs) of 0.67 (95% confidence interval [CI], 0.49-0.85] and 0.68 (95% CI, 0.50-0.86), respectively. Conversely, those of related mortality and DALYs decreased, with AAPCs of -0.64 (95% CI, -0.79 to -0.49) and -0.63 (95% CI, -0.78 to -0.48), respectively. Children aged 2-4 years and those in low-income regions exhibited the highest burden. Negative correlations were found between sociodemographic index and retinoblastoma burden.</p><p><strong>Interpretation: </strong>Advancements in retinoblastoma detection and treatment have increased its reported incidence and prevalence while reducing its mortality and DALYs. Nonetheless, substantial socioeconomic and geographic disparities persist. In low-income countries, the incidence has decreased, possibly reflecting challenges such as limited healthcare access and underreporting, necessitating targeted interventions and improved healthcare access.</p><p><strong>Funding: </strong>National Key R&D Project of China (2020YFA0112701), Natural Science Foundation of Guangdong Province (2024A1515013058), and Science and Technology Program of Guangzhou, China (202206080005).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460599","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":"Increase in colonic PRopionate as a method of prEVENTing weight gain over 12 months in adults aged 20-40 years (iPREVENT): a multi-centre, double-blind, randomised, parallel-group trial.","authors":"Jennifer E Pugh, Katerina Petropoulou, Joana C Vasconcelos, Aisha Anjum, George Thom, Louise McCombie, Martina Tashkova, Sumayya Alshehhi, Daphne Babalis, Leah Holroyd, Barzan A Sadiq, Christina Prechtl, Tom Preston, Edward Chambers, Mike J Lean, Waljit Dhillo, A Toby Prevost, Douglas Morrison, Gary Frost","doi":"10.1016/j.eclinm.2024.102844","DOIUrl":"10.1016/j.eclinm.2024.102844","url":null,"abstract":"<p><strong>Background: </strong>Obesity drives metabolic disease development. Preventing weight gain during early adulthood could mitigate later-life chronic disease risk. Increased dietary fibre intake, leading to enhanced colonic microbial fermentation and short-chain fatty acid (SCFA) production, is associated with lower body weight. Despite national food policy recommendations to consume 30 g of dietary fibre daily, only 9% of adults achieve this target. Inulin-propionate ester (IPE) selectively increases the production of the SCFA propionate in the colon. In previous studies, IPE has prevented weight gain in middle-aged adults over 6 months, compared with the inulin control. IPE is a novel food ingredient that can be added to various commonly consumed foods with a potential health benefit. This 12-month study aimed to determine whether using IPE to increase colonic propionate prevents further weight gain in overweight younger adults.</p><p><strong>Methods: </strong>This multi-centre randomised-controlled, double-blind trial was conducted in London and Glasgow, UK. Recruited participants were individuals at risk of weight gain, aged between 20 and 40 years and had an overweight body mass index. Sealed Envelope Software was used to randomise participants to consume 10 g of IPE or inulin (control), once per day for 12 months. The primary outcome was the weight gained from baseline to 12 months, analysed by an 'Intention to Treat' strategy. The safety profile and tolerability of IPE were monitored through adverse events and compliance. This study is registered with the International Standard Randomised Controlled Trials (ISRCT) Database (ISRCT number: 16299902).</p><p><strong>Findings: </strong>Participants (n = 135 per study arm) were recruited from July 2019 to October 2021. At 12 months, there was no significant difference in baseline-adjusted mean weight gain for IPE compared with control (1.02 kg, 95% CI: -0.37 to 2.41; p = 0.15; n = 226). Neither the IPE (+1.22 kg) nor the control arm (+0.07 kg) unadjusted mean gains in body weight reached the expected 2 kg threshold. In the IPE arm, fat-free mass was greater by 1.07 kg (95% CI: 0.21-1.93), and blood glucose elevated by 0.11 mmol/L (95% CI: 0.01-0.21). Compliance, determined by intake of ≥50% sachets, was reached by 63% of IPE participants. There were no unexpected adverse events or safety concerns.</p><p><strong>Interpretation: </strong>Our study indicates that at 12 months, IPE did not differentially affect weight gain, compared with the inulin control, in adults between 20 and 40 years of age, at risk of obesity.</p><p><strong>Funding: </strong>NIHR EME Programme (15/185/16).