Objectives/Goals: Intra-amniotic inflammation (IAI) is one of the leading causes of maternal/fetal morbidity globally, yet it is undiagnosed in 90–95% of cases. The purpose of this study was to assess precision and accuracy of a novel microsampling device for measuring cytokines in amniotic fluid (AF) to enable noninvasive evaluation of localized inflammation. Methods/Study Population: AF was obtained from discarded amniocentesis samples from 3 deidentified patients without known inflammation. Samples were spiked to 5 concentrations of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), then sampled using the Neoteryx Mitra volumetric microsampling device (20 µL). Dried/reconstituted samples were analyzed using the Luminex R&D Mag XL multiplex (IL-6, TNF-α) and compared to free-flowing AF. Inter-and intra-assay performances were evaluated across 5-runs in 3 standard cytokine concentrations. Recovery/linearity was assessed by a recovery curve and parameter estimates. Precision was assessed between-run and within-run using coefficients of variance (%CV). Accuracy was evaluated as agreement between microsampled and free-flowing AF using Bland–Altman plots. Results/Anticipated Results: TNF-α results were linear for all 3 patients across 5 concentrations. However, accuracy and recovery consistently failed (mean±SD percent recovery 176±21%). TNF-α results had acceptable precision with %CV within-run of 6.8–12.1% and across-runs of 14.0–15.9%. Microsampled TNF-α agreed with free-flowing sample: 16 of 18 (89%) were within 1SD of the mean difference (-24±36 pg/ml). IL-6 results were linear for 1/3 patients and had unacceptable accuracy and recovery for 13/15 samples (mean±SD percent recovery 764±469%). IL-6 results had acceptable precision (%CV within-run 6.2%, 7.5% and 11.2%; across-run .9–15.2%). Microsampled IL-6 agreed with free-flowing sample; 17 of 18 (94%) were within 1SD of the mean difference (-148±180pg/ml). Free-flowing vs. microsampling methods agreed best at low concentration. Discussion/Significance of Impact: This study provides preliminary support for noninvasive measurement of cytokines leveraging small amounts of leaking AF providing a promising alternative to amniocentesis and potential for assessing inflammation intrapartum. Clinical application requires development of reference ranges and association between cytokine levels and outcomes.

ABSTRACT IMPACT: The importance of this study is to evaluate the responses following the exposure of opioid drugs in young adults to address the current opioid epidemics OBJECTIVES/GOALS: To compare the proportion of patients between 18 and 25 years of age, who develop an opioid abuse disorder following dental surgery, to those following other surgical procedures, when an opioid drug is used for acute postoperative pain control. METHODS/STUDY POPULATION: We fashioned an IRB-sponsored retrospective cohort study of patients, ages 18 to 25 years old, who presented for dental surgery or other medical surgical procedures, at Strong Memorial Hospital Medical Center, at the University of Rochester and received opioid drug treatments, for acute surgical pain management. Patients with the diagnosis of acute surgical pain were included in the study. However, those with chronic pain or other related abnormalities were excluded, even if a diagnosis of acute surgical pain was present in the electronic chart. The clinical data were retrieved from electronic medical records and NYS-iStop records. All statistics were significant at the level of <0.1 RESULTS/ANTICIPATED RESULTS: We identified 167 subjects, of whom, only 150 subjects met inclusion criteria (n=100) in dentistry and (n=50) in other medical specialties. Patients were followed up in a 7-year period. Most of the subjects were females (n=91), Caucasian (n=80), and lived in a suburban location (n=78). The most frequently prescribed opioid included hydrocodone (n=119). A significantly higher proportion (8.7%) of patients developed opioid abuse disorders in the control group, compared to 1% of subjects in the experimental group (p 0.02). Those in the control group received marginally significant higher doses of MMEs 447.2 +/-644.8 mg vs 306.2 +/-354.7mg in the experimental group (p 0.086). Those in the control group had significantly longer periods of opioid treatment 10 (+/-12) compared to 6(+/-6) days in the experimental group DISCUSSION/SIGNIFICANCE OF FINDINGS: It is paramount to evaluate the morphine milligram equivalents, and duration of opioid treatment given to the young population with acute surgical pain, to prevent opioid abuse disorders in this vulnerable cohort.

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive and prevalent breast cancer subtype that lacks targeted therapies. This study aims to investigate whether the niclosamide derivative HJC0152 can modulate tumor-derived PD-L1 expression and enhance the effectiveness of anti-PD-1 immunotherapy in treating TNBC. Methods/Study Population: Niclosamide derivative HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human TNBC cell line (MDA-MB-231) was treated with HJC0152, and activation of the STAT3 signaling pathway was evaluated using Western blotting. RNA-Seq was employed to analyze the expression of protein-coding genes, particularly those related to immune response. To study therapeutic potential in vivo, TNBC mouse models will be treated with single agent treatments as well as a combination therapy of HJC0152 and anti-PD-1. Tumor volume and mass will be measured over time to determine growth inhibition. Results/Anticipated Results: Preliminary studies indicate that HJC0152 exhibits enhanced solubility compared to Niclosamide, along with high anticancer potency both in vitro and in vivo. HJC0152 was found to effectively inhibit the activation of phosphorylated STAT3 (p-STAT3) in MDA-MB-231 cells, a key signaling pathway associated with cancer progression and immune evasion. RNA-Seq analysis of HJC0152-treated MDA-MB-231 cells revealed a decrease in PD-L1 expression, an essential immune checkpoint protein involved in tumor immune suppression. These findings suggest that HJC0152 is a promising immune modulator that may enhance the efficacy of immune checkpoint blockade therapy for TNBC. Discussion/Significance of Impact: This study explores an innovative immunotherapy for TNBC using the Niclosamide derivative HJC0152, which inhibits STAT3 signaling and downregulates PD-L1. Results from this study will provide a foundation for HJC0152’s inclusion in clinical trials and potentially offer a new and promising therapeutic option for TNBC treatment.

