In addition to facing numerous healthcare disparities, rural America is chronically underrepresented in clinical research. This gap was made more evident during the COVID-19 pandemic. St Lawrence Health, located in rural Upstate New York, established its Clinical and Rural Health Research Department in 2015 to help close this gap. The research department then launched the DISRUPTS (Developing InfraStructure for Research to Utilize Patient-centered Techniques at St Lawrence Health System) program to build the infrastructure to conduct Patient-Centered Outcomes Research (PCOR). Together with a diverse committee, the team used proven methods and frameworks to develop a model for engagement, content creation, and education delivery that was successfully used to create educational programs on PCOR and COVID-19. The resulting DISRUPTS webinars had a combined total of over 450 live attendees and over 1,110 views on recordings. Furthermore, nearly one-third of those who participated in the COVID-19 vaccines webinar indicated they were more likely to receive a COVID-19 vaccine after taking part. DISRUPTS can serve as an important model for other rural communities that aim to increase access to and engagement in PCOR, and which hope to improve outreach and education efforts in their communities.

ABSTRACT IMPACT: For community engagement to be impactful and reduce health inequity, it needs to address timely needs in the community, including COVID-19 impacts. Here, we describe how pre- and post-COVID-19 food insecurity worsened mental health among community members served by HealthStreet University of Florida community engagement program. OBJECTIVES/GOALS: COVID-19 impacts the economic vitality and the mental health of communities; research and engagement activities must consider the context in which we are practicing and the needs of our community members. METHODS/STUDY POPULATION: HealthStreet, the University of Florida community engagement program, sends Community Health Workers (CHWs) where people congregate to assess social determinants of health and medical histories, used to make referrals to services and research opportunities. CHWs conducted follow-up COVID-19 assessments measuring perceived stress, loneliness, depression, anxiety, binge drinking, and opioid use, as well as high blood pressure and food insecurity. Here, we consider mental health outcomes among 1,300 adults who reported being food insecure either at some time in the past 12 months at baseline, or at the COVID-19 follow-up assessment, and completed both. Chi-Square Test was used to determine p-values. RESULTS/ANTICIPATED RESULTS: Overall, at the COVID-19 follow-up assessment, 37.1% (of 1,300) were still food insecure during COVID-19 (same), 20.3% (had become food insecure during COVID-19 (worse) and 42.6% were no longer food insecure (better). Those who were no longer food insecure were more likely to report less stress, while those still food insecure were more likely to report the highest stress and loneliness (p<0.0001), while the worse off group was in the middle. Those who stayed food insecure were most likely to report depression and anxiety, and also high blood pressure and using opioids (p<.05) compared to those getting worse or better. Binge drinking behavior was not significantly different across groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: Community engagement activities across CTSIs must be sensitive to the needs of their communities. HealthStreet findings show that new and continuing food insecurity negatively influence mental health problems, pointing to the need for engagement to address multiple problems.

OBJECTIVES/GOALS: COPD is a progressive airways disease that results in death or disability. There is poor uptake of clinical guidelines (CPG) to manage COPD and studies to bridge this implementation gap have shown inconsistent results. Using implementation science principles we aim to understand COPD-CPG implementation determinants from providers’perspective. METHODS/STUDY POPULATION: The study is being conducted in ten VA Primary Care Clinics. Guided by the Consolidated Framework for Implementation Research (CFIR), a conceptual framework developed to guide systematic assessment of multilevel implementation contexts, we are using semi-structured guides to conduct key informant qualitative interviews (physicians, physician extenders and nurses), to support a formative evaluation. CFIR domains relevant to the study were determined by a multidisciplinary team. Informants are identified through online outreach and voluntary participation. Sampling adequacy will be assessed by achievement of code saturation. A qualitative template analysis will be used to summarize the barriers and facilitators of each component of COPD-CPG organized by CFIR-domain. RESULTS/ANTICIPATED RESULTS: We anticipate a list of modifiable and non-modifiable contextual, recipient (provider and patient), and COPD CPG content (innovation) barriers to implementation. Many settings do not have critical elements of these CPG, such as a standardized inhaler education/assessment pathway, patient education material, or pulmonary rehabilitation referral pathway. Existing literature indicate reasons behind the insufficient uptake of COPD CPG include low familiarity with guidelines, perception of minimal value of guidelines by physicians, and time constraints; we will present contextual, recipient and innovation determinants specific to our setting. DISCUSSION/SIGNIFICANCE: This comprehensive assessment of barriers and facilitators to COPD-CPG will inform tool development and implementation strategies identification to improve COPD CPG uptake. COPD is the most common veteran lung disease. Improvement in COPD care has enormous potential for benefit for local veterans, as well as potential for wider dissemination.

