Objectives/Goals: This study looks to investigate the relationship between body mass index (BMI) and the treatment effect of cancer immunotherapies. Specifically, we will assess whether there is a significant difference in survival curves associated with varying BMI levels and track trends in BMI reporting over the last decade. Methods/Study Population: An individual patient meta-analysis will be conducted by reanalyzing raw data of phase 3 cancer immunotherapy trials (2013–2023) accessed via the database Vivli. Prior to making a formal data request, an exploratory search will be first done through clinicaltrials.gov to assess viability. Studies that report baseline BMI and treatment efficacy will be included. BMI will be analyzed as a continuous variable, with survival curves compared across different BMI ranges using restricted mean survival time and log-rank tests. Trials will be stratified by drug class and adjusted for race, age, and gender to account for potential sources of confounding/bias. Results/Anticipated Results: Results are currently still a work in progress as I am in the process of getting the dataset from Vivli. I anticipate that treatment effects in cancer immunotherapies will vary significantly by BMI. Furthermore, I expect to see significant disparities in survival outcomes between patients assigned to a low and high BMI category. Lastly, trends in the reporting of BMI across immunotherapy trials are expected to be inconsistent which highlights the need for more standardization in clinical trial datasets. Discussion/Significance of Impact: This study should address critical knowledge gaps in how BMI level is associated with immunotherapy outcomes. These findings could potentially guide personalized treatment strategies and highlight the importance of standardizing the variables clinical trials chose to report.

OBJECTIVES/GOALS: A clinical research coordinator (CRC) digital badge offers a novel approach to addressing the ongoing shortage of CRCs at academic medical centers. We sought to pilot this low-cost, short-term training digital badge to train entry level CRCs and to attract a diverse pool of individuals. METHODS/STUDY POPULATION: Experienced clinical research professionals outlined competencies needed by study coordinators working in an academic center using a Delphi approach. The competencies aligned with 6 of the 8 domains established by the Joint Taskforce for Clinical Trial Competencies. Five course modules were created in a standardized format consisting of instructional videos, handouts, and a 25-question quiz (passing grade: 90%) which was hosted in the university learning management system. Beta testers were recruited to complete surveys at the conclusion of each module addressing both module performance and content accuracy. An item analysis was performed on the 25-question quiz. RESULTS/ANTICIPATED RESULTS: Nine volunteers were recruited for the pilot. Seven completed the badge. All participants, with years of experience from 0 to over 10 in clinical trials, found the course to be informative. The majority (84%) of responses on course logistics were positive or neutral. The quiz item analysis identified most questions (86%) as either Easy or Neutral, which is ideal for a Level 1 Badge addressing foundational skills. Forty percent of the quiz questions scored high on the Discrimination Index, indicating that the quiz could identify those who performed well and those challenged by the quizzes. One negative comment received stated that course was too intense to be completed in 4 weeks. DISCUSSION/SIGNIFICANCE: The results of this pilot study demonstrated that this badging course offers a low cost, easily accessible option for recruiting and training entry level clinical research professionals. The proof-of-concept study encouraged our initiation of the program and attempt to broaden our reach.