OBJECTIVES/SPECIFIC AIMS: Smoking during pregnancy (SDP) is associated with negative health outcomes, both proximal (e.g., preterm labor, cardiovascular changes, low birth weight) and distal (e.g., increased child externalizing behaviors and attention deficit/hyperactivity disorder (ADHD) symptoms, increased risk of child smoking). As pregnancy provides a unique, strong incentive to quit smoking, investigating SDP allows analysis of individual predictive factors of recalcitrant smoking behaviors. Utilizing a female twin-pair cohort provides a model system for characterizing genotype×environment interactions using statistical approaches. METHODS/STUDY POPULATION: Using women from the Missouri Adolescent Female Twin Study, parental report of twin ADHD inattentive and hyperactive symptoms at twin median age 15, and twin report of DSM-IV lifetime diagnosis of major depressive disorder, trauma exposure (physical assault and childhood sexual abuse), collected at median age 22, were merged with Missouri birth record data for enrolled twins, leading to 1553 individuals of European ancestry and 163 individuals of African-American ancestry included in final analyses. A SDP propensity score was calculated from sociodemographic variables (maternal age, marital status, educational attainment, first born child) and used as a 6-level ordinal covariate in subsequent logistic regressions. RESULTS/ANTICIPATED RESULTS: For European ancestry individuals, parental report of hyperactive ADHD symptoms and exposure to childhood sexual abuse were predictive of SDP, while a lifetime diagnosis of major depressive disorder, parental report of inattentive ADHD symptoms, and exposure to assaultive trauma were all not significantly predictive of future SDP. For African-American individuals, none of these variables were significant in predicting future SDP. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding this relationship of risk-mechanisms is important for clinical understanding of early predictors of SDP and tailoring interventions to at risk individuals. Ultimately, the focus of this research is to mitigate risk to pregnant smokers and their children. Additionally, the cohort-ecological approach informs how well research and administrative (vital record) data agree. This allows for evaluation of whether administrative data improve prediction in research cohorts, and conversely if research data improve prediction over standard sociodemographic variables available in administrative data.

OBJECTIVES/SPECIFIC AIMS: 1. Determine positive predictive value, negative predictive value, sensitivity, and specificity of Neuro ICU nurse interpretation of real-time bedside qEEG. 2. Determine difference in time to detection of first seizure between Neuro ICU nurse qEEG interpretation and EEG fellow reads of cEEG. 3. Determine what qualities of seizures make detection by neuro ICU nurses more or less likely – e.g. duration of seizures, type of seizures, spatial extent of seizures. METHODS/STUDY POPULATION: Recruit neuro ICU nurses taking care of 150 patients admitted to the Neuro ICU at Duke University Hospital who are initiated on cEEG monitoring. Nurses will be consented for their participation in the study. Neuro ICU nurses will evaluate the qEE RESULTS/ANTICIPATED RESULTS: From literature estimates of a 20% seizure prevalence in critical care settings, we hope to have 30 patients with seizures and 120 without. Based on prior study in the Duke Neuro ICU, we hypothesize that Neuro ICU nurses will have sensitivity and DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first prospective study of neuro ICU nurse interpretation of real-time bedside qEEG in patients with unknown NCSE/NCS presence. If nurse sensitivity, specificity, and positive predictive value are clinically useful, which we deem would be so at a sensitivity of 70% or greater, with acceptable false alarm rate, nurse readings of qEEG could significantly decrease the time to treatment of seizures in the Neuro ICU patient population, and perhaps could improve patient outcomes.

OBJECTIVES/GOALS: Low statistical power is a problem is many fields. We performed a systematic review to determine the median statistical power of studies of epilepsy surgery outcomes. METHODS/STUDY POPULATION: We performed a PubMed search for studies reporting epilepsy surgery outcomes for the years 1980-2000, focusing on studies using stereo-electroencephalography (SEEG). We extracted patient count data for comparisons of surgical outcome between groups, based on a prognostic factor. We defined a clinically meaningful difference the surgical outcome for MRI positive (66.9%) compared to MRI negative (45.5%) in the largest study in the series. The statistical power of a Chi-square test was computed as the percentage of simulated runs (10,000 repetitions) assuming this difference with a p-value less than 0.05. RESULTS/ANTICIPATED RESULTS: Based on 69 studies, the median sample size was 38 patients, and the median statistical power was 24%. This implies at least a 17% (0.5/[0.24+0.05)) chance a study with a significant result in false, assuming 1:1 pre-test odds. A 'typical’ SEEG study with 33 patients and 2:1 allocation had a median significant odds ratio of 6.5, which over-estimates the true odds ratio of 2.4. DISCUSSION/SIGNIFICANCE: Studies of epilepsy surgery outcomes using SEEG are statistically underpowered. This means true effects will be missed, the chance a study with a significant result is false will be inflated, and significant effects found will be over-estimated. Studies of surgery outcome need better statistical rigor if they are to reliably guide treatment.

