ABSTRACT IMPACT: The car telemetry system may be an ideal method to accurately and reliably evaluate and compare at-risk driving errors between older drivers with and without glaucoma. OBJECTIVES/GOALS: Our project aims to determine whether an in-car telemetry system used during an on-road driving evaluation can accurately and reliably evaluate driving errors in lane maintenance and visual scanning and objectively quantify the frequency and severity of these errors in glaucoma patients. METHODS/STUDY POPULATION: This is a single center, cross-sectional study of 180 participants (125 with glaucoma and 55 controls), ages 55 or older, who underwent a comprehensive clinical assessment, including vision, cognition, motor function, followed by an on-road evaluation by a trained occupational therapist. Driving errors were recorded through a dual method including: 1. An in-car trained occupational therapist 2. In-car telemetry system. The frequency and severity of errors in lane maintenance and visual scanning from the in-car telemetry will be assessed and compared between participants with varying severity of glaucoma and normal controls. In addition, we will compare the frequency and severity of errors in lane maintenance and visual scanning to those recorded by the in-car driving evaluator. RESULTS/ANTICIPATED RESULTS: We anticipate (or predict) that the in- car telemetry system will be able to detect frequency and severity of driving errors in lane maintenance and visual scanning in glaucoma participants. We also predict that participants with worsening glaucoma severity will commit more driving errors. In addition, the in-car telemetry will detect a similar frequency and severity of driving errors as the in-car driving evaluator. DISCUSSION/SIGNIFICANCE OF FINDINGS: The type and frequency of vision-related driving errors that place individuals at risk for a car accident is not well known. Without this critical information, it is extremely challenging to help older adults with glaucoma to be safe drivers.

OBJECTIVES/GOALS: Our primary objective was to determine the demographic and linguistic characteristics of research coordinators (RCs) in a large pediatric emergency medicine research collaborative network. Our secondary objective was to determine if the RCs perceived any impact of those characteristics on their duties. METHODS/STUDY POPULATION: We conducted a 15-question electronic survey of RCs at the member institutions of the Pediatric Emergency Care Applied Research Network (PECARN). A total of 74 potential respondents were identified and received the survey. RESULTS/ANTICIPATED RESULTS: Fifty-three surveys (71.6%) were completed. Most respondents identified as female; white; and not Hispanic or Latino. Fourteen respondents (26.4%) identified as underrepresented minorities in medicine (UIM), which is similar to the percentage of UIM among the general population (30%). Twenty-eight respondents (52%) felt that their race/ethnicity positively impacted recruitment efforts. Twenty-three respondents (43%) felt that their ability to speak a language other than English positively impacted recruitment efforts. Four female respondents felt that their gender hindered their recruitment activities and impacted their sense of belonging within the research team. DISCUSSION/SIGNIFICANCE: RCs felt that their backgrounds and attributes positively impacted subject recruitment. However, some female coordinators felt negatively impacted by their gender. Increasing diversity amongst clinical research professionals and incorporating team cultural humility practices, may help increase diversity among clinical research subjects.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to characterize children with nonalcoholic fatty liver disease (NAFLD) living in the Southeastern United States. METHODS/STUDY POPULATION: This retrospective electronic medical record chart review was conducted on a random sample of 206 children identified with NAFLD. Patients were included if they met the following criteria: confirmed NAFLD through either an ultrasound or liver biopsy or clinical suspicion of fatty liver disease alongside elevated alanine aminotransferase (ALT) in the absence of other etiologies causing elevated transaminases. Patients were excluded if they had hepatitis or other documented liver disease. Data collected at initial presentation included age, gender, ethnicity, height, weight, body mass index (BMI), BMI percentile, blood pressure, HbA1c, aspartate aminotransferase (AST), ALT, γ-glutamyl transferase (GGT), total cholesterol, total triglycerides, low-density lipoprotein, and high-density lipoprotein. Statistical analysis: for descriptive statistics, frequency counts and percentages alongside means, standard deviation, range, min/max values for the continuous variables were calculated. RESULTS/ANTICIPATED RESULTS: This study included 206 children diagnosed with NAFLD. Subjects were primarily male (n=136, 66%) and Caucasian (n=133, 66%), followed by Hispanic (n=42, 21%), Black (n=25, 12%), and Asian (n=2, 1%). Mean age at diagnosis was 12.3±3.5 years. Mean weight (lbs), height (in), and BMI (kg/m2) of subjects at diagnosis were 192±77 lbs, 61.7±6.6 in, 34.6±9.7 kg/m2, respectively. Patients had an average systolic blood pressure of 124±15.4 mmHg and diastolic blood pressure of 69.6±10.6 mmHg. Mean ALT was 91.8±67.2 U/L, AST was 61±38.8 U/L, and GGT was 55.1±64.6 U/L. Mean HbA1c was 5.8±1.4%, cholesterol was 176±36.3 mg/dL, triglycerides were 200±134 mg/dL, low-density lipoprotein was 107.6±32.1 mg/dL, and high-density lipoprotein was 39.9±8.4 mg/dL. DISCUSSION/SIGNIFICANCE OF IMPACT: In addition to having significantly elevated liver enzymes, children with NAFLD had several derangements in their metabolic profile, most notably high triglyceride levels and HbA1c values in the prediabetic range. Although lifestyle modification is the gold standard treatment for NAFLD, pharmacotherapy may need to be included to address metabolic syndrome.

