Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence.

A compilation of factors over the past decade-including the availability of increasingly large and rich healthcare datasets, advanced technologies to extract unstructured information from health records and digital sources, advancement of principled study design and analytic methods to emulate clinical trials, and frameworks to support transparent study conduct-has ushered in a new era of real-world evidence (RWE). This review article describes the evolution of the RWE era, including pharmacoepidemiologic methods designed to support causal inferences regarding treatment effects, the role of regulators and other health authorities in establishing distributed real-world data networks enabling analytics at scale, and the many global guidance documents on principled methods of producing RWE. This article also highlights the growing opportunity for RWE to support decision making by regulators, health technology assessment groups, clinicians, patients, and other stakeholders and provides examples of influential RWE studies.

Double trouble: two retrotransposons triggered a cascade of invasions in Drosophila species within the last 50 years.

Horizontal transfer of genetic material in eukaryotes has rarely been documented over short evolutionary timescales. Here, we show that two retrotransposons, Shellder and Spoink, invaded the genomes of multiple species of the melanogaster subgroup within the last 50 years. Through horizontal transfer, Spoink spread in D.

Denosumab and clinical outcomes among men with osteoporosis: a retrospective cohort study.

Unlabelled: Most subjects in osteoporosis clinical trials were women with postmenopausal osteoporosis and while bridging studies (BMD endpoint) provide an expectation that osteoporosis medications will reduce fracture risk in men. This real-world study shows direct evidence of fracture risk reduction among men with osteoporosis (36% of hip fracture reduction with denosumab).

Purpose: Direct evidence for fracture risk reduction of medications used among men with osteoporosis is very limited.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.

Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan.

Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA-mediated silencing.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) are 21- to 22-nucleotide RNAs that guide Argonaute-class effectors to targets for repression. In this work, we uncover 5-aminolevulinic acid synthase 1 (ALAS1), the initiating enzyme for heme biosynthesis, as a general repressor of miRNA accumulation. Although heme is known to be a positive cofactor for the nuclear miRNA processing machinery, ALAS1-but not other heme biosynthesis enzymes-limits the assembly and activity of Argonaute complexes under heme-replete conditions.

Lithium Use During Pregnancy in 14 Countries.

Importance: In pregnancy, the benefits of lithium treatment for relapse prevention in psychiatric conditions must be weighed against potential teratogenic effects. Currently, there is a paucity of information on how and when lithium is used by pregnant women.

Objective: To examine lithium use in the perinatal period.

Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions.

MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these questions by identifying microRNA expression quantitative trait loci (miR-QTLs), or genetic variants associated with brain miRNA levels, using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex samples of 604 older adult donors of European ancestry.

Parent coaching to target language outcomes for Chinese-learning autistic preschoolers: A preliminary study.

Purpose: The present study evaluates the preliminary effectiveness of a parent-implemented support program to enhance language outcomes in Chinese-learning preschoolers with a confirmed diagnosis or at elevated likelihood of autism, a lifelong neurodevelopmental condition. The program is delivered entirely online with the option of a group format. Because of cross-cultural differences in adult learning and parent-child interaction and because parent coaching programs for autism that are delivered online are only emerging, a specific study to evaluate the effectiveness of online support for Chinese families is warranted.

Trans-arterial chemo-emobilization (TACE) combined with laparoscopic portal vein ligation and terminal branches portal vein embolization for hepatocellular carcinoma: a novel conversion strategy.

Background: Hepatocellular carcinoma (HCC) is currently one of the most common malignant tumors with the highest mortality rates in the world. Most patients with HCC have lost the opportunity for surgery at the time of initial diagnosis. This study aims to introduce a new conversion strategy: trans-arterial chemo-emobilization (TACE) combined with laparoscopic portal vein ligation (PVL) and terminal branches portal vein embolization (PVE).

Validating ICD-10 Diagnosis Codes for Guillain-Barré Syndrome in Taiwan's National Health Insurance Claims Database.

