OBJECTIVES/SPECIFIC AIMS: This study aims to understand the factors influencing engagement with out-patient services from pregnancy to 1 year postpartum among women in recovery from opioid use disorders (OUD). METHODS/STUDY POPULATION: We conducted semi-structured qualitative interviews and a brief survey with 20 mothers in OUD recovery recruited from health care and community organizations in Western MA. Transcripts were coded by two independent coders and analyzed using a qualitative descriptive approach. RESULTS/ANTICIPATED RESULTS: The average duration of any addiction treatment among the 20 participants was 5.6 years with 80% receiving medication-assisted treatment during a pregnancy. Approximately two-thirds experienced relapse during pregnancy or the first year postpartum. We identified 3 themes elucidating women’s experiences around service engagement: “How I see myself” (personal development), “How services see me” (service delivery quality), and “Are you with me?” Personal development included response to past trauma, coping strategies and self-advocacy, and adjusting to parenthood. Service delivery quality was influenced by service design, efficacy of individual providers, and cultural norms (organizational and societal). In the final theme, intersection of individual and service-level factors influenced the degree and quality of the women’s experience engaging with services. DISCUSSION/SIGNIFICANCE OF IMPACT: Women describe successful engagement when they experience service providers as being emotionally supportive, delivering relevant services, and advocating on their behalf. To best support and engage families affected by OUD, relevant and timely services should be linked with compassionate delivery.

OBJECTIVES/SPECIFIC AIMS: Given the poor prognosis of HCC and its increasing incidence worldwide, identifying biomarkers of HCC has been an active area of research. While biomarkers are being identified at a rapid pace, many are still in early phases of clinical study and very few have proven clinical utility. The objective of this study is to identify novel biomarkers of HCC and evaluate their clinical utility as predictors of disease development and prognosis with specific emphasis on disease recurrence after liver transplantation. Biomarkers will be identified through GWAS, as well as through analysis of qualitative and quantitative liver traits by magnetic resonance imaging (MRI). These novel biomarkers will then by implemented into risk prediction models aimed to assess an individual’s risk for development of HCC and stratify their level of risk according to predicted disease prognosis. METHODS/STUDY POPULATION: This will be a case-control study, analyzing data from previously created biorepositories from four cohorts of recipients across multiple centers which have undergone liver transplant. First, a GWAS will be performed to identify genetic variant(s). Second, pre-transplant MRI’s will be evaluated using CAVASS software to assess liver quantitative and qualitative traits, including visceral adiposity. Lastly, these findings will be implemented into risk stratification models to assess each individual’s level of risk for development of HCC and for recurrence of HCC after transplant. RESULTS/ANTICIPATED RESULTS: We hypothesize that genetic variant(s) are associated with positive HCV status and the development of HCC. Additionally, we hypothesize that increased visceral adiposity measured by MRI will have an association with recurrence of HCC after transplant. Lastly, we hypothesize that possession of these aforementioned features will be associated with an increased risk of HCC development and recurrence after transplant. DISCUSSION/SIGNIFICANCE OF IMPACT: As more is learned about the nature and reliability of these biomarkers, their potential clinical applications will be revealed. Ideally these proposed risk score models will ultimately be used by clinicians to provide personalized disease management while optimizing the allocation of health care resources. For instance, this may lead to changes in the MRI screening frequency of patients considered to be at high risk for HCC. The ability to diagnose patients early and provide personalized therapies may ultimately result in fewer disease related mortalities in the future.

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.