OBJECTIVES/SPECIFIC AIMS: There is currently a gap in the literature regarding the relationship between acute cellular rejection and frailty in LT patients. We aimed to evaluate the association between frailty and acute cellular rejection in LT patients. METHODS/STUDY POPULATION: Included were LT recipients from 2014-16 at a single center who had a frailty assessment prior to LT using the Liver Frailty index consisting of grip strength, chair stands, and balance. Frailty was defined by a Liver Frailty Index > 4.5. Data on acute cellular rejection at 3 months (primary outcome) and immunosuppression regimens were collected from medical chart review. Univariable and multivariable logistic regression assessed the associations between frailty and acute cellular rejection. RESULTS/ANTICIPATED RESULTS: A total of 241 LT recipients were included. Of these, 37% were female, 55% had Hepatitis C, and the median (IQR) age was 60 (54-65); 46 (19%) were classified as frail. 98% of patients were on a combination of mycophenolate, corticosteroids and tacrolimus on discharge compared to 80% by 3 months. Within the first 3 months post-LT, 7 (15%) of frail patients versus 10 (5%) (p = 0.02) of non-frail patients experienced acute cellular rejection. In univariable logistic regression, frailty was associated with a 3.3 times higher odds of acute cellular rejection at 3 months (95%CI 1.19, 9.26, p = 0.02); age (OR 0.91), Black race (OR 3.2), autoimmune disease (OR 2.3), and diabetes (OR 0.3) were also associated with acute cellular rejection at 3 months with a p-value<0.20. In a multivariate analysis, after adjusting for age, frailty remained significantly associated with rejection (OR 3.06, 95%CI 1.04, 9.01, p = 0.043). There were no significant differences in immunosuppression regimens or rates of mycophenolate dose reduction in the first 3 months between frail and non-frail patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Frailty is associated with an increased rate of acute cellular rejection within 3 months post-LT, despite similar immunosuppression regimens and doses. Future studies should evaluate whether frailty should be considered in the management of immunosuppression in the early post-transplant period.

OBJECTIVES/SPECIFIC AIMS: 1) Describe strategies pediatric providers perceive improve chlamydia screening of sexually active female adolescents (SA), and 2) describe barriers to regular screening of SA for chlamydia METHODS/STUDY POPULATION: Using qualitative methods, 14 general pediatric providers across 7 clinical sites in Vermont were interviewed to ascertain best practices and remaining challenges. Semi-structured interviews lasting 30-45 minutes were audiotaped and transcribed. Chlamydia screening rates provided by BCBS-VT were used to categorize participant responses across three performance tiers, data were coded, and themes identified within these tiers. RESULTS/ANTICIPATED RESULTS: Facilitators: When asked to describe facilitators of chlamydia screening, providers in the top tier of chlamydia screening emphasized the importance of adequate insurance to cover the cost of testing. Providers in the middle performance tier cited use of pre-visit questionnaires, and those in the bottom performance tier identified no best practices. Other strategies included improving physician confidence and awareness, establishing practice- and individual-level routines, and providing strong leadership and communication of local screening rates. Barriers: Across the 3 performance tiers, the most common challenges to consistent chlamydia screening were threats to patient confidentiality, cost of the screening test, and requirement for patient disclosure of sexual activity. Less commonly, providers were concerned that adolescent patients were not reliable to obtain screens off-site, or fill treatment prescriptions without the help of a parent. DISCUSSION/SIGNIFICANCE OF IMPACT: The need for systematic, confidential, and inexpensive means for screening SA for chlamydia was highlighted in both the best practices and challenges described by providers of pediatric care in the suburban practice setting. Policy and practice interventions may target these needs to improve the reproductive health of female adolescents.

