OBJECTIVES/SPECIFIC AIMS: People with metabolically abnormal obesity (MAO), defined as those with insulin resistance and high intrahepatic triglyceride, are at high risk for developing type 2 diabetes and cardiovascular disease. Weight loss through reduced energy intake and increased physical activity has profound impacts on improving cardiometabolic function. However, the specific additional effects of exercise training with diet-induced weight loss on metabolic function are equivocal. METHODS/STUDY POPULATION: A comparative trial is ongoing in MAO adults undergoing 8-10% weight loss induced by a very-low fat plant-based (PB) diet with structured exercise training (n=8) compared to the same weight loss induced by the PB diet alone (n=3). RESULTS/ANTICIPATED RESULTS: Preliminary results indicate that, PB diet with or without exercise training results in significant weight loss concomitant with enhanced insulin sensitivity, reduced intrahepatic triglyceride, reduced 24-hour postprandial glucose response, reduced fat mass, and reduced diastolic blood pressure. Those undergoing PB diet with exercise training had greater improvements in muscular strength and cardiorespiratory fitness than those undergoing PB diet alone. Differences between intervention groups for other cardiometabolic measures are not yet known. DISCUSSION/SIGNIFICANCE OF IMPACT: Each of the interventions resulted in improved cardiometabolic measures; however the extent of the differences between the interventions is not yet clear. It is hypothesized that compared with weight loss induced by a PB diet, the same weight loss induced by a PB diet and structured exercise training will i) cause greater improvement in skeletal muscle insulin sensitivity, ii) will attenuate the usual decline in muscle mass while increasing strength, and iii) result in greater increases in left ventricular diastolic function. The long-term objective of this proposal is to provide a foundation for future studies evaluating mechanisms for the effects of exercise in cardiometabolic disease prevention and therapy.

ABSTRACT IMPACT: Our research has the potential to impact human health by identifying a neural network that can be used to predict time to relapse in individuals with alcohol use disorder. OBJECTIVES/GOALS: Preoccupation towards alcohol use (e.g. craving, rumination, and poor executive control) is a maladaptive behavior associated with relapse risk. We investigated whether alterations in resting state networks known to mediate preoccupation could predict time to relapse in alcohol use disorder (AUD). METHODS/STUDY POPULATION: 50 participants with alcohol use disorder (AUD) (Age: M=41.76, SD=10.22, 19 females) were recruited from an addiction treatment program at ˜2 weeks of abstinence. fMRI data were preprocessed with the Human Connectome Project pipeline. Strength of resting state functional connectivity (RSFC) within two networks known to mediate the ‘Preoccupation go’ (PG) and ‘Preoccupation stop’ (PS) stages of addiction were calculated. T-tests were conducted to compare RSFC between subsequent abstainers and relapsers (after 4 months). Linear regressions were conducted to determine whether RSFC (of PG and PS networks) can predict time to relapse. Craving measures were included in the model. RESULTS/ANTICIPATED RESULTS: 19 AUD relapsed during the 4-month follow-up period. There were no RSFC group effects (subsequent abstainers and relapsers) in the PG or PS networks. Number of days to relapse could be predicted by PG RSFC (F(1,17)=14.90, p=0.001, r 2=0.47). Time to relapse increased by 13.19 days for each PG RSFC unit increase. Number of days to relapse could be predicted by PS RSFC (F(1,17)=9.39, p=0.002, r ²=0.36). Time to relapse increased by 12.94 days for each PS RSFC unit increase. After adding a self-report craving measure (i.e. Penn Alcohol Craving Scale) in the prediction model, both PG and PS RSFC still significantly predicted time to relapse. Craving metric did not predict time to relapse. DISCUSSION/SIGNIFICANCE OF FINDINGS: RSFC in preoccupation networks during short-term abstinence predicted time to relapse. These preliminary findings highlight promising targets for AUD neuromodulation interventions aimed to reduce relapse. Future larger scale studies that examine the effects of covariates and mediators are needed.

OBJECTIVES/SPECIFIC AIMS: This project has 2 overarching objectives: (1) to investigate the acceptability of the Michigan Surgical and Health Optimization Program (MSHOP) among referred patients, and to describe individual motivations behind enrollment Versus nonenrollment; and (2) to identify patient and program related factors associated with adherence and LOS and readmission rates. METHODS/STUDY POPULATION: Hypothesis—(1) MSHOP participants will report overall satisfaction with the program. Individuals that are satisfied with the program will be likely to perceive the program as effective. Subjects that declined MSHOP will be more likely to perceive their outcomes as immutable. (2) MSHOP patients will have shorter hospital stays and fewer readmission compared with patients who declined MSHOP. Methods—this study will use both qualitative and quantitative methods to investigate patient experiences and program efficacy. First, a convenience sample of patients who were referred to the MSHOP within the previous 12 months will participate in structured interviews to assess program acceptability, patient satisfaction with individual components of MSHOP, and perception of program efficacy. Interviews will also include patients who declined to enroll in MSHOP. Interviews for these subjects will include questions that assess why patients chose to decline enrollment. Second, there will be a retrospective cohort study comparing hospital outcomes among patients who enrolled in MSHOP Versus those who chose not to enroll. Analysis—interviews will be recorded and transcribed for thematic analysis to identify patterns associated with satisfaction or dissatisfaction with the MSHOP. Multivariate regression will be used to determine effect of MSHOP participation on postsurgical length-of-stay and 30-day readmission rate. Demographics and procedure type will be included as covariates. RESULTS/ANTICIPATED RESULTS: In total, 28 interviews have been transcribed, and are in the initial stages of thematic analysis. Interviews have thus far suggested that patients have been satisfied with MSHOP and would recommend the intervention to other patients. Retrospective data regarding hospital length of stay for MSHOP patients from September 2014 to December 2016 has been acquired and is being processed. The characteristics of patients that tend to participate more actively in MSHOP will be explored. We anticipate that active participation in the MSHOP will be associated with shorter hospital stays and fewer readmissions. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will be one of the first to characterize patient perception of MSHOP, in particular its use of tracking step counts and breathing exercises to promote a form of prehabilitation that is easier to integrate into daily life. This project will investigate MSHOP’s effect on patient outcomes, as well as explore factors that may associate with better patient adherence and outcomes. This would help further optimize the MSHOP as an intervention.

