Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Fluorescent identification of axons, dendrites and soma of neuronal retinal ganglion cells with a genetic marker as a tool for facilitating the study of neurodegeneration.

This study characterizes a fluorescent -tdTomato neuronal reporter mouse line with strong labeling of axons throughout the optic nerve, of retinal ganglion cell (RGC) soma in the ganglion cell layer (GCL), and of RGC dendrites in the inner plexiform layer (IPL). The model facilitated assessment of RGC loss in models of degeneration and of RGC detection in mixed neural/glial cultures. The tdTomato signal showed strong overlap with >98% cells immunolabeled with RGC markers RBPMS or BRN3A, consistent with the ubiquitous presence of the vesicular glutamate transporter 2 (VGUT2, SLC17A6) in all RGC subtypes.

Risk of Hypoglycemia Associated with Concomitant Use of Insulin Secretagogues and ACE Inhibitors in Adults with Type 2 Diabetes: A Systematic Review.

Insulin secretagogues and angiotensin-converting enzyme inhibitors (ACEIs) are commonly co-prescribed for patients with type 2 diabetes (T2D). Case reports suggesting that co-administration of insulin secretagogues with ACEIs is associated with an increased risk of serious hypoglycemia have led to warnings regarding a drug-drug interaction in widely used drug compendia. However, subsequent studies have had inconsistent results.

Defining key deprescribing measures from electronic health data: A multisite data harmonization project.

Background: Stopping or reducing risky or unneeded medications ("deprescribing") could improve older adults' health. Electronic health data can support observational and intervention studies of deprescribing, but there are no standardized measures for key variables, and healthcare systems have differing data types and availability. We developed definitions for chronic medication use and discontinuation based on electronic health data and applied them in a case study of benzodiazepines and Z-drugs in five diverse US healthcare systems.

Do mindfulness interventions cause harm? Findings from the Learning to Apply Mindfulness to Pain (LAMP) Pragmatic Clinical Trial.

Background: Although mindfulness-based interventions (MBIs) are widely used in clinical and nonclinical settings, there has been little systematic study of their potential risks. To address this gap, we examined differences in psychological and physical worsening among participants in the usual care and intervention conditions of a 3-group, randomized pragmatic trial (Learning to Apply Mindfulness to Pain [LAMP]) that tested the effectiveness of 2 approaches to delivering MBIs to patients with chronic pain.

Methods: The sample consisted of 374 male and 334 female patients with chronic pain enrolled in the LAMP trial who completed a 10-week follow-up survey, 61% of whom had a mental health diagnosis.

Do relationships between ambient temperature and serious adverse health outcomes vary among users of different antidiabetes drugs? A retrospective cohort study of US Medicaid beneficiaries with type 2 diabetes.

Objective: Prior studies demonstrate that some untoward clinical outcomes vary by outdoor temperature. This is true of some endpoints common among persons with diabetes, a population vulnerable to climate change-associated health risks. Yet, prior work has been agnostic to the antidiabetes drugs taken by such persons.

Early Oral Step-Down Versus Continued Intravenous Antibiotic Treatment of Complicated Intra-Abdominal Infection.

Complicated intra-abdominal infections (cIAIs) require a combined tactic, of source control and antimicrobial therapy. This study aimed to evaluate the safety and efficacy of oral step-down antimicrobial therapy in cIAIs after initial intravenous (IV) antimicrobial therapy. This retrospective cohort study included hospitalized adult patients diagnosed with a cIAI who received more than seven days of IV therapy from March 2017 to October 2021.

Concomitant Use of Oral Anticoagulants with Oral Dipeptidyl Peptidase-4 Inhibitors and Serious Bleeding Events.

In a prior screening study, saxagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i), was found to have an increased rate of serious bleeding when used concomitantly with several oral anticoagulants (OACs). We aimed to confirm or refute the associations between concomitant use of individual OACs and DPP-4is and serious bleeding in a large US database, using self-controlled case series (SCCS) and case-crossover (CCO) designs. The study population was eligible Medicare beneficiaries co-exposed to a DPP-4i (precipitant) and either an OAC (object drug) or lisinopril (negative control object drug) in 2016-2020.

Comparative Cardiovascular Effectiveness of Empagliflozin Versus Dapagliflozin in Adults With Treated Type 2 Diabetes: A Target Trial Emulation.

Background: Empagliflozin and dapagliflozin have proven cardiovascular benefits in people with type 2 diabetes at high cardiovascular risk, but their comparative effectiveness is unknown.

