OBJECTIVES/GOALS: METHODS/STUDY POPULATION: This study utilizes the IeDEA W. Africa cohort to evaluate the prevalence and burden of hypertension and diabetes type II among people living with HIV (PLWH) in sub-Saharan Africa (SSA), and to assess how sex and aging impact the development of these NACM. The cohort is a large, international collaboration across eight countries and 19 treatment centers. Established by the National Institute of Allergy and Infectious Diseases in 2006, the W. Africa cohort is now in its fourth renewal (2021-2026). Participating countries include Senegal, Mali, Cote d’Ivoire, Burkina Faso, Ghana, Togo, Benin, and Nigeria. Data are collected from affiliated cohorts in the regional data center every 24 months. The cohort currently includes >65,000 adult PLWH on anti-retroviral therapy. RESULTS/ANTICIPATED RESULTS: The prevalence of several NACM, such as hypertension and cardiovascular disease, have significantly increased among PWH over time, surpassing prevalence observed in the general population. We therefore expect similar patterns in the W. Africa IeDEA cohort and a high prevalence and burden of both hypertension and diabetes type II in this sample. Additionally, evidence suggests that increasing age and female sex serve as independent risk factors for the development of NACM in PLWH. We anticipate that both increased age and female sex, separately and synergistically, are associated with increased prevalence and burden of hypertension and diabetes type II in this cohort. DISCUSSION/SIGNIFICANCE: With more than 37 million people currently living with HIV, the HIV/AIDS epidemic continues to pose a serious threat to global public health. SSA bears a disproportionate burden of the epidemic with greater than two-thirds of global cases. NACM are now driving morbidity and mortality among PLWH, and increased age and female sex may modify this effect.

We used Cerner Real-World Data™, representing hospital admission records from 2020, to examine patients with co-occurring sickle cell disease and COVID-19 by discharge disposition grouped as death/hospice versus transfers to other facilities, returned home, or left against medical advice. Among the death/hospice group, we found older age and higher rates of congestive heart failure and diabetes. There were also significant differences in tachypnea, mechanical ventilation, minimum O2 saturation, and length of stay with higher rates in the death/hospice group. Awareness of such factors and associated mortality risks for this population may aid in patient care.

OBJECTIVES/GOALS: One in six children in the U.S. has a Neurodevelopmental Disability (NDD). Prechtl’s General Movement Assessment (GMA) is a qualitative predictor of early motor dysfunction. However, no quantitative biomechanical assessment exists to more accurately identify all patients with NDD. METHODS/STUDY POPULATION: With UAMS IRB approval, as part of a larger study, healthy infants were filmed while lying supine on a force plate for 2 minutes. We studied 12 healthy full-term infants (gestational age: 38.9±1.5 weeks, age: 2.1-7.0 months; 7M, 5F; length: 64.0±5.2 cm; weight: 7.2±1.3 kg). Within our data set there were 3 infants transitioning to fidgety period (≤3 months), 4 in the fidgety period, (3-5 months), and 5 that matured beyond fidgety period (>5 months). Center of pressure (COP) path-lengths were gathered from the force plate at 1000 Hz. We grouped our data with K-means clustering and performed statistical analysis with ANOVA. RESULTS/ANTICIPATED RESULTS: We divided our data into 3 distinct clusters. The first group contained infants with moderate variability of movements which included 2 infants between 3 and 5 months and 2 infants slightly outside of this range. The second group, with mild variability in movements, included 4 infants between 2 and 3 months as well as 2 infants just older than 5 months. The third group, with little variability in movements, included 2 infants older than 5 months. A GMA reader (TJ) qualitatively confirmed these findings with video footage. Using a threshold of p<0.05, data sets within the clusters were similar and significantly different from other clusters. DISCUSSION/SIGNIFICANCE OF IMPACT: Fidgety infants have greater variability in COP patterns than their mature counterparts. We anticipate additional COP measurements will correspond with qualitative GMA analyses. Artificial Intelligence-based quantification of the GMA may be useful in earlier detection or prediction of NDD outcomes.

Implementation of clinically useful research discoveries in the academic environment is challenged by limited funding for early phase proof-of-concept studies and inadequate expertise in product development and commercialization. To address these limitations, the National Institutes of Health (NIH) established the National Centers for Accelerated Innovations (NCAI) program in 2013. Three centers competed successfully for awards through this mechanism. Here, we present the experience of one such center, the Boston Biomedical Innovation Center (B-BIC), and demonstrate its remarkable success at the translation of innovations to clinical application and commercialization, as well as skills development and education.