OBJECTIVES/GOALS: This study surveyed parents and/or caregivers of children with Duchenne and Becker muscular dystrophy (DBMD) to obtain their perspectives on experiences during multidisciplinary team (MDT) clinic visits. The goal was to improve DBMD care by identifying positive and negative aspects of the visits. METHODS/STUDY POPULATION: Multidisciplinary care models have been widely used in many disciplines, as they provide excellent opportunities for patient-centered care (PCC). Survival of patients with Duchenne muscular dystrophy (DMD) has improved with multidisciplinary care. As the model continues to evolve, additional services and disciplines are added, and exploring parents’ and caregivers’ perspectives on multidisciplinary care for patients with DBMD must be assessed. A survey, via a non-identifiable Redcap link, was emailed to registered parents/caregivers through The Duchenne Registry provided by Parent Project Muscular Dystrophy (PPMD). The survey contained questions concerning the children’s demographics, medical information, knowledge, and perspectives on MDT visits. RESULTS/ANTICIPATED RESULTS: A total of 186 parents/caregivers of DMBD patients responded to the survey. Respondents were white (83.1%), bi/multi-racial (9.3%), African American (1.6%), and other (2.7%). The average travel distance to the care site was 228.37 miles. Most respondents (75%) had their visits within one day, but 25% had visits over ≥2 days. 89.0% of respondents preferred a single MDT meeting with their child’s care providers; 89.4% indicated they had enough time with each provider, 86.1% were satisfied with the MDT care, and 81% said they received enough information prior to the visit. Scheduling difficulties were rare for MDT visits, but common when arranging care with providers not included in the MDTs. DISCUSSION/SIGNIFICANCE: MDT clinic visits enable patients to see multiple caregivers in a single visit. Our study suggests that parents and caregivers of DBMD patients prefer to have MDT visits and are satisfied with the care. This information will support the DBMD community as they continue to advocate for MDT visits.

OBJECTIVES/GOALS: The goal of this evaluation is to assess the value added by offering a CTSA-funded Translational Science Leadership Academy (TSLA) for faculty research leaders. We aim to disseminate lessons learned to help inform best practices for other CTSA hubs promoting team science, specifically research team leadership. METHODS/STUDY POPULATION: Atrium Health Wake Forest CTSI Team Science Program has completed 3 iterations of the TSLA, offered to all faculty leading research teams. Academies were attended by 16 (2020 cohort), 17 (2021) and 18 (2022) research faculty. For the 2022 Academy, the CTSI Evaluation Program, in collaboration with the Team Science Program, implemented a pre-post assessments for all cohort participants. These assessments tracked self-rated competencies changes, satisfaction with the program, and any recommendations for program improvement. All future cohorts will receive these assessments as well. Results will be presented from 15 semi-structured interviews with participants. We will incorporate continuous improvement cycles to gather future feedback, track recommendations and identify future directions for content. RESULTS/ANTICIPATED RESULTS: Faculty from all ranks (Assistant, Associate, Full Professor, Department Chair) participated. Leadership competencies were assessed through a pre-post comparison, each self-rated by Academy participants. The 2022 cohort showed an increase in every competency at the time of post-assessment. When asked how they would rate the overall quality of their team leadership, cohort average increased from 4.3 to 5.5 (+1.2 on a 7-point scale) from pre- to post-assessment. Additionally, 80% of post-assessment respondents plan to make (or have already made) changes in their team leadership practices. Through the qualitative evaluation, we expect to gain insight into individual experiences, changes made after participation in the Academy, and what needs still exist for research leaders. DISCUSSION/SIGNIFICANCE: Competent team leadership is key to realizing our clinical and research mission. The CTSI Translational Research Leadership Academy is an important way to bolster study team productivity, engagement and satisfaction among research teams. This project provides insight for CTSA hubs interested in promoting team science best practices.