ABSTRACT IMPACT: Better understanding of the factors impacting disease severity and immunological response of MS patients on disease modifying therapy will enable better recommendations for vaccination options and risk mitigation strategies OBJECTIVES/GOALS: The Coronavirus Disease 2019 (COVID-19) and global health crisis has raised health concerns for patients with multiple sclerosis (MS). We aim to study the clinical characteristics, immunological laboratory data, and immunoglobulin response in patients with MS and COVID-19, to identify factors impacting disease severity and immune response. METHODS/STUDY POPULATION: Database search was done using DataDirect to search for MS patients who had tested positive for COVID-19 at the University of Michigan hospital. Patients with a positive nasopharyngeal swab polymerase chain reaction (PCR) for COVID-19 between March 1 and September 2020 were included. The primary outcome was the immunological laboratory data and immunoglobulin levels and the secondary outcome was their disease severity. We collected demographics, neurological history, MS treatment, Expanded Disability Scale Score (EDSS), comorbidities, and COVID-19 characteristics. A 7-point ordinal scale previously used to assess disease severity was used. Univariate and multivariate analyses will be performed to assess relationships between the collected variables. RESULTS/ANTICIPATED RESULTS: A total of 17 patients, mean age 53 (SD 11.6) years, mean disease duration, 6.2(SD 4.1) years were analyzed. 41% of patients had relapsing remitting multiple sclerosis, 17% had primary progressive MS. (88%) patients were on Disease Modifying Therapy (DMT) at the time of COVID-19 diagnosis. 2 patients died from COVID-19 complications. There was a higher proportion of patients with higher disease severity receiving Ocrelizumab. Only one patient showed positive IgG to SARS-CoV-2 after the resolution of infection. CBC with differential was obtained and a longitudinal follow-up of labs will be done. Regression analysis will be done to check the association between the use of DMT, immunological response, and COVID disease severity in them. The impact of COVID-19 on MS relapse, EDSS, and MRI activities will also be studied. DISCUSSION/SIGNIFICANCE OF FINDINGS: Recommendations to continue current DMT have been made, however, the immune response has not been correlated with the individual’s risk profile. Certain therapies may interfere with mounting a protective immune response of COVID-19 and this knowledge is crucial when advising patients regarding the choice of vaccine and risk mitigation strategies.

