Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study.

BACKGROUND: Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD) and its complications. AIM: To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications DESIGN: We used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated two cohorts totalling 1 543 351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), we analysed outcomes and separately examined outcomes in patients starting short-acting (≤1 day) and long-acting (≥5 days) GLP-1 RAs. RESULTS: 177 666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR 1.15; 95% CI 1.09 to 1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR 1.215; 95% CI 1.111 to 1.328), but not long-acting (HR 0.994; 95% CI 0.924 to 1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of oesophageal stricture (HR 1.284; 95% CI 1.135 to 1.453), Barrett's without dysplasia (HR 1.372; 95% CI 1.217 to 1.546) and Barrett's with dysplasia (HR 1.505; 95% CI 1.164 to 1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide. CONCLUSION: Starting shorter-acting GLP-1 RAs is associated with increased risks of GERD and its complications.

How to Treat EGFR-Mutated Non-Small Cell Lung Cancer.

•Mutations in the EGFR gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous EGFR mutations, with the most common being exon 19 deletions and the point mutation L858R in exon 21.•Osimertinib, an oral TKI, is used as the initial therapy for metastatic NSCLC harboring exon 19 deletion and exon 21 L858R mutation. Common side effects include acneiform rash, diarrhea, and paronychia. Osimertinib has also been associated with cardiomyopathy (∼1.4%-2.4%) and prolongation of the QT interval (2.7%).•In our experience, osimertinib-induced cardiomyopathy can be managed with the cessation of osimertinib and the initiation of guideline-directed therapy. Given that osimertinib is often the best available therapy, rechallenging with osimertinib often favors benefit over risk. Safe rechallenge with osimertinib is demonstrated in this case.

Awareness, understanding, use, and impact of the UV index: A systematic review of over two decades of international research.

The ultraviolet radiation index (UVI) was adopted internationally to raise awareness about and encourage the public to protect their skin from skin cancer. The current paper is a systematic review of over 20 years of research investigating awareness, comprehension, use, and impact of the UVI. Thirty-one studies were included from the USA, Canada, Europe, Australia, New Zealand, and elsewhere. Awareness of the UVI varies by country, with samples from some countries demonstrating high awareness. However, comprehension and use of the UVI to inform sun safety behaviors are typically much lower. In fact, greater UVI awareness has sometimes been associated with riskier UV-related behaviors such as intentional tanning. Fewer studies have evaluated interventions, and their results have been mixed. In summary, more research is needed to determine how to help the public understand and use the UVI for effective skin protection. This review offers suggestions for future use of and research with the UVI.