Background: Neoadjuvant chemoradiation and chemotherapy are recommended for the treatment of nonmetastatic esophageal cancer. The benefit of neoadjuvant treatment is mostly limited to patients who exhibit pathologic complete response (pCR). Existing estimates of pCR rates among patients receiving neoadjuvant therapy have not been synthesized and lack precision.Methods: We conducted an independently funded systematic review and meta‐analysis (PROSPERO CRD42023397402) of pCR rates among patients diagnosed with esophageal cancer treated with neoadjuvant chemo(radiation). Studies were identified from Medline, EMBASE, and CENTRAL database searches. Eligible studies included trials published from 1992 to 2022 that focused on nonmetastatic esophageal cancer, including the gastroesophageal junction. Histology‐specific pooled pCR prevalence was determined using the Freeman–Tukey transformation and a random effects model.Results: After eligibility assessment, 84 studies with 6451 patients were included. The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6%–14%), ranging from 0% to 32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26%–39%), ranging from 8% to 66%. For adenocarcinoma, the pooled prevalence of pCR was 6% (95% CI: 1%–12%) after neoadjuvant chemotherapy, and 22% (18%–26%) after neoadjuvant chemoradiation.Conclusions: Under one‐third of patients with esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. Patients diagnosed with squamous cell carcinomas had higher rates of pCR than those with adenocarcinomas. As pCR represents an increasingly utilized endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.

Study Objective: To determine whether there is a signal for gastrointestinal (GI) or intracranial (IC) hemorrhage associated with the use of antiviral medications for influenza in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.Design: Disproportionality analysis.Data Source: The FAERS database was searched using OpenVigil 2.1 to identify GI and IC hemorrhage events reported between 2004 and 2022.Measurements: Antiviral medications for influenza included the following: oseltamivir, zanamivir, peramivir, and baloxavir marboxil. Hemorrhage events were identified using Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries for GI and IC hemorrhages. Reporting odds ratios (RORs) were calculated to compare the occurrence of GI and IC hemorrhage events between antiviral drugs for influenza and (i) all other medications and (ii) antibiotics. RORs were also calculated for each of the individual antiviral medications.Main Results: A total of 245 cases of GI hemorrhage and 23 cases of IC hemorrhage were identified in association with four antivirals. In comparison with all other drugs, the RORs of GI hemorrhage for oseltamivir, zanamivir, peramivir, baloxavir, and all antivirals combined were 1.17, 0.62, 4.44, 2.53, and 1.22, respectively, indicating potential variations in GI hemorrhage risk among the antivirals. In contrast, in comparison with all other drugs, the RORs of IC hemorrhage for oseltamivir (0.44), zanamivir (0.16), baloxavir (0.44), and all antivirals combined (0.41) were less than 1.0 which is consistent with no elevated risk of IC hemorrhage.Conclusion: In this study, some signals for GI hemorrhage were observed, particularly for peramivir and baloxavir marboxil. Further investigation is warranted to better understand and evaluate the potential risks of GI hemorrhage associated with antiviral treatments for influenza.

Background: Icosapent ethyl (ICP), an ethyl ester of eicosapentaenoic acid (EPA), and omega-3 acid ethyl esters (DHA/EPA), comprised of ethyl esters of EPA and doxosahexaenoic acid (DHA), are approved as adjunctive therapy to statins for reducing adverse cardiovascular events (CV) in patients with CV risks. However, there are concerns regarding a potential association between ICP and atrial fibrillation (AF). This study evaluated the incidence of AF onset between ICP and DHA/EPA when used as adjuvant therapy with statins. Methods and Results: This retrospective study utilized administrative healthcare claims to analyze adult AF-naïve patients from one year preceding their first prescription for ICP or DHA/EPA. These patients were followed for two years, spanning from2013-2021. AF incidence was assessed during active treatment with either ICP or DHA/EPA as adjunct statin therapy. A propensity score (PS) matched cohort controlled for baseline characteristics and the effect of calendar year on the use of ICP or DHA/EPA. The cumulative incidence of AF was estimated using a product-limit estimator and compared between groups using a Cox proportional hazards regression model. The PS-matched cohort included 17,638 participants with a mean age 56 years, predominantly male (65.7% ICP vs. 64.5% DHA/EPA). Over two years, the cumulative incidence of AF from ICP and DHA/EPA was 5.32% and 3.99% respectively, resulting in a HR of 1.242 (95% CI: 1.061 to 1.455). Conclusions: In adult AF-naïve patients, ICP, when compared to DHA/EPA in conjunction with statin therapy, was associated with a significantly higher significant risk of developing AF. RESEARCH PERSPECTIVE: What is New?: Does icopasent ethyl (ICP), an ethyl ester of eicosapentaenoic acid (EPA) and omega-3 acid ethyl esters comprised of ethyl esters of EPA and doxosahexaenoic acid (DHA) in atrial fibrillation (AF)-naïve patients taking statins increase the incidence of AF? Over two years, the cumulative incidence of AF from ICP and DHA/EPA was 5.32% and 3.99% respectively, resulting in a HR of 1.242 (95% CI: 1.061 to 1.455). In adult AF-naïve patients, ICP, when compared to DHA/EPA in conjunction with statin therapy was associated with a higher significant risk of developing AF. What Question Should be Addressed Next?: What should be considered as clinical and demographic factors in identifying patients at risk of atrial fibrillation prior to being prescribed ICP or DHA/EPA agents. Investigation into the underlying mechanism of the increase in atrial fibrillation with marine omega-3 ethyl esters should continue. Understanding AF outcomes from ICP or DHA/EPA use including AF burden, need for AF medical or electrophysiological interventions, and health-care total costs.

To evaluate the prevalence of antiviral drug use in US children with influenza at high risk for complications and to identify factors associated with dispensing. We conducted a retrospective cohort study of outpatient visits for individuals < 18 years during the 2016-2020 influenza seasons using the Merative MarketScan Commercial Claims and Encounter database. High-risk status was defined using Infectious Disease Society of America definitions and included: age, specific co-morbidities, pregnancy or post-partum status, and living in a long-term care facility. The primary outcome was antiviral (oseltamivir, zanamivir, baloxavir) dispensing within two days of influenza diagnosis. We determined clinical factors associated with antiviral dispensing using modified Poisson regression. A total of 372,372 influenza episodes were identified among 331,389 children at high risk for influenza complications and included in this study. The median (interquartile range) age was 4.0 years (2.0, 9.0). Overall, during 201,638 (54.1%) episodes of the influenza, antiviral treatment was dispensed. Factors associated with increased antiviral use included asthma, West and South US geographic regions, urgent care settings, and specific health insurance plans. Factors associated with decreased antiviral use include younger age, emergency department setting, Midwest and Northeast geographic regions, and health insurance plans. Despite national guidelines recommending that all children at high risk for influenza complications receive antiviral treatment, nearly half of these children at high-risk did not receive an antiviral in our study. We identify several factors associated with decreased antiviral treatment that may serve to inform future interventions aiming to improve the care of vulnerable children with influenza.