OBJECTIVES/SPECIFIC AIMS: Compare effectiveness of a patient case-based, interactive teaching approach that included optional student genotyping with traditional didactic teaching strategies for increasing students’ knowledge and ability to effectively use pharmacogenomic data in clinical decision making. METHODS/STUDY POPULATION: The UF College of Pharmacy offers a required Personalized Medicine (PM) course for pharmacy students as well as an elective course, Clinical Applications of Personalized Medicine (CAPM). Students dual enrolled in the PM and elective CAPM courses comprised the intervention (INT) group, with interactive patient case-based teaching and the option to undergo personal genotyping, whereas students enrolled in PM alone comprised the control (CTR) group, which primarily used a traditional didactic teaching format and did not include personal genotyping. Both groups completed a pre- and post-course patient case-based test (15 questions/1 point each) to evaluate their knowledge and abilities to apply genotype and other patient-specific data to drug therapy recommendations. Pre- and post-course test scores for knowledge were compared between the INT and CTR groups using the Student t-test. RESULTS/ANTICIPATED RESULTS: In total, 52 students completed surveys (INT group, n=21; CTR group, n=31). Race was similar between groups, but there were fewer females in the INT compared with CTR group (8 vs. 22, p=0.02). Pre-course knowledge scores did not differ between INT and CTR groups (6.8±2.2 vs. 6.3±1.6 respectively, p=0.34), however, post-course scores were significantly higher in the INT Versus CTR group (10.0±2.3 vs. 7.5±1.7, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: There have been significant advancements in the clinical applications of pharmacogenomic and genomic data, however, barriers to routine clinical adoption of genomic medicine persist. Developing education and training methods that equip practitioners to effectively translate genomic data into evidence-based clinical recommendations has been identified as a key strategy to overcome such barriers. Our data suggest that a personalized medicine course that employs patient-centered, case-based teaching strategies and includes optional personal genotyping for students compared with traditional didactic instruction improves students’ knowledge and abilities to apply pharmacogenomic data in practice-based scenarios. These results can inform future strategies for educating healthcare professionals on the clinical use of pharmacogenomic and genomic data.

OBJECTIVES/GOALS: In spite of significant growth in undergraduate research, there is little accessible RCR training material targeting this group. The goal of this project was to develop level appropriate RCR materials and test them for effectiveness of teaching basic knowledge of RCR. It was developed cognizant of the type of learning preferred by this group. METHODS/STUDY POPULATION: Todays undergraduate students are digital natives accustomed to using on-line resources for learning and value the ability to work independently. An asynchronous, online series of eight RCR modules were developed using PowerPoint. Audio instruction was overlaid over the presentations and uploaded to YouTube. Each module includes quiz at the end that must be completed with a 90% score in order to continue and students can retake each quiz until correct. Case studies, a plagiarism game, and additional resources such as infographics created by the Office of Research Integrity were included. 275 first year undergraduates completed the pilot and the on-line retrospective pre-post assessment that included 28 Likert scale items and two open-ended questions that were analyzed with RapidMiner. RESULTS/ANTICIPATED RESULTS: Participants rated their ability prior to and after the course to recognize the roles/responsibilities of a mentor, maintain and organize data records, recognize what constitutes research misconduct and multiple types of plagiarism, define ethics of authorship and the types of peer review, recognize responsible handling of human and animal subjects and to define collaborative research. Responses were analyzed using t-Tests and all items showed a significant increase. Students reported between a 28% and 50% increase in knowledge in each topic and gains in understanding where to report RCR violations. Text analysis using RapidMiner provided developers with suggestions on how to enhance the project. Students reported finding the course concise and easy to understand and valued the included case studies. DISCUSSION/SIGNIFICANCE: This study demonstrated that RCR materials developed specifically for todays undergraduate students, presented an easily accessible format, effectively conveys the basics of RCR. The on-line, asynchronous format made it accessible to those for whom in person course is not possible. This model fills the gap in RCR training for early researchers.

