OBJECTIVES/GOALS: Accumulating evidence supports the involvement of immune and inflammatory pathways in Bipolar Disorder (BD) pathophysiology. This pilot study aims to determine if altered peripheral IL-2, TNF-a, IL-4, IL-6, IL-10, IFN-y, IL-17A levels are associated with BD across mood episodes (euthymic, manic, depressive), and worsen neurocognitive function. METHODS/STUDY POPULATION: Twenty-eight participants (17 cases and 11 controls) were recruited. We assessed the clinical features and cytokine plasma levels of participants. Cytokines were measured using Flow Cytometry. All subjects were interviewed by a trained psychiatrist. Each participant was fasting before the blood sample was taken. Neuropsychological tests were used to measure verbal fluency, speed processing, working memory/attention, visuospatial skills, verbal learning, executive functions, and motor skills. Descriptive statistics were used to calculate the demographic characteristics of the sample. An independent-sample Kruskal-Wallis Test and Mann-Whitney Test were carried out using SPSS version 21. RESULTS/ANTICIPATED RESULTS: Serum biomarker concentration showed a decrease in levels of IL-4 (anti-inflammatory) in BD patients vs healthy controls (p < .05). There was a major concentration of IL-6 (pro-inflammatory) on bipolar patients vs controls (p = .003). When we analyze the results with the mood episodes, we found that patients with bipolar depression showed decreased levels of IL-4 (p = .046) and increase levels of IL-6 (p = .020) in comparison to the manic or euthymic episodes. In the neurocognitive tests, we found that the control participants had better performance in the working memory domain (p = .038) and also in the general performance (p = .036) in comparison to bipolar patients. We found also a positive significant correlation between IL-4 and verbal learning in the control sample (.829, p = .003). DISCUSSION/SIGNIFICANCE: The findings evidence a significant immune activation in bipolar patients, in particular during the depressive episode. Participants with BD have a decrease in the protective levels of IL-4 combined with high levels of IL-6 when compared to healthy controls. Worse neurocognitive functioning was found in bipolar patients.

OBJECTIVES/GOALS: Assess the diagnostic yield and test utilization of WES in patients having complex traits. We aim to evaluate the use of the first genetic approach for the identification of primary variants that contribute to neurogenetic disease etiology and influence onset and progression in Puerto Ricans. METHODS/STUDY POPULATION: Prospective cohort of 45 Puerto Rican probands (19 months - 36 years old) with complex neurogenetic traits that underwent WES (2019 - 2021). WES was performed, including copy number variant analysis and mitochondrial genome sequencing. We evaluated several factors possibly influencing the rate of WES diagnosis including early age, consanguinity, and family history of neurogenetic diseases. In addition, we only evaluated probands rather than dyads/trios and the clinical phenotypes. Descriptive analysis was performed, including a catalog of all variants reported. Multivariate analysis was performed to estimate the statistical association between variants and phenotypes reported and adjusting for potential confounders (age, sex, family history, income, health insurance and zip code). RESULTS/ANTICIPATED RESULTS: Auspiciously, positive pathogenic findings altered the clinical management in 29% of the probands in this study. A likely genetic diagnosis was achieved in 53% of the probands including pathogenic, likely pathogenic and variants of uncertain significance. Intronic variants, copy number variants detection and mitochondrial genome was included in WES methodology. Despite these facts, a 47% of the reported WES were negative, which deserve re-analysis potentially genotype based. Multivariate analysis is expected to adjust for potential confounders to establish a genotype-phenotype correlations in neurogenetic complex traits in this Puerto Rican admixed population. DISCUSSION/SIGNIFICANCE: Clinical WES offers an alternative approach for identification of variants in patients with complex traits. WES is also applicable in genetically heterogeneous individuals when specific genetic tests are not available or unsuccessful. Variants reported contribute to understand complex neurogenetic disease in underrepresented Puerto Ricans.

