OBJECTIVES/GOALS: Barriers to childhood vaccine completion include forgeting vaccine appointments, lack of clinic access (distance and funds), and vaccine hesitancy. We tested the impact of automated and real-time appointment reminders, vaccine hesitancy counseling, and targeted vaccine drives on receiving the third dose of the diphtheria vaccine. METHODS/STUDY POPULATION: An implementation study to determine the feasibility and impact of implementing a mobile health-supported intervention bundle. A digital vaccine registry was developed to manage vaccine uptake data. The intervention bundle was applied sequentially: each registered parent received an automated appointment phone reminder (text and voice). If they delayed for >5 days, they received a real time reminder phone call. If during the real time call vaccine hesitancy was deemed to be a barrier, counseling was provided. If access - lack of funds or long distance - to the clinic was the barrier, vaccination was performed at patient's home on the monthly vaccine drives. We compared vaccine completion (all childhood vaccines before 18 months) during the implementation to the preceding three years. RESULTS/ANTICIPATED RESULTS: We anticipate the implementation will be feasible as >90% of all eligible children will be registered. We expect providers will be accepting and would recommend the intervention to other providers. We anticipate the intervention will result in a >10% increase in childhood vaccine completion compared to the average of the past three years. DISCUSSION/SIGNIFICANCE: We anticipate applying a multifaceted intervention will be acceptable to providers, feasible to implement, and significantly improve childhood vaccine completion rates moving Nigeria closer to achieving the global target of >95% childhood vaccine completion rate.

OBJECTIVES/GOALS: The objective of this study is to investigate the neurophysiological mechanism of vision therapy in male and female adolescents with persistent post-concussion convergence insufficiency (PPCS-CI). This study may improve diagnostics and inform more effective personalized point of care treatment strategies to remediate symptoms. METHODS/STUDY POPULATION: Participants (ages 11-25) were diagnosed with PPCS by a physician, CI was diagnosed by an optometrist and OBVAT was performed by certified therapists. Patients with PPCS-CI were randomly assigned to a therapy type (immediate therapy or natural recovery). Hemodynamic measures were examined in patients with PPCS-CI at baseline (1-3 months post-concussion), and post OBVAT to evaluate recovery outcomes. Non-invasive techniques were used to measure middle cerebral artery velocity (MCAv), blood pressure, heart rate, and end-tidal CO2 at rest and during objective symmetrical convergence step eye movements. Functional magnetic resonance imaging (fMRI) was acquired during convergence step eye movement experiments contrasted to sustained fixation and resting state data collection. RESULTS/ANTICIPATED RESULTS: To investigate the neural mechanism of OBVAT, eye movements, fMRI and physiological measures were collected in 8 patients with PPCS-CI (4 men and 4 women). Results show an 10% decrease in the MCA during 4-degree symmetrical convergent eye movement responses in males post-OBVAT and a 19% increase in MCA during convergent eye movement responses in females. Furthermore, there was a group level activation of the frontal eye fields, which improves post-OBVAT. The beta weights in the left frontal eye fields show a trending decrease in male patients post-OBVAT and trending increase in females. Males had a decrease in MCAv post OBVAT (baseline 83.6 ± 7.5 cm/sec & 75.7 ± 12.5 cm/sec post-OBVAT), while females show a significant increase post-OBVAT (baseline 53.77 ± 5.2 cm/sec & post-OBVAT 65.13 cm/sec ± 12.5). DISCUSSION/SIGNIFICANCE: This initial pilot demonstrates there may be different underlying pathophysiological outcomes associated with a concussion dependent on sex. This work may have direct implications on treatment strategies for male and female adolescent patients with PPCS-CI.

OBJECTIVES/GOALS: The goal of this study is to identify if ocular graft versus host disease (oGVHD) patients treated with a systemic JAK inhibitor have a change in their tear cytokine profile (a possible bio-marker) and oGVHD score. oGHVD is a severe inflammatory dry eye disease and major cause of morbidity after a hematopoietic stem cell transplant. METHODS/STUDY POPULATION: Janus Kinase (JAK) is an upstream regulator of cytokine production. A JAK 1/2 inhibitor, Ruxolitinib, was recently FDA approved for the treatment of chronic GVHD. We propose that JAK inhibition results incytokine changes in tears and improvement of oGVHD. To study this, we will quantify tear cytokines in patients with oGVHD, with and without systemic JAK inhibition treatment. Patients with ‘definite’ oGVHD based on the international chronic oGVHD diagnostic criteria (ICOGVHD) whom we have collected tears will be grouped based on JAK inhibition treatment. Tear cytokines are analyzed using Iso spark Meteor bulk quantitative proteomic analysis. RESULTS/ANTICIPATED RESULTS: Seven patients were identified from our patient cohort who met inclusion criteria (oGVHD; tears collected while on Ruxolitinib), five patients were identified whom we have collected tears with oGVHD who have not taken ruxolitinib. The following 10 cytokines will be analyzed in the tears by the Iso spark Meteor bulk quantitative proteomic analysis: GM-CSF, IFN-g, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17A, TNF-a. The change in cytokine levels will be compared with the ICOGVHD score, corneal fluorescein staining, schirmers test (measurement of tear production), conjunctival injection score, ocular surface disease index score (validated symptomatic score of dry eye disease). DISCUSSION/SIGNIFICANCE: OGVHD is a major cause of morbidity for patients who undergo a hematopoietic stem cell transplant and is the result of a highly complex immune process including dysregulation of pro-inflammatory cytokines. It is critical to understand the effect of cytokine changes on the eyes to potentially identify a biomarker and possible treatment targets.