The rate at which the coronavirus disease (COVID-19) spread required a rapid response across many, if not all, industries. Academic medical centers had to rapidly evaluate, prioritize, and coordinate the multiple requests for clinical trial participation. This involved redirecting resources and developing a collaborative system for assessment, decision making, and implementation. Our institution formed a team with diverse representation from multiple stakeholders to review and prioritize all research protocols related to COVID-19. To accomplish this, a prioritization matrix was developed to help determine the order in which the protocols should be placed for consideration by the treating clinician. The purpose of the team was to review the COVID-19 clinical trials in the pipeline, prioritize those trials that best met the needs of our patients, oversee training and resource needs, and lead the formulation of procedures for integration with clinical care. Resources from the Clinical Research Unit were then allocated to support the swift execution of such studies. This manuscript describes that process, the challenges encountered, and the lessons learned on how to make all clinical trials more successful in a complex and dynamic environment.

Translation of research discoveries into health impact can take many years, creating delays in improving clinical outcomes. One approach to promoting timely translation is to examine successful cases in order to understand facilitators and strategies for overcoming barriers. We examined the development of evidence-based management for neonatal abstinence syndrome (NAS) at one academic medical center, with a primary focus on pharmacologic treatment. Despite a substantial increase in NAS case incidence starting in the early 2000s, significant sociocultural, policy, and regulatory barriers limited collaborative NAS research. Facilitators for translation encompassed: 1) pursuing research of societal interest, 2) building an effective interdisciplinary team, 3) intentionally linking clinical, research, and advocacy efforts, 4) broad stakeholder engagement across clinical, policy, and research arenas, and 5) leveraging local resources. Challenges included lack of commercially available U.S. Food and Drug Administration approved neonatal drug formulations, legal and regulatory barriers related to off-label and illicit use of opioids, recruitment for a treatment associated with drug withdrawal syndromes, misalignment of research design needs with real-world scenarios, and episodic funding. Benefits of successful translation included improvements in clinical care, reduced healthcare costs related to NAS, and enhanced legislative, policy, and research strategies to support broader neonatal investigations.

OBJECTIVES/GOALS: The goal of this study was to perform a comparative, multi-reader, retrospective clinical evaluation of prostate multiparametric MRI (mpMRI) at 3 Tesla (3T) vs. 7 Tesla (7T) primarily in terms of prostate cancer localization. Subjective measures of image quality and artifacts were also evaluated. METHODS/STUDY POPULATION: Nineteen subjects were imaged at 3T and 7T between March 2016 and October 2018 under IRB-approved protocols. Four radiologists retrospectively and independently reviewed the data, and completed a two-part assessment for each dataset. First, readers assessed likelihood of cancer using Prostate Imaging Reporting & Data System (PI-RADS) guidelines. Accuracy of cancer detection was compared to findings from prostate biopsy. The numbers of correctly or incorrectly classified sextants were summed across all four readers, then used to summarize detection performance. Second, readers assigned a score on a five-point Likert scale to multiple image quality characteristics for the 3T and 7T datasets. RESULTS/ANTICIPATED RESULTS: Sensitivity and specificity of 3T and 7T datasets for sextant-wise cancer detection were compared by paired two-tailed t-tests. Readers identified more sextants harboring cancer with the 3T datasets while false-positive rates were similar, resulting in significantly higher sensitivity at 3T with no significant differences in specificity. Likert scores for image quality characteristics for 3T and 7T datasets were compared by applying paired two-tailed t-tests to mean scores of the four radiologists for each dataset. Readers generally preferred the 3T datasets, in particular for staging and assessment of extraprostatic extension as well as overall quality of the contrast-enhanced data. DISCUSSION/SIGNIFICANCE OF IMPACT: Readers agreed 7T prostate mpMRI produced images with more anatomic detail, though with equivocal clinical relevance and more pronounced artifacts. Reader unfamiliarity with 7T images is a major extenuating factor. Forthcoming technological developments are anticipated to improve upon the results.

