OBJECTIVES/GOALS: We developed a non-invasive test of ocular alignment (OA) as a measure of otolith asymmetry, which impacts vestibular function. This test has also been administered on commercial astronauts to study the effect of microgravity on vestibular function. We will assess OA test performance in ground subjects, which has not yet been characterized. METHODS/STUDY POPULATION: Subjects were recruited from visitors to Space Center Houston from June to October 2022. Participants wore red-blue glasses in a darkened room and aligned two vertically or torsionally misaligned line segments, one red and one blue, on a tablet. Each subject underwent 11 vertical and torsional trials. The remaining misalignment was used to calculate ocular misalignment. Subjects self-reported demographic and health data. We calculated descriptive statistics and explored the distribution of overall vertical and torsional OA and distributions by age. Next steps will establish the reliability of the outcome measures with intraclass correlation coefficients and analyze associations between demographic variables and health status with OA performance using linear regression analysis. RESULTS/ANTICIPATED RESULTS: A total of 143 participants (67 female) with a median age of 21 (range 5-74 years old) completed OA testing. Of participants, 64% identified as white, 10% as black, 14% as Asian, 3% as Native American, and 8% as unknown. This test battery was feasible to implement in this mixed-age sample, with a 95% completion rate. Median absolute vertical OA was 0.08 degrees (IQR = 0.17 degrees), and median absolute torsional OA was 0.80 degrees (IQR = 1.20 degrees). Visual analysis of plots of OA by trial number reveals no apparent learning effect within subjects, though some individuals had considerable variation in performance. Average absolute vertical ocular misalignment increased modestly when plotted by age (fitted regression line b = 0.0032 degrees per year of age, p = 0.004), unadjusted for potential confounders. DISCUSSION/SIGNIFICANCE: Ocular alignment testing was feasible in a mixed-age general population sample. Our findings will expand understanding of how OA varies with age. These results will be used to create a normative database to compare and inform analysis of OA results from commercial spaceflights, which include individuals of varying age and health statuses.

OBJECTIVES/GOALS: In 2010, an estimated 65% of antipsychotic prescriptions were given to youth for off-label indications. It is unclear whether subsequent calls for reduced pediatric prescribing led to a decrease in off-label use. This study examined the diagnostic characteristics of the current pediatric population using antipsychotics in the United States. METHODS/STUDY POPULATION: Data from the Clinformatics Data Mart, a database containing longitudinal patient information between 2010-2019 from commercial healthcare insurance claims in the United States was used in this study. We conducted a case-control study, in which antipsychotic initiators were matched 1:1 to non-initiators on age, sex, and insurance enrollment. There were 26,375 included antipsychotic initiators with matched non-initiator controls between the ages of 6-17. Conditional logistic regression was used to examine the odds of being an antipsychotic user among those with past-year psychiatric diagnoses that have been previously found to be associated with antipsychotic use. RESULTS/ANTICIPATED RESULTS: Disorders with psychotic features were associated with the greatest differences in odds of antipsychotic prescription receipt. Specifically, children with bipolar or manic disorders had 145-fold greater odds of antipsychotic receipt than did those without bipolar or manic disorders (OR = 145.45, 95% CI = [95.64, 221.22]), whereas those with schizophrenia had 106-fold greater odds (OR = 105.89, CI = [67.40, 166.37]). However, these disorders occurred in only 12% and 8%, respectively, of the antipsychotic recipients. The most common disorders among those with antipsychotic receipt were depressive disorders and ADHD, which occurred in 46% and 43% of the recipients, respectively. Additionally, conduct disorder was present in 20% of recipients. DISCUSSION/SIGNIFICANCE: As expected, bipolar disorder and schizophrenia were strongly associated with initiation of pediatric antipsychotic treatment. Yet, most initiators did not have a diagnosis for either psychotic disorder or any other FDA-approved indications. This study highlights the critical need for further research on antipsychotic use among youth.

