bluuebunny/crossref_metadata_2025 huggingface dataset:
4113 Infusing a CTSA Program with Causal Pathway Thinking to Transform Evaluation from Operations to Impacts
Authors: Kost Rhonda G , Boone Leslie , Cook Sarah , Nelson Sarah , Wilkins Consuelo Hopkins , Stroud Mary , Dunkel Leah , Byrne Loretta , Jones Michelle , Harris Paul A. , Vaughan Roger
Published: July 2020

OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.
4079 Lessons learned from implementing Quality Improvement (QI) in academic clinical research setting
Authors: Lee Chin Chin , JAYAWEERA DUSHYANTHA , Godfrey Marjorie , Salathe Matthias , Wright Jonelle , Sacco Ralph L.
Published: July 2020

OBJECTIVES/GOALS: We describe here the implementation of a pilot Quality Improvement (QI) program in clinical research processes in order to facilitate translation from bench to community. This presentation will also discuss challenges encountered by the research teams during the implementation of QI activities. METHODS/STUDY POPULATION: Miami CTSI collaborated with University of Kansas’ CTSA to test the implementation of a QI program for clinical research processes. The program has a duration of 1 year and consists of multi-modal training and coaching sessions with different research teams. Six teams comprising of Principal investigators, clinical coordinators, and regulatory specialists participated in the program based in applied clinical microsystem theory science. Team coaches and teams worked together to assess current processes, test new and improved processes, and standardize and disseminate applicable best practices of the QI program. RESULTS/ANTICIPATED RESULTS: The implementation of QI activities in large clinical research settings poses numerous challenges for the research team. We will present survey results from the coaching sessions and follow on feedback from the different teams involved in the program to implement the QI activities. We will describe the modifications and adjustments made to the original conceptual framework of QI program in order for it to be applicable and feasible for the settings of the University of Miami. We will provide recommendations for other academic clinical research centers that are considering implementing a QI program. DISCUSSION/SIGNIFICANCE OF IMPACT: The successful adaptation of a QI process to implement in academic clinical research settings relies on early engagement of the institution leadership, careful selection of team members, as well as developing communication skills to enhance team dynamics as a clinical research unit.
4134 Report from the research trenches: A mixed-methods approach to investigation of how recruitment methods, culture and collaboration impact clinical trial accrual
Authors: Swartz Kitt , Zauflik Meredith , zell Adrienne , Morris Cynthia , Ellison David
Published: July 2020

OBJECTIVES/GOALS: The research project aimed to understand the perceived effectiveness of research recruitment methods, including informatics tool utilization, so that best practices can be established and outcomes measured longitudinally. METHODS/STUDY POPULATION: The mixed-methods study was conducted by the Oregon Clinical and Translational Science Institute, the CTSA at Oregon Health and Sciences University. A survey, clinical trial accrual data, and interviews were used to assess the study aims. The survey asked about utilization and value of specific recruitment tools and methods. Accrual data was obtained from the clinical trial management system and analyzed using parameters from the CTSA “Accrual Metric”. The metric was calculated for clinical trials enrolling during 2017. Interviews were conducted with researchers identified by the survey and over or under-enrolled accrual data, and inquired about recruitment facilitators and barriers. RESULTS/ANTICIPATED RESULTS: The most frequently mentioned facilitator of recruitment was direct patient contact, either in the healthcare setting (58.4% of survey respondents) or through patient outreach (32%). A lack of resources was considered a key barrier (21% of survey respondents) and a stated need (27%). Interview data expanded on these findings, as 23% of interviewees indicated a collaborative culture, which includes clinic integration, was key to recruitment success. Additionally, 20% of interviewees identified resources (i.e. funding, staff, time) as their greatest need. Notably, 13% of studies with an accrual ratio of “0” had frequent staff turnover. DISCUSSION/SIGNIFICANCE OF IMPACT: This approach allowed for a uniquely targeted analysis of accrual facilitators and barriers. Use of the CTSA accrual metric identified high-value interview respondents and will allow for investigation into additional accrual questions, such as the impact of funding sources and departmental factors.
4457 Adopting a Team Science Communication Module for Community-Partnered Teams
Authors: Brown Arleen F , Norris Keith , Bross Rachelle , Castellon Yelba , Mtume Norma , Morris D’Ann , Wright Aziza Lucas , Barron Juan , Hakopian Sarmen , Campo Maritza Salazar
Published: July 2020

