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/GOALS: Hepatitis B and C virus causes inflammation of the liver and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. The aim of this study is to generate a modeled estimate of changes in hepatitis B and C prevalence, and future sequelae, that accounts for recent mass migration to the European Union stemming from 50 high-emigration countries. METHODS/STUDY POPULATION: Total migrant population from 2013-2017 was obtained from the Eurostat population database. Demographics including country-of-origin, sex, and age distributions were used to determine migrant contributions to HBV and HCV prevalence where available. Undocumented migration estimates were obtained from the Institute of Migration database. Country-of-origin HBV and HCV prevalences were obtained for the select 50 country-of-origin nations from the Polaris Observatory and from systematic reviews. Disease progression was estimated using HBV and HCV outcome data for total populations from treatment guideline publication from the European Association for the Study of the Liver. RESULTS/ANTICIPATED RESULTS: Between 2013 and 2017, a total of 11,030,786 documented migrants born outside the EU arrived to the 30 nations. Germany, United Kingdom, and Spain received the greatest influx of persons and the majority of migration stemmed from countries in West Asia, the Middle East, and Africa. A significant proportion of total migration was driven by conflict-related crisis in Syria, and East and North Africa. The most significant increases in estimated total hepatitis case numbers, national prevalence increases, and future sequelae were seen in Germany and Sweden. DISCUSSION/SIGNIFICANCE OF IMPACT: Mass migration has significantly changed HBV and HCV disease burden in Europe over the past 5 years. Consequently, long-term outcomes of cirrhosis and HCC are also expected to increase. These increases are likely to disproportionally impact individuals of the migrant and refugee communities. HBV and HCV surveillance and management programs must strategically focus on individuals from high-burden age cohorts and nations. Screening and treatment would aid WHO elimination efforts while benefiting both the vulnerable individuals and host nations through reduction of morbidity, mortality, and associated healthcare expenses.

Objectives/Goals: Our aim is to compare scores collected from a health utilities measure (Health Utility Index, HUI) to those collected from a profile measure (Child Health Ratings Inventories, CHRIs- Global) among youth with newly diagnosed, high-risk classic Hodgkin lymphoma. Methods/Study Population: We will analyze existing data collected during the Children’s Oncology Group AHOD 1331 trial, which was a phase 3 clinical trial comparing the efficacy of adding brentuximab vedotin to standard-of-care treatment with multiagent chemotherapy in children and adolescents with high-risk Hodgkin lymphoma. The study also had a prespecified patient-reported outcomes (PRO) secondary aim, which involved recruiting a subset of the initial 309 patients aged 11 years or older enrolled in the trial for serial PRO measures taken over the trial period. Health-related quality of life (HRQoL) was assessed by CHRIs, HUI version 2, and HUI version 3 assessments at six planned points throughout treatment. Results/Anticipated Results: The first step of our analysis will be to ascertain agreement in scoring for parent–child dyads for the HUI2, HUI3, and CHRIs scores by comparing mean scores via two-sample t-testing. Bland–Altman plots will be constructed to compare agreement between the scores for HUI2/3 and the CHRIs. Similarly, Spearman’s correlation coefficients will be calculated for CHRIs with HUI2/3 for both parents and children. We hypothesize the CHRIs and HUI scores should roughly correlate with one another, but there may be divergence of correlation because the HUI has greater emphasis on functionality (e.g., sensation, mobility), and the CHRIs further emphasize social and emotional well-being in addition to physical health. Discussion/Significance of Impact: The composite score of the HUI 2/3 has allowed for direct comparison with other global HRQoL measures, providing greater clarity of its performance in different patient populations and clinical settings. The current study will improve understanding of the HUI 2/3 performance in a pediatric cancer population over time.