OBJECTIVES/GOALS: Lung transplant (LTx) candidates benefit from use of non-ideal donor organs. Each organ procurement organization (OPO) defines “acceptable” donor organs introducing unmeasured variation in donor pursuit. We characterized non-ideal donor pursuit among OPOs to identify drivers of risk aversion in LTx. METHODS/STUDY POPULATION: We queried the UNOS registry for adult donors who donated ≥1 organ for transplantation from 12/2007-12/2018. Non-ideal donors were those with any of age>50, smoking history ≥20 pack-years, PaO2/FiO2 (P/F) ratio<350, donation after cardiac death (DCD) status, or CDC increased risk (IRD) status. Non-ideal donor pursuit rate was defined as the proportion of non-ideal donors at each OPO from whom consent for lung donation was requested with lower numbers indicating increased risk aversion. We estimated the correlation between non-ideal and overall donor pursuit using a Spearman correlation coefficient. Adjusted non-ideal donor pursuit rates were estimated using multivariable logistic regression. RESULTS/ANTICIPATED RESULTS: Overall, 18,333 deceased donors were included and classified as ideal or non-ideal. Among 58 OPOs, rates of non-ideal donor pursuit ranged from 0.24-1.00 Figure). Of 5 non-ideal characteristics, DCD and IRD status were associated with the most and least risk aversion, respectively. Non-ideal donor pursuit was strongly correlated with overall donor pursuit (r = 0.99). On adjusted analysis, older age (OR 0.15, 95% CI 0.13-0.16), smoking history (OR 0.38, 95% CI 0.34-0.44), low P/F ratio (OR 0.12, 95% CI 0.11-0.14), and DCD status (OR 0.04, 95% CI 0.03-0.04) were all independently associated with significant risk aversion, corresponding to decreased rates of donor pursuit. DISCUSSION/SIGNIFICANCE OF IMPACT: OPOs differ in their levels of risk aversion in LTx and risk aversion is not uniform across selected categories of non-ideal lung donor. Consideration of new OPO performance metrics that encourage the pursuit of non-ideal lung donors is warranted.

OBJECTIVES/GOALS: Assess molecular and cellular mechanisms of allograft loss in kidney biopsies using digital spatial profiling and clinical outcomes data. METHODS/STUDY POPULATION: Patients with chronic allograft dysfunction (CGD), enrolled in the Deterioration of Kidney Allograft Function (DeKAF) study, with or without eventual allograft loss, were included. CGD was defined as a >25% increase in creatinine over 3 months relative to a baseline. Kidney biopsy tissue was assessed by Nanostring GeoMX digital spatial profiling (DSP) after staining with anti-pan-cytokeratin, anti-CD45, anti-CD68, Syto-13, to identify specific cell populations, and Nanostring’s Whole Transcriptome Atlas (WTA), to quantify the distribution of transcripts across the biopsy. Up to 14 regions of interest (ROIs) were selected, with or without glomerulus. CIBERSORT was used to perform cell deconvolution. Clinical and outcomes data were from the DeKAF study and United States Renal Data System. RESULTS/ANTICIPATED RESULTS: Macrophage (M1) cell population abundance was significantly different in ROIs with glomerulus between graft loss and no graft loss. Principle component analysis of differentially expressed genes resulted in transcriptomes in ROIs that cluster together by clinical outcome of graft loss or no graft loss. There were 203 DEGs in ROIs with glomerulus that were different by graft loss or no graft loss. By pathway analysis, these 203 DEGS were enriched in the T-cell activation, integrin signaling and inflammation pathways. DISCUSSION/SIGNIFICANCE: DSP of kidney allograft biopsies allows for the identification and quantification of specific cell types, such as macrophages and molecular transcripts as potential drug targets. This data can be used to understand mechanisms of kidney allograft loss and may lead to improved immune suppression in kidney transplant recipients.