OBJECTIVES/GOALS: We adapted the Serious Illness Care Program (SICP), an evidence-based intervention designed to promote early serious illness conversation, to be delivered via telehealth for older patients with acute myeloid leukemia and myelodysplastic syndromes. The purpose of this study is to assess the feasibility and usability of the adapted intervention. METHODS/STUDY POPULATION: We are conducting a single-arm pilot study of an adapted SICP that is delivered via telehealth for older patients with AML or MDS (>=60 years) and their caregivers (if available). The adapted SICP includes: 1) Patient preparation pamphlet: sent to patient prior the visit with their clinician, 2) Geriatric assessment: completed by study team and provided to clinician prior to their visit with the patient, 3) A 30-60 minute telehealth visit with their primary oncologist or oncology advance practitioner, 4) Serious Illness Conversation Guide (SICG): used by the clinician during the visit to elicit patient values, 5) Family guide: provided to patient following their visit to help patient’s share their values with their family, 6) Electronic medical record note template for clinicians to document their visit the patient. RESULTS/ANTICIPATED RESULTS: We hypothesize that the adapted SICP intervention will be feasible and usable. We will assess feasibility based on retention rate (percent of patients who consent and complete the visit); >80% is considered feasible. Usability will be assessed using the telehealth usability questionnaire; an average score of >5 is considered usable. Other measures include psychological health, advance care planning engagement, quality of life, and disease understanding. We plan to enroll 20 patients in this study. To date, 11 patients have consented to participate, 10 patients have scheduled SICP visits, 9 patients have completed their visits, 7 patients have completed post-intervention qualitative interviews, and 4 patients have completed post-intervention surveys. DISCUSSION/SIGNIFICANCE: The adapted telehealth-based SICP may promote early serious illness conversation, patient-reported outcomes, and end-of-life experience for older patients with AML and MDS. Results from this study will be used to inform development of clinical trials testing the impact of the adapted SICP on patient- and caregiver-reported outcomes.

OBJECTIVES/GOALS: Nurses are leaving the profession at an alarming rate due to increased workload and burnout.#_msocom_1 Computational models that are reliable and reproducible are needed to quantitatively examine nursing workload and estimate potential effect of interventions. This project developed a logical data model to represent nursing EHR interactions. METHODS/STUDY POPULATION: With nursing EHR interactions as a starting point, we expand upon literature that examined the EHR workload of physicians. We conducted an exploratory analysis of nursing EHR audit log data at a large academic medical center, and explored components of nursing workload that can be extracted from other health system data. Using concepts derived from the studying temporal biomedical data patterns, we formulated a data structure that describes nurse EHR interactions, nurse intrinsic and situational characteristics, and nurse outcomes of interest in a scalable and extensible manner. RESULTS/ANTICIPATED RESULTS: Temporal machine learning models are grounded in the concept of vectors. We developed a logical data model that describes tasks performed by nurses (NTask), nurse types (NType), and nursing outcomes (NOutcome). For each nurse (k), we define a function <NTask (k, i)>, i=1 to N as a vector of dimension N, where N is the number of time periods in the study. The i component corresponds to the activity that the nurse is doing. The model will allow the quantitative classification of activity patterns for any finite number of nurses for an arbitrary set of tasks and for time at any specified resolution. The expected outcome is a set of vectors that can then be utilized to quantitatively model nurse activity trajectories and other patterns of nurse EHR interactions. DISCUSSION/SIGNIFICANCE: By instantiating the logical data model, we will demonstrate how nurse EHR interactions can be studied using temporal unsupervised learning and state-of-the-art artificial intelligence methods. We plan to simulate the potential impact of workload interventions and predict risk for nurse burnout.

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to identify factors influencing parental willingness of adolescent participation in clinical trials. METHODS/STUDY POPULATION: We applied community engaged research principles to conduct a theory-based, cross-sectional study of parental willingness. Parents (N=307) were given a survey from November 2014 to April 2015. Factors influencing parental willingness were identified using binary logistic regression. SPSS version 22.0 was used to perform analyses, and p<0.05 was considered statistically significant. RESULTS/ANTICIPATED RESULTS: The most impactful factor on willingness was Advantages of Adolescent Clinical Research (p = .001), followed by Disadvantages of Clinical Research (p = .006), Knowledge of Adolescent Clinical Trials (p = 0.029), and Perceived Health Status of Adolescent (p = .036). In further exploring the influence of Perceived Advantages and Perceived Disadvantages, “My child will do something to help others.” (p = .026) and “My child is too young to participate in a clinical trial.” was the only significant Perceived Disadvantage (p = .001) were significantly associated with parental willingness. DISCUSSION/SIGNIFICANCE OF IMPACT: Improving parental knowledge and understanding of adolescent clinical trials, the advantages and disadvantages of adolescent participation, and the health status requirements for child participation are important factors to address when influencing parental willingness to allow adolescents to participate in clinical trials. Recruitment strategies that incorporate this information could improve future adolescent participation in clinical trials, ultimately promoting adolescent health and disease prevention.

