OBJECTIVES/GOALS: The Michigan Institute for Clinical & Health Research (MICHR) Community Engagement (CE) Program fosters translational science and community-engaged research (CenR) through education, connecting, supporting, and funding efforts and opportunities. METHODS/STUDY POPULATION: In Michigan’s Upper Peninsula, CE partnered with the Michigan Health Endowment Fund to develop a 3-hour workshop that consisted of a panel discussion on best practices of community engagement and a presentation on community engaged nonprofit management. The workshop was designed from mapping 60 participants’ pre-workshop survey findings and reviewing themes from a planning meeting transcript with six community partners. Key themes that emerged included participatory budgeting, collaborative governance, communications, and community planning. RESULTS/ANTICIPATED RESULTS: A mix methods post-workshop evaluation feedback survey was completed. The 9-item survey assessed workshop content, satisfaction, and knowledge gained using a Likert scale as well as opened questions about key takeaway and value added. Quantitative results to be analyzed. Qualitatively, some participants described the workshop as helpful and thoughtful about how to strengthen community engagement within their organizations. Others expressed a desire for more time. Regarding impact, CE received an uptake in consultations and inquiries into statewide pilot grants. The workshop facilitated new collaborations with philanthropic and community organizations serving the Upper Peninsula. DISCUSSION/SIGNIFICANCE: Lessons learned highlight trust, understanding community culture, and moving slowly in a newly formed collaboration. The approach utilized in the Upper Peninsula can inform translational methods for additional partnerships underway across the state of Michigan.

OBJECTIVES/GOALS: Dystonia is a brain disorder which causes excessive muscle activation, manifesting as abnormal movements. Neuroimaging studies of dystonia have revealed changes in a network involving the cerebellum. We sought out to determine whether subjects with dystonia in the UK Biobank exhibit MRI-based cerebellar pathology. METHODS/STUDY POPULATION: This nested case-control study drew from the UK Biobank, a cohort of >500,000 subjects in the United Kingdom, aged 40-69, enrolled 2006-2010. Eligible subjects must have undergone diffusion-weighted brain MRI. Dystonia cases were ascertained using ICD10 codes. We selected controls without neurologic diagnoses, matched (1:3) on age, sex, imaging site, and medical comorbidities. Mean diffusivity, fractional anisotropy, intracellular and isotropic volume fractions, and orientation dispersion were extracted from four white-matter tracts (inferior, middle, superior cerebellar peduncles; superior thalamic radiations) along with cerebellum, basal ganglia, and whole-brain grey and white-matter volumes. Means were compared using two-tailed t-tests and the Benjamini-Hochberg procedure (FDR = 0.05). RESULTS/ANTICIPATED RESULTS: 23 cases of dystonia and 69 control subjects were selected and ascertained. After correcting for multiple-comparisons (40 volumetric and 35 diffusion-related), intracellular-volume-fraction (ICVF) of the middle- and superior-cerebellar peduncles was significantly lower in subjects with dystonia, suggesting reduced axon density. Volumetric analysis showed significantly reduced volumes of the motor cerebellum (lobules VI and VIII). There were no differences in basal ganglia, cortical, or whole-brain volumes. DISCUSSION/SIGNIFICANCE: These findings support the hypothesis that abnormalities of cerebellar networks contribute to dystonia. In future we will use similar techniques to assess these tracts in subjects with dystonia who are undergoing Deep Brain Stimulation, with the goal of guiding stimulation targeting, and predicting therapeutic outcomes.

