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.

The ability of research networks and individual institutions to effectively and efficiently prepare, respond, and adapt to emergent challenges is essential for the biomedical research enterprise. At the beginning of 2021, a special Working Group was formed by individuals in the Clinical and Translational Science Award (CTSA) consortium and approved by the CTSA Steering Committee to explore “Adaptive Capacity and Preparedness (AC&P) of CTSA Hubs.” The AC&P Working Group took a pragmatic Environmental Scan (E-Scan) approach of utilizing the diverse data that had been collected through existing mechanisms. The Local Adaptive Capacity framework was adapted to illustrate the interconnectedness of CTSA programs and services, while exposing how the demands of the pandemic forced them to quickly pivot and adapt. This paper presents a synopsis of the themes and lessons learned that emerged from individual sections of the E-Scan. Lessons learned from this study may improve our understanding of adaptive capacity and preparedness at different levels, as well as help strengthen the core service models, strategies, and foster innovation in clinical and translational science research.

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.

The National Center for Advancing Translational Science (NCATS) seeks to improve upon the translational process to advance research and treatment across all diseases and conditions and bring these interventions to all who need them. Addressing the racial/ethnic health disparities and health inequities that persist in screening, diagnosis, treatment, and health outcomes (e.g., morbidity, mortality) is central to NCATS’ mission to deliver more interventions to all people more quickly. Working toward this goal will require enhancing diversity, equity, inclusion, and accessibility (DEIA) in the translational workforce and in research conducted across the translational continuum, to support health equity. This paper discusses how aspects of DEIA are integral to the mission of translational science (TS). It describes recent NIH and NCATS efforts to advance DEIA in the TS workforce and in the research we support. Additionally, NCATS is developing approaches to apply a lens of DEIA in its activities and research – with relevance to the activities of the TS community – and will elucidate these approaches through related examples of NCATS-led, partnered, and supported activities, working toward the Center’s goal of bringing more treatments to all people more quickly.

People experiencing incarceration are often invisible to the public due to the restricted settings in which they reside and receive services. Limited access to criminal justice settings leaves policymakers and healthcare professionals with sparse information to understand the unique needs of this population. The unmet needs of justice-involved individuals are more likely observed by professionals who provide services in correctional settings. We provide three distinct examples of projects conducted within correctional settings and how they formed pathways to interdisciplinary research and community partnerships to address the unique health and social needs of incarcerated individuals. Our partnerships in a variety of correctional settings led to exploratory research of women and men’s prepregnancy health needs, participatory workplace health interventions, and process evaluation of reentry programming. The limitations and challenges to research in correctional settings are considered along with the clinical and policy implications of these projects.

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.

Participants in the leadership breakout session at the Clinical Translational Science Awards (CTSA) virtual 2020 conference discussed and ranked six recommendations in terms of feasibility, impact, and priority for advancing Diversity, Equity, and Inclusion (DEI) efforts to elevate underrepresented populations to leadership positions in CTSAs and their broader institutions. A thematic analysis of chat and polling data identified challenges and opportunities to achieve DEI goals, with the three most promising recommendations as: cross-institutional Principal Investigator (P.I.) action-learning workgroups, transparent policies for recruiting and promoting underrepresented minorities (URM) leadership, and a clear succession plan to nurture and elevate URM leaders. Suggestions are made to improve DEI in CTSA leadership and allow for greater representation in the translational science field.

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.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

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.

Tesamorelin, a synthetic growth hormone-releasing hormone, is indicated for the reduction of visceral adipose tissue (VAT) in people with HIV. Here, we performed a post hoc analysis of participants receiving tesamorelin for 26 weeks in a phase III clinical trial. Efficacy data were compared between individuals with and without dorsocervical fat, stratified by tesamorelin response. Among tesamorelin responders, VAT and waist circumference (WC) decreased in both dorsocervical fat groups and did not statistically differ (VAT P = 0.657, WC P = 0.093). These data demonstrate that tesamorelin is equally effective and should be considered in the treatment of excess VAT regardless of the presence of dorsocervical fat.

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.