OBJECTIVES/GOALS: Open surgery prevails in low- and middle-income countries (LMICs) due to scarcity of laparoscopic equipment and poor access to training. LaparosopiX is a box trainer system designed for teaching hospitals in LMICs; it includes an open-source laser print design and an app to allow surgical trainees to receive feedback from laparoscopic experts. METHODS/STUDY POPULATION: This study aims to assess the usability of Laparoscopix for surgical trainees and mentors at five large teaching hospitals in Kenya. Surgical trainees and mentors who participate in this study will be observed while setting up and using the app to identify natural pain-points. A post-session survey will be conducted to assess immediate perceptions of the platform including ease of navigation and intuitive design. Over three months, aggregate data regarding platform usage at these hospital sites will be collected and analyzed to assess user retention rates, usage and traffic patterns, and skill progression over time. Surveys will be sent out to assess attitudes towards the platform and to elucidate any aspects of the system we can improve. RESULTS/ANTICIPATED RESULTS: We hope to find overall positive impressions towards the LaparoscopiX system during this study. We expect there to be some pain-points that arise during navigation of the app, but we expect no large changes to the application architecture required. We anticipate an immediate increase and eventual plateau of users recruited. We hope to see that surgical trainees are advancing through the app while gaining practice and confidence. We will gather insightful data on which aspects of the app were helpful for trainees, and which can be improved. We also hope to learn what factors may play into trainee and mentor retention in the system. DISCUSSION/SIGNIFICANCE: Through this study, we hope to elucidate ways in which we can improve the LaparoscopiX platform, identify which features to prioritize, and determine the direction of future app development. We believe and hope that LaparoscopiX can expand access to laparoscopic surgical mentorship to improve surgical outcomes and health equity worldwide.

OBJECTIVES/SPECIFIC AIMS: Discrimination within the healthcare system and physician distrust have been associated with adverse clinical outcomes for people living with HIV; however, many studies do not link these variables to biological data. We hypothesize that perceived healthcare discrimination and physician distrust associates with higher longitudinal viremia among HIV-positive women. METHODS/STUDY POPULATION: A 2006 cross-sectional survey assessed healthcare-based discrimination and physician trust in 92 HIV-positive and 46 high-risk HIV-negative women from the Washington DC Women’s Interagency HIV Study (DC-WIHS). In addition, we identified HIV viral load trajectories and demographics from the HIV-positive women who contributed≥4 semi-annual visits from 1994 to 2015. Viral suppression was defined by assay detection limits (<80 to <20 copies/mL). Group-based probability trajectory analyses grouped women based on longitudinal viral load patterns, and identified 3 groups: sustained viremia (n=32) with low-viral suppression over time, intermittent viremia (n=27) with varying suppression over time, and non-viremia (n=33) with high-longitudinal viral suppression. Ordinal logistic regression models assessed trajectory group and discrimination variables, controlling for demographics, using stepwise selection with significance level of α=0.05. RESULTS/ANTICIPATED RESULTS: Most women were African American (60%), insured at the time of visit (89%) and nonsmokers (56%). While physician trust did not differ by HIV viral trajectory group, trust was lower among HIV-negative women compared with HIV-positive women (p=0.03). Over 1 in 5 HIV-positive women reported discrimination in the healthcare system based on HIV status (21.3%). Report of discrimination based on drug/alcohol use was higher among HIV-negative participants (19.2% vs. 6.5%, p=0.01). Among women with longitudinal sustained viremia, report of discrimination based on race ethnicity (29%, p=0.004) and sexual orientation (15.6%, p=0.008) were higher than within the nonviremic and intermittent trajectory groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician trust did not associate with increased longitudinal viral suppression among HIV-positive women in Washington, DC. Lack of physician trust among high-risk HIV-negative women could have implications for uptake of prevention methods. Reports of discrimination vary between HIV-positive and HIV-negative women in the Washington, DC area. The findings of healthcare system distrust among HIV-negative women has implications outside the realm of HIV, as this lack of trust may impact risk for other disease states among similar populations of women.

