OBJECTIVES/GOALS: To characterize the various social and health trajectories of women released from jail, and how these trajectories influence women’s risky sexual and drug behaviors. To identify areas in which prevention programs and community interventions can be implemented to improve social and health outcomes. METHODS/STUDY POPULATION: The present study analyzes data collected as part of the sexual health empowerment (SHE Project) health literacy intervention. Participants were recruited from three county jails in the greater Kansas City area. At baseline, participants completed a survey that assessed participants’ sociodemographic characteristics and social histories prior to incarceration. Women were recruited between 2014-2016 and followed up annually after program completion to complete follow-up surveys to assess long-term health and social circumstances. The present study is a secondary analysis of baseline and follow-up data. Final analyses will include survey data from 126 women. RESULTS/ANTICIPATED RESULTS: In this study, we use Hobfoll’s Conservation of Resources (COR) Theory to conceptualize the impacts of stress on the social and health behaviors of justice-involved women in the years following release from jail. We hypothesize that “loss spirals”, a term coined by Stevan Hobfoll, creates psychological stress that drive justice-involved women to assume behaviors that will generate more resources and help to cope with the stress. We expect to find that women struggle to maintain ties to stable housing, employment, and support, which we believe to be central to “loss spirals.” Additionally, we expect to find that these “loss spirals” are associated with sexual and drug health risks. DISCUSSION/SIGNIFICANCE OF IMPACT: This study aims to define a succinct longitudinal timeline assessing biopsychosocial outcomes of women released from jail in order to improve prevention and intervention techniques for the improvement in social and health circumstances of women leaving jail and their reduction in recidivism.

OBJECTIVES/GOALS: There is a need to better understand how governments develop strategies to adopt, evaluate, and implement novel health technologies in a public healthcare system. The goal of this project is to understand this strategy development process for the translation of pharmacogenomic (PGx) testing in Ontario, Canada. METHODS/STUDY POPULATION: This observational case study of the Ontario Health PGx Working Group focused on developing recommendations for a PGx testing implementation strategy in the province. The group included 9 individuals affiliated with Ontario Health and 13 healthcare experts from multiple clinical fields. Ontario Health is the government agency that oversees provincial healthcare planning and service delivery. Guided by the Translational Thinking Framework and qualitative research methods, we observed the working group’s activities for eight months. We collected meeting recordings, slideshow decks, emails, and group characteristics. We used descriptive statistics and a nine-step inductive approach to analyze the data to create process maps, a case report, and key decision summaries. RESULTS/ANTICIPATED RESULTS: There were 19 meetings conducted remotely with videoconferencing technology. Throughout the working group’s activities, we identified 15 key decisions related to either administrative processes or PGx scientific content. We further stratified these two categories into four main themes relating to decisions about 1) membership involvement, 2) logistical management, 3) discussion and recommendation scope, and 4) information dissemination. These four decision themes represent tools by which Ontario Health guided the expert group activities and achieved their goal of generating a strategic roadmap for PGx testing implementation in Ontario. DISCUSSION/SIGNIFICANCE: The Ontario government makes decisions about how expert groups function by monitoring and controlling the group’s activities to ensure efficiency, standardization, and practicality. Describing expert group decision-making increases transparency and highlights the critical role they play in the translational pathway of health technologies.

OBJECTIVES/GOALS: The objective of this study is to examine implementation science and clinical outcomes of telemedicine ID consultation at a rural Missouri hospital. METHODS/STUDY POPULATION: Pilot study, hybrid type 2, studying clinical outcomes (mortality, readmission, hospital transfer) and implementation outcomes assessed by survey and chart review (feasibility, acceptability, appropriateness, fidelity to guideline-based care). Telemedicine ID consultations are carried out for patients at Missouri Baptist Sullivan Hospital (MBSH) with positive blood cultures and charts reviewed for 30 days after hospital discharge. Patients, physicians, and staff complete surveys for implementation outcomes. The practical, robust implementation and sustainability model (PRISM) was chosen as the framework for this study and its future scale-up. RESULTS/ANTICIPATED RESULTS: There were 46 patients with positive blood cultures at MBSH, 20 of which were transferred or left from the ER before consultation could be offered. Eighteen patients had telemedicine ID consultation. The remaining 8 patients had contaminants in their blood cultures and therefore no consultation was offered. Of eligible patients not transferred, recruitment rate was 100% (18/18). Average total time per consult was 52.8 minutes on day 1, 8.5 minutes on day 2. 30-day mortality was 0%, 30-day readmission rate 5.5% (n = 1), hospital transfer rate 5.5% (n = 1). 13 patients and 9 providers completed the feasibility, acceptability, and appropriateness survey with zero negative responses on any measure. DISCUSSION/SIGNIFICANCE OF IMPACT: Telemedicine ID consultation at a single rural hospital has thus far been received as feasible, acceptable, and appropriate. Scale-up of this model of care remains to be studied.