OBJECTIVES/GOALS: We aimed to find the histology-specific markers that were predictive of post-operative long-term chordoma recurrence (≤1 year) using trained multiple tree-based machine learning (ML) algorithms. METHODS/STUDY POPULATION: We reviewed the records of patients who had treatment for clival and spinal chordomas between January 2017 and June 2021 across the Mayo Clinic enterprise (Minnesota, Florida, and Arizona). Patients were excluded if they had no histopathology or recurrence as an outcome. Demographics, type of treatment, clinical and radiological follow-up duration, histopathology, and other relevant clinical factors were abstracted from each patient record. Decision tree and random forest classifiers were trained and tested to predict the long-term recurrence based on unseen data using an 80/20 split. The performance of the model was optimized using tenfold cross-validation. RESULTS/ANTICIPATED RESULTS: One hundred fifty-one patients were identified: 58 chordomas from the clivus, 48 chordomas of the mobile spine, and 45 sacrococcygeal. Subtotal Resection followed by radiation therapy, was the most common treatment modality, followed by Gross Total resection, then radiation therapy. The multivariate analysis defines the molecular predictors of recurrence following resection. S100 and pan-cytokeratin is more likely to increase the risk of post-operative recurrence (OR= 3.67; CI= [1.09,12.42], p=0.03). In the decision tree analysis, a clinical follow-up > 1897 days was found in 37 % of encounters and a 90% chance of being classified for recurrence (Accuracy= 77%). Factors predicting long-term recurrence are the patient’s age, type of surgical treatment, location of the tumor, S100, pan-cytokeratin, and EMA. DISCUSSION/SIGNIFICANCE: Our molecular and clinicopathological variables combined with tree-based ML tools successfully demonstrate a high capacity to individually identify the patient’s recurrence pattern with an accuracy of 77%. S100, pan-cytokeratin, and EMA were the histologic drivers of recurrence.

OBJECTIVES/GOALS: The rapid spread of Monkeypox (MPV) across the US may trigger stress reactions that increase the risk of developing secondary trauma among those most at risk of exposure. The present study aimed to investigate the degree to which vicarious MPV exposure (i.e., knowing people who acquired MPV), was associated with symptoms of secondary traumatization. METHODS/STUDY POPULATION: An online survey was administered to 253 participants enrolled in Keeping it LITE, a prospective U.S. cohort study of ethnically diverse, sexually active, sexual, and gender minority persons aged 19–39 in September 2022. Multiple linear regression was used to examine the association between proximity to MPV and secondary traumatic stress (STS) symptoms. RESULTS/ANTICIPATED RESULTS: Study findings demonstrated that MPV morbidity was low (1%); however, 37% of participants reported knowing at least one person diagnosed with MPV. For most individuals, this person was a friend (28%). 16% of participants were found to have at least one indicator of MPV-related STS. Our multiple linear regression results demonstrated a positive association between an individual’s indirect exposure to MPV via their interpersonal relationships and STS symptoms. DISCUSSION/SIGNIFICANCE: Findings suggest that the more adults’interpersonal relationships are saturated with people who have acquired MPV, the more likely they are to develop symptoms of secondary traumatization. These findings provide initial evidence that secondary exposure to MPV via one’s social network may undermine adults’mental health.

OBJECTIVES/GOALS: METHODS/STUDY POPULATION: This study utilizes the IeDEA W. Africa cohort to evaluate the prevalence and burden of hypertension and diabetes type II among people living with HIV (PLWH) in sub-Saharan Africa (SSA), and to assess how sex and aging impact the development of these NACM. The cohort is a large, international collaboration across eight countries and 19 treatment centers. Established by the National Institute of Allergy and Infectious Diseases in 2006, the W. Africa cohort is now in its fourth renewal (2021-2026). Participating countries include Senegal, Mali, Cote d’Ivoire, Burkina Faso, Ghana, Togo, Benin, and Nigeria. Data are collected from affiliated cohorts in the regional data center every 24 months. The cohort currently includes >65,000 adult PLWH on anti-retroviral therapy. RESULTS/ANTICIPATED RESULTS: The prevalence of several NACM, such as hypertension and cardiovascular disease, have significantly increased among PWH over time, surpassing prevalence observed in the general population. We therefore expect similar patterns in the W. Africa IeDEA cohort and a high prevalence and burden of both hypertension and diabetes type II in this sample. Additionally, evidence suggests that increasing age and female sex serve as independent risk factors for the development of NACM in PLWH. We anticipate that both increased age and female sex, separately and synergistically, are associated with increased prevalence and burden of hypertension and diabetes type II in this cohort. DISCUSSION/SIGNIFICANCE: With more than 37 million people currently living with HIV, the HIV/AIDS epidemic continues to pose a serious threat to global public health. SSA bears a disproportionate burden of the epidemic with greater than two-thirds of global cases. NACM are now driving morbidity and mortality among PLWH, and increased age and female sex may modify this effect.

