OBJECTIVES/GOALS: Chronic or new symptoms after infection with severe-acute-respiratory-coronavirus-2 (SARS-CoV-2) has been termed post-acute sequelae of Covid-19 (PASC) or Long Covid. Our objective is to present results from COVID-OUT, a phase 3 double-blind, randomized controlled trial of early outpatient treatment of Covid-19 with repurposed medications. METHODS/STUDY POPULATION: COVID-OUT enrolled adults age 30 to 85 with overweight or obesity who had proof of SARS-CoV-2 infection and fewer than 7 days of symptoms. In this 2 by 3 factorial design trial of metformin, ivermectin, fluvoxamine, or exact-matching placebo of each medication, participants were randomized 1:1:1:1:1:1 to the 6 treatment allocations. This abstract focuses on whether early treatment with metformin prevented Long Covid. Immediate release metformin was titrated to 1500mg daily over the first 6 days. We assessed the incidence of clinician-diagnosed Long Covid with follow up through 10 months after enrollment. We also assessed where participants were diagnosed with Long Covid, and where they received Long Covid treatment. RESULTS/ANTICIPATED RESULTS: Of 1124 participants, 98 (8.7%) report having a healthcare provider make a diagnosis of long covid. By arm, 6.9% (39/564) of metformin participants report having a diagnosis for long covid as compared with 10.5% (59/560) of matched placebo controls. The absolute reduction attributable to metformin was 3.6% (95%CI, 0.3% to 7.0%; P=0.031) with a relative risk reduction of 34% (95%CI, 3% to 55%). The metformin cost per long covid case averted was $28 (95%CI, $15 to $306). 10-month follow-up data will be available at the time of presentation as well as an analysis of baseline factors associated with the development of Long-Covid, independent of treatment allocation in the trial. DISCUSSION/SIGNIFICANCE: Metformin reduced the incidence of clinician-diagnosed long covid by 34% in a double-blind randomized placebo-controlled trial, and previous research published in-vitro activity by metformin against SARS-CoV-2 and other RNA viruses. Further investigation of metformin as early treatment for SARS-CoV-2 is warranted.

OBJECTIVES/GOALS: 1. Establish the prevalence of amenorrhea among women Ebola survivors of reproductive age. 2. Determine whether amenorrhea in Ebola survivors is associated with hyperthyroidism, primary ovarian failure, and/or low weight METHODS/STUDY POPULATION: This study will enroll a cohort of 150 women Ebola survivors and 150 uninfected controls from Kenema, Sierra Leone. Participants will complete women’s health questionnaires with detailed menstruation history and provide blood samples. Serum levels of thyroid stimulating hormone, follicle stimulating hormone, and albumin will be measured in order to explore the role of thyroid dysregulation, ovarian failure, and low weight in amenorrhea associated with prior Ebola infection. RESULTS/ANTICIPATED RESULTS: Enrollment for the study is still in progress. As of November 14, 2022, 68 female Ebola survivors of reproductive age and 124 uninfected controls have been enrolled. Among this preliminary group, there is a high baseline level of menstrual irregularities in both survivors and controls. Prior to the Ebola outbreak, 97% of all participants reported less than 6 periods per year and 59% reported periods lasting 3 days or less. The prevalence of missed periods increased after the Ebola outbreak in both groups. Four Ebola survivors (5.9%) reported missing periods before infection, compared to 16 (23.5%) survivors after infection. Two uninfected controls (1.6%) reported missing periods before the Ebola outbreak, compared to 12 (9.7%) after the outbreak. DISCUSSION/SIGNIFICANCE: The next steps of this project are to complete enrollment, conduct data analysis, and perform laboratory studies. An enhanced understanding of amenorrhea is needed to develop novel medical interventions, to inform healthcare guidelines and policies, and to develop personalized treatment strategies to better care for women who have survived Ebola.

Clinicians who are interested in becoming principal investigators struggle to find and complete training that adequately prepares them to conduct safe, well-designed clinical and translational research. Degree programs covering these skills require a significant time investment, while online trainings lack engagement and may not be specific to local research contexts. Staff at Tufts Clinical and Translational Science Institute sought to fill the gap in junior investigator training by designing an eight-module, noncredit certificate program to teach aspiring clinician-investigators about good clinical practice, clinical research processes, and federal and local regulatory requirements. The first iteration of this program was evaluated using pre- and posttest questionnaires and by gathering clinician learner feedback in a focus group. Based on the pre- and posttest questionnaires, learners experienced an increase in self-efficacy and confidence related to clinical research competencies. Feedback from learners also highlighted important program strengths, including an engaging program format, a manageable time commitment, and an emphasis on identifying crucial research resources. This article describes one approach to creating a meaningful and efficient clinical trial training program for clinicians.

