EClinicalMedicine最新文献

{"title":"A systematic review and network meta-analysis of psychological, psychosocial, pharmacological, physical and combined treatments for adults with a new episode of depression.","authors":"Ifigeneia Mavranezouli, Odette Megnin-Viggars, Hugo Pedder, Nicky J Welton, Sofia Dias, Edward Watkins, Neil Nixon, Caitlin H Daly, Edna Keeney, Hilary Eadon, Deborah M Caldwell, Katriona J M O'Donoghue, Sarah Stockton, Stephanie Arnold, James Thomas, Navneet Kapur, Stephen Pilling","doi":"10.1016/j.eclinm.2024.102780","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102780","url":null,"abstract":"<p><strong>Background: </strong>Various effective treatments for depression exist. We aimed to identify the most effective first-line treatments for new episodes of less and more severe depression (defined by depression scale cut-off scores), to update NICE guidance on the management of Depression in Adults in England.</p><p><strong>Methods: </strong>Systematic review and network meta-analysis of randomised controlled trials (RCTs) published up to June 2020 (PROSPERO registration number CRD42019151328). We analysed interventions by class and individually. The primary efficacy outcome was depressive symptom change (expressed as standardised mean difference [SMD]). The review for this outcome was updated in November 2023.</p><p><strong>Findings: </strong>We included 676 RCTs, 105,477 participants and 63 treatment classes. For less severe depression, group cognitive/cognitive behavioural therapy (CT/CBT) class was efficacious versus treatment as usual [TAU], the reference treatment for this population [SMD -1.01 (95% Credible Interval [CrI] -1.76; -0.06)]. For more severe depression, efficacious classes versus pill placebo (reference treatment for this population) included combined individual CT/CBT with antidepressants [-1.18 (-2.07; -0.44)], individual behavioural therapies [-0.86 (-1.65; -0.16)], combined light therapy with antidepressants [-0.86 (-1.59; -0.12)], combined acupuncture with antidepressants [-0.78 (-1.12; -0.44)], individual CT/CBT [-0.78 (-1.42; -0.33)], mirtazapine [-0.35 (-0.48; -0.22)], serotonin and norepinephrine reuptake inhibitors [-0.32 (-0.43; -0.22)], tricyclic antidepressants [-0.29 (-0.50; -0.05)], and selective serotonin reuptake inhibitors [-0.24 (-0.32; -0.16)]. Additional treatments showed evidence of efficacy at the intervention level. Evidence for less and more severe depression was of low and low-to-moderate quality, respectively. In the 2023 update, group yoga and self-help without support emerged as efficacious for less severe depression. For more severe depression, combined group exercise with antidepressants emerged as efficacious, whereas combined light therapy with antidepressants failed to remain efficacious.</p><p><strong>Interpretation: </strong>Group CT/CBT (and possibly group yoga and self-help) appears efficacious in less severe depression, whereas antidepressants do not show evidence of effect. Combined antidepressants with individual CT/CBT, acupuncture and, possibly, group exercise, individual psychological therapies (behavioural therapies, CT/CBT) alone, and antidepressants alone appear efficacious in more severe depression. Quality of evidence, cost-effectiveness, applicability and implementation issues also need to be considered when formulating clinical practice recommendations.</p><p><strong>Funding: </strong>National Institute for Health and Care Excellence.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153442","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":"Contribution of ethnicity, area level deprivation and air pollution to paediatric intensive care unit admissions in the United Kingdom 2008-2021.","authors":"Hannah K Mitchell, Sarah E Seaton, Christopher Leahy, Khurram Mustafa, Hannah Buckley, Peter Davis, Richard G Feltbower, Padmanabhan Ramnarayan","doi":"10.1016/j.eclinm.2024.102776","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102776","url":null,"abstract":"<p><strong>Background: </strong>There is emerging evidence on the impact of social and environmental determinants of health on paediatric intensive care unit (PICU) admissions and outcomes. We analysed UK paediatric intensive care data to explore disparities in the incidence of admission according to a child's ethnicity and the degree of deprivation and pollution in the child's residential area.