OBJECTIVES/GOALS: The prevalence of combusted cigarette (CC) smoking among older adults is stagnant, with zero declines attributable to e-cigarette (EC) use. Normative beliefs predict quitting and switching to ECs (a behavior likely to yield health benefits for those unable to quit), so this study seeks to characterize the role of age in norms about CC and EC use. METHODS/STUDY POPULATION: Data come from Wave 5 (2018-2019) of the adult Population Assessment of Tobacco Use and Health (PATH) study, a nationally-representative, U.S. longitudinal cohort. Analyses were restricted to people with established CC use (smoked CCs in the past year, currently smoke regularly, and smoked ≥100 lifetime CCs; n=8,590). Cross-sectional weighted estimates of the prevalence of normative beliefs about CCs and ECs were calculated by age using the Balanced Repeated Replication (BRR) method with Fay=0.3. We used chi-square tests to examine the association of age group (18-24, 25-34, 35-44, 45-54, 55-64, or ≥65) with the prevalence of 2 descriptive and 4 personal social norms. RESULTS/ANTICIPATED RESULTS: The prevalence of the normative belief that most people disapprove of CCs (p DISCUSSION/SIGNIFICANCE: Older adults are more likely than younger adults to endorse anti-tobacco norms, which prior work shows is associated with quitting smoking. These beliefs could be leveraged to create targeted communications towards older adults encouraging smoking cessation. More research is needed to assess age-related tobacco beliefs and switching from CC to EC.

OBJECTIVES/GOALS: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample (e.g. blood) can provide insight into the dynamic, organism-wide changes reflective of health and disease state. Making cfDNA an ideal target for genomic monitoring of disease-related changes. METHODS/STUDY POPULATION: Methylome-wide sequencing (WGBS) data present unique statistical challenges. To this end, we developed a novel statistical method using an Expectation-Maximization algorithm to decode the cellular origins of cfDNA fragments in liquid biopsies. Our flexible, probabilistic method leverages the co-regulation of neighboring CpG sites on the individual sequencing read to facilitate tissue of origin analysis, as opposed to prior methods that focus on the methylation rate of a single CpG site. We assess the performance of our model in various simulated settings and apply our model to an important clinical example in which we are able to detect early off-target tissue damage from radiation therapy via minimally invasive blood draws. RESULTS/ANTICIPATED RESULTS: We found our model more effective at capturing the range of biologically plausible methylation patterns on cfDNA read fragments compared to prior models that use single CpG sites. We also show our model is robust to high levels of noise inherent with WGBS data. We demonstrate the accuracy of cell-type proportion estimation on in-silico mixed cfDNA samples from real WGBS data. Finally, we use our model in a clinical application. We detect significant (p < 0.05) increases in cellular contributions from lung and cardiac tissue in breast cancer patients (n=15) undergoing radiation therapy compared to baseline. We also detect novel signals of radiation induced toxicity to the liver in right-sided breast cancer patients (n=8) receiving radiation treatment compared to matched left-sided breast cancer patients (n=7). DISCUSSION/SIGNIFICANCE: Here we address an unmet need in developing novel statistical methodologies that can handle the unique complexities of methylated cfDNA obtained from liquid biopsy samples. We also demonstrate the far-ranging clinical utility of serial liquid biopsy sampling to complement and advance standards of clinical care in oncology and other pathologies.

OBJECTIVES/GOALS: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by slow gait and subjective cognitive complaints. In the Atherosclerosis Risk in Communities (ARIC) study, we aim to (1) identify plasma proteins and protein modules associated with MCR and (2) compare the proteomic signature of MCR to that of mild cognitive impairment (MCI). METHODS/STUDY POPULATION: Nondemented ARIC participants were classified by MCR status (yes/no) according to a memory questionnaire and 4-meter walk. MCI status (yes/no) was classified by expert diagnosis using standardized criteria. We measured 4,877 proteins in plasma collected at ARIC Visit 5 (late-life) and Visit 2 (midlife) utilizing the SomaScan4 proteomic assay. Multivariable logistic regression”adjusted for demographic variables, kidney function, cardiovascular risk factors, and APOE4 status”related each protein to MCR at late-life. An FDR corrected P RESULTS/ANTICIPATED RESULTS: Proteome-wide association study among 4076 ARIC participants (mean age=75; 58% women, 17% Black, 4% MCR+, 21% MCI+; MCR+ and MCI+ groups overlapped) at late-life identified 26 MCR-associated proteins involved in metabolism, vascular/visceral smooth muscle, and extracellular matrix organization. At an uncorrected P DISCUSSION/SIGNIFICANCE: This proteomic characterization of MCR identifies novel plasma proteins and networks, both distinct from and overlapping with those of MCI, thus highlighting the partially divergent mechanisms underlying these pre-dementia syndromes. These findings may be leveraged toward dementia prognostication and targeted therapeutic approaches.