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: 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/SPECIFIC AIMS: Hepatitis C virus (HCV) has a high prevalence among individuals in jail and prisons. Access to HCV treatment has been restricted in jails and prisons. We hypothesized that HCV infection in inmates would be associated with increased mortality in people who were hospitalized while incarcerated. METHODS/STUDY POPULATION: We created and then linked a database of people who were incarcerated and admitted at Lemuel Shattuck Hospital (2004, 2008, 2011) to the Massachusetts Vital Statistic Registry (updated through end of 2015). Death was classified using the Automatic Classification of Medical Entry Death Code. The primary outcome of interest was mortality within 1 year of hospitalization, and the secondary outcome was mortality at any time. The primary indicator of interest was HCV, defined as the presence of the ICD-9 code for HCV on discharge. Covariates included in univariate and multivariate modeling included age, year of admission, and race/ethnicity classified as: White, Black, Hispanic or Other (i.e., Asian, Native American, Multi-Racial, or No answer). RESULTS/ANTICIPATED RESULTS: Of the 1,541 hospital admissions, 21% had HCV, and 57% were white, 22% black, 8% Hispanic and 12% other. Of the 273 total deaths (18% of cohort), 82 deaths occurred within 1 year of hospitalization (5.3% of the entire cohort, 30% of all deaths). The primary cause of death was vascular (21%), followed by chronic liver disease (18%), cancer (17%), overdose/suicide/trauma (19%), pulmonary (7%) and infection (6%). People with HCV were more likely to die of chronic liver disease (40% vs 7%, p<0.001). In the multivariable adjusted model, people with HCV were more likely to die within 1 year of hospitalization (HR 1.59, 95% CI 1.02, 2.49) and more likely to die at any time (HR 1.38, 95% CI 1.06, 1.79). Age, race and gender were not associated with risk of death. Compared to 2004, people admitted in 2008 (HR 2.05, 95% CI, 1.50-2.80) and 2011 (HR 4.02, 95% CI 2.77, 5.83) were more likely to die within 1 year. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite advances in HCV treatment in the community, HCV in inmates is associated with increased mortality.

OBJECTIVES/SPECIFIC AIMS: Alcohol use disorder (AUD) has previously been studied using Timeline Followback (TLFB) interview measures and administration of alcohol within laboratory sessions. However, most of those studies supplied alcohol orally and analyzed drinking across a range of drinking intensity and frequency measures. High intensity binge drinking, i.e., drinking alcohol at multiple levels of the binge threshold (5+ drinks for males, 4+ drinks for females) has been identified as a significant risk factor for developing AUD. In the present study, we examined the relationship between high intensity binge drinking with the behavioral and subjective response to intravenous alcohol in a lab study. METHODS/STUDY POPULATION: Two hundred participants completed a 90-Day TLFB interview, wherein the maximum number of drinks in a day established the participant’s binge level status as a Non-Binger (N = 37), Binge Level 1 (N = 96), Binge Level 2 (N = 44), or Binge Level 3 (N = 22). Binge Level 1 corresponds with at least one binge (4-7 drinks for women, 5-9 drinks for men); Binge Level 2 requires at least twice the binge level (8-11 drinks for women, 10-14 drinks for men); and Level 3 necessitates a participant to drink at least three times the binge level (12+ drinks for women, 15+ drinks for men) on one day. Non-Bingers had no binge level drinking in the 90-day interview. Participants also underwent a 150-minute intravenous-alcohol self-infusion, where participants would press a button to receive an infusion of an ethanol solution. During this, participants also completed subjective questionnaires including the Alcohol Urge Questionnaire (AUQ), Biphasic Alcohol Effects Scale (BAES), and Drug Effects Questionnaire (DEQ). Kruskal-Wallis and chi-square tests were used to examine the effect of group on alcohol infusion and subjective response measures. RESULTS/ANTICIPATED RESULTS: A chi-square test for association showed significant statistical differences by groups in reaching binge level status (0.08% breath alcohol content) during the alcohol infusion session in the lab, X2 (3) = 23.321, p < 0.001. However, mean difference was not significantly different between Binge Level 2 and Binge Level 3 (0 < 1 < 2 = 3). Binge level groups showed significant differences in the number of button presses during the lab session (H(3) = 36.955, p < 0.001), peak breath alcohol concentration in the lab session (H(3) = 19.870, p < 0.001), and total binges in the TLFB (H(3) = 90.296, p < 0.001). Increased self-administration measures were proportional to the binge intensity level across groups, with no differences between Binge Level 2 and Binge Level 3 (0 < 1 < 2 = 3). For subjective measures, a Kruskal-Wallis H median test showed statistically significant differences between groups in the AUQ score following the priming infusion, H(3) = 11.489, p = 0.009, with bingers at all levels reporting higher scores compared to non-bingers (0 < 1 = 2 = 3). There was also a statistically significant difference between groups in the BAES Stimulation score following the priming infusion, H(3) = 9.023, p = 0.029, with differences seen between non-bingers and level 2 and level 3 bingers (0 = 1 < 2 = 3). DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrated that high intensity binge drinkers were more likely to reach binge level and overall greater alcohol consumption during a human lab alcohol administration study. Binge intensity level was also associated with higher stimulation and urge for alcohol following priming exposures, which may in turn drive the consumption of greater amounts of alcohol, which we know to be associated with greater risk for AUD.

