EClinicalMedicine最新文献

{"title":"Phase 2 dose-ranging study to evaluate the efficacy and safety of liposomal irinotecan (LY01610) as a second-line treatment for patients with relapsed small cell lung cancer.","authors":"Puyuan Xing, Shanbing Wang, Minghong Bi, Yong Liu, Jia Zeng, Xicheng Wang, Ke Xiao, Weidong Li, Jun Guo, Pu Wang, Yueyin Pan, Biyong Ren, Emei Gao, Lei Zhang, Yingchun Wang, Tianyi Gan, Guang Cheng, Yuankai Shi","doi":"10.1016/j.eclinm.2024.102791","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102791","url":null,"abstract":"<p><strong>Background: </strong>This was a multicenter, single-arm dose-ranging phase 2 study aimed to assess the efficacy and safety of LY01610, a liposomal irinotecan, at various doses for patients with relapsed small cell lung cancer (SCLC).</p><p><strong>Methods: </strong>This study (NCT04381910) enrolled patients with relapsed SCLC at 10 hospitals across China, who have failed with previous platinum-based treatments. LY01610 was administered at doses of 60 mg/m², 80 mg/m², and 100 mg/m². Primary endpoints were investigator-assessed objective response rate (ORR) and investigator-assessed duration of response (DoR). Secondary endpoints included investigator-assessed disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Findings: </strong>From September 3, 2020 to March 3, 2022, a total of 66 patients were enrolled, with 6, 30, and 30 allocated to the 60 mg/m², 80 mg/m², and 100 mg/m² dose groups, respectively, with 68% (45/66) having a chemotherapy-free interval <90 days. In all 66 patients, the ORR was 32% (21/66, 95% confidence interval [CI], 21-44), with a median DoR of 5.2 months (95% CI, 3.0-8.3). Median PFS and OS were 4.0 (95% CI, 2.9-5.5) and 9.7 (95% CI, 7.2-12.3) months, respectively. The ORR of 60 mg/m², 80 mg/m², and 100 mg/m² dose group were 33% (2/6), 33% (10/30), and 30% (9/30), respectively. The median DoR of 60 mg/m², 80 mg/m², and 100 mg/m² dose group were 4.2 (95% CI, 2.8-not reached), 6.9 (95% CI, 2.5-9.9), and 4.0 (95% CI, 2.7-6.8) months, respectively. The incidence of ≥ grade 3 treatment-related adverse events (TRAEs) in the 60 mg/m², 80 mg/m², and 100 mg/m² dose group were 33% (2/6), 47% (14/30), and 50% (15/30), respectively. The most common ≥ grade 3 TRAEs of all 66 patients were neutropenia (27%), leukopenia (24%) and anemia (15%).</p><p><strong>Interpretation: </strong>LY01610 exhibited promising clinical efficacy and manageable safety profiles in patients with relapsed SCLC, the 80 mg/m² dose group had the best benefit-risk ratio.</p><p><strong>Funding: </strong>This study was supported by Luye Pharma Group Ltd.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102791"},"PeriodicalIF":9.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282092","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":"Maternal autoimmune disease and offspring risk of haematological malignancies: a case-control study.","authors":"Shu-Ning Liu, Meng-Che Wu, Wei-Szu Lin, Ching-Heng Lin, James Cheng-Chung Wei","doi":"10.1016/j.eclinm.2024.102794","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102794","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune diseases are known to be associated with an increased risk of cancer. Whether maternal immune dysregulation can have an impact on the development of haematological malignancies in offspring remains uncertain. Therefore, we explored the association between offspring risk of haematological malignancies and maternal autoimmune disease using a real-world nationwide population-based study.</p><p><strong>Methods: </strong>In this case-control study, we identified 2172 children with haematological malignancies between 2004 and 2019 from Taiwan's National Health Insurance program and compared them with population-based controls without haematologic malignancies, who were matched with each individual at a ratio of 1:4. The medical information of the autoimmune mothers were obtained from the Taiwan Maternal and Child Health Database. Conditional logistic regression was used to estimate the odds ratio for haematologic malignancy in offspring. Furthermore, subgroup and stratified analyses were conducted.