OBJECTIVES/GOALS: Tubulointerstitial damage in lupus nephritis (LN) is a strong predictor of progression to chronic kidney disease and end stage renal disease (ESRD). While complement activation mediates glomerular injury, the role of complement in renal tubular damage has not been evaluated. We investigated the association between complement activation and tubulointerstitial fibrosis. METHODS/STUDY POPULATION: Patients with LN were selected randomly between July 2014 - July 2016. Chromogenic immunohistochemistry was performed on formalin-fixed, paraffin-embedded, 4-µm human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197) as a marker of the terminal complement activation. Positive control is C3 glomerulopathy and negative control is normal kidney. Tubular basement membrane C9 staining intensity were analyzed on semiquantitative scale 0 to 3 by a renal pathologist. Interstitial fibrosis/tubular atrophy were categorized into low (0–10%), medium (11–20%), or high (≥21%). Clinical parameters were assessed at time of biopsy and 6 months post biopsy. Bivariate associations were assessed between presence of tubular C9 (C9+) and other covariates. RESULTS/ANTICIPATED RESULTS: Renal biopsies from 30 LN studied, 23 (77%) of which had proliferative LN. There were 24 (80%) women, mean (SD) age 33 (12) years. Positive tubular C9 staining was observed in 7/30 (23%) biopsies. At time of renal biopsy, C9+ patients had significantly higher urine protein, compared to C9- patients: median (IQR) 6.2g (3.3-13.1) vs. 2.4g (1.3-4.6), p<0.01. The differences persisted at 6 months after induction therapy: 1.08g (1.0-8.3) in C9+ vs. 0.68g (0.2-2.1) in C9- patients, p = 0.06. There was no significant difference in creatinine at renal biopsy between the two groups. Tubular C9 deposition was associated with interstitial fibrosis: 49% had severe interstitial fibrosis vs. none in the C9- group, p = <0.01. Higher proportion of C9+ patients had moderate NIH Chronicity index: 42.9% vs 8.7% in the C9- group, p = 0.07. DISCUSSION/SIGNIFICANCE OF IMPACT: Tubular C9 deposition is significantly associated with proteinuria, interstitial fibrosis and increased chronicity which predict progression to ESRD and high mortality. This finding suggests that complement activation in the tubules may be linked to proteinuria and contribute to mechanism in tubulointerstitial damage in LN.

OBJECTIVES/GOALS: Dyslexia is a common Reading Disability (RD) affecting 7-12% of the population and is associated with less cortical thickness (CT) in bilateral brain regions. However, the interaction between RD and a bilingual experience on CT is unknown, even though bilingualism is also associated with altered CT. METHODS/STUDY POPULATION: We studied 48 Bilinguals assigned to the Typical Reader group based on Oral Reading Recognition Test (ORRT) scores above 90 (avg=107 ± 14), 47 Bilinguals assigned to the RD group based on ORRT scores below 85 (avg=77 ± 5), 45 English Monolingual Typical Readers with ORRT scores above 90 (avg=102 ± 13) and 47 Monolinguals with RD based on ORRT scores below 85 (avg=78 ± 5). Participants (all from the Adolescent Brain & Cognitive Development Study) were 11.9 ± 0.7 years of age and the 4 groups were matched for sex, self-ratings of English, nonverbal reasoning, and combined household income. Structural magnetic resonance images were analyzed using CAT12 and all four groups were entered into a factorial analysis. RESULTS/ANTICIPATED RESULTS: Surprisingly, the main effect of Reading Ability did not reveal any regions where RD manifested less CT than Controls (raising the possibility that the findings from the only two prior reports were due to small samples). The main effect of Language Background revealed less CT in bilinguals in bilateral perisylvian regions (inferior frontal gyri, superior temporal gyri, and left Heschl's gyrus) consistent with prior reports. There was no interaction of Reading Ability by Language Background. Taken together, we found no differences in CT in those with RD relative to Typical readers and no evidence that the dual language experience affected this result in any way. DISCUSSION/SIGNIFICANCE: The lack of interaction between Reading Ability and Language Background indicates that a dual-language experience does not affect CT differently in those with RD and reduces concerns that RD in those who are bilingual needs to be given separate consideration in studies of CT neuroanatomy.

