OBJECTIVES/SPECIFIC AIMS: We will use a structured evaluation framework, the payback framework, to document the outcomes of 15 case studies of pilot projects supported by Georgia CTSA from 2007 to 2014. METHODS/STUDY POPULATION: We will use a case study approach including bibliometric analyses of publications associated with the selected projects, document review (e.g., investigator curriculum vitae, biannual project reports) and investigator interviews. RESULTS/ANTICIPATED RESULTS: We will document outcomes in 5 “payback categories”: (1) knowledge, (2) research targeting, capacity building, and absorption, (3) policy and product development, (4) health benefits, and (5) broader economic benefits. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will aid in characterizing the returns resulting from this research funding and identify its strengths and weaknesses. This study will inform our understanding of the diversity and breadth of outcomes resulting from Georgia CTSA-supported research, and the value pilot projects provide to clinical and translational science and the broader community.

OBJECTIVES/SPECIFIC AIMS: Dissemination of research findings through the published literature is a complex but critical part of the scholarly communication process. Additionally, this time point on the translational spectrum is a key objective of the National Clinical Association for Advancing Translational Sciences (NCATS). Tracking the dissemination of research outputs can be difficult to identify and evaluate. The purpose of this case study was 2-fold: (1) identify tools and resources available freely to the public and through university subscriptions used to assess research output; and (2) compare the effectiveness of these tools oat tracking output at different levels of granularity. METHODS/STUDY POPULATION: The authors, Spectrum staff (D.A.) and School of Medicine librarian (M.B.), attended webinars hosted by other Academic Medical Center libraries conducting work on impact tracking and learned from vendor product managers about available tools and resources during on-site campus visits. Publications from Stanford’s Clinical and Translational Science Award (CTSA) were used to track the diffusion of research outputs (e.g., number of citations, document types, research areas, relative citation ratio, CTSAs collaboration) via library subscription services (e.g., Web of Science and Scopus) and freely available tools (e.g., iCite and PubMed). RESULTS/ANTICIPATED RESULTS: The authors found certain tools were more inclusive in retrieving grant funded research outputs. For example, in the case of UL1 grant (UL1TR001085, UL1TR000093, UL1RR025744), on a grant-level output, there were discrepancies in the number of publications retrieved: (1) PubMed found 644 outputs; (2) Web of Science found 497 outputs; and (3) Scopus found 190 outputs. After de-duplication, the search across Web of Science (WoS), Scopus, and PubMed yielded 899 publications. In total, 389 outputs were unique to PubMed; 165 were unique to WoS; and 90 were unique to Scopus. Future analysis will be conducted to identify the source of unique outputs from each database (e.g., conference proceeding, specific journals). Additional analysis based on other units of research outputs (e.g., author-level outputs and article-level outputs) are expected to yield similar discrepancies. DISCUSSION/SIGNIFICANCE OF IMPACT: Citation analysis is a valuable method of assessing research output and, to a larger extent, research impact in a given field. It can help investigators illustrate qualifications for undertaking new projects, highlight collaborations across schools and departments, justify a grant renewal, and/or highlight accomplishments for promotion. However, systematic and comprehensive evaluations are needed in tandem with citation analysis/bibliometric analysis to assess the translation and uptake of research outputs and activities that result in research impact. Furthermore, both investigators and staff need adequate time and training to process research outputs/activities and to effectively organize them in easily understood visualizations.

OBJECTIVES/SPECIFIC AIMS: Objectives: Decreasing costs and increasing evidence for clinical utility have contributed to whole genome sequencing (WGS) becoming a clinical reality. While previous studies have surveyed the attitudes of patients and community members towards specific gene tests, an emerging literature has begun to describe the preferences of diverse recipients for WGS results. In this study, we sought to identify and synthesize the quantitative evidence on preferences for results from WGS using a systematic review of the literature. METHODS/STUDY POPULATION: We conducted a search of articles on PubMed including subject index terms WGS, whole exome sequencing, genome sequencing, secondary findings, incidental findings, attitudes, preferences, choices, utilities, stated-preferences, discrete choice experiment, and willingness-to-pay. We conducted 11 formal searches to refine the strategy and conducted a final search in December 2017. Duplicates were eliminated and a title and abstract review was conducted to select articles meeting inclusion criteria. RESULTS/ANTICIPATED RESULTS: Our search strategy identified 79 publications meeting initial search criteria with 30 manuscripts meeting inclusion criteria. Of these, most studies were conducted with patient-participants enrolled in existing sequencing studies, while few engaged members of the general public. Of the studies conducted on patients, most were on the medical setting of cancer and related syndromes. The earliest publication date of a manuscript meeting our inclusion criteria was in 2012, yet the majority were published in 2015 or later. DISCUSSION/SIGNIFICANCE OF IMPACT: Between 2012 and 2015, we saw an increasing focus in the medical literature on understanding public and patient preferences for return of results from WGS and WES. Both public and patient populations participating in surveys expressed preferences for receiving results from next-generation sequencing, even if the results are secondary or incidental findings unrelated to the primary indication for sequencing. A primary factor related to patient interest in incidental or secondary findings is the extent to which these results can inform medical intervention. Few studies surveyed representative population-based samples, and this may be an area for future investigation.

