OBJECTIVES/GOALS: Decongestion, or fluid removal, is an important goal in the management of acute heart failure (AHF) among patients with heart failure with reduced ejection fraction (HFrEF). We sought to examine whether the rate of decongestion is associated with mortality and cardiovascular (CV) outcomes. METHODS/STUDY POPULATION: Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial (n=4133), we evaluated the rate of decongestion by using linear mixed models to derive the in-hospital slope of b-type natriuretic peptide (BNP) and hematocrit as proxies of volume overload and hemoconcentration, respectively. A propensity score was developed to match patients from the quartile with most rapid rates of decongestion to the three quartiles with slower rates. Cox proportional hazards regression models were fitted to assess the association between rate of decongestion with risk of all-cause mortality and a composite of CV mortality or AHF hospitalization. RESULTS/ANTICIPATED RESULTS: Slower rates of in-hospital decongestion were associated with increased risk of both outcomes over a median 10-month follow-up. Those with slower rates of BNP decline, in comparison to the propensity-score matched patients with the most rapid rates of BNP decline, had higher hazards of mortality (HR=1.73 [1.23, 2.42]) and the composite outcome (HR=1.48 [1.18, 1.86]). Those with slower rates of hematocrit increase, in comparison to the propensity-score matched patients with the most rapid rates of hematocrit increase, showed a trend toward higher hazard of mortality (HR=1.17 [0.95, 1.43]) and an increased risk of the composite outcome (HR=1.26 [1.08, 1.47]). DISCUSSION/SIGNIFICANCE: Among patients with HFrEF admitted for AHF, slower rates of decongestion are associated with increased risk of mortality, CV mortality and AHF hospitalization. It remains unknown whether more rapid decongestion provides cardiovascular benefit or if it serves as a proxy for less treatment resistant heart failure.

OBJECTIVES/GOALS: We aim to describe the preschool age developmental outcomes of children born full term or late preterm requiring care in the Childrens Wisconsin (CW) neonatal intensive care unit (NICU). Our objective is to develop a model to predict which NICU infants are at high risk for abnormal preschool age development based on their neonatal characteristics. METHODS/STUDY POPULATION: Retrospective cohort study including full term (≥ 37 weeks) and late preterm (34-36 weeks) infants admitted to the CW NICU between 1/1/2013-12/31/2015 with a developmental assessment by a general practitioner or neuropsychology evaluation between 3-6 years of age. Data extraction will include maternal history, neonatal and delivery factors, and developmental evaluation results. Descriptive statistics will be used to determine the proportion of patients with abnormal preschool development stratified by NICU diagnoses, surgical procedures, subspecialty involvement, and patient demographics. Decision tree analysis will be performed to generate a prediction model identifying those infants at higher risk than their peers for an abnormal developmental assessment at 3-6 years of age. RESULTS/ANTICIPATED RESULTS: Analysis to date reveals 1360 patients ≥ 34 weeks gestation admitted to the CW NICU between 1/1/2013-12/31/2015. 80 patients received neuropsychology evaluations and the remaining 1280 patients had general practitioner developmental assessments. We anticipate that those infants referred for neuropsychology evaluation will have a higher proportion of abnormal developmental assessments when compared to those patients with routine general practitioner assessments. In addition, we hypothesize that common neonatal factors among the infants who received neuropsychology assessments will best predict abnormal preschool development within the decision tree analysis. DISCUSSION/SIGNIFICANCE: This study is one of the first to define risk factors in full term and late preterm infants cared for in the NICU associated with abnormal preschool age development. Identifying these infants at high-risk early on will allow providers to initiate early developmental interventions, schedule close NICU follow-up care, and provide parental counseling.