OBJECTIVES/SPECIFIC AIMS: Incomplete spinal cord injury typically results in life-long disability, often in the form of profound loss of locomotion capability. Individuals who have experienced incomplete spinal cord injury exhibit persistent eccentric motor deficits, which are particularly prevalent in the weight acceptance phase of gait and emphasized in sagittal plane knee motion and frontal plane hip motion. METHODS/STUDY POPULATION: Motion analysis can capture the kinematic and joint-level deficits of these individuals, but it is impossible to directly calculate the contributions of individual muscles to weight acceptance due to the complexity of the musculoskeletal system. Instead, those muscle contributions must be simulated in order to approximate muscle power during locomotion. RESULTS/ANTICIPATED RESULTS: The traditional method for driving these simulations with electromyography readings is unavailable for individuals who have neuromuscular deficits (e.g., spasticity or paralysis), due to the need to generate reliable maximum voluntary isometric contractions for baseline purposes. Instead, this research develops a novel method for using resting electromyography data to drive musculoskeletal simulations using a muscle activation threshold paradigm. DISCUSSION/SIGNIFICANCE OF IMPACT: The simulation results of this method more closely resemble experimental results, but further simulation refinement is needed to fully capture the true muscle activity.

OBJECTIVES/GOALS: Parental SES may influence the trajectory of students applying to orthopaedic surgery residency, perpetuating opportunistic disparities. Thus, we sought to examine the relationship between parental occupation/education and applicant match rate, education financing, and medical school background. METHODS/STUDY POPULATION: Data from the Association of American Medical Colleges (AAMC) documented parental occupation and education levels of 10,697 orthopedics applicants from 2011 to 2021. Parental occupations were categorized into physician vs non-physician, healthcare vs non-healthcare, working class vs non-working class, and STEMM (Science, Technology, Engineering, Mathematics, Medicine) vs non-STEMM. Parental education levels spanned from no college degree to doctorate degrees and were used as a proxy for SES. Outcomes analyzed included match success, premedical and medical school debt, total educational debt, scholarships, and representation from top 40 research medical schools as determined by NIH funding. RESULTS/ANTICIPATED RESULTS: Physician parent applicants (20.1%) had better match rates (75.5% vs. 73.5%), lower debts, lesser scholarships, and higher top 40 school representation. Healthcare parent applicants (37.0%) had similar match rates, less debt and scholarships. Working class parent applicants (6.0%) had more debt and scholarships. STEMM parent applicants (48.6%) had higher match rates, lesser debts and scholarships, and higher top 40 representation. Applicants with parents without college degrees had lower match rates (68.6% vs 74.5%), more debt and scholarships. Doctorate parent applicants had better match success (75.9% vs 72.9%), lesser debts, and higher top 40 school representation (34.9% vs 29.6%). DISCUSSION/SIGNIFICANCE: Parental SES was associated with substantial variation in applicant financial burden and educational pedigree. Notably, applicants with parents lacking degrees had lower match rates, underscoring the need for supportive strategies to ensure equitable opportunities for aspiring orthopaedic surgeons.

