OBJECTIVES/GOALS: The goal of this study is to decipher the mechanisms by which breast cancers evade the immune system to facilitate metastasis through the lymphatic vasculature. We believe this is caused, in part, by semaphorin 7A (SEMA7A) as its expression is associated with increased lymphatic vessels, tumor-associated macrophages, and metastasis in breast cancer. METHODS/STUDY POPULATION: We have observed that breast cancer cells, lymphatics, and macrophages exhibit SEMA7A-dependent expression of PD-L1 in vitro, which may make SEMA7A+ tumors more sensitive to anti-PD-1/PD-L1 immunotherapies. Therefore, we utilized multiple orthotopic, immunocompetent mouse models to determine if SEMA7A expression makes tumors more susceptible to immune checkpoint blockade. E0771 and 66cl4 mouse mammary carcinoma cells were injected orthotopically into the #4 mammary fat pads. Once tumors reached 50-100 mm^3 mice were injected intraperitoneally with 250ug of anti-PD-1, anti-PD-L1, or IgG control every third day. Tumors were measured with calipers every other day and harvested for flow cytometry to determine the effect of immune checkpoint blockade on the TME in SEMA7A+ tumors. RESULTS/ANTICIPATED RESULTS: We reveal that growth of SEMA7A overexpressing (OE) tumors, but not controls, was significantly slowed with both anti-PD-1 and anti-PD-L1 treatments. Flow cytometric analysis of cells from the TME revealed increased LECs, TAMs, and PoEMs in SEMA7A+ tumors, compared to controls – all populations had higher PD-L1 expression, which was decreased with both anti-PD-1 or anti-PD-L1. We also observed a decrease in PD-L1 expression on the tumor cells with treatment. Furthermore, LEC, TAM, and PoEM presence was decreased within the TME alongside increased presence of activated CD4 and CD8 T cells. Collectively, our results suggest that SEMA7A expression in breast cancers activates a major pathway associated with immune evasion and helps to establish a pro-tumor microenvironment. DISCUSSION/SIGNIFICANCE: SEMA7A expression establishes a pro-tumor microenvironment, which can be targeted with readily available FDA approved drugs such as immune checkpoint-based therapies. Since SEMA7A+ breast cancers have high rates of metastasis, more specific treatments for these patient populations should be explored.

OBJECTIVES/GOALS: Undergraduates experience food insecurity at rates 21% higher than the general population. Because professional students have been omitted from these studies, the goal of this project is to determine the prevalence of food insecurity among medical students at one academic institution. METHODS/STUDY POPULATION: A cross-sectional research design was used to quantify the food insecurity status of medical students at the University of Utah. The USDA’s validated 6-item Food Security Survey Module was distributed via email to all currently matriculated medical students. Student’s responses were anonymous but questions about gender and age were included. Respondents (N = 200) were scored per the module as food secure, food insecure, or very low food security. RESULTS/ANTICIPATED RESULTS: Statistical analysis included frequencies and chi-square tests. Medical students (N = 166) showed 50.6% of respondents experienced food insecurity in the past 12 months, 16.3% experienced very low food security.While there were no significant relationships between food security status and gender or age, general trends did show divorced and separated students had higher food insecurity risk 82%. A similar study in 2014 surveyed undergraduates at the same location; 51% of respondents (N = 221) experienced food insecurity. While medical students experience food insecurity at rates much higher than the national average, prevalence is lower than undergraduates at the same institution. DISCUSSION/SIGNIFICANCE OF IMPACT: Burnout and suicide in medical training are at an all-time high; professional and academic pursuits are limited when physiological needs of food security are not being met. Study results suggest, 50% of respondents are food insecure. This should inform the development of supportive programs.

