The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation.

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice.

Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.

The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance in cell therapy. Mitochondrial dysfunction has been implicated in various neurodegenerative disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases. Understanding the impact of mitochondrial biology on these conditions can provide valuable insights for developing targeted cell therapies.

Ethical and regulatory challenges of large language models in medicine.

With the rapid growth of interest in and use of large language models (LLMs) across various industries, we are facing some crucial and profound ethical concerns, especially in the medical field. The unique technical architecture and purported emergent abilities of LLMs differentiate them substantially from other artificial intelligence (AI) models and natural language processing techniques used, necessitating a nuanced understanding of LLM ethics. In this Viewpoint, we highlight ethical concerns stemming from the perspectives of users, developers, and regulators, notably focusing on data privacy and rights of use, data provenance, intellectual property contamination, and broad applications and plasticity of LLMs.

Clinical and treatment characteristics of infants and toddlers less than 2 years of age with hemophilia.

Infants and toddlers (ITs) with hemophilia have unique bleeding features. Factor prophylaxis has been shown to decrease the risk of intracranial hemorrhage (ICH), which supports recommendations to begin at a young age. Clinical and demographic characteristics were analyzed for 883 ITs ≤2 years old with hemophilia A and B, seen at US Hemophilia Treatment Centers and enrolled in the Community Counts Registry, a surveillance program of the Centers for Disease Control and Prevention.

Accurate, Robust, and Scalable Machine Abstraction of Mayo Endoscopic Subscores From Colonoscopy Reports.

Background: The Mayo endoscopic subscore (MES) is an important quantitative measure of disease activity in ulcerative colitis. Colonoscopy reports in routine clinical care usually characterize ulcerative colitis disease activity using free text description, limiting their utility for clinical research and quality improvement. We sought to develop algorithms to classify colonoscopy reports according to their MES.

Algorithmic Identification of Treatment-Emergent Adverse Events From Clinical Notes Using Large Language Models: A Pilot Study in Inflammatory Bowel Disease.

Outpatient clinical notes are a rich source of information regarding drug safety. However, data in these notes are currently underutilized for pharmacovigilance due to methodological limitations in text mining. Large language models (LLMs) like Bidirectional Encoder Representations from Transformers (BERT) have shown progress in a range of natural language processing tasks but have not yet been evaluated on adverse event (AE) detection.

Construction of residential histories to estimate long-term environmental exposures in the California Teachers Study cohort.

Environmental epidemiologic studies using geospatial data often estimate exposure at a participant's residence upon enrollment, but mobility during the exposure period can lead to misclassification. We aimed to mitigate this issue by constructing residential histories for participants in the California Teachers Study through follow-up (1995-2018). Address records have been collected from the US Postal Service, LexisNexis, Experian, and California Cancer Registry.

Characterisation of digital therapeutic clinical trials: a systematic review with natural language processing.

Digital therapeutics (DTx) are a somewhat novel class of US Food and Drug Administration-regulated software that help patients prevent, manage, or treat disease. Here, we use natural language processing to characterise registered DTx clinical trials and provide insights into the clinical development landscape for these novel therapeutics. We identified 449 DTx clinical trials, initiated or expected to be initiated between 2010 and 2030, from ClinicalTrials.

Predictive Modeling of Drug-Related Adverse Events with Real-World Data: A Case Study of Linezolid Hematologic Outcomes.

Electronic health records (EHRs) provide meaningful knowledge of drug-related adverse events (AEs) that are not captured in standard drug development and postmarketing surveillance. Using variables obtained from EHR data in the University of California San Francisco de-identified Clinical Data Warehouse, we aimed to evaluate the potential of machine learning to predict two hematological AEs, thrombocytopenia and anemia, in a cohort of patients treated with linezolid for 3 or more days. Features for model input were extracted at linezolid initiation (index), and outcomes were characterized from index to 14 days post-treatment.

Exploring the Relationship Between Medication Adherence and Diabetes Disparities among Hispanic Patients in a Large Health System.

Background: Sub-optimal HbA1c control is a driver of disparities in diabetes outcomes among Hispanic patients. Differences in medication adherence may underlie racial/ethnic differences in HbA1c level.

Objective: To examine the relationship between medication adherence and disparities in HbA1c level among Hispanic patients, relative to other racial/ethnic groups, obtaining care in the University of California Health System (UC Health).

Experience of Induced Lactation in a Transgender Woman: Analysis of Human Milk and a Suggested Protocol.

A growing number of diverse familial structures wish to colactate their infant. For transgender and gender diverse (TGD) individuals, chestfeeding or breastfeeding may be within their goals of parenthood. There is limited evidence on how to induce lactation for a nongestational parent on gender affirming estrogen treatment.

A Multisite Electronic Health Record Integrated Remote Monitoring Intervention for Hypertension Improvement: Protocol for a Randomized Pragmatic Comparative Effectiveness Trial.