OBJECTIVES/GOALS: Examining the impact of the Building Capacity for Research and Action (BCRA) Award created by the Community Engagement (CE) Program at the Michigan Institute for Clinical & Health Research (MICHR)--a Clinical & Translational Science Award (CTSA) site at the University of Michigan--in partnership with Community Based Organization Partners (CBOP). METHODS/STUDY POPULATION: The BCRA is a funding mechanism that supports new community-engaged research (CEnR) partnerships and projects that address community-identified health needs in Flint, Michigan. BCRA projects are required to be Flint-based and inclusive of both community and academic partners. A study section consisting of 10 MICHR-affiliated faculty and community partners reviewed proposals and made funding decisions. Funded teams were trained on Institutional Review Board (IRB) and reporting requirements by CE staff. MICHR provides support to BCRA-funded teams through monthly email correspondence with the CE Flint connector, budget review, mediation, regulatory assurance of IRB and the National Center for Advancing Translational Science (NCATS) requirements, coordinating six-month and final reporting, and hosting an annual stakeholder meet and greet. RESULTS/ANTICIPATED RESULTS: In 2017, the BCRA Award submitted its first request for proposals. It received 20 applications in 2018, and selected eight awardees, providing them with a total of $60,000 in funding. Four received $5,000 for partnership development and another four received $10,000 for their research projects. The BCRA Award received 16 applications in 2019, expanding its academic pool to include the University of Chicago, U-M Flint, Michigan State University, and Michigan State University-Flint in addition to the University of Michigan. Five recipients were selected and received a total of $45,000 in funding. One was awarded $5,000 for partnership development and another four were awarded $10,000 for their research projects. MICHR has invested over $100,000 in Flint through this mechanism, which was renewed in 2019. DISCUSSION/SIGNIFICANCE OF IMPACT: Each awardee presented at the annual stakeholder meet and greet. They showcased their projects with a brief overview and spoke about their expectations, lessons learned, partnership strengths and challenges, translational issues, and proposed next steps for subsequent grants, publications.

ABSTRACT IMPACT: These findings identify a new way in which the COVID-19 pandemic exacerbates racial/ethnic health disparities, and will thus direct future research to explore potentially avoidable hospitalizations, as well as direct health policy to improve the value of this specific aspect of care without further widening the disparity. OBJECTIVES/GOALS: Racial and ethnic disparities in potentially avoidable hospitalizations predate COVID-19. In order to identify and address healthcare disparities exacerbated by the pandemic, we examined whether and to what extent the pandemic affected numbers of potentially avoidable hospitalizations by race and ethnicity. METHODS/STUDY POPULATION: This single-center pre-post study of 904 patients at UCLA included all patients admitted to an internal medicine service for an ambulatory care sensitive condition (ACSC) between March-August of 2020 (post) and March-August of 2019 (pre). We measured the change in number of potentially avoidable hospitalizations (defined per the Agency for Healthcare Research and Quality guidelines) stratified by race and ethnicity. We calculated 95% CIs for the number of potentially avoidable hospitalizations using a cluster bootstrap procedure, clustering at the level of patients. We inverted the bootstrap CIs to calculate p-values for overall changes within racial/ethnic groups as well as differential changes between groups. Patients with missing or unspecified racial/ethnic data were excluded (n=1,003; 7.8%). RESULTS/ANTICIPATED RESULTS: Between March 1 and August 31, 2020, 347 out of 4,838 hospitalizations (7.2%) were potentially avoidable, compared to 557 out of 6,248 (8.9%) during the same 6-months of 2019. Reductions in potentially avoidable hospitalizations among Non-Hispanic White (-50.3%; 95% CI, -60.9 - -41.2; p<0.001) and Latinx (-32.3%; 95% CI, -59.8 - -12.2%, p<0.001) patients were statistically significant, whereas reductions among African American (-8.0%; 95% CI, -39.9 - +16.2) and Asian (-16.1%; 95% CI, -75.7 - +20.4) patients were not statistically different from 0%. The relative differences in magnitudes of reduction were only statistically significant between African American and non-Hispanic White patients (-50.3% v. -8.0%; 95% CI as above; p=0.015). DISCUSSION/SIGNIFICANCE OF FINDINGS: Racial disparities in potentially avoidable hospitalizations increased during the COVID-19 pandemic at this large urban health system. Healthcare leaders, researchers, and policy makers should focus on efforts to prevent a post-pandemic resurgence of low-value hospitalizations in ways that do not further widen disparities.