OBJECTIVES/GOALS: Social anhedonia is considered a key feature of schizophrenia that leads to social withdrawal. Research in general anhedonia suggests those with schizophrenia exhibit deficits in anticipated (predicted), but intact consummatory (in-the-moment), pleasure. This study will determine if these temporal differences apply to daily social anhedonia. METHODS/STUDY POPULATION: This project will use experience sampling methods (ESM) to measure real-world social pleasure in people with schizophrenia and healthy controls. Using electronic surveys, participants will predict social activities they plan to do throughout their day and report anticipated pleasure for each. Then, in subsequent surveys, participants will report their consummatory social pleasure shortly after engaging in each of these activities. We will use a time-lagged approach to match anticipated/consummatory pleasure ratings for specific social events and compute a difference score to determine discrepancy. Multi-level modeling will be used to determine if clinical status (schizophrenia/control) predicts anticipated pleasure, consummatory pleasure, and/or their discrepancy. RESULTS/ANTICIPATED RESULTS: Data collection for this project was recently completed. The schizophrenia and control groups (n = 30 per group) were demographically matched for age, sex, race, and ethnicity. Data processing and analyses are currently underway. We hypothesize that, in line with laboratory research in general anhedonia, those with schizophrenia will exhibit deficits in anticipated, but not consummatory, social pleasure throughout their daily lives. Moreover, when anticipated and consummatory pleasure ratings for the same social activities are matched, we expect those with schizophrenia to exhibit larger discrepancies between predicted and in-the-moment pleasure. DISCUSSION/SIGNIFICANCE: This project serves as a critical intermediate step to bridge the gap between laboratory research and patient treatment. ESM bypasses limitations of laboratory studies and increases ecological validity. Results will provide a nuanced understanding of social anhedonia and help identify precise targets to treat social withdrawal in schizophrenia.

OBJECTIVES/GOALS: Research in Non Alcoholic Fatty Liver Disease Genetics is ongoing. In this project, we aim to: 1.Identify and describe a histological NAFLD Cohort in the MVP Biobank by extracting liver biopsy proven NAFLD patients using natural language processing (NLP) 2.Confirm previously defined NALFD genetic loci (via look up-GWAS) in the histological NLP cohort METHODS/STUDY POPULATION: We will utilize the Million Veteran Program Biobank where a total of 10,959 subjects have been identified using liver biopsy reports in the EMR via CPT codes. Cases will be based on i) steatosis, steatohepatitis, inflammation or fibrosis in liver biopsy reports with ii) exclusion of other causes of liver disease. Controls will be comprised of the general VA population. In collaboration with the Applied NLP and Precision Medicine groups at the VA Informatics and Computing Infrastructure(VINCI); we will attempt to create and validate a histological cohort of NAFLD in the MVP database by: 1)Annotation of biopsy reports for the NLP algorithm 2)Automation/training of the NLP algorithm We will then perform a multi-ancestry genetic lookup of previously established genetic loci among the cases identified. RESULTS/ANTICIPATED RESULTS: Recently published data: the MVP NAFLD research led by Dr. Chang and Dr. Vujkovic had first validated a proxy NAFLD phenotype based on chronic alanine aminotransferase elevation (cALT). A GWAS was then performed using this phenotype which revealed 77 loci of genome-wide significance including 10 established NAFLD- and 52 ALT-associated SNPs were identified. Replication in external Liver Biopsy and Imaging Cohorts validated 17 SNPs of which 9 were novel. Preliminary data on Liver Biopsy reports: Using CPT codes for Liver Biopsy we estimated a total of 10,959 unique patients and 18,812 notes in the MVP biobank. We anticipate 2,000-3,000 NAFLD cases (based on the prevalence of NAFLD in the general population). Initial review reveals 90% concordance between analysts for the purposes of developing an NLP. DISCUSSION/SIGNIFICANCE: NAFLD is a major cause for morbidity and mortality in liver disease. Gold standard for diagnosis is based on biopsy. GWAS studies with biopsy proven phenotypes are limited. The study will aim to isolate a histologically defined NAFLD cohort in MVP to conduct further GWAS that can provide new clinically relevant knowledge for future research.