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/GOALS: Provider and hospital factors influence quality, but granular data is lacking to assess their impact on renal cancer surgery. The Maryland Health Service Cost Review Commission (HSCRC) is an independent state agency that promotes cost containment, access to care and accountability. Within HSCRC, we aimed to assess the impact of surgeon and hospital volume on 30-day outcomes after renal cancer surgery. METHODS/STUDY POPULATION: Data on renal surgery were abstracted from the Maryland HSCRC from 2000-2018. We excluded patients younger than 18, patients without a diagnosis of renal cancer, and patients concurrently receiving another major surgery. Volume categories were derived from the distribution of mean cases performed per year. We used adjusted multivariable logistic and linear regression models to identify associations of surgeon and hospital volume with the length of stay, days in intensive care, cost, 30-day mortality, readmission, and complications. RESULTS/ANTICIPATED RESULTS: A total of 10,590 surgeries, completed by 669 surgeons at 48 hospitals, met criteria. The 25th percentile for cases per year was 1, the 50th percentile was 1.2, and the 75th percentile was 2.6. After adjusting for patient factors and cumulative surgeon experience, high volume surgeons had the greatest decrease in length of stay (β: −1.65, P<0.001) and mortality risk (OR: 0.27, 95% CI: 0.10-0.71) compared to rare volume surgeons. Low volume surgeons had the greatest cost decrease (β: -$7,300, P<0.001) compared to rare volume surgeons. Medium volume hospitals had statistically lower average costs than rare volume hospitals (β: $−2,862, P = 0.005). There were no other clinically and statistically significant relationships between volume and measured outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: Almost half of the urologists studied performed an average of one renal cancer case per year. Greater surgeon volume was associated with shorter length of stay and decreased mortality risk. Hospital volume did not have a meaningful relationship to outcomes. Other factors such as tumor, surgeon, and hospital characteristics or case-mix may associate with outcomes and could be confounders.

OBJECTIVES/GOALS: Maternal mental health, such as post-traumatic stress disorder (PTSD), is closely linked to child mental health. PTSD in mothers is associated with their children’s emotional responses. We examined associations between maternal PTSD and child brain function during emotion regulation. METHODS/STUDY POPULATION: Eight children ages 10-12 years, whose mothers had trauma histories, performed the Emotional N-Back task during functional MRI scanning. Mothers and children each reported on their trauma exposure and PTSD symptom severity. BOLD response to fearful faces during the Emotional N-Back was extracted from two specific brain regions of interest, amygdala and anterior cingulate cortex. These regions are involved in emotional response and attentional control, which are processes intrinsic to emotion regulation. An independent samples t-test was conducted on children’s BOLD response to fearful faces, with maternal PTSD symptom severity (high, low) as the independent variable. A parallel analysis was conducted with child PTSD symptom severity (high, low) as the independent variable. RESULTS/ANTICIPATED RESULTS: We found a main effect of maternal PTSD within brain regions of relevance to implicit emotion regulation. Compared to children whose mothers reported low PTSD symptom severity (n=4), children whose mothers reported high PTSD symptom severity (n=4) showed greater responsiveness to fearful faces in anterior cingulate cortex (t=2.04, p=.09,d=1.44) and amygdala (t=2.44, p=.05, d=1.72) at trending significance. A parallel analysis with child PTSD symptom severity showed no differences in brain function by this factor (ps=.55-.61). DISCUSSION/SIGNIFICANCE: Our pilot study is the first, to our knowledge, to examine associations between maternal PTSD and brain function during emotion regulation in their children. This study lays a foundation for future work; our goal is to explore dysfunction in emotion regulation neurocircuitry as one mechanism linking maternal PTSD to their children’s mental health.

OBJECTIVES/GOALS: The major obstacle to an effective cure or remission for HIV infection is the integration of HIV into the genome of long-lived resting cells which constitute the so-called viral reservoir. With this study we want to elucidate the changes of the gut-associated HIV reservoir at different stages of viral suppression METHODS/STUDY POPULATION: Recent studies have shown that after long-term (>7 years) clinical suppression of peripheral HIV RNA, the circulating viral reservoir does not seem to decline further and, in fact may expand. The gastrointestinal associated lymphoid tissue (GALT) harbors by far the largest fraction of the latently infected cells, however not much is known about its changes over time.We thus quantified the HIV viral reservoir in the GALT by identifying HIV viral transcripts via 10X single-cell RNA sequencing at two GALT-sites in five PWH and compared the amount of HIV RNA found in the group of PWH with early (< 7years) vs late (> 7years) peripheral virological suppression (plasma HIV RNA <20copies/mL). RESULTS/ANTICIPATED RESULTS: Study participants had been diagnosed with HIV infection for a median (IQR) of 31 (32-34) years and had consistently undetectable peripheral blood HIV RNA for the previous 8 (4-15) years. In PWH with consistent viral suppression < 7yrs, 4 (2-6) HIV transcripts were identified in the ileum and 25 (13 – 38) in the colon. In PWH with consistent viral suppression > 7yrs, 0 (0-4) HIV transcripts were identified in the ileum and 7 (14-11) in the colon. Based on these preliminary results we plan to expand our cohort and confirm these results using Proviral DNA quantification. We anticipate that the viral decay in the GALT will follow a slower dynamic than what has been reported for the peripheral blood achieving a steady state after more than 7 years of peripheral viral suppression. DISCUSSION/SIGNIFICANCE: Despite the remarkable progress the survival and quality of life of PWH, after forty years from its first discovery, HIV infection remains uncurable. Considering its critical role, efforts are needed to better understand the dynamics of the GALT-associated HIV reservoir.