OBJECTIVES/SPECIFIC AIMS: Electronic health records have become the fulcrum for efforts by institutions to reduce errors, improve safety, reduce cost, and improve compliance with recommended guidelines. In recent times they are also being considered as a potential game changer for improving patient recruitment for clinical trials (CT). Although the use of CDS for clinical care is partially understood, its use for CT patient identification and recruitment is young and a great deal of experimental and theoretical research is needed in this area to optimize the use of CDS tools that personalize patient care by identifying relevant clinical trials and other research interventions. The use of CDS tools for CT recruitment offers a great deal of possibilities, but some initial usage has been disappointing. This may not be surprising because, while the implementation of these interventions is somewhat simple, ensuring that they are embedded into the right point of the care providers workflow is highly complex and may affect many actors in a clinical care setting, including patients, nurses, physicians, clinical coordinators, and investigators. Overcoming the challenges of alerting providers regarding their patient’s eligibility for clinical trials is an important and difficult challenge. Translating that effort into effective recruitment will require understanding of the psychological and workflow barriers and facilitators for how providers respond to automated alerts requesting patient referrals. Evidence from using CDS for clinical care that shows alerts become increasingly ignored over time or with more exposure (1, 2). The features, timing, and method of these alerts are important usability factors that may influence effectiveness of the referral process. Focus group methods capture the shared perspectives of a phenomenon and have been shown to be an effective method for identifying perceptions, attitudes, information needs, and other human factors effecting workflow (3, 4). Our objective was to develop a generalizable method for measuring physician and clinic level factors defining a successful point of care recruitment program in an outpatient care setting. To achieve this we attempted to (a) Characterize provider’s attitudes regarding CTs referrals and research. (b) Identify perceived workflow strategies and facilitators relevant to CT recruitment in primary care. (c) Develop and test a pilot instrument. METHODS/STUDY POPULATION: The methods had 3 phases: focus groups, development of item pool, and tool development. Focus group topics were developed by 4 experienced investigators, with training in biomedical informatics, cognitive psychology, human factors, and workflow analysis, based upon a knowledge of the literature. A script was developed and the methods were piloted with a group of 4 clinicians. In all, 16 primary care providers, 5 clinic directors, and 6 staff supervisors participated in 6 focus groups, with an average of 5 participants each, to discuss clinical trial recruitment at the point of care. Focus groups were conducted by the development team. Audio recording were content coded and analyzed to identify themes by consensus of 3 authors. Item Pool generation involved extracting items identified in the focus group analysis, selecting a subset deemed most interesting based on knowledge of the recruitment literature and iteratively writing and refining questions. Instrument development consisted of piloting an initial 7-item questionnaire with a local primary provider sample. Questions were correlated with the item pool and limited to reduce provider burden, based on those that the study team deemed most applicable to information technology supported recruitment. Descriptive statistical analysis was performed on the pilot survey results. An online survey was developed based on the findings of the focus groups and emailed to 127 primary care providers who were invited to participate. In total, 36 questionnaires were completed. This study was approved by the University of Utah Institutional Review Board. RESULTS/ANTICIPATED RESULTS: The results section is organized into 3 sections: (a) Focus groups, (b) Item generation; and (c) Questionnaire pilot. (I) (1) Focus Groups. Themes identified through a qualitative review are presented below with illustrative comments of participants. The diversity of attitudes and willingness to support clinical trial recruitment varied so substantially that no single pattern emerged. Attitudes ranged from enthusiastic support, to interest in some trials to disinterest or distrust in trials in general. Compensation for time spent, which could be monetary, informational, or through professional recognition; and provider relationship with the study team or pre-selection of specific trials by a clinic oversight committee, and importance to providers practice positively affected willingness to help recruit. “I would love to get people into clinical trials as much as possible... If it works for them you are going to help a whole lot of other people.” If we felt like we have done every possible thing that was already established as evidence-based and it didn’t work out, then we would consider the trials. I think that studies are more beneficial for specific specialists... There might be a whole slew of things that I never deal with or don’t care about because it’s not prevalent for my patient population. Local and reputable... A long distance someone asking to do something is just not the same as someone in the trenches with you. The bottom line is how much work is involved at our end and if there is going to be any compensation for that. I think also the providers would like have feedback on what they referred them to. And how did it go? So did we pick the right patient? ... It helps us to know, did they even sign up for the study? Getting your name on a research paper would be nice too. Lack of information regarding trials reduced support for recruitment of patients. Providers stated that they do not know how to quickly find information about studies, nor do they have time to find the information, and therefore cannot efficiently council patients regarding trial participation. Notifications regarding clinical trials that were deemed to be important included: Trial coordinator intention to recruit patients, enrollment of a patient in a clinical drug trial, trial progress and result updates, and reports of effectiveness of provider recruitment efforts. Perceived information needs regarding trials that providers are referring patients to included: trial purpose, design, benefits and risks, potential side effects, intervention details, medication class (mechanism of action), drug interactions with study drug, study timeline, coordinator contact information, link to print off patient handouts, enrollment instructions, and a link to study website. (2) It’s just we don’t know any of the information ... and it can’t take any of our time. ... I don’t have time to research it. Sometimes the patients ask me questions about it and I would like to be in a position where I have some information about it before I am asked. It would be nice to be notified if they [my patients] are enrolled in the trial, when it turns into actual recruitment. I do like to know if they’re in [a trial] so that when they come in for problems, I at least know that they might be on a study medication so I can be safe. I’ll get an ER message, “The patient got admitted. There blood pressure’s, you know, tanked, because they’re on a study drug I didn’t know anything about.” if there’s certain side effects that I need to be watching out for. It would also be good to have a contact person from the study in case we need to notify them of. “this person’s possible having an adverse event. Look into it more.” (3) Provider burden associated with patient recruitment appeared to be a deterrent. These burdens included adding to the providers task list, increasing the time required to complete a visit, and usurpation of control over the patients care plan with the associated effect on provider quality scores. We don’t have time. I mean, we don’t even take a lunch break. I have 15 minutes and now this is taking this many minutes away from my 15 minutes. I am just sick of extra work. We already have so much extra work. It’s just more stuff to do. We are maxed out on stuff to do. Right now, part of our compensation depends on having our patients A1Cs controlled. And so if we’re taking a chance that maybe they’re getting a medicine, maybe they’re not, maybe it’ll help, maybe it won’t, its gonna further delay our ability to get paid. Cause they’re like “I’m not going to let you go mess up my patient and I’m going to have to deal with the consequences is kind of the way they think. If you’re going to put the patient in a study, being able drop them from our registry so we don’t get penalized for a negative outcome [is important]. (4) Patient’s needs were a priority among factors influencing likelihood to help recruitment patients. Providers considered perceived benefit or risk to the patient, such as additional healthcare services, increased monitoring, financial assistance, or access to new treatments when other options have been ineffective, important; as well as continuance of established care that has proven effective, and ethical recruitment that addresses language and mental health to ensure that patients can make decisions regarding study participation. If there’s something great that’s gonna benefit a patient, I would definitely wanna know about it to give them that option. You know that’s what we wanna try to do is make our patients better. Someone who is really well controlled and doing well, I would not tend to put them toward the study. Just keep going with what’s working right now. Sometimes there’s financial incentives for them to participate, so you know, if its a good fit its easy to at least offer that to the patient. They get treatment maybe that they can’t afford. You don’t want to be seen as somebody who's forcing a patient... if their provider is telling them this is a good idea you are more likely to get your patient to do it. I think they have to understand what a clinical trial is, first of all, in that it’s a trial. Right? We’re trying to figure out if a certain treatment is good or not. It may not work. It may work. With many patients, they don’t only have medical problems, but significant mental illness that sometimes interferes a lot with just our treatment of them here for their clinical problems. And so, that probably would interfere with someone’s ability to understand and consent to a trial. And the patients have the right to make that choice. I don’t need to be—I don’t mind influencing them on things I know about, I think are invaluable, but I don’t need to be a barrier to them. (5) Perceived responsibility in trial recruitment varied substantially, from no involvement at all, to prescreening, counseling, or recruiting patients. Some providers felt that they should have the right to say “no” to recruitment of their patients while others believed prescreening was an unnecessary burden, outside of their role as a primary care provider. if someone prescreens and thinks its appropriate and gives me that judgment call to say, do you think it would be a good fit? I think one of them, they sent, and I said, Oh, I don’t think it would be a good fit because of this...So that would be fine. I don’t think I need to be a gatekeeper for studies. I mean, if there’s people that qualify for a study, and there’s a great study that’s been approved, and they can recruit them without me knowing, that doesn’t bother me in the slightest. I liked how it was—I could do a simple referral ... someone else figured out the qualifications. if we knew of ongoing studies and if we thought a certain patient may qualify for a certain study, we just contact the coordinator, and then they just take care of the rest. I think that appropriate ... from our perspective, would be, “Are you interested?” “This is the number for a person who can sit with you, talk with you about a trial, tell you everything about it, answer your questions, and then you can make a decision.” I’m not going to let you go mess up my patient and I’m going to have to deal with the consequences. (6) A clinic-implementation approach that systemizes workflow, limits the number of trials providers are asked to recruit for, and minimizes provider time burden is needed. Suggested methods for informing providers of patient clinical trial eligibility included: email, alerts, in-basket messages, texts, phone-calls, and in-person contact. People are so sick of change, change, change, change ... if there’s no stability whatsoever, then people get frustrated and start to burn out. Having my staff remember how to do it correctly and I remember what studies we have going ... it becomes somewhat of a burden... it’s hard for us to remember as we are flying through our day. There just needs to be a clear understanding with those roles... Who does the patient call? We don’t want to look like we don’t know what we are doing. There probably should be a selection committee put together from various people who have stakes in the community, at least who can say, “This would be applicable for xx clinic.” (7) Provider Suggestions Providers had multiple suggestions regarding notification methods. (II) Development of item pool and construction of questionnaire The specific items were constructed from literature review on physician’s attitudes and results from the focus group. The overarching concern was on readability, brief questionnaire size, and relevance. A large item were constructed and then reduced through piloting. (III) Questionnaire Pilot Results: The 7-item pilot questionnaire was completed by 36 physicians (28% response rate). In this section, we report the empirical results. DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion Relevance of Methods. Overall, the described methods for determining components for a recruitment program in primary care shows early promise. The focus groups that consisted of providers, staff and administrators resulted in insights as to workflows, attitudes, and clinical processes. These insights significantly varied across clinics. This variation supported the need for an individualized clinic-based approach that will meet local needs. During the course of the study, participants were willing to participate in all activities (although some requested payment). We were able to conduct the focus groups as scheduled and obtained the desired input. The analysis of the focus group transcripts was performed using iterative discussions and did not needed any special adaptation for this area of study. The pilot survey response rate was within the expected for this type of study. Focus groups can rapidly provide rich information regarding attitudes and other factors affecting provider participation at the point of care. However, findings from focus groups must always be confirmed through larger studies. It is important to keep the focus groups small and to hold multiple focus groups to offset the more vocal participants that may influence comments of others. This study shows that using our 3-step approach it is possible to gather important information on clinician’s and staff perceptions and needs to participate in point of care patient recruitment for CT. The focus groups also provide an important step for survey construction. Designing surveys empirically requires multiple validation efforts, which will be conducted in the future. However, we can draw preliminary conclusions from the results of the pilot study which are quite informative and they are discussed below. Near future work will be to expand the response rate through additional local survey and conduct formal psychometric testing and validation both locally and nationally. A final validation will be proposed through the CTSA consortiums. Variation in responses. There was a lack of normal curves in our survey results. This points to the need to target education and recruitment efforts by provider type (with similar perspectives). Identification of these types would be useful. Some specific points regarding variability that should be considered in program design. Preferences for trail recruitment methods. Many trial recruitment notification methods have the potential to be successful when used judiciously and done well, particularly if the trial coordinator/provider relationship is supported by reciprocal benefits to the provider. Consistency in workflow within seems paramount to success. Providers can pull some notifications at a time they choose, while other notifications interrupt and must be used sparingly. Some allow review of multiple patients at the same time, and some foster easy access to the patient’s medical record. Conclusions. The authors recommend that recruitment HIT be customizable at the clinic and provider level by responsibility and interest to allow selection of level of information, delivery method, that is, email, text, in-basket, alert, dashboard, mail; frequency of notification, and an opt out feature. These customizable options will allow for better support of clinic workflow or goals. There is the potential with machine learning technology to monitor provider interactions with trial notifications and for the system to automatically make adjustments to the method and level that best supports each physician. Limitations: The major limitation is the focus on one site only and one delivery system (university based). The low response makes generalization difficult. Efforts to improve the rate are underway. Many populations are under-represented in Utah. Full psychometric analysis was not conducted but will part of the final project.