OBJECTIVES/GOALS: To tackle population-level health disparities, quality dashboards can leverage individual socioeconomic status (SES) measures, which are not always readily accessible. This study aimed to assess the feasibility of a population health management strategy for colorectal cancer (CRC) screening rates using the HOUSES index and heatmap analysis. METHODS/STUDY POPULATION: We applied the 2019 Minnesota Community Measurement data for optimal CRC screening to eligible Mayo Clinic Midwest panel patients. SES was defined by HOUSES index, a validated SES measure based on publicly available property data for the U.S. population. We first assessed the association of suboptimal CRC screening rate with HOUSES index adjusting for age, sex, race/ethnicity, comorbidity, and Zip-code level deprivation by using a mixed effects logistic regression model. We then assessed changes in ranking for performance of individual clinics (i.e., % of patients with optimal CRC screening rate) before and after adjusting for HOUSES index. Geographical hotspots of high proportions of low SES AND high proportions of suboptimal CRC screening were superimposed to identify target population for outreach. RESULTS/ANTICIPATED RESULTS: A total of 58,382 adults from 41 clinics were eligible for CRC screening assessment in 2019 (53% Female). Patients with lower SES defined by HOUSES quartile 1-3 have significantly lower CRC screening compared to those with highest SES (HOUSES quartile 4) (adj. OR [95% CI]: 0.52 [0.50-0.56] for Q1, 0.66 [0.62-0.70] for Q2, and 0.81 [0.76-0.85]) for Q3). Ranking of 26 out of 41 (63%) clinics went down after adjusting for HOUSES index suggesting disproportionately higher proportion of underserved patients with suboptimal CRC screening. We were able to successfully identify hotspots of suboptimal CRC (area with greater than 130% of expected value) and overlay with higher proportion of underserved population (HOUSES Q1), which can be used for data-driven targeted interventions such as mobile health clinics. DISCUSSION/SIGNIFICANCE: HOUSES index and associated heatmap analysis can contribute to advancing health equity. This approach can aid health care organizations in meeting the newly established standards by The Joint Commission, which have elevated health equity to a national safety priority.

OBJECTIVES/SPECIFIC AIMS: (1) Determine the anti-proliferative effect of Copanlisib (α/δ PI3 kinase inhibitor) in CTCL cell lines and synergy with other anti-tumor drugs such as HDAC inhibitors. (2) Determine the effect of Copanlisib treatment on downstream targets of the PI3K/AKT/mTOR pathway. METHODS/STUDY POPULATION: We will test the anti-proliferative effect of Copanlisib on the cell lines H9 and HH, which are well characterized for evaluating new therapies for CTCL (Netchiporouk et al., 2017). We will also test the anti-proliferative effect of Copanlisib in combination with HDAC inhibitors on CTCL cell lines. Cell Titer Glo (Promega) will be used for the proliferation assay. Briefly, Cell-Titler Glo will be added after 24, 48, and 72 hours and luminescence will be measured as a % of maximal growth. Inhibitory effect will be determined by comparison to % growth of the control cultures without Copanlisib treatment. Our next objective is to determine the effect of Copanlisib treatment on downstream targets of the PI3K/AKT/mTOR pathway using Western blot analysis. In brief, 30 μg of each lysate will be subjected to 4%–12% gradient SDS-PAGE gel eletrophoresis. All primary antibodies were purchased from Cell Signaling Technology. Membranes will be washed with TBST and incubated with 1:10,000 dilution of IRDye-conjugated secondary antibody (Licor) for 1 hour. Results will be expressed as relative intensity: the intensity of each band adjusted to that of GAPDH. Experiments will be done in triplicate and 1-way analysis of variance followed by multiple comparison test will be applied to compare the cell proliferation between different treatment groups. RESULTS/ANTICIPATED RESULTS: Previous results from the Ai lab have demonstrated the importance of the PI3 kinase signaling cascade using high-throughput proliferation assays and siRNA knockdown of individual and double PI3 kinase isoforms (unpublished data). So far I have successfully established culture of HH and H9 cells in 96 well plates (100,000 cells/200 μL). We are titrating Copanlisib at doses from 20 nm to 20 μM. Initial results suggest a promising anti-proliferative effect and currently we are optimizing the most effective pharmacologic dose. Thus we anticipate that Copanlisib will exhibit a potent anti-proliferation activity in CTCL cell lines. H9 and HH cell lysates have been collected and preserved for Western blot analysis. We anticipate that Copanlisib treatment will significantly decrease the phosphorylation of AKT and 4EB-P1, both downstream targets of PI3 kinase signaling. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings will elucidate the importance of the PI3 kinase/AKT/mTOR pathway in tumor proliferation in CTCL. Identifying the importance of specific isoforms of PI3 kinase in CTCL will allow for more targeted selection of treatment. Copanlisib targets α and δ isoforms of PI3K and is newly approved by the FDA for low grade B cell lymphoma. Our results seek to quantify the anti-proliferative effect of Copanlisib and determine an on-target mechanism of action by investigating the drug’s effects on downstream signaling molecules of the PI3 kinase pathway. This project will elucidate the disease process of CTCL and provide important insight for its management.