</p><p><strong>Methods: </strong>Data were extracted on children <16 years admitted to UK PICUs between 1st January 2008 and 31st December 2021 from the Paediatric Intensive Care Audit Network (PICANet) database. Ethnicity was categorised as White, Asian, Black, Mixed or Other. Deprivation was quantified using the 'children in low-income families' measure and outdoor air pollution was characterised using mean annual PM2.5 level at local authority level, both divided into population-weighted quintiles. UK population estimates were used to calculate crude incidence of PICU admission. Incidence rate ratios were calculated using Poisson regression models.</p><p><strong>Findings: </strong>There were 245,099 admissions, of which 60.7% were unplanned. After adjusting for age and sex, Asian and Black children had higher relative incidence of unplanned PICU admission compared to White (IRR 1.29 [95% CI: 1.25-1.33] and 1.50 [95% CI: 1.44-1.56] respectively), but there was no evidence of increased incidence of planned admission. Children living in the most deprived quintile had 1.50 times the incidence of admission in the least deprived quintile (95% CI: 1.46-1.54). There were higher crude admission levels of children living in the most polluted quintile compared to the least (157.8 vs 113.6 admissions per 100,000 child years), but after adjustment for ethnicity, deprivation, age and sex there was no association between pollution and PICU admission (IRR 1.00 [95% CI: 1.00-1.00] per 1 μg/m³ increase).</p><p><strong>Interpretation: </strong>Ethnicity and deprivation impact the incidence of PICU admission. When restricting to unplanned respiratory admissions and ventilated patients only, increasing pollution level was associated with increased incidence of PICU admission. It is essential to act to reduce these observed disparities, further work is needed to understand mechanisms behind these findings and how they relate to outcomes.</p><p><strong>Funding: </strong>There was no direct funding for this project. HM was funded by an NIHR Academic Clinical Fellowship (ACF-2022-18-017).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153443","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":"Tumor contour irregularity on preoperative CT predicts prognosis in renal cell carcinoma: a multi-institutional study.","authors":"Pingyi Zhu, Chenchen Dai, Ying Xiong, Jianyi Qu, Ruiting Wang, Linpeng Yao, Feng Zhang, Jun Hou, Mengsu Zeng, Jianming Guo, Shuo Wang, Feng Chen, Jianjun Zhou","doi":"10.1016/j.eclinm.2024.102775","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102775","url":null,"abstract":"<p><strong>Background: </strong>Radiology-based prognostic biomarkers play a crucial role in patient counseling, enhancing surveillance, and designing clinical trials effectively. This study aims to assess the predictive significance of preoperative CT-based tumor contour irregularity in determining clinical outcomes among patients with renal cell carcinoma (RCC).</p><p><strong>Methods: </strong>We conducted a retrospective multi-institutional review involving 2218 patients pathologically diagnosed with RCC. The training and internal validation sets included patients at Zhongshan Hospital between January 2009 and August 2019. The external test set comprised patients from the First Affiliated Hospital, Zhejiang University School of Medicine (January 2016 to January 2018), the Xiamen Branch of Zhongshan Hospital (November 2017 to June 2023), and the Cancer Imaging Archive. The contour irregularity degree (CID), quantified as the ratio of irregular cross-sections to the total tumor cross-sections, was analyzed for its prognostic relevance across different subgroups of RCC patients. A novel CID-based scoring system was developed, and its predictive efficacy was evaluated and compared with existing prognostic models.</p><p><strong>Findings: </strong>The CID exhibited significant discriminatory power in predicting overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) among patients with RCC tumors measuring 3 cm or larger (all p < 0.001). Multivariate analyses confirmed the CID as an independent prognostic indicator. Notably, the CID augmented prognostic stratification among RCC patients within distinct risk subgroups delineated by SSIGN models and ISUP grades. The CID-based nomogram (C-Model) demonstrated robust predictive performance, with C-index values of 0.88 (95%CI: 0.84-0.92) in the training set, 0.92 (95%CI: 0.88-0.98) in the internal validation set, and 0.86 (95%CI: 0.81-0.90) in the external test set, surpassing existing prognostic models.</p><p><strong>Interpretation: </strong>Routine imaging-based assessment of the CID serves as an independent prognostic factor, offering incremental prognostic value to existing models in RCC patients with tumors measuring 3 cm or larger.