OBJECTIVES/GOALS: Children with Down syndrome are at increased risk of respiratory diseases including asthma. Prenatal antibiotic exposure has been shown to be associated with the development of childhood asthma. We aim to estimate the association between prenatal antibiotic exposure and childhood asthma among children with Down syndrome. METHODS/STUDY POPULATION: We conducted a retrospective cohort study of mother-child dyads of children with Down syndrome who were born 1995-2013. Both children and mothers were continuously enrolled in the Tennessee Medicaid Program (TennCare). Prenatal antibiotic exposure was measured using mother’s prescription fill records. Childhood asthma was defined between age 4.5-6 years by asthma-related healthcare encounters and asthma-specific medication fills. We assessed the association between prenatal antibiotic exposure and childhood asthma among children with Down syndrome using modified Poisson regression adjusting for maternal age, race, residence, education, marital status, smoking during pregnancy, maternal asthma status, delivery method, number of siblings, and children’s sex. RESULTS/ANTICIPATED RESULTS: Among 346 mother-child dyads of children with Down syndrome, 273 (78.9%) children were exposed prenatally to antibiotics and 104 (30.0%) had asthma by age 4.5-6 years. Among those who were exposed to at least one course, the median antibiotic course equaled 2 (interquartile range: 1-4). Prenatal antibiotic exposure was associated with a 20% increase in risk of childhood asthma in the unadjusted analysis (risk ratio [RR] 1.20, 95% confidence interval [CI] 0.78, 1.83) and a 26% increase in risk after adjustment (adjusted RR 1.26, 95% CI 0.79, 2.01). DISCUSSION/SIGNIFICANCE: In our study population, the majority of children with Down syndrome were exposed to antibiotics prenatally and the prevalence of asthma was high. Prenatal antibiotic exposure was associated with an increased risk of childhood asthma among children with Down syndrome; however, this increase was not statistically significant.

OBJECTIVES/GOALS: There is evidence that lesbian, gay, and bisexual (LGB) adults have poorer cardiovascular health than their heterosexual peers, but studies of the association between sexual orientation (SO) and diabetes mellitus (DM) have been few with mixed findings. To further investigate this association, large cohorts with objective data capture are needed. METHODS/STUDY POPULATION: We used data from the Veterans Healthcare Administration Lesbian, Gay, Bisexual, Transgender EHR cohort which includes veterans with at least 2 encounters October 1, 2009-September 30, 2019. The first clinic visit in this window was the index date with the baseline date one year later; the intervening year served as a baseline period for observation of prevalent disease and comorbidities. We did not include transgender veterans in this analysis in order to focus on SO rather than on the intersection of SO with gender identity. The SO of 1,108,990 veterans was identified using a natural language processing tool; 185,788 veterans were classified as LGB. We first examined sample characteristics by sex and SO and then used logistic regression to assess the association between SO and prevalent DM. RESULTS/ANTICIPATED RESULTS: DM was present among 193,330 veterans (32,986 LGB). Mean age was similar across SO in women (41) and men (53). Distribution of race was similar across groups, but LGB veterans were more likely to be Hispanic (11%, both sexes) than non-LGB men (6%) and women (8%). Current smoking was more prevalent among LGB (44% men, 39% women) than non-LGB veterans (40% men, 30% women). Adjusting for age, sex, race, Hispanic ethnicity, BMI, smoking status, health insurance, marital status, and enrollment priority, LGB veterans had 1.12 [1.10, 1.13] times the odds of DM vs. non-LGB veterans. Bisexual (0.87 [0.74, 1.01]) or lesbian (1.03 [0.97, 1.10]) women did not have significantly different DM odds than non-LGB women. Bisexual men had lower DM odds (0.86 [0.80, 0.93]) while gay men had higher odds (1.04 [1.01, 1.06]) than non-LGB men. DISCUSSION/SIGNIFICANCE: This is one of the first studies to report DM in a veteran cohort stratified by SO. Our findings highlight the importance of examining SO groups separately and jointly, as to further elucidate the association between SO, cardiovascular risk factors, and general cardiovascular health. Future work will examine the intersection of SO and gender identity.