Contemporary Research Challenges

Within Wisconsin, our residents experience some of the worst health disparities in the nation. Public reporting on disparities in the quality of care is important to achieving accountability for reducing disparities over time and has been associated with improvements in care. Disparities reporting using statewide electronic health records (EHR) data would allow efficient and regular reporting, but there are significant challenges with missing data and data harmonization. We report our experience in creating a statewide, centralized EHR data repository to support health systems in reducing health disparities through public reporting. We partnered with the Wisconsin Collaborative for Healthcare Quality (the “Collaborative”), which houses patient-level EHR data from 25 health systems including validated metrics of healthcare quality. We undertook a detailed assessment of potential disparity indicators (race and ethnicity, insurance status and type, and geographic disparity). Challenges for each indicator are described, with solutions encompassing internal (health system) harmonization, central (Collaborative) harmonization, and centralized data processing. Key lessons include engaging health systems in identifying disparity indicators, aligning with system priorities, measuring indicators already collected in the EHR to minimize burden, and facilitating workgroups with health systems to build relationships, improve data collection, and develop initiatives to address disparities in healthcare.

OBJECTIVES/GOALS: Primary care practices struggle to identify which combination of care structures and processes need to be implemented to improve practice performance and subsequently, patient outcomes. The goal of this study is to develop and validate a tool to assess care structures and processes that are associated with better quality and patient outcomes. METHODS/STUDY POPULATION: Data from a scoping review, Delphi study, and qualitative interviews with high-performing primary care practices contributed to the development and content validation of the Tool for Advancing Practice Performance (TAPP). From these sources we identified 314 items representing care structures (e.g., care team makeup, use of electronic health records) and processes (e.g., care coordination, panel management). We developed criteria for deleting and rescuing items and received input from our expert panel to refine the pool of items. We eliminated items that were redundant and lacked clarity/specificity. The tool was further modified based on feedback from cognitive interviewing and pilot testing with practice managers, quality improvement leaders, and physicians from primary care practices. RESULTS/ANTICIPATED RESULTS: The pool of 314 items was winnowed to 188 after applying criteria for deleting and rescuing items. During the expert review, 70 items were eliminated and 8 new items were added, resulting in a working tool of 126 items. We conducted eight cognitive interviews with the 126-item tool and received feedback on the content, item structure, and language, which led to the elimination of 13 items that were poorly or incorrectly understood by respondents. We also modified the language of 23 items for clarity. After cognitive interviewing, the resulting tool comprised 113 items. Fifteen practices piloted the tool and no additional items were eliminated. We modified the instructions for completing the tool and resolved technical issues related to online administration. DISCUSSION/SIGNIFICANCE: TAPP is a novel tool for assessing care structures and processes that are associated with better quality and patient outcomes in primary care settings. The tool can be used by researchers and primary care clinicians to identify areas for improvement in practice performance and patient outcomes related to chronic disease prevention and management.

OBJECTIVES/GOALS: Obesity is associated with gut dysbiosis, inflammation, and increased intestinal permeability. Probiotic consumption may reverse these outcomes. The goal of this study is to evaluate the evidence linking probiotic consumption to changes in intestinal permeability in subjects with overweight or obesity. METHODS/STUDY POPULATION: Articles were searched in Pubmed, Web of Science, and CAB Direct through February 2022 using search terms: intestinal permeability, overweight or obesity, and probiotic supplementation. 694 articles were exported, and 289 duplicates were identified. Titles and abstract were screened in the 405 remaining references by two investigators to determine eligibility. Eligible studies had data extracted on study participant characteristics, probiotic strain used, probiotic dosage, length of intervention, and intestinal barrier outcomes. Results were summarized in tabular form based on intestinal permeability response to probiotics. Quality of the studies was assessed based on Cochrane–Risk of Bias’ tool (RoB2). RESULTS/ANTICIPATED RESULTS: Thirteen eligible studies were identified. Probiotic genera included Akkermansia, Bifidobacterium, Lactobacillus, Streptococcus, Lactococcus, and Bacillus. Single strain probiotics were used in 3 studies, while the other 10 used multi-strain formulas. Dosage and length of probiotic supplementation ranged from 2.4 x 10^7 to 5 x 10^10 CFU/person/day and 3 to 26 weeks, respectively. The most widely used gut permeability outcomes were serum lipopolysaccharide (LPS) (n=10) and mixed sugar solution consumption with urine analysis (n=6). Five of the 10 studies reported decreases in serum LPS following probiotic consumption, while the other 5 showed no effect. Urinary lactulose/mannitol ratio decreased in 1 of the 4 studies, and urinary lactulose percent decreased in 2 studies. DISCUSSION/SIGNIFICANCE: Probiotic supplementation may be remediating an obesity-induced increase in intestinal permeability as evidenced from the effect on serum LPS and mixed sugar solution assays. However, additional studies are needed to further clarify which strain of probiotic bacteria is most effective and the optimal intervention length in subjects with obesity.