Objectives/Goals: Identify host ecology factors that lead to the emergence of highly pathogenic avian influenza (HPAI) variants shown to be more fit than others and that become variants of concern to agriculture, wildlife, and humans. Goals include targeted surveillance for these variants for enhanced biosecurity measures in agriculture and pandemic preparedness. Methods/Study Population: The study dataset of 721 HPAI-positive cases in wild birds in New England since 2022 was collected through a robust sampling effort by Tufts’ Runstadler Laboratory together with a large network of wildlife rescue and rehabilitation partners. We will fit mixed-effects models to measure the association of variant fitness as a fixed effect with the odds of infection in species of either of the two bird orders most associated with HPAI – gulls and shorebirds or ducks and geese. Variant will be fit as a random effect, and covariates will include ecological factors. Fitness will be a leveled variable based on prevalence, geographic spread and host range. Using centroid spatial statistics, we will determine whether these variants traveled geographically distinct transmission routes, indicating distinct host ecologies. Results/Anticipated Results: We anticipate that birds of the order Charadriiformes (seagulls and shorebirds) will be more associated than Anseriformes (ducks, geese) with HPAI variants that were not transmitted beyond the region and that the reverse will be true with variants that did achieve prevalence over a wide geographic range and range of host species, including agricultural species. We also anticipate that there are distinct transmission routes by variant that could better illuminate host ecology dynamics in this region that contribute to variant fitness. Discussion/Significance of Impact: The current HPAI virus outbreak is perpetuated by evolution to new variants through co-infections in wild birds with low pathogenic avian influenza viruses they carry. This research could lead to study of the virulence to different wild bird host species of low pathogenic avian influenza subtypes that contributed genetic material to an HPAI variant.

OBJECTIVES/SPECIFIC AIMS: The morbidity and mortality in adults with single ventricular hearts who have undergone Fontan palliation is poorly defined. These patients have a high burden of arrhythmia, heart failure, and re-operation. We hypothesized that age and type of Fontan predict occurrence of arrhythmia. METHODS/STUDY POPULATION: In total, 205 patients aged 18 years who had undergone a Fontan procedure were identified. Those with incomplete data were excluded. Demographic, anatomic, pharmacologic, imaging, hemodynamic, and electrophysiologic data were collected. The χ2 and Mann-Whitney U tests were used to test significance defined as p<0.05. RESULTS/ANTICIPATED RESULTS: Of the 205 patients identified, 59 had been lost to follow-up. Of the 146 patients (77, 53% female) actively followed 18 (12%) had died at a median (IQR) age of 27 (21–34.3); in patients alive as of 10/2016 the median age was 26 years (22–34). Fontan types were lateral tunnel (LT) (n=79, 54.1%), extracardiac (EC) (n=32, 22%), right atrial to pulmonary artery (RV-PA) (n=28, 19%), and Fontan with Bjork modification (n=4, 2.7%). Systemic left ventricle (n=96, 66%) was more common than systemic right ventricle (n=43, 30%). Of the 146 patients, 101 (69%) had significant morbidity or mortality: 86 (59%) were diagnosed with arrhythmia, 18 (12%) died, and 11 (8%) underwent heart transplants. Frequent procedures included: Fontan revisions/cryoablation in 28 (19%), electrophysiology studies with ablation in 73 (50%), and pacemakers in 53 (36%). Of the arrhythmia diagnoses, 57 (64%) were atrial tachyarrhythmias. RV-PA Fontan procedures were associated with significantly more atrial arrhythmia than all other Fontan types (70% vs. 30%; p<0.01). There was no statistical difference in occurrence of atrial arrhythmia in adults with LT Versus EC Fontans (p=0.3). While patients who had undergone RV-PA and Bjork Fontans were older with median age 34 years, there was no significant difference in age between LT and EC (median 24.0 and 24.5). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult survivors of the Fontan procedure suffer from significant morbidity and mortality. The single most prevalent morbidity is atrial arrhythmia. We conclude that RV-PA Fontans, now obsolete, have the highest prevalence of arrhythmia and that there is no difference in arrhythmia burden between LT and EC Fontans. Given the high prevalence of morbidity and mortality in this population, it is imperative that they be followed by cardiologists with expertise in congenital heart disease.