ABSTRACT IMPACT: To date, our Scholars have been highly productive in the conduct of impactful research and have contributed to the literature through dissemination of their findings. OBJECTIVES/GOALS: The primary purpose of the Great Plains IDeA Research Scholars Program (RSP) is to support the development and retention of early-career faculty preparing to compete for external funding as clinical-translational research (CTR) investigators. We developed processes for RSP applications, prioritization, and selection criteria. METHODS/STUDY POPULATION: In year 1, we admitted 4 Scholars and have since added 5 additional Scholars. Scholars are retained in the program until they receive R- or K-level funding or if progress is deemed to be substandard on two consecutive 6-month reviews (no awards revoked to date). Each scholar was assigned a mentor(s) or mentoring team. Each participant developed 1-year goals and a 4-5-year plan that included a refined proposal to collect preliminary data, a timetable for grant submissions (with a focus on R01 applications or equivalent), and personal goals to enhance chances of success. Scholars composed an Individual Development Plan (IDP) with mentor(s) feedback to identify the skills needed to achieve goals. Each Scholar completed pilot work to generate the requisite preliminary data for an extramural grant application. RESULTS/ANTICIPATED RESULTS: Over four years, we have had 9 scholars from 4 sites with 51 total applications. All scholars completed required grant writing seminar courses, an 8-hour Responsible Conduct of Research course, and were given access to seminars and workshops sponsored by the Great Plains IDeA CTR. Scholars received 0.5 FTE in research support and $50,000 annual funding to support their research and/or career development activities. Seven of 9 scholars have completed the program to date, collectively receiving an R01 (1), a U01 (1), a K23 (1), a VA Career Development Award (1), or COBRE pilot projects leadership roles (3). All remain active faculty at their institution. Two remaining scholars are working towards independent funding: both have submitted extramural grant applications with anticipated funding this year. DISCUSSION/SIGNIFICANCE OF FINDINGS: To date, our Scholars have been highly productive in the conduct of impactful research. They have submitted 36 grants; culminating in 27 funded projects and >$7.5 million in total funding for 7 graduates. They have disseminated their findings through 121 publications and 48 invited regional/national presentations.

OBJECTIVES/GOALS: Familial Hypercholesterolemia (FH) is a common disorder that is vastly underdiagnosed and causes an increased risk for sudden cardiac death. Cardiology providers (CHCPs) are in an ideal position to care for patients with FH. This research aimed to assess the knowledge of CHCPs in the screening, diagnosis, and management of FH. METHODS/STUDY POPULATION: Adaptation of an existing knowledge tool guided survey development. FH knowledge domains included description of FH, prognosis, prevalence, inheritance, diagnostic criteria, and management options. CHCPs were asked to select their provider type (MD, PA, NP, RN) and years in clinical practice (less than 1-5 years, 6-10 years, 11-20 years, and greater than 20 years).Convenience and snowball sampling recruited CHCPs in the Division of Cardiology at Columbia University Irving Medical Center (CUIMC). Descriptive statistical analysis was performed on quantitative survey data using R. Frequency counts of provider type and years in clinical practice were calculated. Comparisons of scores between provider types and years in clinical practice were made using ANOVA. RESULTS/ANTICIPATED RESULTS: 70 surveys were analyzed (30.2% response rate). 50% of CHCPs identified as MDs, 24.2% as RNs, 12.9% as NPs, and 12.9% as PAs. With regards to clinical experience, 21.4% of CHCPs had 1-5 years, 25.7% had 6-10 years, 24.3% had 11-20 years, and 28.6% had greater than 20 years. The average overall score across all CHCPs was 55.4%, with the highest on the description knowledge domain (81.4% correct), followed by management (61.8%), diagnostic criteria (60.6%), inheritance (58.6%), prevalence (44.3%), and prognosis (25.2%). Physicians had the highest average score of 66.0%, followed by NPs (50.3%), PAs (49.7%), and RNs (39.3%). There was no significant difference in scores across experience levels, provider types, and knowledge domains based on experience levels. DISCUSSION/SIGNIFICANCE: CHCPs across all provider types and years of experience had limited FH knowledge. There exists an opportunity to improve CHCPs’ knowledge of FH through education (didactic knowledge) or practice (experiential knowledge). Future interventions should aim to increase didactic and experiential knowledge of CHCPs through a variety of methods.