OBJECTIVES/GOALS: Patient recruitment, enrollment, and retention continues to be one of the leading barriers to successful clinical trials, and results do not always reflect the diversity of the general population. This systematic review aims to assess the impact of decentralized methods on recruitment, retention, and diversity on recent clinical research. METHODS/STUDY POPULATION: A systematic search of the literature, using databases such as PubMed, Cochrane Library and EMBASE to find publications reporting on the aspect of recruitment in decentralized clinical trials was performed. The titles and abstracts of the publications were assessed, excluded those lacking sufficient or pertinent information regarding decentralization in clinical trials. The remaining publications were reviewed for those reporting sufficient data regarding the impact of decentralization on the aspect of recruitment in clinical trials to be included in the focused analysis. Studies reporting on participant retention and diversity in addition to recruitment were emphasized. RESULTS/ANTICIPATED RESULTS: This systematic search returned 13 studies highlighting the role of decentralized clinical trial methods impacting participant recruitment, retention, and diversity in clinical trials. Out of the 13 studies, 10 reported improved recruitment using virtual or decentralized methods, and 7 of these reported improvements when compared alongside with traditional methods. 7 studies reported a positive impact on participant retention, with 4 of these directly comparing decentralized methods with traditional methods. Lastly, of these studies, 5 were reported to have trended towards diversity in the demographics of the sample population, including race or geographic location. DISCUSSION/SIGNIFICANCE: Related reviews have stated a lack of published comparable data to determine if DCTs (Decentralized Clinical Trials) improved recruitment and retention. Results suggest this review addresses such a gap, by providing data on how decentralized methods can benefit recruitment and retention, potentially highlighting a new standard.

OBJECTIVES/GOALS: Aim 1: To explore methodologies to identify gender minorities, and Filipinos, separately, in an electronic health record system. Aim 2: To characterize the similarities and differences in demographic, socioeconomic, and mental health of Filipinos gender minorities compared to Native Hawaiian Pacific Islanders, and White/ European Americans. METHODS/STUDY POPULATION: This study was approved by the University of Hawaii Institutional Review Board. Cross-sectional retrospective data were obtained from a collaborative community clinic’s electronic health record system. Patients were age 18 and older with a clinical diagnosis for gender dysphoria and from Native Hawaiian Pacific Islander, White/ European American, and Filipino backgrounds. RESULTS/ANTICIPATED RESULTS: Preliminary data revealed that 11% of the clinical population were diagnosed with gender dysphoria (N=373) with 57.6% (n=215) who met the inclusion criteria with complete health registration forms. Patients were from Filipino (21.8%), Native Hawaiian Pacific Islander (23.3%), White/ European American (31.6%), and multiethnic (23.3%) backgrounds. Most patients reported mental health (e.g., depression) conditions (50.6%-64.7%). Further statistical analyses will reveal if Filipinos have higher or lower levels of anxiety, depression, and suicide risks than Native Hawaiian Pacific Islander, and White/ European American gender minority individuals. DISCUSSION/SIGNIFICANCE: In Hawaii, one person dies by suicide every two days; suicide is the lead cause of fatal injuries. Study findings can inform future methodology studies to identify gender minorities and develop culturally relevant gender affirming mental health programs for gender minorities.