Methods: This study used nationwide, population-based Danish health registries to emulate a hypothetical target trial comparing empagliflozin versus dapagliflozin initiation, in addition to standard care, among people with treated type 2 diabetes from 2014 through 2020. The outcome was a composite of myocardial infarction, ischemic stroke, heart failure (HF), or cardiovascular death (major adverse cardiovascular event).

Antibiotic use among extremely low birth-weight infants from 2009 to 2021: a retrospective observational study.

Objective: To assess trends in antibiotic use across a large cohort of extremely low birth-weight (<1000 g; ELBW) infants admitted to academic and community neonatal intensive care units (NICUs) across the USA over a 13-year period.

Design: Repeated cross-sectional cohort study.

Setting: Premier Health Database, a comprehensive administrative database of inpatient encounters from academic and community hospitals across the US.

Email recruitment for chronic pain clinical trials: results from the LAMP trial.

Background: Recruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain.

Fluorescent identification of axons, dendrites and soma of neuronal retinal ganglion cells with a genetic marker as a tool for facilitating the study of neurodegeneration.

This study characterizes a fluorescent -tdTomato neuronal reporter mouse line offering strong labeling in axons throughout the optic nerve, dendrites and soma in 99% of retinal ganglion cells (RGCs). The model facilitates neuronal assessment with wholemounts quantified to show neurodegeneration following optic nerve crush or elevated IOP as related to glaucoma, with robust Ca responses to P2X7 receptor stimulation in neuronal cultures, and using a confocal scanning laser ophthalmoscope (cSLO). While the tdTomato signal showed strong overlap with RGC markers, BRN3A and RBPMS, there was no cross-labeling of displaced amacrine cells in the ganglion cell layer.

Direct-Acting Oral Anticoagulants and Antiseizure Medications for Atrial Fibrillation and Epilepsy and Risk of Thromboembolic Events.

Importance: Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk.

Objective: To assess the rates of thromboembolic and major bleeding events in adults with AF and epilepsy dispensed DOACs and EI ASMs vs DOACs with non-EI ASMs.

Unique affective profile of music-evoked nostalgia: An extension and conceptual replication of Barrett et al.'s (2010) study.

Nostalgia is a mixed emotion, often evoked by music. This study sought to conceptually replicate and extend Barrett et al.'s (see record 2010-09991-008) pioneering work exploring music-evoked nostalgia, where the authors identified person- and context-level predictors of the experience of nostalgia in music.

Severe Acute Liver Injury After Hepatotoxic Medication Initiation in Real-World Data.

Importance: Current approaches to classify the hepatotoxic potential of medications are based on cumulative case reports of acute liver injury (ALI), which do not consider the size of the exposed population. There is little evidence from real-world data (data relating to patient health status and/or the delivery of health care routinely collected from sources outside of a research setting) on incidence rates of severe ALI after initiation of medications, accounting for duration of exposure.

Objective: To identify the most potentially hepatotoxic medications based on real-world incidence rates of severe ALI and to examine how these rates compare with categorization based on case reports.

Thinking Three-Dimensionally: A Self- and Externally-Controlled Approach to Screening for Drug-Drug-Drug Interactions Among High-Risk Populations.

The global rise in polypharmacy has increased both the necessity and complexity of drug-drug interaction (DDI) assessments, given the growing potential for interactions involving more than two drugs. Leveraging large-scale healthcare claims data, we piloted a semi-automated, high-throughput case-crossover-based approach for drug-drug-drug interaction (3DI) screening. Cases were direct-acting oral anticoagulant (DOAC) users with either a major bleeding event during ongoing dispensings for potentially interacting, enzyme-inhibiting antihypertensive drugs (AHDs) (Study 1), or a thromboembolic event during ongoing dispensings for potentially interacting, enzyme-inducing antiseizure medications (ASMs) (Study 2).

Key messages on obesity care from the 2023 ASPEN Physician Preconference Course: A narrative review.

Obesity is a challenging chronic disease process that continues to affect a large percentage of the population at large. With the advent of new therapeutic options and interventions and a deeper scientific understanding of obesity as a complex illness, there is hope in curtailing this evolving pandemic. In this article, we present key medical information to engage and empower nutrition-focused providers to manage obesity and its nutrition complications.

Causally Probing the Role of the Hippocampus in Fear Discrimination: A Precision Functional Mapping-Guided, Transcranial Magnetic Stimulation Study in Participants With Posttraumatic Stress Symptoms.

Background: Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety. A dominant model posits that hippocampal pattern separation failures drive overgeneralization. Hippocampal network-targeted transcranial magnetic stimulation (HNT-TMS) has been shown to strengthen hippocampal-dependent learning/memory processes.