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399725","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":"Burden of disease attributable to high body mass index: an analysis of data from the Global Burden of Disease Study 2021.","authors":"Xiao-Dong Zhou, Qin-Fen Chen, Wah Yang, Mauricio Zuluaga, Giovanni Targher, Christopher D Byrne, Luca Valenti, Fei Luo, Christos S Katsouras, Omar Thaher, Anoop Misra, Karim Ataya, Rodolfo J Oviedo, Alice Pik-Shan Kong, Khalid Alswat, Amedeo Lonardo, Yu Jun Wong, Adam Abu-Abeid, Hazem Al Momani, Arshad Ali, Gabriel Alejandro Molina, Olivia Szepietowski, Nozim Adxamovich Jumaev, Mehmet Celal Kızılkaya, Octavio Viveiros, Carlos Jesus Toro-Huamanchumo, Kenneth Yuh Yen Kok, Oral Ospanov, Syed Imran Abbas, Andrew Gerard Robertson, Yasser Fouad, Christos S Mantzoros, Huijie Zhang, Nahum Méndez-Sánchez, Silvia Sookoian, Wah-Kheong Chan, Sombat Treeprasertsuk, Leon Adams, Ponsiano Ocama, John D Ryan, Nilanka Perera, Ala I Sharara, Said A Al-Busafi, Christopher Kenneth Opio, Manuel Garcia, Michelle Ching Lim-Loo, Elena Ruiz-Úcar, Arun Prasad, Anna Casajoana, Tamer N Abdelbaki, Ming-Hua Zheng","doi":"10.1016/j.eclinm.2024.102848","DOIUrl":"10.1016/j.eclinm.2024.102848","url":null,"abstract":"<p><strong>Background: </strong>Obesity represents a major global health challenge with important clinical implications. Despite its recognized importance, the global disease burden attributable to high body mass index (BMI) remains less well understood.</p><p><strong>Methods: </strong>We systematically analyzed global deaths and disability-adjusted life years (DALYs) attributable to high BMI using the methodology and analytical approaches of the Global Burden of Disease Study (GBD) 2021. High BMI was defined as a BMI over 25 kg/m² for individuals aged ≥20 years. The Socio-Demographic Index (SDI) was used as a composite measure to assess the level of socio-economic development across different regions. Subgroup analyses considered age, sex, year, geographical location, and SDI.</p><p><strong>Findings: </strong>From 1990 to 2021, the global deaths and DALYs attributable to high BMI increased more than 2.5-fold for females and males. However, the age-standardized death rates remained stable for females and increased by 15.0% for males. Similarly, the age-standardized DALY rates increased by 21.7% for females and 31.2% for males. In 2021, the six leading causes of high BMI-attributable DALYs were diabetes mellitus, ischemic heart disease, hypertensive heart disease, chronic kidney disease, low back pain and stroke. From 1990 to 2021, low-middle SDI countries exhibited the highest annual percentage changes in age-standardized DALY rates, whereas high SDI countries showed the lowest.</p><p><strong>Interpretation: </strong>The worldwide health burden attributable to high BMI has grown significantly between 1990 and 2021. The increasing global rates of high BMI and the associated disease burden highlight the urgent need for regular surveillance and monitoring of BMI.</p><p><strong>Funding: </strong>National Natural Science Foundation of China and National Key R&D Program of China.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388872","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":"Advancing patient-centric care: integrating patient reported outcomes for tolerability assessment in early phase clinical trials - insights from an expert virtual roundtable.","authors":"Christina Yap, Olalekan Lee Aiyegbusi, Emily Alger, Ethan Basch, Jill Bell, Vishal Bhatnagar, David Cella, Philip Collis, Amylou C Dueck, Alexandra Gilbert, Ari Gnanasakthy, Alastair Greystoke, Aaron R Hansen, Paul Kamudoni, Olga Kholmanskikh, Bellinda L King-Kallimanis, Harlan Krumholz, Anna Minchom, Daniel O'Connor, Joan Petrie, Claire Piccinin, Khadija Rerhou Rantell, Saaeha Rauz, Ameeta Retzer, Steven Rizk, Lynne Wagner, Maxime Sasseville, Lesley K Seymour, Harald A Weber, Roger Wilson, Melanie Calvert, John Devin Peipert","doi":"10.1016/j.eclinm.2024.102838","DOIUrl":"10.1016/j.eclinm.2024.102838","url":null,"abstract":"<p><p>Early phase clinical trials provide an initial evaluation of therapies' risks and benefits to patients, including safety and tolerability, which typically relies on reporting outcomes by investigator and laboratory assessments. Use of patient-reported outcomes (PROs) to inform risks (tolerability) and benefits (improvement in disease symptoms) is more common in later than early phase trials. We convened a two-day expert roundtable covering: (1) the necessity and feasibility of a universal PRO core conceptual model for early phase trials; (2) the practical integration of PROs in early phase trials to inform tolerability assessment, guide dose decisions, or as real-time safety alerts to enhance investigator-reported adverse events. Participants (n = 22) included: patient advocates, regulators, clinicians, statisticians, pharmaceutical representatives, and PRO methodologists working across diverse clinical areas. In this manuscript, we report major recommendations resulting from the roundtable discussions corresponding to each theme. Additionally, we highlight priority areas necessitating further