OBJECTIVES/SPECIFIC AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease in the United States characterized by fat accumulation, inflammation, and fibrosis. Higher amounts of fat-free mass (FFM) and lower amounts of fat mass (FM) have been associated with better outcomes in several chronic diseases, recently also in NASH. Body composition is highly influenced by diet. However, the role of diet on body composition in patients with NASH is largely unknown. We hypothesized that consumption of polyunsaturated fatty acids (PUFA), healthy fatty acids mainly found in fish, nuts, and some vegetable oils, is associated with improved body composition, specifically greater FFM and lower FM, in NASH patients. METHODS/STUDY POPULATION: In total, 13 patients with histologically confirmed NASH underwent body composition testing via bioelectrical impedance analysis to estimate FFM% (% of body weight), FM% (% of body weight), and FFM/FM ratio. PUFA and saturated fat consumption was determined by standardized 5-pass 24-hour dietary recall. Correlations were computed using the Spearman rank test. RESULTS/ANTICIPATED RESULTS: Median body mass index (BMI) was 35.7 kg/m2 (32.8–42.7), median age of the sample was 50 years (46.3–57.3), and 73% were female. Median percent of calories from polyunsaturated fat was 6.8% (5.4–9.6). Percent of calories from PUFA was positively and significantly associated with greater FFM% (R=0.56, p=0.049), lower FM% (R=−0.59, p=0.035), and greater FFM/FM ratio (R=0.58, p=0.037). Additionally, a higher PUFA to saturated fatty acids ratio was also significantly correlated with greater FFM% (R=0.58, p=0.039), lower FM% (R=−0.64, p=0.020), and greater FFM/FM ratio (R=0.57, p=0.043). DISCUSSION/SIGNIFICANCE OF IMPACT: In patients with NASH, the consumption of PUFA is associated with higher FFM and lower FM, which suggests a protective role of these nutrients on body composition. A larger study on patients with NASH is warranted to confirm our findings on PUFA consumption and body composition, as well as to determine whether these effects will improve clinical outcomes.

ABSTRACT IMPACT: The proposed research study will provide critical pilot data on the effect of using the prebiotic (HAMS-AB) on the gut microbiome profile, Beta-cell function and immune markers in humans with T1D. OBJECTIVES/GOALS: The overall objective of this study is to assess how the prebiotic high amylose maize starch that has been acetylated and butyrylated (HAMS-AB) impacts the gut microbiome profile, short chain fatty acid (SCFA) production, glycemia, Beta-cell function/health and immune responses in newly diagnosed youth with type 1 diabetes (T1D). METHODS/STUDY POPULATION: We are performing a pilot randomized cross-over trial. We plan to recruit 12 newly-diagnosed T1D youth with residual Beta-cell function between 12-16 years of age. We will profile the gut microbiome using metagenomics, measure stool SCFA levels using mass spectrometry, assess glycemia using continuous glucose monitoring, assess insulin production using mixed meal tolerance testing, assess Beta-cell stress using proinsulin/C-peptide levels, and test immune responses by examining cytokine levels and frequency, phenotype and function of T cell markers in peripheral blood. RESULTS/ANTICIPATED RESULTS: Thus far, we have enrolled 3 participants, 1 has completed the study. Baseline assessments indicate that we have technical feasibility of performing the above studies and measurements. Recruitment and enrollment are ongoing. We hypothesize that the use of HAMS-AB in newly diagnosed youth with T1D will (i) improve the gut microbiome profile, (ii) increase SCFA production, (iii) improve overall glycemia and Beta-cell function and (iv) modulate the immune system and mitigate autoimmunity. DISCUSSION/SIGNIFICANCE OF FINDINGS: Given the failure to develop a cure for T1D despite multiple completed intervention studies and the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, prebiotics such as HAMS-AB may offer a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.

OBJECTIVES/GOALS: Clinical trials demonstrate that axillary lymph node dissection (ALND) is unnecessary for most breast cancer patients with 1-3 involved nodes, but whether this is true for those with ILC is unknown. We evaluate the impact of ALND on recurrence-free survival (RFS) in ILC and 1-3 positive nodes. METHODS/STUDY POPULATION: We performed a retrospective cross-sectional analysis of patients with ILC treated between 1992-2019 at our institution. All patients received either sentinel lymph node biopsy (SLNB) or ALND and underwent either breast conservation surgery (BCS) or mastectomy. The primary outcome was RFS, defined as the absence of locoregional or distant recurrence. RESULTS/ANTICIPATED RESULTS: Of 496 cases, 250 (50.4%) underwent BCS, and 246 (49.6%) underwent mastectomy. A total of 93% of patients were hormone receptor positive, and 89% had low or intermediate grade disease. Among patients with 1-3 positive nodes, there was no significant difference in 5- and 10-year RFS based on receipt of ALND for both BCS and mastectomy cohorts. Using a multivariate model, we found no association between ALND and RFS overall (HR = 0.98, 95% CI 0.36-2.7, p>0.20) and among those with 1-3 positive nodes (HR = 0.60, 95% CI 0.12-3.4, p>0.20). DISCUSSION/SIGNIFICANCE OF IMPACT: These findings support the safety of omitting ALND in patients with ILC and 1-3 positive nodes, regardless of whether they receive BCS or mastectomy. Further studies of axillary management in ILC, including imaging tools to predict nodal involvement and response to therapy, are warranted.