OBJECTIVES/GOALS: As the number of older adults (≥65 years) with T1D grows, there are limited data to guide care. In a six-month trial, CGM reduced hypoglycemia in older adults, yet there are challenges for widespread uptake. Our objective is to characterize older adults experiences with using CGM and define suboptimal responses signaling a need for resources or support. METHODS/STUDY POPULATION: The study will engage key stakeholders (i.e., older adults with T1D, caregivers [recruited as patient-caregiver dyads], and providers [endocrinologists, geriatricians, diabetes educators]) for a Group Model Building (GMB). GMB is a participatory approach to system dynamics in which participants share perceptions and experiences with a problem and collaboratively explore the system structure that shapes those trends. A series of 8 GMB workshops will be held with 3-8 participants. The final study n will be determined by thematic saturation. Workshops comprise 1) a questionnaire, 2) a GMB session, and 3) a focus group discussion. GMB will follow a replicable process to generate a model of the complex web of causal determinants affecting CGM-related experiences, including optimal and suboptimal CGM responses. RESULTS/ANTICIPATED RESULTS: To date, the study has enrolled 33 participants, including 28 older adults living with T1D and 5 caregivers (mean age = 74 years, range 67-83 years). Twenty-four patient participants will be active CGM users and 4 will be CGM non-users. The study will report on patient data capture from the questionnaire and EMR, including demographics, experiences, familiarity, and confidence surrounding CGM use; diabetes duration; insulin pump use; history of severe hypoglycemia. Analysis of aggregated data will generate causal loop diagrams that integrate pertinent theoretical frameworks, lived experiences, and CGM outcomes. Maps will be used to identify a set of suboptimal CGM responses (i.e., key outcome trajectories) that signal a need for action, with a diagram of factors that interact to produce each response. DISCUSSION/SIGNIFICANCE: Delivering CGM to older adults with T1D demands new approaches. This study will yield critical evidence to tailor support and resources for effective CGM use in older adults. Findings may be translated into suite of pragmatic interventions to bolster CGM use and matched to individual patients expected to benefit using a precision medicine framework.

OBJECTIVES/GOALS: Several studies compare perioperative parameters and postoperative morphology of open cranial vault remodeling (CVR) and endoscopic-assisted craniectomy (EAC) in the treatment of sagittal craniosynostosis. However, data on neurodevelopmental outcomes comparing these techniques is lacking. METHODS/STUDY POPULATION: Patients with repaired sagittal synostosis were enrolled from a single tertiary care center between five and fifteen years of age. Patients with any craniofacial syndrome (e.g., 22q11.2 deletion) or other medical conditions that could affect neurodevelopment were excluded. Neurodevelopment was measured using the Differential Ability Scale-II (DAS-II). The General Cognitive Ability (GCA) score was the primary outcome measure, describing overall intellectual ability. Secondary outcome measures were measurements of cephalic index (CI) from pre- and postoperative imaging studies. Family socioeconomic status (SES) was estimated using the Hollingshead index (total score, continuous). RESULTS/ANTICIPATED RESULTS: 26 patients [10 CVR (2 Female:8 Male), 16 EAC (6 F:10 M)] were studied. Mean age at repair was greater with CVR than EAC (15.5 ± 8.5 months vs 3.5 ± 1.3 months, respectively, p < 0.001). Mean age at DAS-II testing was 9.0 ± 2.2 years. Patients GCA scores were within the average range relative to test norms (CVR 95.7 ± 15.4 vs EAC 102.6 ± 17.4). After adjusting for SES and preoperative CI, group differences in GCA were modest and statistically nonsignificant (p = 0.646). GCA scores were associated with SES (p = 0.054) but not preop CI (p = 0.479). Differences between CVR and EAC were not statistically significant for any of the imaging parameters (pre and postop CI, pre to postop change in CI, or age at postop imaging; 0.131 <= p <= 0.867). None of the independent variables were significantly associated with postop CI (0.140 <= p <= 0.689). DISCUSSION/SIGNIFICANCE: Interim analysis of the preliminary data suggests no association between surgical procedure and cognitive and morphological outcomes at school-age in patients with sagittal craniosynostosis who underwent CVR versus EAC. Collection of data continues, with the goal to enroll 50 participants in each group by 2022.