OBJECTIVES/SPECIFIC AIMS: The primary aim of this study is to conduct a within-child comparison of in-school PA while attending nature-based and traditional preschool programs. The secondary aim is to observe the types of activities performed at each preschool location to determine which activities lead to greater and lesser amounts of school-based PA. METHODS/STUDY POPULATION: This will be a within-subjects repeated measures study in which participants will be recruited from a single preschool program where they spend two days per week (Monday/Wednesday) at a nature-based site, and two days per week (Tuesday/Thursday) at a traditional preschool location. All participants will be outfitted with a waist-worn Actigraph GT3X accelerometer, which they will wear from the moment they arrive to their preschool location until the moment they leave. Measurements will be conducted for four consecutive school days across two separate measurement periods, once in the winter and once in the spring. Additionally, a trained researcher will be present for the entirety of each measured day to document the types of activities participants engage in throughout the day, when these activities occur, and for how long. Accelerometer data will be analyzed using total counts, a reflection of total PA across all intensities, to determine school-based PA. Total activity counts will also be reduced to counts per minute and cross referenced with direct observation data to determine which activities contribute to higher and lower periods of PA throughout the day. Within child comparisons using two-tailed t-tests be made at both measurement periods between both preschool sites to determine whether significant differences in PA levels exist in children while attending either a nature-based or traditional preschool program. Logistic regression will also be applied to assess variables contributing to children’s PA including, preschool location, weather, and time spent outside. RESULTS/ANTICIPATED RESULTS:. It is hypothesized that preschool children will engage in significantly more PA while attending a nature-based preschool program compared to a traditional preschool classroom setting. Opportunities for free and unstructured play will be greater in a nature-based setting compared to a traditional preschool location. Time spent outdoors will be the determining difference between preschool children’s PA behaviors at a nature-based versus traditional preschool program. Variations in PA levels as a result of seasonal weather differences will be minimized on days in which children attend a nature-based preschool program. DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge, this will be one of the first studies conducting a within child comparison of preschool-aged children’s PA levels between a nature-based and traditional classroom setting. If, as hypothesized children engage in significantly more PA while attending their nature-based preschool program, the comparison to their traditional preschool site will provide insight into the magnitude of differences and where these differences in PA behaviors may occur throughout the school day. This information may then be used to inform future intervention’s focusing on better aligning children’s PA levels in a traditional school setting with what might be achieved through a nature-based educational program.

