Faculty Bibliography

BACKGROUND:Eicosanoids are derivatives of polyunsaturated fatty acids (PUFAs) and participate in the inflammatory response as well as the maintenance of endothelial function. Specific eicosanoids have been linked to various diseases, including hypertension and asthma, and may also reduce renal blood flow. A systematic investigation of eicosanoid-related metabolites and adverse kidney outcomes could identify key mediators of kidney disease and inform ongoing work in drug development. METHODS:Profiling of eicosanoid-related metabolites was performed in 9,650 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 2; mean age, 57 years). The associations between metabolite levels and the development of end-stage kidney disease (ESKD) was investigated using a series of progressively adjusted models and Cox proportional hazards regression (N= 256 events; median follow-up, 25.5 years). Metabolites with statistically significant associations with ESKD were evaluated for a potential causal role using bidirectional Mendelian randomization techniques, linking genetic instruments for eicosanoid levels to genome-wide association study summary statistics of estimated glomerular filtration rate (eGFR). RESULTS:The 223 eicosanoid-related metabolites that were profiled and passed QC were generally uncorrelated with eGFR in cross-sectional analyses (median Spearman correlation, -0.03; IQR -0.05 to 0.002). In models adjusted for multiple covariates, including baseline eGFR, three metabolites had statistically significant associations with ESKD (p-value <0.05/223). These included a hydroxyoctadecenoic acid, a dihydroxydocosapentaenoic acid, and arachidonic acid, with higher levels of the former two protective against ESKD and higher levels of arachidonic acid having a positive association with risk of ESKD. Mendelian randomization analyses suggested a causal role for the hydroxyoctadecenoic and arachidonic acid in determining eGFR. Spectral analysis identified the former metabolite as either 11-hydroxy-9-octadecenoic acid or 10-hydroxy-11-octadecenoic acid. CONCLUSIONS:High throughput eicosanoid profiling can identify metabolites that may play a protective role in the development of kidney disease.

Background: The EQUIPPED (Enhancing Quality of Prescribing Practices for Older Adults Discharged from the Emergency Department) medication safety program is an evidence-informed quality improvement initiative to reduce potentially inappropriate medications (PIMs) prescribed by Emergency Department (ED) providers to adults aged 65 and older at discharge. We aimed to scale-up this successful program using (1) a traditional implementation model at an ED with a novel electronic medical record and (2) a new hub-and-spoke implementation model at three new EDs within a health system that had previously implemented EQUIPPED (hub). We hypothesized that implementation speed would increase under the hub-and-spoke model without cost to PIM reduction or site engagement. Methods: We evaluated the effect of the EQUIPPED program on PIMs for each ED, comparing their 12-month baseline to 12-month post-implementation period prescribing data, number of months to implement EQUIPPED, and facilitators and barriers to implementation. Results: The proportion of PIMs at all four sites declined significantly from pre- to post-EQUIPPED: at traditional site 1 from 8.9% (8.1"“9.6) to 3.6% (3.6"“9.6) (p < 0.001); at spread site 1 from 12.2% (11.2"“13.2) to 7.1% (6.1"“8.1) (p < 0.001); at spread site 2 from 11.3% (10.1"“12.6) to 7.9% (6.4"“8.8) (p = 0.045); and at spread site 3 from 16.2% (14.9"“17.4) to 11.7% (10.3"“13.0) (p < 0.001). Time to implement was equivalent at all sites across both models. Interview data, reflecting a wide scope of responsibilities for the champion at the traditional site and a narrow scope at the spoke sites, indicated disproportionate barriers to engagement at the spoke sites. Conclusions: EQUIPPED was successfully implemented under both implementation models at four new sites during the COVID-19 pandemic, indicating the feasibility of adapting EQUIPPED to complex, real-world conditions. The hub-and-spoke model offers an effective way to scale-up EQUIPPED though a speed or quality advantage could not be shown.

Study advisory committees (SACs) provide critical value to clinical trials by providing unique perspectives that pull from personal and professional experiences related to the trial's healthcare topic. The Emergency Medicine Palliative Care Access (EMPallA) study had the privilege of convening a 16-person SAC from the project's inception to completion. The study team wanted to understand the impact this project had on the SAC members. In this narrative, we use reflective dialogue to share SAC members"™ lived experiences and the impact the EMPallA study has had on members both personally and professionally. We detail the (1) benefits SAC members, specifically patients, and caregivers, have had through working on this project. (2) The importance of recruiting diverse SAC members with different lived experiences and leveraging their feedback in clinical research. (3) Value of community capacity building to ensure the common vision of the clinical trial is promoted.