OBJECTIVES/GOALS: Untargeted metabolomics platforms are powerful biomarker discovery tools. However, the absence of uniform study design, data analysis, and reporting standards limits translation of this research into the clinical lab. The goal was to critically appraise existing untargeted metabolomics platforms that analyzed inborn errors of metabolism. METHODS/STUDY POPULATION: A search strategy was conducted in MEDLINE via PubMed from January 16, 2013, to January 16, 2023. The search strategy was limited to primary literature articles written in English that evaluated human subjects with inborn errors of metabolism (IEMs). Articles that performed targeted metabolomic analysis or analyzed non-human samples were excluded. Information on patient cohorts analyzed, sample types, and method design were extracted using a template. Categorical data are summarized as frequencies and percentages. RESULTS/ANTICIPATED RESULTS: A total of 96 distinct IEMs were evaluated by the different untargeted metabolomics methods included in this review. However, most IEMs (55/96, 57%) were evaluated by a single platform, in a single study, with a limited cohort size. Only one study validated their results using a separate, validation cohort. There was considerable diversity in the separation techniques and mass spectrometry instrumentation used by the studies to create their untargeted metabolomics methods. Slightly over half (59%) of the studies identified at least some of the metabolites detected in their samples with the highest level of confidence. Importantly, most of the included studies reported adherence to quality metrics, including use of quality control material (65%) and internal standards in their analysis (61%). DISCUSSION/SIGNIFICANCE: Future studies analyzing IEM patient samples with untargeted metabolomics platforms should progress beyond single-subject studies and evaluate the reproducibility of the research using a prospective, or validation cohort as well as confirm metabolite annotations with reference metabolites standards to generate clinically useful data.

OBJECTIVES/GOALS: Social isolation/loneliness is a public health crisis and one that is unlikely to be solved through pharmacology. Nonpharmacological approaches, such as dance, are needed. The objective of this study is to investigate the physiological correlates of dance-induced improvements in social connection. METHODS/STUDY POPULATION: Participants were randomly assigned to participate for 4 weeks (2 times per week, 90-minute sessions) in either 1) improvisational dance training (experimental group; n=7); or a 2) dance movie watching experience (control group; n=7). Before and after the intervention, using mobile brain-body imaging techniques, participants and their instructor had their brain (via electroencephalography) and body physiology (via photoplethysmography) recorded during a series of verbal and nonverbal interactive experiences. Participants were also video recorded via 4 surrounding cameras for later motion capture analysis. Neuropsychological assessments were also conducted before and after the intervention. RESULTS/ANTICIPATED RESULTS: We found that dance significantly increased social skills including empathy, interpersonal skills, emotional regulation, mindfulness, and attention. Additionally, we found that dance significantly increased interbrain synchrony during nonverbal experiences including theta (4-8 Hz), beta (12-35 Hz), and gamma (35-45 Hz) frequencies in the occipital lobe. Increases in interbrain synchrony were also positively correlated with increases in empathy. Additionally, intercardiac synchrony between the participant and instructor showed a significant correlation at post-intervention only. Future investigations will focus on the relationship between interbrain, intercardiac, and movement synchrony. DISCUSSION/SIGNIFICANCE: Our findings support the idea that dance increases interpersonal synchrony at the level of the brain, heart, and behavior. Understanding the neural and somatic mechanisms of social behaviors will help promote understanding and development of interventions for the critical problem of social isolation and loneliness.

OBJECTIVES/SPECIFIC AIMS: We sought to solicit and synthesize stakeholders’ ideas for how the Advance-CTR program can best increase the quality and quality of clinical and translational research in Rhode Island, and to apply these findings to address barriers and strengthen research capabilities across our partner institutions. METHODS/STUDY POPULATION: We utilized a Group Concept Mapping approach, involving university and Institution-based researchers and administrators. The process was conducted using the web-based concept mapping application CS Global Max (Concept Systems, Inc). Respondents were asked to provide their best ideas for promoting clinical and translational research in RI. These ideas were then organized by our project team into a set of unique items for consideration by attendees of an Advance-CTR retreat. Participants were tasked with sorting these ideas by theme (cluster), and were also asked to rate each idea according its importance and feasibility. Using the online software, these clusters and ratings were analyzed to identify key themes and to explore differences among sub-groups. RESULTS/ANTICIPATED RESULTS: The Group Concept Mapping exercise yielded 150 statements that were edited down to 78 unique ideas, and clustered into nine themes (e.g., institutional collaboration, training). Fifty-seven retreat participants completed the sorting and rating tasks of the concept mapping exercise. Overall, ideas rated as highly important and highly feasible included “providing seed grants to encourage new collaborations across basic science,” and “connecting researchers with common interests.” Top rated items varied across institutions and according to respondent demographics, allowing us to consider the unique issues relevant to particular groups. Relative rankings of clusters across groups revealed notable differences, such as higher importance placed on community engagement among administrators as compared with researchers, and differences in needs for internal support for research between universities. DISCUSSION/SIGNIFICANCE OF IMPACT: Group Concept Mapping was an effective and insightful participatory approach to engage our program’s stakeholders in developing ideas and identifying challenges to enhancing clinical and translational research in Rhode Island. Our results have implications for project decision-making and initiatives to facilitate translational research in RI. Thus, results have been presented to the Advance-CTR community via webinar, as well as Advance-CTR project leadership and advisory committees.