OBJECTIVES/GOALS: We created an online, competency-based training program for Healthcare Delivery Science (HDS) that incorporates a wide range of disciplines and best educational practices. METHODS/STUDY POPULATION: In collaboration with a curriculum design expert and thirteen content experts from multiple schools and departments, we reviewed and adapted a published set of competencies for learning health system researchers. We followed educational best practices to collaboratively create learning objectives, aligned content with the objectives, and created quiz questions that addressed the objectives. After recording the coursework and building the program in a learning management system, we tested, evaluated, and revised the courses. RESULTS/ANTICIPATED RESULTS: The systematic approach resulted in a novel set of eight online courses: Introduction to Healthcare Delivery Science, Research Methods, Dissemination & Implementation Science, Behavioral Economics, Leadership & Management, Quality Improvement, Systems Engineering, and Multi-Stakeholder Engagement. The courses are applicable to learners from diverse fields, including medicine, public health, pharmacy, engineering, health system administration, and translational science. Students can earn digital badges for individual courses and a certificate of completion for the entire set of courses. DISCUSSION/SIGNIFICANCE: Compared to previously available offerings, the new training program offers a more comprehensive view of this important field. Next, we plan to develop additional courses and create a Masters program that includes synchronous learning and a complementary experiential component for hands-on application of HDS principles.