OBJECTIVES/GOALS: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample (e.g. blood) offers the potential to provide insight into the dynamic, organism-wide changes reflective of health and disease. Thus, making cfDNA an ideal target for serial, minimally invasive monitoring of disease-related changes. METHODS/STUDY POPULATION: We develop a probabilistic method that leverages the co-regulation of neighboring CpG sites on individual methylome-wide sequencing (WGBS) reads to more flexibly model cell-specific methylation compared to prior methods that focus on the methylation rate of a single CpG site. We then extend our cross-sectional model to account for sequential sampling within the same subject. The increased sampling frequency is critical to identifying the evolutionary dynamics of disease progression influencing treatment response and resistance, and disease recurrence. We utilize Bayesian inference techniques to model patient-specific longitudinal profiles of cell-type turnover in simulated serial samples. RESULTS/ANTICIPATED RESULTS: We found our model more effective at capturing a range of methylation patterns on cfDNA fragments with lower Root Mean Square Error across simulations compared to a single CpG model. We apply our model to detect significant (p < 0.05, Friedman’s test) increases in cellular contributions from lung and cardiac tissue in breast cancer patients (n=15) undergoing radiation therapy compared to baseline. We also identify signals of radiation induced toxicity to the liver in right-sided breast cancer patients (n=8) receiving radiation treatment compared to left-sided breast cancer patients (n=7). Finally, we show our extended model results in more efficient estimates of simulated cell-type turnover profiles compared to analyzing serial samples cross-sectionally, ignoring the longitudinal nature of the data. DISCUSSION/SIGNIFICANCE: Here we address an unmet need in developing novel statistical methodologies to decode the origins of methylated cfDNA obtained from liquid biopsy samples. We demonstrate the far-ranging clinical utility of serial liquid biopsy sampling to complement and advance the standards of clinical care in oncology and other pathologies.

OBJECTIVES/GOALS: We aim to develop an understanding of how polysubstance use (PSU) relates to the general psychopathology factor (p-factor), as well as to individual components of the Hierarchical Taxonomy of Psychopathology (HiTOP) model (e.g., fear, distress). This insight can help identify treatment targets related to substance use and psychopathology. METHODS/STUDY POPULATION: Psychopathology and substance use data, collected at a Baltimore treatment center over several years, will be analyzed. The center aids about 6000 underserved clients per year, and the population is primarily African American clients of all genders. Structural equation modeling (using Mplus software) will be used to develop the latent models and identify relationships between psychopathology and PSU (i.e., direct and indirect pathways). The current latent HiTOP model was developed from symptom checklists completed upon entry at the treatment center. The PSU latent factor will be developed from a biopsychosocial assessment where clients list their drug of choice. Due to the varying organizations of the datasets, smaller-scale preliminary models will be developed to ensure an accurate large-scale final model. RESULTS/ANTICIPATED RESULTS: Current models being tested are derived from January to September 2023 data (i.e., completed months' data), with an N of 1,564. From symptom checklist data collected at the treatment center, a preliminary HiTOP model was derived with reasonable fit (χ2 = 4532.35 (df = 321, p<.001), CFI = .77, SRMR = .07, RMSEA = .09 (.089, .094)). Data analysis is being conducted to derive the PSU factor before relating PSU to the HiTOP model. Given previous work at a local treatment center (Pavuluri etal., 2022) and with the National Comorbidity Survey-Replication data, we expect all positive direct relationships, negative indirect relationships between internalizing factors (fear and distress) and PSU when accounting for p-factor, and a positive indirect relationship between antagonism and PSU when accounting for p-factor. DISCUSSION/SIGNIFICANCE: Given our previous work to develop such models, we want to establish proof of concept in alarger treatment center population. This confirmation will help provide a path towards conducting therapeutic trials to target psychopathology when treating substance use given the shared relations, some of which are less understood (e.g., fear and PSU).