OBJECTIVES/SPECIFIC AIMS: This study aims to examine the relative impact of aortic arch and carotid artery anatomy on the procedural times and clinical outcomes in patients who have suffered acute ischemic strokes (AIS). Mechanical thrombectomy remains the gold-standard of care for large vessel ischemic stroke. Given that short procedural times are necessary for good clinical outcomes, arterial access is an important technical consideration. It has been recently demonstrated that abnormal carotid artery anatomy can increase endovascular procedure times in this patient population. However, there are no studies examining the impact of aortic arch anatomy on operative times. Additionally, no studies have looked at the impact of aortic arch and carotid artery tortuosity on clinical outcomes in AIS. Thus, we sought to exam the influence of various aortic arch and carotid artery anatomic variables on interventional procedure times and clinical outcomes. METHODS/STUDY POPULATION: We included 56 patients who underwent embolectomy with successful revascularization for acute ischemic stroke in the anterior circulation from a period of 01/2016-05/2018. The average age was 71 (+/− 17 years) with 39% being male. We calculated anatomic variables on the affected side from CT angiograms immediately prior to embolectomy including the medial-to-lateral span, as well as the anterior-to-posterior span, of both the aortic arch and carotid arteries. In addition, the take-off angle of the respective vessel (left common carotid or right brachiocephalic) was calculated. Charts were reviewed for procedural times and epidemiologic information (HTN, HLD, DM, CAD and Afib). Modified Rankin Scale (mRS) was calculated from PT/OT and outpatient neurology notes. Partial correlation coefficients were performed between anatomic variables, temporal variables and outcome variables after adjustment for age, gender and epidemiologic information. RESULTS/ANTICIPATED RESULTS: There was a significant positive correlation between procedure time (time at groin puncture to time at reperfusion) and take-off angle. There were no other significant correlations between anatomic measures and procedure time. In addition, there was as a significant positive correlation between both procedure time and time from last seen normal to reperfusion and delta mRS (the difference between pre-stroke and post-stroke mRS). DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that patients with larger take-off angles have an association with longer procedural times and worse outcomes. If these patients can be effectively identified prior to the procedure, operators could feasibly use a non-femoral access method initially to reduce procedure time.

OBJECTIVES/GOALS: The current proposal seeks to investigate the effect of early life antibiotic use in the development of functional gastrointestinal (GI) disorders. We propose that infants exposed to antibiotics will present with gut microbial dysbiosis, changes in fecal bile acid concentrations and develop more GI symptoms compared to unexposed children. METHODS/STUDY POPULATION: We analyzed fecal samples from 174 subjects at 12 months of age, of whom 52 were exposed to antibiotics in their first year of life. Of these, 33 subjects were sampled again at 24 months of age. DNA from 200mg of frozen stool (−80C) was isolated with the Qiagen DNeasy PowerSoil kit. Shotgun libraries were generated using the NexteraXT kit and sequenced on the Illumina HiSeq 2500 using 2x125 bp chemistry. Sequence data were analyzed using the Sunbeam metagenomics pipeline. The abundance of bacteria was estimated using Kraken version 2.0.8. Fecal bile acids will be quantified by liquid chromatography–mass spectrometry (LC-MS). RESULTS/ANTICIPATED RESULTS: Overall bacterial community composition at 12 or 24 months was not associated with antibiotic exposure (PERMANOVA test, Bray-Curtis distance). An increase in Enterobacteriaceae, in particular Escherichia coli, is a signature of antibiotic-induced dysbiosis, but also of early infant gut. Children with antibiotic exposure had slightly higher abundance of Escherichia coli compared to those with no exposure (p = 0.03). At 24 months, the abundance of Bacteroides caccae, a commensal gut species, was decreased for children exposed to antibiotics in the first year of life (fdr = 0.02). We will perform further analysis of bile acid modifying bacteria, fecal bile acid concentrations and correlate to GI symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest a significant but nuanced impact of early life antibiotic use on the composition of the gut microbiota. The association of antibiotic exposure with B. caccae and E. coli warrant further attention in the context of the rapidly developing early-life microbiome. CONFLICT OF INTEREST DESCRIPTION: The authors declare no conflicts of interest relevant to this work.