OBJECTIVES/SPECIFIC AIMS: To analyze how consumer physical activity monitors are currently used in biomedical research. METHODS/STUDY POPULATION: Searches were conducted in Ovid Medline, PubMed Medline, clinicaltrials.gov, and NIH RePORTER using search terms including Fitbit, Jawbone, Apple watch, Garmin, Polar, Microsoft band, Misfit, Nike, Withings, and Xiaomi. Results were quantitated by category: condition/topic, intervention, enrollment status, study type and design, age, grant mechanism, and primary outcome. RESULTS/ANTICIPATED RESULTS: Fitbit is used >80%. There are 127 clinical studies using Fitbit devices listed in clinicaltrials.gov. In total, 48 have been completed while 79 are ongoing. Some studies have already published their findings; 40 papers cited in Ovid MEDLINE report use of a Fitbit device. NIH is now funding research that uses consumer physical activity monitors, and the NIH RePORTER shows the number of grants using Fitbit is rapidly increasing. DISCUSSION/SIGNIFICANCE OF IMPACT: The current state and potential growth of this technology is transforming biomedical research and is enabling us to ask new and more granular questions about activity and sleep in health and disease.

OBJECTIVES/GOALS: We aim to describe the preschool age developmental outcomes of children born full term or late preterm requiring care in the Childrens Wisconsin (CW) neonatal intensive care unit (NICU). Our objective is to develop a model to predict which NICU infants are at high risk for abnormal preschool age development based on their neonatal characteristics. METHODS/STUDY POPULATION: Retrospective cohort study including full term (≥ 37 weeks) and late preterm (34-36 weeks) infants admitted to the CW NICU between 1/1/2013-12/31/2015 with a developmental assessment by a general practitioner or neuropsychology evaluation between 3-6 years of age. Data extraction will include maternal history, neonatal and delivery factors, and developmental evaluation results. Descriptive statistics will be used to determine the proportion of patients with abnormal preschool development stratified by NICU diagnoses, surgical procedures, subspecialty involvement, and patient demographics. Decision tree analysis will be performed to generate a prediction model identifying those infants at higher risk than their peers for an abnormal developmental assessment at 3-6 years of age. RESULTS/ANTICIPATED RESULTS: Analysis to date reveals 1360 patients ≥ 34 weeks gestation admitted to the CW NICU between 1/1/2013-12/31/2015. 80 patients received neuropsychology evaluations and the remaining 1280 patients had general practitioner developmental assessments. We anticipate that those infants referred for neuropsychology evaluation will have a higher proportion of abnormal developmental assessments when compared to those patients with routine general practitioner assessments. In addition, we hypothesize that common neonatal factors among the infants who received neuropsychology assessments will best predict abnormal preschool development within the decision tree analysis. DISCUSSION/SIGNIFICANCE: This study is one of the first to define risk factors in full term and late preterm infants cared for in the NICU associated with abnormal preschool age development. Identifying these infants at high-risk early on will allow providers to initiate early developmental interventions, schedule close NICU follow-up care, and provide parental counseling.

ABSTRACT IMPACT: We are adapting a global telehealth platform and model of care to the U.S. context in order to solve the problem of undertreatment of age-related hearing loss and, in turn, facilitate healthy aging and social engagement among older adults. OBJECTIVES/GOALS: Intelehealth is a nonprofit startup that provides medical care to last-mile populations in India by equipping frontline health workers with an open-source digital assistant and telemedicine platform. Here, we explore how this technology and model of care might be adapted to address health inequities in the context of the U.S. healthcare system. METHODS/STUDY POPULATION: We first sought to identify a specific healthcare need that we could address as a case study on applying the Intelehealth model more broadly in the U.S. context. We began with a needs assessment, wherein we conducted primary ethnographic research, expert interviews, and literature review to identify problems in the general areas of health disparities, community health workers, and telemedicine accessibility. We then scored each need on clinical impact, feasibility, business potential, and strategic fit. After a top need was selected, a root cause analysis was performed. Brainstorming and solution concepting will be followed by prototyping, iterative design with primary stakeholder feedback, usability testing, and finally implementation and validation of the solution. RESULTS/ANTICIPATED RESULTS: Of 106 needs, the most highly scored was undertreatment of age-related hearing loss (ARHL). The third most common chronic condition in the U.S., ARHL presents a significant barrier to healthy aging and the single largest modifiable risk factor for dementia; yet only 15% of those with ARHL regularly use hearing aids. Thus, a large market segment - nearly 30 million Americans - is underserved by the current hearing care paradigm. Root cause analysis revealed that the primary reasons for hearing aid non-use include stigma around aging, denial of hearing loss, poor awareness of resources, and insufficient education around proper use and maintenance. These barriers, being primarily sociocultural in nature, may be optimally addressed by community health workers, making ARHL an ideal fit for the Intelehealth model. DISCUSSION/SIGNIFICANCE OF FINDINGS: We have identified ARHL as an optimal test market for Intelehealth in the U.S. By developing a targeted intervention to improve hearing aid access and acceptability among older adults, we will create a generalizable model for delivering care through community health workers equipped with a decision support and telemedicine platform.

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.