OBJECTIVES/SPECIFIC AIMS: Family members are often critical in the delivery of hands-on care and decisions about care for persons approaching end-of-life (EOL). Prompted by concerns about the poor quality and high costs of care at the EOL, recent delivery reform efforts—such as the growth of hospice and palliative care—have been directed at improving EOL care for both patients and family. Trends of the characteristics of EOL family caregivers and care recipients over time have not been well described. The goal of this study is to evaluate changes in EOL family caregiving from 1999 to 2015. METHODS/STUDY POPULATION: This study uses reconciled data from two nationally representative surveys and their linked caregiver surveys: the 1999 wave of the National Long-Term Care Survey (NLTCS) and the Informal Care Survey (ICS), and the 2015 wave of the National Health and Aging Trends Study (NHATS) and the National Survey of Caregiving (NSOC). RESULTS/ANTICIPATED RESULTS: Crude analysis shows that older adults living in the community and receiving help from family caregivers in the last year of life were significantly better educated (72% with greater than 12 years of education vs. 46%), and more diverse (78% White vs. 89%) in 2015 compared with 1999. Family caregivers in the last year of life were less likely to be female in 2015 compared with 1999 (74% vs. 68%, NS) and significantly less likely to be spouses (45% vs. 38%) in 2015. In 2015, a significantly greater proportion of older adults received help with five or more activities of daily living (47% vs. 34%), but family caregivers reported significantly lower levels of caregiving-associated distress: financial strain (80% reporting none in 2015 vs. 53%), emotional (51% vs. 39%), and physical strain (70% vs. 45%). In addition, a significantly greater proportion of EOL family caregivers used respite care in 2015 compared to 1999 (15% vs. 4%). DISCUSSION/SIGNIFICANCE OF IMPACT: Changes in the experience of EOL family caregiving may be impossible to capture in studies of single interventions, but tracking nationally representative trends can be used as an indicator of broader changes that take place cumulatively over time. Although studies of this nature cannot identify causal mechanisms of change, they are important to monitor long-term impact of program implementation and to guide future research, policy, and resource allocation.

OBJECTIVES/SPECIFIC AIMS: Approximately 25%–45% of veterans are dual users of VA and civilian healthcare. In order to maximize patient outcomes, understanding factors related to dual use is important. This study examined mental and physical health factors related to dual use of VA and civilian healthcare among U.S. National Guard and Reserve (NG/R) soldiers. METHODS/STUDY POPULATION: NG/R soldiers and their partners (n=411 couples) participated in an electronic survey assessing health and health behaviors. Logistic regression models were used to examine the relationship between mental health (anxiety, depression, PTSD, anger), general health, and VA disability status at baseline, with usage of both VA and civilian healthcare among male soldiers (n=109) at the second year follow-up, controlling for age and race. RESULTS/ANTICIPATED RESULTS: In the final adjusted models, of the mental health conditions, only anxiety was related to dual use (OR: 1.08, 1.01–1.16, p<0.05). Having a VA disability rating (OR: 4.00, 1.22–13.18; p<0.05) was also related to being a dual user. General health was not related to dual use. DISCUSSION/SIGNIFICANCE OF IMPACT: While research has identified demographic characteristics (e.g., rurality, race, income) related to dual healthcare use, our results indicate that mental health, particularly anxiety, may also be related to dual use. Further study is needed to tease out the prime drivers of dual use to identify future care delivery mechanisms that will maximize treatment outcomes and minimize duplicative care.

OBJECTIVES/GOALS: This social justice-oriented, multi-method study aims to gain an understanding of the unique sources of stress and resilience impacting Black women in Milwaukee. As clinical researchers, it is imperative that we understand the mechanisms underlying the relationship between marginalized identities and substantial health disparities. METHODS/STUDY POPULATION: Participants were Black women, diverse in age, income, and sexual orientation to emphasize an intersectional approach (current N = 87 of 160). Our interdisciplinary team collected two interrelated data types: narrative and survey. Participants completed a 1.5-hour life story interview in which they were asked to share stories from their lives, their backgrounds, plans for the future, forces that shaped their stories, and how their identities have influenced their experiences. Interviews were done one-on-one and conducted by Black women interviewers. They were also asked to complete an online survey protocol including measures of stress, trauma, microaggressions, coping, and well-being. Transcribed life story interviews will be coded utilizing grounded theory, an intensive qualitative analysis method. RESULTS/ANTICIPATED RESULTS: The presentation will focus on the unique methodological approach, which emphasizes community empowerment through collaboration and cultural competency. Data collection is still in progress, but initial relationships between key variables will be discussed. It is anticipated that greater frequency and appraisal of microaggressions will significantly predict higher reported stress, anxiety, and depression. Within-group diversity will be examined as well. Relevant themes emerging from grounded theory will also be presented. Results will directly inform community outreach aimed at improving the lives of Black women. DISCUSSION/SIGNIFICANCE OF IMPACT: This study sheds light on unique, identity-related stressors believed to contribute to mental and physical health disparities. It also builds on current theories, filling voids in the research literature by taking a psychosocial perspective, emphasizing the voices of participants, and channeling the findings to specific programs in the community.

