Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.

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: Due to increased experience and favorable outcomes, the use of partial nephrectomy (PN) to treat renal cell carcinoma has grown in the past decade, with expansion to larger tumors. Performing PN for larger tumors could potentially increase the number of patients up-staged to pT3a after surgery, who may have instead been treated with radical nephrectomy (RN), if known preoperatively. We aimed to estimate the proportion of patients up-staged to T3a disease after PN stratified by size. We also compared size-stratified survival outcomes of up-staged patients to those with T1a, T1b, or T2 kidney cancer. METHODS/STUDY POPULATION: From 1998 to 2013, patients undergoing PN or RN were identified from Surveillance Epidemiology and End Results registries. The proportion of patients receiving PN found to have pT3a disease was quantified by size. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease with appropriately size-stratified pT3a patients. Also, PN patients with pT3a disease were compared to size-stratified RN patients with pT3a disease. Comparisons by size were performed within pT3a patients receiving PN. RESULTS/ANTICIPATED RESULTS: From a total of 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a increased along with increasing tumor size: 4.2% for T1a, 9.5% for T1b, and 19.5% for T2. Among patients receiving PN, adjusted survival analysis demonstrated worse CSS for up-staged pT3a patients Versus appropriately stratified pT1a (CSS: HR=1.87, p=0.02), pT1b (CSS: HR=1.91, p=0.01), and pT2 (CSS: HR=2.33, p=0.01) patients. However, when assessing OS, only the size-stratified comparison of up-staged pT3a Versus pT1a disease demonstrated worse OS for the up-staged cohort (OS: HR=1.25, p=0.04). Comparing PN and RN for pT3a disease, size-adjusted analysis revealed no statistical difference in CSS or OS. Lastly, among patients undergoing PN with pT3a disease, patients with larger tumors, measuring 4–7 cm (CSS: HR=2.83, p<0.01; OS: HR=1.44, p=0.04) or 7–16 cm (CSS: HR=8.22, p<0.01; OS: HR=2.64, p<0.01), experienced worse survival than those with smaller pT3a tumors, <4 cm. DISCUSSION/SIGNIFICANCE OF IMPACT: A greater proportion of patients appear to experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse cancer specific survival after PN compared to those with similarly sized localized tumors. Furthermore, the up-staged pT3a patients after PN appear to experience similar survival to pT3a patients undergoing RN. However, pT3a patients undergoing PN had worse survival with increasing tumor size, reinforcing the need for improvements in preoperative staging and identifying patients at risk of up-staging.

OBJECTIVES/GOALS: People engaging in high-risk substance use or experiencing food insecurity or housing instability are at increased risk to develop end-stage kidney disease. This study will examine associations between these risk factors, patient indicators of socioeconomic position, and hospitalization rates and quality of life after initiation of hemodialysis. METHODS/STUDY POPULATION: The proposed study will leverage a prospective cohort design. We will enroll a convenience sample of 330 participants from the same large dialysis organization. Participants will complete measures of socioeconomic position (age, gender, race, ethnicity, education, income, occupation and community poverty); substance use; food insecurity; housing instability; and quality of life at baseline. We will follow participants for 6 months and extract hospitalization counts from the dialysis facility medical record. RESULTS/ANTICIPATED RESULTS: We will generate risk scores (low, medium, high) from measures of substance use, food insecurity and housing instability. We will conduct multiple logistic regression to generate odds ratios comparing risk group membership by indicators of socioeconomic position. We anticipate that low or medium-risk groups will differ from high risk groups by indicators of socioeconomic position. We will conduct Poisson regression to generate incidence rate ratios for 6-month hospitalization rates comparing low or medium-risk and high-risk groups. Lastly, we will conduct multiple linear regression to generate beta coefficients for changes in quality of life scores comparing low or medium-risk and high-risk groups. We anticipate that high-risk groups will have higher hospitalization rates and lower quality of life scores. DISCUSSION/SIGNIFICANCE OF IMPACT: As the prevalence of end-stage kidney disease continues to increase, there is a need for tertiary prevention interventions that reduce costly inpatient utilization and improve health-related quality of life. The proposed study will lay groundwork for the development of interventions to improve patient outcomes and reduce Medicare spending.