OBJECTIVES/GOALS: In 2018, the United Network for Organ Sharing began prioritizing patients on temporary MCS over those on durable MCS for OHT in an effort to prioritize sicker patients and decrease waitlist mortality. We explored the impact of this change by examining if the type of MCS prior to transplant affects the risk of post-transplant infection. METHODS/STUDY POPULATION: We will conduct a retrospective cohort study of approximately 350 patients that have undergone OHT at Tufts Medical Center between January 2014 and July 2021 who survived at least 72 hours post-transplant and have minimum post-transplant follow-up of one year or time to death if before one year. Chart review will determine the type of MCS in place prior to transplant and the occurrence of infections within one year of transplant. Data will also be collected on patient’s age, sex, medical comorbidities, lab values, and open chest management practices. We will examine differences in the incidence rates of a composite outcome (blood stream infection, invasive fungal infection, skin and soft tissue infection of device sites, and mediastinitis) between patients that were on temporary versus durable MCS. RESULTS/ANTICIPATED RESULTS: We anticipate that this study will show a greater frequency of infections of all types in patients that received temporary as compared with durable mechanical circulatory support prior to transplantation. We will use Cox proportional hazards survival models to model multivariable relationships for predictors of infection. DISCUSSION/SIGNIFICANCE: This study will provide insights into the magnitude and type of infectious complications that patients experience after OHT and the impact that type of MCS and other factors have on their outcomes. The data obtained may have implications for choice of mechanical device prior to undergoing OHT surgery as well as antimicrobial prophylaxis.

OBJECTIVES/SPECIFIC AIMS: Reducing radiologic exams has been a focus of cost reduction in healthcare systems. The utility and justification of obtaining cross-sectional imaging (PPCSI) before surgical intervention continues to be evaluated. For peripheral artery disease (PAD) consensus guidelines regarding PPCSI do not exist and may be influenced by patient complexity, variation of disease presentation, and physician preference. The objective of this study was to determine the utility of PPCSI before percutaneous PAD intervention. METHODS/STUDY POPULATION: Patients receiving first-time endovascular revascularization procedure for PAD from 2013 to 2015 were evaluated for PPCSI done within 180 days prior to revascularization. Patient and physician demographics, perioperative characteristics, and disease distribution/severity were evaluated. The primary outcome was technical success defined as improving inflow and/or revascularization of the target outflow vessels to <50% stenosis. RESULTS/ANTICIPATED RESULTS: Of the 348 patients who underwent an attempted revascularization procedure 159 (45.7%) patients underwent PPCSI, including 151 CTA and 8 MRA. Of these, 48% were ordered by the referring provider (84% at an outside institution), and 52% were ordered by the treating physician. PPCSI was performed a median of 26 days (IQR 9-53) prior to procedure. Individual vascular surgeon practice identified PPCSI rates ranging from 31% to 70%. On multivariate analysis chronic kidney disease (OR=0.35; CI 0.17–0.73) had the strongest effect against of PPCSI, and Inpatient/ED evaluation (OR=3.20; CI 1.58–6.50), aorto-iliac (OR=2.78; CI 1.46–5.29) and femoral-popliteal occlusions (OR=2.51; CI 1.38–4.55) most strongly predicted PPCSI. After excluding 31 diagnostic procedures, technical success did not differ between endovascular procedures with PPSCI (91.3%) or without PPCSI (85.6%), p=0.11. When analyzing 89 femoral-popliteal occlusions, technical success was higher with PPCSI (88%) compared to procedures without PPSCI (69%), p=0.026. DISCUSSION/SIGNIFICANCE OF IMPACT: PPCSI use is influenced by inpatient status, chronic kidney disease, and anatomic consideration. PPCSI was not associated with overall technical success although it appeared beneficial for femoral-popliteal occlusions. Routine practices of ordering of PPCSI may not be warranted when considering technical success but may be important in treatment planning. Further studies are warranted to determine if radiation, cost, and contrast load justify PPCSI.

