ABSTRACT IMPACT: This project demonstrates that addressing low-value care, which has the potential to cause patient harm, relies on novel data tools and collaboration between health system and research stakeholders. OBJECTIVES/GOALS: Reducing low-value care, or patient care that offers no net benefit in specific clinical scenarios, is an important approach to improving value as it can simultaneously lower health care spending and improve quality. We describe an initiative to identify such care in a large statewide employer. METHODS/STUDY POPULATION: Claims data for self-funded University of California (UC) Preferred Provider Organization (PPO) plan members during 2019 were abstracted from the University of California Health (UCH) Clinical Data Warehouse, a unique central database that includes electronic medical record data from >5 million patients across UC medical campuses and all claims from UC self-funded health plans. UCH spans six academic health systems across California. The Milliman MedInsight Health Waste Calculator, a proprietary algorithm-based software tool, was used to identify low-value care and estimate associated spending. The HWC measures 48 low-value services using recommendations from the Choosing Wisely Campaign, the US Preventive Services Task Force, and other clinical specialty guidelines. RESULTS/ANTICIPATED RESULTS: Of 43,882 members of the UC PPO, 11,174 (25.4%) received at least one low-value service. The HWC identified 50,103 eligible services and classified 35% as low-value. Total spending on low-value services ranged between $2,209,516 and $5,089,866, based on a more or less conservative estimate. Across the five sites, the proportion of low-value services ranged from 31% to 39%. Five services comprised 65% of costs from low-value care: annual EKGs, preoperative baseline labs for low-risk surgeries, vitamin D deficiency screening, imaging for eye disease, and headache imaging. The top five services by order frequency were annual EKGs, vitamin D tests, preoperative labs, antibiotics for upper respiratory infections, and imaging for eye disease. DISCUSSION/SIGNIFICANCE OF FINDINGS: Low-value care is prevalent and costly within a large statewide employer. Collaborative multidisciplinary partnerships between employers, health systems, informatics, and researchers can leverage existing data to identify opportunities for improving the value of care for covered populations.

Objectives/Goals: Adolescence is a critical period where brain networks are thought to be influenced by environmental factors. This presentation examines violence exposure’s impact on brain connectivity and identifies potential protective factors. Methods/Study Population: A secondary data analysis was conducted using data from a subsample of the Adolescent Brain Cognitive Development Study (release 5.1). Youth who completed victimization questionnaires at two time points were eligible for inclusion, resulting in 2016 participants. Linear regression was utilized to analyze associations between violence exposure measured by the juvenile victimization questionnaire and functional connectivity of specified regions of interests using the Gordon functional parcellation for cortical regions and the Freesurfer parcellation for subcortical regions. Moderation analysis will be utilized to assess the effects of peer and caregiver support on the associations between violence exposure and functional connectivity, currently ongoing. Results/Anticipated Results: Between 18 and 59% of the sample reported experiencing at least one form of violence exposure, with racial differences noted in missing versus complete data. Multiple domains of violence and cumulative exposure were associated with both increased and decreased functional connectivity across within-network, between-network, and network-subcortical regions. At baseline, internet violence was linked to lower within-network connectivity, while peer victimization was associated with higher connectivity at both baseline and follow-up. Between network analysis showed lower connectivity with witnessing violence at baseline and higher connectivity with internet victimization at follow-up. Discussion/Significance of Impact: These findings emphasize the need for further exploration of the underlying mechanisms that link violence exposure to developmental trajectories and identification of protective factors such as caregiver and peer support, to inform interventions and promote resilience in affected youth.