OBJECTIVES/GOALS: Study the regulatory role of sodium glucose co-transporter 1 (SGLT1) in cardiomyocytes and the therapeutic potential of sotagliflozin in hypertrophic cardiomyopathy (HCM) by (a) quantifying SGLT1 expression in HCM and (b) examining the impact of sotagliflozin on cardiac mechanics. METHODS/STUDY POPULATION: * Use Western Blot in cardiac tissue from HCM and non-HCM patients and pre-existing RNA seq and proteomics datasets to quantify SGLT1 levels in HCM. Hypothesis: SGLT1 is upregulated in HCM * Determine how SGLT1/2 inhibition by sotagliflozin will affect cardiac mechanics using living myocardial slice (LMS) preparations. A vibratome creates 200um-thick slices from (a) failing HCM heart explants, (b) septal myectomy samples from HCM patients, and (c) nonfailing rejected donor hearts. LMS are mounted on a force transducer and work-loops are stimulated under varying pre- and after-loads. Collecting baseline and post-drug work loops allows each slice to function as its own control. Hypothesis: sotagliflozin will improve diastolic mechanics by reducing stiffness in the end-diastolic pressure-volume relationship RESULTS/ANTICIPATED RESULTS: * Preliminary results from RNA seq data indicate that SLC5A1 mRNA (encoding gene for SGLT1) is significantly decreased in HCM. No proteomics study examined thus far has detected SLC5A1, indicating that overall SGLT1 levels in cardiac tissue are quite low. We will examine SGLT1 levels in our own HCM and non-HCM tissue samples with both mass-spectrometry and Western Blot. * We analyze six slices from each heart and expect 15 donor hearts and 15 HCM hearts/myectomy samples. We visualize the work loop by plotting stress/strain. Stress/strain at mitral valve closure represents exponential end diastolic pressure-volume relationship; Stress/strain at aortic valve closure represents linear end systolic pressure volume relationship. A two-sample paired t-test will compare change in stiffness and elastance. DISCUSSION/SIGNIFICANCE: This project contributes to a growing body of research surrounding the currently unknown cardioprotective mechanism of SGLT 1/2 inhibitors, furthers the technique of using living myocardial slices to study cardiac mechanics, and supports a trial examining sotagliflozin in HCM, for which disease modifying therapy remains a prevailing unmet need.

OBJECTIVES/GOALS: Congenital anomalies (CAs) affect 3% of live births, yet the cause of 80% of CAs is unknown and for the 20% with an identified cause, variability in penetrance suggests additional risk drivers exist. Our method for identifying and categorizing CAs in electronic health record (EHR) linked biobank databases can expand and improve CA etiologic research. METHODS/STUDY POPULATION: We identified individuals with CAs in three groups: 1. Those with at least one CA 2. Those with multiple CAs (MCA), those with two or more ‘major’ CAs, and 3. Those with CAs in a specific organ system. We also created a novel quantitative approach, using phenome-wide association studies (pheWAS), for determining CA-associated genetic disease billing codes in order to separate individuals that have a known genetic cause for their CAs from those with idiopathic CAs. We updated CA phecodes, aggregates of clinical billing codes, which we used to identify CA cases in Vanderbilt’s EHR-linked biobank database, BioVU. We create a new phecode, ‘All CAs’, for researchers to quickly identify all individuals with at least one CA. We evaluate the definition of MCA using pheWAS analyses to compare ‘minor’ vs ‘major’ CA. RESULTS/ANTICIPATED RESULTS: The new CA phecode nomenclature includes 5.8 times more codes for CAs compared with the previous version (365 vs 56), improving granularity. 85 (19.7%) CA-associated genetic disease billing codes were identified through literature review. PheWAS analyses revealed an additional 16 (3.7%) genetic disease billing codes with one or more significant (p< 2.75 x10-5) association with CA-related phecodes. Identifying CA-associated genetic disease billing codes allows researchers to differentiate between idiopathic CAs and those that have a known genetic cause. PheWAS analyses of individuals with previously considered “minor” CAs showed many associated severe health problems, revealing that the differentiation between “minor” vs “major” CAs when identifying individuals with MCA in the EHR is arbitrary. DISCUSSION/SIGNIFICANCE: Our CA identification method is scalable for the growing number of EHR-linked biobanks. Differentiating between idiopathic CAs from those with known causes will increase power in studies discovering additional genetic drivers of CAs. Our novel method allows for expansion and acceleration of CA epidemiological research in EHR-linked biobank data.