OBJECTIVES/SPECIFIC AIMS: More than half a million adult patients nationally undergo cardiac surgery each year. Reintubation following cardiac surgery is common and associated with higher short- and long-term mortality, increased cost, and longer lengths of stay. The reintubation incidence is estimated at 5-10%. Patients undergoing cardiac surgery are increasing in age and comorbidity burden, and receive increasingly complex cardiac surgical procedures, complicating decision making around when to extubate postoperative patients. Compounding this complexity are financial pressures to maintain high throughput and maximize ICU bed availability. Providers are often compelled to extubate high-risk patients earlier, despite the potential for an increased risk of reintubation. Understanding the risk factors for reintubation after cardiac surgery and identifying effective interventions to reduce these reintubations is of critical importance to optimize patient outcomes. High-flow nasal cannula (HFNC) provides up to 60 liters per minute of 100% oxygen, dead space washout, and humidification to improve secretion clearance, and has shown some benefits in improving hypoxia and reducing reintubation in select populations. However, its benefit in high-risk patients undergoing cardiac surgical procedures is not known and therefore clinicians may still be reluctant to extubate these patients early and introduce HFNC, despite the known risks of prolonged intubation. To address this important issue, we aim to develop and validate a model to predict postoperative reintubation after cardiac surgery using data readily available from the electronic health record (EHR) and use this data to complete a pilot randomized controlled trial (RCT) of post-extubation HFNC to prevent reintubation in cardiac surgery patients identified as at high risk for reintubation. METHODS/STUDY POPULATION: Based on retrospective data demonstrating a 4.7% reintubation incidence within 48 hours in our CVICU, we estimate that there will be 340 reintubations available for analysis of the risk factors for reintubation to develop our predictive model from November 2, 2017 (our EHR go-live). We require 15 events per predictive variable to avoid overfitting the model, giving us at least 22 variables for analysis and inclusion in the model. Model validation and calibration will be performed using a bootstrapped validation cohort. Next, we will prospectively study 120 patients with a greater than 10% predicted risk of reintubation (double the baseline risk of the overall population) and randomly assign them to either HFNC or usual care, to test the hypothesis that HFNC decreases the rate of reintubation in high-risk patients. RESULTS/ANTICIPATED RESULTS: In addition to developing a predictive model, refining it, and validating its ability to predict the primary outcome of reintubation within 48 hours, I will further assess whether HFNC reduces total duration of mechanical ventilation, hospital length of stay, and ICU length of stay in this high-risk population. I will use these data to establish the feasibility of EHR-integrated predictive modeling and randomization, as well as to guide a future multicenter clinical trial that will pragmatically leverage the EHR for patient selection, enrollment, randomization, and data collection. DISCUSSION/SIGNIFICANCE OF IMPACT: Assuming HFNC decreases reintubation rates by 50%, at a 1:1 ratio of cases to controls, we will require 435 patients in each group (970 total), to have an 80% power and alpha of 0.05 to detect a difference. As this will require a multicenter study, we will instead focus on using data from this pilot study to: 1) refine our sample size estimates. 2) demonstrate the feasibility of our novel EHR-integrated pragmatic trial design. 3) identify and screen collaborators at other institutions, including obtaining important regulatory and legal approval. 4) establish a data safety monitoring board for the trial. 5) refine the data collection infrastructure, leveraging commercially available resources in one of the largest enterprise EHR systems (Epic) and associated resource-sharing products, such as Epic’s App Orchard.

OBJECTIVES/GOALS: The use of Human Centered Design (HCD) to improve the quality of team science is a recent application, and HCDs benefits and challenges have not been rigorously evaluated. We conducted a qualitative study with health sciences researchers trained in HCD methods to determine how they applied HCD methods and perceived its benefits and challenges. METHODS/STUDY POPULATION: The University of Pittsburgh offered HCD training to three cohorts of research scientists (staff as well as faculty) over a three-year period. The training was provided by the LUMA Institute, a premier HCD design firm with a highly regarded training program. We then evaluated this training by conducting 1-hour, semi-structured interviews with trainees from three training cohorts. Interviews focused on perceptions of the training, subsequent uses of HCD, barriers and facilitators, and perceptions of the utility of HCD to science teams. Data analysis was conducted using Braun and Clarkes process for thematic analysis. RESULTS/ANTICIPATED RESULTS: We interviewed 18 researchers (nine faculty and nine staff) trained in HCD methods and identified distinct themes regarding HCD use and its perceived benefits and challenges. Trainees found HCD relevant to research teams for stakeholder engagement, research design, project planning, meeting facilitation, and team management. They also described benefits of HCD in five distinct areas: creativity, egalitarianism, structure, efficiency, and visibility. We also identified challenges, including tensions between HCD approaches and academic culture. DISCUSSION/SIGNIFICANCE: Our data suggest that HCD has the potential to help researchers work more inclusively and collaboratively on interdisciplinary teams and generate more innovative and impactful science. The application of HCD methods is not without challenges; however, we believe these challenges can be overcome with institutional investment.