OBJECTIVES/GOALS: This study aimed to determine the prevalence of cardiovascular risk factors in a group of victims of CSA in Puerto Rico and determine the impact of both the offender and the number of victimizations on the presentation of cardiovascular risk factors. METHODS/STUDY POPULATION: A study design of a retrospective chart review at a clinical forensic service in Puerto Rico. The demographic variables were age, sex, and health plan; the CV risk factors were family health history, level of physical activity, blood pressure, BMI, and lipid profile. Sexual violence experience variables were sexual assault, sexual molestation, the relationship with the offender, and the number of victimizations. Medical records were used to identify cardiovascular risk factors and variables associated with child sexual abuse victimization. Central tendency and frequencies were used to describe the risk factors and victimization. The Mann–Whitney and Fisher exact tests were used to determine the differences between the type of victimization and the risk factors for cardiovascular health. RESULTS/ANTICIPATED RESULTS: Most of the victims were female (81%), with an average age of 10 (SD 3.8). According to the 31 reviewed charts, 55% were victims of sexual assault, the offender was a family member (84%), and the assault had occurred more than once (81%). The study also found that systolic blood pressure, diastolic blood pressure, total cholesterol, and body mass index (BMI) were at unhealthy levels (based on age and sex); when the victim reported sexual assault, the offender was a family member, and more than one assault occurred. Systolic blood pressure, diastolic blood pressure, and fasting blood sugar were statistically significant among victims who reported being either sexually assaulted or sexually molested when the offender was a family member, and the victimization occurred more than once. DISCUSSION/SIGNIFICANCE: This study indicated a higher prevalence of CVD risk factors in children victims of sexual assault. The blood pressure, lipid profiles, and BMIs were much higher than the standards. Early childhood screening is crucial in alerting health professionals to a child’s exposure to trauma.

OBJECTIVES/GOALS: Our goal is to explore the complex, the non-linear interplay among chronic conditions collectively contributing to a greater detrimental impact on the progression of Alzheimer’s disease (AD) than a single chronic condition alone in individuals with normal cognition, MCI, and AD. METHODS/STUDY POPULATION: We used longitudinal data from National Alzheimer Coordinating Center (n = 41,437) and focused on individuals with normal cognition (n =16,884, mean age (SD) = 70.72 (9.7)). Random forest models were used to predict newly developed MCI or AD from baseline to the most recent visits. We used self-reported baseline data on 50 chronic conditions and comprehensive clinical and demographic information (e.g., age, sex, APOE status, mini-mental status exam (MMSE) scores, education, BMI, and depressive symptoms). A binomial random forest was used to identify significant interactions (with p-values RESULTS/ANTICIPATED RESULTS: Our model demonstrated an AUC of 0.708 and a classification error rate of 25.4%. Variables of importance for predicting MCI or dementia were age, coronary artery bypass, depression, APOE status, smoking, and depressive symptoms. Two-way interactions, such as age X MMSE score, age X depressive symptoms, and age X BMI, were significant. Three-way interactions, including age X depressive symptoms X MMSE score, or depressive symptoms X BMI X MMSE score, were significant. However, when we explored the random forest model using only the chronic condition data, we found an AUC of 0.602 and an error rate of 27.15%. We found that depression, anxiety, hypercholesterolemia, stroke, and the interaction between BMI and anxiety were significant. DISCUSSION/SIGNIFICANCE: Random Forest models indicate that not only known factors including age, baseline cognitive status, and APOE status, but also chronic conditions like depression, anxiety, hypercholesterolemia, and stroke may predict cognitive impairment.

OBJECTIVES/GOALS: The mission of our new Anti-racism in Data and Analysis seminar series is to provide a forum for researchers to discuss the ways that race and racism show up in data and analysis so that we as scientists may work together to advance racial equity and justice in society. METHODS/STUDY POPULATION: Our CTSA’s Biostatistics, Epidemiology, and Research Design (BERD) Program has initiated a seminar series that focuses on the ways that race and racism show up in all phases of the research process. We have hosted guest speakers who have shared their cutting-edge research as well as their reflections on race in research, and have facilitated breakout discussions to provide a forum for researchers to discuss specific questions. Our seminars are intended for practicing clinicians, clinical and population researchers, basic scientists, students, and others. RESULTS/ANTICIPATED RESULTS: We have sponsored three discussion-based seminars and two guest speaker seminars, and have several seminars of each type in the planning stages. We have collaborated with another CTSA to sponsor a discussion-based seminar at their institution, thus outfitting them with the tools to initiate a seminar series of their own. Our seminars have been extremely well attended, attracting researchers from a broad base of departments at our institution, from students to full professors. Feedback has been very positive; complaints cluster around paucity of similar opportunities, and students have asked why such material is not included as a required part of their respective training programs. DISCUSSION/SIGNIFICANCE: Race and racism permeate research, and failure to recognize and address the issues involved perpetuates racism in our society. Researchers want to learn more, but there are few opportunities for them to do so. Our seminar series provides one such forum to researchers at our institution and beyond.