OBJECTIVES/GOALS: Artificial intelligence (AI) depends on quality machine learning (ML) algorithms constructed with high-quality training data. This TL1 trainee project develops a disease-agnostic computable phenotype framework for ML algorithm construction, modeling male puberty as a case example. METHODS/STUDY POPULATION: A computable phenotype of male puberty was constructed to answer the question: “Does early pubertal timing increase the risk of developing type II diabetes (T2D) in males?” A computable phenotype of males < 18 years old was created in the TriNetX© Diamond Network utilizing Boolean operator data queries. TriNetX© contains patient electronic health record information (ICD-10 diagnoses, anthropometric measures). An exploratory analysis of patient counts reflecting various computable phenotypes allowed for outcome (T2D) comparison of males diagnosed with precocious puberty (E30.1, ICD code for early pubertal timing) to those without, controlling for body mass index (BMI). RESULTS/ANTICIPATED RESULTS: Subjects (n=12,996,132) displayed the following computable phenotype: Male, < 18 years old, without ever having a BMI documented >85th percentile. Males diagnosed with precocious puberty (E30.1) were 6.89 times more likely to develop T2D when aged 14-18 years old than those without (OR 6.89, 95% CI: 5.17-9.19, p<0.0001). Next steps involve training a ML model on each computable phenotype groupings’ health data, with anticipated results identifying underlying salient pathophysiologic variables. A generalized computable phenotype approach is further developed to: 1) explore clinical questions in large databases like TriNetX©, and 2) model disease development with AI/ML algorithm construction. DISCUSSION/SIGNIFICANCE: Computed phenotypes reveal males with precocious puberty may have increased T2D risk. Next steps utilize subject data to train an AI/ML algorithm, model development to identify salient pathophysiologic variables, and synthesize a generalized AI/ML developmental research framework for dissemination.

OBJECTIVES/GOALS: Research on the safety of perinatal kratom use - an herb that acts on opioid receptors - is scarce. Our transdisciplinary clinical and translational science (CTS) team is conducting parallel qualitative analyses of subreddit posts related to kratom use during (1) pregnancy and (2) breastfeeding. METHODS/STUDY POPULATION: Pregnancy- and breastfeeding-related keywords are being used to extract posts and selected metadata from the following subreddit communities: r/kratom, r/quittingkratom, r/pregnant, and/or r/breastfeeding. After the removal of duplicate posts, posts written in a non-English language and those that state in the post text and/or title that they were published by minors ( RESULTS/ANTICIPATED RESULTS: Among the eligible posts, the number of unique usernames of the sources publishing the posts; the range of publication dates; and the mean, median, & range of the number of comments per post will be presented. Inter-rater concordance in thematic coding will be computed. A word cloud will be created with the most used nouns from the eligible posts. Verbatim quotes will be shown to illustrate themes depicted in the sample. The quantitative and qualitative analyses will be conducted separately for the posts related to kratom use during pregnancy and breastfeeding. DISCUSSION/SIGNIFICANCE: These findings could assist clinicians in identifying questions that obstetric patients may have regarding the perinatal use of this emerging substance of concern. Further research is needed to validate these findings using other social media data, such as Twitter.

OBJECTIVES/GOALS: Fetal glucose dynamics mediate many of the adverse outcomes seen in infants of diabetic mothers (IDM). The goals of this study are to identify: (1) rates of blood glucose change in normoglycemic and hypoglycemic IDM; (2) their relation to in-utero insulin exposure; and (3) their transcriptional impacts on placental and umbilical vasculature. METHODS/STUDY POPULATION: Using a longitudinal prospective study design, placental/umbilical cord tissue and maternal hemoglobin A1c (HbA1c) are being collected from mothers diagnosed with Type 1, Type 2, or gestational diabetes mellitus. Blood glucose levels are also collected from their infants at birth, and every 3-4 hours for up to 9 hours to determine the rate of change. Linear regression modeling will be used to determine associations between placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic sub-type. Gene expression from endothelial specimens will be compared between diabetic sub-types and between normoglycemic and hypoglycemic infants via paired t-tests using Benjamini-Hochberg procedure for false discovery rate correction. RESULTS/ANTICIPATED RESULTS: We hypothesize the following; (1) glucose levels will have a steeper rate of change in hypoglycemic infants; (2) maternal HbA1c and in-utero insulin levels will correlate with the level of transcriptional change identified in placental and umbilical endothelial samples; (3) a negative association will exist between cord insulin levels and the rate of change in infant glucose levels; and (4) a positive association will exist between cord insulin level and transcriptional change on the placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Identifying gene expression changes in diabetic placental/umbilical endothelium, and the role of insulin/glucose in these changes, is key to managing diabetic vasculopathy and its adverse outcomes. Understanding infant insulin response may also guide management of hypoglycemia and decrease the risk for neonatal intensive care unit admission.