</p><p><strong>Findings: </strong>Among the rheumatologic diseases in our study, Crohn's disease was the most common disease both in the haematological malignancy group (1.1%) and the control group (0.9%). In multivariable analysis, the odds ratio for haematological malignancy in offspring with maternal autoimmune diseases was 1.2 (95% confidence interval [CI] 0.91-1.58). The overall risk of haematologic malignancy was not significantly higher when adjusted for specific risk factors, including neonatal age, maternal age, family income, urbanization, maternal occupation, birth weight, or maternal comorbidity, except for prematurity. When comparing different autoimmune diseases among haematological malignancies and the control group, maternal psoriatic arthritis/psoriasis had the highest adjusted overall risk for haematological malignancies (adjusted OR 2.11, CI 0.89-5), followed by ankylosing spondylitis (adjusted OR 1.45, CI 0.7-3), autoimmune thyroiditis (OR 1.26, CI 0.57-2.81), systemic lupus erythematosus (OR 1.21, CI 0.48-3.02), Crohn's disease (OR 1.19, CI 0.75-1.9), and Sjogren's syndrome (OR 1.18, CI 0.65-2.15), but no significance was reached in these analyses. Multivariable analysis of risk factors associated with haematological malignancy subtypes was done. It showed no associations between maternal autoimmune disease and childhood haematological malignancies.</p><p><strong>Interpretation: </strong>We found no significant relationship between maternal autoimmune disease and childhood haematological malignancies. The influence of maternal immune dysregulation on the next generation with respect to haematological malignancies development may be limited.</p><p><strong>Funding: </strong>There was no funding source for this study.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102794"},"PeriodicalIF":9.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282091","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 survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial.","authors":"Ruixi Wang, Yihong Ling, Baoqing Chen, Yujia Zhu, Yonghong Hu, Mengzhong Liu, Yadi Yang, Li Zhang, Yingxin Lv, Shiliang Liu, Qiaoqiao Li, Mian Xi","doi":"10.1016/j.eclinm.2024.102806","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102806","url":null,"abstract":"<p><strong>Background: </strong>In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses.</p><p><strong>Methods: </strong>This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m² of paclitaxel and 25 mg/m² of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170).</p><p><strong>Findings: </strong>With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, <i>P <</i> 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, <i>P <</i> 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, <i>P</i> = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, <i>P</i> = 0.027) than those without irAEs. <i>GON4L</i> mutation was associated with a lower incidence of irAEs (<i>P</i> = 0.036).</p><p><strong>Interpretation: </strong>The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis.</p><p><strong>Funding: </strong>National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102806"},"PeriodicalIF":9.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282090","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 external validation of temporal fusion transformer models for continuous intraoperative blood pressure forecasting.","authors":"Lorenz Kapral, Christoph Dibiasi, Natasa Jeremic, Stefan Bartos, Sybille Behrens, Aylin Bilir, Clemens Heitzinger, Oliver Kimberger","doi":"10.1016/j.eclinm.2024.102797","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102797","url":null,"abstract":"<p><strong>Background: </strong>During surgery, intraoperative hypotension is associated with postoperative morbidity and should therefore be avoided. Predicting the occurrence of hypotension in advance may allow timely interventions to prevent hypotension. Previous prediction models mostly use high-resolution waveform data, which is often not available.</p><p><strong>Methods: </strong>We utilised a novel temporal fusion transformer (TFT) algorithm to predict intraoperative blood pressure trajectories 7 min in advance. We trained the model with low-resolution data (sampled every 15 s) from 73,009 patients who were undergoing general anaesthesia for non-cardiothoracic surgery between January 1, 2017, and December 30, 2020, at the General Hospital of Vienna, Austria. The data set contained information on patient demographics, vital signs, medication, and ventilation. The model was evaluated using an internal (n = 8113) and external test set (n = 5065) obtained from the openly accessible Vital Signs Database.</p><p><strong>Findings: </strong>In the internal test set, the mean absolute error for predicting mean arterial blood pressure was 0.376 standard deviations-or 4 mmHg-and 0.622 standard deviations-or 7 mmHg-in the external test set. We also adapted the TFT model to binarily predict the occurrence of hypotension as defined by mean arterial blood pressure < 65 mmHg in the next one, three, five, and 7 min. Here, model discrimination was excellent, with a mean area under the receiver operating characteristic curve (AUROC) of 0.933 in the internal test set and 0.919 in the external test set.</p><p><strong>Interpretation: </strong>Our TFT model is capable of accurately forecasting intraoperative arterial blood pressure using only low-resolution data showing a low prediction error. When used for binary prediction of hypotension, we obtained excellent performance.