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/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/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/SPECIFIC AIMS: Our primary objectives were to examine the impact of biologic cost sharing on 1) adherence to biologics and 2) persistence on biologics in inflammatory bowel disease (IBD) patients. Our secondary objective was to assess the effect of biologic cost sharing on clinical IBD outcomes, including rates of hospitalization, abdominal surgery, and corticosteroid treatment. METHODS/STUDY POPULATION: This retrospective cohort analysis used a national insurance claims database (Optum Clinformatics DataMart) to assess adult IBD patients enrolled in medium or large private insurance plans from 2007-2016. Patients were followed for one year of continuous enrollment after their index biologic claim. We assessed adherence to biologic medications (medication possession ratio >0.8) dependent on patient cost sharing, as measured by an employer-plan’s average out-of-pocket biologic medication cost. We also examined the effects of patient cost sharing for biologics on need for hospitalization, abdominal surgery, or corticosteroid treatment. We used multivariate logistic regression models adjusting for clinical and demographic characteristics. We estimated the effect of cost sharing on biologic therapy persistence using repeated measures proportional hazard survival models. RESULTS/ANTICIPATED RESULTS: We identified 2,193 adult IBD patients who initiated biologic therapy and met study criteria (Crohn’s disease 66.1% vs. ulcerative colitis 24.9%, mean age 40.8 years, mean Charlson index 0.50). Median [IQR] out-of-pocket cost per 30-day biologic prescription was $62 [$34 - $157]. 66.9% of patients were adherent to biologic therapy. Higher out-of-pocket costs for biologics were associated with increased odds of nonadherence; patients with ulcerative colitis were more price-responsive than patients with Crohn’s disease or indeterminate colitis (Figure 1). However, higher out-of-pocket biologic costs were not associated with increased odds of all-cause or IBD-related hospitalization, IBD-related surgery, or corticosteroid prescriptions for IBD flares. Patients whose out-of-pocket costs were less than $10 per 30-day biologic prescription persisted on biologic therapy for significantly longer than patients who paid >$10 (Figure 2). DISCUSSION/SIGNIFICANCE OF IMPACT: Nonadherence to biologics increases when IBD patients face higher out-of-pocket costs, particularly for ulcerative colitis patients. However, this is not associated with worse clinical outcomes. Patients with cost-sharing<$10 persisted on biologics longer than patients whose cost sharing exceeded $10.

OBJECTIVES/SPECIFIC AIMS: Intrahepatic Cholestasis of Pregnancy (ICP) is the most common liver disease unique to pregnancy. Progression of non-alcoholic fatty liver disease (NAFLD) has been linked to the dysregulation of bile acid homeostasis. However, an association of NAFLD with ICP has not been previously evaluated. We evaluated the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. METHODS/STUDY POPULATION: A single-center, retrospective case-control study was conducted between January and December 2017 in a primarily Latina population in a New York City health system with a high prevalence of ICP, 2.53% of all pregnancies (compared to 0.32% nationally). Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests were performed to evaluate association of ICP with categorical variables and continuous variables, respectively. Unadjusted odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in comparison with the control group for clinically significant outcomes. RESULTS/ANTICIPATED RESULTS: 149 pregnancies complicated by ICP were identified from electronic medical records; 200 controls were matched by delivery year. Hispanic women were more likely to be diagnosed with ICP than non-Hispanic women (OR 1.90, 95% CI 1.87-3.03). ICP and control patients were similar for: median age (OR 1.02, 95% CI.99-1.06), nulliparity (OR.79, 95% CI.48-1.30) and prevalence of hepatitis C (OR 1.35, 95% CI.08-21.67). In regards to metabolic risk factors, ICP patients and control patients were similar in prevalence of obesity (body mass index>30kg/m^2; OR 1.01, 95% CI.62-1.61), hemoglobin A1c>5.5% (OR.80, 95% CI.34-1.9), total cholesterol >200 mg/dL (OR 4.15, 95% CI.83-20.84), and prevalence of hypertension (OR.69, 95% CI.31-1.52). Median bile acid levels were 30.6 µmol/L (IQR 11.6, 32.7) in the ICP group. ICP patients had higher median alanine aminotransferase (ALT) (32 vs. 16 U/L, p<.0001), alkaline phosphatase (181 vs 128 U/L, p<.0001) and total bilirubin levels (0.5 vs 0.35, p<.0001) compared to controls. ICP patients were more likely to have ALT levels > 50 U/L (2 times the upper limit of normal; OR 3.22, 95% CI 1.48-7.03). ICP patients were significantly more likely to have a history of biliary disease (OR 3.29, 95% CI 1.39-7.80). ICP patients were more likely to have evidence of steatosis on liver imaging (OR 4.69, 95% CI 1.68-13.12) than non-ICP patients. When evaluating a diagnosis of NAFLD based on ICD-10 code or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR 5.7, 95% CI 2.08-15.65). DISCUSSION/SIGNIFICANCE OF IMPACT: ICP appears to be associated with NAFLD independently of metabolic risk factors such as obesity, dyslipidemia, hypertension, and diabetes, suggesting a direct link between NAFLD and ICP. If findings are confirmed, ICP patients, especially those with elevated ALT, would benefit from screening for NAFLD and linkage to liver specialty care postpartum.