Objectives/Goals: To use patient-level Center for Medicare and Medicaid Services (CMS) mandated quality metrics for inpatient rehabilitation facilities (IRFs) to develop and validate predictive models of functional recovery and interactions of baseline characteristics with therapy time. Methods/Study Population: Retrospective cohort study of a national US sample of ~40,000 adults with a primary diagnosis of stroke admitted to IRFs in 2023. Records will be randomly allocated to equal training and validation samples. We will use a random forest approach to generate predictive models for self-care and mobility functional outcomes using patient baseline and demographic data from a CMS-mandated assessment for IRFs (Section GG). We will also examine how predictive variables modulate the effects of occupational, physical, and speech-language therapy minutes. The random forest is a machine-learning approach that trains multiple models and combines their predictions to improve their overall performance. Results/Anticipated Results: Predictive models developed from the training sample will be applied to the validation sample to confirm their capacity to support new observations. Preliminary results will be reported, including the F1 score and area under the curve (AUC), with 95% confidence intervals. A unique feature of this study is the large sample, which contrasts with prior research in stroke rehabilitation using machine learning approaches. This study will produce powerful models that will inform the design of a clinical decision-support tool for application into clinical practice in a future study. Discussion/Significance of Impact: By using CMS-mandated quality metrics that are collected as part of standard clinical practice in IRFs, results will support clinical interpretation and application of metrics and inform the development of a clinician-facing intervention to support personalized rehabilitation approaches.

Objectives/Goals: Accurately stratifying patients with clinically isolated syndrome by risk of developing multiple sclerosis is of great clinical importance. Though numerous prediction models attempt to achieve this goal, no systematic review exists to independently evaluate these models. We aim to systematically identify and assess the risk of bias in all such models. Methods/Study Population: Studies developing or validating prediction models to assess risk of developing MS in patients with CIS who are not receiving an MS-indicated disease-modifying therapeutic will be identified via a systematic literature search. Studies will be evaluated for overall risk of bias using PROBAST (Prediction model Risk Of Bias Assessment Tool). Briefly, data sources, predictor, and outcome definition and assessment, applicability, and analysis will be assessed for each model in each identified study, and an overall risk of biased judgment will be assigned. Identified studies, predictors incorporated, results, and risk of bias assessment with accompanying rationale will be summarized in the final report. Results/Anticipated Results: Based on an initial exploratory search, we anticipate that most, if not all, identified prediction models will have high risk of bias. We anticipate that many studies will have limited applicability due to the use of outdated diagnostic criteria for definition of outcomes, or high risk of bias concerns originating from their analysis due to insufficient volume of included participants or poor model validation practices. We further anticipate that most, if not all, of the identified prediction models will have limited potential to be translated to use in a clinical setting. Discussion/Significance of Impact: Understanding how to identify patients with high-risk CIS may inform and improve clinician treatment decisions, patient outcomes, and future research study design. This work may also reveal flaws in current prediction models for CIS, opening new avenues of research and prompting development of improved prognostic models for patients with CIS.