OBJECTIVES/GOALS: Using a cell culture model, we will determine the effects of phosphate on primary lung cell cultures and use our results to delineate a pathway through which these changes are carried out. Using animal models, we will determine the effects of phosphate on inflammatory and fibrotic lung injury, both in the presence and absence of CKD. METHODS/STUDY POPULATION: For our in vitro experiments, human lung fibroblasts were treated with concentrations of 1 to 5 mM sodium phosphate and FGFR inhibitors. Expression levels of interleukin (IL)-1beta, IL-6, and IL-8 were analyzed by qPCR and secretion of these cytokines was measured by ELISA. Phosphorylation of PLCy and ERK was measured by western blot. Using an in vivo approach, we placed C57Bl/6 mice on a high phosphate (3%) diet to elevate serum phosphate levels in the absence of kidney injury and administered bleomycin via oropharyngeal aspiration to generate an acute inflammatory response. Serum FGF23 levels were measured by ELISA and serum analysis for phosphate and renal function were obtained. Furthermore, expression of FGF23 pathway and inflammatory markers were analyzed in murine lung tissue using qPCR and western blotting. RESULTS/ANTICIPATED RESULTS: Augmented phosphate concentrations led to increased cytokine expression and secretion from human lung fibroblasts as well as a concomitant increase in PLCy and ERK phosphorylation. Inhibition of FGFR1 reversed the effects of phosphate on the inflammatory cytokines and PLCy/ERK phosphorylation. Serum FGF23 levels were significantly upregulated in mice on a high phosphate diet and further increased in mice subjected to a high phosphate diet with exposure to bleomycin. Both serum phosphate and creatinine levels were significantly elevated as well. Additionally, high phosphate and bleomycin increased local FGF23 expression in murine lung tissue, when compared to controls or each stimulus alone. DISCUSSION/SIGNIFICANCE: Phosphate has a significant impact on inflammation and fibrosis in the lung, indicating that the existence of pulmo-renal crosstalk exaggerates pulmonary injury and that there are biological pathways that may be targeted therapeutically to mediate these effects. These results could have a substantial impact on the quality of life for CKD patients.

ABSTRACT IMPACT: The broad goal of this investigation is to inform the development of culturally sensitive HIV prevention strategies to reduce specific challenges pertaining to PrEP uptake and utilization for Latino men. OBJECTIVES/GOALS: HIV is a significant public health concern affecting Latinos in the U.S. Daily use of pre-exposure prophylaxis (PrEP) effectively prevents HIV infection and has the potential to curb HIV epidemics. The objective of this study is to examine how sociocultural variables impact PrEP-related services among HIV-negative Latinxs. METHODS/STUDY POPULATION: The current study is a mixed-method investigation. Participants will include Latinx adult patients seeking services at an HIV community clinic. Approximately 150 participants will be recruited for the study. Participants who are eligible will complete sociocultural, mental health and PrEP-related measures. For the applied aim, community stakeholders will be recruited who serve the Latinx community. Upon completion of data collection, the data analytic plan is as follows: Aim 1, to establish the relationship between each sociocultural variable and PrEP uptake/utilization, preliminary analyses (i.e., correlations and regression analyses considering co-variates) will be conducted. Aim 2, grounded theory techniques will be conducted to establish community-informed practices to increase the use of PrEP. RESULTS/ANTICIPATED RESULTS: Relatively little is known about cultural factors that may impede PrEP uptake among Latinx MSM. Several researchers have identified specific factors such as language, acculturation, familismo, and similar cultural norms as significant barriers to care (Page et al., 2017). It is expected that each of these variables will contribute significant variance to willingness to use PrEP. Specifically, negative relationships are expected between fatalism and machismo and lower stages on the PrEP Contemplation Ladder. Comparably, a negative relationship is expected between the Hispanic acculturation subscale and lower stages on the PrEP Contemplation Ladder. It is however, hypothesized that there will be a positive relationship between familism and the non-Hispanic acculturation sub-scale. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite important advances in health to prevent HIV infection, HIV rates among Latinx MSM continue to rise. This investigation will have the potential to inform the development of culturally sensitive prevention strategies. By collecting qualitative data from key community stakeholders, this project will also directly inform a CBPR prevention.