OBJECTIVES/SPECIFIC AIMS: The study aims to determine the baseline knowledge, attitudes and practices of the professionals (i.e., doctors and nurses) that provide the end-of-life care at an acute community hospital. By obtaining information on what is known, what is believed and what is done by doctors and nurses in end-of-life care, we can identify needs, problems, barriers and possible solutions. METHODS/STUDY POPULATION:. Develop a questionnaire in Spanish addressing knowledge, attitudes and practices about end-of-life care in an acute hospital, define the survey objectives, and develop the survey protocol. o To validate the pertinence and usefulness of each questionnaire item, a panel of experts in palliative and end-of-life care will be consulted. o To finalize the questionnaire, it will be pre-tested with a small number of healthcare providers randomly selected from the survey’s intended population. Implement the questionnaire to doctors/nurses providing direct end-of-life care by purposeful sampling at an acute community hospital. o Beforehand, survey interviewers will be recruited and trained. Perform quantitate and qualitative analyses o Answers to closed-end questions and quantitative data will be tallied using Microsoft Excel and analyzed using STATA statistical software. o Relationship between the participant’s characteristics and their knowledge, attitudes and practices will be assessed using chi-square test. o Answers to open-ended questions in the questionnaire will be collected, analyzed based on their content, and placed in more comprehensive categories by NVivo software. RESULTS/ANTICIPATED RESULTS: It is expected to capture variations and/or consistencies in the amount of knowledge, the type of attitudes and the actual practices among and within physicians and nurses on end-of-life care in a community acute hospital. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed research is expected to contribute key information from the perspectives of physicians and nurses who deliver end-of-life care in an acute community hospital in Puerto Rico. This contribution is significant because it will serve as the platform to develop culturally-appropriate educational/training materials and, subsequently, implement culturally-responsive guidelines for the care of seriously ill Hispanics, with the expectation of improving their quality of life, and perhaps reducing their medical care costs.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the potential immunomudualtory effect of APOL1 variants in auto-antigen activated myeloid cells by assessing lysosomal integrity in activated cells expressing APOL1. The primary stimuli were: 1. ssRNA hY3 as a proxy for the Ro immune complex; 2. in an bulk RNA seq model, interferon-response gene, Siglec 1, as a read out of interferon activity. The primary outcomes were: 1. Myeloid cell APOL1 expression both in primary macrophage cultures and ex-vivo patient derived macrophages; 2. Lysosome integrity as measured by fluorescence intensity of lysotracker dye on light microscopy. METHODS/STUDY POPULATION: All recruited subjects provided written informed consent as per the NEW YORK UNIVERSITY Division of Rheumatology-wide Specimen and Matched Phenotype Linked Examination (SAMPLE) protocol. Subjects were African American; SLE subjects met 4 American College of Rheumatology criteria for SLE. Healthy donor monocytes representing each genotype in duplicate (reference allele: G0/G0; heterozygote variant: RV/G0; and homozygote variant RV/RV) were cultured with GM-CSF to yield macrophages which were incubated in serum free media or with hY3 ssRNA (TLR 7/8 agonist) to yield inflammatory M1 macrophages. Fold increase of APOL1 in untreated vs hY3 treated macrophages was measured using qPCR. Live cells were then cultured on glass chamber slides with DNA dye, DAPI, and Lysotracker red, a fluorescent dye that stains acidic lysosomes. As a proof of concept, interferon response gene, Signlec1, and APOL1 transcriptional activity in peripheral blood monocytes (PBMCs) were measured and correlated in 17 SLE patients by RNA seq. RESULTS/ANTICIPATED RESULTS: Regardless of genotype, hY3 increased APOL1 expression by 29 (+/−18.4) fold (P = 0.007 vs no treatment). Genotyping of the qPCR product showed concordance with the chromosomal DNA with the RV heterozygotes expressing both alleles. To examine lysosomal membrane integrity, live hY3-treated macrophages were stained with lysosotracker dye and fluorescence intensity was measured. Compared to reference allele carrying macrophages, each additional variant allele corresponded with a lesser degree of lysosome compartment staining. In SLE PBMCs, we found that APOL1 was highly expressed, and significantly correlated with Siglec1 (F=10.5; P = 0.005) supporting an association between circulating interferons and APOL1 accumulation in monocytes. DISCUSSION/SIGNIFICANCE OF IMPACT: Given that the “cytokine milieu” in SLE elicits APOL1 expression, induces inflammatory cell metabolic rewiring, and stimulates autophagy thereby exposing defects in autophagic flux, this gene-environment interaction may underpin the relationship between chronic inflammation and heightened APOL1 polymorphism-attributed cardiovascular risk. These data support further inquiry into the intersection between chronic autoimmunity and APOL1’s functional role in the vascular microenvironment. The in vitro studies herein extend our prior work by demonstrating a mechanistic link between SLE-associated inflammation, APOL1 risk variant status and CVD via a lysosomal defect which converges on common autophagic and metabolic pathways in mononuclear cells.