OBJECTIVES/SPECIFIC AIMS: The Rockefeller University-Center for Clinical and Translational Science and Clinical Directors Network (RU-CCTS/CDN) community-academic-partnership engaged with Carter Burden Center for the Aging (CBCA), a multisite senior community services organization serving Upper Eastside and East Harlem, NY, to develop community-engaged research. Many seniors served by CBCA are racial/ethnic minorities, live in poverty, suffer from multiple chronic conditions, depression, and food insecurity; there is no simple measure routinely used to characterize the health/health risks of program participants. Multiple biological, musculoskeletal, psychosocial and nutritional factors collectively contribute to frailty a construct that is variously defined, and has been used as a surrogate or predictor for health outcomes. Aim 1: We will engage seniors, CBCA leadership, New York City Department for the Aging, staff and other stakeholders in research priority-setting, joint protocol writing, research conduct, analysis and dissemination to cultivate a population of elder stakeholders interested in designing and participating in this and future research. Aim 2: We will characterize the health status of the resident and nonresident populations by collecting data across 3 sessions to include validated cardio-metabolic, musculoskeletal, chronic condition prevalence, quality of life, psychosocial, and nutritional assessments. METHODS/STUDY POPULATION: Stakeholders will be engaged through the process of Community Engaged Research Navigation and a series of meetings and exercises to refine priorities and research design, co-write the protocol, provide feedback on conduct, analyze and disseminate results of the project. RESULTS/ANTICIPATED RESULTS: Outcomes will include rates of participation and retention in assessments and engagement activities, themes from qualitative research, contributions to study design, placement of aims on the T0-T48 spectrum, social network analysis, classification of engagement on the spectrum of Community-based Participatory Research (CBPR) and partnership assessment. The primary outcome is frailty (6-minute walk test); We will examine associations among these measures with services utilization data captured electronically by CBCA. A key deliverable of this project will be a REDCap data capture platform that integrates and displays these measures that will be sustainable for CBCA. DISCUSSION/SIGNIFICANCE OF IMPACT: This practice-based research partnership will allow us to extract, replicate and extend the lessons learned about engaging stakeholders in generating hypotheses, operationalizing research, collecting and analyzing data, and disseminating results. The collaboration is built around generating and testing rigorous clinical an health services hypotheses that are derived from real-world practice-based needs and also incorporate basic science measures to embed and examine mechanistic hypotheses. Testing a simple to implement validated surrogate frailty measure will accelerate progress on evidence-based practices to test interventions that enhance healthy aging and serve as a model for future similar partnerships to form a network for community-based senior research. This work aligns with the RU-CCTS grant Hub Research goal to engage populations across the life span, including hard-to-reach and underserved populations, such as minority seniors.

OBJECTIVES/GOALS: Our objectives are to: 1) characterize opioid treatment providers in North Carolina according to payment methods accepted and ability to provide medications for opioid use disorder and 2) use geomapping technology to characterize geographic access to treatment for opioid use disorder in NC. METHODS/STUDY POPULATION: We will identify opioid treatment providers using resources published by SAMHSA and NC DHHS. We will characterize all providers identified according to provision of medications for opioid use disorder, payment or insurance accepted, and services provided. ArcGIS will be used to characterize geographic distribution of treatment resources after filtering for these key characteristics and determine access according to driving radius. RESULTS/ANTICIPATED RESULTS: We anticipate that the geographic analysis of opioid treatment provider availability will reveal limited access to treatment, particularly in rural areas. We anticipate that further filtering for factors such as provision of medications for opioid use disorder--a first-line, evidence-based intervention—and payment or insurance accepted will demonstrate that the availability of evidence-based, financially accessible treatment for opioid use disorder in North Carolina is critically limited. DISCUSSION/SIGNIFICANCE: We anticipate that an analysis of treatment options available for opioid use disorder, particularly when considering insurance status and drive times, will clearly demonstrate the need for development and expansion of opioid treatment options, and in which areas those efforts are likely to have the highest impact.