Acute rheumatic fever (ARF) is an immune-mediated nonsuppurative complication of group A streptococcal (GAS) pharyngitis. Approximately 470,000 new cases of ARF occur annually, with a more significant disease burden in developing countries with higher rates of untreated or inadequately treated GAS infections. Globally, over 275,000 deaths yearly are attributed to rheumatic heart disease (RHD). The most significant contributors to the spread of GAS pharyngitis are household overcrowding, poor sanitation, and inadequate access to healthcare. The pathophysiology of ARF is characterized by an aberrant immune response to GAS infection triggered by molecular mimicry between GAS antigens and self-antigens. This immune response typically manifests 2 to 4 weeks after the initial GAS infection and may lead to the development of carditis, valvulitis, Sydenham chorea, subcutaneous nodules, erythema marginatum, and polyarthritis that is usually migratory. The severity and distribution of these manifestations vary significantly between individuals making the diagnosis of ARF challenging. Early recognition of ARF using the modified Jones criteria is essential in treating acute infection and preventing complications. A major long-term consequence is RHD, which carries significant morbidity and mortality.

BACKGROUND:In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures. OBJECTIVES:The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses. METHODS:We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, fellows, administrative support, funding sources, and expenses. We surveyed program directors of programs accredited by the Accreditation Council for Graduate Medical Education between 2014 and 2021. RESULTS:We invited 54 program directors, of which 41 (76%) completed the survey. The average administrative support received was $27,732/year. Most programs (85.4%) were accredited to have two or more fellows per year. Programs were administratively housed under six departments: Internal Medicine (17; 41.5%), Pediatrics (7; 17.1%), Pathology (6; 14.6%), Family Medicine (6; 14.6%), Emergency Medicine (4; 9.8%), and Anesthesiology (1; 2.4%). Funding sources for CI fellowship program directors included: hospital or health systems (28.3%), clinical departments (28.3%), graduate medical education office (13.2%), biomedical informatics department (9.4%), hospital information technology (9.4%), research and grants (7.5%), and other sources (3.8%) that included philanthropy and external entities. CONCLUSION:CI fellowships have been established in leading academic and community health care systems across the country. Due to their unique training requirements, these programs require significant resources for education, administration, and recruitment. There continues to be considerable heterogeneity in funding models between programs. Our survey findings reinforce the need for reformed federal funding models for informatics practice and training.

BACKGROUND:Geriatric emergency department (GED) guidelines endorse screening older patients for geriatric syndromes in the ED, but there have been significant barriers to widespread implementation. The majority of screening programs require engagement of a clinician, nurse, or social worker, adding to already significant workloads at a time of record-breaking ED patient volumes, staff shortages, and hospital boarding crises. Automated, electronic health record (EHR)-embedded risk stratification approaches may be an alternate solution for extending the reach of the GED mission by directing human actions to a smaller subset of higher risk patients. METHODS:We define the concept of automated risk stratification and screening using existing EHR data. We discuss progress made in three potential use cases in the ED: falls, cognitive impairment, and end-of-life and palliative care, emphasizing the importance of linking automated screening with systems of healthcare delivery. RESULTS:Research progress and operational deployment vary by use case, ranging from deployed solutions in falls screening to algorithmic validation in cognitive impairment and end-of-life care. CONCLUSIONS:Automated risk stratification offers a potential solution to one of the most pressing problems in geriatric emergency care: identifying high-risk populations of older adults most appropriate for specific GED care. Future work is needed to realize the promise of improved care with less provider burden by creating tools suitable for widespread deployment as well as best practices for their implementation and governance.

The objective of the study is to identify healthcare events leading to a diagnosis of dementia from a large real-world dataset. This study uses a data-driven approach to identify temporally ordered pairs and trajectories of healthcare codes in the electronic health record (EHR). This allows for discovery of novel temporal risk factors leading to an outcome of interest that may otherwise be unobvious. We identified several known (Down syndrome RR = 116.1, thiamine deficiency RR = 76.1, and Parkinson's disease RR = 41.1) and unknown (Brief psychotic disorder RR = 68.6, Toxic effect of metals RR = 40.4, and Schizoaffective disorders RR = 40.0) factors for a specific dementia diagnosis. The associations with the greatest risk for any dementia diagnosis were found to be primarily related to mental health (Brief psychotic disorder RR = 266.5, Dissociative and conversion disorders RR = 169.8), or neurologic conditions or procedures (Dystonia RR = 121.9, Lumbar Puncture RR = 119.0). Trajectory and clustering analysis identified factors related to cerebrovascular disorders, as well as diagnoses which increase the risk of toxic imbalances. The results of this study have the ability to provide valuable insights into potential patient progression towards dementia and improve recognition of patients at risk for developing dementia.