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/GOALS: The new Kidney Allocation System (KAS) was implemented in 2014 and it is not fully understood how its changes to patient incentives may have impacted dialysis facility waitlisting rates. We examine differences in facility performance and how such differences may have been impacted by this policy change. METHODS/STUDY POPULATION: We used Dialysis Facility Report data from 2011 to 2017 to study waitlisting rates at 3,392 dialysis facilities in the US, using waitlisting counts in the numerator, and the total number of ESRD patients in a facility as the denominator. We examined changes in waitlisting rates over by year at the facility, regional, and national level, and report national trends in waitlisting pre- and post-KAS. Facilities were stratified based on waitlisting rate in 2011 and then we examined whether each facility moved into a higher or lower quartile or stayed in the same quartile in 2017. RESULTS/ANTICIPATED RESULTS: Among n = 3,392 dialysis facilities, the average change in dialysis facility waitlisting rates from 2011 to 2017 was −4.74 percentage points (range -54.4% to 42.3%). Average change in dialysis facility waitlisting rates from 2011 to 2014 was −0.57 percentage points while the average change in dialysis facility waitlisting rates from 2014 to 2017 was −4.17 percentage points. Half of facilities in the 2011 lowest quartile remained in the lowest quartile in 2017; 45% of facilities in the top 2011 quartile dropped into a lower quartile. The middle 2 quartiles were fairly evenly split between worsening, improving, and not changing. DISCUSSION/SIGNIFICANCE OF IMPACT: Average waitlisting rates have declined since KAS implementation. Many facilities switched quartiles from 2011-17 suggesting that facility waitlisting rates are unstable over time. The decline in waitlisting rates post-KAS suggests that new allocation rules may be discouraging patients and/or providers from getting ESRD patients waitlisted.

OBJECTIVES/GOALS: The goal of this project is to characterize the efficacy of FOXA2 as a potential biomarker for patients with metastatic castrate-resistant prostate adenocarcinoma (CRPC) before transitioning to neuroendocrine prostate cancer (NEPC). NEPC currently has no therapeutic options and poor mechanistic understand of its origins. METHODS/STUDY POPULATION: In our study, we have utilized a multi-omics approach to characterize the potential efficacy of FOXA2 as a prognostic biomarker in numerous patient-derived castrate-resistant prostate cancer (CRPC) models. We have performed ATAC-, ChIP-, RNA-seq and proteomics to fully characterize where FOXA2 is binding genome-wide, how FOXA2 alters chromatin accessibility dynamics, identify regulatory gene targets of FOXA2, and identify FOXA2 protein-protein interactors. We have supported these findings using publicly available data from independent CRPC and NEPC patient cohorts and prostate cancer cell models. RESULTS/ANTICIPATED RESULTS: Our findings show that FOXA2 overexpression suppressed androgen signaling and promoted progression to a NEPC phenotype under short- and long-term androgen deprivation conditions, respectively. Further, FOXA2 redirected the chromatin accessibility landscape to be consistent with an NEPC gene expression program, including increased chromatin accessibility for key NEPC transcription factors. FOXA2 ChIP-seq showed FOXA2 to be bound at known NEPC driver genes and epigenetic modifiers across multiple stages of prostate cancer progression. Lastly, we discovered that FOXA2 physically interacts with key NEPC TFs and epigenetic regulators, suggesting that these FOXA2 physical interactions are required for NEPC progression. DISCUSSION/SIGNIFICANCE: This project will determine the efficacy of FOXA2 as a biomarker in advanced prostatecancer samples, which will translate as a potentially useful tool for clinicians to use for treatment of advanced prostate cancer patients.

The All of Us Research Program is an historic effort to gather data over 10+ years from one million or more people living in the United States to accelerate research and advance precision medicine. There is a particular focus on populations historically underrepresented in biomedical research who are often served by Federally Qualified Health Centers (FQHCs). However, FQHCs face significant challenges in participating in research. This paper addresses three common barriers faced by FQHCs and describes a management model that was used to support a group of FQHCs participating in the All of Us Research Program. Specifically, the paper addresses the challenges of building FQHC research capacity to operationalize and manage research activities, transforming and sharing Electronic Health Records and other data, and recruiting and retaining research participants. The central coordination management model, which was used to support the FQHCs, is a generalizable framework and can serve as an exemplar of how to engage FQHCs in other longitudinal research efforts. To date, the FQHCs have enrolled more than 10,000 participants in the All of Us Research Program. Their success is an indicator that with the proper support, FQHCs can successfully implement a complex biomedical research program in the context of their health centers.