OBJECTIVES/SPECIFIC AIMS: Perineal urethral sling placement is an option for men with mild to moderate post-prostatectomy stress urinary incontinence (SUI). However, men with persistent incontinence after sling placement often require secondary artificial urinary sphincter (AUS) placement, made difficult by the sling occupying the proximal bulbar urethra. This proximal section has a thicker corpus spongiosum which may mitigate cuff-induced ischemia and subsequent urethral atrophy. The authors report a series of AUS placements after failed sling, using sling revision or removal to access the proximal urethra. METHODS/STUDY POPULATION: Cutting the sling arms during urethral cuff placement increased urethral exposure and mobility. If feasible, completely removing the sling allowed the most proximal cuff site; but if dissection was felt unsafe, the mesh was left in situ and the cuff placed distally. This study is a retrospective cohort design of patients with SUI who underwent AUS placement after failed sling from 2010 to 2016. Variables included baseline patient characteristics, SUI severity, intraoperative variables, and postoperative outcomes. AUS failure, defined as infection, erosion or urethral atrophy, was analyzed at 12 and 96 months using univariate and multivariable logistic regression. RESULTS/ANTICIPATED RESULTS: Over the study period, 29 patients underwent AUS placement after failed sling. At the time of AUS placement, mean urethral circumference was 6.2 cm and 68% of patients had a 4.5 cm cuff placed; no cases required a 3.5 cm cuff. Seventy-three percent of cases were after transobturator sling placement (27% bone-anchored) and 45% of slings were explanted. AUS failure rate at 12 and 96 months was 17.8% and 45%, respectively; atrophy was the most common indication. Prior transobturator sling placement had lower rates of both 12 month (9.1% vs. 57%, p=0.006) and 96 month (36% vs. 71%, p=0.11) failure, though the latter was not statistically significant. Sling explant was not a significant predictor of 12 month (p=0.12) or 96 month failure (p=0.17). DISCUSSION/SIGNIFICANCE OF IMPACT: Sling revision during AUS placement helps expose the wider proximal urethra, allowing larger cuff size placement. This procedure appears safe, with low rates of erosion and short-term failure—albeit with high rates of long-term urethral atrophy possibly due to more significant dissection causing devascularization. However, sling removal was not a significant predictor of failure. The transobturator sling’s smaller profile may result in less trauma to urethra—possibly explaining the improved outcomes.

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.

ABSTRACT IMPACT: This study will be used to culturally tailor interventions to reduce maternal and infant health disparities in a Marshallese community. OBJECTIVES/GOALS: Inadequate prenatal care is associated with adverse birth outcomes including preterm births, low birth weight infants, and neonatal mortality. Marshallese Pacific Islanders are less likely to receive early and consistent prenatal care compared to other racial/ethnic groups and are thus at a higher risk for maternal and infant health disparities. METHODS/STUDY POPULATION: This article used a qualitative comparative analysis method to compare and contrast the perceived barriers to prenatal care for the prospective of Marshallese mothers and Maternal Health Care Providers (MHCPs). RESULTS/ANTICIPATED RESULTS: Marshallese mothers and MHCPs identified the same structural barriers to prenatal care: health insurance, transportation, and language. The socio-cultural barriers to prenatal care were depicted quite differently by Marshallese mothers verses MHCPs. DISCUSSION/SIGNIFICANCE OF FINDINGS: While the description of structural barriers were consistent among Marshallese mothers and MHCPs, the socio-cultural barriers and the value assigned to those barriers was quite different. Understanding the perspectives from both lenses is an important step towards addressing the barriers to prenatal care among Marshallese.