OBJECTIVES/GOALS: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes. Though largely preventable, DKA is one of the most common acute complications of diabetes. In the US, rates of DKA hospitalization and associated costs have been increasing over the past two decades. METHODS/STUDY POPULATION: In this study, we used the Kentucky Statewide Inpatient Database (2010-2019) and the Nationwide Readmission Database (2010-2018) to explore variation in rates of DKA hospitalization across key sociodemographic subgroups (age, sex, race/ethnicity, rural/urban, insurance coverage, and county-level poverty index) and identify clinical predictors of DKA hospitalization. The primary outcome was hospitalization with a first diagnosis of DKA identified using ICD-9 and -10 codes. Crude rates were calculated using state- and county-level population estimates obtained from the US Census Bureau and are presented as the total number of events per 10,000 people. Regression models will be used to examine the associations between DKA hospitalization and clinical predictors. RESULTS/ANTICIPATED RESULTS: In Kentucky, from 2010-2019, rates of DKA hospitalization increased by 45% (from 65.5 to 94.8 per 100,000). The largest variation was observed by age, race/ethnicity, and insurance. In those aged 15-44, rates of DKA hospitalization were three times higher than rates in the youngest (<15) and oldest (>75) groups (>130 vs <45 per 100,000). Non-Hispanic Blacks experienced rates of DKA hospitalization that were 2x higher than rates observed in non-Hispanic Whites (183.9 vs 92.6 per 100,000). Those covered by Medicaid had the highest rates of DKA hospitalization (171.3 vs 32.4 per 100,000 in commercially insured). Small, but consistent, disparities were observed in rural vs urban counties and higher poverty rates. Predictors of DKA hospitalization are being examined in the Nationwide Readmission Database. DISCUSSION/SIGNIFICANCE: Our findings underscore significant variation in DKA risk across key sociodemographic subgroups and will examine and confirm previously identified clinical predictors of DKA. Because DKA is largely preventable, identifying individuals at higher risk and targeting interventions and services to these individuals may help reduce DKA rates.

OBJECTIVES/GOALS: Individuals with intellectual and developmental disabilities (IDD) have lower levels of moderate-to-vigorous physical activity (MVPA) and a greater risk for sedentary-related comorbidities compared to their typically developing peers. Understanding activity patterns may provide opportunities for targeted physical activity interventions. METHODS/STUDY POPULATION: Secondary analyses were performed on baseline accelerometer data pooled from 2 clinical trials and a pilot study in adolescents (11-17 years) and young adults (18-21 years) with IDD. MVPA was assessed using accelerometers worn on the non-dominant hip during waking hours over 7 consecutive days. Data were collected at 60 hertz and activity counts were aggregated over 60 second epochs. Wear time was determined with the Choi algorithm and MVPA was classified using the Troiano adult or Freedson age-specific child cut-points. Mixed effects linear regressions were used to determine the effects of day of the week, time of the day, and season on MVPA. Diagnosis, gender, and age were used as fixed effect covariates with random intercepts varying among the participants and days of observation within each participant. RESULTS/ANTICIPATED RESULTS: There were 231 individuals (15.6 ± 2.8 years, 51.5% female) who had IDD (36.8% Autism, 48.1% Down syndrome) with 22,498 minutes of MVPA. Individuals with IDD wore the accelerometers an average of 592 ± 254 min./day and completed 13.5 ± 17.9 min./day of MVPA. Average MVPA was lowest in individuals with Autism (12.6 ± 11.4 min./day) and Down syndrome (13.2 ± 9.3 min./day) when compared to those with other IDDs (16.8 ± 10.8 min./day). Participation in MVPA was similar in males (13.4 ± 10.7 min./day) and females (13.7 ± 9.9 min./day). Mixed effects linear regressions showed that individuals participated in fewer minutes of MVPA on the weekend (β = -0.75, p < 0.001) and from 12-3 pm (reference) when compared to before 12 pm (β = 0.87, p < 0.001) and 3-7 pm (β = 0.66, p=0.007). No significant seasonal effects were found. DISCUSSION/SIGNIFICANCE: Individuals with IDD were significantly less active on the weekend, but they did participate in more minutes of MVPA in the morning and late afternoon/early evening. Physical activity interventions aiming to increase MVPA on the weekend and during the early afternoon may increase the number of weekly minutes of MVPA in individuals with IDD.

OBJECTIVES/GOALS: In preclinical Alzheimer disease (AD), biomarkers such as amyloid protein, decreased hippocampal volume, and weaker network connections are apparent in the brain, but memory symptoms assessed by paper and pencil tests have not yet appeared. Performance tests of complex daily tasks may be more sensitive and detect early functional impairment. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing cohort study. Cognitively normal (CN) older adults completed 3 standardized complex daily tasks from the Performance Assessment of Self-Care Skills (PASS) in their home. Biomarkers of AD were assessed within 2-3 years of an individuals completion of the PASS and include: amyloid accumulation, hippocampal volume, and resting-state functional connectivity (rs-fc) signature. Associations between performance on PASS tasks and the biomarkers of AD were quantified by Pearson point-biserial correlations, as biomarker data was normally distributed and PASS scores fell between two categories (acceptable or optimal quality of performance). Correlations with a 95% confidence interval (CI) that did not include 0 were considered significant. RESULTS/ANTICIPATED RESULTS: 161 CN participants (mean age 74.3 years, 55% female) were included. Mean score on the 3 PASS tasks ranged from 2.67 [standard deviation (SD): .47] to 2.90 (SD: .16) out of 3. Mean amyloid PET on Centiloid scale was 23.8 (SD: 34.8); mean partial volume corrected hippocampal volume was 7448.5 (SD: 909.8); mean rs-fc signature was .805 (SD: .164). After controlling for age and gender, worse performance of complex daily activities was associated with smaller hippocampal volumes (Pearsons r: 0.302, p=.02, 95% CI: .179 to .416) and weaker rs-fc network connections (Pearsons r: 0.276, p=.03, 95% CI: .078 to .453), but not amyloid accumulation. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks may be associated with markers of neurodegeneration. These findings could lead to a better understanding of functional changes that may occur during the preclinical stage of AD.