OBJECTIVES/GOALS: There is increased recognition that patients and community members are critical to creating impactful research. To this end the UCLA CTSI Community Engagement & Research Program modified an established multidisciplinary team science communication module to train academic-community research teams. METHODS/STUDY POPULATION: Community partners who have had previous experience in participatory research provided input such as limiting the emphases of individual academic introductions to group icebreakers (to level the playing field), reduced academic jargon to lay language, reducing the amount of text to key principles, and changed academic team scenarios for the team activity to represent community-academic teams. Academic partners articulated institutional barriers to integrating community into institutional systems. Iterative testing and modifications occurred through pilots with eleven teams (49 individuals). RESULTS/ANTICIPATED RESULTS: Embedding community partners in team science training involved creating a level playing field with less emphasis on academic credentials, using lay language in the didactic sessions and ensuring accessibility in all aspects of the training. An example of modifications: communication scenarios were read out loud by participants, which community partners felt were not inclusive of potential varying literacy levels and all partners may not feel comfortable reading aloud in a group setting. The vignettes were replaced with short videos of the scenarios with audio recordings. Several modifications were made the training’s team activity of the training module. DISCUSSION/SIGNIFICANCE OF IMPACT: Traditional academic team science training required significant modifications for an academic/community-partnered team to allow for optimal collaboration, inclusion, and strategically reduce the power dynamics that can naturally occur. Long-term followup to assess their effectiveness is needed.
4428 Harnessing Community Paramedicine for Transformative Fall Prevention Solutions
Authors: Quatman Carmen , Gabriel Melinda , Wisner David , Weade Mark , Garvin Jennifer , Sheridan Elizabeth , Wiseman Jessica , Quatman-Yates Catherine
Published: July 2020

OBJECTIVES/GOALS: Healthcare costs for falls are expected to reach nearly 55 billion dollars annually in the US by 2020. Leveraging 911 calls as trigger events to activate fall prevention solutions could transform our ability to identify high-risk individuals and significantly improve fall prevention strategies globally. METHODS/STUDY POPULATION: An innovative pilot program entitled Community-centered Fall Intervention Team (Community FIT). Community FIT that leverages 911 calls, implementation science approaches, community partnerships, and collaboration among multiple healthcare disciplines including physical therapists, community paramedics, physicians, and social service coordinators was used to design and implement a community paramedicine fall intervention program. 911 call reports from February 2016 – August 2019 were analyzed using time series analyses to measure community level outcomes in fall-related calls and transports. RESULTS/ANTICIPATED RESULTS: 224 grab bars were installed free of charge to local residents (averaging approximately $125 per home for modifications).Over an 18-month period, time series analysis indicated an approximate demonstrated a consistent drop in the average fall-related 911 calls per month from 11.6 to 4.5 calls (a change of 61.21%) and a decrease of 58% in the transport rates to the hospital for fall-related 911 calls. 911 referrals to the community paramedicine program have also increased by 83%, demonstrating increased activation of fall prevention strategies with Community FIT. DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these pilot study results provide preliminary support for individual and system level improvements in fall prevention by leveraging 911 calls to activate a community medicine fall prevention program. Future studies are needed to determine reach, long-term effectiveness, and sustainability of the program. CONFLICT OF INTEREST DESCRIPTION: Johnson & Johnson Hip Fracture Advisory Board (not related to project submission)
4255 Indiana Clinical and Translational Sciences Institute (CTSI) – CTSA-wide podcast opportunity
Authors: Drury Christine , Carroll Aaron E.
Published: July 2020

OBJECTIVES/GOALS:

The podcasts highlight work from our partners: Indiana University, Purdue University and the University of Notre Dame.

Our goal is to expand our podcast reach to include work from at least three additional CTSAs, as well as highlighting the benefits of translational research to the public.

METHODS/STUDY POPULATION:

Aaron E. Carroll, is the director of Education and Workforce Development for the Indiana CTSI and a popular writer covering health, research, and policy for The New York Times. He is host of the Indiana CTSI-sponsored Healthcare Triage podcasts as well as the Healthcare Triage YouTube show, with 340,000 subscribers. We will leverage his audience and research expertise to grow the Indiana CTSI podcast participation and increase audience engagement.

We will eventually allow the nation-wide network of CTSAs to pitch guests and shows covering Translational Research, and invite local CTSA leadership or faculty to participate in the podcast.

RESULTS/ANTICIPATED RESULTS:

Utilizing quantitative analytics, we expect to see a significant increase in podcast downloads and listeners as we expand our offering to other CTSAs, beyond Indiana

We expect that the CTSA-wide podcast will increase the nationwide level of knowledge and understanding of NCATS, translational research, and its benefits to society and healthcare.

We anticipate, through this expanded podcast offering, a growing number of community members who are informed and engaged on the topics of translational research, clinical and translational sciences and beyond.

DISCUSSION/SIGNIFICANCE OF IMPACT:

Podcasts are a convenient, portable, and efficient form of science communication.

Podcasts also make information personal and offer us an excellent and innovative communications vehicle to spread the word about translational research, as well as the excellent work happening at each of our CTSAs.
4343 Utilization of quantitative and qualitative methodology to characterize patient-level factors associated with sustained data transmission and clinical benefit from remote patient monitoring over 12 months
Authors: Kirkland Elizabeth Barnhardt , Sterba Katie , Mauldin Patrick , Moran William P.
Published: July 2020

OBJECTIVES/GOALS:

1.