Commercializing biomedical discoveries is a challenging process for many reasons. However, Academic Medical Centers (AMC) that have teaching, patient care, research, and service engrained in their mission are well poised to host these discoveries. These academic discoveries can lead to improvement in patient health and economic development if supported to cross the “valley of death” through institutional assistance, by providing guidance, gap funding and product development expertise. Colorado has a vibrant local startup ecosystem, state support for commercialization and entrepreneurship as well as critical mass of product development expertise. University of Colorado Anschutz Medical Campus, as a major AMC, is an engine for growth for the region. This article discusses innovation efforts at the University of Colorado Anschutz Medical Campus as a case study, which is built around two major efforts: the CCTSI and CU Innovations. I-Corps at CCTSI and the SPARK|REACH program of CU Innovations have been instrumental in fostering innovation, commercialization, and entrepreneurship on the campus.

OBJECTIVES/GOALS: To assess labels of drugs approved for Type 2 Diabetes (T2D) for the inclusion of geriatric sub-population data (ages 65-74, 75-84, ≥85) since January 1, 2013, in accordance with international guidance and US regulations in recognition of an aging populations and global demographics. METHODS/STUDY POPULATION: Utilizing FDA Guidance for Industry: Labeling for Human Prescription and Biological Products - Implementing the Physician’s Labeling Rule (PLR) Content and Format Requirements and the International Council for Harmonization of Technical Requirements (ICH) E7 guidance “Studies in Support of Special Populations: Geriatrics” as reference for assessing labels. The Center for Drug Evaluation and Research (CDER) new drugs/biologic approvals database was filtered for drugs approved between Jan. 1, 2013 and Dec. 31, 2022 with approved T2D indications. Examined original drug labels and supplements from Drugs@FDA for geriatric use efficacy and safety wording in Section 8.5 (Use in Specific Populations, Geriatric Use), for labels. Subpopulation data in labeling for ages 65-74, 75-84, and ≥85 was analyzed. RESULTS/ANTICIPATED RESULTS: Seven T2D drugs (Trulicity, Tresiba, Adlyxin, Ozempic, Steglatro, Kerendia, Mounjaro) approved within the specified time period were analyzed. In the current examination, all labels contain information regarding efficacy differences between ages 65+ and 75+, however, none contain information on efficacy for ≥85 populations. Four of the seven drugs have been updated with increased data from further efficacy trials for older adults conducted after initial approval. The remaining three drugs have only been reworded, or not changed at all, with no further efficacy trials conducted. DISCUSSION/SIGNIFICANCE: This research shows the gap in representation of older adults in clinical trial data and T2D drugs’ labeling. Despite having a higher usage of T2D drugs compared to the general population, older adults and especially the oldest-old (≥85) are underrepresented. Additional demographic requirements ensuring diversity in clinical trials is needed.

OBJECTIVES/GOALS: Electronic cigarettes have become increasingly popular, with various combustion products generated in the process. Dihydroxyacetone (DHA), a carbohydrate made during the heating process. Exposures may reach high micromolar to low millimolar doses of DHA per day and no studies have been done to understand the effects of DHA in the heart. METHODS/STUDY POPULATION: Here, we examine if DHA contributes to these using rat cardiomyocytes, H9c2 cells, and rat cardiac tissues to DHA evaluating metabolic and mitochondrial effects. Using the cells, we will investigate metabolic and mitochondrial pathways using Seahorse, protein expression changes in nutrient sensing pathways, and understand dose-dependent effects of DHA in the heart. Metabolite pools will also be evaluated to understand the changes promoted by DHA. Oxidative stress as previously observed in other cell models will also be measured. Key findings in the cardiac cells will be investigated in the cardiac tissues exposed to DHA. RESULTS/ANTICIPATED RESULTS: We have previously shown DHA induces oxidative stress, metabolic changes, and mitochondrial dysfunction in various cell line models. Interestingly, these effects are highly cell-type dependent. E-cigarettes are known to have toxic cardiac effects, including arterial stiffness, endothelial dysfunction, vascular injury, and oxidative stress. Changes in glycolytic, fatty acid synthesis, and the citric acid cycle enzymes and metabolites were found in the H9c2 cells. We also observed increased mitochondrial ROS and fuel changes due to DHA exposure. In DHA exposed cardiac tissues, we observed oxidative stress and mitochondrial fission and fusion dynamics altered. DISCUSSION/SIGNIFICANCE: These data suggest further study at physiologically relevant doses is warranted to understand how DHA inhaled impacts the long-term health of vapers. As well as the regulation of DHA in e-cigarettes as it has been deemed as safe for topical applications and warned against inhalation.