INTRODUCTION/UNASSIGNED:Many hospitals are unable to determine toxic alcohol concentrations in a clinically meaningful time frame. Thus, clinicians use surrogate markers when evaluating potentially poisoned patients. INDEX CASE/UNASSIGNED:A patient presented after an intentional antifreeze (ethylene glycol) ingestion with an osmol gap of -10.6 that remained stable one hour later. Further investigation revealed that the serum osmolality was calculated and not measured. The true osmol gap was 16.4, which correlated to a measured ethylene glycol concentration of 808 mg/L (80.8 mg/dL, 13.0 mmol/L). SURVEY/UNASSIGNED:A telephone survey of hospital laboratories in our catchment area was performed to investigate the potential for similar events. RESULTS/UNASSIGNED:Thirty-eight (47 percent) hospitals responded. No laboratories were able to test for toxic alcohols. One hospital (2.6 percent) reported routinely calculating osmolality based on chemistries, while two hospitals (5.3 percent) reported scenarios in which this might occur. Thirty-five (92.1 percent) hospitals could directly measure osmolality. Two hospitals (5.3 percent) were reliant on outside laboratories for osmolality measurement. LIMITATIONS/UNASSIGNED:The 47 percent response rate and one geographic area are significant limitations. DISCUSSION/UNASSIGNED:Over 10 percent of hospitals that responded could have significant difficulty assessing patients with toxic alcohol ingestion. CONCLUSIONS/UNASSIGNED:Until the standard of rapidly obtaining toxic alcohol concentrations is broadly implemented, we recommend that policies and procedures be put in place to minimize errors associated with the determination of the osmol gap.

INTRODUCTION/UNASSIGNED:Chronic nitrous oxide use can lead to neurological findings that are clinically and radiographically identical to those found in patients with pernicious anemia, specifically subacute combined degeneration of the spinal cord and peripheral neuropathy. CASE SUMMARY/UNASSIGNED:A 22-year-old man presented with lower extremity weakness and ataxia in the setting of inhaling 250 nitrous oxide cartridges two to three times weekly for two years. IMAGES/UNASSIGNED:Magnetic resonance imaging showed T2 hyperenhancement of the dorsal columns of the cervical spine from the first to the sixth vertebrae, which helped to establish a diagnosis of nitrous oxide-induced subacute combined degeneration of the spinal cord. CONCLUSIONS/UNASSIGNED:Chronic nitrous oxide use should be included in the differential diagnosis of any patient with otherwise unexplained neurological complaints that localize to the dorsal columns and has the changes on magnetic resonance imaging described here.

IMPORTANCE/UNASSIGNED:First-generation (FG) medical students remain underrepresented in medicine despite ongoing national efforts to increase diversity; understanding the challenges faced by this student population is essential to building holistic policies, practices, and learning environments that promote professional actualization. Although FG students have been extensively studied in the undergraduate literature, there is little research investigating how FG students experience medical education or opportunities for educators to intervene. OBJECTIVE/UNASSIGNED:To explore challenges that FG students experience in undergraduate medical education and identify opportunities to improve foundational FG support. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This qualitative study was conducted using an online platform with 37 FG students enrolled in 27 US medical schools. An interprofessional team of medical educators and trainees conducted semistructured interviews from November 2021 through April 2022. Participants were recruited using a medical student listserv. Data were analyzed from April to November 2022. MAIN OUTCOMES AND MEASURES/UNASSIGNED:After conducting a preliminary analysis using open coding, a codebook was created and used in a thematic analysis; the codebook used a combination of deductive and inductive coding. RESULTS/UNASSIGNED:Among the 37 students recruited for this study, 21 (56.8%) were female; 23 (62.2%) were in the clinical phase of training; 1 (2.7%) was American Indian or Alaska Native, 7 (18.9%) were Hispanic, Latino, or of Spanish origin, 8 (21.6%) were non-Hispanic Asian or Asian American, 9 (24.3%) were non-Hispanic Black or African American, and 23 (32.4%) were non-Hispanic White; mean (SD) age was 27.3 (2.8) years. Participants described 4 major themes: (1) isolation and exclusion related to being a newcomer to medicine; (2) difficulty with access to basic resources (eg, food, rent, transportation) as well as educational (eg, books); (3) overall lack of faculty or institutional support to address these challenges; and (4) a sense of needing to rely on grit and resilience to survive. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Although grit and resilience are desirable traits, results of this study suggest that FG medical students face increased adversity with inadequate institutional support, which forces them to excessively rely on grit and resilience as survival (rather than educational) strategies. By applying the holistic model often used in admissions to the postmatriculation educational process, targeted and flexible initiatives can be created for FG students so that all students, regardless of background, can achieve robust professional actualization.