investigation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global, regional, and national burden of preterm birth, 1990-2021: a systematic analysis from the global burden of disease study 2021.","authors":"Xifeng Liang, Yaning Lyu, Jing Li, Yu Li, Cheng Chi","doi":"10.1016/j.eclinm.2024.102840","DOIUrl":"10.1016/j.eclinm.2024.102840","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Preterm birth and its complications are leading causes of mortality among children under five years of age. Given the increasing burden of preterm birth on neonatal mortality and long-term health outcomes worldwide, a comprehensive global analysis is essential to guide effective public health interventions and policies. This study aims to assess the burden of preterm birth at the global, regional, and national levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Using data from the Global Burden of Disease (GBD) 2021 database, this study analysed trends in age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and disability-adjusted life-years (DALYs) as primary outcomes for preterm birth from 1990 to 2021 at global, regional, and national levels. Data were assessed using joinpoint regression analysis, decomposition analysis, and the health inequality concentration index.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Globally, the incidence, mortality and DALYs due to preterm birth have shown a declining trend, but ASIR started to increase in 2016. Males were more commonly born preterm than females (12329075.82, 95% uncertainty interval [UI]: 12192632.55-12464605.4 vs. 9224694.94, 95% UI: 9113876.1-9330107.89). Changes in DALYs were primarily due to epidemiological change (111.97%) and population (-21.59%). Low Socio-demographic Index (SDI) regions increased in annual incidence cases (43.1%, 95% UI: 40.17-46.09), while high SDI regions decreased in annual incidence cases (-9.6%, 95% UI: -11.45 to -7.79). The highest annual mortality and DALYs respectively occurred in sub-Saharan Africa (295490.66, 95% UI: 241762.78-353624.41) and South Asia (32760273.93, 95% UI: 27295547.76-39070225.69). Western sub-Saharan Africa showed the largest increase in annual incidence (98.95%, 95% UI: 94.77 to 103.09), and Australasia had the lowest annual mortality (287.18, 95% UI: 244.26-339.42) and DALYs (61081.4, 95% UI: 50897.33-73069.96). Western sub-Saharan Africa also had the highest ASMR (21.57, 95% confidence interval [CI]: 17.9-25.89). The highest ASIR (543.78, 95% CI: 535.11-553.21) and age-standardized DALYs (2064.65, 95% CI: 1717.27-2473.36) both occurred in South Asia, while the lowest ASIR and age-standardized DALYs were seen in East Asia (147.31, 95% CI: 144.22-150.85) and High-income Asia Pacific (143.32, 95% CI: 117.9-167.25). India, Nigeria, and Pakistan ranked highest globally in terms of annual incidence cases, mortality, and DALYs, while the lowest annual incidence, mortality and DALYs respectively occurred in Tokelau (2.34, 95% UI: 2.12-2.56), San Marino (0.04, 95% UI: 0.02-0.07) and Tokelau (17.22, 95% UI: 11.11-24.95).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;While the global burden of preterm birth has decreased, significant disparities persist, especially in low SDI regions. There is a need for more refined policies and preventive measures to effectively address preterm birth.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;No","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388873","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":"Changes in memory and cognition during the SARS-CoV-2 human challenge study.","authors":"William Trender, Peter J Hellyer, Ben Killingley, Mariya Kalinova, Alex J Mann, Andrew P Catchpole, David Menon, Edward Needham, Ryan Thwaites, Christopher Chiu, Gregory Scott, Adam Hampshire","doi":"10.1016/j.eclinm.2024.102842","DOIUrl":"10.1016/j.eclinm.2024.102842","url":null,"abstract":"<p><strong>Background: </strong>Patient-reported outcomes and cross-sectional evidence show an association between COVID-19 and persistent cognitive problems. The causal basis, longevity and domain specificity of this association is unclear due to population variability in baseline cognitive abilities, vulnerabilities, virus variants, vaccination status and treatment.</p><p><strong>Methods: </strong>Thirty-four young, healthy, seronegative volunteers were inoculated with Wildtype SARS-CoV-2 under prospectively controlled conditions. Volunteers completed daily physiological measurements and computerised cognitive tasks during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Linear modelling examined differences between 'infected' and 'inoculated but uninfected' individuals. The main cognitive endpoint was the baseline corrected global cognitive composite score across the battery of tasks administered to the volunteers. Exploratory cognitive endpoints included baseline corrected scores from individual tasks. The study was registered on ClinicalTrials.gov with the identifier NCT04865237 and took place between March 2021 and July 2022.