OBJECTIVES/GOALS: The goal of the study is to provide insights into the use of machine learning methods as a means to predict heterogeneity of treatment effect (HTE) in participants of randomized clinical trials. METHODS/STUDY POPULATION: Using data from 2,441 participants enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial of daily low-dose aspirin vs placebo in the United States, we developed multivariable risk prediction models for the composite outcome of dementia, disability, or death. We used two machine learning techniques, decision trees and random forests, to develop novel non-parametric outcomes classifiers and generate risk-based subgroups. The comparator method was an extant semi-parametric proportional hazards predictive risk model. We then assessed HTE by examining the 5-year absolute risk reduction (ARR) of aspirin vs placebo in each risk subgroup. RESULTS/ANTICIPATED RESULTS: In the random forest classifier, the ARR at 5 years in the highest risk quintile was 13.7% (95% CI 3.1% to 24.4%). For the semi-parametric proportional hazards model, the ARR in the highest risk quintile was 15.1% (95% CI 4.0% to 26.3%). These results were comparable and provide evidence of the viability of internally developed parsimonious non-parametric machine learning models for HTE analysis. The decision tree model results (5-year ARR = 17.0%, 95% CI= -5.4% to 39.4% in the highest risk subgroup) exhibited more uncertainty in the results. DISCUSSION/SIGNIFICANCE: None of the models detected significant HTE on the relative scale; there was substantial HTE on the absolute scale in three of the models. Treatment benefit on the absolute scale may be regarded as bearing greater clinical importance and may be present even in the absence of benefit on the relative scale.

OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.

In a prospective, remote natural history study of 277 individuals with (60) and genetically at risk for (217) Parkinson’s disease (PD), we examined interest in the return of individual research results (IRRs) and compared characteristics of those who opted for versus against the return of IRRs. Most (n = 180, 65%) requested sharing of IRRs with either a primary care provider, neurologist, or themselves. Among individuals without PD, those who requested sharing of IRRs with a clinician reported more motor symptoms than those who did not request any sharing (mean (SD) 2.2 (4.0) versus 0.7 (1.5)). Participant interest in the return of IRRs is strong.

OBJECTIVES/SPECIFIC AIMS: The objective of this partnership was to create a global network of clinical and public health researchers and communities conducting technology-assisted research in noncommunicable disease. METHODS/STUDY POPULATION: The University of Rochester’s Clinical and Translational Science Institute (CTSI) has successfully leveraged the informatics core’s capacity into an emerging network of organizations that focus on technology and health in settings outside of the mainland United States. The CTSI coordinated with another NIH-funded infrastructure program [the RCMI Translational Research Network (RTRN)] to identify partner institutions interested in technology and health. RTRN identified the University of Puerto Rico and the University of Hawaii, both of which serve as hubs for common research interests in technology and health throughout the Caribbean and the Pacific. This network was formalized as the CDC’s Coordinating Center for its Global and Territorial Health Research Network (the “Global Network”), with additional US partners (Yale, University of Illinois at Chicago, University of North Caroline Chapel Hill, and the University of South Florida) within a wider scope of the CDC’s Prevention Research Centers (PRC) program. RESULTS/ANTICIPATED RESULTS: Through combining 2 main NIH-funded research infrastructure networks (CTSA and RTRN), with a large CDC-funded PRC, the University of Rochester’s Informatics Core was successful in establishing a new productive global health network throughout Latin America and the Caribbean, and in the Pacific, garnering additional research support from NIH Fogarty and other programs. The resulting network not only supports locally-important research in technology and health on compelling health issues (eg, diabetes, ZIka, participation in research), but also facilitates community engagement through local partnerships and the cores of the involved networks. In addition, much of the information and communications technology (ICT)-related research and learnings from the Global Network activity is immediately applicable to populations in the United States, served by the various collaborative networks. In total, while new, the Global Network supports a wide range of projects and engagements throughout the world that expand local informatics capacity and use of technology in the research process and to address global health problems, further enhancing the CTSI’s informatics core to serve the needs of its own constituency and promote research engagement with technology within this population. Local research collaborative projects reinforce the utility of the network and its resources, evidenced by tools, publications, partnerships, and conference presentations that have arisen. Lessons to date from this Global Network collaboration include: specific global research projects provide opportunities for partnership building and meaningful collaboration, team science is of central importance in distributing the work of the network, synergy is multidirectional with expertise and need flowing in all directions, and project team members in all locales learned and contributed substantially in ways that carried into their other responsibilities. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall partnership has created opportunity for South-South collaboration, for adaptation of projects among locales, and has helped boost reputational value for all partners involved. Implications for other CTSA awardees include: global collaboration can serve core research and technical needs for the CTSA itself and its local partners, CTSA status can be leveraged to access resources to support local research, and collaboration in other federally-funded research networks helps expand the insight, scope, and potential for new research.

The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.