OBJECTIVES/GOALS: Platform trials gain efficiency by sharing placebo controls among different study arms. However, the varying routes of administration make it unclear whether participants exposed to different placebos have similar outcomes. As such, we seek to compare outcomes between participants receiving tablet and inhaler placebos in the ACTIV-6 trial. METHODS/STUDY POPULATION: ACTIV-6 is a large, decentralized platform trial exploring repurposed drugs for the treatment of adults with mild to moderate COVID-19. Enrolled participants were randomly assigned to a study arm vs. placebo and then mailed the study drug. They were monitored until symptom resolution or Day 28. Here, we compare outcomes for control participants contributing to the fluticasone furoate study arm, in which 251 were assigned to a tablet placebo and 370 an inhaler placebo. Time to sustained recovery and time to resolution of individual symptoms are compared between groups using Kaplan-Meier curves and unadjusted log-rank tests. A step-down procedure is applied to control the false discovery rate. RESULTS/ANTICIPATED RESULTS: Control participants assigned to tablet placebos had shorter time to sustained recovery (adjusted hazard ratio (HR) 1.34 (95% CI 1.11, 1.62)). When examining each of the eleven individually reported symptoms on study Day 14, nasal symptoms (adjusted odds ratio (OR) 0.44 (0.27, 0.72), p<0.01), dyspnea (OR 0.44 (0.22, 0.87), p = 0.02), and cough (OR 0.54 (0.35, 0.83), p<0.01) were identified as symptoms in which the tablet-placebo group performed notably better than those who received inhaler-placebos. In the follow-up, longitudinal analysis, we anticipate similar results. DISCUSSION/SIGNIFICANCE: Among ACTIV-6 control participants, those receiving a tablet placebo had a significantly shorter time to sustained recovery than those receiving an inhaler placebo. Platform trials using shared controls should consider efficiency in the context of the additional variability when sharing controls with a different route of administration.

OBJECTIVES/GOALS: Super refractory status epilepticus (SRSE) is associated with high mortality, often due to withdrawal of life sustaining therapy (WLST) based on perceived poor neurological prognosis. Factors influencing decision making are underreported and poorly understood. We surveyed clinicians who treat SRSE to identify factors that influence WLST. METHODS/STUDY POPULATION: Health care providers (HCP), including physicians, pharmacists, and advanced practice providers, who treat SRSE answered a 51-question survey on respondent demographics, institutional characteristics and SRSE management that was distributed though professional societies. Respondents described approaches to prognostication and rated the importance of clinical factors in the management of two hypothetical clinical cases followed by their prediction of recovery potential for the same two cases. Neurointensivists and other HCP responses were compared using descriptive statistics to differentiate group characteristics; a p-value <0.05 was considered significant. Logistical regression models were employed to identify associations between clinician specific factors and prognostication. RESULTS/ANTICIPATED RESULTS: One-hundred and sixty-four respondents were included in the analysis. Compared to other HCPs (neurologists, epileptologists, neurosurgeons, other intensivists; n=122, 74%), neurointensivists (n=42, 26%) [Odds ratio (OR) 0.3, 95% confidence interval (CI) 0.14-0.68), p=.004)] were less likely to use prognostic severity scores and were less likely to prognosticate likelihood of good functional recovery (OR: 0.28 (95% CI: 0.13-0.62), p=.002) compared to non-neurointensivist HCPs, controlling for potential confounders including professional degree, years of experience, country of practice, and annual volume of SRSE cases. There was, however, significant overlap in factors deemed necessary for determining futility in care escalation. DISCUSSION/SIGNIFICANCE: Neurointensivists value similar clinical factors to other HCPs when evaluating medical futility in SRSE but are less likely to predict definitive outcomes. Pending final survey results, future studies aimed at understanding why neurointensivists may be less likely to decisively prognosticate (i.e. avoiding nihilism) in SRSE may be warranted.

OBJECTIVES/GOALS: Xylazine is a strong sedative and fentanyl contaminant which has been increasingly detected in drug overdose deaths in Maryland. The goal of this project is to analyze the demographic characteristics and time trends of xylazine-related overdose deaths (XROD) in Maryland from 2020-2022. METHODS/STUDY POPULATION: This cross-sectional study utilizes the Maryland medical examiner's autopsy reports from 2020-2022. These reports include every death in the state that was investigated by the medical examiner, with demographic and toxicological data showing the presence of various substances at the time of death. An XROD was defined as someone who died from drug overdose and had a positive serum xylazine test at time of death. Demographic characteristics and time trends for XROD were analyzed. Multivariable logistic regression modeled associations between demographic variables and the presence of other substances with XROD. RESULTS/ANTICIPATED RESULTS: A total of 1,509 people died from XROD, of which the mean age was 44.4 years and 73.3% were male. The majority were White (57.6%), 39.2% were Black, and 3.2% identified as another race. Over 99.9% of individuals who died from XROD tested positive for fentanyl. XROD peaked in January 2021 and has been trending downwards since then. Adjusted multivariable logistic regression revealed that White individuals had greater odds of XROD relative to Black individuals (OR=1.22, 95% CI=1.07-1.37), and adults aged 30-45 years had higher odds of XROD relative to adults over age 60 (OR=1.26, 95%CI=1.04-1.54). Individuals who used fentanyl had higher odds of XROD relative to those who did not use fentanyl (OR=327.4, 95%CI=46.0-2331.3). DISCUSSION/SIGNIFICANCE: This study demonstrates that middle age, White race, and fentanyl use are associated with xylazine-related overdose deaths in Maryland. Efforts to reduce xylazine-related mortality in the state should address the unique social and geographic factors that influence substance use in this population.

