Navigating the Challenges of Cyclosporine as an Alternative to Rifampicin as an OATP1B Index Inhibitor.

Rifampicin is a widely employed index inhibitor to assess the impact of organic anion transporting polypeptide 1B (OATP1B) inhibition on investigational drugs. The observation of nitrosamines in certain drug products, including rifampicin, has impacted the conduct of clinical drug-drug interaction (DDI) studies with rifampicin drug products. Cyclosporine is a recommended alternative to assess in vivo OATP1B activity; however, challenges exist in its use due to pharmacokinetic (PK) variability and non-selective inhibition of other drug disposition mechanisms.

It's Getting Better All the Time: Decreased Cumulative Incidence of Waitlist Mortality in Pediatric Candidates Following 2018 Heart Allocation Policy Change.

Purpose: In October 2018, the OPTN changed adult heart transplant (HT) allocation policy, increasing the number of adult candidates that had higher priority than pediatric candidates, potentially disadvantaging pediatric waitlist registrants.

Methods: To understand the impact of this policy change, we used SRTR data to identify 1469 pre-policy (7/2016-9/2018) and 2901 (10/2018-12/2022) post-policy pediatric (< 18 years) HT registrants. We quantified mortality and transplant risks using weighted cause-specific hazard models, and then using weighted competing risks regression.

Reader's digest version of scientific writing: comparative evaluation of summarization capacity between large language models and medical students in analyzing scientific writing in sleep medicine.

Introduction: As artificial intelligence systems like large language models (LLM) and natural language processing advance, the need to evaluate their utility within medicine and medical education grows. As medical research publications continue to grow exponentially, AI systems offer valuable opportunities to condense and synthesize information, especially in underrepresented areas such as Sleep Medicine. The present study aims to compare summarization capacity between LLM generated summaries of sleep medicine research article abstracts, to summaries generated by Medical Student (humans) and to evaluate if the research content, and literary readability summarized is retained comparably.

Positioning Enzyme- and Transporter-Based Precipitant Drug-Drug Interaction Studies in Drug Design.

assessment of the potential of compounds to affect drug metabolizing enzymes and transporters and perpetrate drug-drug interactions (DDIs) is a common practice in drug research. For the development phase, regulators define an exhaustive list of enzymes and transporters to consider, but DDIs associated with many of these are minor and can be well-managed in the clinic; thus, progression of drug candidates that address unmet medical needs should not be curtailed due to this property. However, some enzymes and transporters are very important in drug disposition, so it is important to avoid/reduce inhibition or induction of these through drug design.

Ralstonia pickettii bacteremia: A retrospective review of records.

Introduction: Ralstonia pickettii is a non-fermenting gram-negative bacillus rarely associated with hospital-acquired infections. The study aimed to characterise the clinical profile and outcomes of R. pickettii bacteremia cases.