OBJECTIVES/GOALS: This project’s objective is to empower verbally-communicating autistic adults to express their mental health needs to mental health professionals, regardless of their training or experience in autism. By enhancing empowerment in this area, we aim to enhance their self-awareness and confidence in navigating and accessing mental health support. METHODS/STUDY POPULATION: Following the Toronto Translational Framework (TTF), our approach involves co-designing and testing an intervention directly with the autistic population through three phases. Phase I will review published literature on autism, mental health, and patient empowerment, validate our identified need through informal meetings with stakeholders, and assemble an autistic advisory committee (AAC) of 5-8 members who are able to provide informed conset without assistant, are fluent in English, and 18 years of age or older. Phase II will involve participatory design sessions with our AAC to develop a low-fidelity prototype to address the identified need. Phase III will evaluate our prototype’s effectiveness through a separate series of focus groups, which will consist of members from our target population. RESULTS/ANTICIPATED RESULTS: We are anticipating that by the end of our research, we have successfully co-designed an intervention that effectievly empowers autistic adults in their mental health journey through increasing their self-awareness and confidence in navigating and receiving mental health support. At a larger scale, results may include the empowerment of autistic adults to seek and receive mental health care from mental health professionals, regardless of professionals’ prior autism expertise. DISCUSSION/SIGNIFICANCE: By enhancing self-awareness of their mental healthcare needs and boosting self-reported confidence in communicating with mental health professionals, we aim to take the first step in creating timely, patient-centered solutions, and bridging gaps in the evolving neuro-affirmative healthcare system.

OBJECTIVES/SPECIFIC AIMS: Our study aims to create a novel state level HIV-ESRD dataset and compare patient-level characteristics on rates of transplant referral, evaluation, waitlisting, and transplantation for HIV-positive versus HIV-negative patients. Our main hypothesis is that HIV-positive patients in Georgia are less likely to be referred to kidney transplant compared with HIV-negative patients. METHODS/STUDY POPULATION: Three datasets will be merged in order to create the HIV-ESRD dataset. The datasets are United States Renal Data System (USRDS), a southeast Transplant Referral Dataset and patient-level Georgia Department of Public Health HIV Incidence Database. The resulting study population will include patients that are older than 18, but less than 70, are HIV-positive and are on dialysis in Georgia. This dataset will also identify those patients who have been referred to transplantation, have been waitlisted, and have received kidney transplants between January 2012 and December 2017. If within a 1-year period, the prevalence of HIV-positive patients referred to transplant was lower than the 1-year period prevalence of HIV-negative patients for 3 consecutive years, the dialysis facility will be classified as having a within-facility disparity. We will then characterize patient level and dialysis facility-level factors that may contribute to observed findings. Patient characteristics will include demographic, clinical data, proxies of socioeconomic status, and geospatial relationships to transplant centers and rural vs urban neighborhoods. Facility-level characteristics includes profit status (profit vs. nonprofit), total number of staff (including full-time and part-time employees), aggregate demographic and clinical facility characteristics, and total number of treated patients. RESULTS/ANTICIPATED RESULTS:. We anticipate the successful creation of the proposed dataset that will allow for accurate identification of HIV-positive patients on dialysis in Georgia.. This dataset will provide the ability to determine referral, waitlisting, and transplantation rates.. We predict the overall rate of referral, waitlisting, and kidney transplantation in HIV patients will be relatively low, and that dialysis facilities with a higher proportion of HIV-positive will have lower referral rates compared to dialysis facilities treating a higher proportion of HIV-negative patients. It is foreseen that among patient-level characteristics, the strongest predictor for decreased referral rates will be HIV serostatus and among dialysis facility factors, profit status will be associated with decreased referral rates. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study offers the creation of the first regional dataset of HIV-ESRD patients that will include patient-level characteristic of HIV-positive patients and provide a model for other states to adopt. We will contribute improved state-level description of incidence data of HIV-positive patients on dialysis, current rates of transplant referral, waitlisting, and transplantation, and offer potential associated factors that influence these processes. This knowledge will be used to determine the next steps in improving access to care; conducting qualitative research to understand dialysis facility views on transplant in HIV patients, understanding HIV patient’s position on transplantation, providing education on the value of kidney transplant referral, and expanding the approach of combining patient level HIV data to the southeast.