OBJECTIVES/GOALS: Approximately 10% of COVID-19 patients experience multiple symptoms weeks and months after the acute phase of infection. Our goal was to use advanced machine learning methods to identify PASC phenotypes based on their symptom profiles, and their association with critical adverse outcomes, with the goal of designing future targeted interventions. METHODS/STUDY POPULATION: Data. All COVID-19 outpatients from 12 University of Minnesota hospitals and 60 clinics. Independent variables consisted of 20 CDC-defined PASC symptoms extracted from clinical notes using NLP. Covariates included demographics, and outcomes included New Psychological Diagnostic Evaluation, and Number of PASC Hospital Visits (>=5). Cases (n=3235) consisted of patients with at least one symptom, and controls (n=3034) consisted of patients with no symptoms. Method. (1) Used bipartite network analysis and modularity maximization to identify patient-symptom biclusters. (2) Used multivariable logistic regression (adjusted for demographics and corrected through Bonferroni) to measure the odds ratio of each patient bicluster to adverse outcomes, compared to controls, and to each of the other biclusters. RESULTS/ANTICIPATED RESULTS: The analysis identified 6 PASC phenotypes (http://www.skbhavnani.com/DIVA/Images/Fig-1-PASC-Network.jpg), which was statistically significant compared to 1000 random permutations of the data (PASC=.31, Random Median=.27, z=11, P<.01). Three of the clusters (Cluster-1, Cluster-4, and Cluster-5 encircled with ovals in Fig. 1) contained CNS-related symptoms, which had statistically significant risk for one or both of the adverse outcomes. For example, Cluster-1 with critical CNS symptoms (depression, insomnia, anxiety, brain-fog/difficulty-thinking), had a significantly higher OR compared to the controls for New Psychological Diagnostic Evaluation (OR=6.6, CI=4.9-9.1, P-corr<.001), in addition to having a significantly higher ORs for the same outcome compared to all the other clusters. DISCUSSION/SIGNIFICANCE: The results identified distinct PASC phenotypes based on symptom profiles, with three of them related to CNS symptoms, each of which had significantly higher risk for specific adverse outcomes compared to controls. We will test whether these phenotypes replicate in the N3C data, and explore their translation into triage and treatment strategies.

OBJECTIVES/GOALS: The aim of this study is to examine the prevalence of communication sources about genetic testing among adult women with a higher risk of cancer in the U.S. and identify factors associated with these communication sources by analyzing the Health Information National Trends Survey (HINTS; 2017-2020) data, a large, nationally representative sample. METHODS/STUDY POPULATION: HINTS aims to gain knowledge about the use of and access to cancer information by the public. Used data was collected between 2017 and 2020 from a sample of adult participants who self-reported as female, aged 18+, having no personal cancer diagnosis, and having a family history of cancer. The primary outcome measure is source of communication about genetic testing. Some categories are the media, family members, or a healthcare professional. Analytical approaches include the Pearsons Chi-squared test and poisson regression model to estimate prevalence ratios and examine the association between sociodemographic characteristics and sources of communication, adjusting for clinical and health belief factors as covariates. RESULTS/ANTICIPATED RESULTS: This study is in progress. It is anticipated that the most overall prevalent method of communication about genetic testing will be via the media. In multivariate models, it is anticipated that women who are younger, Black, have a lower education, have lower income, and no health insurance are more likely to receive communication about genetic testing from a source other than a health professional or not at all. After adjusting for clinical and health belief factors such as co-morbid conditions, having a primary care physician, and general knowledge about genetic testing, there may be some association between the above mentioned sociodemographic factors and receiving communication about genetic testing via a healthcare professional. DISCUSSION/SIGNIFICANCE: Reporting on the association between sociodemographic factors and sources of communication can aid in an intervention design to better promote genetic testing. This can be most beneficial among vulnerable groups like Black women to better understand their own genetic risk of cancer and to make informed decisions about their health.

