ABSTRACT IMPACT: This study highlights the importance of creatine in developmental myelination and remyelination to investigate whether creatine provides a therapeutic value during a central nervous system (CNS) demyelinating insult with a potential value in patients with Multiple Sclerosis. OBJECTIVES/GOALS: Creatine is vital for ATP buffering in the brain. Interestingly, the cells that generate myelin express the main enzyme for creatine synthesis, Gamt. Patients with Gamt mutations display intellectual delays and impaired myelination. Therefore, we hypothesize that creatine is essential for developmental myelination and improves remyelination. METHODS/STUDY POPULATION: To investigate these hypotheses, we developed a new transgenic mouse model with LoxP sites flanking exons 2-6 of the guanidinoacetate methyltransferase (Gamt) gene where excision leads to expression of a green fluorescent tag allowing us to track the cells normally expressing Gamt. We used immunohistochemistry techniques to look at the corpus callosum, the main white matter tract in the brain, and evaluate the number of oligodendrocytes (OL), glial cells responsible for generating myelin. We also used the cuprizone model of toxic demyelination to investigate whether dietary creatine and cyclocreatine, a planar analog of creatine that more efficiently crosses the blood-brain barrier, can enhance remyelination. RESULTS/ANTICIPATED RESULTS: In this mouse model, we show a 95% (+/-0.47%, n=3) co-localization of Gamt within mature OL during postnatal (P) day P14 with no co-localization in neurons or other glial cells. This suggests that mature OL are the main cells making creatine in the CNS. Next, we show that knocking out Gamt leads to a significant reduction in OL in the developing corpus callosum, at P14 and P21 (P14: 0.007, n=3; P21: 0.04, n=3). We also show that creatine supplementation causes a trending increase in mature OL density in the corpus callosum following cuprizone demyelination (2% creatine; p=0.052; n=4). Interestingly, cyclocreatine supplementation significantly increased mature OL density in the corpus callosum following cuprizone demyelination (0.1% cyclocreatine; p=0.034; n=4). DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies highlight the important role creatine plays in developmental myelination and remyelination to investigate whether creatine and cyclocreatine provide a therapeutic value during a CNS demyelinating insult. This work investigates a potential therapeutic value of creatine to patients with Multiple Sclerosis.

OBJECTIVES/SPECIFIC AIMS: Chronic obstructive pulmonary disease (COPD) is a leading cause of both hospitalizations and readmissions in the United States, and about 1 in 5 hospitalized patients with COPD will be readmitted within 30 days. COPD-focused self-management programs are frequently used to help patients better manage their symptoms and prevent hospitalization. However, while the majority of patients with COPD have at least one comorbidity, most trials of COPD self-management programs either excluded patients with significant comorbidities or did not analyze the impact of comorbidities on patient outcomes. Using data from the BREATHE trial of a COPD self-management program, this study aims to determine if patient post-intervention outcomes differ based on the intensity and type of patient comorbidities. METHODS/STUDY POPULATION: In total, 240 patients hospitalized for COPD were randomly assigned to either a comprehensive self-management intervention or usual transitional care. Primary outcomes for this trial were the number of COPD-related hospitalizations and emergency department visits at 6 months and changes in COPD-specific quality of life. To determine whether patient comorbidities modify the effect of the self-management intervention on readmission and quality of life outcomes, we will compare patient outcomes across groups stratified by comorbidity burden (Charlson Comorbidity Index) and type (baseline diagnosis of congestive heart failure, diabetes, and depression). In addition, we will use regression analysis with interaction terms to test for interaction between comorbidity burden/type and intervention assignment. RESULTS/ANTICIPATED RESULTS: We hypothesize that the effect of the self-management intervention will differ in patients with greater comorbidity burden due to competing medical demands for patients with multimorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study will help clinicians better target disease-specific self-management programs to the groups of patients with COPD who are likely to receive the greatest benefit from this type of intervention.

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.