OBJECTIVES/GOALS: Familial Hemophagocytic Lymphohistiocytosis (FHL) is a systemic inflammatory disease, causing acute liver failure (ALF). Elevated Interferon gamma (IFN-γ) results in increased hepatic transcription of the chemokines CXCL9 and CXCL10. Inhibition of their receptor CXCR3 may reduce leukocyte recruitment and ameliorate hepatitis. METHODS/STUDY POPULATION: To determine the functional role of the IFN-γ-induced ligands, CXCL9 and CXCL10, in hepatic leukocyte recruitment via CXCR3 we used a prf-/- mouse infected with Lymphocytic Choriomeningitis Virus (LCMV) in our well-established model mimicking human FHL. We used AMG487, a small molecule CXCR3 antagonist, while maintaining intact IFN-γ signaling. Mice were sacrificed 10 days after infection when mice developed features of FHL: cytopenias, organomegaly, elevated serum ferritin and sCD25, and hepatic inflammation. Hepatic inflammation was characterized using flow cytometry, liver histology and noninvasive markers of hepatitis (ALT, liver size). RESULTS/ANTICIPATED RESULTS: AMG487 did not ameliorate the overall disease phenotype with mice developing similar FHL characteristics compared to control, including weight loss, elevation of ALT and sIL-2r as well as degree of thrombocytopenia and anemia. There was significant reduction of recruitment of CXCR3+CD4+ T cells and B cells in mice treated with AMG487. This indicates the importance of CXCR3 receptor in humoral response in FHL hepatitis. In addition, treatment with AMG487 resulted in reduction of CXCR3 expression in hepatic inflammatory monocyte (iMonos) measured by mean fluorescence intensity (MFI). DISCUSSION/SIGNIFICANCE: This is the first pre-clinical experience using AMG487, a small molecule CXCR3 antagonist, to treat FHL hepatitis. AMG487 changed the hepatic inflammatory milieu, reducing CD4 T-cell and B-cell recruitment, as well as CXCR3 expression on iMonos. However, it did not ameliorate FHL hepatitis and other therapeutic approaches should be pursued.