OBJECTIVES/SPECIFIC AIMS: Across the Clinical and Translational Science Award (CTSA) Consortium, participant recruitment into clinical trials is essential to advance science. Without proper participant recruitment, clinical trials do not result in gains in scientific knowledge, wastes time, funds, and other resources (Mahon et al., 2015). METHODS/STUDY POPULATION: Participant recruitment programs across the consortium are inconsistent in staffing, program services, and program goals. The participant recruitment program at the University of Michigan’s (U-M) Michigan Institute for Clinical & Health Research (MICHR) provides expertise, tools, and resources to facilitate participant recruitment in clinical and health research studies. RESULTS/ANTICIPATED RESULTS: We will explain our program infrastructure, staffing, services, and discuss how we maintain an engaged registry with over 27,000 participants interested in research studies at U-M. DISCUSSION/SIGNIFICANCE OF IMPACT: Proper recruitment into clinical trials results in findings that are relevant for genetic, cultural, linguistic, racial/ethnic, gender, and age differences (Cottler et al., 2013). We hope to share our best practices that aid in the development and success of participant recruitment across the CTSA Consortium.

OBJECTIVES/GOALS: Our long-term goal is to understand how both genetic and environmental (GxE) factors contribute to neurodevelopmental disorders (NDDs) so that we may potentially intervene in disease pathogenesis and design therapies to address functional deficiencies. METHODS/STUDY POPULATION: Our studies use a novel GxE model to determine how cephalosporin antibiotic exposure alters the gut microbiome, hippocampal neurogenesis, and behavior in the genetically vulnerable 16p11.2 microdeletion (16pDel) mouse. This mouse models one of the most frequently observed genetic risk variants implicated in NDDs, including ~1% of autism diagnoses. Wildtype and 16pDel littermates were exposed to saline or the cephalosporin, cefdinir, from postnatal days 5-9. We quantified changes in gut microbiota composition using 16S rRNA gene sequencing and utilized immunoblotting, immunohistochemistry, and bulk RNA gene sequencing to assess changes in hippocampal neurogenesis. An additional cohort of saline or cefdinir-exposed mice were subjected to a behavioral battery to assess changes in sociability and anxiety. RESULTS/ANTICIPATED RESULTS: We leveraged the next-generation microbiome bioinformatics platform, Quantitative Insights Into Microbial Ecology 2 (QIIME2) to analyze 16S rRNA gene sequencing datasets of P13 cecal samples from saline- and cefdinir-exposed mice. We found successful perturbations to the gut microbiome following early life cefdinir exposure. Further, we found a robust 50% reduction in hippocampal cyclin E protein in cefdinir-exposed 16pDel male mice, which was replicated in a second independent experiment. This reduction extended to the S-phase cell entry and general stem cell population, quantified by EdU+ and Ki67+ cell numbers, respectively. Lastly, in our first cohort of mice for behavioral studies, we found reduced sociability and increased anxiety-like behaviors in cefdinir-exposed mice. DISCUSSION/SIGNIFICANCE: The findings from this GxE model will provide mechanistic insights into the causes of NDDs; they may inform practice guidelines so as to reduce this environmental exposure; and may suggest interventions like probiotics for those at risk in order to overcome altered gut microbiome composition and restore hippocampal neurogenesis defects.