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to determine if trimethylamine N-oxide (TMAO) alone could acutely alter cardiac contractile function on a beat-to-beat basis. METHODS/STUDY POPULATION: CD1 adult mouse hearts were extracted, attached to a force transducer, oxygenated, and paced within an organ bath. Changes in contractility were measured after pipetting or reverse perfusing TMAO through the aorta via a modified Langendorff apparatus to facilitate TMAO delivery into the myocardium. To determine if our findings translated to the human heart, we performed contractility experiments using human right atrial appendage biopsy tissue retrieved during cardiopulmonary bypass procedures. To investigate whether TMAO alters contractile rate, in a separate series of experiments, the atria and sinoatrial node of isolated hearts were kept intact to allow for spontaneous beating without artificial pacing and were treated with TMAO or vehicle. In addition, intracellular calcium measurements were performed on spontaneously beating embryonic rat cardiomyocytes after TMAO or vehicle treatment. RESULTS/ANTICIPATED RESULTS: We found acute exposure to TMAO, diluted into the organ bath, increased average contraction amplitude 20% and 41% at 300 µM and 3000 µM, respectively (p<0.05, n=6). Langendorff reverse perfusion of mouse hearts ex vivo with 300 µM TMAO generated an even greater response than nonperfusion peripheral exposure and increased isometric force 32% (p<0.05, n=3). Consistent with what we observed in mouse hearts, incubation of human atrial muscle tissue with TMAO at 3000 µM increased isometric tension 31% compared with vehicle (p<0.05, n=4). TMAO treatment (3000 µM) also increased average beating frequency of ex vivo mouse hearts by 27% compared with vehicle (p<0.05, n=3) and increased the spontaneous beating frequency of primary rat cardiomyocytes by 13% compared with vehicle treatment (p<0.05, n=4). DISCUSSION/SIGNIFICANCE OF IMPACT: TMAO, at pathological concentrations, directly increases the force and rate of cardiac contractility. Initially, these inotropic and chronotropic effects may be adaptive during CKD; however, chronic increases in isometric tension and beating frequency can promote cardiac remodeling and heart failure. Further translational studies are needed to understand the intricate relationship between the microbiome, kidneys, and heart and to examine if TMAO represents a therapeutic target for reducing cardiovascular mortality in CKD patients.

ABSTRACT IMPACT: Melatonin use could alleviate virus-induced respiratory illnesses. OBJECTIVES/GOALS: Melatonin was identified as a potential repurposable drug in the fight against SARS Cov-2. Its ability to attenuate some virus inoculation effects raises the question whether melatonin use could alleviate virus-induced respiratory illness. Here we evaluated the occurrence of respiratory conditions in melatonin users and non-users surveyed. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to evaluate whether melatonin may be associated with reduced viral respiratory disease burden. First, all subjects reporting melatonin use (1996-2017) were collected along with records for all subjects reporting respiratory diseases as identified by consolidated ICD-9/10 codes. Second, all diagnosis codes were retrieved for all individuals identified in the first step. In total there were 201,490 occurrences of the specified conditions among 180,468 unique individuals. The relative risk of specific respiratory disease occurrence was computed for melatonin users and non-users. Population estimates for melatonin use were also determined. RESULTS/ANTICIPATED RESULTS: Among 221 melatonin users, 132 had at least one respiratory illness. Among the 180,468 total subjects reporting at least one respiratory condition, melatonin use was associated with a lower rate of the common cold, pharyngitis, strep throat, scarlet fever, and sinusitis. Furthermore, melatonin was associated with a significantly reduced risk of common cold (RR 0.760, CI 0.587-0.985) and sinusitis (RR 0.407, CI 0.186-0.890). Due to low subject counts, the reduced risk observed for scarlet fever and strep throat was not considered significant. Melatonin users had a higher relative risk of allergic rhinitis (RR 1.393, CI 1.043-1.862) and asthma (RR 2.166, CI 1.672-2.806), probably due to melatonin active prescribing in these patients as sleep aid. DISCUSSION/SIGNIFICANCE OF FINDINGS: Although melatonin showed a lower relative risk of certain viral respiratory conditions, the low melatonin user numbers and their heterogeneous distribution over the time interval led to highly variable population estimates. Yet, our data suggests that melatonin may alleviate viral respiratory illness and deserves further investigation.