</p><p><strong>Findings: </strong>Eighteen volunteers developed infection by qPCR criteria of sustained viral load, one without symptoms and the remainder with mild illness. Infected volunteers showed statistically lower baseline-corrected global composite cognitive scores than uninfected volunteers, both acutely and during follow up (mean difference over all time points = -0.8631, 95% CI = -1.3613, -0.3766) with significant main effect of group in repeated measures ANOVA (F (1,34) = 7.58, p = 0.009). Sensitivity analysis replicated this cross-group difference after controlling for community upper respiratory tract infection, task-learning, remdesivir treatment, baseline reference and model structure. Memory and executive function tasks showed the largest between-group differences. No volunteers reported persistent subjective cognitive symptoms.</p><p><strong>Interpretation: </strong>These results support larger cross sectional findings indicating that mild Wildtype SARS-CoV-2 infection can be followed by small changes in cognition and memory that persist for at least a year. The mechanistic basis and clinical implications of these small changes remain unclear.</p><p><strong>Funding: </strong>This study was funded through the UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy (BEIS) of Her Majesty's Government. WT was funded by the EPSRC through the CDT for Neurotechnology Imperial College London.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371310","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":"Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for initially unresectable locally advanced colon cancer: short-term outcomes of an open-label, single-centre, randomised, controlled, phase 3 trial.","authors":"Zi-Tong Zhang, Wei-Wei Xiao, Li-Ren Li, Xiao-Jun Wu, Qiao-Xuan Wang, Hui Chang, Xue Tian, Wu Jiang, Jun-Zhong Lin, Rong-Xin Zhang, Wen-Hua Fan, Zhi-Zhong Pan, Rong Zhang, Yuan-Hong Gao","doi":"10.1016/j.eclinm.2024.102836","DOIUrl":"10.1016/j.eclinm.2024.102836","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor in locally advanced colon cancer (LACC) and improve the R0 resection rate. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC remain poorly understood. This study aimed to compare the effects and safety of NACRT and NACT on R0 resection and survival rates in initially unresectable LACC.</p><p><strong>Methods: </strong>This was an open-label, single-center, randomized, controlled trial conducted between May 11, 2019 and May 30, 2022. Forty-five patients with initially unresectable LACC were randomly allocated to the NACT (control, n = 20) or NACRT (research, n = 25) group. The NACT group received XELOX (oxaliplatin 100-130 mg/m², qd, d1, every 3 weeks; and capecitabine 1000 mg/m², bid, d1-d14, every 3 weeks) for 4 cycles. The NACRT group, in addition to chemotherapy, received daily irradiation (GTV 45-50 Gy/25 F; CTV 42.5-45 Gy/25 F). Surgery was scheduled 6-12 weeks after neoadjuvant treatment and adjuvant chemotherapy was administered if the patient developed resectable LACC. The primary endpoint was the 5-year overall survival (OS) rate. The secondary outcomes included the 3-year progression-free survival (PFS) and R0 resection rates. This study was registered with ClinicalTrials.gov (NCT03970694).</p><p><strong>Findings: </strong>In short-term outcome analysis, NACRT significantly improved the R0 resection rate (80% for NACRT vs. 20% for NACT, P < 0.001). The NACRT and NACT groups had a 3-year OS of 87.6% and 75% (P = 0.037) and a 3-year PFS of 76% and 45% (P = 0.049), respectively. The 5-year OS was not reached. In the NACRT group, no local or regional recurrence was observed in patients who underwent surgery during the follow-up period, compared to two patients in the NACT group. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. The most commonly observed grade 3-4 AE was myelosuppression (39% for NACRT and 47% for NACT, P = 0.609). No grade 5 AEs were observed between the two groups.</p><p><strong>Interpretation: </strong>Adding radiation to NACT increased the R0 resection rate, prolonged the PFS, and potentially improved OS in selected patients with initially unresectable LACC. The trial findings indicate that this approach is safe, feasible, and may confer a survival benefit.</p><p><strong>Funding: </strong>This study was supported by grants from the National Natural Science Foundation of China (82373213 to Dr Gao, 82202952 to Dr Wang); and the Natural Science Foundation of Guangdong Province (2023A1515010290 to Dr Chang). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371312","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":"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}