OBJECTIVES/SPECIFIC AIMS: This study seeks to understand the relationship between opioid prescribing and patient satisfaction among non-surgical, hospitalized patients. As part of this study, we qualitatively examined challenges in delivering safe and patient-centered care through voices of physicians’, and nurses.’ METHODS/STUDY POPULATION: We collected data through in-person interviews using semi-structured guides tailored to the informant roles. Study participants came from 1 healthcare system located in a mid-Western state. Each interview lasted 30–45 minutes, was audio-recorded with consent, and transcribed for analysis. Two researchers each coded 17 transcripts for discussions around patient-centeredness (including patient satisfaction, patient experiences), and patient safety for hospitalized patients experiencing pain. Analysis followed a general inductive approach, where researchers identified themes related to the research questions using an open coding technique. They discussed and reached consensus on all codes, and extracted several preliminary themes. The analysis was supported by NVivo software. RESULTS/ANTICIPATED RESULTS: The following themes emerged: (1) complex decision-making process to prescribe opioids for hospitalized patients; (2) the role of objective findings in prescribing decisions; (3) bargaining process in prescribing opioids; (4) balancing patient-centeredness and patient safety for selected populations; (5) opioids are the predominant medications for pain care. DISCUSSION/SIGNIFICANCE OF IMPACT: Clinicians’ decision to prescribe opioids for nonsurgical hospitalized patients is based on multiple factors, including patient’s condition, patient’s preference for pain medications, or standard hospital’s pain care regimen. Interventions that improve clinicians’ ability to prescribe opioids may be needed to improve delivery of patient-centered and safe pain care.

OBJECTIVES/SPECIFIC AIMS: (1) Evaluate the relative incremental cost-effectiveness [cost per quality-adjusted life year (QALY) gained] of antibiotics, laparotomy, and laparascopy for the initial treatment of uncomplicated appendicitis. (2) Detect if the relative incremental cost-effectiveness of each treatment differs by age, namely in pediatric patients, adult patients, and geriatric patients. (3) Use deterministic and probabilistic sensitivity analyses to assess the robustness of our findings when varying multiple model parameters. METHODS/STUDY POPULATION: Study Population and Analytic Approach: The population under analysis is a simulated population of those aged 1–90 diagnosed with uncomplicated appendicitis with computed tomography (CT) in the emergency department. Pregnant women and those younger than 1 year old were excluded from our analysis. We simulated our population through a Markov state-transition simulation model. Using this model, we estimated the lifelong costs and effects on QALYs from the use of antibiotics, laparoscopy, and laparotomy for a given hypothetical individual with uncomplicated appendicitis. This model allowed for the incorporation of both the short-term and long-term effects of each respective treatment option. The primary outcome of the model was the cost per additional QALY gained. The analysis was conducted using a healthcare perspective. A 100 age-year time horizon was used. A 3% discount rate was applied to both the costs and effects in the model. Transition states are depicted. Surgical state rates were derived from HCUP. Treatment failure of antibiotics was defined as recurrent appendicitis within one year of antibiotic treatment. This was determined using results from prior RCTs and a Cochrane review of antibiotic management for uncomplicated appendicitis. Recurrent appendicitis was defined as recurrent appendicitis after 1 year of antibiotic treatment, using rates of appendicitis applied to the general population by age group. National age-adjusted mortality rates were applied to account for death due to causes unrelated to appendicitis. To assess differential results by age, different acute and long-term outcome, cost, and state transition rates were applied to 3 age groups: a pediatric group (1–17 years old), an adult group (18–64 years old), and a geriatric group (65+ years old). As an individual progressed through the model until age 100, the respective parameters would change to adjust for the transitions between the 3 life stages. Outcomes After Appendicitis: Lifetime QALYs were incorporated throughout the study for short-term and long-term health states. There is limited availability of QALY data in the literature pertaining to the health states specific to appendicitis. Due to this limitation, however, calculated quality of life (QoL) indices for 2015 created by Wu et al. were utilized for this study. QALYs were subsequently derived by multiplying QoL by the appropriate duration of time spent in a respective health status. Transition rates between health states were abstracted from the existing literature. Costs: Direct medical costs were obtained from HCUP statistics from the 2014 fiscal year for all age groups in the nationwide network. This database contains all costs of care related to surgical appendicitis intervention, however it lacks costs associated with antibiotic-only management. To account for these costs, data was extracted from current available literature, and the resulting average was applied to our model. Sensitivity Analysis: One-way analyses by cost of procedure and effectiveness of antibiotic protocol were undertaken to account for regional variation in costs and improvements in antibiotic therapy, respectively. For cost of procedure sensitivity analysis, costs were varied by 1 standard deviation below and above the mean cost per treatment group per age. These costs were then compared to a designated reference group. Antibiotic sensitivity analysis was conducted by reducing the effectiveness of antibiotics from the maximum reported effectiveness down to 0, with the goal of obtaining a level of effectiveness at which antibiotics were no longer cost-effective. A probabilistic Monte-Carlo sensitivity analysis was then employed to determine the percent likelihood of each treatment arm being cost-effective at a level of $100,000 per additional QALY. The probabilistic sensitivity analysis was then repeated to determine the percent likelihood of each treatment arm being the dominant option, in that it lowers costs and adds QALYs. RESULTS/ANTICIPATED RESULTS: Our model examined the cost-effectiveness of 3 different treatment options for patients with acute uncomplicated appendicitis: laparoscopic appendectomy, laparotomy appendectomy, and an antibiotic regimen. We first examined the cost-effectiveness of each of these strategies in comparison to laparotomy. Laparoscopic appendectomy was shown to be superior to laparotomy in regards to costs and QALYs for patients ages 18 to 65+, while there was very little difference for patients ages 1–17. For those aged 1–17, laparoscopy had an additional cost of $90.00 with an associated gain of 0.1 QALYs compared with laparotomy. For those aged 18–64, laparoscopy had a net cost-savings of $3437.03 with an associated gain of 0.13 QALYs compared with laparotomy. For those aged 65+, laparoscopy had a net cost-savings of $5713.55 with an associated gain of 0.13 QALYs compared to laparotomy. Antibiotic management was superior to laparotomy as it relates to both costs and QALYs for all 3 age cohorts. For those aged 1–17, antibiotic management had a net cost-savings of $5972.55, with an associated gain of 0.6 QALYs compared with laparotomy. For those aged 18–64, antibiotic management had a net cost-savings of $6621.00 with an associated gain of 0.5 QALYs compared with laparotomy. For those aged 65+, antibiotic management had a net cost-savings of $11,953.00 with an associated gain of 0.21 QALYs compared with laparotomy. We then assessed the cost-effectiveness of antibiotics relative to laparoscopy. In all 3 age groups, antibiotics added QALYs and were cost-saving. For those aged 1–17, antibiotic management had a net cost-savings of $6062.55, with an associated gain of 0.6 QALYs compared with laparotomy. For those aged 18–64, antibiotic management had a net cost-savings of $3183.97 with an associated gain of 0.5 QALYs compared with laparotomy. For those aged 65+, antibiotic management had a net cost-savings of $6239.45 with an associated gain of 0.21 QALYs compared with laparotomy. Sensitivity Analysis: We first examined the effect of varying costs on our results. Costs for all interventions were varied by 1 standard deviation above and below the average costs used in our original model, yielding 3 cost estimate levels: high cost (1 standard deviation above), middle cost (average cost reported in model), low cost (1 standard deviation below). For all 3 cost estimate levels of antibiotics, antibiotics persistently dominated laparotomy for all 3 age groups. Laparoscopy dominated at all cost levels in age groups 18–64 and 65+ but had a positive ICER for both high and medium cost levels in the 1–17 age group. We then varied effectiveness (one minus the failure rate) of antibiotic treatment in each age group to assess at what level of effectiveness to antibiotics become dominant relative to laparotomy. In ages 1–17, antibiotic treatment became dominant at 43.8%; in ages 18–64, antibiotic treatment became dominant at 33%; and in ages 65+, there was no level of antibiotic effectiveness that did not result in this therapy being dominant over laparotomy. Probabilistic Monte-Carlo sensitivity analysis is pending, but we anticipate antibiotics having a high likelihood of being both cost-effective and dominant relative to the other 2 treatment options. DISCUSSION/SIGNIFICANCE OF IMPACT: We performed a cost-effective analysis comparing surgery versus antibiotic management for uncomplicated appendicitis. Our study found that antibiotic therapy was the dominant strategy in all age groups as it yielded lower costs and additional QALYs gained compared with laparotomy and laparoscopy. Appendicitis is the most common surgical emergencies worldwide, with a lifetime risk of 6.9% in females and 8.6% in males (Körner 1997). For over 100 years, open appendectomy had been the established treatment for appendicitis, but current management has evolved with the advent of laparoscopy and now growing use of antibiotics for treatment of appendicitis. There is growing interest in nonoperative management of uncomplicated appendicitis, given both an aging population that is increasingly frail and vulnerable to surgical complications and concerns over skyrocketing medical costs. Our model showed that antibiotic-only management was cost-effective in all age groups. This has important implications for management of appendicitis, where current management is to offer antibiotic-only management only in the “rare cases” where the patient is unfit for surgery or refuses surgery. Our data show that medical management of appendicitis not only is cheaper, but also provides more QALYs in all age groups. Our study has several limitations. First, we conducted our analysis under the assumption that all patients will be cured of appendicitis following surgical intervention. Some patients following appendectomy will develop symptoms of appendicitis and be diagnosed with “stump appendicitis,” which can occur in stumps as short as 0.5cm and can present as late as 50 years following initial surgery (Kanona, 2012). Additionally, any intraperitoneal surgery can lead to late complications such as small bowel obstruction from adhesions following surgery. Thus, our assumption that patients following appendectomy will return to the general population’s QALYs and mortality rate is not necessarily an accurate reflection of all clinical courses. However, the overwhelming majority of appendectomy patients recover fully post-surgery and we do not believe the above complications would significantly change our analysis. We also assumed that all patients with recurrent appendicitis following medical management would undergo surgery. However, patients who underwent nonoperative management at initial appendicitis may be more likely to be ineligible for surgery or refuse surgery during this second case of appendicitis. In addition, data were sparse for QALYs for the complications of open and laparoscopic surgery. We estimated these numbers from the EQ-5D, which while perhaps not accurate, we believe to be the best approximation given the available data. The next steps in evaluating the use of nonoperative management in uncomplicated appendicitis would be to validate the use of nonoperative management in elderly populations and to develop more accurate diagnostic criteria for uncomplicated Versus complicated appendicitis. Additionally, with increasing attention on antibiotic-resistant micro-organisms, policy decisions on the use of nonoperative management must also consider antibiotic stewardship. While one dose of perioperative antibiotics is indicated for appendectomy, treatment strategies from trial protocols for antibiotic-only management require significantly more antibiotics—some protocols require 1–3 days of IV antibiotics followed by up to 10 days of oral antibiotics. This study provides a cost-effectiveness analysis of treatment options for acute uncomplicated appendicitis among varying age groups. Our analysis demonstrates the benefit of antibiotics for initial therapy in the management of acute uncomplicated appendicitis. While the historic gold standard of laparotomy still is present as the first line treatment option in many physicians’ minds, new evidence indicates that the advancement of other methods, whether surgical via laparoscopic removal of the appendix or medical via improved antibiotic regimens, suggests better alternatives exist. Our study builds upon a growing body of literature supporting initial treatment of acute uncomplicated appendicitis with antibiotics, before surgical intervention.