OBJECTIVES/SPECIFIC AIMS: 1. To evaluate the effects of masculinizing chest reconstruction on the quality of life of female-to-male transgender individuals. 2. To develop and validate a quality of life survey for female-to-male transgender individuals undergoing masculinizing chest reconstruction gender-affirming surgery. METHODS/STUDY POPULATION:. We developed and refined the GENDER-Q using focus groups and exploratory interviews with FTM individuals that were recorded, transcribed, and coded. All consenting FTM patients undergoing chest reconstruction at UCSF Parnassus Medical center between 2017-2019 who meet World Professional Association for Transgender Health (WPATH) criteria for gender dysphoria will be enrolled in the study. The GENDER-Q will be co-administered with the WHO Quality of Life-BREF survey pre-operatively, 6 weeks post-operatively, and one year post-operatively through REDCAP, an online survey database. RESULTS/ANTICIPATED RESULTS: Approximately 70 patients will be enrolled in the study. Preliminary results detect statistically significant mean quality of life post-operative improvements in all three sections (Physical Health, Gender Presentation, Psychological Health) of the GENDER-Q at 6-week follow up that is maintained at one-year (p< 0.005). Statistically significant improvements were similarly achieved and maintained with the WHO QOL-BREF survey (p< 0.05). The mean reported improvement from baseline to follow-up appears to be more pronounced in the GENDER-Q survey compared to WHO QOL-BREF. The median time to complete the pre and post-operative surveys was 10 minutes. Calculation of Cronbach’s (0.67-0.81) and the Pearson Correlation Coefficient for each section revealed excellent internal validity. DISCUSSION/SIGNIFICANCE OF IMPACT: There are few studies assessing quality of life outcomes in transgender patients undergoing gender-affirming surgeries. A standardized and validated assessment tool will provide the means for which data can be pooled in large multi-center studies. Providing further evidence to support the positive health outcomes of gender-affirming surgeries can lead to broader access and reduce healthcare disparities among transgender populations.

OBJECTIVES/GOALS: Agitation has high prevalence in the emergency department (ED), but limited evidence exists regarding clinical decisions to use sedatives and physical restraint. We examined clinical factors and agitation attributes impacting thresholds for sedative and restraint use in the emergency setting. METHODS/STUDY POPULATION: We conducted a prospective cohort study of adult patients (318 yo) with acute or escalating agitation during their ED visit at an urban tertiary care referral center. Consecutive patients requiring security presence or scoring >1 on an agitation scale were enrolled during randomized 8-h blocks. We recorded patient characteristics, staff/team factors, and environmental/systems data as well as scores on 3 validated agitation scales: Agitated Behavior Scale, Overt Aggression Scale, and Severity Scale. We performed descriptive analyses, bivariable analyses, and logistic regression modeling of factors with relation to sedative/restraint use. We observed 95 agitation events on unique patients over 2 months. RESULTS/ANTICIPATED RESULTS: Median age was 42, and 62.1% were male. Most frequent chief complaints were alcohol/drug use (37.9%) and psychiatric (23.2%). Majority of events (73.7%) were associated with sedative/restraint use. Factors related to treatment course or staff interactions were the primary reasons for agitation in 56.8% of events. A logistic regression model found no association between demographics and odds of sedative/restraint use. Overt Aggression Scale scores were associated with significantly higher odds of sedative use (AOR 1.62 [1.13–2.32]), while Severity Scale scores had significantly higher odds of restraint use (AOR 1.39 [1.12–1.73]) but significantly lower odds of sedative use (AOR 0.79 [0.64–0.98]). DISCUSSION/SIGNIFICANCE OF IMPACT: External factors may be important targets for behavioral techniques in ED agitation management. Further study of the Severity Scale may allow for earlier detection of agitation and identify causal links between agitation severity and use of sedatives and restraints.