OBJECTIVES/GOALS: ICD-10 coding inconsistencies hinder timely recognition and treatment of metabolic syndrome (MetS), posing a significant risk for cardiometabolic disease progression. This study employed a digital phenotype for MetS and compared odds for medication and lifestyle intervention compared to those coded for MetS. METHODS/STUDY POPULATION: MetS is a cluster of cardiometabolic risk factors that increase risk for numerous adverse clinical outcomes. Patients with MetS were identified through electronic medical records on TriNetX LLC using the standard ICD-10 code or through a digital phenotype, involving grouping codes for the individual components. Percentage of patients with MetS not captured with the standard code was identified. In addition, disparities in blood pressure, glucose, lipid-lowering medication, and lifestyle intervention between the coding schemas were assessed, shedding light on healthcare inequities and informing targeted interventions. Odds ratios (RR) were presented for all outcomes. RESULTS/ANTICIPATED RESULTS: Patient demographics and lab values were similar between the standard code and digital phenotype cohorts. Of the 4.3 million individuals aged 50 to 80 identified as having MetS using the digital phenotype in the TriNetX research network, only 1.78% of participants shared the standard code. Individuals with the digital phenotype for MetS were at lower odds in receiving glucose lowering medication (OR: 2.11, 95% CI: 1.98–2.13, p <0.001) and exercise or nutrition-based intervention advice (OR: 1.76, 95% CI: 1.55–1.96, p <0.001) after controlling for demographics and lab values for each MetS component. DISCUSSION/SIGNIFICANCE: This project utilized TriNetX to create a digital phenotype for MetS, and suggests most patients are not coded for it using the standard ICD-10 system. This is troublesome given those with the standard code are less likely to receive certain interventions.

OBJECTIVES/GOALS: The goal of this study is to leverage a national database to see if autologous reconstruction rates differ in patient and clinical characteristics, readmission rates, and overall survival (OS) compared to other forms of reconstruction. Autologous reconstruction has not been looked at in this way before. METHODS/STUDY POPULATION: • Aim 1: Use the National Cancer Data Base to construct three patient cohorts for women under 70 and above 18 treated surgically for breast cancer with A) mastectomy only, B) implant-based reconstruction, and C) autologous breast reconstruction. • Aim 2: Examine receipt rates of surgical intervention in Cohorts A vs. B vs. C based on clinical and patient demographic/socioeconomic characteristics. • Aim 3: Compare readmission and overall survival (OS) rates for Cohorts A vs. B vs. C while controlling for age and other key variables. RESULTS/ANTICIPATED RESULTS: Based on the literature, we expect rates of autologous reconstruction (Cohort C) to be lower for patients of minority backgrounds compared to white individuals. In addition, we do not expect overall survival to differ between implant-based (Cohort B) and Cohort C reconstruction. Still, we expect mastectomy-only (Cohort A) survival to vary from the two cohorts even when adjusting for different clinical factors, as similar but smaller studies have shown. Finally, we expect readmission rates to be higher for Cohort C, compared to Cohorts A & B, as it is a more complicated procedure typically done in academic institutions with skilled surgeons. DISCUSSION/SIGNIFICANCE: Autologous reconstruction is now considered the gold standard due to its ability to restore the breast shape with higher patient satisfaction and superior long-term outcomes. Multiple studies have documented ongoing racial disparities in post-mastectomy breast reconstruction and autologous reconstruction, with lower rates and referrals.

OBJECTIVES/GOALS: The primary objective is to measure the independent association of hospital-level and sociodemographic variables on the rate of hospital-onset bacteremia among infants admitted to the neonatal intensive care unit in a United States of America retrospective cohort. The secondary outcome will be relative blood culture collection rate. METHODS/STUDY POPULATION: The study is an analysis of a retrospective cohort comprised of infants admitted to 322 neonatal intensive care units (NICUs) in the United States of America between 2016-2021. The primary outcome will be hospital-onset bacteremia (HOB), defined as a positive blood culture with a bacteria or fungi after day 3 of admission. Independent risk factors will include birthweight, postnatal age, central venous catheter presence, sociodemographic variables (race, ethnicity, insurance status and ZIP code-level demographic data from the US Census American Community Survey (ACS), and hospital-level variables. Infants will be stratified by sociodemographic groups and a Poisson model will be utilized to measure the adjusted association between risk of HOB and clinical and hospital-level variables. RESULTS/ANTICIPATED RESULTS: I anticipate that infants in sociodemographic groups with a history of socioeconomic marginalization will have a higher unadjusted rate of HOB; however, sociodemographic variables will not be independently associated with HOB risk after adjusting for markers of hospital quality and acuity, such as quartiles of the following: mean admissions per year, percentage of infants born <1500g, annual blood culture contamination rate, and percentage infants born at another facility. DISCUSSION/SIGNIFICANCE: Neonatal bacteremia has high morbidity and mortality; however, its contribution to known infant mortality inequities is unknown. This study will estimate the burden of infant HOB stratified by sociodemographic groups and measure the independent association of sociodemographic and hospital-level variables on the adjusted rate of HOB.