OBJECTIVES/GOALS: The aim of this study is to analyze electronic health record (EHR) data using Mapper PLUS (MP), a new mathematical model, to classify acute myocardial infarction (MI) patients by risk of major adverse events (AE). We tested MP’s ability to define patient subgroups with distinctive risk for death, heart failure or recurrent MI after revascularization. METHODS/STUDY POPULATION: An EHR retrospective analysis of 797 MI patients and 29 variables (i.e., laboratory tests, imaging, vitals, and clinical traits) collected at the time of hospitalization was conducted. All patients received percutaneous coronary intervention and standard pharmacotherapy. MP analysis produced a multi-dimensional nodal graph of the patients based on similarities found within variables. Two algorithms, Walk Likelihood and Walk Likelihood Community Finder were applied to the graph which formed joint clusters according to spatial distance within nodes. The final output was three clusters for risk level evaluation. Risk level (low vs. high) was relative to the average risk of AEs for the entire cohort one year post MI. RESULTS/ANTICIPATED RESULTS: Of three patient subgroups, one (n= 318) had a >1 fold change for the probability of survival without AE when compared to the overall cohort and thus was defined as the low-risk group. The second group (n=304) had DISCUSSION/SIGNIFICANCE: MP stratifies patients into three groups according to predictive variables which relate to the risk for AE following an acute MI treatment. This is a new topological method for patient classification based on minimal input strictly from pre-collected EHR data. More cohort studies are needed to validate MP to classify patients for precision medicine.

OBJECTIVES/GOALS: The goal of this study is to evaluate the role of WNT5A and WNT5a-AS1 in sex-differences of GBM progression. In our preliminary studies, we found that a long non-coding RNA WNT5A-AS1 is overexpressed in male GBM patients. We also found that WNT5A-AS1s expression shows a negative correlation with overall survival within male patients. METHODS/STUDY POPULATION: We will define the mechanism by which WNT5A-AS1 regulates WNT5a-mediated glioma stem cell (GSC) maintenance by assessing the effects of inhibiting WNT5A-AS1 expression on transcriptional activity and stemness in GSCs. We will determine if there are distinct Wnt-signaling patterns in male and female isogenic murine astrocytes by examining the expression of downstream proteins in the Wnt signaling pathway and how inhibition of WNT5A-AS1 alters this expression. We will then examine the impact of WNT5A-AS1 on temozolomide (TMZ) resistance in-vitro and in-vivo. We will assess the cell viability and survival of GBM PDX cells upon treatment with TMZ in vitro. Next, we will assess the capacity of knockdown of WNT5A-AS1 to increase sensitivity to TMZ-induced cell death and prolong survival in vivo in intracranial models. RESULTS/ANTICIPATED RESULTS: We hypothesize that WNT5A-AS1 targets Wnt5a and regulates its expression. We anticipate that knockdown of WNT5A-AS1 will upregulate WNT5A expression. We also expect that inhibiting WNT5A-AS1 will alter GSC stem maintenance and functional effects. We expect to see an increase in downstream Wnt5a signaling proteins in males vs females when treated with exogenous Wnt5a. We hypothesize that knockdown of both, WNT5A-AS1 and WNT5A will alter the expression of downstream proteins. We hypothesize that knockdown of WNT5A-AS1 will decrease tumor growth and therapeutic resistance to TMZ while increasing survival in patient derived xenographs in vivo and in vitro. DISCUSSION/SIGNIFICANCE: This study will provide insight into the mechanisms underlying the difference in GBM onset and progression between male and female patients, which is clinically important. We will also characterize the biological role WNT5A-AS1 which is currently unknown to date and elucidate differential role of GSCs in GBM progression between male and female.