OBJECTIVES/GOALS: Asthma is a life-long, chronic lung disease that inflames and narrows the airways. Its effects on quality of life in children can be exacerbated. The goal of this study was to investigate the link between asthma, family structure and demographics and how it impacts quality of life in children. METHODS/STUDY POPULATION: We analyzed data from a cross sectional study of the 2016-2017 National Survey of Children’s Health, NSCH, to assess the relationship between determinants of health variables and the outcome variable of parent’s report of child’s perceived health status (quality of life). The study population was children under the age of 18. Data were analyzed using descriptive, bivariate analysis using Chi square, and multiple logistic regression of quality of life and family structure adjusting for confounding variables. RESULTS/ANTICIPATED RESULTS: The study included 5,687 children. Significant predictors of asthmatic children’s quality of life were severity of asthma, self-perceived mental/physical health status of adults, neighborhood safety for children (p <0.05). The interaction between family structure and asthma severity was significant indicating that asthma severity was an effect modifier. Among children with mild asthma, predictors of quality of life were self-perceived mental/physical health status of adults in the household, neighborhood safety of children, physical activity status of children (p<0.05). Among children with severe asthma, predictors were family structure and physical/mental health of adults (p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: This study suggests children with severe asthma who are born to single mothers with lower parental reporting of physical/mental health status had a lower quality of life. A longitudinal study could be implemented to target these three measures to improve quality of life among these children. Also, a culturally adapted intervention involving community, parents, and providers is needed to improve the quality of life of the children with asthma.

OBJECTIVES/GOALS: Glioblastoma (GBM) patients face a poor prognosis. Glioma stem cells (GSCs), a chemo resistant GBM subpopulation, possess enhanced DNA repair and elevated levels of epigenetic modifier KDM1A. This study aims to establish the significance of KDM1A in DNA repair and determine the potential of novel KDM1A inhibitor NCD38 to enhance TMZ efficacy in GSCs. METHODS/STUDY POPULATION: Patient derived GSCs were obtained via IRB-approved protocol from patient samples at UT Health San Antonio. KDM1A knockdown and knockout cells were generated by transduction of validated KDM1A-specific shRNA or gRNA, respectively. Brain bioavailability of KDM1A inhibitor NCD38 was established using LS-MS/MS. Effect of combination of KDM1A knockdown, knockout, or inhibition with TMZ was studied using cell viability, neurosphere, and self-renewal assays. Mechanistic studies were conducted using CUT&Tag-seq, RNA-seq, immunofluorescence, comet, Western blotting, RT-qPCR, homologous recombination (HR) or non-homologous end-joining (NHEJ) DNA repair reporter assays. In vivo efficacy of KDM1A knockdown or inhibitor alongside TMZ treatment was determined using orthotopic murine GBM models. RESULTS/ANTICIPATED RESULTS: KDM1A knockdown, knockout, or inhibition increased efficacy of TMZ in reducing cell viability and self-renewal of GSCs. Pharmacokinetic studies demonstrated KDM1A inhibitor NCD38 is readily brain penetrable. CUT&Tag-seq studies revealed KDM1A is enriched at DNA repair gene promoters. RNA-seq studies suggest KDM1A inhibition reduces DNA double strand break repair gene expression, with these findings validated using RT-qPCR and Western blotting. Knockdown, knockout, or inhibition of KDM1A attenuated HR and NHEJ-mediated DNA repair capacity. Immunofluorescence and comet assay support findings of increased DNA damage in NCD38/TMZ combination treated GSCs. Importantly, KDM1A knockdown or inhibition enhanced efficacy of TMZ and significantly improved survival of orthotopic GBM tumor-bearing mice. DISCUSSION/SIGNIFICANCE: Our results show compelling evidence that KDM1A is essential for DNA repair in GSCs and that KDM1A inhibition sensitizes GBM to TMZ via attenuation of DNA repair pathways. These findings suggest combination of KDM1A inhibitor NCD38 with TMZ could serve as a promising novel therapeutic strategy that can be translated to improve GBM patient outcomes.