OBJECTIVES/GOALS: Endovascular peripheral vascular interventions (PVIs) are increasingly utilized for the treatment of peripheral artery disease (PAD). We aimed to assess characteristics of patients receiving PVI at ambulatory surgical centers and office-based labs (ASC/OBL) versus the outpatient hospital (hospital) site of service. METHODS/STUDY POPULATION: We performed a retrospective analysis using 100% Medicare fee-for-service claims data between January 1, 2017 and December 31, 2022. We used Current Procedural Terminology (CPT) codes to identify patients undergoing angioplasty, stenting, or atherectomy. Patient demographics were collected from the Medicare Master Beneficiary Summary File and associated comorbidities and PVI indications were identified using International Classification of Disease (ICD)-10 codes. We used patient ZIP codes to determine patients’ residence densities and regions. We used site of service codes to determine whether PVI were performed in the ASC/OBL versus hospital. Results were analyzed with descriptive statistics. RESULTS/ANTICIPATED RESULTS: Of 817,241 patients undergoing PVI for PAD, 461,068 (56.4%) were treated in an ASC/OBL. Compared to patients treated in the hospital, patients receiving PVI at ASC/OBLs were more likely to be older, female, non-white race, with fewer comorbidities (end stage renal disease, diabetes, hypertension, and any history of tobacco use) (all, P<0.001). Patients treated in ASC/OBLs more frequently resided in urban (vs. rural) locations, and in the South and West (both, P<0.001). Indication for PVI was predominately chronic limb-threatening ischemia, and clinically similar between groups (77.1% vs. 76.2%). There was a significant change in site of service over time: a minority (47.6%) of PVIs were performed in the ASC/OBL in 2017, whereas the majority (64.7%) of PVIs were performed in the ASC/OBL in 2022 (P<0.001). DISCUSSION/SIGNIFICANCE: Patients treated in ASC/OBLs were less medically complex compared to those treated in the outpatient hospital setting. Further study is needed to examine whether differences in patient characteristics versus other factors (e.g. reimbursement) are driving the increase in PVIs performed in the ASC/OBL over time.

OBJECTIVES/GOALS: Antibiograms are used to guide empiric antibiotic selection. However, it is unclear if antibiotic profiles differ between symptomatic urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB). We aimed to compare antibiotic susceptibility profiles of urinary E. coli isolates from patients with a symptomatic UTI to those with ASB. METHODS/STUDY POPULATION: We conducted a cohort study of 1,140 urinary E. coli isolates from unique patients that received care through Vanderbilt University Medical Center (VUMC) from Nov 2020 – Jun 2021. We included any patient that was seen at VUMC as an inpatient, outpatient or at the emergency department with ≥ 105 colony forming units/mL E. coli detected from a clinical urine specimen. Chart abstractions were performed to capture reported UTI symptoms and demographic information. Descriptive statistics were conducted to compare antibiotic susceptibility profiles (i.e., susceptible, intermediate, resistant) between symptomatic and ASB groups. The risk of detection of a multidrug-resistant organism (MDRO) (intermediate, or resistant to at least one antibiotic in three or more classes) was assessed between groups. RESULTS/ANTICIPATED RESULTS: Among 1,140, 1,018 (89%) and 122 (11%) were symptomatic and ASB, respectively. When comparing symptomatic and ASB, the median ages were 50 and 46. Groups had similar proportions of no indwelling catheter (94% v. 95%) and without diabetes (87% v. 88%). The collection setting between inpatient, emergency department, and outpatient were similar with most being outpatient (79% v. 83%). The proportion of patients who were pregnant, immuno compromised, or had a structural/functional urinary tract abnormality were higher in the symptomatic group. The proportion of isolates resistant and susceptible to tested antibiotics were similar between groups, with only ciprofloxacin showing slightly higher resistance among ASB (16% v. 25%). The risk of MDRO detection was similar between groups (RR: 0.858, 95% CI: 0.64, 1.15). DISCUSSION/SIGNIFICANCE: Antibiotic susceptibility comparison demonstrated similar profiles, which suggests antibiogram use as appropriate to guide ASB treatment. Results offer insight on whether traditional methods for assessing antibiotic susceptibility on population-levels could benefit from further refinement by patient-specific clinical parameters.