OBJECTIVES/GOALS: Determine if the Conserved Transcriptional Response to Adversity transcriptomic profile established in primary blood mononuclear cells (PBMC) of chronically stress caregivers, is present in individuals with early Alzheimer’s disease. Chronic stress is a risk factor for Alzheimer’s, and may be an untapped biomarker for disease risk and pathology. METHODS/STUDY POPULATION: To collect preliminary data on the Conserved Transcriptional Response to Adversity profile in individuals with Alzheimer’s disease, we were able to utilize primary blood mononuclear cell samples from a small open label pilot study called Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease, designed to clear stressed senescent cells. We hypothesized senolytics may beneficially reverse this stress profile. We developed a NanoString assay (measuring 19 inflammatory, 31 type-1 interferon, and 3 antibody synthesis genes) to compare these transcriptomic changes within 4 individuals measured at baseline, post-treatment with an intermittent 12-week senolytic therapy, and at an optional extended post-treatment follow-up time point > 3 months after their post treatment visit. RESULTS/ANTICIPATED RESULTS: There was relative downregulation of expression in transcription in 7 of 19 measured inflammatory genes (FOS, PTGS2, IL8, FOS, Il1b, JUNB, and JUN) in Alzheimer’s disease participants after receiving senolytic treatment (baseline vs. post-treatment). This is consistent with a decrease in the inflammatory arm of the Conserved Transcriptional Response to Adversity profile. These differences were not significant between baseline and the extended follow-up, indicative of a transient effect of senolytic. There were no changes in type 1 interferon or antibody synthesis genes. This data provides preliminary evidence for larger controlled studies to further establish this profile in Alzheimer’s disease, providing exciting evidence for transcript changes that may be reproducible with senolytic therapy. DISCUSSION/SIGNIFICANCE: Literature relevant to Alzheimer’s disease indicates global increases in inflammation paired with deficits in immune response, capturing some genes associated with the Conserved Transcriptional Response to Adversity. This profile may be a useful biomarker for prediction of disease severity or risk of dementia due to chronic stress.

OBJECTIVES/GOALS: Win ratio (WR) is an increasingly popular composite endpoint in clinical trials. A typical set up in cardiovascular trials is to use death as the first and hospitalization as the second layer. However, the power of WR may be reduced by its strict hierarchical structure. Our study aims to release the oracular hierarchical structure of the standard WR. METHODS/STUDY POPULATION: Addressing the power reduction of WR when treatment effects lie in the subsequent layers, we propose an improved method, Shrinking Coarsened Win Ratio (SCWR), that releases the oracular hierarchical structure of the standard WR approach by adding layers with coarsened thresholds shrinking to zero. A weighted adaptive approach is developed to determine the thresholds in SCWR. We conducted simulations to compare the performance of our improved method and the standard Win Ratio (WR) under different scenarios of follow-up time, association between events, and treatment effect levels. We also illustrate our method by re-analyzing real-world cardiovascular trials. RESULTS/ANTICIPATED RESULTS: First, the developed Shrinking Coarsened Win Ratio (SCWR) method preserves the good statistical properties of the standard WR and has a greater capacity to detect treatment effects on subsequent layer outcomes. Second, the SCWR method outperforms the standard approach under the scenarios in our simulations in terms of gaining higher power. In practice, we expect that SCWR can better detect the treatment effects. Finally, we will offer convenient software tools and clear tutorials for implementing the SCWR method in future studies, which include both unstratified and stratified designs. DISCUSSION/SIGNIFICANCE: The developed SCWR provides a more flexible way of combining the top layer and subsequent layers (e.g., the fatal and non-fatal endpoints) under the hierarchical structure and achieves a higher power in simulation. This nonparametric approach can accommodate different types of outcomes, including time-to-event, continuous, and categorical ones.