OBJECTIVES/GOALS: The current opioid epidemic has placed post-operative pain management under scrutiny. Limiting post-operative pain can decrease overall opioid usage in the recovery period, especially after orthognathic surgery. Several studies have illustrated the efficacy of pregabalin in decreasing postoperative pain and opioid usage in adults undergoing orthognathic surgery. We aim to study the effects of a single dose of preoperative pregabalin on postoperative pain and total opioid consumption after orthognathic surgery in individuals with cleft lip and palate. METHODS/STUDY POPULATION: This was a retrospective cohort study of consecutive patients who received Le Fort I midface advancement between June 2012 and July 2019 by one of two surgeons at a single institution. We took advantage of our institution’s implementation, beginning in 2016, of a one-time dose of preoperative pregabalin for LeFort I midface advancement. All patients had diagnosed cleft lip and palate. The treatment group received a one-time preoperative dose of pregabalin. The control group did not receive pregabalin. Total morphine milligram equivalents (MME) consumption was calculated by adding intraoperative opioid administration and postoperative opioid consumption during admission. Postoperative pain control during admission consisted of oral oxycodone and intravenous (IV) hydromorphone or morphine. Duration of hospitalization and pain intensity assessed with the numeric pain rating scale (0-10) were also recorded. The mean postoperative pain assessment scores during admission was calculated for each patient. The median of these individual mean pain assessment scores for each group was subsequently computed. RESULTS/ANTICIPATED RESULTS: Twenty-three patients (14 males, 9 females) were included in this study; 12 patients received pregabalin (median dose: 150mg, range: 100-200mg). Mean age (years) at operation of the pregabalin (18.3 ± 1.9) and control groups (17.8 ± 1.9) were also equivalent (p = 0.571). Median hospital stay for both groups was 1.0 day. The pregabalin group had significantly lower consumption of total opioids during admission (total MME 70.95 MME; IQR: 24.65-150.17) compared to the control group (138.00 MME; IQR: 105.00-232.48) (MU = 31.00, p = 0.031). Although pain scores in the treatment group (3.21 ± 2.03) were lower than in the control group (3.71 ± 2.95), the difference was not statistically significant (p = 0.651, 95% Cl [−1.75, 2.75]). DISCUSSION/SIGNIFICANCE OF IMPACT: Based on the results, a one-time preoperative oral dose of pregabalin before orthognathic surgery in patients with cleft lip and palate reduced total opioid consumption during admission. However, there was no difference in length of stay or pain scores within the two groups. A single preemptive oral dose of pregabalin should be considered an effective adjunct to pain management protocols in patients undergoing orthognathic surgery.

OBJECTIVES/GOALS: The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research. METHODS/STUDY POPULATION: An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams' perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: There was a total of 63 responses. A majority of respondents have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts. Approximately half of the respondents believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues, distrust in doctors and/or researchers, fear of unknown side effects, and unavailability of medical interpreters. Respondents report that they are not discouraged from enrolling URGs and would utilize resources related to encouraging the inclusion of URGs DISCUSSION/SIGNIFICANCE: Language appears more influential than ethnicity or race when it comes to enrolling and retaining URGs. Additionally, it appears that enrolling is a bigger challenge than retaining. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation.

ABSTRACT IMPACT: Younger patients receiving biologics for rheumatoid arthritis have higher medical expenditure. OBJECTIVES/GOALS: TNF inhibiting biologic disease modifying antirheumatic drugs are among the most highly regarded treatment options for rheumatoid arthritis (RA). We aimed at evaluating the medical and prescription costs associated with monoclonal antibody use vs. other RA treatment options in subjects diagnosed with RA. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to identify all RA subjects (n=_____). Demographics and MEPS-provided flags for RA were abstracted from the medical condition files for all the subjects surveyed (2008-2018). Prescribed biologics were identified based on generic and brand names following a manual review to detect any misspellings. Total medical expenses and prescription expenses were abstracted for all identified RA subjects. Subject were surveyed for two consecutive years, thus expenses were assessed for each of the two surveyed years. Costs were adjusted for inflation and expressed in 2018 dollars. The relationship between biologics use, cost and age or gender was evaluated by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: Most RA subjects did not use biologics. RA was more prevalent in women than in men with no significant correlation between sex and the use of biologics in year 1, year 2, or the combined years (p=.44, p=.63, and p=.65, respectively). Biologics users were found to be significantly younger (p<.001), with a mean of 52.8 years compared to 59 years in those who did not use biologics. The 95% confidence interval was 3.7 to 8.6 years younger than non-users. Total medical and prescription costs were higher for biologics users (p<.001) in all analyses. The mean prescription cost difference was $24,038 more per year for biologics users, and $26,296 more total medical expenses, CI $20,502-$27,230 and CI $21,947-$30,646, respectively. There was a trend for biologics users to have higher non-prescription medical expenses (p=.05). DISCUSSION/SIGNIFICANCE OF FINDINGS: Interestingly, biologics non-users had some extreme outliers with expenses far higher than any biologics users, possibly due to poorly controlled RA due to age and/or comorbidities. Yet, our most interesting findings are the higher use of biologics among younger RA subjects and the elevated costs of care being driven mainly by prescriptions cost.