Purpose: To validate the International Classification of Diseases, 10th Revision (ICD-10) codes for Guillain-Barré syndrome (GBS) in Taiwan's insurance claims database.

Methods: We identified adult patients hospitalized at any Chang Gung Memorial Foundation branch hospital between January 1st, 2017, and December 31st, 2022, with ICD-10 code G61.0 in any of the five discharge diagnosis positions, indicating possible Guillain-Barré syndrome.

The structural landscape of Microprocessor-mediated processing of pri-let-7 miRNAs.

MicroRNA (miRNA) biogenesis is initiated upon cleavage of a primary miRNA (pri-miRNA) hairpin by the Microprocessor (MP), composed of the Drosha RNase III enzyme and its partner DGCR8. Multiple pri-miRNA sequence motifs affect MP recognition, fidelity, and efficiency. Here, we performed cryoelectron microscopy (cryo-EM) and biochemical studies of several let-7 family pri-miRNAs in complex with human MP.

Intraoperative Complications as Predictors of Flap Failure in Autologous Breast Reconstruction.

Background:  Intraoperative microvascular complications in autologous breast reconstruction significantly increase the risk of postoperative complications. No study has identified which specific intraoperative complications contribute to partial or total flap loss.

Methods:  A retrospective chart review of microsurgical breast reconstructions by five surgeons between 2009 and 2020 analyzed operative variables and patient outcomes, with complications determined from the operative report.

Augmented reality visualization for ultrasound-guided interventions: a pilot randomized crossover trial to assess trainee performance and cognitive load.

Background: Augmented reality (AR) technology involving head-mounted displays (HMD) represents a significant innovation in medical education, particularly for training in guided invasive procedures. Novice physicians often face challenges in simultaneously identifying anatomical landmarks and performing procedures when learning point-of-care ultrasound (POCUS). Our primary objective was to determine the effectiveness of AR in enhancing physician training for ultrasound-guided interventions using AR visual overlays.

PIWI-interacting RNAs: who, what, when, where, why, and how.

PIWI-interacting RNAs (piRNA) suppress selfish genetic elements and are essential for germ cell biology in animals. They also play critical roles in regeneration in planaria, regulate gene expression in adult mammalian testes, and participate in antiviral defense in mosquitoes. Inspired by a recent workshop on PIWI proteins and piRNAs, this commentary aims to summarize fundamental aspects of piRNA biology, highlight recent advances, and discuss key outstanding questions.

Genetic regulation of microRNAs in the older adult brain and their contribution to neuropsychiatric conditions.

MicroRNAs are essential post-transcriptional regulators of gene expression and involved in many biological processes; however, our understanding of their genetic regulation and role in brain illnesses is limited. Here, we mapped brain microRNA expression quantitative trait loci (miR-QTLs) using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex (dlPFC) samples of 604 older adult donors of European ancestry. miR-QTLs were identified for 224 miRNAs (48% of 470 tested miRNAs) at false discovery rate < 1%.

Usability and Tolerability of Virtual Reality-Based Cognitive Stimulation in Healthy Elderly Volunteers-A Feasibility Clinical Trial.

The aim of the current pilot study was to evaluate the usability, acceptability, and tolerability of virtual reality (VR)-based cognitive stimulation exercises (CSEs) in healthy young versus old populations before health care integration. A secondary aim was to assess the accuracy of VR games as a proxy for cognitive stimulation, specifically for attention. VR-based CSEs promise to improve attention and brain function through varied learning systems.

Cataract Surgery and Incidence of Retinal Vascular Occlusion: Population-Based Cohort Study Using a Target Trial Emulation Framework.

Background: Previous studies suggested an association between cataract surgery and retinal vascular occlusion. However, the association may be attributable to detection bias because postoperative monitoring may be more frequent for those who receive cataract surgery than for those who do not.

Design: Population-based cohort study using target trial emulation framework.

Risk of age-related macular degeneration in men receiving 5α-reductase inhibitors: a population-based cohort study.

Background: Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration.

Objective: To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin.

Design: Retrospective, population-based cohort study using new-user and active-comparator design.