OBJECTIVES/SPECIFIC AIMS: Patient factors such as body mass index and functional status are commonly used in surgical decision-making and prediction of outcomes. Morphomic analysis uses semi-automated 3D cross-sectional imaging analysis to quantify tissue, organ, and bone geometry and density. These data can be used to assess patient health status. There is an emerging trend of using morphomic variables such as muscle mass and bone mineral density to predict surgical and medical outcomes. In certain cases, it has been shown to predict cancer survival more accurately than conventional staging methods. With the growing popularity of morphomic analysis, it is vital to establish baseline variability against which patient populations can be validated. Of populations receiving radiographic imaging, trauma patients are approximately representative of the general population. We created a reference population of morphomic variables from over 6000 University of Michigan patients presenting with trauma. METHODS/STUDY POPULATION: Computed tomography (CT) scans were obtained for all patients who underwent scans for trauma indications at the University of Michigan starting from April 1998. High throughput image processing algorithms written in MATLAB 2015a were used to semi-automatically process chest, abdomen, and pelvis CT scans. Scans were referenced to a common coordinate system based on vertebral levels and body anatomy. Measurements of adiposity, muscle group, and bone density measurements were performed at each level. Percentile curves of morphomic measures of body composition by age and sex were created. The reference population dataset is periodically updated and is publicly accessible. RESULTS/ANTICIPATED RESULTS: As of July 2017, over 6000 patients aged 1–81 years have been included in the Reference Analytics Morphomics Population. Patient CT scans were analyzed at the T10, T11, T12, L1, L2, L3, and L4 vertebral levels. Morphomic measures analyzed include body depth, body cross-sectional area, vertebral trabecular bone density, visceral fat area, fascia area, subcutaneous fat area, central back fat, and psoas muscle area. DISCUSSION/SIGNIFICANCE OF IMPACT: We created reference curves for several morphomic variables from a Reference Analytic Morphomics Population of over 6000 University of Michigan patients presenting with trauma.