OBJECTIVES/SPECIFIC AIMS: Anxiety is prevalent in early childhood and, when left untreated, increases children’s risk for chronic anxiety and depression later in life. Maternal risk factors (e.g. income and marital status) have also been shown to heighten their children’s risk for the development of the aforementioned psychopathology. Sleep plays a critical role in behavior regulation, is affected in depression, and is influenced by a wide range of demographic and psychological variables. The purpose of this study was to examine the relationship between maternal sleep and the presence in their children of reported symptoms relating to anxiety, depression, and behavior regulation. METHODS/STUDY POPULATION: Children (n=59, aged: 4-9 years (M = 6.069, SD = 1.006, 59.3% female) and their mothers were sampled from clinic and community settings and were administered questionnaires. Maternal sleep quality was assessed by the Pittsburgh Sleep Quality Index, which captures both numeric and self-reported categories relating to an individual’s perception of their sleep. Child anxiety and depression were assessed via parent-reported Child Behavioral Checklist (CBCL). Maternal depression symptoms were assessed with the Beck Depression Inventory (BDI). Associations between these measures were analyzed by ANOVA with post-hoc analysis and linear regression as appropriate. RESULTS/ANTICIPATED RESULTS: A statistically significant difference was observed in the mean child CBCL scores when children were sub-set into maternal categories of self-reported days of dysfunction due to sleepiness over the past month. Mean child CBCL T-score domains with statistically significant differences were: attention problems (F = 4.935, p = 0.004), depression problems (F = 3.073, p = 0.035), ADHD (F = 4.422, p = 0.007), oppositional defiant (F = 2.865, p = 0.045), and total t-score (F = 3.073, p = 0.035). Maternal mean DBI scores were also statistically significantly different when grouped by days of maternal dysfunction due to sleepiness (F = 9.791, p < 0.001). There was no relation between these CBCL categories and maternal DBI scores. DISCUSSION/SIGNIFICANCE OF IMPACT: Maternal self-reported days of dysfunction due to sleepiness may potentially increase risk for their children to develop further psychopathology independent of mothers’ depression symptomatology. These findings highlight the need for broader assessment clinically of children’s environments with additional focus on maternal function given the potential impact on their children’s functional outcomes.