OBJECTIVES/GOALS: To evaluate the usability of a HIE interface design among community pharmacists and technicians to identify opportunities for design improvements METHODS/STUDY POPULATION: Pharmacists and pharmacy technicians employed at Indiana community pharmacies participated in formative usability testing, via a Rapid Usability Evaluation (RUE), with an interactive, PDF prototype of the HIE interface. Participants were video-recorded to capture first impressions on the usability of the HIE prototype via the think aloud technique. Each participant had up to 1 hour to complete 4 clinical scenarios. Afterwards, participants completed the System Usability Scale (SUS; scale 0–100, with 100 being the best) to rate their satisfaction with the HIE prototype. RESULTS/ANTICIPATED RESULTS: Across 3 community pharmacies, 16 individuals participated in usability testing: 8 pharmacists and 8 technicians. The average SUS score for the HIE interface across participants from all sites was 70. Pharmacists on average scored the interface higher than technicians, 74 vs. 65, respectively. Initial findings from one pharmacy revealed that both pharmacists and technicians expressed a desire for improved efficiency (i.e. fewer clicks ) to access HIE data, alternative placement of HIE links within existing systems, and improved navigation to exit HIE links. DISCUSSION/SIGNIFICANCE: Initial results reveal opportunities to improve the HIE interface usability. Findings will inform design improvements to the interface and the creation of a toolkit to support the sustainable and scalable participation in HIE by community pharmacies.

ABSTRACT IMPACT: If successful, this program can provide a scalable, patient-centered intervention to help patients taper off opioid medications in primary care settings. OBJECTIVES/GOALS: Tapering of chronic opioid therapy is often desirable but challenging in primary care and specialty clinics that lack behavioral health expertise. The objective of this pilot study is to determine the feasibility of testing a peer-delivered pain self-management program to assist primary care patients through an opioid taper. METHODS/STUDY POPULATION: To provide critical support to patients and providers during opioid medication tapering, we propose to conduct a 40 patient randomized controlled pilot of a 12-week telecare collaborative care program administered by a psychiatrist and peer recovery specialist team. The intervention will incorporate a validated positive psychology intervention for treating chronic pain. Additionally, participants will be invited to participate in semi-structured individual interviews to discuss their experience in the trial, what worked well, what could be improved, and potential strategies to bolster recruitment of additional patients in future studies. RESULTS/ANTICIPATED RESULTS: Our primary aim is to determine the effectiveness of our intervention in facilitating opioid medication weaning, with reduction in opioid dose as the primary outcome. Our secondary aims will be to assess pain outcomes, adherence to tapering, patient satisfaction, and barriers to adherence as described by patients. DISCUSSION/SIGNIFICANCE OF FINDINGS: This trial proposes a novel collaborative care approach for opioid weaning using proven, easy-to-deliver positive psychology tools for pain management that, if successful, could be implemented broadly in many clinics struggling to safely reduce opioid prescribing.

Objectives/Goals: Early identification and profiling of planned studies is a critical administrative challenge in providing timely support for clinical trials. Here we describe the collaborative design and development of a clinical trial tracking dashboard to enhance support and quality improvement for investigator-initiated clinical trials at our institution. Methods/Study Population: Trial-CARE organized a workgroup with key stakeholders from WashU business units that manage grants, information technology, bioinformatics, data repository stewardship, and clinical trial support. The workgroup strategized next steps in a “proof-of-concept” effort to determine whether NIH investigator-initiated clinical trial metrics would be accessible via the WashU Data Warehouse. The WashU Data Warehouse is a data repository that pulls in pre-award and post-award data from sources such as the WashU Research-Grant Management System (RMS) and the NIH Reporter Tool. The proof-of-concept findings lead to implementing a plan for Phase 1 of the design, development, and piloting of a visual dashboard to track and offer targeted and timely support to NIH investigator-initiated clinical trials at WashU. Results/Anticipated Results: WashU currently has 217 grants submitted and 114 grants awarded for NIH clinical trials. In the proof of concept, we confirmed and successfully matched over 100 awarded NIH investigator-initiated clinical trials at WashU across RMS and the NIH Reporter Tool. We determined Phase I of the dashboard would track clinical trial data from these two sources via the WashU Data Warehouse. The pilot of Phase I of the dashboard will begin in February 2025. We also identified mission critical data elements not accessible via the WashU Data Warehouse (e.g., enrollment diversity, IND, and IDE). The plan to procure this data will require continued stakeholder support in Phase II of the dashboard to (1) expand data capture in RMS and (2) ingest additional data into the WashU Data Warehouse from RMS or new systems (e.g., ClinicalTrials.gov). Discussion/Significance of Impact: Early access to robust data about NIH investigator-initiated clinical trials via our newly created Phase I dashboard will better position our centralized service cores to support trial success, compliance, and quality improvement across the lifecycle of these clinical trials. In Phase II, we plan to expand the data available in the dashboard.