ABSTRACT IMPACT: This poster will demonstrate how a community issue from a CTSI Community Advisory Board member organization initiated a collaborative, community-engaged project to identify priority areas of concern and culturally appropriate mitigation strategies. OBJECTIVES/GOALS: Little is known about the health and psychosocial impact of construction on older adults living near construction sites. We applied a mixed methods approach to identify evidence-based strategies to mitigate community prioritized health and psychosocial concerns related to long-term construction on older adults in NYC’s Manhattan Chinatown. METHODS/STUDY POPULATION: In Chinatown, where approximately 20% of its residents are seniors, many are poor, have a disability, and experience ambulatory difficulties. We used a mixed methods approach including: 1) a high level scoping review of the published literature on the health impact of long-term construction for older adults; 2) key informant interviews with stakeholders; and 3) a two-part community-engaged modified Delphi process to identify priority topic areas related to construction and older adults and evidence-informed, culturally-relevant mitigation strategies. Using priority areas identified through the modified Delphi process, we conducted a literature review on the health and psychosocial impact of construction on older adults. RESULTS/ANTICIPATED RESULTS: We identified five priority topics: construction site emissions; noise; outdoor nocturnal lighting; neighborhood changes; and relocation. Long-term construction is associated with environmental and psychosocial consequences with greater negative impacts on vulnerable populations. Current NYC mitigation policies are based on general population and need revisions to consider impacts for the most vulnerable, e.g. older adults and children, to mitigate adverse health outcomes. Findings were shared with City Council members and resulted in enacting specific recommended mitigation strategies, e.g. double paned windows, etc. Seniors are highly susceptible to the effects of air pollution, noise, and environmental changes, with exposure associated with higher morbidity, mortality, and social isolation. DISCUSSION/SIGNIFICANCE OF FINDINGS: Long-term construction may pose serious health implications for seniors residing near construction sites. Standards and guidelines for the general population may not protect them. Community-driven coalitions, like community-academic partnerships, can successfully advance community priorities and inform strategies to protect the elderly.

OBJECTIVES/SPECIFIC AIMS: Fifty percent of adolescents have tried an illicit drug and 70% have tried alcohol by the end of high school. Further, despite 7-9% of youth 12-17 meeting criteria for a substance use disorder only 1 in 10 actually receive it. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence based process that facilitates early identification and treatment for adults and adolescents in community (primary care) facilities. Despite the documented effectiveness of SBIRT, no research has examined the implementation of SBIRT in school settings by school-based mental health personnel. The purpose of the present study was to identify facilitators and barriers to SBIRT implementation by school-based personnel in secondary schools. METHODS/STUDY POPULATION: Participants included 30 school and community service providers including: teachers, school counselors, school psychologists, school administrators (principals and central office staff), city council members, school board members, community mental health services providers as well as state level individuals from the department of Adolescent Substance Use and the Office of Drug Control Policy. Interview guides were developed using the Consolidated Framework for Implementation Research (CFIR) to identify facilitators and barriers regarding the following: inner setting, outer setting, individuals involved, and intervention (SBIRT). The six-phase framework of Thematic Analysis (TA) was employed to analyze the data. We specifically used the deductive method to analyze the data with a pre-determined theory in mind (CFIR) to move to hypothesis building, and coding the data. RESULTS/ANTICIPATED RESULTS: Contrary to research conducted outside of the schools under the auspices that schools do not have the time or interest in providing school-based substance use interventions, several themes emerged identifying a receptivity, willingness, and eagerness to provide these services. Specifically, school-based mental health professionals (i.e., school counselors, school psychologists) being aware of adolescent substance use in their schools, but not knowing how to appropriately handle such disclosures. Further, school-based mental health personnel indicated that they would want additional training on how to identify and provide services to adolescents with substance use needs. School-based administrators also indicated a receptivity to addressing substance use with an acknowledgement that schools would need to move from a punitive model for substance use infractions to a treatment model. Some identified barriers to implementation included lack of awareness of community treatment settings for referrals and anonymity or lack thereof of substance use screening. DISCUSSION/SIGNIFICANCE OF IMPACT: While the data analyzed come from a limited sample in one school district, the present study found that schools could be potential settings for the early identification and intervention of adolescent substance use. Findings from this study contribute to our understanding of school and community receptivity to school-based interventions. Future research should identify training needs of school-based mental health personnel to assist in the early identification and prevention of substance use disorders.