OBJECTIVES/SPECIFIC AIMS: About 75% of the estimated 2.5 million traumatic brain injuries (TBIs) diagnosed annually classify as mild TBI (mTBI); yet cognitive impairments associated with poor patient outcomes can persist for weeks to years. mTBI symptoms are difficult to measure objectively and often remain undiagnosed in the context of an unknown cognitive baseline. Formal neuropsychological exams hold limited utility due to their extensive resource burden. We aimed to define the clinical importance of a 4-question assessment of subjective cognitive complaints (SCC) in predicting return to work at 6 months following mTBI. METHODS/STUDY POPULATION: mTBI participants from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study were included. A self-report affirmation to at least 1 of 4 subjective cognitive symptoms yielded positive SCC. Regression analysis was used to determine factors associated with return to work by 6-months. RESULTS/ANTICIPATED RESULTS: Of 479 enrolled participants with mTBI, 271 (57%) had complete follow-up data. Of which, 156 (58%) had at least sheltered employment at enrollment. Thirty-four (22%) of workers had no return to work at 6-months. Demographics, prior education, presenting injury severity, work status, and post-traumatic stress disorder were associated with return to work. SCC was associated with lower odds of return to work by 6-months (OR=0.11, p=0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: We suggest a concise 4-question assessment of SCC may be clinically relevant in estimating the likelihood of return to work by 6 months post-mTBI.

OBJECTIVES/GOALS: A group of leading students was integrated as part of the collaborators of the Title V MSC Project with the objective of promoting UgS and GS from Puerto Rico to start and get involved in CTR with an interdisciplinary approach (IA) through the course of INTD 5998: Clinical and Translational Research: Introduction and Principles. METHODS/STUDY POPULATION: The Title V MSC Project of the UPR institutionalized the INTD 5998 course. This course offers UgS and GS the opportunity to start and get involved in CTR. Students with leadership from different universities and from different geographic regions of Puerto Rico were identified and recruited to collaborate in the recruitment of students interested in taking the INTD 5998 course. Since April 2022, the student leaders implemented different strategies to make known about the course and its benefits among their peers. RESULTS/ANTICIPATED RESULTS: For the course of INTD 5998 that began in August 2022, they achieved a contact list of 97 interested students from different geographic areas of Puerto Rico, 21 students applied for the course and 15 enrolled (71% of those who applied and 75% of the maximum course quota). DISCUSSION/SIGNIFICANCE: The student leaders have been an effective promotion and marketing strategy to make known the INTD 5998 course among their peers from the different Universities of Puerto Rico. Their integration as collaborators to the Title V MSC Project has been successful and valuable.

Objectives/Goals: To develop a novel meta-analysis model that estimates pooled risk ratios (RR) at prespecified milestones, accounts for unequal follow-up across trials, and leverages between-time correlation, thereby providing clinically interpretable estimates under potential non-proportional hazards (PH). Methods/Study Population: Our model combines study-specific RRs – the ratios of cumulative event probabilities – from Kaplan-Meier curves at prespecified times (12, 24, 36 months, etc.). Using the delta method, we derive within-trial variances for log-RRs and cross-time covariances to reflect correlation among milestones. These study-level estimates and variance-covariance matrices enter a multivariate random effects model to obtain pooled RRs. We illustrate this method with a meta-analysis of progression-free survival in 7 randomized clinical trials of first-line therapy immunotherapy combinations in metastatic renal cell carcinoma. Results/Anticipated Results: Follow-up for PFS across the 7 trials was heterogeneous: all 7 trials contribute at 12 months, 6 at 24 months, 5 at 36 months, 4 at 48 months, and only 2 contributing at 54 and 60 months. This heterogeneity motivates a multivariate approach that borrows strength across times. PH diagnostics indicate deviations from PH for PFS in 3 trials, supporting the need for pooled effects at milestones rather than a single summary measure. We will report pooled RRs at 12, 24, 36, 48, 54, and 60 months. We expect the multivariate model to improve precision at shared milestones while honestly reflecting increasing uncertainty at sparse later times. Discussion/Significance of Impact: When follow-up differs across trials and PH is questionable, a multivariate RR meta-analysis preserves interpretability and efficiently uses all available milestones without forcing a single-number summary. This approach clarifies when benefits accrue and provide clinically interpretable results.