OBJECTIVES/SPECIFIC AIMS: Expanded Access is an avenue for patients with no available treatment options to access investigational drugs and devices for clinical therapy. This process requires physicians treating these patients to submit requests to the FDA and the local IRB, processes which are typically unfamiliar to clinicians. METHODS/STUDY POPULATION: With the goal of reducing burden and ensuring access to investigational products, Michigan Medicine established the Expanded Access Oversight Committee in January 2015. This committee brought together key stakeholders to develop appropriate policy and infrastructure to support these requests. RESULTS/ANTICIPATED RESULTS: Outcomes from this committee have resulted in a uniform process with a single point of entry for interested physicians and patients. With standardized policy implemented across the institution, a revised IRB application has been developed that is more tailored to Expanded Access and an informed consent document has been developed specific to the clinical use of investigational therapies. To ensure timely execution of these agreements, the contracts office has streamlined the process for negotiating Expanded Access agreements with manufacturing companies. Further development has begun with the Michigan Clinical Research Unit to provide space for clinical visits in Expanded Access cases, allowing for initiation of outpatient therapy. These changes have allowed Michigan Medicine to support triple the number of Expanded Access requests, including more than 45 Expanded Access requests in fiscal year 2018. DISCUSSION/SIGNIFICANCE OF IMPACT: Institutional support for Expanded Access requests within a large academic medical center is feasible and can increase access to investigational therapies bfor patients.

OBJECTIVES/SPECIFIC AIMS: This study seeks to test the feasibility and effectiveness of a brief Acceptance and commitment therapy (ACT) treatment for patients with persistent pain in a patient-centered medical home. METHODS/STUDY POPULATION: Participants are recruited via secure messaging, clinic advertisements and clinician referral. Primary care patients age 18 and older with at least 1 pain condition for 12 weeks or more in duration are stratified based on pain severity ratings and randomized into (a) ACT intervention or (b) control group [Enhanced Treatment as Usual (E-TAU)]. Participants in the ACT arm attend 1 individual visit with an integrated behavioral health provider, followed by 3 weekly ACT classes and a booster class 2 months later. E-TAU participants will receive usual care plus patient education handouts informed by cognitive behavioral science. Currently, 17% of our overall goal of 60 patients have completed ACT or enhanced treatment as usual. Average participant age is 49 years old, 70% female, and 70% Hispanic/Latino. Most report multisite pain conditions (e.g., musculoskeletal, fibromyalgia) and 30% are taking opioid medications. Data analysis in this presentation will include early correlational findings from baseline assessments. Upon study completion, we will analyze data using a general linear mixed regression model with repeated measures. RESULTS/ANTICIPATED RESULTS: The overall hypothesis is that brief ACT treatment reduces physical disability in patients with persistent pain when delivered by an integrated behavioral health provider in primary care. By examining a subset of patients on opioid medications, we also anticipate a reduction in opioid misuse behaviors. Additionally, it is anticipated that improvements in patient functioning will be mediated by patient change in pain acceptance and patient engagement in values-consistent behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study will establish preliminary data about the feasibility and effectiveness of addressing persistent pain in a generalizable, “real-world” integrated primary care setting. Data will help support a larger trial in the future. If effective, findings could improve treatment methods and quality of life for patients with persistent pain using a scalable approach.

OBJECTIVES/SPECIFIC AIMS: The National Institutes of Health (NIH) has provided continual support for the Georgia Clinical and Translational Science Alliance (CTSA) since 2006. An overarching goal of the Georgia CTSA is to accelerate clinical and translational research to impact health in Georgia and beyond. Toward these ends, a primary objective has been to support interdisciplinary research projects encompassing 2 or more disciplinary domains. The goal of the present study is to evaluate the degree to which interdisciplinary research projects increased in prevalence during the first decade of funding. METHODS/STUDY POPULATION: We began by using PubMed to identify all publications citing the Georgia CTSA hub (n=1865), categorizing each article as encompassing 1 or more research domain using a taxonomy derived from the Web of Science. We created 1 network for each of the 10 years with nodes representing research areas and ties between pairs of nodes representing the presence of 1 or more publication integrating both research areas. We conducted longitudinal network analyses using an approach called MCMC MLE Temporal Exponential Random Graph Models, which models the antecedents of networks over time. RESULTS/ANTICIPATED RESULTS: Supporting Georgia CTSA objectives, results suggest the probability of publications connecting multiple research areas increased over time, with substantially greater increases appearing initially as compared to later years. DISCUSSION/SIGNIFICANCE OF IMPACT: This study advances an innovative approach to modeling the system-wide impact of CTSA hub funding.