OBJECTIVES/GOALS: This study aimed to characterize urinary exosomal miRNA content in African American adults with diabetic kidney disease. METHODS/STUDY POPULATION: Male and female participants between the ages of 18 and 65 were recruited from the Diabetes Treatment Center and the Nephrology Clinic at the Howard University Hospital. Exosomes were isolated from cleared urine of healthy controls (n=3), type 2 diabetics (n=3), and participants with chronic kidney disease (n=3). The purity and size of isolated microparticles was evaluated using NanoSight technology (30nm to 120nm size range) and western blot analysis for exosome-specific markers (TSG101 and CD81) RESULTS/ANTICIPATED RESULTS: Expression of 5 selected microRNAs, miR-4534, miR-320c, miR-451, miR-362-3p and miR-877-3p were evaluated by qRT-PCR. miR-4534 and miR-451 was increased between healthy controls and the type diabetic group. MiR-320c was increased in the CKD group, in comparison to healthy controls. Conversely, there was no difference in miR-877-5p between the three groups. DISCUSSION/SIGNIFICANCE: These findings will provide insight into the use of circulating miRNAs as early markers of DKD, ultimately creating more effective treatments and preventive measures.

Underrepresentation of people from racial and ethnic minoritized groups in clinical trials threatens external validity of clinical and translational science, diminishes uptake of innovations into practice, and restricts access to the potential benefits of participation. Despite efforts to increase diversity in clinical trials, children and adults from Latino backgrounds remain underrepresented. Quality improvement concepts, strategies, and tools demonstrate promise in enhancing recruitment and enrollment in clinical trials. To demonstrate this promise, we draw upon our team’s experience conducting a randomized clinical trial that tests three behavioral interventions designed to promote equity in language and social-emotional skill acquisition among Latino parent–infant dyads from under-resourced communities. The recruitment activities took place during the COVID-19 pandemic, which intensified the need for responsive strategies and procedures. We used the Model for Improvement to achieve our recruitment goals. Across study stages, we engaged strategies such as (1) intentional team formation, (2) participatory approaches to setting goals, monitoring achievement, selecting change strategies, and (3) small iterative tests that informed additional efforts. These strategies helped our team overcome several barriers. These strategies may help other researchers apply quality improvement tools to increase participation in clinical and translational research among people from minoritized groups.