OBJECTIVES/GOALS: At UNC-Chapel Hill’s CTSA hub – the NC Translational and Clinical Sciences Institute (NC TraCS) – we conducted a participatory evaluation of a new community and patient advisory board (CPAB) to assess member experiences, and the outcomes and early impacts of their work on institutional programming related to equity and inclusivity in research. METHODS/STUDY POPULATION: NC TraCS staff conducted informal interviews with CPAB members to discuss how they envision success in their work, ideas for measuring progress towards their goals, and how they have seen similar work measured by others. These conversations guided the development of outcomes, indicators, and data collection methods for the CPAB evaluation plan. CPAB member satisfaction, experiences, and perceptions of accomplishments were assessed via an online survey. Concurrently, an Outcome Harvesting approach was used, through which NC TraCS staff retrospectively identified key outcomes of the CPAB’s work through team discussion of programmatic changes and review of internal documents and data. RESULTS/ANTICIPATED RESULTS: CPAB members (n=10) were highly satisfied with meetings, group dynamics, activities and accomplishments, and 90% of members felt that NC TraCS was very responsive to their feedback. Key outcomes included: 1) co-creating a shared vision, goals, and operational policies for the CPAB; 2) co-developing a training series for research teams about patient and community engagement; 3) disseminating best practices for co-developing advisory boards; 4) providing guidance to improve NC TraCS consultations, services, and resources related to enhancing equitable participation in research (e.g., developing an Equity in Research Framework); and 5) contributing to institutional initiatives related to diversity, equity, and inclusion (e.g., improving compensation processes for research participants and partners). DISCUSSION/SIGNIFICANCE: Evaluations of CPABs often focus on process measures, while assessments of outcomes and impacts are lacking. Our evaluation data highlight the early outcomes and value of a newly formed CPAB. Furthermore, our approach can inform the creation and evaluation of equity-focused advisory boards within other research institutions.

OBJECTIVES/GOALS: Persons with Parkinson’s disease (PwPD) have set-shifting impairments that may limit motor learning of protective responses to prevent falls. This study compares the effect of blocked versus random practice schedules on acquisition and retention of protective stepping stability in PwPD & age-matched controls. METHODS/STUDY POPULATION: Twenty PwPD & 20 age-matched controls will be randomly assigned to random or blocked practice groups to experience slip and trip-like perturbations which induce stepping responses. Blocked practice is repeating a task (e.g., slip) several times before the next task, while random practice is randomly practicing two or more tasks (e.g., slips & trips). Each subject will wear a safety harness to prevent falls, each fitted with a load cell that indicates when a fall would have occurred. We will assess the anterior-posterior and mediolateral margin of stability at 1st protective step, step length, and in-task fall incidence before, 10 minutes, and two days after practice. We will also compare outcomes between participants in the blocked vs. random practice schedule using two ANOVA. RESULTS/ANTICIPATED RESULTS: To date, we have recruited three control subjects. We anticipate that blocked practice will be superior to random practice for protective stepping acquisition and retention PwPD. Existing literature on motor learning of voluntary tasks indicates that PwPD have difficulty acquiring and retaining motor skills via random practice due to the higher cognitive processing required than blocked practice. Furthermore, since the basal ganglia’s set-shifting role is crucial for random practice, it is expected that random practice will limit protective steps acquisition and retention in PwPD. In healthy control, while blocked practice is better for acquisition, random practice will be superior for retention. DISCUSSION/SIGNIFICANCE: The study’s findings will provide knowledge that may foster the development of robust balance rehabilitation protocols to improve postural responses in PwPD and reduce delayed and ineffective stepping responses that results in falls among PwPD.

OBJECTIVES/GOALS: This project aims to ensure that the age ranges of participants in OHSU studies for specific diseases match the demographics of the populations the diseases occur in, as mandated by the new NIH Inclusion of Individuals Across the Lifespan as Participants in Research Involving Human Subjects policy. METHODS/STUDY POPULATION: This study involves retrospective and prospective data. The retrospective phase (“Look Back”), reviewed all investigator-initiated OHSU studies between 2017 and 2018 with prospective consent that were disease related (N = 63). Age range per IRB protocol and per subject enrollment were graphically compared to disease demographics to determine if study age ranges were a “match” or “mismatch” to disease demographics (0 = mismatch, 1 = partial match, 2 = full match). This data will inform the upcoming prospective phase of the study, when the study team will reach out to primary investigators of enrolling studies with education and resources, and track whether this reduces demographic “mismatch.” RESULTS/ANTICIPATED RESULTS: Of the studies, 51 were evaluated in the “Look Back” analysis. 40 studies were full matches for age inclusion matching disease demographics (78%), 40 for disease prevalence range (78%), and 38 for enrolling subjects within the disease demographic range (74%). Studies received the lowest scores in enrolling subjects that match disease prevalence, with 19 earning full points (37%) and 17 earning 0 points (33%). Limitations include difficulty in finding and applying disease demographic and prevalence ranges. In addition, in this data, 12 of the original 63 total studies could not be scored because no subjects had been enrolled or prevalence ranges were not in line with clinical expertise. DISCUSSION/SIGNIFICANCE OF IMPACT: This study highlights that many trials exclude older subjects at the upper age ranges. Future analysis of the prospective phase of the study will allow us to assist research teams in closing these gaps and will determine the Policy’s impact on the recruitment of older adults into research.