OBJECTIVES/GOALS: Sodium (Na) intake can elevate blood pressure and is a factor in developing chronic kidney disease (CKD). Twenty-four-hour urinary Na (24hUNa) is the gold standard for assessing Na intake but is burdensome. Validated equations estimate 24hUNa (e24hUNa) from a spot urine sample, but these estimations are not validated against a known Na intake in CKD. METHODS/STUDY POPULATION: The current study is a secondary analysis of a 9-day controlled feeding study in moderate CKD patients matched to healthy adults. Only CKD patients were used for the current analyses (n = 8). Participants consumed a controlled diet for 9 days, providing ~2400 mg Na/d as determined by inductively coupled plasma optical emission spectroscopy (ICP). On days 7 and 8, participants collected all urine in an inpatient setting, beginning with a fasting sample on day 7. Urine sample mineral analyses were performed by ICP and urinary creatinine by the Jaffe reaction. The day 7 fasting urine sample was used to calculate e24hUNa using 6 published equations. Log-transformed Na intake, measured 24hUNa, and e24hUNa were compared by repeated-measures ANOVA with planned contrasts using SAS. RESULTS/ANTICIPATED RESULTS: Fifty percent of the CKD patients (n = 4) were female; 63% (n = 5) were white, and 37% (n = 3) were black. On average, participants were aged 56.6 ± 13.8 y with a BMI of 31.7 ± 9.4 kg/m2 and eGFR of 40.7 ± 7.9 mL/min. Based on actual food intake, average Na intake on day 7 was 2024 ± 388 mg. Average measured 24hUNa was 2529 ± 1334 mg. The main ANOVA was significant (p = 0.02). Results from the planned contrasts found that e24hUNa from the SALTED cohort, an equation developed specifically for CKD patients, was significantly higher than both Na intake (p<0.001) and measured 24hUNa (p = 0.007). For the remaining 5 equations, e24hUNa was not significantly different from measured 24hUNa nor dietary Na intake. DISCUSSION/SIGNIFICANCE OF IMPACT : Our results suggest that e24hUNa calculated using most published equations may provide a reliable and low-burden method of assessing dietary Na intake in moderate CKD patients. These findings should be confirmed in larger samples. Additional studies are needed to validate or dispute the use of the SALTED equation for estimating Na intake.