OBJECTIVES/GOALS: Ecotin is a potent periplasmic serin protease inhibitor that was first described in Escherichia coli (E. coli). Ecotin is known to inhibit a broad range of serine proteases including NE. Therefore, we hypothesized that ecotin can inhibit the NE activity present in CF clinical sputum samples. METHODS/STUDY POPULATION: To investigate the function of ecotin on CF sputum, orthologues from Campylobacter rectus and Campylobacter showae were recombinantly expressed and purified from E. coli to generate C. rectus ecotin, C. showae ecotin, and E. coli ecotin. Ecotin was added to CF sputum supernatant samples at various concentrations and NE enzymatic activity was measured by a fluorometric assay kit. In addition, CF sputum and healthy sputum was added to PMNs isolated from healthy donors for 3.5 hours and NE was measured with immunofluorescence staining. The sputum was washed two times prior to measuring NE released and on the PMNs, and PBMCs was used as a control. RESULTS/ANTICIPATED RESULTS: Our results indicate a clear inhibition of NE activity in CF sputum supernatant. C. showae ecotin showed the greatest inhibitory effect on NE activity in CF sputum supernatant. We also saw that CF sputum supernatant causing healthy PMNs to release more NE suggesting that NE in the CF airway may trigger more NE release from newly incoming PMNs to the lung. Our next steps will be to determine if ecotin can inhibit NE on the PMN surface and released from PMNs. DISCUSSION/SIGNIFICANCE: Neutrophil elastases are produced by PMNs to kill microbial pathogens in the lung, however in CF, the pathogens are unable to be killed by NE and instead causes severe lung damage. PMNs and NE has been shown to be elevated in the sputum of CF patients and there is currently no NE therapeutic inhibitor that has been effective in these patients.

COVID-19 has widened the existing digital divide, especially for people from socially and economically deprived communities. We describe a program evaluation using a community participatory approach to develop self-reported items of patient experience with technology inclusive of digital access and literacy. The feedback received from Community Advisory Boards and Community Engagement Studio members led to the evaluation and refinement of the individual items. The community-based participatory approach highlighted in our paper to develop these items could serve as a model for other screening tool development for enhancing equity and inclusiveness in clinical care and research.

OBJECTIVES/GOALS: Patients utilizing dialysis receive fewer primary care services, especially during the time of initiation of dialysis. This project aims to identify clinical or demographic factors that are associated with either initiation or continuity of PCP use after initiating home dialysis. METHODS/STUDY POPULATION: Using Medicare claims data from the United States Renal Data System (USRDS), we analyzed PCP use for patients aged 67 years or older. We included patients who initiated either peritoneal or home-hemodialysis between 2008-2014. Patients were followed for 2 years: 1 year before and after home dialysis initiation. We used a multivariable logistic model to control for various demographic and clinical factors believed to be confounders and to ascertain factors (i.e. age, race/ethnicity, area of residence, comorbidities, frailty scores) associated with initiation of PCP use or continuity of PCP use. RESULTS/ANTICIPATED RESULTS: Among the 9,854 patients analyzed, 68% of patients used PCP after dialysis initiation. 85% of patients who used PCP before dialysis continued PCP use after home dialysis initiation. Only 29% of patients who had not used PCP before dialysis initiated PCP use after. Employment (vs. unemployment) and use of home-hemodialysis (vs peritoneal) were associated with lower odds of PCP continuity of care. Diabetes and pre-dialysis nephrology care were associated with greater odds of PCP continuity of care. Black race (vs White) and high frailty scores were associated with lower odds of PCP initiation. Those with cardiovascular disease, residence in the South (vs the Northeast), and residence in more urban areas (vs low urban) were associated with greater odds of PCP initiation. DISCUSSION/SIGNIFICANCE: This study highlights the prevalence of PCP use, as well as the factors and subgroups that are associated with lower PCP use among patients receiving home dialysis. These findings will guide future research, interventions and policies in order to improve our understanding of the barriers to PCP use in that population.