OBJECTIVES/GOALS: The overarching goal of the Mayo Clinic in Florida Clinical Research New Hire Training Programis to create a standardized work force development model that ensures all new research coordinators receive the same high-quality training and can perform their role. METHODS/STUDY POPULATION: Mayo Clinic implemented a comprehensive six-week in-class training program to teach research coordinators how to conduct clinical research studies and trials. A multi-disciplinary team with expertise in education, operations, study coordination, and human resources assisted in development. The program approaches education through the lens of application. Staff start on designated hire dates and have an assigned trainer, allowing them to complete the program in cohorts and build connections with one another. During the program, they complete assignments, checkpoints, and shadow within their units. At the conclusion, they take a one-on-one assessment with a trainer to confirm they can work independently. If a learner cannot pass, the trainer and supervisor implement a learning plan targeting their needs. RESULTS/ANTICIPATED RESULTS: The program has had 110 graduates since its April 2022 inception, with a steady improvement in learner satisfaction scores. Based on the question “My site’s new hire education program was good,” with 5 being strongly agree and 1 being strongly disagree, learners rate the current iteration as 4.38. The program has a positive correlation with retention and favorable quality reviews. 23.8% of new coordinators hired from April of 2021 to March of 2022 left within the first year. From April 2022 to September 2023, the first-year turnover rate fell to 14.55%. Additionally, 43% of quality reviews completed for graduates required no follow-up, compared to 35% of staff hired before implementation of the program. Only 5% of reviews for graduates required urgent follow-up, compared to 15% of those completed for existing staff. DISCUSSION/SIGNIFICANCE: Research Coordinators who complete the training program report a higher confidence level and demonstrate they can perform their role. The effects of our program have been so pronounced that the curriculum is being translated within Clinical Research across all of Mayo Clinic and our Florida site is researching ways to market it outside of Mayo Clinic.

OBJECTIVES/GOALS: Military personnel are at significantly greater risk for developing tinnitus, due to increased exposure to acoustic trauma. Many psychiatric disorders are common among individuals with chronic tinnitus, including posttraumatic stress disorder (PTSD). Although tinnitus and PTSD are clearly different, research supports the notion of shared mechanisms between both disorders. First, there are overlapping symptoms between tinnitus-related distress and PTSD, including irritability, distorted cognitions, persistent negative emotional states, diminished interests in activities, exaggerated startle response, sleep disturbance, concentration problems, and hypervigilance. Second, tinnitus and PTSD are highly comorbid with one another, whereas 34% of veterans with tinnitus also carry a PTSD diagnosis. Third, those with both disorders are significantly more emotionally impaired compared to those with tinnitus and any other psychiatric disorder. Lastly, neuroimaging research has shown similar regions within the auditory vigilance network are implicated among those with tinnitus, and separately, among combat PTSD patients, suggesting shared neurobiological mechanisms between both disorders. Though we are aware that tinnitus and comorbid PTSD presents as a significantly greater clinical concern, the relationship between tinnitus-related distress and PTSD symptomotology it is still unknown. Canonical correlation analyses will be conducted to examine the relationship between tinnitus-related distress and PTSD among veterans as a part of a larger clinical trial for posttraumatic headache. Results of the study will shed light on the relationship between tinnitus-related distress and PTSD, and may suggest a different phenotype for those with both disorders. Researchers and clinicians will further understand and conceptualize the relationships among the cognitive, emotional, and behavioral symptoms associated with tinnitus and PTSD, both individually and conjointly. METHODS/STUDY POPULATION: Baseline data (N = 112) from a larger clinical trial examining the effectiveness of two different psychotherapies for the alleviation of posttraumatic headache was examined. The primary aim of this project was to evaluate the relationship between tinnitus-related distress and PTSD based on the eight subscale scores of the Tinnitus Functional Index (TFI) and the four scales of the Clinician Administered PTSD Scale for the DSM-5 (CAPS-5), respectively. To address this aim, canonical correlation analysis was used where the tinnitus-related symptom subscales made up one variable set and PTSD symptom subscales made up the second variable set. First, we evaluated the overall model fit based on Wilks Lambda to determine if the two variable sets were related at the p < .05 level. Next, we evaluated the canonical correlations (comparable to an eigenvalue) for each canonical dimension to determine the required number of significant canonical dimensions (or latent constructs) that were necessary to understand the association between the two variable sets. Finally, the standardized canonical coefficients, which are analogous to regression coefficients, evaluate the magnitude of variate relationships and determine which subscales best describe significant canonical dimensions. RESULTS/ANTICIPATED RESULTS: Prior to the canonical correlation analysis, total score descriptive statistics and subscale score zero-order correlations were carried out. The CAPS-5 total score was 33.24 (SD = 9.39) and the TFI total score was 50.81 (SD = 21.88) in this sample. Interpretation of the zero-order correlations indicated that TFI Relaxation subscale was the only tinnitus-related subscale moderately associated with a PTSD subscale (i.e., Reexperiencing, r = .35). Canonical correlation omnibus model fit analysis via the Wilks Lambda overall multivariate test indicated that the tinnitus variable set was significantly associated with the PTSD variable set, F = 1.55, p = .04. Evaluation of the canonical correlations indicated that one dimension was significant in explaining the relationship between the two variable sets and accounted for 25% of the overall variance, F = 1.55, p < .04, R2 = .249. Standardized canonical coefficients indicated that the PTSD subscales Reexperiencing (b = 0.64) and Negative Alterations in Cognition and Mood (b = 0.55) were the most representative of the identified canonical dimension. In terms of the TFI, the Relaxation (b = 1.28) and Sleep (b = 0.72) subscales appeared to be most related to the canonical dimension. The TFI subscales Auditory Difficulty (b = −0.30) and Quality of Life (b = 0.30) also appeared to be related the canonical dimension to a lesser degree. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings support prior research suggesting particularly deleterious functional outcomes among individuals with comorbid tinnitus and PTSD. Results of this study suggest a latent variable that can explain the unique experience of individuals with both disorders. This latent variable consists of two PTSD constructs: Reexperiencing traumatic events (i.e., flashbacks, nightmares, intrusive memories), and Negative Alterations in Cognition and Mood (i.e., self- and other-blame, strong negative feelings, loss of interest, feeling distant). This latent variable also consists of two tinnitus-related constructs: Sleep (i.e., trouble falling and staying asleep, peaceful sleep) and Relaxation (i.e., ability to relax, enjoyment of peace and quiet). Auditory Difficulty (i.e., hear clearly, understand people) and Quality of Life (i.e., social activities, relationships, difficulty performing tasks) also contributed to the latent variable, but to a lesser degree. It is suggested that the constellation of symptoms related to the latent variable is a Dysphoric Factor, unique to individuals with PTSD, tinnitus, and posttraumatic headache. It may be necessary to incorporate different techniques into existing evidence-based treatments for both tinnitus and PTSD, for optimal symptom improvement.