Identify patient-level factors associated with hemoglobin A1c reduction and sustained device use after 12months of participation in a diabetes and hypertension remote monitoring program

2.

Utilize qualitative methodology to characterize key barriers and facilitators to remote monitoring engagement

METHODS/STUDY POPULATION: All participants in statewide quality improvement initiative utilizing a cellular-enabled device with glucose and blood pressure monitoring capability will be included in quantitative analysis (N = 302 at baseline and N = 125 at 6 months at the time of analysis). We developed multilevel regression analyses to model factors associated with clinical outcome (hemoglobin A1c change) and transmission frequency over time. Focus groups and surveys will be conducted to identify barriers and facilitators to continued data transmission and hemoglobin A1c change over 12 months. Semi-structured interview guides are mapped to Wagner’s Chronic Care Model. RESULTS/ANTICIPATED RESULTS: Overall, program participation was associated with 1.8% and 1.3% A1c reduction at 6 (n = 302) and 12 months (n = 125). Regression models showed no association of age, gender, race, income, or insurance with hemoglobin A1c change. Modeling of patient factors associated with sustained transmission frequency or device use is ongoing. Patient focus groups and surveys are currently being scheduled and qualitative data will be analyzed using content analysis. After completing qualitative and quantitative data analyses independently, we will use graphical matrix configurations (“joint displays”) to synthesize findings. DISCUSSION/SIGNIFICANCE OF IMPACT: Our goal is to identify variables associated with the likelihood of patients to engage in and benefit from sustained remote monitoring. Results may inform health policy and guide recruitment approaches, implementation strategies, and methodologic design for future trials. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest or disclosures to report
4086 HIV-Associated Myocardial Diastolic Dysfunction and Soluble ST2 Concentration in Tanzanian Adults: A Cross-Sectional Study
Authors: Kingery Justin , Hosalli Rahul , Desdarius Bernard , Kalokola Fredrick , Damas Edmund , Reis Karl , Lee Hyung Hee , McNairy Margaret , Fitzgerald Daniel , Peck Robert
Published: July 2020

OBJECTIVES/GOALS: To determine the prevalence of myocardial diastolic dysfunction (DD) and association of serum concentration of the cardiac biomarker serum soluble ST2 in HIV-infected as compared to uninfected Tanzanian adults at the time of HIV diagnosis. METHODS/STUDY POPULATION: In this cross-sectional study we consecutively enrolled HIV-infected participants and uninfected controls at a large, referral HIV clinic in Mwanza, Tanzania. Standardized history, physical examination, echocardiography and serum samples were obtained. The primary outcome was prevalence of myocardial diastolic dysfunction in HIV-infected as compared to uninfected adults. The secondary outcome was the association of baseline serum sST2 concentration with diastolic dysfunction prevalence. Regression models were used to quantify the associations. RESULTS/ANTICIPATED RESULTS: We enrolled 388 HIV-infected, ART naïve and 461 HIV-uninfected controls. Participants with HIV had a higher prevalence of DD (OR = 2.44, p = 0.001, controlled for age, sex, hypertension and BMI) and more severe dysfunction (66.7% vs 42.5%, p = 0.056) at an earlier age. Baseline serum sST2 concentration was significantly associated with DD in HIV-infected but not uninfected participants (p = 0.04 and 0.90, respectively). More HIV-infected adults with concurrent DD exceeded the threshold of 35ng/mL as compared to controls (15.7% vs 5.3%, p<0.0001). Additionally, a significant population level shift to higher sST2 concentration was observed in HIV-infected adults with dysfunction as compared to both HIV-infected without and HIV-uninfected adults with dysfunction (Kolmogrov-Smirnov test: p = 0.02 and 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: In a large population of HIV-infected adults in sub-Saharan Africa, HIV infection is associated with myocardial diastolic dysfunction. This dysfunction is associated with higher sST2 concentrations. Therefore, we conclude that the sST2 pathway may provide insight into the pathophysiologic mechanisms of dysfunction in HIV-infected adults.
4472 Plasma Neurofilament Light as a Biomarker for Pediatric Patients with Huntington’s Disease
Authors: Schultz Jordan L
Published: July 2020