ABSTRACT IMPACT: Extrapolating from mouse data we explored eosinophil content in human adipose tissue and its effect on adipocyte biology potentially leading to the discovery of novel therapeutic targets for treatment of obesity and insulin resistance. OBJECTIVES/GOALS: The interaction between immune cells and adipose tissue (AT) in obesity has not been fully elicited. Mouse models of diet-induced-obesity show AT resident eosinophils (EOS) help preserve insulin sensitivity (IS). As data in human obesity are lacking, here we explored AT-EOS content and their role in AT metabolism in subjects with and without obesity. METHODS/STUDY POPULATION: We recruited lean (L) subjects and patients with obesity (Ob) to undergo abdominal subcutaneous AT biopsy and evaluation of insulin resistance (IR) by determination of HOMA-IR. Circulating EOS were isolated from all participants under fasting conditions and exposed to high glucose (HG) or high lipids (HL) for 4 hrs. AT EOS number was assessed via FACS analysis. Circulating EOS and AT mRNA was assessed by qPCR for multiple genes involved in inflammation and cell migration. To evaluate the effect of EOS on primary human adipocytes, in vitro cultures were exposed for 4 days to either interleukin-4 (IL-4), interleukin-13 (IL-13) or to human EOS. Adipocytes mRNA levels were evaluated for genes involved in adipogenesis and lipid metabolism. RESULTS/ANTICIPATED RESULTS: 16 lean, IS subjects (BMI 22.5+ 0.4kg/m2) and 22 age-matched IR patients with obesity (BMI: 38.9 + 1.0kg/m2) participated. We observed a ratio of 2:1 in AT EOS content of L vs Ob subjects (P<0.03). To assess the reduced AT-EOS content in obesity, we evaluated expression of Chemokine-C receptor 3 (CCR3) in circulating EOS. We show decreased CCR3 mRNA levels in Ob vs L subjects (P=0.006). We expect HL in vitro experiments on peripheral EOS of L subjects to affect CCR3 mRNA levels. In AT of Ob subjects, we found a significant decreased expression of Eotaxin 2, the main EOS chemokine binding CCR3 expressed on EOS. Preliminary data from in vitro primary adipocytes culture suggest for IL-4 and IL-13 to increase mRNA level of Peroxisome Proliferator Activated Receptor Gamma (PPARG), the master regulator of adipogenesis. DISCUSSION/SIGNIFICANCE OF FINDINGS: Comparable to animal studies, we found a decrease of AT-EOS content in patients with obesity. Alterations in CCR3/Eotaxin 2 signaling may be involved. IL-4 &IL-13 are secreted predominantly by EOS and appear to directly regulate gene expression in human adipocytes. These data represent the first evidence for a novel role of EOS in human AT biology.

ABSTRACT IMPACT: Use of this novel murine model of inflammatory bowel disease (IBD) and C. difficile infection (CDI) will aid in developing new clinical approaches to predict, diagnose, and treat CDI in the IBD population. OBJECTIVES/GOALS: IBD is associated with intestinal inflammation and alterations of the gut microbiota, both of which can diminish colonization resistance to C. difficile. Here, we sought to determine if IBD is sufficient to render mice susceptible to C. difficile colonization and infection in the absence of other perturbations, such as antibiotic treatment. METHODS/STUDY POPULATION: C57BL/6 IL-10-/- mice were colonized with Helicobacter hepaticus to trigger colonic inflammation akin to human IBD. Control mice, not colonized with H. hepaticus, were pretreated with the antibiotic cefoperazone to render the gut microbiota susceptible to CDI. Mice were then gavaged with spores of the toxigenic C. difficile strain VPI 10463 and monitored for C. difficile colonization and disease. The fecal microbiota at the time of C. difficile exposure was profiled by 16S rRNA gene sequencing and analyzed using mothur. Statistical analyses were performed using R. RESULTS/ANTICIPATED RESULTS: Mice with IBD harbored significantly distinct intestinal microbial communities compared to non-IBD controls at the time of C. difficile spore exposure (14 days post-IBD trigger). Mice with IBD were susceptible to persistent C. difficile colonization, while genetically identical non-IBD controls were resistant to C. difficile colonization. Concomitant IBD and CDI was associated with significantly worse clinical and intestinal disease than unaccompanied IBD. DISCUSSION/SIGNIFICANCE OF FINDINGS: Patients with IBD who develop concurrent CDI experience increased morbidity and mortality. These studies in a novel mouse model of IBD and CDI emphasize the dual importance of host responses and alterations of the gut microbiota in susceptibility to C. difficile colonization and infection in the setting of IBD.