ABSTRACT IMPACT: Limited research has been conducted on the survival of men with castration-resistance prostate cancer (CRPC) with a pre-existing history of cardiovascular disease, receiving oral androgen signaling inhibitors. This study highlights all-cause and prostate cancer-specific mortality for elderly patients with CRPC with pre-existing history of cardiovascular disease. OBJECTIVES/GOALS: Inadequate knowledge is known about the survival of men with castration-resistance prostate cancer (CRPC) with pre-existing history of cardiovascular disease (CVD), receiving oral androgen signaling inhibitors (OASI). We compared all-cause and prostate cancer-specific mortality for elderly patients with CRPC with pre-existing history of CVD. METHODS/STUDY POPULATION: An active comparator, new user design, was used to identify 2,608 men older than age 65 years with CRPC using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2011 to 2015. Patients were grouped into two analytical cohorts by CVD history. Within each analytical cohort patients were divided into two arms based on their new-user status (OASI vs. chemotherapy). All demographics and clinical characteristics were adjusted by inverse probability treatment weights (IPTWs). Unadjusted and IPTW-adjusted time-dependent Cox models, and Fine and Gray’s models were conducted to evaluate associations between OASI and all-cause and prostate cancer-specific mortality. RESULTS/ANTICIPATED RESULTS: Nearly 64.5% of patients had pre-existing CVD. We observed a lower all-cause mortality in the pre-existing CVD cohort compared to the no pre-existing CVD cohort (IPTW-adjusted hazard ratio [AHR], 0.59; 95% Confidence Interval [CI], 0.54 to 0.64; IPTW-AHR, 0.68; 95% CI, 0.59 to 0.78, respectively). Similarly, the prostate cancer specific-mortality was showed to be lower in the pre-existing CVD cohort compared to the no pre-existing CVD cohort when comparing OASI versus chemotherapy by the IPTW-adjusted time-dependent Fine and Gray’s models (IPTW-AHR, 0.60; 95% CI, 0.55 to 0.66; IPTW-AHR, 0.68; 95% CI, 0.59 to 0.80, respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: OASI showed a significant protective effect against all-cause and prostate cancer-specific mortality compared with chemotherapy; however, were less protective among patients without pre-existing CVD. Further studies are needed to investigate OASI in patients with and without pre-existing CVD.

Objectives/Goals: To probe microbe and bacterial extracellular vesicle (bEV) mobility through biological barriers, we use novel multiple-particle tracking technology. The goal is to evaluate changes caused by extracellular vesicles relevant to placental function and neonatal development. Methods/Study Population: We conducted multiple particle tracking to assess whole bacterial and bEV mobility in cervicovaginal mucus. To accomplish this, cervicovaginal mucus was self-collected from 10 women. Mucus samples were characterized via wet mount, Nugent score, and pH measurements. In parallel, we cultured commercially available vaginal bacteria strains in anaerobic conditions. We isolated bEVs via ultracentrifugation, and subsequently characterized them via nanoparticle tracking analysis to measure size, ζ-potential, and concentration. We investigated reproductive tract tissues response to bEVs. We dosed vaginal, endometrial, myometrial, and placental cells lines with bEVs over a 24 h period and determined uptake, viability, and cytokine production. One-way analysis of variance was used for statistical analysis. Results/Anticipated Results: Based on our previous work, size and ζ-potential greatly affect particle mobility in mucus. G. vaginalis and M. mulieris were smaller than L. crispatus and L. iners. G. vaginalis had a more net-neutral ζ-potential compared to other bEVs. During multiple-particle tracking analysis, whole bacteria were unable to diffuse through vaginal mucus, while bEVs showed increased mobility. Through fluorescence levels, we determined M. mulieris bEVs reach >90% uptake at 24 h. Uptake was verified via microscopy. Across all strains, bEVs were not detrimental to placental viability. When investigating cytokine production in placental cells, an increase in IL-6 was seen after treatment with L. iners bEVs, while TNFα was increased after treatment with G. vaginalis bEVs. Discussion/Significance of Impact: Vaginal microbiome dysbiosis increases adverse obstetric indications. We demonstrate that bacteria are unable to ascend to reproductive tissues. We propose that bEVs travel through vaginal mucus, facilitating microbe–host communication. This impacts obstetric disease pathology and is relevant for diagnostic criteria during pregnancy.