</p><p><strong>Funding: </strong>This study was funded by grants from National Natural Science Foundation of China; Shanghai Municipal Health Commission; China National Key R&D Program and Science and Technology Commission of Shanghai Municipality.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153446","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-based therapies for the treatment of resistant hypertension in individuals with overweight or obesity: a review.","authors":"Candace Jarade, Tetiana Zolotarova, Areesha Moiz, Mark J Eisenberg","doi":"10.1016/j.eclinm.2024.102789","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102789","url":null,"abstract":"<p><p>Despite the availability of a wide range of antihypertensive agents, a significant proportion of individuals with resistant hypertension (RHTN) struggle to achieve blood pressure (BP) control. Obesity ranks among the most significant modifiable risk factors for RHTN, with 56-91% of patients with RHTN classified as overweight or obese. Glucagon-like peptide-1 receptor agonist (GLP-1 RAs) are a class of anti-obesity medications that have recently demonstrated efficacy in reducing BP and improving cardiovascular (CV) outcomes in individuals with overweight or obesity. Among the available GLP-1-based therapies, liraglutide, semaglutide, and tirzepatide have been approved for chronic weight management in this population. Tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist, has the greatest effect on weight loss and BP reduction compared to GLP-1 RAs alone. To our knowledge, no trials have directly evaluated the effect of GLP-1 RAs or dual GLP-1/GIP receptor agonists on RHTN management. In this review article, we propose that targeting weight loss through GLP-1-based therapies should be explored as a treatment option for individuals with RHTN who are overweight or obese.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153444","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":"Incidence of new onset type 2 diabetes in adults living with obesity treated with tirzepatide or semaglutide: real world evidence from an international retrospective cohort study.","authors":"Matthew Anson, Alex E Henney, Nicholas Broadwell, Sizheng S Zhao, Gema H Ibarburu, Gregory Y H Lip, John P H Wilding, Daniel J Cuthbertson, Uazman Alam","doi":"10.1016/j.eclinm.2024.102777","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102777","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Tirzepatide, a novel dual agonist of glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), has demonstrated greater magnitude of weight loss compared to semaglutide in a phase 3 clinical trial. However, the effect of tirzepatide on incidence of type 2 diabetes (T2D) in individuals with overweight and obesity, and the effect on major adverse cardiovascular outcomes in individuals with pre-existing T2D, remains unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a retrospective cohort study of anonymised electronic medical records using the TriNetX network (TriNetX LLC, Cambridge, MA, USA) a global federated database. The data used in this study was collected on 5th June 2024. Two cohorts of individuals were generated: &lt;b&gt;1)&lt;/b&gt; without pre-existing T2D and, &lt;b&gt;2)&lt;/b&gt; with T2D. We adopted an active comparator new user design on new initiations of either tirzepatide &lt;i&gt;or&lt;/i&gt; semaglutide therapy. Analysis began from the index event which was defined as individuals on respective therapy for 6 months only. Analysis of outcomes was conducted off-drug, in individuals without a pre-existing history of the disease of interest. Individuals were followed up for 12 months post the index event. &lt;b&gt;Primary outcome&lt;/b&gt; for &lt;b&gt;cohort 1&lt;/b&gt; was incidence of T2D, and for &lt;b&gt;cohort 2&lt;/b&gt; was composite: all-cause mortality, cerebral infarction, acute coronary syndrome, and heart failure. &lt;b&gt;Secondary outcomes&lt;/b&gt; for &lt;b&gt;cohort 1&lt;/b&gt; were change in HbA1c and body weight and for &lt;b&gt;cohort 2&lt;/b&gt;: incidence of micro- and macrovascular complications, suicidal ideation and/or attempt, and all-cause mortality. We propensity score matched (1:1) for potential confounders: baseline demographics, socioeconomic circumstances, HbA1c, weight, relevant co-morbidities, and anti-obesity, hypoglycaemic and cardioprotective agents.