OBJECTIVES/GOALS: The objective was to examine the American Heart Association’s (AHA) Essential Eight metrics of cardiovascular (CV) health among Black and White adults with peripheral arterial disease (PAD) collected via validated surveys and medical records. Each metric was examined in association with available social determinants of health (SDoH) factors. METHODS/STUDY POPULATION: This observational study completed data collection through surveys and medical record review. Validated surveys were used to collect Essential Eight metrics of diet, physical activity, sleep, and smoking status. Medical records were used to collect data on body mass index, blood lipids, blood glucose, and blood pressure. Participants with a diagnosis of lower extremity PAD, ability to complete surveys, and provided informed written consent were eligible. Equal numbers of Black and White participants were enrolled. Essential Eight metrics were used to calculate CV health scores for each participant. Scores were examined for association with SDoH factors and by race using Student’s T-test or ANOVA for continuous variables or Chi-Square tests for categorical variables. RESULTS/ANTICIPATED RESULTS: A total of 50 participants will be enrolled, with the expected majority being men and half self-reporting as Black individuals. Worse SDoH is expected to be associated with lower CV health metrics, including lower levels of physical activity and higher levels of saturated fatty food consumption. Higher levels of blood lipids, blood glucose, and blood pressure are expected to be associated with worse SDoH factors. We expect this association to be attenuated by rates of CV medications, such as statin therapy, antiglycemic medications, and antihypertensive medications. No effect modification by rurality is expected, although our projected sample size is small and may impact the ability to examine this interaction. DISCUSSION/SIGNIFICANCE: Black Americans, particularly in the Deep South, are at elevated risk for PAD and critical limb ischemic events, such as amputation. Understanding CV health metrics and SDoH characteristics among adults with PAD is essential to reduce disparities in care and provide valuable information for those at highest risk for complications.

OBJECTIVES/GOALS: Single nucleotide polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with Type 2 Diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). The metabolic function of TCF7L2 in the liver remains to be fully elucidated, but we hypothesized that TCF7L2 contributes to NAFLD through regulation of zonal metabolic pathways. METHODS/STUDY POPULATION: Using single nuclei RNA sequencing, we examined Tcf7l2 expression in periportal (PP) hepatocytes around the portal triad and pericentral (PC) hepatocytes surrounding the central vein of the liver. To visualize TCF7L2 transcriptional activity we used a TCF reporter mice, which expresses an H2B-eGFP fusion protein downstream of the conserved TCF DNA binding site. We disrupted Tcf7l2 transcriptional activity in mouse liver by breeding mice with a floxed Tcf7l2 exon 11, which encodes part of the DNA binding domain (DBD), to albumin-Cre mice (Hep-TCF7L2ΔDBD). Eight-week-old mice were fed a choline-deficient amino acid-defined high fat (CDAHFD) diet for 8 weeks. In liver samples harvested from these mice, we examined disruption to several key zonated metabolic pathways, and quantified the development of fibrosis. RESULTS/ANTICIPATED RESULTS: Single nuclei analysis revealed that Tcf7l2 mRNA was expressed primarily in parenchymal cells of the liver but was ubiquitous across the liver lobule. However, in immunofluorescence analysis of TCF reporter mice, the transcriptional activity of TCF7L2 was highly restricted to PC hepatocytes. Classic PC hepatocyte markers, including glutamine synthetase (Glul), were absent in Hep-TCF7L2ΔDBD mice. Following the CDAHFD, Hep-TCF7L2ΔDBD mice developed more severe fibrosis in histological analysis, and expressed elevated levels of genes involved in fibrogenesis, collagen synthesis and TGFβ signaling. Hep-TCF7L2ΔDBD mice also displayed hepatic cholesterol accumulation following the CDAHFD, which was likely the result of impaired pericentral bile acid synthesis. DISCUSSION/SIGNIFICANCE: Our results suggest that TCF7L2 plays an important role in the regulation of zonated metabolic pathways, which may contribute to the development of fibrosis. Ongoing analyses are exploring the mechanisms regulating the zonal transcriptional activity of TCF7L2.