OBJECTIVES/SPECIFIC AIMS: If intranasal ketamine can be utilized for pain control in cancer patients, this could provide them with superior analgesia and better quality of life, without the risk of significant respiratory depression associated with opioid medications. We seek to obtain preliminary data via a clinical trial addressing safety, feasibility, and utility of this novel technique for the treatment of persistent uncontrolled cancer pain. These findings would be an important initial step towards testing the effectiveness of intranasal ketamine as a non-opioid medication for cancer pain used as potential maintenance outpatient therapy. These initial findings would be applied to a subsequent trial to determine the effectiveness and associated toxicities of ketamine in a larger sample of cancer patients, and address the compelling need to identify new, successful management therapies for cancer pain. Specific Aims: 1. To evaluate (pharmacodynamic) effects of NAS ketamine on Patient Reported Outcomes (PROs), such as pain scores, side effects, depression, quality of life, and functional status. A clinical trial will be conducted where NAS ketamine will be given to a sample of patients with cancer related pain. Patient Reported Outcomes (PROs), such as pain scores, depression, quality of life, and functional status will be noted on Numerical Pain Rating Scale (NPRS), Montgomery Asberg Depression Rating Scale (MADRS), and Edmonton Symptom Assessment (ESAS), Eastern Cooperative Oncology Group (ECOG) and Patient Reported Outcome Measurement Information System (PROMIS) scales respectively. 1. To measure pharmacokinetics of NAS ketamine through analysis of ketamine and its metabolite norketamine to determine pharmacokinetic properties. During this clinical trial blood samples will be drawn at specified intervals and sent for analysis. 3. To determine opioid sparing effect of NAS ketamine. Opioid use will be measured by documenting use of rescue medications prior to and during the study and by evaluating total opioid consumption prior to and during the study. METHODS/STUDY POPULATION: Study sample: In the search for improved therapies for chronic cancer pain, medications with novel mechanisms of action have been sought. One such promising pharmacologic approach is ketamine. We specifically intend to measure utility of ketamine in patients with pain related to cancer or cancer treatment. Ketamine has shown to reverse central sensitization and opioid tolerance in rat models. Since ketamine is Scheduled III in United States and has abuse potential, we do not intend for ketamine to replace opioids, but use in patients who have failed opioid therapy. Since the investigators of the study practice at Emory, subjects will be from oncology and pain clinics (the supportive oncology clinic, oncology clinics, the pain clinic and Acute Pain Service) at Emory. The trial will be conducted at the Phase 1 Unit of the Winship Cancer Institute (WCI) at Emory. Subjects may be identified and contacted via telephone with information about the study prior to their next clinic appointment in order to allow time for them to consider the study. Eligibility criteria: Patients will be eligible to participate if they are: 1. Adults with uncontrolled cancer related pain a. Male and female subjects at least 18 years of age. b. Patients with uncontrolled pain related to cancer or cancer treatment. c. Uncontrolled pain will be defined as i. pain which persists for more than 7 days and is rated >/=4 on NPRS, and/or ii. use of breakthrough medication more than 4 times in 24 hours d. Failed other pain medications such non-steroidal anti-inflammatories such as ibuprofen, acetaminophen, opioids such as tramadol, hydrocodone, oxycodone etc. and antineuropathics such as gabapentin. 2. Able to provide informed consent a. Patients who are able to understand written and verbal English. Patients will be excluded from the study if they have any of the following: 1. Conditions increasing the risk of side effects from ketamine a. Conditions not safe due to cardiovascular effects of ketamine i. Presence of severe cardiac disease-EF <15% in patients with known history of cardiac disease ii. Uncontrolled Stage 2 hypertension or greater (systolic blood pressure > 160 and/or diastolic blood pressure >100) iii. Baseline tachycardia, HR >100 b. Conditions not safe due to potential effect of ketamine on intracranial and intraocular pressure i. Presence of elevated ICP ii. Uncontrolled glaucoma c. Presence of uncontrolled depression or other psychiatric comorbidity with psychosis 2. Conditions not safe due to potential side effects reported in ketamine abusers a. History of liver disease b. History of interstitial cystitis 3. Conditions where delivery of intranasal medications may be unreliable a. Active allergic or infectious rhinitis b. Patients with lesions of nasal mucosa 4. Conditions where fetus may be exposed to ketamine in utero (ketamine is category C medication) a. Pregnant women, nursing mothers and women of childbearing potential not using contraception known to be highly effective. b. Highly effective contraception methods include combination of any two of the following: Use of oral, injected or implanted hormonal methods of contraception or; Placement of an intrauterine device (IUD) or intrauterine system (IUS); Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; Total abstinence; Male/female sterilization. 5. Conditions with medication abuse potential a. Illicit substance abuse within the past 6 months b. Documented history of medication abuse/misuse (e.g. Unsanctioned dose escalation, broken opioid agreement etc.) 6. Conditions where ketamine metabolism may be altered, resulting in erroneous dose response relationship a. Clinical requirement for medications that are concurrent inducers or strong inhibitors of CYP3A4. CYP3A4 substrates are allowed. (Ketamine is metabolized by CYP3A4) Study sample limitations: Subject factors that may affect the final resultant study sample of subjects with full data for analysis. 1. Subjects who may not get pain relief with ketamine may not follow up and resulting incomplete data not eligible for analysis that may erroneously enhance positive effect of ketamine on pain relief. To account for this effort will be made to document the reason for lack of follow-up by contacting patient via telephone or at next scheduled clinic visit within Emory Healthcare. 2. Since patients coming to Emory are typically insured, the study will not adequately capture indigent population. It is not the intention of the current study to investigate differences in pain characteristics or responses of patients with insurance vs indigent population and will need to be addressed via future trials. Since this is a single center trial, the results of this trial might lack external validity required to support widespread changes in practice. This will be a pilot trial to figure out likely most efficacious dose. If this trial is successful, a multi-site randomized clinical trial will be conducted next. Primary Study Measures Primary exposure Intranasal Ketamine for cancer related pain Ketamine is an FDA approved anesthetic with amnesic, analgesic, dissociative, and sedative properties. It is unique among anesthetic agents in that it does not depress cardiovascular and respiratory systems. Ketamine is a noncompetitive, antagonist of N-methyl-D-aspartate (NMDA) receptors that blocks the NMDA channel in the open state by binding to the phencyclidine (PCP) site located within the lumen of the channel. Antagonism of NMDA receptors produces antinociception of persistent or neuropathic pain in animal models and analgesia in pain states in humans. The NMDA receptor is believed to play a role in the development of opioid tolerance and ketamine has been shown in a rat model to prevent fentanyl-induced hyperalgesia and subsequent acute morphine tolerance 5. Ketamine also interacts at a number of other receptor sites to block pain. Some of these sites include voltage-sensitive calcium channels, depression of sodium channels, modulation of cholinergic neurotransmission, and inhibition of uptake of serotonin and norepinephrine. Ketamine also interacts with kappa and mu opioid receptors; however, in humans, naloxone, an opioid antagonist, does not antagonize the analgesic effects of ketamine. Safety and efficacy of ketamine as an anesthetic and analgesic agent is well-documented 2-4. Ketamine is not labeled by the FDA as an analgesic agent. Low (subanesthestic) doses of ketamine have minimal adverse impact upon cardiovascular or respiratory function but produce analgesia and modulate central sensitization, hyperalgesia, and opioid tolerance. Cancer pain, especially in end stages, can be very complicated and is mediated by a variety of pathways: visceral, nociceptive, neuropathic and central. If ketamine can be utilized for pain in end stage cancer patients, this could provide them with superior analgesia and better quality of life, without the risk of significant respiratory depression associated with opioid medications. One of the challenges that we face with ketamine is the route of administration. The most common route is intravascular or intramuscular. Although it has been given orally and rectally, the bioavailability of ketamine when given via these routes is limited to 20-30%. Intranasal (NAS) administration has advantages of being needle free method of administration with potential for outpatient therapy. It lacks hepatic first pass effect resulting in higher bioavailability compared to oral route. Large surface area, uniform temperature, high permeability and extensive vascularity of the nasal mucosa facilitate rapid systemic absorption of intranasal administered drugs 6. In the pilot trial conducted by the study investigators, single dosage of intranasal ketamine has been shown to be feasibility and effective option for temporary pain reduction in patients with cancer related pain. The investigators now seek to obtain feasibility and efficacy data on long-term use of intranasal ketamine for cancer related pain. Ketamine is a scheduled III medication. A physician with a DEA license can order intranasal ketamine from a compounding pharmacy. Primary outcome of interest: Pain scores will be recorded on Numerical Pain Rating Scale (NPRS) at regular intervals throughout the study. NPRS is the most responsive tool to document pain intensity when compared to Visual Analogue Scale (VAS) and Visual Rating Scale (VRS) for measuring pain, 7 showing higher compliance rates, better responsiveness, ease of use, and good applicability relative to VAS/VRS8. Minimal clinically important differences (MCIDs) for pain ratings varies substantially based on patient population and statistical technique used, range of 0.4 to 3.7 points has been reported as a MCID. In general, improvements of pain severity</=1.5 points on NPRS could be seen as clinically irrelevant 9-13. Above that value, the cutoff point for “clinical relevance” depends on patients’ baseline pain severity, and ranges from 2.4 to 5.3 11-13. Higher baseline scores require larger raw changes to represent clinically important differences 14. Primary aim: To determine efficacy of intranasal ketamine in reducing cancer related pain. A clinical trial will be conducted to determine effect of intranasal ketamine on cancer related pain. Pain scores will be recorded on Numerical Pain Rating Scale (NPRS) at regular intervals throughout the study. Minimal clinically important differences (MCIDs) for pain ratings varies substantially based on patient population and statistical technique used, range of 0.4 to 3.7 points has been reported as a MCID. In general, improvements of pain severity</=1.5 points on NPRS could be seen as clinically irrelevant 9-13. Above that value, the cutoff point for “clinical relevance” depends on patients’ baseline pain severity, and ranges from 2.4 to 5.3 11-13. Higher baseline scores require larger raw changes to represent clinically important differences 14. Several clinical trials for pain have reported a reduction of 2 points on NPRS to be clinically important.15-17 Therefore for the purposes of this study, MCID of 2 was used for sample size calculations. A prior research study done by Carr et al. studied effects of intranasal ketamine for breakthrough pain in patients with chronic pain of various etiologies. 18 Total number of subjects in this study was 20 (4 of these had cancer related pain).This study demonstrated a mean reduction of 2.7 units on NPRS (P<0.0001), with standard deviation of 1.87. Since MCID is 2, effect size using this (MCID/SD) = 1.05. Power and sample size table: Assumptions: 1. T-test is the appropriate test (may not be the appropriate test since we have a small sample size and may not be able to assume normality of means based on the central limit theorem) 2. Distribution of reductions in pain score is normal 3. Effect size of 1.05 is clinically meaningful; Sample Size: A sample size of 7 from a population of 20 (in the study done by Carr etal.) achieves 80% power to detect a NPRS difference of −2 between the null hypothesis mean of 0.0 and the alternative hypothesis mean of 2 with an estimated standard deviation (SD) of 1.87 and with a significance level (alpha) of 0.05 using paired t-test assuming that the actual distribution is normal. We will include 10 patients to account for the possibility that the observed pain reduction in the current study may be different than the study done by Carr, as in this study patients were given ketamine for breakthrough pain, as opposed to for baseline pain. We will enroll 25 patients in the study to account for potential dropouts. RESULTS/ANTICIPATED RESULTS: Majority of subjects experienced the largest decrease in their pain with the 10mg IV dose. Side effects included nausea/vomiting and a feeling of unreality. All side effects resolved by the end of each study visit. No severe adverse events occurred. DISCUSSION/SIGNIFICANCE OF IMPACT: Further study is required to elucidate safety of NAS ketamine with long term use for cancer related pain.