</p><p><strong>Funding: </strong>No external funding.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102797"},"PeriodicalIF":9.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282069","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 of a real-time intelligent quality-control system for the detection of early upper gastrointestinal neoplasms: a multicentre, single-blinded, randomised controlled trial.","authors":"Ruchen Zhou, Jing Liu, Chenchen Zhang, Yusha Zhao, Jingran Su, Qiong Niu, Chengxia Liu, Zhuang Guo, Zhenqin Cui, Xiaoqin Zhong, Weidong Zhao, Jing Li, Xiaodong Zhang, Hongyan Wang, Shidong Sun, Ruiguang Ma, Xinyu Chen, Xinyan Xu, Yiqing Zhu, Zhen Li, Xiuli Zuo, Yanqing Li","doi":"10.1016/j.eclinm.2024.102803","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102803","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Oesophagogastroduodenoscopy (OGD) quality and identification of the early upper gastrointestinal (UGI) neoplasm play an important role in detecting the UGI neoplasm. However, the optimal method for quality control in daily OGD procedures is currently lacking. We aimed to evaluate the efficacy of a real-time intelligent quality-control system (IQCS), which combines OGD quality control with lesion detection of early UGI neoplasms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a multicentre, single-blinded, randomised controlled trial at 6 hospitals in China. Patients aged 40-80 years old who underwent painless OGD were screened for enrolment in this study. Patients with a history of advanced UGI cancer, stenosis, or obstruction in UGI tract were excluded. Eligible subjects were randomly assigned (1:1) to either the routine or IQCS group to undergo standard OGD examination and OGD examination aided by IQCS, respectively. Patients were masked to the randomisation status. The primary outcome was the detection of early UGI neoplasms. All analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, NCT04720924.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between January 16, 2021 and December 23, 2022, 1840 patients were randomised (IQCS group: 919, routine group: 921). The full analysis set consisted of 914 in the IQCS group and 915 in the routine group. The early UGI neoplasms detection rate in the IQCS group (6.1%, 56/914) was significantly higher than in the routine group (2.3%, 21/915; &lt;i&gt;P&lt;/i&gt; = 0.0001). The IQCS group had fewer blind spots (2.3 vs. 6.2, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001). The IQCS group had higher stomach cleanliness on cardia or fundus (99.5% vs. 87.9%, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), body (98.9% vs. 88.0%, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), angulus (99.8% vs. 88.4%, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and antrum or pylorus (100.0% vs. 87.4%, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001). The inspection time (576.2 vs. 574.5s, &lt;i&gt;P&lt;/i&gt; = 0.91) and biopsy rate (57.2% vs. 56.6%, &lt;i&gt;P&lt;/i&gt; = 0.83) were not different between the groups. The early UGI neoplasms detection rate in the IQCS group increased in both non-academic centres (RR = 3.319, 95% CI 1.277-9.176; &lt;i&gt;P&lt;/i&gt; = 0.0094) and academic centres (RR = 2.416, 95% CI 1.301-4.568; &lt;i&gt;P&lt;/i&gt; = 0.0034). The same improvements were observed for both less-experienced endoscopists (RR = 2.650, 95% CI 1.330-5.410; &lt;i&gt;P&lt;/i&gt; = 0.0034) and experienced endoscopists (RR = 2.710, 95% CI 1.226-6.205; &lt;i&gt;P&lt;/i&gt; = 0.010). No adverse events or serious adverse events were reported in the two groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The IQCS improved the OGD quality and increased early UGI neoplasm detection in different hospital types and endoscopist experiences. IQCS could play an important role in primary basic hospitals and non-expert endoscopists to improve the diagnostic accuracy of early UGI neoplasms. The effectiveness of IQCS in real-world clinical settings needs a larger population validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102803"},"PeriodicalIF":9.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282086","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":"GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review.","authors":"Nasreen Alfaris, Stephanie Waldrop, Veronica Johnson, Brunna Boaventura, Karla Kendrick, Fatima Cody Stanford","doi":"10.1016/j.eclinm.2024.102782","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102782","url":null,"abstract":"<p><p>Obesity and type 2 diabetes mellitus (T2DM) present major global health challenges, with an increasing prevalence worldwide. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a pivotal treatment option for both conditions, demonstrating efficacy in blood glucose management, weight reduction, cardiovascular disease prevention, and kidney health improvement. GLP-1, an incretin hormone, plays a crucial role in glucose metabolism and appetite regulation, influencing insulin secretion, insulin sensitivity, and gastric emptying. The therapeutic use of GLP-1RAs has evolved significantly, offering various formulations that provide different efficacy, routes of administration, and flexibility in dosing. These agents reduce HbA1c levels, facilitate weight loss, and exhibit cardiovascular protective effects, making them an integral component of T2DM and obesity management. This review will discuss the currently approved medication for T2DM and obesity, and will also highlight the advent of novel agents which are dual and triple hormonal agonists which represent the future direction of incretin-based therapy.</p><p><strong>Funding: </strong>National Institutes of HealthNIDDKU24 DK132733 (FCS), UE5 DK137285 (FCS), and P30 DK040561 (FCS).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102782"},"PeriodicalIF":9.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transformer-based deep learning model for early prediction of lymph node metastasis in locally advanced gastric cancer after neoadjuvant chemotherapy using pretreatment CT images.","authors":"Yunlin Zheng, Bingjiang Qiu, Shunli Liu, Ruirui Song, Xianqi Yang, Lei Wu, Zhihong Chen, Abudouresuli Tuersun, Xiaotang Yang, Wei Wang, Zaiyi Liu","doi":"10.1016/j.eclinm.2024.102805","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102805","url":null,"abstract":"<p><strong>Background: </strong>Early prediction of lymph node status after neoadjuvant chemotherapy (NAC) facilitates promptly optimization of treatment strategies. This study aimed to develop and validate a deep learning network (DLN) using baseline computed tomography images to predict lymph node metastasis (LNM) after NAC in patients with locally advanced gastric cancer (LAGC).</p><p><strong>Methods: </strong>A total of 1205 LAGC patients were retrospectively recruited from three hospitals between January 2013 and March 2023, constituting a training cohort, an internal validation cohort, and two external validation cohorts. A transformer-based DLN was developed using 3D tumor images to predict LNM after NAC. A clinical model was constructed through multivariate logistic regression analysis as a baseline for subsequent comparisons. The performance of the models was evaluated through discrimination, calibration, and clinical applicability. Furthermore, Kaplan-Meier survival analysis was conducted to assess overall survival (OS) of LAGC patients at two follow-up centers.</p><p><strong>Findings: </strong>The DLN outperformed the clinical model and demonstrated a robust performance for predicting LNM in the training and validation cohorts, with areas under the curve (AUCs) of 0.804 (95% confidence interval [CI], 0.752-0.849), 0.748 (95% CI, 0.660-0.830), 0.788 (95% CI, 0.735-0.835), and 0.766 (95% CI, 0.717-0.814), respectively. Decision curve analysis exhibited a high net clinical benefit of the DLN. Moreover, the DLN was significantly associated with the OS of LAGC patients [Center 1: hazard ratio (HR), 1.789, P < 0.001; Center 2:HR, 1.776, P = 0.013].</p><p><strong>Interpretation: </strong>The transformer-based DLN provides early and effective prediction of LNM and survival outcomes in LAGC patients receiving NAC, with promise to guide individualized therapy. Future prospective multicenter studies are warranted to further validate our model.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (NO. 82373432, 82171923, 82202142), Project Funded by China Postdoctoral Science Foundation (NO. 2022M720857), Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (NO. U22A20345), National Science Fund for Distinguished Young Scholars of China (NO. 81925023), Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (NO. 2022B1212010011), High-level Hospital Construction Project (NO. DFJHBF202105), Natural Science Foundation of Guangdong Province for Distinguished Young Scholars (NO. 2024B1515020091).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102805"},"PeriodicalIF":9.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282061","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 scale up of status quo hypertension care against dual combination therapy as separate pills or single pill combinations: an economic evaluation in 24 low- and middle-income countries.","authors":"Brian Hutchinson, Muhammad Jami Husain, Rachel Nugent, Deliana Kostova","doi":"10.1016/j.eclinm.2024.102778","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102778","url":null,"abstract":"<p><strong>Background: </strong>International hypertension treatment guidelines recommend initiating pharmacological treatment with combination therapy and using fixed dose single pill combinations (SPCs) to improve adherence. However, few countries have adopted combination therapy as a form of first-line treatment and SPC uptake in low- and middle-income countries is low due in part to cost and availability. Evidence on costs and cost-effectiveness is needed as health authorities consider incorporating new recommendations into national clinical practice guidelines.