OBJECTIVES/GOALS: Insulin dosing is crucial for regulating blood glucose in cardiac surgery patients, yet it requires the use of cumbersome insulin dosing charts. To streamline this process, an electronic insulin calculator (IC) is trialed in the cardiac operating rooms and intensive care unit. This study compares glycemic control prior to and after institution of IC. METHODS/STUDY POPULATION: Using the EHR, a retrospective population of 3,164 cardiac surgery patient charts from 12/19/19 - 11/06/20 were obtained. Baseline, intra-operative, and ICU blood glucose values were obtained from each patients admission. Using this data, a baseline level of glycemic control throughout a cardiac surgery patients stay was established. A preliminary cohort of 244 patients were then chosen to be managed with the new IC. Baseline, intra-operative, and ICU blood glucose values were obtained in this group for comparison. Paired t tests were used to compare the IC group of patients to the retrospective group of patients. Additional subgroup analysis was performed to assess IC efficacy for on pump vs off pump cardiac surgeries. RESULTS/ANTICIPATED RESULTS: The 244 patients managed with the IC showed significantly reduced average blood glucose values during their time in the ICU compared to those previously not managed with the IC (185 mg% vs 153 mg%, p= 0.02). Additionally, a trend towards a reduction in last operating room blood glucose level was also noted. Lastly, average blood glucose levels were significantly reduced for patients undergoing on pump cardiac surgeries compared to off pump surgeries (157 mg% vs 149 mg%, p = 0.03). DISCUSSION/SIGNIFICANCE: Preliminary results suggest IIC to be associated with better intra and postoperative blood glucose control. More data is being collected to test its association with outcomes.

OBJECTIVES/SPECIFIC AIMS: To evaluate the determinants of non-adherence to guideline treatment and surveillance and unique barriers to care in LIU Latinos with NMIBC that will inform the development of novel patient educational materials and navigation programs that could improve adherence and thus, oncologic outcomes. METHODS/STUDY POPULATION: We will recruit 40 Latino patients with new or existing NMIBC diagnoses who present to the Urology clinic at a large, tertiary public hospital in Los Angeles from November 2018 to March 2019. Quantitative (surveys) and qualitative (semi-structured interviews) data will be collected, analyzed and integrated in order to comprehensively determine patient-level barriers to adherence. RESULTS/ANTICIPATED RESULTS: We expect to identify a unique set of patient-level barriers to adherence to NMIBC care that is unique to this population that center around 1) structural barriers to care, 2) knowledge, attitudes, and beliefs that pertain to education, acculturation, gender and values, and 3) general and disease-specific health literacy. DISCUSSION/SIGNIFICANCE OF IMPACT: The barriers to surveillance and treatment NMIBC care are significant, particularly in LIU and minority patients, which is important as non-adherence to guideline care is linked to poorer cancer outcomes. The data generated herein will inform the development of tools and programs to aid in reducing or eliminating these barriers, but also will inform discussions on the effectiveness of current clinical practices for low-income Latino patients.