OBJECTIVES/SPECIFIC AIMS: We developed a multilevel hierarchical statistical model which describes the association of prophylactic interventions to patient PONV risk, and provides an intuitive summary for anesthesiologists to understand how well they are adhering to PONV guidelines. METHODS/STUDY POPULATION: Accepted PONV risk factors as well as preventative interventions to reduce the PONV risk, (e.g. total intravenous anesthesia or pharmacological prophylaxis) are retrieved from the electronic medical record (EMR). Risk is regressed against interventions. Fig 1, Panel A visualizes adherence for an individual provider by plotting anesthesia cases, with PONV risk in the x-axis and the number of interventions in the y-axis. Fig 1, Panel B shows a “Jitterplot”, jittering individual cases, which would otherwise plot onto the same coordinates (Panel A). The distribution of the number of interventions in each risk category is better summarized in Fig 1 Panel C by overlaying a violin plot onto the “Jitterplot”. Finally, a fitted regression line provides a summary measure for the individual provider’s risk-adjusted utilization of PONV prophylaxis in Fig 1, Panel D. The model can control for confounders and interactions, such as patient or procedure characteristics, such as supervision by attending physicians, institutional culture, and surgical procedure. RESULTS/ANTICIPATED RESULTS: Fig. 2, Panel A demonstrates good adherence. The provider responded to increased risk with additional interventions leading to a steep regression line. Less discriminate administration of prophylaxis is shown in Fig 2, Panel B. The graphical representation of our proposed measure of individual provider performance is intuitive, allowing us to compare adherence of two distinct groups of providers (light lines) and institutional averages (dark lines) as shown in Fig 2, Panel C. Controlling for known risk factors and potential confounders renders the assessment irrepudiable. The rigorous statistical approach allows for multi-level modeling and comparative effectiveness research, realistically evaluating process changes and interventions like CDS in the hierarchical structure of contemporary healthcare delivery. DISCUSSION/SIGNIFICANCE OF IMPACT: The strength of our novel measure of individual provider performance is its generalizability to other care settings, as well as the intuitive graphical representation of risk-adjusted individual performance. However, accuracy, precision and validity, sensitivity to system perturbations (like the implementation of CDS), and acceptance among providers remain to be evaluated. Fig 1. Risk-Adjusted Utilization of Antiemetic Prophylaxis Fig 2. Comparing Performance between Provider Groups

OBJECTIVES/GOALS: Little is known about the effect of hemodilution with crystalloid on blood coagulation in obstetric patients. The purpose of our study was to examine the impact of hemodilution on components of blood coagulation using rotational thromboelastometry (ROTEM®) in term parturients METHODS/STUDY POPULATION: This is a prospective, observational pilot study including 35 healthy, pregnant patients at term (≥37 weeks) without history of bleeding or clotting disorder or on medication affecting coagulation. Venous blood samples were collected from all patients and divided into specimen tubes to generate varying degrees of hemodilution with Plasma-Lyte (0%, 20%, 25%, 30%, 35%, 40%, 45%, 55%, 60%, 65%, 70%, 75%, 80%). Rotational thromboelastometry was then performed on samples to assess for coagulation changes. RESULTS/ANTICIPATED RESULTS: EXTEM (extrinsically activated assay) clotting time (CT) became prolonged at 65% hemodilution and above, and the median CT was in the coagulopathic range (>80 seconds) at a dilution of 80%. FIBTEM (extrinsically activated assay with platelet inhibitor, primarily measuring contribution of fibrinogen to coagulation) amplitude at 5 minutes (A5) began to diminish at 35% hemodilution, with the median A5 in the coagulopathic range (<12 mm) at 55% hemodilution. The area under the curve (AUC), a marker of clot strength, for EXTEM and FIBTEM consistently declined as hemodilution increased. Greater decreases in FIBTEM AUC were seen compared to EXTEM AUC, with the ratio of FIBTEM:EXTEM AUC at each dilution demonstrating a statistically significant difference from baseline. DISCUSSION/SIGNIFICANCE OF IMPACT: All thromboelastometry values demonstrated a hypocoagulable trend as hemodilution increased. However, the samples analyzed by the FIBTEM assay trended toward a coagulopathy at a lower degree of hemodilution compared to the EXTEM assay. As FIBTEM tests analyze the role of fibrinogen in hemostasis and EXTEM tests analyze the role of platelets, our findings suggest that platelets may be able to withstand higher degrees of hemodilution before impairing hemostasis compared to fibrinogen. These findings support the growing body of literature that in early stages of severe obstetric hemorrhage, the prioritization of fibrinogen replacement may be critical in preventing further coagulopathy. CONFLICT OF INTEREST DESCRIPTION: All authors have no conflicts of interest to report.