OBJECTIVES/GOALS: Myocarditis is an inflammatory cardiomyopathy commonly caused by viral infections. The residual burden of this disease after guideline-based therapies is substantial, as there are no pathway-specific therapies. Our long-term goal is to find and translate treatments that reduce acute myocarditis severity and prevent progression of disease. METHODS/STUDY POPULATION: Of available therapies, extracellular vesicles (EVs) are ideally suited to the task of simultaneous, specific reprogramming of multiple pathogenesis mechanisms necessary in diseases like myocarditis, without similar immunosuppressive risks as their pharmacologic counterparts. We obtained plasma from healthy men and women and isolated nanoparticles, which were analyzed for physiochemical markers of human EVs. After confirming presence of EVs, we injected these plasma-derived extracellular vesicles (PEV) into male BALB/c mice vs. PBS control intraperitoneally on days -1, 0, 1 of viral infection (day 0) in a highly translational, mouse model of myocarditis. Hearts were examined at day 10 at the peak of acute myocarditis, using standard histological and cell composition analyses. RESULTS/ANTICIPATED RESULTS: Mice treated with PEV had significantly less myocardial inflammation both histologically and by gene expression of immune markers in the heart. The immunoregulation by PEV treatment decreased many key components of innate immune response networks that are known to be upregulated during acute myocarditis: TLR4+ mast cells and macrophages and complement. These pathways drive the profibrotic gene and protein changes that lead to remodeling, fibrosis, and disease progression observed in patients. We anticipate that when we analyze later timepoints in this model (day 35 post infection) which are normally associated with development of chronic myocarditis, dilated cardiomyopathy, we will see reduction of this fibrosis and of damage-associated changes. DISCUSSION/SIGNIFICANCE: These data suggest that EVs from plasma may be a novel treatment for viral myocarditis, but translation of EVs is hindered by their heterogeneity. We demonstrate characterization both physiochemically and functionally in a well-defined model. Such practices are necessary as these contemporary products challenge current regulation standards.

OBJECTIVES/GOALS: The goal of this project was to inform four chronic disease initiatives, working together on the team Connections IN Health, and counties in Indiana on certain areas of need to assist them in collaborative planning. The chronic diseases focused on include diabetes, cardiovascular disease, stroke, asthma, lung cancer and obesity. METHODS/STUDY POPULATION: Chronic disease health outcomes and social determinants of health indicators were identified in all 92 Indiana counties. Counties were compared by composite z scores in a matrix to determine the 23 counties with the poorest health statistics for diabetes, cardiovascular disease, stroke, asthma, lung cancer, obesity and life expectancy. Qualitative data were used to identify local health coalitions that have the capacity and desire to work with Connections IN Health to improve these health outcomes. With input from partners, the counties were narrowed to 10 that were identified as those with the most need in the specific areas of chronic disease that the initiatives focus on. The team will begin listening sessions with two of these counties to identify strategic partnerships, funding sources, and evidence-based programs to address community-identified health priorities. RESULTS/ANTICIPATED RESULTS: The 23 counties with the poorest health outcomes related to chronic disease and factors were Blackford, Clark, Clay, Fayette, Fulton, Grant, Greene, Howard, Jay, Jennings, Knox, Lake, LaPorte, Madison, Marion, Pike, Scott, Starke, Sullivan, Vanderburgh, Vermillion, Vigo, and Washington. There was significant overlap in low z score rankings for individual health and social determinants of health measures among these 23 counties. The following 10 counties were selected for focus in the next five years based on partner input: Blackford, Clay, Grant, Jennings, Lake, Madison, Marion, Starke, Vermillion, and Washington. The Connections IN Health team has initiated listening sessions in Grant and Vermillion Counties (with data for presentation at the ACTS meeting). DISCUSSION/SIGNIFICANCE OF IMPACT: This mixed methods approach using existing data and partner input on county capacity/readiness directed Connections IN Health to counties with the most need for coalition efforts. Engagement within each county will inform next steps (e.g., capacity building, partnership development, applications for funding, implementation of evidence-based programs) and specific health focus area(s).