OBJECTIVES/GOALS: The goal of this study is to compare plasma neurofilament light (NfL) concentrations in asymptomatic children and young adults that carry the gene expansion (GE group) that causes Huntington’s Disease to similar subjects that do not carry this genetic mutation (GNE group). METHODS/STUDY POPULATION: Subjects from the Kids-HD study in the GE group were divided into groups based on their estimated years to motor onset. Each subgroup was compared to the subjects from the GNE group. Additionally, a group of participants with juvenile HD were compared to the GNE group. These comparisons were made by utilizing linear mixed effects regression models that included a random effect per subject and family and also included the covariates of age and parental socioeconomic status. A post-hoc analysis of subjects in the GE group who were within 20 years from their predicted motor onset was conducted to assess the relationship between striatal volume and plasma NfL concentrations. RESULTS/ANTICIPATED RESULTS: GE participants more than 20 years from their predicted motor onset did not have elevated plasma NfL concentrations relative to the GNE group. However, participants who were 15-20 years from their predicted motor onset had a mean NfL concentration of 1.61 pg/uL compared to 1.31 pg/uL in the GNE group (p = 0.036). Participants who were within 15 years from their predicted motor onset had a mean NfL concentration of 2.08 pg/uL, which was also significantly elevated relative to the GNE group (t = 3.03, p = 0.003). Additionally, the participants with juvenile HD had a mean NfL level of 3.22 pg/uL, which was significantly elevated compared to the GNE group (p<0.0001). NfL concentrations were significantly correlated with striatal volume amongst participants who were within 20 years of onset (p = 0.017). DISCUSSION/SIGNIFICANCE OF IMPACT: The huntingtin protein is essential to neurodevelopment but current gene therapies for HD focus on blocking production of this gene. These results will provide guidance on the optimal timing of administration of gene therapies by identifying neurodegeneration decades prior to motor onset of HD.
4369 Reprogramming of vascular smooth muscle cells to multipotent progenitor cells contributes to progression of atherosclerosis
Authors: Dubner Allison Milfred , Lu Sizhao , Jolly Austin , Strand Keith , Mutryn Marie , Tucker Rebecca , Moulton Karen , Nemenoff Raphael A. , Weiser-Evans Mary C.M.
Published: July 2020

OBJECTIVES/GOALS: Our lab previously identified a population of vascular smooth muscle (SMC)-derived progenitor cells (AdvSca1-SM) which expand robustly in response to disease and can differentiate into multiple cell types. We now aim to define the role of these AdvSca1-SM cells in atherosclerotic plaque progression. METHODS/STUDY POPULATION: Goal one uses SMC lineage tracing mice and a model of atherosclerosis to track reprogramming of SMCs to AdvSca1-SM cells in the setting of disease. Arteries are analyzed using flow cytometry and immunofluorescence to quantify changes in number of mature SMCs and AdvSca1-SM cells. Goal two uses AdvSca1-SM lineage tracing mice with high cholesterol-induced atherosclerosis and plaque neovascularization. Arteries are analyzed to quantify expansion of AdvSca1-SM cells, subsequent re-differentiation into mature SMC, endothelial cells, or macrophages, and contribution to plaque neovascularization. Mechanistic findings from both goals are being investigated in diseased human coronary arteries. RESULTS/ANTICIPATED RESULTS: Flow cytometry from SMC lineage tracing mice revealed a 7- to 13-fold expansion of AdvSca1-SM cells in carotid arteries (p<0.001) and aortas (p = 0.03) after 6 weeks of western diet; no differences in macrophage numbers were observed. Additional SMC and AdvSca1-SM cell lineage tracing mice are on atherogenic diets to assess early and advanced atherosclerosis. We predict that AdvSca1-SM cells will contribute to macrophage accumulation as well as plaque neovascularization in the setting of severe atherosclerosis. Translational relevance of mechanisms driving SMC reprogramming and AdvSca1-SM cell contribution to plaque progression are being applied to studies of diseased human coronary arteries. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest a role for AdvSca1-SM cells in atherosclerosis. Ongoing work will clarify the mechanisms driving plaque-associated AdvSca1-SM expansion and define the ultimate fates of these cells. In vivo modulation of this process could provide the basis for future anti-atherosclerotic therapies. CONFLICT OF INTEREST DESCRIPTION: AD - CCTSI TOTTS TL1TR002533; SL - 18POST34030397 from the American Heart Association; AJ – no conflicts; KS - 1F31HL147393 from the National Heart, Lung, and Blood Institute, NIH; MM – no conflicts; RT – no conflicts; KSM – no conflicts; RAN - R01CA236222 from the National Cancer Institute, NIH, and 2018-03 from the Lungevity Foundation; and MCMW-E - R01 HL121877 from the National Heart, Lung, and Blood Institute, NIH, and 25A8679 from the Chernowitz Foundation.
4190 White Matter Integrity in Hemodialysis Patients
Authors: Richerson Wesley , Wolfgram Dawn , Schmit Brian
Published: July 2020