OBJECTIVES/GOALS: The primary aim of this study is to explore the relationship between neighborhood deprivation index as measured by the Social Vulnerability Index (primary predictor) and anxiety and depression in primary caregivers of hospitalized children, measured using the Hospital Anxiety and Depression Scale (primary outcome). METHODS/STUDY POPULATION: Design: This descriptive, comparative, non-intervention, cross-sectional substudy is is a secondary analysis of survey data collected from parents of hospitalized children staying at Ronald McDonald Houses. Regression models will examine the relationship between a parent’s social determinants of health and their anxiety and depression in the context of their child’s hospitalization. Setting/Study population: Parents/primary caregivers were recruited from the following sites: RMH of the Greater Philadelphia Region, RMH of San Diego, RMH of Greater Cincinnati, RMH of the Bluegrass (Lexington, KY), and RMH of Alabama. RESULTS/ANTICIPATED RESULTS: In the DAG below I hypothesize the associations between the variables and anxiety and depression based on what has been reported in the literature. The analysis is in progress. [blob:https://acts.slayte.com/50293cb7-4274-49bb-998d-7601dffd23cb] DISCUSSION/SIGNIFICANCE: Parents of hospitalized children experience a high burden of anxiety and depression. Pre-existing indicators of social determinants of health may contribute or compound parental anxiety and depression. A better understanding of this association can lead to improved screening and interventions to better support parents and their children.

OBJECTIVES/GOALS: Assess the association of PK-related single nucleotide variants (SNVs) with the risk of bleeding from DOACs in non-valvular AF patients. METHODS/STUDY POPULATION: A retrospective cohort study was carried out with 2,364 Caucasians with non-valvular AF and treated with rivaroxaban or apixaban. Patients were genotyped as part of the genomic biobank at the University of Michigan Health System. The primary endpoint was a composite of major and clinically relevant non-major (CRNM) bleeding. Cox proportional hazards regression with time-varying analysis assessed the association of 8 SNVs in 5 PK genes (ABCB1, ABCG2, CYP3A4, CYP3A5, CYP2J2) with the risk of bleeding from DOACs in unadjusted and covariate-adjusted models. Six tests were performed as 3 of the SNVs are in the same haplotype. P-values below the Bonferroni-corrected level of 8.33e-3 were considered statistically significant. RESULTS/ANTICIPATED RESULTS: A total of 412 (17.4%) major and CRNM bleeding events occurred over 2.27 ± 2.03 years of follow-up. None of the PK SNVs were significantly associated with bleeding risk on DOACs in both unadjusted and covariate-adjusted Cox regression models. DISCUSSION/SIGNIFICANCE: The effects of these eight genetic variants on exposure to DOACs may not be strong enough to translate into differences in clinical outcomes. Especially if the genetic inheritance underlying the risk of bleeding from DOACs is polygenic, reinforcing the need for further genomic studies on this subject.

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.