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;The study population without T2D consisted of 13,846 individuals, equally split between tirzepatide and semaglutide users. Tirzepatide was associated with both lower risk for incident T2D (HR 0.73, 95% CI 0.58-0.92, p &lt; 0.001) and greater weight loss (-7.7 kg, [95% CI -6.8, -8.5 kg], p &lt; 0.001), compared to semaglutide (-4.8 kg, [95% CI -3.9, -5.6 kg], p &lt; 0.001). In individuals with pre-existing T2D (n = 8446), tirzepatide was associated with lower risk of the composite outcome (HR 0.54, 95% CI 0.38-0.76, p &lt; 0.001), cerebral infarction (HR 0.45, 95% CI 0.24-0.84, p = 0.010) and all-cause mortality (HR 0.33, 95% CI 0.15-0.73, p = 0.004) compared to semaglutide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Tirzepatide is associated with significantly reduced risk of developing T2D and major adverse cardiovascular events in individuals living with obesity and T2D respectively. Randomised controlled trials investigating the utility of dual incretin agonists in the primary prevention of T2D and cardiovascular disease in higher risk populations are now required.&lt;/p&gt;&lt;p","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153445","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 a precision hepatocellular carcinoma surveillance strategy in patients with cirrhosis.","authors":"Szu-Yu Zoe Kao, Kinpritma Sangha, Naoto Fujiwara, Yujin Hoshida, Neehar D Parikh, Amit G Singal","doi":"10.1016/j.eclinm.2024.102755","DOIUrl":"10.1016/j.eclinm.2024.102755","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) surveillance is currently performed using a one-size-fits-all strategy with ultrasound plus AFP (US + AFP). There is increasing interest in risk-stratified and precision surveillance strategies incorporating individual risk and variance in surveillance test performance; however, the cost-effectiveness of these approaches has not been evaluated.</p><p><strong>Methods: </strong>We conducted a cost-effectiveness analysis to evaluate four surveillance strategies (no surveillance, universal US + AFP surveillance, risk-stratified surveillance, and precision surveillance) in a simulated cohort of 50-year-old patients with compensated cirrhosis. The most cost-effective strategy was that with the highest incremental cost-effectiveness ratio (ICER) and below the willingness-to-pay (WTP) threshold of $150,000/QALY gained. Model inputs were based on literature review, and costs were derived from the Medicare fee schedule.</p><p><strong>Findings: </strong>The precision surveillance strategy demonstrated variation in recommended surveillance test based on HCC risk category and patient factors. US + AFP, risk-stratified, and precision surveillance detected more HCC cases per 100,000 population than no surveillance, with a higher proportion of early-stage cases for precision surveillance (67.6%) than risk-stratified (63.8%), universal ultrasound (63.2%), and no surveillance (38.0%). Compared to no surveillance, precision surveillance was most cost-effective, with an ICER of $104,614/QALY gained, whereas US + AFP and risk-stratified surveillance were both dominated. Compared to US + AFP, risk-stratified surveillance was cost saving and dominated US + AFP, whereas precision surveillance was cost-effective, with an ICER of $98,103/QALY gained. Results were sensitive to survival with early-stage HCC, cost of early-stage HCC treatment, and surveillance utilization. Precision surveillance remained the most cost-effective when WTP thresholds exceeded $110,000/QALY gained.</p><p><strong>Interpretation: </strong>A precision surveillance strategy is the most cost-effective method for HCC surveillance. This approach could maximize surveillance benefits in high-risk patients, while minimizing surveillance harms in low-risk individuals.</p><p><strong>Funding: </strong>National Cancer Institute (U01 CA230694, R01 CA222900, R01 CA212008, and U24ca086368) and Cancer Prevention Research Institute of Texas (CPRIT) (RP200554).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132146","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":"Earnings and work loss after colon and rectal cancer: a Swedish nationwide matched cohort study.","authors":"S E Boman, I Hed Myrberg, G Bruze, A Martling, C Nordenvall, P J Nilsson","doi":"10.1016/j.eclinm.2024.102770","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102770","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is common and prognosis is improving. The conditions of survivors of treatment, including financial consequences, are thus important. The aim of this study was to quantify loss of earnings and work loss in working-age patients with colon and rectal cancer relative to matched comparators.