OBJECTIVES/GOALS: The purpose of this study is to understand how hemodynamics during dialysis in End-Stage Renal Disease (ESRD) patients on hemodialysis (HD) affect white matter health and how those effects cause cognitive impairments. METHODS/STUDY POPULATION: We collected demographic data, comorbidities, intradialytic measurements of blood pressure and cerebral oximetry, cognitive measures in several domains using NIH Toolbox Cognition Battery, diffusion-weighted and anatomical MRIs for 20 participants on HD. Specific tracts were identified using tractography and were used to calculate the average DTI measurements in each tract. Regression analysis was used to examine the relationship between mean DTI measurements of white matter integrity and cognitive performance scores. In addition, we compared diffusion MRI and T1 anatomical images of 16 healthy age-matched controls from a previous study. RESULTS/ANTICIPATED RESULTS: In our cohort 18 participants had imaging data that could be used in the analysis. We found widespread decreases in DTI white matter integrity compared to healthy age-matched controls, mean whole-brain fractional anisotropy was .3218 in the HD cohort and .3472 in controls p = .0018. Decreased integrity was found in most of the tracts identified but more decreased in tracts implicated in cognition. Partial regression analysis identified significant relationships between the white matter integrity of the left superior longitudinal fasciculus and overall fluid cognitive performance, R = .5525, p = .0174 before multiple comparisons correction when controlling for differences due to age. DISCUSSION/SIGNIFICANCE OF IMPACT: We found a widespread decrease in white matter integrity and significant correlations between cognitive performance and specific tract integrity in our HD cohort using regions identified by tractography imaging analysis. This analysis shows that HD patients have decreased white matter health and identifies several tracts that are important for cognitive performance in HD patients.
4360 Black Bone MRI from the Lab to Clinical Practice: Eliminating Radiation Exposure in Reconstructive Surgery Patients
Authors: Suchyta Marissa , Hunt Christopher , Gibreel Waleed , Sabbagh Diya , Gorny Kryzysztof , Mardini Samir
Published: July 2020

OBJECTIVES/GOALS: Virtual surgical planning and 3D printing enable streamlined surgeries and increased complexity. These technologies, however, require CT scans and radiation exposure. This project’s goal is to optimize and demonstrate the accuracy of Black Bone MRI for surgical planning in reconstructive surgery. METHODS/STUDY POPULATION: Four common craniofacial surgeries were planned and performed on cadaver specimens (maxillary advancement, orbital floor reconstruction with patient-specific implants, cranial vault reconstruction, and fibular free flap reconstruction of the mandible). For each surgical procedure, ten cadaver heads were used. Five of each surgery were planned and 3D printed guides were created utilizing Black Bone MRI versus five with CT scans. Following mock surgeries, all specimens underwent a post-operative CT scan. 3d reconstruction was performed and surgical accuracy compared to the plan was assessed using GeoMagic Wrap, assessing average post-operative deviation from plan. RESULTS/ANTICIPATED RESULTS: In all surgeries, guides created from Black Bone MRI demonstrated high accuracy to surgical plan. Average osteotomy (cut) deviation from plan was not statistically significantly different when Black Bone MRI was used compared to CT scans for planning and guide creation in the wide variety of craniofacial surgeries performed. The average deviation of post-operative anatomy from pre-operative plan was also not statistically significant when Black Bone MRI versus CT scans were utilized in the surgeries. These results then enabled the translational application of this technology clinically, and we demonstrate a clinical reconstructive craniofacial case planned utilizing Black Bone MRI. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that virtual surgical planning and 3d surgical guide creation can be performed using Black Bone MRI with comparable accuracy to CT scans in a wide variety of craniofacial procedures. This could dramatically reduce radiation exposure for patients. The successful segmentation, virtual planning, and 3d printing of accurate guides from Black Bone MRI demonstrate potential to change the pre-operative planning standard of care. This project, overall, also demonstrates the development of new solutions to advance clinical care, thus serving as an example of moving translational science from a concept to the operating room.
4061 Clinical utility of precision medicine approaches to guide anti-platelet selection for adult patients with acute coronary syndromes (ACS), following percutaneous coronary intervention (PCI)
Authors: Mosley Scott , Yeung Samantha , Shavelle David , Clavijo Leonardo , Ng Tien
Published: July 2020

OBJECTIVES/GOALS: Our goal is to determine if a precision medicine approach to guide anti-platelet therapy for patients with ACS, post PCI, is feasible for a diverse urban population. Also, we will evaluate if guided therapy reduces major adverse cardiovascular events (MACE) while remaining economically sustainable. METHODS/STUDY POPULATION: This prospective, pragmatic study will enroll two-hundred patients with ACS undergoing PCI, receiving DAPT. Patients will receive point-of-care CYP2C19 genotyping. Patients with at least one loss-of-function (LoF) allele will be recommended prasugrel. Those without LoF alleles, will be recommended to take prasugrel for 7 days then clopidogrel for 7 days, followed with platelet reactivity phenotyping. Patients with HPR >208 P2Y12 reaction units will take prasugrel; the remainder will take clopidogrel. We will review electronic health records and contact patients at baseline, then at 1, 3, 6, and 12 months to collect data for cardiovascular and health-related quality of life (HRQoL) outcomes. RESULTS/ANTICIPATED RESULTS: Feasibility and clinical utility will be measured by the proportion of patients with a genotype or phenotype leading to a clinical recommendation of alternative therapy and whether or not recommendations were accepted by clinicians. Effectiveness will be measured by combined MACE (composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), stent thrombosis, and major and minor bleeding over the study period. Cost of testing, 30-day hospital readmission, and HRQoL questionnaires will be included for pharmacoeconomic analysis from an institutional perspective. DISCUSSION/SIGNIFICANCE OF IMPACT: There are no studies investigating the clinical utility of implementing guided anti-platelet selection, combining CYP2C19 genotyping and HPR phenotyping. We anticipate incorporating this precision medicine approach to guide P2Y12 inhibitor selection will be feasible while improving patient outcomes.
4167 Peri-transplant Lung Microbiome Reveal Oral Bacteria, Pepsin And Inflammatory Markers Co-associate With Primary Graft Dysfunction, Implicating Aspiration As A Potential Contributor
Authors: McGinniss John Evan , Diamond Joshua M. , Brown Melanie C. , Cantu Ed , Christie Jason D. , Bushman Rick D. , Collman Ronald G.
Published: July 2020