OBJECTIVES/SPECIFIC AIMS: The goal of this abstract/presentation is to share lessons learned from participation in the NIH SBIR I-Corps Train-The-Trainer Program, discuss our experiences offering programs at our local institutions, and communicate our plans to develop an I-Corps@NCATS program that can be disseminated across the CTSA network. We believe that an I-Corps@NCATS program will enhance the process of scientific translation by taking best practices from NSF I-Corps and adapting the program to meet the needs of biomedical scientists in academic medical centers. By integrating I-Corps@NCATS training, we hypothesize that the clinical and translational investigator base will be better prepared to identify new innovations and to accelerate translation through commercialization. METHODS/STUDY POPULATION: The diverse, interdisciplinary team of investigators involved in this project span 9 CTSA Hubs, including UAB, Rockefeller, UC Denver, HMC-Penn State, UMass, UC Davis, Emory/Georgia Tech, Miami and Michigan. This team was funded by NCATS in 2015–2016 to participate in the CTSA I-Corps Train-The-Trainer Program in conjunction with the NIH-SBIR/STTR I-Corps national program. The goals were to observe the curriculum, interact with and learn from the NSF National Teaching Team and begin implementation of similar programs at our home institutions. Our I-Corps@NCATS team has been holding monthly, and more recently weekly, conference calls to discuss our experiences implementing local programs and to develop a strategy for expanding CTSA offerings that include innovation and entrepreneurship. Our experience revealed several challenges with the existing NSF/NIH I-Corps program offerings: (1) there is no standard curriculum tailored to academic clinical and translational research and biomedical innovations in the life sciences, and (2) the training process to certify instructors in the I-Corps methodology is a much more rigorous and structured process than just observing an I-Corps program (eg, requires mentored training with a national NSF I-Corps trainer). Our team is proposing to address these gaps by taking best practices from NSF I-Corps and adapting the program to create the I-Corps@NCATS Program, tailored to meet the needs of researchers and clinicians in academic medical centers. RESULTS/ANTICIPATED RESULTS: There are 3 primary anticipated results of our project. First, develop a uniform curriculum for the I-Corps@NCATS Program using the National Teaching Team of experts from the NIH’s SBIR I-Corps program. Second, build the I-Corps@NCATS network capacity through a regional Train-The-Trainer Program. Third, develop a set of common metrics to evaluate the effectiveness and impact of the I-Corps@NCATS Program across the community of CTSA Hubs and their respective collaborative networks. DISCUSSION/SIGNIFICANCE OF IMPACT: Over the past 10 years, CTSA Hubs have accelerated science by creating/supporting programs that provide research infrastructure, informatics, pilot funding, education/training, and research navigator services to investigators. These investments help to ensure that we are “doing science right” using the best practices in clinical research. Even so, it is equally important to make investments to ensure that we are “doing the right science.” Are our investigators tackling research problems that our stakeholders, patients, and communities want and need, to make sure that our investments in science have real-world impact? In order to accelerate discoveries toward better health, scientists need to have a better way to understand the needs, wants and desires of the people for whom their research will serve, and how to overcome key obstacles along the path of innovation and commercialization. To fill this gap, we propose that the CTSA Hubs should include in their portfolio of activities a hands-on, lean startup program tailored after the highly successful NSF Innovation Corps (I-Corps) program. We hypothesize that by adapting the NSF I-Corps program to create an I-Corps@NCATS program tailored to medical research, we will better prepare our scientists and engineers to extend their focus beyond the laboratory and broaden the impact of their research. Investigators trained through I-Corps@NCATS are expected to be able to produce more innovative ideas, take a more informed perspective about how to evaluate the clinical and commercial impact of an idea, and quickly prototype and test new solutions in clinical settings.