OBJECTIVES/SPECIFIC AIMS: The study aims to measure the associations between nonclinical factors and the likelihood of electing contralateral prophylactic mastectomy [(CPM) i.e. bilateral mastectomy for unilateral cancer] among women with breast cancer, with a focus on the roles of race, relationship status, and geographic location. The outcome of interest is a dichotomized surgery type variable (i.e. CPM versus other surgery). METHODS/STUDY POPULATION:. The Surveillance, Epidemiology, and End Results registry was queried to identify female breast cancer patients diagnosed at stage IA through IIIC from 2010 through 2015 and received surgery as part of their primary treatment (n=174,776). A multilevel logistic regression was used to model likelihood of CPM versus less aggressive surgical treatment (i.e. breast conserving surgery or unilateral mastectomy). Fixed-effects included age at diagnosis, race, relationship status, insurance type, county-level median income, county-level population density, stage at diagnosis (low-stage, IA-IIB; advanced-stage, IIIA-IIIC), an interaction term between race and stage at diagnosis, and breast tumor subtype. County of residence was used as a random-effect. RESULTS/ANTICIPATED RESULTS: Among women with low-stage cancer, compared to the reference class of white women, black women had 0.57 times lower odds of CPM (p<0.0001), Hispanic women had 0.69 times lower odds of CPM (p<0.0001), and Asian women had 0.60 times lower odds of CPM (p<0.0001). Among women with advanced-stage cancer, compared to white women, black women had 0.42 times lower odds of CPM (p<0.0001), Hispanic women had 0.51 times lower odds of CPM (p<0.0001), and Asian women had 0.45 times lower odds of CPM (p<0.0001). Compared to the reference class of single, never-married women, divorced/separated women had 1.25 times greater odds of CPM (p<0.0001), widowed women had 1.11 times greater odds of CPM (p=0.009), and married/partnered women had 1.18 times greater odds of CPM (p<0.0001). County-level variation from the random-effect (MOR, 1.49; p<0.001) had a greater influence on CPM election than fixed-effects for insurance class, breast tumor subtype, county median income, county population density, and year of surgery. DISCUSSION/SIGNIFICANCE OF IMPACT: The nonclinical factors associated with variation in breast cancer surgical decision-making suggest patients and providers both may benefit from further education about surgical treatment options. Providers may also benefit from educational materials that highlight treatment selection disparities within specific contexts, such as surgery for primary unilateral breast cancer. To more narrowly tailor future policy interventions, an additional mixed-methods exploration is recommended to clarify how relationship status and location serve as mechanisms for breast cancer decision-making.

OBJECTIVES/SPECIFIC AIMS: Examine data from PNID patients to evaluation the strength of associations between pre-operative and post-operative levels of pain, quality of life, and emotional reactions to pain to determine if one or more can serve as better predictors of surgical success than pain. METHODS/STUDY POPULATION: In our preliminary study, we gathered data from a pre-existing database of 464 PNID patients that contains self-reported visual analog scale scores (VAS) of pain intensity, QoL, and depression. We measured these variables at three time points: pre-operatively, post-operatively, and at the final visit. We used the Wilcoxon signed rank test to determine if each of these three variables differed significantly between the pre-operative visit and the post-operative visit period and from the pre-operative visit to the final visit. RESULTS/ANTICIPATED RESULTS: Median time from the pre-operative visit to surgery was 9 weeks; median time from surgery to the post-operative visit was 4 weeks; and median time from the post-operative visit to the final visit was 23.5 weeks. There was a clinically meaningful difference in pain scores between the pre-operative and post-operative visits (median difference 1.15; 95% CI 0.75-1.55). In the period between the post-operative visit and the final visit there was also a decrease in pain (0.90; 95% CI 0.55-1.30). The magnitude of change in median difference of 1.85 (95% CI 1.50-2.20) between the pre-operative visit and the final visit was larger than the change in median difference of 0.90 (95% CI 0.55-1.30) between the post-operative visit and the final visit. The pre-operative visit median QoL score was higher than the median score at the post-operative visit (1.65; 95% CI 1.25-2.10). The smallest median difference in QoL of occurred between the post-operative and the final visit (1.10; 95% CI 0.60-1.45). As seen with the pain scores, the magnitude of change in median difference of 2.50 (95% CI 2.20-2.85) for QoL was greatest between the pre-operative and the final visit. Depression scores showed the least amount of change amongst all the variables, between the pre-operative and the post-operative visit (1.00; 95% CI (0.70-1.40), and similarly between the post-operative visit and the final visit (0.15; 95% CI (0-.40). The median differences between the pre-operative and final visit were greatest in QoL (2.50; 95% CI 2.20-2.85), followed by pain scores (1.85; 95% CI 1.50-2.20), and finally, depression (1.05; 95% CI 0.70-1.40). DISCUSSION/SIGNIFICANCE OF IMPACT: Our results show that all three variables measured improve with surgery and continue to improve over the post-operative course to the final visit. This suggest that the relationships between pain, QoL, and depression should be further investigated. We are hopeful that elucidating how these variables interact in the PNID patient population, will encourage peripheral nerve surgeons to use these parameters in conjunction with pain intensity to measure outcomes. A follow-up study expanding on these results and including measures of anger and frustration in a larger sample is underway.