</p><p><strong>Methods: </strong>Over a 30-year time horizon, we used an Excel-based Markov cohort state-transition model to assess the financial costs (screening, treatment, program, and supply chain costs) and socio-economic outcomes (health outcomes, value of lives saved, productivity losses averted) of three antihypertensive treatment scenarios. A baseline scenario scaled treatment among adults age 30 plus while assuming continuation of the widespread practice of initiating treatment with monotherapy. Scenarios one and two scaled treatment while initiating patients on two antihypertensive medications, either as separate pills or as a SPC. Analysis inputs are informed by country-specific data, meta-analyses of the blood-pressure lowering of antihypertensive medications, and own-studies of medication costs. We compared costs, cost-effectiveness, and net-benefits across scenarios, and assessed uncertainty in a one-way sensitivity analysis.</p><p><strong>Findings: </strong>Using dual combination therapy (with or without SPCs) as first-line treatment would increase costs relative to current practices that largely use monotherapy. Required additional annual resources averaged as much as 3.6, 0.9, and 0.2 percent of government health expenditures in the analysis' low-, lower-middle, and upper-middle income countries. However, across 24 countries, over the next 30 years, combination therapy with separate pills could save 430,000 more lives and combination therapy with SPCs could save 564,000 more lives compared to baseline treatment practices. Administration of two or more medications using SPCs generated higher net benefits in most countries (16/24) compared to the baseline scenario.</p><p><strong>Interpretation: </strong>First line treatment employing SPCs is likely to generate higher net benefits compared to status quo treatment practices in countries with relatively higher incomes. To improve population health, national health systems would benefit from reducing structural and other barriers to the use of combination therapy and SPCs.</p><p><strong>Funding: </strong>This journal article was supported by TEPHINET cooperative agreement number 1NU2HGH000044-01-0 funded by the US Centers for Disease Control and Prevention.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102778"},"PeriodicalIF":9.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11400602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282066","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":"Detection of thyroid cancer among children and adolescents in Fukushima, Japan: a population-based cohort study of the Fukushima Health Management Survey.","authors":"Hideto Takahashi, Seiji Yasumura, Kunihiko Takahashi, Tetsuya Ohira, Hiroki Shimura, Hitoshi Ohto, Satoru Suzuki, Shinichi Suzuki, Tetsuo Ishikawa, Satoshi Suzuki, Enbo Ma, Masanori Nagao, Susumu Yokoya, Kenji Kamiya","doi":"10.1016/j.eclinm.2024.102722","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102722","url":null,"abstract":"<p><strong>Background: </strong>Thyroid ultrasound examinations using a cohort study design (from the Fukushima Health Management Survey [FHMS]) were conducted after the nuclear power plant accident caused by the Great East Japan Earthquake in 2011. This study investigated the association between radiation exposure and the detection of thyroid cancer in children and adolescents.</p><p><strong>Methods: </strong>The cohort study has been conducted in Fukushima prefecture in Japan since 2011. The primary outcome was the external dose. We enrolled 253346 examinees who lived in Fukushima at the time of the accident (Dataset A), including 113120 examinees who had data on external radiation exposure (ERE) (Dataset B). The median dose in the examinee's district was used for missing dose. The association between ERE and detection of thyroid cancer or suspected thyroid cancer was analyzed using Poisson regressions with two types of explanatory variables: sex, age, overweight status, and district (Model 1), and past medical history, family history of thyroid cancer, frequency of seafood consumption, and frequency of seaweed consumption in addition to Model 1 (Model 2).