OBJECTIVES/GOALS: In this study we sought to determine the role of glucagon-like peptide-1 (GLP-1), one of the main gut hormones in regulating glucose metabolism, after protein ingestion in patients with a history of Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG). METHODS/STUDY POPULATION: We examined the glucose and islet-cell secretory responses to 50 g protein ingestion with and without a potent GLP-1 receptor antagonist, exendin-(9-39) [Ex-9], in 10 GB-treated subjects, 9 SG-treated, and 7 non-operated controls (CN). The groups were matched for age, BMI, fat-free mass, fasting glucose and insulin, and HbA1c. The surgical groups also were matched for weight loss and time post-surgery. No subjects had diabetes. RESULTS/ANTICIPATED RESULTS: Protein ingestion resulted in an early rise in glycemia (AUCGlucose1hr) in GB and SG, whereas CN had minimal change in glucose (p<0.05). Protein ingestion enhanced C-peptide responses in all groups, but to a larger extent in GB and SG when compared to CN (p<0.05). Early glucagon response to protein ingestion (AUCGlucagon1hr) tended to be larger in GB and SG subjects when compared to CN (p=0.07). Ex-9 increased premeal and prandial glycemia in all groups (p<0.05), but increase in early glycemia (AUCGlucose1hr) was most notable in GB (p=0.1, interaction). This glycemic effect of Ex-9 was associated with a ~25% reduction in prandial C-peptide secretion in GB and SG and ~8% increase in CN (p<0.05, interaction). Early prandial glucagon responses were larger during studies with Ex-9 compared to those without (p<0.05). DISCUSSION/SIGNIFICANCE: Our findings indicate that glucose metabolism after protein ingestion is altered after GB and SG. To our knowledge, this is the first report to demonstrate that endogenous GLP-1 contributes to glucose and islet-cell secretory response to protein ingestion, and that GB and SG exaggerate GLP-1 contribution to insulin secretion after protein ingestion.

OBJECTIVES/GOALS: Clinical research professionals (CRPs) are vital for high quality research. Professional development opportunities for CRPs help improve job satisfaction and retention. This poster will present data on peer-presenter satisfaction and their assessment of co-leading a workshop as an important professional development and networking activity. METHODS/STUDY POPULATION: Developing a Research Professionals Network Workshop is an important professional development opportunity for peer-presenters in a mentored, collaborative environment that encourages networking and inter-institutional teamwork. Presenters are connected by the leadership team and then work together to develop the workshop’s learning objectives, presentation, and activities. A summary of learner evaluations are provided to the presenting team to provide constructive feedback for future presentations. A survey to assess experience in leading the workshops is sent to presenters after the workshop to assess overall satisfaction and assessment of importance in their professional development. RESULTS/ANTICIPATED RESULTS: Presenter evaluation response data from the years of 2019-2022 showed high rates of agreement that presenters’ participation 1) increased their knowledge of the topic, 2) appreciated the support provided by the leadership team, 3) felt adequately prepared to lead the workshop, and 4) were overall satisfied with the experience. Questions specifically around the inter-institutional collaboration and professional development of the workshop experience were added in 2021 and similarly showed high marks of satisfaction. Qualitative response data showed that some presenters continued collaborations after workshop completion. DISCUSSION/SIGNIFICANCE: Overall results show that workshop presenters felt that leading an RPN workshop with collaborators from the other participating sites was a useful experience that supported their ongoing professional development. High marks on satisfaction by presenters is attributed to the multi-hub partnership and guidance from the leadership team.

OBJECTIVES/GOALS: Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells. Emerging data suggest that differences in intestinal microbiota might be critically involved both in autoimmunity and in glucose homeostasis. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites positively by increasing production of beneficial short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity and secretion in healthy non-diabetic adults. Further, an acetylated and butyrylated form of HAMS (HAMS-AB) that increases beneficial SCFA production, namely acetate and butyrate, has been safe and effective in disease prevention in mouse T1D models. The objective of the proposed study is to assess the effect of administering a prebiotic, such as HAMS-AB, on the gut microbiome profile, SCFA production, glycemia and β-cell function in humans with T1D. METHODS/STUDY POPULATION: We hypothesize that administration of HAMS-AB will (i) improve the gut microbiome profile in humans with T1D, (ii) increase SCFA production, and (iii) improve β-cell health, β-cell function and overall glycemia. We propose a pilot randomized controlled cross-over trial of HAMS-AB in 12 youth with newly-diagnosed T1D. We will use state-of-the-art markers to profile the gut microbiome (using 16S rRNA sequencing), measure stool SCFA levels (using gas chromatography), asses β-cell stress/death (by measuring proinsulin to C-peptide ratios) and glycemia (assessed by continuous glucose monitoring and HbA1c measurements). RESULTS/ANTICIPATED RESULTS: We expect that the use of HAMS-AB in newly diagnosed youth with type 1 diabetes will alter the gut microbiome profile (thus increasing the number of fermenters and SCFA levels), β-cell function and glycemia in humans with T1D. DISCUSSION/SIGNIFICANCE OF IMPACT: Given the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, the use of a prebiotic such as HAMS-AB offers a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.