</p><p><strong>Methods: </strong>The study utilised data from the CRCBaSe database that is generated from the nationwide Swedish ColoRectal Cancer Register and includes data from several Swedish nationwide registers. The study period was 1995-2020 for rectal cancer patients and 2007-2020 for colon cancer patients. A retrospective population-based nationwide cohort study on earnings, disposable income, and work loss, in survivors of stage I-III colorectal cancer treatment was undertaken. Median regression was used to analyse earnings and disposable income, and logistic regression to analyse the probability of work loss.</p><p><strong>Findings: </strong>A cohort of 8863 colorectal cancer survivors diagnosed before 2017 and 52,514 comparators matched on birth year, legal sex, and county of residence, was analysed. There was a clear reduction in earnings between the calendar year prior to and the calendar year after diagnosis, from € 31,319 to € 23,924 for colon cancer patients and from € 32,636 to € 22,647 for rectal cancer patients, and earnings never fully recovered during the 5-year follow-up. Disposable income was practically unaltered. The probability of work loss increased in the calendar year of diagnosis, from 29.8% to 25.3% the previous year to 83.3% and 84.4% for colon and rectal cancer patients respectively, and never fully recovered. The probability of work loss was similar between colon and rectal cancer survivors, but was higher among patients with rectal cancer who had received neoadjuvant therapy.</p><p><strong>Interpretation: </strong>This study shows that despite an extensive welfare system providing maintained disposable income, there is a financial burden in the form of increased risk of work loss and a reduction in earnings among survivors of colorectal cancer.</p><p><strong>Funding: </strong>The study was supported by the Swedish Cancer Society, the Swedish Cancer and Allergy Foundation, and the Stockholm Cancer Society, and supported by grants provided by the Regional Agreement on Medical Training and Clinical Research (ALF) between the Stockholm County Council and Karolinska Institutet.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105460","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":"Prevalence of exocrine pancreatic insufficiency at 12 months after acute pancreatitis: a prospective, multicentre, longitudinal cohort study.","authors":"Anna Evans Phillips, Joseph Bejjani, Stacey Culp, Jennifer Chennat, Peter J Lee, Jorge D Machicado, Vikesh K Singh, Elham Afghani, Mitchell L Ramsey, Pedram Paragomi, Kimberly Stello, Melica Nikahd, Phil A Hart, Georgios I Papachristou","doi":"10.1016/j.eclinm.2024.102774","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102774","url":null,"abstract":"<p><strong>Background: </strong>Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort.</p><p><strong>Methods: </strong>In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 μg/g; severe FE-1 level ≤100 μg/g; mild FE-1 101-200 μg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398.</p><p><strong>Findings: </strong>EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%).</p><p><strong>Interpretation: </strong>EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening.</p><p><strong>Funding: </strong>This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105461","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 efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial.","authors":"Lichun Weng, Liutong Wei, Qiuwan Zhang, Taotao Sun, Xiaojun Kuang, Qin Huang, Yunyun Cao, Xiaoyi Liu, Qian Wang, Ying Guo, Junyan Sun, Lulu Wang, Haihong Tang, Haiou Yang, Qian Chen, Jian Zhang, Bingshun Wang, Zhaoxia Qian, Dongmei Lai","doi":"10.1016/j.eclinm.2024.102744","DOIUrl":"10.1016/j.eclinm.2024.102744","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF.</p><p><strong>Methods: </strong>A total of 35 patients received 6 × 10⁷ hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104.</p><p><strong>Findings: </strong>No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT.</p><p><strong>Interpretation: </strong>hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008494","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":"European Society of Human Reproduction and Embryology annual meeting 2024.","authors":"Ben Burwood","doi":"10.1016/j.eclinm.2024.102781","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.102781","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008493","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}