OBJECTIVES/GOALS: Asymmetries in lung pathophysiology can result in a maldistribution of gas between regions of the lungs which may generate dangerous pressures that are not observable by clinicians. Our study aims to demonstrate and quantify this through use of high-fidelity simulators to represent a range of commonly encountered clinical pathologies. METHODS/STUDY POPULATION: A benchtop study was performed with two high-fidelity breathing simulators, each representing one lung. This system allows for real-time monitoring of pressure and lung dynamics in a two-lung asymmetric injury model. One simulator was set to a fixed compliance and a resistance. A second simulator had a range of compliance and resistance values. Data were collected for 15 different test cases across a distribution of asymmetries. Each test case is run for 30 cycles. At the end of each ventilatory cycle, a short expiratory hold is performed, allowing pressure in the lung simulator, tubing, and ventilator circuit to equilibrate between cycles. RESULTS/ANTICIPATED RESULTS: Maldistribution of tidal volume was demonstrated when the compliance ratio between lung models (CL1/CL2) was 0.2 and the resistance ratio (RL1/RL2) was 10 with 23.9% (99% CI: 23.9-24.0%) of the gas volume distributed to lung 1 (103 mL L1 vs 327 mL in L2). Additionally, the injured lung when compared with the normal lung experienced higher peak pressures (12.8 cm H2O vs. 6.9 cm H2O, L1 and L2 respectively) and higher compartmentalized plateau pressures (11.5 cm H2O vs. 6.8 cm H2O, L1 and L2 respectively). DISCUSSION/SIGNIFICANCE: We demonstrate significant maldistribution of volume and pressures between two lungs in an asymmetric injury model. This study suggests significant impact of asymmetry in current lung-protective mechanical ventilation strategies and calls for better understanding of case-specific pathophysiologic changes affecting each of the two lungs.

OBJECTIVES/GOALS: Neonatal endotracheal tubes (ETTs) are usually uncuffed to avoid subglottic stenosis and other complications, but cuffed ETTs allow better ventilation. Our goal was to detect and control pressure in the cuff below the limit of occluding venous flow to minimize the risk of subglottic stenosis. METHODS/STUDY POPULATION: We designed a pressure sensor to fit on a 2.5 ETT for prototype testing in 8 age adult female rabbits. Eight uncuffed age- and sex- matched rabbits served as control. Study duration was 2 hours during which pressure in the cuff was limited by novel sensor (intervention) or auscultation (control). Anesthesia was maintained with sevoflurane. Ventilation was provided mechanically. Subsequently the tracheae were removed, sectioned crosswise, and compared histologically for mucosal damage. RESULTS/ANTICIPATED RESULTS: Preliminary data demonstrated an almost 30% greater amount of intact mucosa in the intervention group. The sensor also provided data on heart rate and respiratory rate, although this signal was not optimal. After filing an invention disclosure and provisional patent, we are refining our device to include multiple compartments for local control of cuff pressure and applying for a STTR Phase I/II application. DISCUSSION/SIGNIFICANCE: Ventilation in neonates with uncuffed ETTs can be suboptimal due to leak around the tube, but cuffed ETTs pose the threat of subglottic stenosis and other complications. We have designed a prototype cuffed ETT with a sensor to maintain low cuff pressure while preventing leaks and largely avoiding damage to the tracheal mucosa.

OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.

OBJECTIVES/GOALS: To assess the impact of federal regulations and policies relating to disposable Electronic Nicotine Delivery Systems (ENDS) on youth consumption of these products by identifying factors enabling its growing consumption among youth users and its relation to adolescent addiction to nicotine. METHODS/STUDY POPULATION: Disposable ENDS are all-in-one devices with pre-filled nicotine liquid and a built-in battery. Recent data shows increased sales as users, including youth, are switching from pod-based to disposable ENDS. Thus, an understanding of the regulatory landscape for these products will provide insight on how to mitigate youth nicotine addiction. Data from the Centers for Disease Control and Prevention 2021 National Youth Tobacco Survey (NYTS) was analyzed for patterns of adolescent use. FDA statements and actions involving disposable ENDS companies were reviewed to evaluate the current FDA stance. Analyses of both data sets identified factors enabling the growth in sale of disposable ENDS. RESULTS/ANTICIPATED RESULTS: The NYTS reported 53.7% of youth ENDS users report using disposable ENDS and Puff Bar is the leading ENDS device among youth consumers. In March 2021, Puff Bar announced a return to market with “tobacco-free nicotine” after ceasing sales following an FDA warning letter in July 2020. But synthetic nicotine retains the same chemical properties as tobacco-derived nicotine and the same risks for addiction and abuse. The Food and Drug Administration (FDA) maintains synthetic nicotine products will be regulated on a case-to-case basis, suggesting “closed system devices” containing synthetic nicotine may not be regulated as tobacco products. DISCUSSION/SIGNIFICANCE: The growing popularity of disposable ENDS among youth is problematic. Awareness of strategic regulatory defiance (i.e., Puff Bar), will bring light to industry sales tactics. To develop comprehensive data on disposable ENDS use by young adults, an anonymous survey of college students will be conducted.