</p><p><strong>Findings: </strong>During the second and third rounds of examinations, a total of 97 thyroid patients were detected, for a detection rate of 10.328 [ <math><msup><mn>10</mn> <mn>5</mn></msup> <msup><mtext>year</mtext> <mrow><mo>-</mo> <mn>1</mn></mrow> </msup> </math> ] (95% confidence interval: 8.464-12.602 [ <math><msup><mn>10</mn> <mn>5</mn></msup> <msup><mtext>year</mtext> <mrow><mo>-</mo> <mn>1</mn></mrow> </msup> </math> ]). Multivariate Poisson regression showed that the detection rate ratio of the ERE (1+ mSv) to <1 (mSv) was 1.577 (0.715-3.394) in Model 1 and 1.596 (0.726-3.512) in Model 2, for Dataset A; and 1.677 (0.746-3.773) in Model 1 and 1.669 (0.743-3.748) in Model 2, for Dataset B.</p><p><strong>Interpretation: </strong>Our study showed no association between radiation exposure with extremely low dose which were more than 99.9% of all the exposure was less than 5 mSv, and thyroid cancer detection, when the follow-up period was an average of 3.7 years at the present, using the cohort study design.</p><p><strong>Funding: </strong>The National Health Fund for Children and Adults Affected by Nuclear Incidents in Japan.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102722"},"PeriodicalIF":9.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11400584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282068","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 a mortality risk prediction model for chronic obstructive pulmonary disease: a cross-sectional study using probabilistic graphical modelling.","authors":"Tyler C Lovelace, Min Hyung Ryu, Minxue Jia, Peter Castaldi, Frank C Sciurba, Craig P Hersh, Panayiotis V Benos","doi":"10.1016/j.eclinm.2024.102786","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102786","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in patients with COPD can be important for disease management strategies. Although all-cause mortality predictors have been developed previously, limited research exists on factors directly affecting COPD-specific mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In a retrospective study, we used probabilistic graphs to analyse clinical cross-sectional data (COPDGene cohort), including demographics, spirometry, quantitative chest imaging, and symptom features, as well as gene expression data. COPDGene recruited current and former smokers, aged 45-80 years with &gt;10 pack-years smoking history, from across the USA (Phase 1, 11/2007-4/2011) and invited them for a follow-up visit (Phase 2, 7/2013-7/2017). ECLIPSE cohort recruited current and former smokers (COPD patients and controls from USA and Europe), aged 45-80 with smoking history &gt;10 pack-years (12/2005-11/2007). We applied graphical models on multi-modal data COPDGene Phase 1 participants to identify factors directly affecting all-cause and COPD-specific mortality (primary outcomes); and on Phase 2 follow-up cohort to identify additional molecular and social factors affecting mortality. We used penalized Cox regression with features selected by the causal graph to build VAPORED, a mortality risk prediction model. VAPORED was compared to existing scores (BODE: BMI, airflow obstruction, dyspnoea, exercise capacity; ADO: age, dyspnoea, airflow obstruction) on the ability to rank individuals by mortality risk, using four evaluation metrics (concordance, concordance probability estimate (CPE), cumulative/dynamic (C/D) area under the receiver operating characteristic curve (AUC), and integrated C/D AUC). The results were validated in ECLIPSE.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Graphical models, applied on the COPDGene Phase 1 samples (n = 8610), identified 11 and 7 variables directly linked to all-cause and COPD-specific mortality, respectively. Although many appear in both models, non-lung comorbidities appear only in the all-cause model, while forced vital capacity (FVC %predicted) appears in COPD-specific mortality model only. Additionally, the graph model of Phase 2 data (n = 3182) identified internet access, CD4 T cells and platelets to be linked to lower mortality risk. Furthermore, using the 7 variables linked to COPD-specific mortality (forced expiratory volume in 1 s/forced vital capacity (FEV&lt;sub&gt;1&lt;/sub&gt;/FVC) ration, FVC %predicted, age, history of pneumonia, oxygen saturation, 6-min walk distance, dyspnoea) we developed &lt;i&gt;VAPORED&lt;/i&gt; mortality risk score, which we validated on the ECLIPSE cohort (3-yr all-cause mortality data, n = 2312). VAPORED performed significantly better than ADO, BODE, and updated BODE indices in predicting all-cause mortality in ECLIPSE in terms of concordance (VAPORED [0.719] vs ADO [0.693; FDR p-value 0.014], BODE [0.695; FDR p-value 0.0","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102786"},"PeriodicalIF":9.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11388367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282070","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}