Objectives/Goals: To assess the association between pollution and CVD outcomes in a high-risk CAD population, and investigate how social drivers intersect with this association. Methods/Study Population: 1,602 participants enrolled in the Emory Cardiovascular Biobank were stratified into high vs. low pollutant exposure groups based on PM₂.₅ (median 10.6 μg/m³), NOx (median 39.4 ppb), and CO (median 635 ppb) levels. Demographics, cardiovascular (CV) risk factors, comorbidities, and SVI domains including socioeconomic status (RPL_THEME1), household characteristics (RPL_THEME2), racial/ethnic minority status (RPL_THEME3), housing and transportation (RPL_THEME4), and overall SVI ranking (RPL_THEMES) were compared between groups. Cox proportional hazards models were used to assess associations between pollutants and CVD outcomes (CV death, myocardial infarction [MI], stroke, heart failure, and the composite MACE. Results/Anticipated Results: Higher PM₂.₅ exposure was associated with a greater prevalence of hypertension (82.7% vs. 74.6%, p<0.001), female sex (39.7% vs. 34.1%, p=0.023), and elevated SVI scores (RPL_THEME1–4, all p<0.05). Similar gradients were observed across NOx and CO strata, particularly in SVI metrics (p<0.001). In fully adjusted models, MACE were associated with PM₂.₅ (HR 1.73, 95% CI: 1.22–2.44, p = 0.002) and CO (HR 1.00, 95% CI: 1.0005–1.003, p = 0.005) levels. Additionally, HF admissions were associated with PM₂.₅ levels (HR 1.16, 95% CI: 1.05–1.28, p = 0.003). SVI measures interacted significantly with the impact of NOx on HF risk [RPL_THEME1 (HR 1.03, p = 0.033) and RPL_THEME2 (HR 1.05, p = 0.008)] and stroke risk [RPL_THEME4 (HR 1.07, p = 0.025)]. Discussion/Significance of Impact: In patients with CAD, higher PM₂.₅ exposure is independently associated with risk of MACE. Social vulnerability amplified the adverse risk relationships for NOx exposure highlighting the need to consider neighborhood-level risk in pollution-related CV disease prevention.

OBJECTIVES/GOALS: To construct an assessment scale capable of evaluating a trial’s gender literacy or the extent to which biologically assigned “sex” is understood as separate from culturally defined and personally embodied “gender”. This scale in tandem with a policy brief will outline recommendations for inclusive medical nomenclature in the clinical space. METHODS/STUDY POPULATION: Using clinicaltrials.gov, inclusion/exclusion criteria was recorded for PrEP interventional trials (i.e., Truvada, Descovy). To evaluate these trials, an assessment scale for “gender literacy” is necessary. This scale relies on the fact that sex and gender are distinct elements to one’s identity and ought to be reported as such. As a form of content analysis, where literary information (eligibility criteria) is evaluated based on set rubric, this scale will require validation through inter-coder agreement. Evaluated in a group of 5 college-age students, this scale was used on selected PrEP clinical trials to verify if there was high agreement in the scores given. After validation, the dataset from clinicaltrials.gov underwent evaluation using the proposed assessment scale for gender literacy. RESULTS/ANTICIPATED RESULTS: The student coders had a Kalpha of 0.4 in the first round of grading. After retraining, their Kalpha increased to 0.68. The grading involved a subjective language rating (LIR), evaluating the usage of inclusive language, and a numerical score (GR) for the demographics of inclusion in a trial. After this inter-coder agreement validation, 216 active PrEP clinical trials (as of March 2023) were downloaded from clinicaltrials.gov. Grading of these trials showed that cisgender males represented 40% of participants, while 28% represented both transgender men and women, and less than 1% represented non-binary individuals. Moreover, more than half of the trials (52%) exhibited cisgender-oriented language or made no reference to gender identity. DISCUSSION/SIGNIFICANCE: It is a scientific imperative for clinical trials to have representative participant bases in order to derive data that is generalizable to afflicted populations. Especially for PrEP clinical trials, where gender-diverse individuals need visibility, trial design must be carefully crafted so as not to exclude through dated or exclusionary language.