OBJECTIVES/GOALS: Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is the standard of care treatment for non-metastatic prostate cancer (NMPC). Despite the efficacy, treatment-related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. METHODS/STUDY POPULATION: Sixty-four participants with NMPC were enrolled. Fatigue was assessed using the Functional Assessment of Cancer Therapy–Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMCs) extracted from participants’ whole blood. An ADT/RT-induced fatigue mouse model was developed with fatigue measured as a reduction in voluntary wheel-running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the ADT/RT mouse brains using Western blot analysis of Glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). RESULTS/ANTICIPATED RESULTS: Fatigue in the ADT group was exacerbated during RT compared to the non-ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMCs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non-fatigued subjects, indicative of mitochondrial dysfunction. The ADT/RT mice demonstrated a synergistic effect of ADT and RT in decreasing VWRA. Brain tissues of ADT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (CNS). The synergistic effect of ADT/RT is behaviorally reproducible in a mouse model, and its mechanism may be related to bioenergetics in the CNS.

OBJECTIVES/GOALS: ACTA2 R179 carriers present with early-onset stroke; occlusive lesions of the distal internal carotid artery and branches are filled with cells staining positive for smooth muscle cell (SMC) markers. We will identify pathways leading to increased SMC proliferation and migration and thus occlusion. METHODS/STUDY POPULATION: We generated an Acta2SMC-R179C/+ mouse model, which expresses the Acta2 R179C mutation in SMCs via the SM22a-Cre-Lox system. rt-PCR performed in aortic tissue confirms the presence of the mutation in the mutant mice and absence in mice with only the floxed allele (WT). We will determine phenotypic differences between mutant and WT brains using micro CT, vascular casting, histology, and immunostaining. We will characterize mutant SMC phenotype in culture by assessing expression of contractile genes and stem cell markers, proliferation, and migration. Single cell RNA (scRNA) sequencing of the brain will assess differential gene expression and cell populations between mutant and WT mice. RESULTS/ANTICIPATED RESULTS: Mutant mice have decreased blood pressure compared to WT mice from 8-24 weeks old, consistent with the phenotype seen in ACTA2 R179 patients. We expect to see occluded and straighter cerebrovascular arteries and white matter changes in the Acta2SMC-R179C/+ mice. iPSC-derived SMCs from patients show de-differentiation, continued expression of stem cell markers, and increased proliferation and migration. We expect to see a similar phenotype in Acta2SMC-R179C/+ mouse SMCs in culture. Via scRNA sequencing, we expect to see altered transcriptional profiles in mutant mice brains including upregulated proliferative pathways in SMCs, glial cell activation, and gene expression changes in neurons. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will contribute important information on the pathogenesis of the cerebrovascular disease in ACTA2 R179 patients. These results may aid in identifying treatments to prevent or decrease risk of developing strokes in those with known predisposition to cerebrovascular occlusive disease.