ABSTRACT IMPACT: This is the first examination of risk factors for prolonged opioid use after an ICU stay and will inform efforts to strengthen prescribing guidelines and care transition models for patients after critical illness. OBJECTIVES/GOALS: The majority of patients in intensive care units (ICU) receive opioids during admission, and up to 25% receive a prescription at discharge. However, transitions of care and prolonged use after discharge remain unknown. We aim to characterize risk factors for prolonged opioid use after an ICU stay. METHODS/STUDY POPULATION: A retrospective study using insurance claims from Optum Clinformatics ®Data Mart was conducted for opioid-naive adult patients (18-64 years) with an ICU admission from 2010 to 2019. The primary outcome was new persistent opioid use, defined as a continued prescription fill 91-180 days after discharge, in addition to a fill in the first 90 days. The primary exposure was an opioid fill at discharge. The ICU admission was characterized using the Clinical Classification System from the Agency of Healthcare Research and Quality, based on patients’primary diagnosis code. Diagnoses were combined into 11 groups highlighting the affected organ system/mechanism of injury. Logistic regression evaluated the associations of patient demographic and clinical characteristics with the probability of persistent opioid use. RESULTS/ANTICIPATED RESULTS: In this cohort of 90,721 patients discharged from the ICU, 3.3% continued to fill opioids at 6 months. An opioid prescription fill (OR 3.1; 95% CI 28 - 3.3) and benzodiazepine prescription fill (OR 1.6; 95% CI 1.4 - 1.8) within 3 days of ICU discharge were each significantly associated with the development of new persistent opioid use. Patient diagnosis groups of Musculoskeletal/Trauma (OR 2.3; 95% CI 2.0 - 2.6), Neoplasms (OR 1.6; 95% CI 1.5 - 1.9), and GI/Hepatobiliary (OR 1.5; 95% CI 1.3 - 1.8) were significantly more likely to develop new persistent use when compared to the Cardiovascular diagnosis group. DISCUSSION/SIGNIFICANCE OF FINDINGS: Opioid prescriptions at discharge after an ICU stay increase the odds of prolonged opioid use. These results will inform efforts to strengthen prescribing guidelines and care models after a critical illness. Further work will characterize the trajectory of prescribing and patient exposure to high-risk prescribing after ICU discharge.

OBJECTIVES/GOALS: This study examines sex differences in brain structure in youths with disruptive behavior disorders (DBD). We use measures of gray matter volume (GMV) in regions-of-interest implicated in the pathophysiology of conduct problems and a whole-brain analysis of cortical thickness. We also examine unique associations between brain structure and callous-unemotional traits. METHODS/STUDY POPULATION: This study included 90 children with a DBD (30 females) aged 8-16 and 50 Healthy Controls (20 females) matched for age and IQ. Children received a diagnostic evaluation using the K-SADS. Pre-processing was conducted using FreeSurfer. For ROI analyses, multivariate GLM models were conducted in SPSS for estimates of GMV to examine the main effects of diagnosis and sex, and sex-by-diagnosis interactions. Whole-brain analyses were conducted in FreeSurfer. Associations were examined between structure and parent ratings of callous-unemotional (CU) traits using the Inventory of Callous-Unemotional Traits in regression analyses in the DBD group, while controlling for the variance in aggressive behavior using the Child Behavior Checklist Aggressive Behavior Scale. All analyses controlled for differences in intracranial volume. RESULTS/ANTICIPATED RESULTS: Relative to controls, children with DBD showed reduced GMV in the bilateral amygdala (left: p = .004; right: p = .04). Sex-by-diagnosis interactions were observed in the left ventromedial prefrontal cortex (p = .004), right insula (p = .001), right inferior frontal gyrus (p = .02), and bilateral anterior cingulate (left: p = .02; right: p = .01) in which DBD males showed lower and DBD females showed higher GMV relative to respective controls. For whole-brain analyses, a significant sex-by-diagnosis interaction was observed in the left ventromedial prefrontal cortex and supramarginal gyrus indicating that DBD males showed lower and DBD females showed higher cortical thickness relative to respective controls. Sex-by-CU traits interactions were observed for left amygdala and ACC volumes. DISCUSSION/SIGNIFICANCE OF IMPACT: The current study provides evidence of reduced amygdala volume in children with DBD, and interactions between sex and diagnosis in the ventromedial prefrontal cortex and supramarginal gyrus, which may have implications for identifying sex-sensitive neural biomarkers. CONFLICT OF INTEREST DESCRIPTION: Disclosures: Dr. Sukhodolsky receives royalties from Guilford Press for a treatment manual on CBT for anger and aggression in children. Drs. Ibrahim, He, Pelphrey, McCarthy, and Mr. Li have no biomedical financial interests or potential conflicts of interest to declare related to this present study.