Pathologic complete response in patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A systematic review and meta-analysis.

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.

Adherence to prescription proton pump inhibitor therapy amongst individuals diagnosed with Barrett's esophagus.

INTRODUCTION: In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described. METHODS: We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups. RESULTS: 79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year. DISCUSSION: Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy.

Optimizing large real-world data analysis with parquet files in R: A step-by-step tutorial.

PURPOSE: The use of open-source programming languages can facilitate open science practices in real-world evidence (RWE) studies. Real-world studies often rely on using big data, which makes using such languages complicated. We demonstrate an efficient approach that enables RWE researchers to use R to undertake RWE analysis tasks from cohort building to reporting. METHODS: Using the Merative Marketscan data (2017-2019), we developed an R function to transform the data into parquet format to be used in R. Then, we compared the differences in data size before and after transformation. We compared the performance of the transformed data in R to the original data in terms of numerical consistency and running times required to complete simple exploratory tasks. To show how the transformed databases can be used in practice, we conducted a simplified replication of an active comparator new user study from the literature. All codes are available on GitHub. RESULTS: Our approach exhibited high efficiency in data storage, as evidenced by the converted data size, which ranged from 10% to 43% of that of the original data files. The runtime of the exploratory tasks in R generally outperformed that of the original data with SAS. We showed, through example, how the converted data can be efficiently used to implement an RWE study. CONCLUSION: We demonstrate a free and efficient solution to facilitate the use of open-source programming languages with big real-world databases, which can facilitate the adoption of open science practices.

Sustained Virologic Response Rates Before and After Removal of Sobriety Restriction for Hepatitis C Virus Treatment Access.

OBJECTIVES: Until November 1, 2018, Illinois Medicaid restricted coverage of hepatitis C virus (HCV) medication to patients with sobriety from alcohol and illicit substances for ≥12 months. This policy limited treatment access for patients with a high risk of HCV transmission, despite clinical trial and real-world data demonstrating high sustained virologic response (SVR) rates among patients with substance use. The objective of this study was to compare HCV SVR rates between patients treated before and after removal of the Illinois Medicaid sobriety restriction. METHODS: We performed a retrospective cohort study of Medicaid-insured patients who completed direct-acting antiviral treatment at an urban, academic medical center in Illinois from January 1, 2014, through October 21, 2020. The primary endpoint was SVR. We compared group characteristics using χ2 or Fisher exact tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. We used logistic regression to compare SVR rates before and after the policy change, adjusting for differences between groups. RESULTS: A total of 496 patients (348 pre-policy change; 148 post-policy change) started treatment; excluding loss to follow-up/early discontinuation, SVR rates were 95.4% (309 of 324) pre-policy change and 97.1% (134 of 138) post-policy change. SVR rates did not differ after adjusting for the use of historic HCV regimens and the higher cirrhosis rate in the pre-policy change group compared with the post-policy change group (odds ratio = 0.98; 95% CI, 0.32-3.67). CONCLUSION: HCV SVR rates were similar before and after removal of the Illinois Medicaid sobriety restriction, regardless of group differences. Results support HCV treatment regardless of documented sobriety to facilitate progress toward HCV elimination.

Role of cytokines produced by T helper immune-modulators in dengue pathogenesis: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Modulation of the immune reaction is essential in the development of various diseases, including dengue's "Cytokine Tsunami", an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis. MATERIAL AND METHODS: Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230. RESULTS: A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively. CONCLUSIONS: This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

Assessment of community pharmacy management towards self-medication requests of tetracyclines for pregnant women: a simulated client study in Upper Egypt.

Background Self-medication is a worldwide phenomenon of using medications without medical supervision. It is even more prevalent in low-income countries, where individuals seek community pharmacies because of accessibility and affordability. Although self-medication is associated with an increased risk of medication errors, few studies have been conducted to examine the quality of community pharmacy management towards self-medicating individuals of at-risk populations such as pregnant women. Objective We sought to investigate the quality of community pharmacies management of self-medication requests of tetracyclines for pregnant women. Setting The study was conducted in community pharmacies in Minya, Egypt. Methods A random sample of 150 community pharmacies was chosen from the urban areas of five districts of Minya, Egypt. To evaluate the actual practice, a simulated client was trained to visit pharmacies and purchase doxycycline for a pregnant woman. In a random subset of the sampled pharmacies (n = 100), interviews were conducted to evaluate pharmacy staff knowledge and attitudes regarding information gathering and dispensing practice. Main outcome measure Dispensing rate of doxycycline for pregnant women. Results From simulated client visits, almost all pharmacy staff (99.1%) dispensed doxycycline without requesting a prescription or collecting any information. About 25% of staff members did not abstain from dispensing even after knowing about pregnancy. On the other hand, most interviewed pharmacy staff (91.5%) reported that they ask about pregnancy before dispensing. Conclusion Our findings show that the current community pharmacy practice puts pregnant women at high risk of experiencing harmful self-medication outcomes. Therefore, strict legislative measures and pharmacy education programs should be considered in Egypt to lessen inappropriate dispensing rates in community pharmacies.

Quality of Community Pharmacy Practice in Antibiotic Self-Medication Encounters: A Simulated Patient Study in Upper Egypt.

Antibiotic misuse, either by patients or healthcare professionals, is one of the major contributing factors to antimicrobial resistance. In many Middle Eastern countries including Egypt, there are no strict regulations regarding antibiotic dispensing by community pharmacies. In this study, we examined antibiotic dispensing patterns in Egyptian community pharmacies. About 150 community pharmacies were randomly chosen using convenience sampling from the five most populous urban districts of Minia Governorate in Egypt. Two simulated patient (SP) scenarios of viral respiratory tract infection requiring no antibiotic treatment were used to assess the actual antibiotics dispensing practice of. Face-to-face interviews were then conducted to assess the intended dispensing practice. Descriptive statistics were calculated to report the main study outcomes. In 238 visits of both scenarios, 98.3% of service providers dispensed amoxicillin. Although stated otherwise in interviews, most pharmacy providers (63%) dispensed amoxicillin without collecting relevant information from presenting SPs. Findings showed high rates of antibiotic misuse in community pharmacies. Discrepancies between interviews and patient simulation results also suggest a practice‒knowledge gap. Corrective actions, whether legislation, enforcement, education, or awareness campaigns about antibiotic misuse, are urgently needed to improve antibiotic dispensing practices in Egyptian community pharmacies.