OBJECTIVES/GOALS: Our objective is to investigate the antibacterial and regenerative properties of a novel AHA dental coating for the prevention and treatment of deep caries (cavities). Further, we aim to investigate and compare these properties through in vivo murine models and assessment on human saliva samples and human pulpal cells collected from clinical samples. METHODS/STUDY POPULATION: In vitro antibacterial studies were performed by collecting and culturing human salivary bacteria with AHA substrates and quantifying survival of cariogenic Sm (S. mutans). In vivo, C57BL/6 mice were treated with AHA composite fillings, infected with Sm clinical isolates, and fed a high sucrose diet with cavity formation assessment after 6 weeks. To evaluate regeneration, mice were similarly given composite with AHA or MTA (standard of care) upon pulpal exposure with regeneration quantified by microCT and histological analysis of dentin bridge formation, ALP production, and odontoblast migration. In vitro, AHA substrates were cultured with MC3T3-E1 pre-osteoblast cells and dental pulp stem cells obtained from clinical samples over 21 days, with mineralization and ALP assessed indicating osteogenesis. RESULTS/ANTICIPATED RESULTS: In vivo studies have shown the reduction of cavity formation in mice treated with AHA as well as dentin regeneration upon pulpal exposure using microCT and histological image analysis. Coinciding with these findings, AHA substrates eradicated cariogenic Sm in human saliva samples and single species cultures in vitro. Further, preliminary results in vitro have shown increased mineralization of MC3T3-E1 cells when cultured with AHA substrates in comparison to uncoated substrates. We anticipate similar increased mineralization as well as increased ALP production of human pulpal stem cells from clinical samples when cultured with AHA substrates, suggesting osteogenesis. Further, we anticipate increased odontoblast migration and ALP production upon additional analysis of in vivo tissue samples. DISCUSSION/SIGNIFICANCE: This work will elucidate the antibacterial and regenerative properties of AHA dental coatings. These results further support the translation of AHA coatings into the clinic as a novel therapeutic for the prevention and treatment of dental decay, which may overcome the limitations associated with the current treatments.

OBJECTIVES/GOALS: Using a human-centered approach, IDEO, a nationally-renown human-centered design team, and Research Jam, Indiana CTSI’s patient engagement core, integrated and tailored complimentary programs to address the challenges of engaging mothers with opioid misuse around the time of birth. METHODS/STUDY POPULATION: Gathered data through focus groups, site visits, and one-on-one interviews with key stakeholders: mothers in opioid use recovery, peer recovery coaches, and other people living with or directly affected by opioid use disorder (OUD). RESULTS/ANTICIPATED RESULTS: Themes emerged around stigma (e.g., constant judgment, majority of interactions focused on addiction, addiction comes from bad choices), the healthcare system (e.g., healthcare system bias and stigma, misalignment of services and timing of need, no support for support network), and relating to recovery (very variable but generally ambiguous and uncertain process and outcomes, importance of peer recovery coaches, importance of community resources). Identified themes were used to create insights that informed the underlying concepts of an engagement strategy including support and resources for recovery coaches, and education materials for mothers with OUD. One of human-centered design’s strengths is iteration, and the materials created for this have yet to be tested and refined thoroughly to be meaningful and lasting interventions. DISCUSSION/SIGNIFICANCE OF IMPACT: Considerable insights into the lived experience of those experiencing OUD and those who support these individuals yielded tangible ways to test improved engagement and recruitment of women with OUD at the time of birth.

OBJECTIVES/GOALS: To describe the strategies our newly created Patient Partners Program has planned for engaging diverse patients in the co-creation of our planned Patient Partner Academy. We will elicit feedback from other CTSAs about their strategies for promoting individual patient partnerships in research. METHODS/STUDY POPULATION: Our program to promote authentic patient-researcher partnerships to advance clinical and translational research is grounded in participatory approaches to maximize meaningful engagement. The process of creating our Patient Partners Academy is co-led by a patient partner and national leader in re-envisioning the role of patients in research, and a University of Michigan faculty member who advocates for patient partnerships in research. Listening sessions and community engagement studios will involve the developers of patient partner training programs, patient partners who have received research capacity training (as well as researchers and patient partners interested in collaborative research. Insights from these sessions will inform the development of learning models and curriculum content. RESULTS/ANTICIPATED RESULTS: Through individual listening sessions and community engagement studios we will collect data on the barriers and facilitators to patient partner engagement in research and the experiences and preferred learning models in patient partner training programs. Both the listening sessions and community engagement studios will be recorded, transcribed, and analyzed for common themes. We aim to answer three questions: What do patient partners need to be meaningfully engaged as equal partners across the research continuum? How can we best engage people who experience serious illness or chronic conditions and may be underserved by healthcare systems? What do researchers, faculty, and clinicians need to create trusting, collaborative relationships with patient partners? DISCUSSION/SIGNIFICANCE: Integrating patient partners into study teams accelerates innovation and translational science, increases the relevance of research findings, improves health outcomes and patient empowerment, and elevates the value of the patient perspective allowing researchers to gain a new point of view from an individual with lived experience.

