PROTON-PUMP INHIBITORS ARE ASSOCIATED WITH AN INCREASED RISK OF MICROSCOPIC COLITIS: A POPULATION-BASED STUDY AND REVIEW OF THE LITERATURE.

BACKGROUND: •The study evaluated the risk of developing microscopic colitis and its subtypes in patients on PPI therapy. BACKGROUND: •Using a large multicenter database, a retrospective cohort analysis was conducted, excluding patients with autoimmune diseases, and adjusting for confounders. BACKGROUND: •An increased risk of developing microscopic colitis was associated with female gender, smoking, and the use of PPI, SSRI, and NSAIDs. BACKGROUND: •The use of PPI represented the highest odds of developing microscopic colitis. BACKGROUND: Microscopic colitis is a relatively new diagnosis that was first described in the 1980s. Patients usually present with chronic watery and non-bloody diarrhea and are typically characterized by an unremarkable gross appearance of the colon on lower endoscopy while having evidence of lymphocytic infiltration of the lamina propria and the epithelium on histology. Two subtypes have been described in the literature: Collagenous colitis, with marked thickening of the subepithelial layer, and Lymphocytic colitis. Multiple risk factors such as female gender, older age and celiac disease have been associated with this entity. A few studies have found an association between microscopic colitis and proton-pump inhibitor (PPI). The aim of our study was to evaluate the risk of developing microscopic colitis and its subtypes for patients who are on PPI therapy. METHODS: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have been diagnosed with any autoimmune disease have been excluded. A multivariate regression analysis was performed to assess risk of developing microscopic, lymphocytic, and collagenous colitis by accounting for potential confounders including female gender, smoking history, and the use of proton pump inhibitor, nonsteroidal anti-inflammatory drugs, and selective serotonin receptor inhibitors. A two-sided P value <0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). RESULTS: 78,256,749 individuals were screened in the database and 69,315,150 were selected in the final analysis after accounting for inclusion and exclusion criteria. The baseline characteristics of patients with microscopic, lymphocytic, and collagenous colitis is seen in table 1. Using a multivariate regression analysis, the risk of developing microscopic, lymphocytic, and collagenous colitis was calculated and illustrated in table 2. DISCUSSION: Our study showed that the risk of microscopic colitis, lymphocytic colitis and collagenous colitis was higher in females and smokers. Although medications like SSRI and NSAIDs showed a positive correlation with colitis, the highest likelihood of developing this disease was associated with PPIs. Lansoprazole has been documented to be associated with microscopic colitis as it is believed to inhibit colonic proton pumps, and subsequently promote diarrhea and inflammation. Interestingly, the prevalence of lymphocytic colitis and collagenous colitis was similar in the cohort of patients treated with PPIs, indicating no specific predisposition to either subtype. This study further confirms the risk factors associated with microscopic colitis. It can help guide physicians to recognize and eliminate these risk factors prior to initiating treatment for this disease. Future studies can focus on identifying the incidence of microscopic colitis with the different types of PPIs in the market.

•The study evaluated the risk of developing microscopic colitis and its subtypes in patients on PPI therapy. •Using a large multicenter database, a retrospective cohort analysis was conducted, excluding patients with autoimmune diseases, and adjusting for confounders. •An increased risk of developing microscopic colitis was associated with female gender, smoking, and the use of PPI, SSRI, and NSAIDs. •The use of PPI represented the highest odds of developing microscopic colitis.

A Precision Oncology Platform to Support Genotype-Tailored Therapy Selection.

There is a critical need for a streamlined process to identify genotype-matched individuals eligible for enrollment into clinical trials and/or targeted therapies, as current methodologies face challenges in integrating diverse molecular data sources. We have developed a precision oncology platform to assist molecular tumor boards and community oncologists in reviewing patients' phenotypes, evaluating related knowledge, and identifying genotype-matched therapies.

Adverse Event Reporting in Randomized Clinical Trials for Multiple Myeloma.

Importance: Cancer treatment can result in burdensome toxic effects that profoundly affect patient quality of life. In seeking to emphasize the efficacy of tested treatments, clinical trial reports may use subjective or minimizing terms to describe adverse events (AEs). Objective: To evaluate patterns of AE reporting in multiple myeloma (MM) randomized clinical trials (RCTs) published between 2015 and early 2023. Design, Setting, and Participants: For this cohort study, the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched to assess the prevalence of minimizing terms in MM RCTs published between January 1, 2015, and March 1, 2023. Minimizing terms were defined as subjective terms used to favorably describe the safety profile of the intervention. The terms searched included convenient, manageable, acceptable, expected, well-tolerated, tolerable, favorable, and safe. Final data analysis was performed on July 21, 2023. Main Outcomes and Measures: The primary outcome was the occurrence of at least 1 minimizing term in an article. Univariate logistic regression analyses were performed to evaluate the association between the presence of at least 1 minimizing term and the actual incidence of grade 3 or 4 AEs, serious AEs, or grade 5 AEs. Results: Of the 65 RCTs included, 56 (86%) used minimizing terms when describing treatment-emergent AEs. The most frequently used minimizing terms were well-tolerated or tolerable in 29 trials (45%), manageable in 18 (28%), and acceptable in 16 (25%). Grade 3 or 4 AE rate in the examined RCTs ranged from 23% to 94%, with a median of 75% (IQR, 59%-82%). A univariate regression analysis demonstrated no association between the use of minimizing terms and grade 3 or 4 AE rates (odds ratio [OR], 1.35 [95% CI, 0.88-2.10] per 10% AE rate increase; P = .17) or grade 5 AE rates (OR, 3.16 [95% CI, 0.27-12.7] per 10% AE rate increase; P = .45). Conclusions and Relevance: These findings suggest that trial investigators and sponsors regularly use minimizing terms to describe toxic effects in MM trials, and use of this terminology may not reflect actual AE rates in these studies. Instead of using these terms, trial investigators should highlight event rates and patient-reported outcomes, to allow clinicians and patients to better evaluate the true tolerability of AEs.