OBJECTIVES/GOALS: Review all approved companion diagnostics (CDxs) labeling for therapeutic class language. Examine the regulatory pathways of CDx products whose labels contain therapeutic class labeling. Develop recommendations for pharmaceutical industry professionals on best practices in the co-development of CDxs and oncology therapeutic products. METHODS/STUDY POPULATION: Literature discussing companion diagnostics was reviewed from EBSCOhost, PubMed, and OVID. The Intended Use language within CDx labels on the Food and Drug Administrations “List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools)” website were reviewed on November 1, 2021 for therapeutics class language. For CDx products with therapeutic class label language, the regulatory history was evaluated to determine the development approach taken to achieve the language. RESULTS/ANTICIPATED RESULTS: A total of 45 CDxs were identified, of which only 2 contained therapeutic class labeling, both of which were devices for the identification of epidermal growth factor receptor (EGFR) mutations for the treatment of non-small cell lung cancer (NSCLC). Three additional EGFR CDxs were approved; however, they did not contain therapeutic class labeling. The first CDx was the Cobas EGFR Mutation Test V2, which received therapeutic group label language as an update on October 27, 2020; however, prior to the therapeutic class labeling, three oncology products were named in the Intended Use: Tarceva (erlotinib), Tagrisso (osimertinib), and Iressa (gefitinib). The second CDx to incorporate therapeutic class labeling was the ONCO/Reveal Diagnostic Lung and Colon Cancer Assay upon initial approval on July 30, 2021. DISCUSSION/SIGNIFICANCE: EGFR CDxs are the first to shift towards therapeutic class labeling. Indication, molecular alterations, and mechanism of action of the approved therapeutic class products, number of products approved, as well as CDx analytical and clinical validation influence class label relevance. Discussions with the FDA are encouraged early in development.

OBJECTIVES/GOALS: Antiretroviral treatments (ART) suppress retroviruses, like the human immunodeficiency virus (HIV). The goal is to understand how antiretroviral drug patents contribute to overpriced HIV medications, thereby causing cost-related treatment non-adherence and inhibiting viral suppression. METHODS/STUDY POPULATION: Currently, HIV affects 57,700 individuals in Los Angeles County (LAC). Data was compiled from Centers for Disease Control and Prevention (CDC), hiv.gov, lacounty.HIV, publichealth.lacounty.gov, and the U.S. Patent and Trade Office. A review of existing literature examined the role of ART patents on cost-related non-adherence and declining viral suppression on individuals living with HIV in LAC. Lastly, a comparison of HIV medication prices of expired and non-expired patents was conducted, indicating the effects of undue extensions of market exclusivity on ART regimen pricing, and how this affects treatment adherence. RESULTS/ANTICIPATED RESULTS: Of the ten ARTs examined, four had expired patents and six had active patents. Those with active patents cost more than those with inactive patents because active patent status prevents price reductions. Patent strategies–pay-for-delay settlements and patent evergreening–unduly extend market exclusivity, keeping ART at prohibitive costs and preventing generic competition. Individuals facing cost-related non-adherence were less virally suppressed at their last viral load test (64%) and at all tests during the year (54%). Thus, over-patented ARTs increase treatment prices, causing cost-related non-adherence to ART regimens. The implications include disease progression and less viral suppression. DISCUSSION/SIGNIFICANCE: The U.S. has the highest ART prices, yet the lowest rate of HIV viral suppression (54%) among all well-resourced countries. Undue extensions of market exclusivity cause ARTs to remain at prohibitive costs, preventing some patients from affording ART treatments, minimizing their viral suppression.