OBJECTIVES/GOALS: The increasing frequency and severity of heat waves due to climate change present unique risks to children. We aim to assess how various heat wave definitions impact pediatric acute care utilization across California. We also hope to examine heat waves’localized effects at the zip code level and how contextual factors modulate these effects. METHODS/STUDY POPULATION: A time-stratified case crossover will evaluate the association between different heat wave definitions and pediatric acute care utilization throughout California. A within-community matched design analysis coupled with a bayesian model will examine heat waves’ effects at the zip code level. A random effect meta-regression will determine which contextual factors modulate heat waves’ impact on different zip codes. Temperature data will be pulled from Cal-Adapt and interpolated to each zip code population centroid. Data for all unscheduled pediatric hospitalizations and ED visits for selected ICD codes in California from 2000–2019 will be obtained from the California Department of Health Care Access and Information. Contextual factors will be sourced from the US Census and the Healthy Places Index. RESULTS/ANTICIPATED RESULTS: We anticipate that heat waves will be associated with increased pediatric acute care utilization throughout California for select ICD codes. At the zip code level, we anticipate that there will be considerable spatial variation in the association between heat waves and care utilization based on region and zip code characteristics. Furthermore, we expect to see significant variation in the association between heat waves and hospitalizations based on the selected heat wave definition. We predict that zip codes with the highest increases in care utilization will have higher percentages of non-white residents, lower socioeconomic status, and fewer heat protective factors like park density and tree coverage. DISCUSSION/SIGNIFICANCE: As global temperatures continue to rise, children will be increasingly susceptible to health consequences associated with heat exposure. Understanding which pediatric populations are most vulnerable during heat waves is critical for designing policies and interventions that protect the most vulnerable communities.

OBJECTIVES/GOALS: The primary objective of this study is to evaluate the risk of an early syphilis diagnosis following a chlamydia, gonorrhea, or HIV diagnosis, and to determine differences by race, repeat infection, diagnosing provider and STI/HIV risk behavior among cisgender women in Baltimore, MD. METHODS/STUDY POPULATION: Public health surveillance data from 2009-2021 was used to examine the overall incidence of syphilis infections among cisgender women ages 13-50 diagnosed with a reportable STI (chlamydia, gonorrhea, or HIV) and the percentage of total infections that were early infections (primary, secondary, or early latent syphilis) in Baltimore City. Data were collected on age, race, diagnosing location (i.e., STI clinic, private provider, etc.), preceding STI diagnoses, and sexual risk behaviors. STI-specific cumulative incidence and incidence rate ratios were used to compare syphilis diagnoses among Black vs. white women, women with repeat STI diagnoses vs. one STI diagnosis, women diagnosed at a public vs. private clinic, and commercial sex workers and substance users vs. those not reporting these risk behaviors. RESULTS/ANTICIPATED RESULTS: Based on recent surveillance data, we expect approximately 79,000 chlamydia, gonorrhea, and HIV diagnoses among cisgender women between 2009-2021. We hypothesize that 3% of chlamydia, gonorrhea, and HIV diagnoses among cisgender women will be followed by a syphilis diagnosis within the study period. Extrapolating from previous studies of early syphilis in men who have sex with men in Baltimore, we expect the rate of syphilis diagnosis following STI diagnosis will be higher in Black vs. white women, women with a prior gonorrhea or HIV diagnosis vs. chlamydia diagnosis, women with repeat STI diagnoses vs. one STI diagnosis, women diagnosed at public STI clinics vs. those diagnosed by private providers, and women reporting commercial sex work and/or substance use vs. those not reporting these risk behaviors. DISCUSSION/SIGNIFICANCE: Local healthcare providers should offer syphilis screening to any woman diagnosed with a chlamydia, gonorrhea, or HIV infection. The higher rates of early syphilis diagnosis among women with repeat STI diagnoses or a prior gonorrhea or HIV diagnosis suggests regular screening is critical in these populations.

OBJECTIVES/GOALS: During the pandemic, alcohol related deaths increased by 25%. To help understand how we might mitigate this negative outcome, we sought to examine the association of new diagnosis of alcohol use disorder (AUD) with SARS-CoV2 through two years of the pandemic. METHODS/STUDY POPULATION: Using a non-date-shifted TriNetX database, we conducted a retrospective cohort analysis of electronic health records of patients age ≥12 years who had been diagnosed either with COVID-19 (n=1,359,817) or other respiratory infections with no record of COVID-19 (n=2,013,031). Patients were then matched for propensity score risk for AUD, and results were analyzed by three-month intervals from January 2020 through January 2022, in blocks numbered 1-8. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CI) for diagnosis of AUD from two weeks to six months following COVID-19 diagnosis. RESULTS/ANTICIPATED RESULTS: There was significant excess risk compared to control cohorts of AUD following COVID-19 diagnoses made during the first three months of the pandemic (HR (CI)): block 1: 2.41(1.89,3.08); no excess risk was seen for the remainder of 2020 (blocks 2-4) (HR1.01-1.14, NS). The excess risk increased again in 2021 as the delta and omicron variants emerged (HR and 95% CI): block 5 were: 1.26(1.11, 1.43)); block 6: 1.88(1.62-2.18)); block 7: 1.24(1.10,1.41); block 8: 1.12(1.0-1.25). COVID-19 diagnosis was associated with clinically-evident AUD under some pandemic circumstances. DISCUSSION/SIGNIFICANCE: COVID-19 early in the pandemic (block 1) was associated with substantial excess risk for new diagnosis of AUD, with smaller excess risk after COVID-19 during 2021 (blocks 5-7), and no excess risk otherwise. Diagnosis of COVID-19 and pandemic contextual factors are associated with increased risk for AUD.