OBJECTIVES/GOALS: Chronic kidney disease (CKD) impacts 15% of US adults and African American (AA) persons are disproportionately affected with more than 3 times higher risk of kidney failure when compared to Caucasian persons. This study evaluated the physiological and metabolomic effects of increased fruits and vegetables (F&V) on cardio-renal risk factors. METHODS/STUDY POPULATION: This pilot trial used a prospective, 2-group, randomized study design to evaluate a F&V intervention (N=46), where participants received a prescribed amount of fresh, base-producing F&V compared to a wait-list control (WL) condition (N=45). All participants were African American adults (≥18 years), had self-reported hypertension, and had CKD (Stage 1-3) on screening spot-urine microalbumin test. Participants were measured at baseline and 6 weeks post-intervention. Clinical data (i.e., systolic and diastolic blood pressure, lipid panel, hemoglobin A1C, BMI [body mass index], and albumin to creatinine ratio) were collected. Targeted metabolomic quantitative analysis was performed followed by LC-MS/MS and FIA-MS/MS. Linear mixed models evaluated analyte expression and clinical data. RESULTS/ANTICIPATED RESULTS: AA participants (N=91) were aged 58 ± 10.2 years, 66% female, and 54% had incomes ≤$50,000. T-tests compared change scores (baseline to 6-weeks) between groups. The F&V group demonstrated a significant reduction in BMI of -4.7 ± 10.5 kg/m² compared to a 1.9 ± 8.3 kg/m² increase in the WL group, p<.01. Further, the F&V group demonstrated a reduction in total cholesterol of -15.4 ± 58.8 mg/dL compared to a 17.7 ± 68.8 mg/dL increase in the WL group, p<.05. Non-significant reductions in hemoglobin A1c were found in the F&V versus the WL group. Metabolomic analysis indicated significant variation with an increase of suggestive key biomarkers for worse CKD in the WL versus F&V groups at 6-weeks. DISCUSSION/SIGNIFICANCE: Consumption of only 2 cups of F&V via a community-based intervention reduced CVD risk factors in AA adults with CKD and HTN and resulted in molecular/biochemical changes which may improve long-term kidney health. Further investigation may lead to development of cost-effective dietary intervention models to improve CKD outcomes in AA persons.

OBJECTIVES/GOALS: The goal of this study was to examine the change in the odds of being diagnosed with metastatic cancer after the Affordable Care Act (ACA) among low-income, privately insured, nonelderly patients with newly diagnosed cancer. Low-income was defined as having income<250% FPL (federal poverty level). METHODS/STUDY POPULATION: Using Ohio cancer registry data linked with census tract-level income data, individuals aged 18-64 years diagnosed with one of the 15 leading cancers and reported being privately insured or uninsured were identified. Low-income patients were isolated using probability weighting, a process in which each observation was assigned a weight equal to the probability of a patient having an income <250% FPL based on the patient’s census tract of residence. Then, a multivariable logistic model was fitted to examine the independent association between the exposure (Post-ACA, years 2015-2016 versus Pre-ACA, years 2012-2013) and the outcome (metastatic versus non-metastatic disease at diagnosis). RESULTS/ANTICIPATED RESULTS: Between the Pre-ACA and Post-ACA periods, the percent uninsured in the low-income study population decreased from 14.1% to 4.5% (p <0.01). In the Post-ACA period, among those with insurance coverage, an estimated 11.7% of individuals had Marketplace coverage. After adjusting for potential confounders (sex, age, race-ethnicity, marital status, community-level income, rurality, and cancer type), individuals diagnosed Post-ACA had 5% lower odds of having metastatic disease relative to Pre-ACA (Adjusted Odds Ratio: 0.95, 95% Confidence Interval: 0.91 - 0.99, p = 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: The shift towards non-metastatic disease likely reflects increases to coverage brought on by the marketplaces. However, the shift is smaller than those observed in Medicaid enrollees, suggesting that policy refinements in the marketplaces can further improve outcomes in low-income cancer patients.