OBJECTIVES/GOALS: Atopic Dermatitis (AD) affects 10% of people globally and is studied widely in clinical trials. However, clinical outcomes assessment (COA) for AD are not standardized, hindering easy comparisons across different studies. This study examines AD studies to identify the most used COAs. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched to identify AD trials conducted between 2011 and 2021. Ongoing and completed trials were classified according to the therapeutic modality: Biologic, Immunosuppressive, or Other (botanicals and antibiotics). Further, AD trials were examined to determine which of the COAs listed in the FDA compendium issued in 2021 were included: the Investigators Global Assessment (IGA), the Eczema Area and Severity Index (EASI-75), and the Pruritus Numeric Rating Scale (NRS). The results were analyzed to determine which COA is most frequently used and if there were differences across therapeutic modalities or trial phases. RESULTS/ANTICIPATED RESULTS: Across a total of 50 AD trials registered in clinicaltrials.gov, EASI-75 was the most used COA; the item was included in 12 of 16 biologics, 5 of 14 immunosuppressives, and 7 of 20 other products. Moreover, AD trials of biologics included more of the FDA-suggested COAs than those studying other modalities. There were also differences across the clinical trial phases in that most phase III AD trials (83.33%, n=8) included two of the three COAs listed (IGA and EASI-75) compared to less than half of phase I/II trials (vs. 43.75%, n=32). DISCUSSION/SIGNIFICANCE: Findings from this study indicate a lack of COA harmonization across AD trials, impeding comparative analysis of the trial results. Establishing a common standard for COA would foster communication and transparency among key stakeholders including researchers, healthcare providers, and patients.

OBJECTIVES/GOALS: The University of Michigan Frankel Cardiovascular Center (FCVC) Innovation Challenge is an annual competition offering funding for innovative ideas to improve cardiovascular care. Due to the COVID-19 pandemic, administrators converted the recruitment process and pitch event to fully virtual. METHODS/STUDY POPULATION: We detail the process of converting the event from a hybrid process (virtual and in-person recruiting and in-person event) to a fully virtual one. Changes to the event included implementing a virtual recruiting process utilizing short video recordings as submission format; a new tool for storing and displaying submissions; fully virtual finalist selection and coaching; and a fully virtual pitch and judging event. The submission process tracked information about submissions that include the type of idea (process or product), role of team lead, and department of team lead. RESULTS/ANTICIPATED RESULTS: The FCVC Innovation Challenge was successfully converted to a fully virtual event. Methods and tools will be shared to allow similar institutions to replicate a successful virtual pitch event. These include methods and tools utilized to allow participants to describe their ideas, strategies to select and coach finalists, and to host a virtual pitch event. Data will be shared on the number of ideas and category (product/process) of projects submitted, and number and category of finalists selected. DISCUSSION/SIGNIFICANCE: This case review can demonstrate how institutions can use a similar virtual idea submission and pitch process to (1) catalyze innovative ideas that can impact patient care by accessing its communitys ideas and (2) fund innovative ideas that do not fit traditional mechanisms.

OBJECTIVES/GOALS: This presentation reports activities of a NCATS-funded collaborative working group created to promote dissemination and implementation (D&I) research within the CTSA landscape. Our working group seeks to meet both the conceptual as well as practical challenges to advancing the utilization of D&I across the translational science spectrum. METHODS/STUDY POPULATION: A fundamental focus of D&I is supporting the movement of effective health interventions into real-world use so that they benefit population health. Yet, this process remains unpredictable, with some interventions receiving widespread uptake in practice and others (of similar potential benefit) failing to translate. The value of research efforts is wasted when directed toward the “wrong” interventions. Recent discussion and experience amongst investigators in our collaborative working group has resulted in new ways of addressing this problem. Specifically, tools borrowed from business and management have shown promise in predicting which health interventions have the highest potential for commercialization and dissemination. RESULTS/ANTICIPATED RESULTS: We will conduct an environmental scan of CTSA hubs to understand their approaches to supporting commercialization and business development around research products, identifying the most promising and effective methods and processes. We will compile various tools for identifying and supporting interventions with the highest potential for commercialization, including how to form the multidisciplinary and stakeholder-engaged teams necessary to make these determinations. Finally, we will further explore the differences between patentable and non-patentable innovations and make recommendations for CTSAs in supporting the latter. DISCUSSION/SIGNIFICANCE: Commercialization of non-patentable interventions is an essential and underexplored element of the translational science spectrum. The perspectives and methods of D&I should not be relegated to late-stage translational steps, but rather inform the conduct of translational science writ large.