ABSTRACT IMPACT: Analyzing the types of technical assistance (basic, targeted or intensive) provided by the Opioid Response Network (ORN) to unique and hard-to-reach populations (UHRP) informs addiction health services and translational research by identifying technical assistance needs in these populations which may require a higher level of intensity. OBJECTIVES/GOALS: To improve ORN dissemination and implementation efforts, the project classifies TA requests into one of three categories: basic, targeted, and intensive. This TA Framework assists the ORN project team in understanding the level of TA required in the delivery of evidence-based practices to address opioids with communities with respect to UHRP. METHODS/STUDY POPULATION: TA requests from April 1, 2019, to April 1, 2020, were selected. The ORN classifies TA requests in one of three categories: basic (dissemination & brief consultation), targeted (services to enhance readiness and capacity), and intensive (full incorporation of innovation considering context, culture, and linguistics) (Fixsen, et. al., 2009; Becker, et al., 2020). Unique and hard-to-reach populations (UHRP) are defined based on physical location (i.e., remote or isolated), social position, or other vulnerabilities (i.e. member of an ethnic or racial minority group) (Thurman, & Harrison, 2020). ORN classifies 26 types of UHRP these types are not mutually exclusive. A frequency analysis of the UHRP types was conducted. Bivariate correlations between UHRP types that had a minimum of 30 cases were performed. RESULTS/ANTICIPATED RESULTS: Among 746 TA requests selected, 226 had missing information about UHRP types and 29 had missing information TA levels. These requests were excluded from the frequency analysis. The three most common UHRP types were people living in rural or remote areas (n=262, 50%), people who are uninsured or underinsured (n=162, 31%), and people who inject drugs (n=158, 30%). Most TA requests were targeted (69%), 23% were intensive, and 9% were basic. Bivariate correlations were performed between 21 UHRP types. Moderate (Pearson’s r=0.4-0.6) or strong correlations (r>0.6) were found for 11 occurrences for the UHRP type of ‘LGBT’, 8 for ‘Mental Illness’, and 7 for ‘Veterans’. Strong correlations were found between ‘Justice Involved’ and ‘Incarcerated’ (r=0.645), and between ‘Disabilities’ and ‘Chronic Pain’ (r=0.603). DISCUSSION/SIGNIFICANCE OF FINDINGS: There were more TA requests at targeted and intensive levels than basic levels suggesting the need for services to enhance readiness and build capacity. The moderate/strong correlations indicate that UHRP types were likely to coexist with other types. Future research can explore combining UHRP types that have moderate/strong correlations.