OBJECTIVES/GOALS: Primary graft dysfunction (PGD) is acute lung injury in the first three days after lung transplant. Patients that experience PGD have increased mortality and an increased risk of chronic lung allograft dysfunction. The pathogenesis is thought to be an ischemia-reperfusion injury but is incompletely understood and there are no specific therapies. We investigated the role of the microbiome in PGD and associations with inflammation and markers of aspiration. METHODS/STUDY POPULATION: We collected airway lavage samples from lung transplant donors before procurement and recipients after reperfusion. We extracted DNA, amplified the bacterial 16S rRNA gene, and sequenced on the Illumina MiSeq platform. QIIME2 and Deblur were used for bioinformatic analysis. R packages were used for downstream analysis and visualizations. The host response was quantified using the Milipore 41-plex Luminex and an ELISA for pepsin. Clinical data was collected by the Penn Lung Transplant Outcomes Group. PGD was assessed by degree of hypoxemia and chest X-ray findings in the 72 hours after transplant. RESULTS/ANTICIPATED RESULTS: There was no significant difference in alpha diversity (Shannon index, p = 0.51), biomass (via comparison of 16S amplicon PicoGreen, p = 0.6), or beta diversity (Weighted UniFrac, p = 0.472, PERMANOVA) between subjects with PGD grade 3 (n = 36) and those that did not (n = 96). On taxonomic analysis, we found an enrichment of Prevotella in donor and recipient lungs that went on to develop PGD (p = 0.05). To follow up this finding we measured immune response and pepsin concentrations in recipient lungs. We found elevated levels in 35/41 cytokines measured in subjects that developed PGD as well as an elevation in pepsin and a correlation between pepsin concentration and Prevotella relative abundance (Figure 1). Additionally, Prevotella relative abundance had statistically significant positive correlations with multiple cytokines such as IL-6 (Pearson’s = 0.26, p = 0.009) and eotaxin (Pearson’s = 0.24, p = 0.016). DISCUSSION/SIGNIFICANCE OF IMPACT: There is an enrichment of oral anerobes in lung allografts that eventually develop PGD. This is associated with elevated levels of pepsin and markers of inflammation. These lines of evidence suggest aspiration contributes to priming the allograft for PGD.
4203 Re-engineering the Approach to Extremely Preterm Breech Deliveries with Student Led Team Science
Authors: Dangel Alissa , House Michael , Kolandaivelu Kumaran , Huggins Gordon , Hanumara Nevan , Slocum Alexander
Published: July 2020

OBJECTIVES/GOALS: Vaginal delivery is typically avoided in extremely preterm breech fetuses due to the concern for head entrapment by the cervix. Development of a device to prevent head entrapment would be best addressed by a multidisciplinary approach incorporating engineering principles with clinical obstetrics. METHODS/STUDY POPULATION: Construction of a collaborative multidisciplinary team to address the clinical challenge of preventing head entrapment was initiated through a unique course at the Massachusetts Institute of Technology (Course 2.75, Medical Device Design). The course would provide a structured means by which students (senior undergraduate and graduate students in Mechanical Engineering) would be paired with a clinical advisor and faculty in their department. Weekly team meetings were scheduled to review the clinical context pertinent to the problem and review engineering principles needed to develop a solution. The course also provided a small monetary budget ($4K) for the students to purchase supplies. RESULTS/ANTICIPATED RESULTS: During the semester long course, several iterations of a prototype were designed. Each subsequent rendition was evaluated from both an engineering and manufacturing perspective, as well as clinical appropriateness. The weekly meetings allowed for rapid re-design and assured that all necessary parameters were considered by the entire team. Students also had access to lab facilities and additional mentorship that allowed for supplementary input beyond that generated by core team members. These interactions, along with those of their classmates working on other projects, provided a strong base for exploring subsequent device development. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful medical device development requires a collaborative process and students can be ideal members of these teams as they reside in an environment that is conducive to exploration and novel idea generation. Course-based student led team science platforms can provide an excellent foundation for solving uniquely challenging medical problems.
4256 Association Between Injury Intent and Emergency Department and Hospital Charges for Pediatric Firearm Injuries in the United States
Authors: Bongiorno Diana Marie , Badolato Gia M. , Boyle Meleah D. , Vernick Jon S. , Levy Joseph F. , Goyal Monika K.
Published: July 2020