OBJECTIVES/GOALS: We are launching a multi-center prospective registry for patients with metastatic invasive lobular carcinoma (ILC), the second most common type of breast cancer, to better understand patterns of progression, imaging features of metastatic sites, and if serial cell free DNA measurements can serve as a surrogate marker of disease progression. METHODS/STUDY POPULATION: Patients with biopsy proven metastatic ILC of any receptor subtype will be included in the registry. We will exclude patients with ductal histology only or those with multiple primary malignancies. Patients will be enrolled at four large academic medical centers across the country. Cell free DNA measurements using a tumor informed assay will be obtained every 3 months concurrent with regular clinical imaging. Disease status will be determined by the patient’s medical oncologist by taking into account imaging, tumor markers, symptoms, and cell free DNA measurement. At each time point, patients will be surveyed on their quality of life and their medical oncologists will be asked to rate the clinical utility of the cell free DNA value. Patients will be followed indefinitely. RESULTS/ANTICIPATED RESULTS: We will explore whether the use of serial cell free DNA or a combination of blood-based biomarkers and clinical endpoints can reliably identify treatment response and disease progression in patients with metastatic ILC. Many patients with metastatic ILC have unmeasurable disease on imaging and are thereby excluded from clinical trials. The end goal of this registry is to determine if blood-based biomarkers can be used as a proxy for measurable disease in ILC patients and therefore increase clinical trial enrollment for this subgroup of patients. DISCUSSION/SIGNIFICANCE: The creation of this prospective registry will open the door for future studies of blood-based markers that reflect disease stability and progression, which is an unmet need specifically in ILC. Identification of such markers could lead to a novel treatment response endpoint, changing the way patients are enrolled in trials and managed clinically.

OBJECTIVES/GOALS: The Diabetes Prevention Program (DPP) has been shown to reduce diabetes risk by 58%. Men, particularly men of color, are underrepresented in DPP, while they experience higher diabetes-related morbidity. We examine whether race, ethnicity, and gender disparities in engagement are associated with the risk of referral to DPP in primary care METHODS/STUDY POPULATION: Using electronic health record (EHR) from a large urban health system in the Bronx, NY, with an in-house DPP, we examined patient, visit, referral data for DPP-eligible, adult patients with a primary care visit between July 2015 and December 2017. Eligibility included: hemoglobin A1c between 5.7-6.4%; a body mass index (BMI)≥24 kg/m2 (≥22 if Asian); and having no prior diagnosis of diabetes. A total of 26987 patients were included in this study. We examined patient race, ethnicity, preferred language, visit and prescription history, and health payer, among other characteristics. SPSS was used for univariate and bivariate analyses to examine associations between patient characteristics and referral followed by a logistic regression to examine the multivariate association between predictors and referrals. RESULTS/ANTICIPATED RESULTS: Of all DPP-eligible patients, 49% were Hispanic/Latino, and 39% were non-Hispanic Black. Around one-third (34%) of all eligible patients were men. Among all eligible patients in the sample, only 10% were referred to DPP. There were significant differences in the proportion of eligible patients who were referred versus those who were not referred. Women were referred at more than twice the prevalence of men (8.26% to 2.41%), with Hispanic women being referred most frequently (3.59%), and non-Hispanic white men being referred least frequently (.07%) Ethnicity, race, sex, age, number of provider visits, and number of chronic conditions all impacted healthcare provider referral rates to DPP. The health system’s unique free-of-charge DPP likely influenced the lack of significance of patient health insurance. DISCUSSION/SIGNIFICANCE: Given the implementation of DPP at-scale there is an urgent need to understand the patient and systems-level factors that are associated with referring individuals in the DPP. By detecting characteristics of health systems and patients that warrant special attention, we can improve equitable access to evidence-based diabetes prevention.