OBJECTIVES/SPECIFIC AIMS: Acculturation and discrimination are associated with negative health outcomes including functional disability. The effect of these on functional disability in older African immigrants in the United States is not well understood. The purpose of this study is to describe and examine the experiences of acculturation, racial discrimination and functional disability in older African immigrants. METHODS/STUDY POPULATION: This study will use cross-sectional quantitative and qualitative mixed methods design. We plan to recruit 150 older (>55 years) participants through the African Immigrant Health Study and community-based organizations serving African immigrants. We will use the PROMIS physical function measure to assess functional disability, the Everyday Discrimination scale and the Psychological Acculturation scale will be used to measure discrimination and acculturation respectively. Higher scores indicate greater severity. RESULTS/ANTICIPATED RESULTS: We have recruited 12 participants so far. The mean age is 57 years and mean length of stay in the United States is 23 years. Mean disability score is 6.5 (range 1–38). Mean discrimination is 8.2 (range 4–15). The prevalent acculturation strategy of these participants (7) is marginalization (neither identified with the American nor African cultures). DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results indicate pervasive discrimination and marginalization of study participants. Exploring these experiences can inform preventive strategies of coping and health behaviors that can decrease the negative effects of discrimination, acculturation and functional disability in African immigrants.

OBJECTIVES/SPECIFIC AIMS: Approximately 25%–45% of veterans are dual users of VA and civilian healthcare. In order to maximize patient outcomes, understanding factors related to dual use is important. This study examined mental and physical health factors related to dual use of VA and civilian healthcare among U.S. National Guard and Reserve (NG/R) soldiers. METHODS/STUDY POPULATION: NG/R soldiers and their partners (n=411 couples) participated in an electronic survey assessing health and health behaviors. Logistic regression models were used to examine the relationship between mental health (anxiety, depression, PTSD, anger), general health, and VA disability status at baseline, with usage of both VA and civilian healthcare among male soldiers (n=109) at the second year follow-up, controlling for age and race. RESULTS/ANTICIPATED RESULTS: In the final adjusted models, of the mental health conditions, only anxiety was related to dual use (OR: 1.08, 1.01–1.16, p<0.05). Having a VA disability rating (OR: 4.00, 1.22–13.18; p<0.05) was also related to being a dual user. General health was not related to dual use. DISCUSSION/SIGNIFICANCE OF IMPACT: While research has identified demographic characteristics (e.g., rurality, race, income) related to dual healthcare use, our results indicate that mental health, particularly anxiety, may also be related to dual use. Further study is needed to tease out the prime drivers of dual use to identify future care delivery mechanisms that will maximize treatment outcomes and minimize duplicative care.

OBJECTIVES/SPECIFIC AIMS: Family members are often critical in the delivery of hands-on care and decisions about care for persons approaching end-of-life (EOL). Prompted by concerns about the poor quality and high costs of care at the EOL, recent delivery reform efforts—such as the growth of hospice and palliative care—have been directed at improving EOL care for both patients and family. Trends of the characteristics of EOL family caregivers and care recipients over time have not been well described. The goal of this study is to evaluate changes in EOL family caregiving from 1999 to 2015. METHODS/STUDY POPULATION: This study uses reconciled data from two nationally representative surveys and their linked caregiver surveys: the 1999 wave of the National Long-Term Care Survey (NLTCS) and the Informal Care Survey (ICS), and the 2015 wave of the National Health and Aging Trends Study (NHATS) and the National Survey of Caregiving (NSOC). RESULTS/ANTICIPATED RESULTS: Crude analysis shows that older adults living in the community and receiving help from family caregivers in the last year of life were significantly better educated (72% with greater than 12 years of education vs. 46%), and more diverse (78% White vs. 89%) in 2015 compared with 1999. Family caregivers in the last year of life were less likely to be female in 2015 compared with 1999 (74% vs. 68%, NS) and significantly less likely to be spouses (45% vs. 38%) in 2015. In 2015, a significantly greater proportion of older adults received help with five or more activities of daily living (47% vs. 34%), but family caregivers reported significantly lower levels of caregiving-associated distress: financial strain (80% reporting none in 2015 vs. 53%), emotional (51% vs. 39%), and physical strain (70% vs. 45%). In addition, a significantly greater proportion of EOL family caregivers used respite care in 2015 compared to 1999 (15% vs. 4%). DISCUSSION/SIGNIFICANCE OF IMPACT: Changes in the experience of EOL family caregiving may be impossible to capture in studies of single interventions, but tracking nationally representative trends can be used as an indicator of broader changes that take place cumulatively over time. Although studies of this nature cannot identify causal mechanisms of change, they are important to monitor long-term impact of program implementation and to guide future research, policy, and resource allocation.