Objectives/Goals: Cardiovascular disease, particularly myocardial infarction (MI), is a leading cause of death in the USA. Previous studies have identified CD8+ T-cells as adverse regulators post-MI. We hypothesized that CD8+ T-cells impair cardiac function by altering scar composition. Methods/Study Population: MI was induced by permanent ligation of the coronary artery in C57BL6/J (WT; 3–7 mo) and CD8atm1mak mice (CD8-/-; 3–7 mo). CD8-/- mice were injected with either vehicle or naïve splenic CD8+ T-cells (2x10^6 cells/injection) via tail vein, 4 hours after ligation. Tissue was collected at Day 7 post-MI for biomechanical testing and further downstream analyses. Granzyme (Gzm)A, B, and K were tested for collagen cleavage using a fluorogenic cleavage assay. Effect on collagen production in TGF-β-activated cardiac fibroblasts was assessed in vitro by stimulating cells with GzmA, B, and K (25 AU) for 24 hours. Results/Anticipated Results: CD8-/- mice had improved ejection fraction and LV dilation at Day 7 post-MI compared to WT and CD8-/- mice resupplemented with splenic CD8+ T-cells (p Discussion/Significance of Impact: Our study demonstrates that CD8+ T-cells regulate cardiac fibrosis partially through Gzm release, resulting in left ventricular biomechanical impairments and increased dilation.

OBJECTIVES/GOALS: Our objective is to develop a patient-friendly application addressing the progression of cognitive impairments in multiple sclerosis (MS) patients. This initiative aims to augment individualized care and precision management of a major MS comorbidity by generating a cognitive health brain map for each patient. METHODS/STUDY POPULATION: Using the UAMS COMS Database, featuring high-resolution multi-contrast MRIs, and a comprehensive clinical, behavioral, and demographic dataset, we are developing a hierarchical learning-based software tool to compute maps correlating brain structure-function and individual cognitive function. Our MRI analysis employs a three-compartment model (NNLS>0.96). Functional scores are defined by individualized accuracy during the modified information processing speed task (e.g., m-SDMT). We utilize a Bayesian classifier with explicit Pearson’s correlation for tissue classification (BF10>100) to compute an index of the likelihood of correlation with cognitive impairment throughout brain tissue. RESULTS/ANTICIPATED RESULTS: This approach allows us to reveal subtle cognitive changes and their potential links to myelin integrity, offering vital insights into disease progression and management. The m-SDMT strongly correlates with the standard SDMT (r=0.79, p<0.001), confirming reliability as a cognitive assessment tool in clinical and research contexts. Analysis of the COMS dataset emphasized insights into the role of fine myelin structure in MS patients' cognitive functionality. Our findings heightened the pivotal significance of myelin integrity in preserving cognitive abilities and identify disruptions in myelin synthesis and homeostasis as primary contributors to cognitive decline. This discovery stresses the critical role that specialized brain pathways, influenced by myelin integrity, play in the pathology of MS. DISCUSSION/SIGNIFICANCE: This development bridges advanced neuroimaging techniques with practical clinical applications, emphasizing the nuanced role of myelin integrity in MS-related cognitive deficits. Our findings advocate for a multidisciplinary approach to MS management, demanding collaborative workforce development and education in translational science.