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

OBJECTIVES/GOALS: Autologous periodontal ligament cells (PDLCs) are a promising tool for rebuilding tooth-supporting (periodontal) tissues but require scaffolds that enable delivery while maintaining PDLC bioactivity. The goal of this study was to design a synthetic hydrogel that fulfilled these criteria to support clinical translation of PDLC delivery. METHODS/STUDY POPULATION: Hydrogels were formed using poly(ethylene glycol) (PEG) polymers and synthetic peptides. PDLCs were isolated from human 3rd molars following informed consent and were cultured using established techniques. Integrin-binding peptides were utilized to promote specific PDLC behaviors, testing PDLCs from 3 human donors in a design of experiments (DOE) approach. Two promising hydrogel designs, identified in the DOE, were selected for validation testing using PDLCs from 3 additional donors. Finally, a small animal model for hydrogel-mediated PDLC delivery was used to determine if benchtop outcomes could predict in vivo tissue regeneration. RESULTS/ANTICIPATED RESULTS: Hydrogel scaffolds maintained high PDLC viability and controlled differentiation of each donor’s PDLCs based on differential presentation of integrin-binding peptides RGD and GFOGER. Two hydrogel designs were selected that optimized either PDLC alkaline phosphatase (ALP) activity or matrix mineralization, outcomes typically associated with cementum and bone formation. ALP activity-optimized hydrogels displayed enhanced PDLC pyrophosphate regulation while mineralization-optimized hydrogels promoted PDLC osteogenic differentiation. When used to deliver PDLCs to periodontal defects, both ALP activity-optimized and mineralization-optimized hydrogels stimulated new cementum formation with inserting PDL fibers, while mineralization-optimized hydrogels promoted enhanced bone formation. DISCUSSION/SIGNIFICANCE: Numerous challenges remain for translating PDLC regenerative potential to clinical practice. This study demonstrates that a synthetic hydrogel scaffold could overcome certain barriers, including controlling PDLC bioactivity with a simplified fabrication and delivery scheme, and may be a promising scaffold for periodontal tissue regeneration.

This study proposes a new practical approach for tracking institutional changes in research teamwork and productivity using commonly available institutional electronic databases such as eCV and grant management systems. We tested several definitions of interdisciplinary collaborations based on number of collaborations and their fields of discipline. We demonstrated that the extent of interdisciplinary collaboration varies significantly by academic unit, faculty appointment and seniority. Interdisciplinary grants constitute 24% of all grants but the trend has significantly increased over the last five years. Departments with more interdisciplinary grants receive more research funding. More research is needed to improve efficiency of interdisciplinary collaborations.

OBJECTIVES/GOALS: Misprescription of opioids has led to an epidemic of opioid use disorder (OUD). Females, among other differences, have increased susceptibility to the addictive properties of opioids. Yet, the exclusion of female subjects from many foundational studies on reward processing had hindered our ability to fully understand these disparities. METHODS/STUDY POPULATION: Estradiol (E2), a neuronal sex steroid, may play a role in sex differences in OUD. In this study, we used fadrozole, an aromatase inhibitor, to characterize the role of centrally produced E2 in heroin cue extinction memory retention (EMR, “remembering to forget”). Male and female rats self-administered heroin in a long-access paradigm (6hr/day) for 8 days, where a light/tone cue was co-presented with each infusion of heroin. This was followed by 1 day of cued extinction (6hr; light/tone but no heroin). Just prior to this session, fadrozole was infused into the basolateral amygdala (BLA) through implanted cannulas. The next day, subjects were given a cued EMR test (1hr; light/tone but no heroin) following another infusion of fadrozole. RESULTS/ANTICIPATED RESULTS: Females took more heroin than males (mg/kg) despite having similar active nose poke responding during acquisition. Regardless of aromatase inhibition, females had higher active nose pokes during the first hour of cued extinction relative to males. Both males and females treated with fadrozole in the BLA prior to cued extinction had impaired EMR on test, evidenced by increased active nose pokes and lower extinction indices relative to vehicle controls. Upon examination of the brains, we expect that aromatase inhibition will have impaired neuronal plasticity, as evidenced by decreases in numerous measures of plasticity. Furthermore, we expect to find sex differential expression of estrogen receptor (ER) subtypes throughout the BLA, suggesting a convergent sex effect of E2 on heroin EMR. DISCUSSION/SIGNIFICANCE: This study is the first to examine a behavioral role for central E2 in the BLA. Future studies will examine specific roles for ER subtypes on this behavior and synaptic plasticity. A better understanding of sex specific E2 signaling will promote further research on sex differences and allowing us to better address disparities in disorders like OUD.