OBJECTIVES/SPECIFIC AIMS: Objective: Identify barriers and facilitators of positive patient-provider interactions for AAN patients. METHODS/STUDY POPULATION: Methods: Using a mixed-methods, longitudinal, patient-interview design, N = 29 (to date) women with a history of AAN have been enrolled. Each patient completed a diagnostic interview and standardized surveys to establish ED diagnosis, severity, and associated psychopathology. Transcribed, semi-structured qualitative interviews are assessed for common themes using content analysis methods. RESULTS/ANTICIPATED RESULTS: Anticipated Results: Patients aged 18 to 74 (M = 36.3, SD = 12.0), with mean BMI = 39.8 (22.7-61.1; SD = 11.3), and mean weight suppression (lbs) during their illness = 119.41 (SD = 69.3). Women reported a mean=12.75 years (0-37 years, SD = 10.5) treatment delay. Qualitative analysis revealed the following barriers in healthcare provider interactions: 1) experiences of provider weight-bias, 2) low specificity in ED screening questions, 3) lack of indicated screening procedures/diagnostic tests (orthostatic screening, EKG, food log, labs), and 4) provider praise of ED behaviors. Facilitators: 1) lower BMI at presentation, 2) provider education in EDs, 3) community-provider collaboration, and 4) patient self- and family- advocacy. DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: Unfortunately, while early intervention best predicts positive outcomes, higher-weight patients in this study experienced significant treatment delay. Translationally, it is taking too long for AAN patients to receive the right treatment at the right time. However, findings indicate that interventions at the provider level (increasing ED education, building community partnerships, increased adherence to screening protocols) could improve screening, diagnostic, and referral practices—and ultimately long-term outcomes for this unique patient population.

OBJECTIVES/SPECIFIC AIMS: The accurate and efficient serial measurement of patient centered outcomes is a priority in the clinical care of systemic lupus erythematosus (SLE). Patient-Reported Outcomes Measurement Information Systems (PROMIS®) Global Health Short Form (PROMIS10) is a 10-item universal patient reported outcome measure of global physical and mental health with construct validity in SLE. The longitudinal responsiveness (sensitivity to change) of PROMIS10 in SLE patients is unknown. We aimed to evaluate the responsiveness of PROMIS10 in SLE outpatients using patient and physician-derived anchors. METHODS/STUDY POPULATION: Adults meeting SLE classification criteria were recruited from an SLE Center of Excellence. Subjects completed PROMIS10 at two visits a minimum of one month apart. SLE disease activity was measured with a patient global assessment of change, a physician global assessment and the physician-derived SELENA-SLEDAI. Responsiveness over time of PROMIS10 scores was evaluated using known-groups validity. Effect sizes of changes in PROMIS global physical health and global mental health scores from baseline to follow up were compared across groups of patients who differed in their patient global assessment of change, physician global assessment, and SELENA-SLEDAI using Kruskal-Wallis tests. RESULTS/ANTICIPATED RESULTS: A diverse cohort of 228 SLE patients completed baseline surveys (Table 1), with 190 (83%) completing a follow up survey. Using the patient-based anchor, PROMIS10 demonstrated mild to moderate responsiveness to improvement (effect size 0.29) and worsening (effect sizes −0.27 and −0.54) of health status for both global physical health and global mental health (Table 2). Using the physician global assessment and SELENA-SLEDAI as anchors, there were no statistically significant differences in effect sizes across groups. DISCUSSION/SIGNIFICANCE OF IMPACT: PROMIS10 showed responsiveness over time to patient-reported, but not physician-derived changes in lupus health status. These data suggest that PROMIS10 can be used to efficiently measure and monitor important aspects of the patient experience of lupus not captured by physician-derived metrics. Further studies are needed to evaluate the role of PROMIS in optimizing longitudinal disease management in SLE.