OBJECTIVES/GOALS: In 2016, more than 3,100 children died, and an estimated 17,000 children had non-fatal injuries, from firearms in the United States. In this study, we used hospital charges as a proxy for medical resource utilization, and compared differences in charges by intent of firearm injury among children. METHODS/STUDY POPULATION: In this cross-sectional study of the 2016 Nationwide Emergency Department Sample, we identified firearm injury cases among children aged 19 years or younger using ICD-10-CM external cause of morbidity codes. Injury intent was characterized as unintentional, assault, self-inflicted, undetermined, or due to legal intervention. We included patients treated and released from the emergency department (ED) or admitted alive to the hospital, and excluded those who were transferred or died in the ED. We used linear regressions with survey weighting to compare differences in mean healthcare charges by firearm injury intent, with and without adjustment for ED disposition. RESULTS/ANTICIPATED RESULTS: Among 12,469 cases in the weighted sample, mean age was 16.5 years, a majority were male (88.2%) and Medicaid-insured (57.8%), and 64% were discharged from the ED and 36% admitted. Injuries were 49.0% unintentional, 45.1% assault-related, and 1.8% self-inflicted. Compared to children with self-inflicted injuries (charges $115,224), children with assault-related injuries (charges $55,052; p<0.007) and unintentional injuries (charges $38,643; p<0.001) had lower mean charges per visit. Differences in charges were no longer significant after adjusting for ED disposition, as 85.8% of self-inflicted injuries were admitted, compared to 46.5% of assault-related and 24.3% of unintentional injuries. DISCUSSION/SIGNIFICANCE OF IMPACT: Although the majority of pediatric firearm-related injuries resulting in emergency department care are unintentional or assault-related, self-inflicted injuries result in greater per visit hospital charges, attributable to higher hospitalization rates, and likely due to more severe injuries.
4224 Development of a Patient Registry and Biospecimen Repository to Identify Biomarkers in Nontuberculous Mycobacteria Lung Disease
Authors: Garcia Bryan , Grady Abigail , Christon Lilian , Flume Patrick , Dorman Susan
Published: July 2020

OBJECTIVES/GOALS: Non-tuberculous mycobacteria (NTM) is an emerging infection in the United States. Therapeutic development is impaired in NTM due to lack of biomarkers associated with disease activity and treatment response. To address this, we established a cross-sectional patient registry and biorepository from NTM patients. METHODS/STUDY POPULATION: Beginning August 2019 patients were recruited in a cross-sectional format from the bronchiectasis and NTM clinics at our institution. All patients provided at least one sputum sample in the six months prior to inclusion. Clinical and epidemiologically relevant data was obtained, patient reported outcome measures including the SGRQ were provided, and blood specimens were processed and preserved. Patients were grouped based on clinical phenotype and descriptive statistics were reported as means and standard deviations. Serum inflammatory profiles will be analyzed using standard Luminex assays. RESULTS/ANTICIPATED RESULTS: 72 patients with prior NTM isolation from sputum have been recruited including 28 patients that do not meet ATS guidelines for NTM treatment (colonized), 29 patients are currently receiving treatment, and 15 patients that have a history of completing therapy. Among all NTM patients, the mean age was 59.5 ±17.6 years and 80.8% were female. The mean FEV1 percent predicted among these patients was 68.0 ±21.5% and mean BMI was 22.35 ±4.1. The most common mycobacterial species isolated was Mycobacterium Avium Complex (47%). The mean SGRQ total score was 40.2 ±20.3 among all NTM patients. We plan to perform standard Luminex assays to identify inflammatory profiles associated with disease phenotype. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed a cross sectional cohort of NTM patients including a registry of clinically relevant data for phenotyping and an accompanying biospecimen repository. Our long-term goal is to identify biomarkers indicative of disease activity and treatment response using these components.
4381 Examination of FDA Pediatric Regulations: Inclusion of Pediatric Populations in Clinical Trials, 2016 - 2018
Authors: Ly Annie , Uniyal Apurva , Church Terry
Published: July 2020