Inadequate training in the interpersonal skills of conducting informed consent conversations has long been noted as a challenge for clinical research recruitment and retention. To address this critical gap, Tufts Clinical and Translational Science Institute developed regular trainings for clinical research coordinators and other research staff on the practical skills of communicating informed consent using community members as simulated patients for role-playing exercises. In this paper, we assess the reach and effectiveness of these trainings and describe the impact of employing community stakeholders as simulated patients. We found that by embedding community members in the trainings, clinical research coordinators get to hear diverse perspectives, experience a range of patient responses, and learn from the lived experience of the communities that research tries to serve. Utilizing community members as trainers also helps to dismantle traditional power dynamics by demonstrating the organization’s commitment to inclusiveness and community engagement. Based on these findings, we suggest that training on informed consent include more simulated consent exercises that feature interaction with community members who can provide real-time feedback to coordinators.

OBJECTIVES/GOALS: The Translational Science Benefits Model (TSBM), developed at Washington University in St. Louis, was used to create a survey to collect group-level data on the real-world impacts of research. It was used with two cohorts of CTSA-supported pilot studies to compare the benefits of campus-community partnerships to campus-only projects. METHODS/STUDY POPULATION: Investigators from two funding streams were surveyed: a campus-based cohort (n=31), and a campus-community partnership cohort (n=6). All studies were related to COVID-19. The Translational Benefits Survey collected quantitative and qualitative data for each of the 30 TSBM benefits, in 4 benefit categories: clinical, community, economic and policy. Text provided by investigators to support each reported benefit was evaluated by two coders through a process that required coder consensus to verify a benefit as realized. Verified benefits were aggregated for each cohort, and the percentage of projects per cohort with realized clinical, community, economic and policy benefits were calculated. RESULTS/ANTICIPATED RESULTS: Campus-community partnerships did not realize any clinical benefits, whereas 26% of campus-based projects realized at least one clinical benefit. In contrast, campus-community partnerships were more likely to realize community health benefits (17% vs 10% of campus projects) and economic benefits (17% vs 13% of campus projects). We identified a substantial amount of self-reported benefits (64% across all categories) that were unable to be confirmed as realized using the provided text, which either described activities not relevant to the selected benefit, or lacked critical details needed to verify that the benefit was realized. DISCUSSION/SIGNIFICANCE: This project demonstrates that the TSBM can be utilized to collect group-level data and to compare cohorts’real-world benefits. It also illuminates the need to improve the process for verifying self-reported benefits. Sharing data on these real-world impacts has the potential to convey the strengths of translational science to the public.

Clinical trials conducted with incarcerated populations are rare. We present a case example of one such jail-based cancer prevention clinical trial to demonstrate the importance of including a theory-driven approach to intervention framing, novel experimental designs to boost access to low-risk trials, and retention strategies for long-term follow-up of hard-to-reach populations. As such we offer a social determinant of health framework to ensure cancer prevention research is conducted through the lenses of health promotion and health equity. Deviations from the gold-standard randomized control design, transparent systematic allotment, and street-based outreach retention strategies contribute to the feasibility of conducting clinical trials in carceral settings and after people leave jail. Best practices presented can be used in design and conduct of future clinical trials with criminal legal system-involved populations.

Clinical trials face many challenges with meeting projected enrollment and retention goals. A study’s recruitment materials and messaging convey necessary key information and therefore serve as a critical first impression with potential participants. Yet study teams often lack the resources and skills needed to develop engaging, culturally tailored, and professional-looking recruitment materials. To address this gap, the Recruitment Innovation Center recently developed a Recruitment & Retention Materials Content and Design Toolkit, which offers research teams guidance, actionable tips, resources, and customizable templates for creating trial-specific study materials. This paper seeks to describe the creation and contents of this new toolkit.

Structured processes to improve the quality and impact of clinical and translational research are a required element of the Clinical and Translational Sciences Awards (CTSA) program and are central to awardees’ strategic management efforts. Quality improvement is often assumed to be an ordinary consequence of evaluation programs, in which standardized metrics are tabulated and reported externally. Yet evaluation programs may not actually be very effective at driving quality improvement: required metrics may lack direct relevance; they lack incentive to improve on areas of relative strength; and the validity of inter-site comparability may be limited. In this article, we describe how we convened leaders at our CTSA hub in an iterative planning process to improve the quality of our CTSA program by intentionally focusing on how data collection activities can primarily advance continuous quality improvement (CQI) rather than strictly serve as evaluative tools. We describe our CQI process, which consists of three key components: (1) Logic models outlining goals and associated mechanisms; (2) relevant metrics to evaluate performance improvement opportunities; and (3) an interconnected and collaborative CQI framework that defines actions and timelines to enhance performance.