OBJECTIVES/GOALS: The clinical management of differences of sex development (DSDs) aims to guarantee best practices in medical care while addressing concerns related to non-reversible surgeries. Rhetorical analysis was conducted to study the balance between science policy and patient advocacy related to DSD surgeries as depicted in medical education materials METHODS/STUDY POPULATION: Unrestricted transcripts of two educational videos and text from all chapters of a handbook addressed to medical learners and faculty by the Association of American Medical Colleges (AAMC) were submitted to automated word cloud analysis (NVivo, QSR International®). Words with a weighted percentage > 0.19% from total words of a given source were defined as words of frequent use and were selected for further analysis after exclusion of words as conjunctions, prepositions, pronouns, or conversational fillers. Words sharing noun, adjective and adverb forms were coded and weighed as a single word following the Oxford dictionary. Discrepancies on word selection, exclusion or coding were resolved between four raters. The rhetorical context of most frequent words was identified. RESULTS/ANTICIPATED RESULTS: The word cloud analysis of the video resource intended for medical learners (n=104 words of frequent use) and the video intended for medical faculty (n= 94 words of frequent use) depicts a patient-centered approach (word people’) that is based on expert opinion (word [I] think’). The handbook (n= 998 words of frequent use) makes reiterated reference to patients’; lgbt’; gender’; health’; and caring’ while underscoring health concerns that are unrelated to genital variance (health’; caring’ and medical’). The noun surgery’ did not figure among the most frequent words in spoken language nor in written text even when summing its adjective and adverb forms. DISCUSSION/SIGNIFICANCE: Educational materials by the AAMC on DSDs accentuate patient-centered care within a medical humanism framework. However, the lack of discussion of DSD surgeries is an educational gap that should be addressed by key science policy and patient advocacy stakeholders.

OBJECTIVES/GOALS: The present study sought to investigate kratom use motives among the U.S population with the goal of discovering previously unknown health-related reasons for kratom use by the general public. METHODS/STUDY POPULATION: To guide decisions regarding kratom regulation, the FDA solicited comments from the public regarding the abuse potential of these substances, medical usefulness, and impact of scheduling changes from July 2021 until August 2021. Comment participation was open to the public. The first 6,353 consecutive comments posted on the Federal Register website were retrieved and analyzed. Duplicate comments and comments not pertaining to kratom were excluded from the analysis. The comment submissions were reviewed and categorized using an inductive approach via thematic content analysis. RESULTS/ANTICIPATED RESULTS: Respondents reported over 108 independent health-related reasons for kratom self-medication. Most often fell under the categories of mental health (1911 counts), pain management (1873 counts), substance use disorder (1635 counts), rheumatic diseases (613 counts), and degenerative spine diseases (247 counts). Many comments (701 counts) reported use for miscellaneous purposes, which included to increase focus (212 counts), treat insomnia (127 counts), and decrease fatigue (99 counts). Neurological diseases (e.g., migraines, restless legs syndrome, and multiple sclerosis) and digestive disorders (e.g., irritable bowel syndrome and Crohns Disease) were also reported (147 and 96 counts, respectively). Respondents also reported on the abuse potential and adverse effects of Kratom (122 counts). DISCUSSION/SIGNIFICANCE: This is the first study to delineate and classify motives for kratom use among Americans. Individuals reported using kratom for a wide spectrum of health-related reasons. Though these results may be influenced by the placebo effect, they suggest that kratom alkaloids may possess therapeutic activity for previously unknown applications.

OBJECTIVES/GOALS: The present work aims to use baseline data to identify demographic, clinical, and psychosocial factors associated with patients who receive analgesic benefit from temporary neurostimulation. METHODS/STUDY POPULATION: This study presents baseline data from our descriptive, prospective, longitudinal study. Consecutive patients who present to the University of Arkansas for Medical Sciences Interventional Pain Management Clinic for implantation of a neurostimulation device, have met clinical criteria for implantation of a neuromodulation device, and are able to speak and understand English are invited to participate. Prior to the placement of the temporary stimulator, each patient completes demographic and symptom-related questionnaires. Clinical characteristics are obtained through medical record review. RESULTS/ANTICIPATED RESULTS: We anticipate enrolling 50 participants in order to have 30 patients that report analgesic benefit from temporary neurostimulation. Variability in demographics, clinical characteristics, and psychosocial factors will be reported between patients who receive and those who do not receive analgesia following temporary neurostimulation. Gender differences will also be reported. DISCUSSION/SIGNIFICANCE: Despite the use of varying outcome measures, studies to date have not incorporated validated patient reported outcomes or controlled for key demographic and clinical characteristics. Our analysis evaluates clinical and psychosocial variables associated with successful temporary neurostimulation.