OBJECTIVES/SPECIFIC AIMS: Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice, and has widely varying treatments for stroke prevention and rhythm management. Some of these therapies are increasingly being prescribed by primary care physicians (PCPs). We therefore sought to investigate if healthcare plans with PCP gatekeeping for access to specialists are associated with different pharmacologic treatment strategies for the disease. In particular, we focused on oral anticoagulants (OACs), non-vitamin K-dependent oral anticoagulants (NOACs), rate control, and rhythm control medications. METHODS/STUDY POPULATION: We examined a commercial pharmaceutical claims database (Truven Marketscan™) to compare the prescription frequency of OAC, rate control, and rhythm control medications used to treat AF between patients with PCP-gated health plans (where the PCP is the gatekeeper to specialist referral—i.e., HMO, EPO, POS) and patients with non-PCP-gatekeeper health plans (i.e., comprehensive, PPO, CHDP, HDHP). To control for potential confounders, we also used multivariable logistic regression models to calculate adjusted odds ratios which accounted for age, sex, region, Charlson comorbidity index, CHADS2Vasc score, hypertension, diabetes, stroke/transient ischemic attack, prior myocardial infarction, peripheral artery disease, and antiplatelet medication use. We also calculated median time to therapy to determine if there was a difference in time to new prescription of these medications. RESULTS/ANTICIPATED RESULTS: We found only small differences between patients in PCP-gated and non-PCP-gated plans regarding prescription proportion of anticoagulants at 90 days following new AF diagnosis (OAC 44.2% vs. 42%, p<0.01; warfarin 39.1% vs. 37.1%, p<0.01; NOAC 5.9% vs. 6.0%, p=0.64). We observed similar trends for rate control agents (76.4% vs. 73.4%, p<0.01) and rhythm control agents (24.4% vs. 24.6%, p=0.83). We found similar odds of OAC prescription at 90 days following new AF diagnosis between patients in PCP-gated and non-PCP-gated plans (adjusted OR for PCP-gated plans relative to non-gated plans: OAC 1.006, p=0.84; warfarin 1.054, p=0.08; NOAC 0.815, p=0.001; dabigatran 0.833, p=0.004; and rivaroxaban 0.181, p=0.02). We observed similar trends for rate control agents (1.166, p<0.0001) and rhythm control agents (0.927, p=0.03). Elapsed time until receipt of medication was similar between PCP-gated and non-gated groups [OAC 4±14 days (interquartile range) vs. 5±16 days, p<0.0001; warfarin 4±14 vs. 5±14, p<0.0001; NOAC 7±26 vs. 6±23, p=0.2937; rhythm control 13±35 vs. 13±34, p=0.8661; rate control 10±25 vs. 11±30, p<0.0001]. DISCUSSION/SIGNIFICANCE OF IMPACT: We found that plans with PCP gatekeeping to specialist referrals were not associated with clinically meaningful differences in prescription rates or delays in time to prescription of oral anticoagulation, rate control, and rhythm control drug therapy. In some cases, PCP gatekeeping plans had very small but statistically significant lower odds of being prescribed NOACs. These findings suggest that PCP gatekeeping does not appear to be a major structural barrier in receipt of medications for AF, although non-PCP-gated plans may vary slightly favor facilitating the prescription of NOACs. Our findings that overall OAC prescriptions did not differ by PCP gating status may suggest completion of the rapid dissemination and uptake phase for most AF treatments. The small but statistically significant odds ratios favoring the non-PCP-gated populations in NOACs further suggests that in this newer drug group, the process is ongoing, with more specialists representing early adopters. Interestingly, the low primary care odds ratio of rivaroxaban use, relative to dabigatran, may be indicative of a gradient of uptake of later-generation NOACs, although interpretability is limited by the small number of patients in the rivaroxaban group.

OBJECTIVES/SPECIFIC AIMS: The central goal is to predict the metabolites of varenicline and predictively evaluate their propensities for eliciting an increased binding effect in the brain. METHODS/STUDY POPULATION: Molecular modeling computational software and other cheminformatic tools present a strategic in silico strategy to predict a complete metabolic transformation for the varenicline molecule. Molecular docking tools help to highlight key interactions of the varenicline with key metabolizing enzymes that are differentially expressed across a population. This will assist in validating clinical models for smoking cessation. RESULTS/ANTICIPATED RESULTS: Differentialized binding results depending on whatever metabolite is produced. DISCUSSION/SIGNIFICANCE OF IMPACT: Products of metabolism of varenicline may differ in individuals and across groups, thus, binding effects and the propensity for adverse effects may differ in individuals.

Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.