OBJECTIVES/GOALS: To assess whether FDA regulations aimed at the pediatric population following the Best Pharmaceuticals for Children Act (BPCA) of 2002 are effective, this study examines the inclusion of the pediatric population in recent clinical trials for drugs used by both adult and pediatric groups. METHODS/STUDY POPULATION: From the U.S. Food and Drug Administration (FDA) a list of drugs approved between 2016 and 2018 was compiled. A search of clinicaltrials.gov provided corresponding clinical trials for the approved drugs. Study information such as eligibility criteria and demographics was gathered from each trial. From studies that included both adult and pediatric populations, the percentage of pediatric and adult subjects was calculated, resulting in values expressing exclusively pediatric subjects or the pediatric subjects as part of a category that included both populations (i.e. 18 years old). RESULTS/ANTICIPATED RESULTS: Between 2016 and 2018, 26 drugs were approved under the BPCA. From an assessment of 220 total studies, a lack of standardization is evident in terms of which ages constitute a particular pediatric sub-population even though guidelines for these sub-populations already exist under the BPCA. This lack of standardization resulted in the separate examination of each drug for pediatric inclusion. For the majority of the trials evaluated, 1% of the pediatric population was represented in trials that were open to both adult and pediatric populations. DISCUSSION/SIGNIFICANCE OF IMPACT: There is a need for more effective regulations and incentives for the pharmaceutical industry to standardize data presentation and better incorporate the pediatric population in clinical trials, especially for drugs targeted for this group.
4231 Identifying Educational Needs of Researchers and Health System and Health Agency Leaders in the Science of Implementation and Improvement: Report from California CTSAs
Authors: Inkelas Moira , Mittman Brian , Handley Margaret , Bender Miriam , Pollock Brad , Nguyen Oanh , Aarons Greg , Cousineau Michael , Sak Rachael
Published: July 2020

OBJECTIVES/GOALS: We conducted interviews with investigators, clinicians, and health system and health agency leaders to assess regional educational needs in implementation and improvement science, including content (knowledge and skill), format, experiential learning, and mentoring, to identify barriers and guide planning. METHODS/STUDY POPULATION: Five CTSAs in the University of California Biomedical Research Acceleration, Integration, & Development consortium (UC BRAID) plus a fifth affiliated CTSA developed a common protocol and interviewed 31 California-based learners (current fellows, early and mid-career investigators, clinicians, and health agency personnel) and system leaders from health care and health agencies. Interviews focused on impact goals, educational needs in dissemination, implementation, and improvement (DII) science, challenges in DII research, preferred learning formats, desired proficiencies and skills, and barriers such as cost, time, awareness, terminology, and suitability and availability of training. A rapid review of literature identified potential domains of knowledge and skills for a proposed curriculum. RESULTS/ANTICIPATED RESULTS: Areas of emphasis varied among interviewees; identified learning needs differed between traditional research perspectives (emphasizing areas such as partner engagement, grant writing, frameworks, study design) and applied perspectives (emphasizing areas such as managing change, complex systems, learning system capacity). Learners had a range of preferences; most interviewees desired formats that are longitudinal, experiential, applied, cooperative, and affordable. Variation in knowledge of, and interpretations of, DII terms and goals limited the ability of some interviewees to specify educational needs. A synthesis reveals areas for potential future co-development and networked approaches to regional training and capacity enhancement. DISCUSSION/SIGNIFICANCE OF IMPACT: In response to a rapidly changing health landscape, our academic health systems are developing capabilities to improve care for their populations. Our work informs the training and education needs that are critical to translation at a system-wide level. Regional convenings can raise awareness while translational programs fill educational gaps.
4411 Identifying Environmental Barriers to Participation for Community-Dwelling Adults with Stroke: A Descriptive Pilot Study
Authors: Neff Anna J , Lau Stephen , Wong Alex Wing-Kai , Baum Carolyn
Published: July 2020

OBJECTIVES/GOALS: The purpose of this study is to identify and quantitatively describe environmental barriers to community engagement and activity participation for adults with stroke and low income. Repeated electronic surveys collected in real time will reduce recall bias and improve characterization of barriers. METHODS/STUDY POPULATION: 20-30 community-dwelling adults with stroke and low income will be recruited for this pilot study. Inclusion criteria: > 1 month post stroke and evidence that they have the vision, literacy, and cognitive capacities to answer survey questions on a smart device. Exclusion criteria: severe aphasia, severe mental illness or substance abuse within 3 months, and ataxia. Participants will complete standardized assessments of daily activities, engagement in and perceptions about community activities, social support, and perceived environmental barriers. Participants then complete four surveys per day for 14 days using an app on an iPod Touch, reporting activities attempted and barriers encountered. RESULTS/ANTICIPATED RESULTS: This is the first study of this kind and is a work in progress. We anticipate that the environmental barriers reported will include physical (e.g. built structures, climate, and natural terrain), social (e.g. support or lack thereof; stigma), political (e.g. access to transportation; healthcare services), and technological barriers (e.g. difficulties with personal equipment and/or technologies such as elevators, ticket kiosks, etc.). DISCUSSION/SIGNIFICANCE OF IMPACT: An increased understanding of the barriers facing community-dwelling adults with stroke and low income will facilitate the development of culturally-appropriate and more accessible self-management programs to help this population re-engage in their communities and return to pre-stroke activities.