OBJECTIVES/GOALS: Childhood survivors of ALL are at considerable risk for late effects which are exacerbated by excess weight. The proposed study involves the adaption and evaluation of the first empirically supported intervention for childhood survivors of ALL that is consistent with all national recommendations for the treatment of childhood obesity. METHODS/STUDY POPULATION: The proposed intervention will be adapted from family-based behavioral weight loss treatment (FBT) a multicomponent intervention which targets diet, activity, behavioral skills, parenting, and social facilitation among children and their parents. The Framework for Reporting Adaptations and Modifications-Enhanced structure (FRAME), a dissemination and implementation framework, will guide the adaptation, allowing for the incorporation of feedback previously gathered from key stakeholders. A single-arm, non-randomized trial of the adapted intervention will then be conducted to evaluate its acceptability, feasibility, and preliminary indications of efficacy including measures of relative weight change and associated health-related behaviors among 40 childhood ALL survivors and their families. RESULTS/ANTICIPATED RESULTS: Self-reported feedback from families at the end of treatment (EoT) is anticipated to demonstrate that this intervention will be regarded as both acceptable and feasible. Other measures of feasibility will include attendance and retention rates, which are expected to reflect to those of previous FBT trials (92% and 85%, respectively). Preliminary indications of the efficacy of the adapted intervention will be investigated through the comparison of a series of measurements taken at both baseline and EoT. Changes in relative weight will be assessed and are expected to meet a previously established range of clinically meaningful reduction in child percent overweight of 9 units or more. Improvements in dietary intake, physical activity, and health related quality of life are also anticipated. DISCUSSION/SIGNIFICANCE: Knowledge gained from the implementation of the first evidence-based intervention adapted for childhood survivors of ALL will be critical to the justification of a larger-scale, randomized controlled trial and holds promise to effectively modify the risk for chronic disease among a vulnerable population.

OBJECTIVES/GOALS: Minimal human investigations have assessed the effect of synbiotics (combination of pre- and probiotics) on anxiety symptoms, despite evidence from preclinical research. Our study aimed to determine the feasibility of a randomized, placebo-controlled trial utilizing synbiotics to reduce anxiety symptoms in older female breast cancer survivors. METHODS/STUDY POPULATION: We aimed to recruit older female breast cancer survivors experiencing anxiety symptoms to a 4-week randomized, placebo-controlled clinical trial. At commencement of the project, participants were eligible if they : 1) were 50-75 years old; 2) completed primary treatment for breast cancer; 3) were experiencing clinical anxiety symptoms 4) agreed to not change dietary supplements 5) were willing to comply with daily supplement regimen; and 6) were able to read and speak English. Use of anxiolytic or microbiome-altering medications, or changes to anxiety treatment within 4 weeks of enrollment were criteria for exclusion. Due to budgetary limitations, we were unable to recruit from state cancer registries, and instead recruited via newspaper advertisements and flyer distribution. RESULTS/ANTICIPATED RESULTS: One participant has successfully been recruited and completed the duration of the clinical trial, and two others have expressed interest but were deemed ineligible. Barriers in recruitment resulted in the following modifications to protocol: we expanded our eligibility criteria by removing the upper age limit (now 50+ years old) and now are recruiting females with a personal or family history of breast cancer. We partnered with the Spencer Cancer Center of East Alabama Health to aid in recruitment. DISCUSSION/SIGNIFICANCE: Integrative approaches to improved patient outcomes are needed, however, recruitment remains a paramount barrier for clinical trials. Addressing our issues for recruitment has opened eligibility to more individuals and allows us to continue our investigations, answer our research questions, and advance translational science.