ABSTRACT IMPACT: With a growing number of Americans enrolled in high-deductible health plans, patients, especially those with chronic conditions, face increasing cost-sharing burden. We aim to develop a novel behavioral intervention to help patients use consumer strategies to better manage their health care spending. OBJECTIVES/GOALS: To assess patient preferences to develop an intervention to encourage the use of cost-conscious strategies to manage out-of-pocket health care spending among high-deductible health plan (HDHP) enrollees with chronic conditions. METHODS/STUDY POPULATION: This mixed-methods study is first conducting semi-structured telephone interviews of up to 20 adults with one or more chronic conditions who are enrolled in an HDHP. Preliminary findings from these interviews are being used to inform the design of a national internet panel survey of at least 300 HDHP enrollees. Collectively, the interviews and survey will assess experiences of HDHP enrollees and their preferences for the content, design, format, and mode of an intervention to help them engage in cost-conscious health care behaviors. These findings will then be used to develop a novel behavioral intervention that will subsequently be pilot tested for acceptability, feasibility, and preliminary efficacy. RESULTS/ANTICIPATED RESULTS: Early interview data identified gaps in knowledge of health care consumer strategies among HDHP enrollees with low confidence in being able to engage in cost-conscious health care behaviors. Several participants indicated interest in an intervention to learn more about how to engage in cost-conscious strategies (e.g., putting aside money for anticipated health care expenses, comparing cost and quality for services at different places, and talking to providers about health care costs). Most early interview participants preferred an easily accessible technological intervention, such as a website or app. Interviews are continuing, and the national survey will be fielded in early 2021. DISCUSSION/SIGNIFICANCE OF FINDINGS: HDHP enrollees with chronic conditions could benefit from an intervention that helps them manage their high cost-sharing. Based on the results of interviews and a national survey, we will develop and pilot test a novel behavioral intervention to promote use of cost-conscious health care behaviors.

OBJECTIVES/GOALS: Rodents are the most widely used experimental animals to study disease mechanisms due to their availability and cost-effectiveness. An international drive to investigate the pathophysiology of COVID-19 is inhibited by the resistance of rats and mice to SARS-CoV-2 infection. Our goal was to establish an appropriate small animal model. METHODS/STUDY POPULATION: To recreate the cytokine storm that is associated with COVID-19, we injected angiotensin converting enzyme 2 knockout (ACE2KO) mice (C57BI/6 strain) with lipopolysaccharide (LPS) intraperitoneally and measured the expression of multiple cytokines as a function of time and LPS dose. We then chose a minimum dose (500ug/kg) and time (3h) when multiple cytokines were elevated to measure lung injury scores using a point-counting technique on tissue sections stained with hematoxylin and eosin. The data are expressed as mean percentage of grid points lying within the peribronchial and superficial area in up to 20 fields. Percentage of peribronchial and superficial intrapulmonary hemorrhage, congestion, neutrophil infiltration and area of alveolar space were all assessed. RESULTS/ANTICIPATED RESULTS: Compared to the wildtype group (WT-G), the LPS-injected ACE2KO mice (LPS-G) exhibited a higher percentage of peribronchial intrapulmonary hemorrhage [(%): LPS-G, 10.56 ± 2.06 vs. WT-G, 5.59 ± 0.53; p DISCUSSION/SIGNIFICANCE: Establishing this novel mouse model of COVID-19 will facilitate studies investigating tissue-specific mechanisms of pathogenesis in this disease. This model can also be used to discover novel therapeutic targets and the design of clinical trials focusing on diagnostics, treatments and outcomes in COVID-19.

Over 80% of CTSA programs have a community advisory board (CAB). Little is known about how research discussed with CABs aligns with community priorities (bidirectionality). This program evaluation assessed researcher presentations from 2014 to 2018 to the CABs linked to our CTSA at all three sites (Minnesota, Arizona, and Florida) for relevance to local community needs identified in 2013 and/or 2016. From content analysis, of 65 presentations total, 41 (63%) addressed ≥1 local health needs (47% Minnesota, 60% Florida, and 80% Arizona). Cross-cutting topics were cancer/cancer prevention (physical activity/obesity/nutrition) and mental health. Results could help to prioritize health outcomes of community-engaged research efforts.

Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of “adaptive” clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint. Emerging topics related to borrowing information from historic or supplemental data sources, sequential multiple assignment randomized trials (SMART), master protocol and seamless designs, and phase I dose-finding studies are also presented. Each design element includes a brief overview with an accompanying case study to illustrate the design method in practice. We close with brief discussions relating to the statistical considerations for these contemporary designs.