OBJECTIVES/GOALS: The aim of this study was to design and implement the Pharos application to map the cellular network support structure around Lake Victoria in Western Kenya. Additionally, the Pharos app was used to collect images of disease-relevant vector and plant life surrounding the study sites to train a computer vision algorithm to map disease-relevant areas. METHODS/STUDY POPULATION: Pharos was provided to a 4-person team of healthcare workers. The app was pre-loaded on both iOS and Android devices to be used during the course of normal field activity. Pharos ambiently collects network data and the team was asked to capture images of landmarks relevant to their work in schistosomiasis control. The field team traveled to 4 counties of differing schistosomiasis risk surrounding Kisumu, Kenya in autumn 2022 and will return to these areas in early spring 2023. Cell signal indicators (upload and download speed) were collected and asynchronously uploaded to a database for further analysis. Additionally, all landmark images (cell network towers, landmarks (e.g. schools, churches, public centers), plant life, vectors, and water bodies) were recorded and tagged with GPS coordinates and time stamps. RESULTS/ANTICIPATED RESULTS: Iterative development powered by small, informal, user-centered focus group discussions with the field team led to several key adaptations to the Pharos software. On the first deployment, 1,297 unique upload and download events were recorded across 3 Kenyan cell providers and 1 American provider. 1,197 data points were collected in Kenya using both Android and iOS devices using several versions of the Pharos application. 154 unique landmarks were photographed, but a distinct difference in landmark recording was observed between devices, prompting a transition to iOS-only data collection. Of the landmarks recorded, the majority (120, 77.9%) were landmarks or cell network towers, while 22.1% were water bodies, plant life, or schistosomiasis vectors. DISCUSSION/SIGNIFICANCE: For the first time, high-detail maps of cellular signal and critical schistosomiasis-related landmarks were generated. Future work on this project is focused on training computer vision algorithms using the captured images of environmental and ecological factors to isolate possible areas of human disease transmission.

The first human case of monkeypox virus (Mpox) was reported in 1970. In the years after 1970, human infection with Mpox and human-to-human transmission was not widely observed, and more cases were seen in endemic areas. In that year, Mpox spread was confirmed through the export of infected animals to other parts of the world. Every few years, sporadic infections were reported in different parts of the world from human contamination and human-to-human transmission. In recent years, with the slow decline of the COVID-19 pandemic, the outbreak of Mpox was observed in many countries of the world. To deal with the spread of this viral infection, we need to know the ways to diagnose the infection, treat the infection, care for the patients, and implement a wide program of vaccination. Currently, there are no specific drugs available for this virus, but according to previous studies related to smallpox, drugs such as tecovirimat, cidofovir, and brincidofovir, which were used for smallpox and other orthopoxviruses in the past, can be considered to deal with Mpox. Also, some vaccines such as JYNNEOS, IMVAMUNE, and MoVIHvax that have been used against smallpox can be useful to some extent in preventing Mpox.

OBJECTIVES/GOALS: The purpose of this small survey-based study was to characterize the current role of neurocritical care physicians in traumatic brain injury (TBI) systems of care and research. In doing so, we aim to highlight potential roles of neurology providers in the medical management and enhancement of translational science in the field of TBI. METHODS/STUDY POPULATION: Between April and June 2021, a web-based survey was disseminated by email to members of the Neurocritical Care Society. The survey was open to all physician providers. A total of 36 surveys were completed. The survey consisted of 18 questions with pre-defined answer choices. Survey questions aimed to determine areas of practice, primary clinical specialty, hospital practice setting, provider involvement in TBI care, provider involvement in TBI research, and current research roles. RESULTS/ANTICIPATED RESULTS: 92% of survey respondents were in the United States (n=33), representing all national regions. 75% of the physicians were neurocritical care trained (n=27). 69% of providers were practicing in academic institutions while 78% were at sites designated as Level I trauma centers. All respondents managed acute TBI, but 50% served as consultants rather than being the primary service provider. At their sites of practice, 31% of patients were on non-neuroscience services, especially those with non-neurologic traumatic injury. Only 36% reported that TBI protocols were written and adhered to at their site. Only 44% reported that TBI research was performed at their site, while 50% had interest in participating in TBI research. TBI was the primary area of research for 17% of physicians. DISCUSSION/SIGNIFICANCE: This small physician survey highlights heterogeneity in TBI systems-based practice and research roles. Areas of potential improvement include greater involvement of neurocritical care physicians in TBI management, protocol-building and implementation, and TBI research. Reasons for current barriers are multifactorial and will be discussed.