OBJECTIVES/SPECIFIC AIMS: Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice, and has widely varying treatments for stroke prevention and rhythm management. Some of these therapies are increasingly being prescribed by primary care physicians (PCPs). We therefore sought to investigate if healthcare plans with PCP gatekeeping for access to specialists are associated with different pharmacologic treatment strategies for the disease. In particular, we focused on oral anticoagulants (OACs), non-vitamin K-dependent oral anticoagulants (NOACs), rate control, and rhythm control medications. METHODS/STUDY POPULATION: We examined a commercial pharmaceutical claims database (Truven Marketscan™) to compare the prescription frequency of OAC, rate control, and rhythm control medications used to treat AF between patients with PCP-gated health plans (where the PCP is the gatekeeper to specialist referral—i.e., HMO, EPO, POS) and patients with non-PCP-gatekeeper health plans (i.e., comprehensive, PPO, CHDP, HDHP). To control for potential confounders, we also used multivariable logistic regression models to calculate adjusted odds ratios which accounted for age, sex, region, Charlson comorbidity index, CHADS2Vasc score, hypertension, diabetes, stroke/transient ischemic attack, prior myocardial infarction, peripheral artery disease, and antiplatelet medication use. We also calculated median time to therapy to determine if there was a difference in time to new prescription of these medications. RESULTS/ANTICIPATED RESULTS: We found only small differences between patients in PCP-gated and non-PCP-gated plans regarding prescription proportion of anticoagulants at 90 days following new AF diagnosis (OAC 44.2% vs. 42%, p<0.01; warfarin 39.1% vs. 37.1%, p<0.01; NOAC 5.9% vs. 6.0%, p=0.64). We observed similar trends for rate control agents (76.4% vs. 73.4%, p<0.01) and rhythm control agents (24.4% vs. 24.6%, p=0.83). We found similar odds of OAC prescription at 90 days following new AF diagnosis between patients in PCP-gated and non-PCP-gated plans (adjusted OR for PCP-gated plans relative to non-gated plans: OAC 1.006, p=0.84; warfarin 1.054, p=0.08; NOAC 0.815, p=0.001; dabigatran 0.833, p=0.004; and rivaroxaban 0.181, p=0.02). We observed similar trends for rate control agents (1.166, p<0.0001) and rhythm control agents (0.927, p=0.03). Elapsed time until receipt of medication was similar between PCP-gated and non-gated groups [OAC 4±14 days (interquartile range) vs. 5±16 days, p<0.0001; warfarin 4±14 vs. 5±14, p<0.0001; NOAC 7±26 vs. 6±23, p=0.2937; rhythm control 13±35 vs. 13±34, p=0.8661; rate control 10±25 vs. 11±30, p<0.0001]. DISCUSSION/SIGNIFICANCE OF IMPACT: We found that plans with PCP gatekeeping to specialist referrals were not associated with clinically meaningful differences in prescription rates or delays in time to prescription of oral anticoagulation, rate control, and rhythm control drug therapy. In some cases, PCP gatekeeping plans had very small but statistically significant lower odds of being prescribed NOACs. These findings suggest that PCP gatekeeping does not appear to be a major structural barrier in receipt of medications for AF, although non-PCP-gated plans may vary slightly favor facilitating the prescription of NOACs. Our findings that overall OAC prescriptions did not differ by PCP gating status may suggest completion of the rapid dissemination and uptake phase for most AF treatments. The small but statistically significant odds ratios favoring the non-PCP-gated populations in NOACs further suggests that in this newer drug group, the process is ongoing, with more specialists representing early adopters. Interestingly, the low primary care odds ratio of rivaroxaban use, relative to dabigatran, may be indicative of a gradient of uptake of later-generation NOACs, although interpretability is limited by the small number of patients in the rivaroxaban group.

OBJECTIVES/SPECIFIC AIMS: ClinicalTrials.gov (CTgov) compliance has received much international attention as a significant regulatory, scientific, and ethical responsibility. Compliance rates for both industry and academia are held up for scrutiny by transparency advocates, but solutions for achieving compliance in academia have proven to be—because of its focus on innovation and multiple disciplines—significantly more complex than those employed by industry. Added challenges for academic medical centers (AMCs) are both increased researcher responsibilities under the new NIH Policy on Clinical Trial Dissemination and system-wide changes to requirements for “clinical trial only” Funding Opportunity Announcements. At Stanford University, a multifaceted approach toward improving CTgov outreach, education, and reporting led to a dramatic turnaround in compliance over 17-month period. METHODS/STUDY POPULATION: Stanford University School of Medicine’s Senior Associate Dean for Research and PI of Stanford’s CTSA applied a 3-part strategy to address unacceptable rates of results reporting. The strategy included (1) regular compliance reports to department chairs, (2) establishment of a central office, Clinical Research Quality (CRQ), to provide consistent training and support, and (3) interdepartmental cooperation across the school and university. Compliance reports, identifying all studies late for results reporting were sent monthly to all department chairs, with heightened focus on departments that conduct the most clinical trials. Senior leadership described the process in executive meetings and set improvement goals. Reports included multiple data points to help departments mobilize resources and identify trends; half-way through the period, soon-to-be late study records were included. CRQ hired 2 fulltime employees tasked with all aspects of managing the CTgov process and designed a portfolio of activities including: (1) a master list of all Stanford studies in the CTgov system; (2) a process for generating and distributing monthly reports; (3) an education program; and (4) support services, including an administrator working group. RESULTS/ANTICIPATED RESULTS: Since December 2015, Stanford has had the second-highest compliance rate improvement out of the 20 schools of medicine that receive the most NIH funding (+ 62%). DISCUSSION/SIGNIFICANCE OF IMPACT: Managing ClinicalTrials.gov compliance requires a high degree of technical knowledge of regulations, NIH policy, and the CTgov system. But without an equally high degree of engagement from senior leadership, results would not have been achieved. Central resources are critical to set policy and establish consistent processes, but without regular and repeated interactions between faculty, a multitude of administrators and staff, more central resources would have been required. By working simultaneously “down from the top” and “up from the bottom,” communication and education expanded rapidly, ineffective efforts were quickly transformed, and what began as an irritating and cumbersome problem became an occasion for collaboration and celebration of increased transparency.

OBJECTIVES/SPECIFIC AIMS: To outline 4 categories of ethics needs identified at a translational science center. To map how research ethics has been further integrated into the center’s culture in response to these needs. To provide insights into how research ethics can be integrated into the translational team science environment. METHODS/STUDY POPULATION: The Institute for Translational Sciences (ITS) at the University of Texas Medical Branch is studied on an organizational level using polyphonic organizational theory and the results of an ethics needs assessment completed in 2010. RESULTS/ANTICIPATED RESULTS: The results will be a map indicating how research ethics has been further integrated into the culture of the ITS in response to the needs identified to ensure the responsible practice of translational science. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful translational science requires shared understanding of communication and values. Achieving agreement in these areas requires the development of strategies for communicating and reinforcing common goals. Research ethics has often been considered an “add on” rather than a “part of” science. Through integrating ethics into various aspects of translational science, the ITS has taken important steps toward achieving the goal of culture change. The map of how the ITS has integrated ethics into organizational activities and structures will serve as a model for other organizations and institutions.