Tesamorelin, a synthetic growth hormone-releasing hormone, is indicated for the reduction of visceral adipose tissue (VAT) in people with HIV. Here, we performed a post hoc analysis of participants receiving tesamorelin for 26 weeks in a phase III clinical trial. Efficacy data were compared between individuals with and without dorsocervical fat, stratified by tesamorelin response. Among tesamorelin responders, VAT and waist circumference (WC) decreased in both dorsocervical fat groups and did not statistically differ (VAT P = 0.657, WC P = 0.093). These data demonstrate that tesamorelin is equally effective and should be considered in the treatment of excess VAT regardless of the presence of dorsocervical fat.

Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.

ABSTRACT IMPACT: The results from this study will improve needs assessment practices. OBJECTIVES/GOALS: The discovery phase in project development is necessary to better understand the needs and requirements of the intended market. This paper compares the outcomes of two virtual data collection methodologies, NSF I-Corps Customer Discovery interviews and REDCap surveys, for a needs assessment. METHODS/STUDY POPULATION: Clinical and Translational Science Award (CTSA) Directors and Academic Administrators across the Consortium were asked about the types of skills needed to assess clinical research professional competencies and the need for a competency-based self-assessment tool (CBST). Parallel methods were used to extract qualitative and quantitative data. The first approach was to conduct interviews using I-Corps customer discovery guidelines, and data was collected using Innovation Within software. Targeted requests were sent via cold email outreach to 102 individuals within 63 CTSA hubs. The second approach involved the use of the NJ ACTS Training and Education Offering Inventory REDCap Survey which was distributed via LISTSERV to 63 CTSA hubs. Response rates and user insights from each method were compared. RESULTS/ANTICIPATED RESULTS: Twenty-one of 63 CTSA hubs responded to the survey (response rate: 33%) while 18 of 63 hubs participated in an interview (response rate: 28%). Twenty-two individuals out of 102 were interviewed (response rate: 21%). Fifty-nine percent of interviewees and 62% of survey respondents indicated a clear need for a CBST; types of responses varied. Forty user insights were obtained from ten interviews. Two insights were gained in the survey from the eight who were prompted to fill out the free-text response. Both survey participants and interviewees indicated that communication and team science soft skills were the most important competencies. Regarding hard skills, interviewees preferred written skills while survey participants favored ‘scientific design and concept’ skills. DISCUSSION/SIGNIFICANCE OF FINDINGS: Results suggest the use of a survey or an interview for a needs assessment is dependent on several factors: need for insights, burden of time, desire to obtain quantitative vs. qualitative data, and question format. The interview was more effective than the survey in addressing the key question and obtaining insights from the intended market.

OBJECTIVES/GOALS: Evaluation of the contributions of the CTSI core services to the science of translational science requires focused protocols that are rigorous developed and piloted. The goal of this presentation is to report on the process of protocol development and present the results of protocol pilot implementation. METHODS/STUDY POPULATION: Translational science’ (TS) is the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process (Austin, Clin Trans Sci. 2021; 14:1629-1647). A key tenet of translational science is to understand common causes of inefficiency and failure in translational research projects (e.g., incorrect predictions of the toxicity or efficacy of new drugs, lack of data interoperability, ineffective clinical trial recruitment). The navigation steps and mapping to resources for translational researchers provides an opportunity to develop effective navigation tools and study the barriers to effective translation. RESULTS/ANTICIPATED RESULTS: The UF-FSU Evaluation Committee has developed and piloted an evaluation protocol that aims to assess the role of CTSI service centers in addressing specific TS barriers. The protocol is informed by interviews with CTSI service users, and is grounded in the Donabedian Framework of Quality Assessment and Lean principles. The pilot implementation of the protocol showed its relevance and applicability across multiple UF-FSU core service centers. DISCUSSION/SIGNIFICANCE: The barriers to translational science are not unique but addressing them is rarely within the scope of individual translational research projects. Conversely, service centers within the CTSA institutions are uniquely positioned to address TS barriers thus enhancing to the operational efficiency of the CTS enterprise and promoting the science of TS.