OBJECTIVES/SPECIFIC AIMS: This study aims to describe factors impacting older adult OTC selection and use so they can be targeted with a community pharmacy intervention to improve older adult medication safety. The primary outcome is the characterization of the relationship between health literacy, risk perception, and OTC misuse. These results will directly inform the refinement of the community pharmacy intervention such that it is tailored more precisely to the older adult patient population. METHODS/STUDY POPULATION: This cross-sectional study administers face-to-face surveys to 72 older adults (age 65+) at three locations of a mass-merchandise chain pharmacy. This study is one component of a larger study to develop and implement a community pharmacy intervention to improve OTC safety for older adults. The Protection Motivation Theory (PMT) provides a framework for evaluating the interplay of threat and coping appraisals in the assessment of perceived risk severity and OTC misuse. Health literacy, known to contribute to coping appraisals, is measured with the Newest Vital Sign survey. The TRI-RISK model, originally used to measure risk perception of disease, was adapted and subject to rigorous cognitive interviewing and testing with 8 older adults. This adapted survey is used to measure older adult risk perception of adverse drug events. Walking interviews with older adult participants are conducted in a community pharmacy. In these interviews, participants verbalize their process of selection and use of an OTC to treat a pain, cough/cold, or sleep issue. Additional patient factors such as age, race, gender, education level, and co-morbidities are collected in a survey. Structural equation modeling is used for data analysis. RESULTS/ANTICIPATED RESULTS: It is hypothesized that poor health literacy leads to lower risk perception, which will result in increased instances of potential adverse drug events. Data collection will be complete by Spring 2019 and preliminary results will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Few interventions have attempted to decrease misuse of high-risk OTC medications in older adults, and not one has addressed system barriers. Compared to efforts to improve prescription medication safety, efforts to decrease OTC medication misuse in community-dwelling older adults have been practically ignored. This is the first study to characterize and operationalize health literacy and risk perception of adverse drug events in the development of a system-level intervention to address OTC safety for older adults. The population aged 65 and older is expected to increase by 38.5 million from the year 2020 to 2050. Interventions tailored to target the older adult patient population are expected to have greater efficacy in improving older adult medication safety and in alleviating the significant corresponding strain on the US healthcare system.

Increasingly, basic, translational, and clinical research has become more collaborative, resulting in multi-institutional studies that involve common approaches to a central question. For multi-institutional projects that involve recombinant or synthetic nucleic acids, Institutional Biosafety Committee (IBC) review is generally required at each separate site. Duplicative review may result in both administrative costs and delays, without evidence of increased safety or protections, and investigator frustration. To address these inefficiencies, IBC leaders drafted a collaborative IBC Reliance Authorization Agreement. The Agreement allows one or more institutions to cede IBC review to a reviewing IBC that accepts the responsibility. The ability to cede IBC review, and the ability to rely on one decision on behalf of all collaborating institutions for a given protocol, removes delays in approval of multi-center protocols, and collaborating principal investigators are able to focus on research rather than administrative tasks. In the process, we found promotion of this collaborative model led to stronger connections among institutions and among IBC members. The requirement for IBC member representation from the local community, however, limits its broader dissemination; we make several recommendations to mitigate this challenge.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.