OBJECTIVES/SPECIFIC AIMS: In combination with 3 waves of individual-level data on children age 5–18 from the Panel Study of Income Dynamics, we exploit exogenous variation at the level of the state to determine whether SNAP generosity modifies the effect of SNAP participation on overweight/obesity status. We do so using a newly created and powerful data set including information on state-level SNAP generosity between the years 1996 to 2011. METHODS/STUDY POPULATION: Data and sample. We drew individual-level data from the Child Development Supplements of the Panel of Income Dynamics (PSID), a nationally representative longitudinal study gathering data since 1968 on US individuals and the families in which they reside. Aged 0–12 years in 1997, these children of PSID sample members were surveyed roughly every 5 years through 2007. The total number of observations over the study period is just over 8093, representing 3563 children. We drew state-level data from the State Welfare Generosity Index. This is a decomposable index of State welfare generosity capturing state policy variation across 4 programs (TANF, SNAP, Unemployment Insurance and Medicaid/CHIP) and 2 dimensions (eligibility requirements and benefit levels). Measures. Child weight status was determined using the Center for Disease Control (CDC) body mass index (BMI)-for-age gender-specific growth charts: underweight (BMI <5th percentile), healthy weight (BMI >5th percentile and BMI <85th percentile), overweight (BMI >85th percentile and BMI <95th percentile) or obese (BMI >95th percentile). From this, we constructed an indicator for overweight/obese Versus normal or underweight status. SNAP participation is a dichotomous indicator based on the head-of-households or their spouses reported receipt of SNAP benefits during the previous calendar year from the interview. SNAP generosity is scored on a scale of 0–100, with more generous states receiving higher scores than less generous states. Covariates include sex, race, age, head-of-household years of education and a continuous measure of household income adjusted for family size. Estimation techniques. We merged the child, parent/caregiver, family and main PSID files to obtain the most comprehensive data on each sample child. We first generated, descriptive statistics for the Wave 1 sample of 3563 children. We then present the mean, standard deviation and the ratio of the 2 (coefficient of variation) for state-level variables. We present χ2 tests of difference for non-SNAP compared to SNAP participants in terms of overweight/obesity, and pairwise correlation coefficients among the 3 state-level variables. Next, we conducted a series of simple and multivariate logistic regressions estimating the odds of being overweight or obese. As we are assessing the risk of adverse weight status, those of normal or underweight status are the reference group for all regression analysis. Because height and weight reports are known to be unreliable below the age of 5, regression analyses impose an age restriction of greater than 5 years old. We include adjustment for the clustered nature of data. RESULTS/ANTICIPATED RESULTS: The individual-level statistics indicate that roughly one-third of the CDS sample is overweight or obese at Wave I in 1997. About a fifth of them live in families receiving SNAP. The mean SNAP generosity score is 10 on a possible range of 0 to 1 (observed range of 0.037 to 0.290 not shown). Variation across state-years is greatest for the SNAP participation variable, as reflected by the coefficient of variation. In the period 1997–2007, the proportion of children who are overweight or obese is 5% higher among those in families receiving SNAP program benefits than among those in families not receiving SNAP benefits. Similarly, SNAP participation is positively, moderately and significantly (with an α of 0.05) correlated with overweight/obesity. Examines the relationship between overweight/obesity and the SNAP measures using individual-level data on overweight/obesity and SNAP participation and state-level data on SNAP generosity. Model 1 estimates and exponentiates the log odds of overweight/obesity based on individual-level SNAP participation. Model 2 does the same using state-level SNAP generosity as the predictor. Results indicate that both variables are positively associated with a child’s chance of being overweight/obese. But only in the case of SNAP participation is the SNAP variable statistically significant. Children living in families receiving SNAP benefits are more likely to be overweight/obese by a factor of 1.23. A set of potential confounders to the analysis and tests for interaction effects between SNAP participation and SNAP generosity (Model 3). Controlling for a variety of demographic and socio-economic factors, the positive effect of SNAP participation on overweight/obesity is rendered negative. The nonsignificant effect of SNAP generosity remains. In Model 3, the interaction effect for SNAP participation and generosity is positive and marginally significant. This suggests that the generosity of benefits changes the basic relationship between SNAP participation and overweight/obesity among children in families receiving benefits. To help convey the meaning of this coefficient, we generated marginal effects of SNAP participation based on SNAP generosity, setting all covariates equal to their means. This figure shows a small negative effect of SNAP participation at the lowest levels of generosity (a score of around 4, the sample minimum). This negative effect crosses 0 at a score of around 12, then becomes positive. The magnitude of the positive effect grows up to the sample max (index=28), although with widening confidence intervals. DISCUSSION/SIGNIFICANCE OF IMPACT: The focal interest of this study lies in the potential interaction effect between SNAP generosity and SNAP participation on overweight/obesity. Although the effects were only marginally significant, we find that SNAP generosity does interact with SNAP participation. More specifically, the effects of SNAP participation appear negative at lower levels of generosity, becoming positive as generosity scores exceed the sample mean (index=10). In other words, state-level SNAP generosity appears to exacerbate the adverse effects of SNAP participation on overweight/obesity. Although we submit that our current findings contribute to the literature on the SNAP-health link, we intend to strengthen our analysis in several ways. First, we will fit models that exploit the strengths of the PSID and the welfare generosity index in terms of causal inference. We will use fixed effects models to control not only for potential unobserved confounders related to the child but also observable baseline characteristics. Leveraging the fact that PSID samples up to 2 children from each family, we will further refine our estimates towards a causal interpretation with the use of sibling fixed effects, in which we additional account for unmeasured time-invariant family-level variables that encapsulate a variety of factors including learned behaviors, cultural influences, genetic predispositions that contribute to child health outcomes. Second, research has clearly shown that compared with higher-SES individuals, lower-SES individuals have higher BMI regardless of welfare program participation. These selection effects are addressed somewhat by the PSID’s intentional over-representation of low-income individuals. But we can much more convincingly address these potential problems with endogeneity by refining our analyses to compare SNAP participants to SNAP-eligible nonparticipants, thereby isolating the effect of the SNAP “treatment.” Lastly, we intend to include a wide array of state-level covariates that may be related to our independent and dependent variables of interest, such as poverty rate, unemployment rate, and racial/ethnic composition.