Background: Hypertension is a major contributor to various adverse health outcomes. Although previous studies have shown the benefits of home blood pressure (BP) monitoring over office-based measurements, there is limited evidence comparing the effectiveness of whether a BP monitor integrated into the electronic health record is superior to a nonintegrated BP monitor.

Objective: In this paper, we describe the protocol for a pragmatic multisite implementation of a quality improvement initiative directly comparing integrated to nonintegrated BP monitors for hypertension improvement.

Second-Line Pharmaceutical Treatments for Patients with Type 2 Diabetes.

Importance: Assessing the relative effectiveness and safety of additional treatments when metformin monotherapy is insufficient remains a limiting factor in improving treatment choices in type 2 diabetes.

Objective: To determine whether data from electronic health records across the University of California Health system could be used to assess the comparative effectiveness and safety associated with 4 treatments in diabetes when added to metformin monotherapy.

Design, Setting, And Participants: This multicenter, new user, multidimensional propensity score-matched retrospective cohort study with leave-one-medical-center-out (LOMCO) sensitivity analysis used principles of emulating target trial.

Pharmacist-Led Diabetes Control Intervention and Health Outcomes in Hispanic Patients With Diabetes.

Importance: Among patients with type 2 diabetes (T2D), Hispanic individuals are more likely than non-Hispanic White individuals to develop diabetes-related complications.

Objective: To examine the association of a pharmacist-led intervention (UCMyRx) with hemoglobin A1c (HbA1c) and systolic blood pressure (SBP) among Hispanic patients with T2D.

Design, Setting, And Participants: This quality improvement study used electronic health record data and a difference-in-differences study design to evaluate the association of UCMyRx exposure with changes in HbA1c concentration and SBP among Hispanic patients with T2D, relative to usual care, at University of California, Los Angeles primary care clinics between February and April of 2023.

Palliation of Intractable Cancer-Related Pain With Low-Dose Epidural Bupivacaine.

Patients with advanced cancer nearing end of life often present with complex multifactorial pain. Although epidural analgesia is routinely used in inpatient hospital settings for targeted pain control, there is scant description in the literature of the use of low-dose epidural analgesia for relief of cancer-related pain at end of life. In this study, we present a case of difficult to control cancer-related rectal and pelvic pain in a patient who responded well in her last days of life to a low-dose bupivacaine epidural.

A Chief Health Security Officer for Every Academic Health Center: Improving Readiness, Response, Recovery, and Resilience.

Academic health centers (AHCs) require expertise to ensure readiness for health security events, such as cyberattacks, natural disasters, and pandemics, as well as the ability to respond to and recover from these events. However, most AHCs lack an individual to coordinate efforts at an enterprise level across academic and operational units during an emergency; elevate the coordination of individual AHCs with local and state public health entities; and through professional organizations, coordinate the work of AHCs across national and international public health entities. Informed by AHCs' responses to the COVID-19 pandemic and a series of focused meetings in 2021 of the Association of Academic Health Centers President's Council on Health Security, the authors propose creating a new C-suite role to meet these critical needs: the chief health security officer (CHSO).

A certified de-identification system for all clinical text documents for information extraction at scale.

Objectives: Clinical notes are a veritable treasure trove of information on a patient's disease progression, medical history, and treatment plans, yet are locked in secured databases accessible for research only after extensive ethics review. Removing personally identifying and protected health information (PII/PHI) from the records can reduce the need for additional Institutional Review Boards (IRB) reviews. In this project, our goals were to: (1) develop a robust and scalable clinical text de-identification pipeline that is compliant with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule for de-identification standards and (2) share routinely updated de-identified clinical notes with researchers.

A Specialist Palliative Pharmacist Enriches the Interdisciplinary Team: A Case Series Discussion Illustrating the Entrustable Professional Activities for Specialist Hospice and Palliative Care Pharmacists.

Palliative care (PC) pharmacists are an integral member of the PC team. Essential roles have been defined and entrustable professional activities (EPAs) have been recently developed for hospice and PC pharmacists. We review four different complex patient cases where the specialist PC pharmacist worked with the interdisciplinary team to address whole patient suffering.

Developing a clinical research infrastructure embedded in an academic medicine center that equitably supports future clinician scientists.

Clinical research in academic medical centers can be difficult to conduct and meet enrollment goals. Students under-represented in medicine (URiM) are also under-represented in academic leadership positions and as physician-scientists but are critical to help solve health disparities. Barriers in pursuing medicine as a career may be high for URiM students, therefore it is important to create pre-medicine opportunities accessible to all students interested in healthcare careers.

Novel computational methods on electronic health record yields new estimates of transfusion-associated circulatory overload in populations enriched with high-risk patients.

Background: Transfusion-associated circulatory overload (TACO) is a severe adverse reaction (AR) contributing to the leading cause of mortality associated with transfusions. As strategies to mitigate TACO have been increasingly adopted, an update of prevalence rates and risk factors associated with TACO using the growing sources of electronic health record (EHR) data can help understand transfusion safety.

Study Design And Methods: This retrospective study aimed to provide a timely and reproducible assessment of prevalence rates and risk factors associated with TACO.