OBJECTIVES/SPECIFIC AIMS: Clinical trials (CTs) play an important role in developing new treatments, expanding or refining treatments that are already available, and/or identifying behavioral changes that can prolong or improve the lives of subjects. CTs are also conducted to understand normal human physiology, pathophysiology, and factors associated with health outcomes. Results from CTs are then used to determine the safety and efficacy of medications or treatment. CT participants should reflect the diversity of those receiving the treatments because, exclusion of specific populations in CTs may potentially result in knowledge gaps for clinicians and regulators. Historically, women and geriatrics have been underrepresented as CT participants. For women, this is the result of Food and Drug Administration (FDA) action in 1977 which restricted women with childbearing potential from participating in phase I and early phase II CTs after thousands of birth defects resulted from thalidomide usage during pregnancy. While the U.S. Government Accountability Office’s 1992 and 2001 reports documented an increased female inclusion in later stages of CTs, earlier phases of CTs were still lacking. Likewise, older adults and geriatrics have been excluded in CTs arbitrarily or to avoid adverse events associated with drug-drug interactions and comorbidities. Over the past few decades, the FDA has worked to address this issue and increase diversity and transparency in CTs. In 2015, the FDA’s Action Plan for Food and Drug Administration Safety and Innovation Act (FDASIA) Section 907 called for improved CT inclusion and reporting of demographic subgroups (sex, age, race, and ethnicity), highlighting three priority areas: quality, participation, and transparency. This research examines the current state of female inclusion in phase I and II CTs (2016 to 2017) and geriatric inclusion in phase III CTs (2010 to 2017). METHODS/STUDY POPULATION: To assess female representation in phase I and II CTs, data from 2016 CTs was extracted from clinicaltrials.gov. The average percentage of male and female participation in trials recruiting for males and females was determined; CTs conducted in only males or females (due to sex specific disease states) were excluded. The data was further differentiated into investigator-initiated and industry-sponsored trials to determine any differences in sex representation. Data from 2017 CTs on clinicaltrials.gov will be extracted and analyzed as well as 2016 to 2017 data from FDA novel drug approvals. To assess geriatric representation in phase III CTs, geriatric subsections of drug labels from novel drug applications approved between 2010 to 2017 were assessed for geriatric-specific information based on four areas: 1) reporting of CT including geriatrics, 2) reporting of percentage of CT participants ages 75+, 3) providing geriatric dosage recommendations, 4) determining product safety and efficacy for geriatrics. RESULTS/ANTICIPATED RESULTS: It is mandatory that all US CTs are registered on clinicaltrials.gov with the exception of Phase I studies, and results posted within 1 year of CT completion. In 2016, 916 phase I and 713 phase II CTs were registered on clinicaltrials.gov. Of these registered CTs, 4% of phase I and 9% of phase II CTs posted results. Of these, phase I studies included more males than females. Of these, phase I studies showed higher percentage of males (58%) than females (42%). In phase I/II, phase II, and phase II/III CTs, females were represented at a higher levels than males by 8-20% (Table 1). Phase I industry-sponsored and investigator-initiated trials and phase II/III investigator-initiated trials included less females than males (Table 2); all other types of CTs had more female than male subjects (Table 2). Preliminary findings will be expanded to include 2017 CTs and a wider pool of clinical trials will include all those associated with FDA novel drugs approved in 2016 and 2017. Of the 250 labels of novel drugs approved from 2010 to 2017 assessed for geriatric inclusion, 74% reported a CT including geriatrics, and 55% reported including CT participants ages 75+. Further, 31% provided geriatric dosage recommendations and 62% indicated insufficient evidence to determine product safety/efficacy for geriatrics (Figure 1). There was no consistent increase following the 2015 implementation of FDASIA section 907 in any of the four areas examined (Figure 2). Labels providing geriatric dosage recommendations were consistently the least fulfilled area across all years analyzed (Figure 3). DISCUSSION/SIGNIFICANCE OF IMPACT: A lack of inclusion of specific populations in CTs can lead to serious complications. For example, in 2013, the FDA required a lower recommended dose for women for drugs containing the sedative-hypnotic zolpidem (i.e. Ambien) due to persisting next morning drowsiness; the FDA arbitrarily recommended the dosage be halved from 10 mg to 5 mg as it found that women appeared to eliminate zolpidem from their bodies more slowly than men. Additionally, $35.7 million is spent annually on hospitalization from adverse drug reactions in the elderly. And, although government acts and initiatives have called for greater inclusion of certain populations like females and geriatrics in CTs, there is no penalty for exclusion. Problems like these may be avoided if these specific populations are included in CTs so that drugs can be properly studied. It may be preliminary to make conclusions about female representation in phase I clinical trials because it is not mandatory to register all phase I trials on clinicaltrials.gov, but further investigation will be conducted into FDA summary reports. Preliminary findings indicate that efforts to include female subjects may be effective in the subset of studies that reported their results. As of 2017, 51.3% of the U.S. population over 18 years old is female (U.S. Census Bureau). Early clinical trials often help to establish safety and dosing for phase III trials. Thus, it is pertinent that the inclusion rate is reflective of the general population at all clinical trial stages, not just pivotal, phase III trials. It would be prudent to monitor this trend as more studies report their results. Given that the average US life expectancy is now 78 years and that elderly population is expected to double in coming decades (NIH, 2016), there is an urgent need to include this population in current and future clinical research. Geriatrics, particularly those age 75+, use more than a third of total prescription and over-the-counter medications sold in US (Merck Institute, 2014), but is severely underrepresented in CTs. The effects of polypharmacy and changes in drug metabolism with age increase the need for specific drug dosage recommendations for geriatrics. As there was no discernable difference in drug labels fulfilling areas examined before and after 2015, FDASIA implementation may not have impacted geriatric inclusion in CT for drugs approved between 2010 to 2017. As many of these CTs began prior to FDASIA 2012 signing and 2015 implementation, the legislation’s full impact may occur in future years. Nonetheless, inadequate language currently found in geriatric drug labels can create challenges for clinicians when prescribing these medications for geriatric patients, potentially contributing to adverse drug events.