OBJECTIVES/SPECIFIC AIMS: Educate the general public, investigators, and institutional leadership on the importance of clinical trial registration and results reporting. Share success as a means to develop national best practices. METHODS/STUDY POPULATION: Developed a Project Charter; Spoke to several peer institutions; Update institutional policy. RESULTS/ANTICIPATED RESULTS: Since launching the Program in June 2016, the number of records submitted to ClinicalTrials.gov has increased 14% (852–971). At the same time, compliance with late results has increased by over 92% (111–9). DISCUSSION/SIGNIFICANCE OF IMPACT: Clinical Trial registration and results reporting is sub-par at many institutions. We have established a successful program that others can emulate. Institutions can increase transparency of clinical trials as well as prevent civil monetary penalties ($11,569/d/study) and loss of grant funding.

OBJECTIVES/SPECIFIC AIMS: Long-acting reversible contraception (LARC) has been well established as the most cost-effective form of contraception, but LARC usage in developing countries remains low. As part of a multi-center parent study on HIV incidence, we implemented an integrated family planning program to increase LARC uptake in single women in Rwanda and Zambia. We aim to evaluate rates of LARC uptake, LARC discontinuation and incident pregnancy following family planning counseling. METHODS/STUDY POPULATION: We enrolled 3 cohorts of single sexually active HIV-negative women between the ages of 18–45 years: single mothers (SM) in Zambia, female sex workers (FSW) in Zambia and FSW in Rwanda. Participants were followed every 3 months for up to 5 years. At each visit, we discussed fertility goals and counseled participants on HIV risk reduction and contraceptive options. Eligible participants (not pregnant, already using a LARC method, or using a permanent contraceptive method) were offered a LARC method, specifically the copper IUD or Jadelle implant. Data was collected on demographic factors, sexual behavior, sexual and reproductive history, and gynecological exams and laboratory tests were performed if necessary. RESULTS/ANTICIPATED RESULTS: In total, 458 Rwandan FSW, 555 Zambian FSW, and 521 Zambian SM were enrolled, with a median follow-up time of 6 months, 12 months, and 9 months, respectively. Accounting for any LARC uptake during longitudinal follow-up, our preliminary results show an increase in LARC usage from 21% at screening to 51% at the end of follow-up among Rwandan FSW, an increase from 12% to 42% in Zambian FSW and an increase from 18% to 44% in Zambian SM. We hypothesize that demographic factors (e.g., younger age, higher education level) and sexual history (e.g., greater number of sexual partners, any STIs or reproductive health disturbances) will be associated with increased rates of LARC uptake. We also hypothesize that LARC users will have significantly lower proportions of contraceptive method discontinuation and incident pregnancy compared to non-LARC users. DISCUSSION/SIGNIFICANCE OF IMPACT: FSW and SM are disproportionately affected by high rates of unintended pregnancy, which can lead to obstetric complications and poor psychosocial outcomes. It is imperative that family planning interventions in developing countries target these populations to overcome obstacles in reproductive health and promote gender equality. Our study will provide necessary insights to an integrated family planning program, which will guide future efforts to design, implement and evaluate family planning initiatives for high-risk populations.

OBJECTIVES/SPECIFIC AIMS: Brain tumors are the most common solid tumor diagnosed in children and their location predisposes patients to oromotor dysfunction leading to feeding difficulties. Brain tumor patients experience feeding difficulties more frequently than other pediatric malignancies, largely due to central nervous system directed chemotherapy, radiation, and surgery. Treatment increases the risk of malnutrition and increases risk for infection, ICU admissions, and death. Infants and children (less than 3 years of age) are at higher risk for malnutrition due to rapidly changing nutritional requirements and the underdevelopment of motor skills. Incidence and prevalence of malnutrition in pediatric cancer patients is not well known. METHODS/STUDY POPULATION: This is an observational, retrospective study of our center’s pediatric cancer patients. Patients are classified by diagnosis, treatment intensity (ITR-2), vital status, and heights and weights (with standardized Z-scores) will be recorded with through 2 years after diagnosis. Adaptation of Intensity of Treatment Rating ITR-2. Nutrition consultation, ICU admissions, and use of parenteral or enteral nutrition will be recorded. Weight loss greater than a 5-percentile point change or Z-score decrease greater than 0.5 will be treated as a binary outcome and considered significant weight loss. RESULTS/ANTICIPATED RESULTS: Preliminary analysis has identified 465 eligible subjects as described above: brain tumor (n=45) and nonbrain tumor patients (n=420). Patient Schema. This study is still in progress and aims to better identify incidence of malnutrition during pediatric cancer therapy. It is expected that a greater number of nonbrain tumor patients compared with brain tumor patients will be malnourished as defined by decrease in Z-score greater than 0.5 at any point in therapy or falling below the 5th percentile of weight for age. Weight loss will be associated with higher number of ICU admissions and higher treatment intensity score. Finally, we expect to find that patients with a larger decrease in Z-score for age will be more likely to die during therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: In addition to this study being valuable in better defining incidence of malnutrition, this data will serve as preliminary data in defining target populations for focused nutritional intervention during cancer therapy. Using this established and published intensity rating scale, we may be able to identify better methods of identifying and preventing malnutrition during cancer therapy.

OBJECTIVES/SPECIFIC AIMS: To identify new ethical challenges in human subject research related to the use of cloud-based platforms for data collection. METHODS/STUDY POPULATION: Ethical analysis. RESULTS/ANTICIPATED RESULTS: The OHRP regulations protecting the data, privacy and confidentiality of human subjects and the Terms of Service regulations governing data use by cloud-based platforms are vastly different. The gap between these 2 sets of laws and regulations leaves human subjects vulnerable to harm during the data collection process via clod-based tools. DISCUSSION/SIGNIFICANCE OF IMPACT: Recognizing the risks related to data gathering via cloud-based platforms, and educating researchers and research subjects about these risks and how to minimize them will strengthen the protections of participants and will enhance the informed consent process resulting in increased trust and greater willingness to participate in human subject research.