OBJECTIVES/GOALS: High serum copper (Cu) levels have previously been described in bariatric patients. The kidneys are a target organ for Cu toxic insult but the role of Cu on kidney function (eGFR) is uncertain. This study examines the association between Cu and eGFR in a bariatric population in Southeast Louisiana. METHODS/STUDY POPULATION: Seven hundred fifty patients will be recruited from the Bariatric Center of the University Medical Center in New Orleans. Inclusion criteria include: age ≥ 18 years, clinic visit between June 1, 2018 – May 31st 2024, and having a serum Cu test result. Covariables such as inflammatory markers and hormonal contraception use will be assessed as potential confounders. Blood pressure will be assessed as a potential effect modifier. Data will be obtained from electronic medical records. Two cohorts will be assembled, a pre-surgery cross-sectional cohort and another followed post-surgery. Separate models will be developed stratified by race-ethnicity. RESULTS/ANTICIPATED RESULTS: In a pilot study of bariatric patients 26% had elevated (>155 mcg/dl) serum Cu and pronounced racial differences were noted. Characteristics consisted of a mean BMI of approximately 50 kg/m2; 91% were female and 69% were Black. Black patients had approximately double the prevalence (OR 1.98; 95% CI: 1.15, 3.4) compared to white patients. Due to the dual nature of the kidneys’ involvement in metabolism via excretion and being the target organ for toxic insult, racial differences in exposure, coupled with the disproportionate rates of chronic kidney disease in Black adults, may be an explanation for the association between elevated Cu levels and eGFR in Black adults in this study. DISCUSSION/SIGNIFICANCE: Results from this study will provide insight into the prevalence of Cu and its association with kidney function in a bariatric population. Chronic kidney disease or other forms of renal impairment may result in the need for more conservative guidelines for dietary copper in bariatric medicine.

OBJECTIVES/GOALS: The project investigates the role that resiliency may play within individual, interpersonal, social, and structural contexts in protecting against acute lethal stimulant (meth/amphetamine or cocaine) toxicity. Identifying preventative factors is crucial in developing and implementing risk reduction strategies for people who use stimulants. METHODS/STUDY POPULATION: This is a qualitative study involving in-depth interviews via questionnaire assessing resiliency factors among persons living in San Francisco who have used primarily either meth/amphetamine or cocaine for at least 5 years. The interviews will be coded for salient and recurrent themes and analyzed for code frequency, cooccurrences, clustering of themes and representative excerpts to highlight emergent themes as well as stressors and resilience factors at multiple levels. We aim to assess for substance use patterns, multiple domains of resiliency, medical and psychiatric complaints, and risk reduction strategies. We will recruit participants to match recent decedents from acute stimulant toxicity in various domains including salient demographic information and neighborhood characteristics. RESULTS/ANTICIPATED RESULTS: The anticipated results include a qualitative interview guide for living persons using stimulants in San Francisco to be used to gain insight into the community, illustrate participants’ substance use practices, and allow for better characterization of several discrete resiliency factors that have protected the participants and other community members from suffering lethal stimulant toxicity. We expect to identify individual components (e.g. use patterns, use of harm reduction supplies), interpersonal/social factors (e.g. drug using network, friendships, community connection), and structural influences (e.g. access to care, safe use sites, house and economic stability) that all play a role in resiliency against lethal stimulant toxicity. DISCUSSION/SIGNIFICANCE: Stimulant use is common, along with rising deaths involving stimulants in urban counties and in smaller rural/non-metro counties which are disproportionately affected, posing a public health challenge. We will find discrete, modifiable risk and resiliency factors that can be manipulated to minimize the chances of outcomes like overdose and death.

OBJECTIVES/GOALS: This study examined racial-ethnic differences in antipsychotic initiation within psychiatric diagnostic groups. This is a follow-up to our prior work, which reported that, overall, youth from minority backgrounds had 30-65% lower odds of initiating antipsychotics compared to White youth. METHODS/STUDY POPULATION: This study used 2009-2021 data from Optum’s® Clinformatics® Data Mart, a database containing longitudinal patient information from nationwide commercial insurance claims. We created three separate samples of antipsychotic users and matched non-user controls between the ages of 6-17 years old. These groups contained individuals with clinically diagnosed ADHD, conduct disorder, and depressive disorder, respectively. We used conditional logistic regression to estimate the odds of antipsychotic initiation based on race-ethnicity within each diagnostic group. RESULTS/ANTICIPATED RESULTS: There were no racial-ethnic differences in the odds of antipsychotic initiation among youth diagnosed with ADHD. Among youth with depression diagnoses, Asian youth had 19% lower odds of initiating antipsychotics and Hispanic youth had 11% lower odds compared with White youth. Similar results were observed for conduct disorders, with Asian and Black youth having approximately 10% lower odds of initiating antipsychotic treatment and Hispanic youth having 18% lower odds relative to White youth. DISCUSSION/SIGNIFICANCE: Previously observed lower rates of antipsychotic initiation among racial-ethnic minority groups may be at least partially due to factors leading to disparities in diagnosis. Further research is needed to evaluate factors that may lead to differential antipsychotic use, as the disparities may occur upstream of receiving clinical diagnoses.