OBJECTIVES/SPECIFIC AIMS: Inpatient palliative care consultation (PCC) of terminally ill patients has been shown to improve patient’s understanding of their poor prognosis. In heart failure patients, PC improves transfer to hospice (or home with hospice) and decreases readmission rates. In patients with end-stage liver disease (ESLD), factors affecting having PCC has been studied, but the impact of PCC on ESLD readmissions has not been evaluated in a nationwide analysis in the US. In this study, among patients with ESLD, we evaluate the impact of inpatient PCC on 1) 30- and 90-day readmission rates, 2) hospital charges (cost) and length of stay (LOS) during subsequent 30- and 90- day readmission. METHODS/STUDY POPULATION: All ESLD hospitalizations within the first nine months of the National Readmissions Database (2010-2014) were used in this study, to allow up to 3 months to follow up. Frequencies and yearly trends of all-cause 30- and 90-days readmissions, and of PCC referral were computed. A propensity-based greedy-algorithm was used to match (1:1) patients with PCC to those without PCC (no-PCC), to create a pseudorandomized clinical study. Comparing PCC to no-PCC, generalized estimating equations were used to estimate the adjusted odds (AOR) of 30- and 90-day readmissions, and of cost and LOS during subsequent readmissions (SAS 9.4) RESULTS/ANTICIPATED RESULTS: In the United States, from January 1st to September 30th of years 2010-2014, there were 67,271 (approximating 150,396 patients) individual records of ESLD patients who survived index hospitalization. The average annual rate of PCC was 5.4%, which steadily increased from 3.84% to 6.50% over the years (p-trend <0.0001). The average 30- and 90-day readmissions rate were respectively 34.9% and 52.3%, and both remained relatively unchanged over the years (p-trends: 0.1948 & 0.5277). After matching, index PCC was associated with 68% decreased odds for 30 day readmissions (AOR: 0.32[0.28-0.37], p-value < 0.0001). When subsequently readmitted within 30 days, previous PCC resulted in a 17% shorter stay (5.7- vs. 6.9- days, p-value:0.0014) and 30% decreased cost ($47,612 vs. $68,043, p-value:<0.0001). Similarly, index PCC was associated with 74% decreased odds for 90 day readmissions (AOR: 0.26[0.24-0.29], p-value<0.0001). With subsequently readmission within 90 days, previous PCC resulted in a 17% shorter stay (5.7- vs. 6.9- days, p-value:0.0013) and 30% decreased cost ($47,520 vs. $68,016, p-value:<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: Patients with ESLD who received PCC had a significantly lower rate of all-cause 30- and 90- day readmissions, and consumed fewer resources (hospital stay and cost) during subsequent readmissions. Although PCC resulted in a less futile use of health care resources, its adoption is still remarkably low among ESLD patients. Studies are needed to understand the barriers to PCC and to increase its use.

OBJECTIVES/GOALS: The research objectives of this project are to elucidate the effects of Bruton’s tyrosine kinase inhibitors (BTKi) of varying target specificity on platelet function with regard to platelet aggregation, adhesion, spreading, and intracellular signaling as measured by kinase phosphorylation. METHODS/STUDY POPULATION: Blood from healthy volunteers was obtained and processed to obtain both washed platelets and platelet-rich plasma. The samples were then treated with one of the BTKi drugs or with vehicle (DMSO) at concentrations matching patient blood concentrations derived from clinical trials and pharmacokinetic studies. The incubated samples were then analyzed in an aggregometer using one of several agonists. Aggregation was stopped after five minutes with a perchloric acid-based lysis buffer. The samples were then analyzed by SDS-PAGE and immunoblotting to quantify BTK protein and BTK phosphorylation. Adhesion was assessed by incubating washed platelets treated with BTKi on microtiter wells coated with fibrinogen or collagen and quantifying adherent platelets by their endogenous acid phosphatase activity. RESULTS/ANTICIPATED RESULTS: We found that ibrutinib, zanubrutinib, and pirtobrutinib all completely inhibited collagen-induced platelet aggregation, whereas they did not inhibit aggregation induced by thrombin, ristocetin, arachidonic acid, or the PAR1 activator peptide SFLLRN (T6). Acalabrutinib inhibited collagen-induced platelet aggregation only at high concentrations (1-2 micromolar). At the lower concentration of 200 nanomolar, comparable to the concentration required for the other BTK inhibitors to completely inhibit platelet aggregation, acalabrutinib failed to inhibit aggregation but did inhibit auto-phosphorylation, indicating an impact on signaling. None of the BTKi drugs inhibited adhesion of platelets to collagen-coated surfaces. DISCUSSION/SIGNIFICANCE: Our data show the inhibitory effect of BTKi on collagen-induced platelet aggregation and signaling. However, it remains unclear whether the inhibition is due to an effect on BTK itself or other related kinases. Better insight into the mechanisms of platelet inhibition by BTKi may help guide the development of BTKi with a lower risk of hemorrhage.