OBJECTIVES/GOALS: This investigation aimed to mitigate barriers to father involvement in communication intervention for children with ASD and contribute to clinical practice by examining the effects of a hybrid parent coaching intervention for fathers of children with ASD that is tailored to fit both father’s interaction and communication styles as well as individual child characteristics. The Hybrid Father Communication Coaching (HFCC) combined online parent coaching lessons with in-person father-child aquatics sessions in order to increase father’s use of responsive verbal and play strategies. Distal effects on child communication were also investigated. METHODS/STUDY POPULATION: A single subject, multiple baselines across strategies experiment was conducted with one dyad (i.e., father, child with ASD). In the present study, a hybrid father coaching model was used. Parent communication coaching sessions were delivered online, and weekly, father-child aquatics sessions were conducted in person, to provide opportunities for the father to use three targeted responsive strategies (i.e., follow-in comments, follow-in directives, responsive object play) during father-child physical activity. Collateral measures of child communication skills were also investigated. Single subject designs are particularly suitable for autism interventions, as they allow for experimental control with participants who are from heterogeneous populations (McReynolds and Kearn, 1983). The child participant was 5 years, 6 months at the start of intervention and had previously received a community diagnosis of ASD. Throughout the duration of the study, the child attended full-time kindergarten and received in-school speech-language therapy, as a well as 18-20 hours per week of Applied Behavioral Analysis intervention, occupational therapy, physical therapy and speech-language therapy after school. The participating father was a biological parent who resided with the child continuously since birth. The participating father had no other formal parent training in communication intervention before participating. RESULTS/ANTICIPATED RESULTS: The hybrid father communication coaching program (HFCC) yielded positive results for both father and child participant. The father quickly achieved a high level of competency using two of the three, targeted strategies (i.e., follow-in comments, follow-in directives). However, use of a third strategy (i.e., responsive object play) was not maintained above baseline levels. The follow-in comments strategy was used by the participating father more frequently than the follow-in directives strategy. Small increases were documented for child use of spontaneous single words across intervention phases and increased single word use over was maintained eight weeks following intervention. DISCUSSION/SIGNIFICANCE OF IMPACT: The present study provided information regarding the efficacy of a clinically relevant hybrid parent-coaching program, tailored to both father and child characteristics, to enhance fathers’ use of responsive strategies and increase communication skills for children with ASD.

OBJECTIVES/SPECIFIC AIMS: Recent data suggest that fecal microbiota and intraluminal organic acids may play an important role in irritable bowel syndrome (IBS) pathogenesis through effects on intestinal secretion and motility. Understanding their contribution will be critical in developing diagnostic and treatment strategies. Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in IBS patients and controls and (2) investigate the association between colonic transit and fecal microbiota in IBS patients and controls. METHODS/STUDY POPULATION: We propose a prospective investigation of fecal organic acids, colonic transit and fecal microbiota in 36 IBS patients and 18 healthy controls. The target population will be adults ages 18–65 years meeting Rome IV criteria for IBS (both diarrhea predominant and constipation-predominant, IBS-D, and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0x the upper limit of normal, (b) prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy>6 months before study initiation, (c) ingestion of prescription, over the counter, or herbal medications affecting gastrointestinal transit or study interpretation within 6 months of study initiation for controls or within 2 days before study initiation for IBS patients, (d) pregnant females, (e) antibiotic usage within 3 months prior to study participation, (f) prebiotic or probiotic usage within the 2 weeks prior to study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid (SCFA) excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100-g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis and frozen. Frozen aliquots will be shipped to the Metabolite Profiling Facility at Purdue University and the Mayo Clinic Department of Laboratory Medicine and Pathology for SCFA and bile acid measurements, respectively. Analysis of fecal microbiota will be performed in the research laboratory of Dr. David Nelson in collaboration with bioinformatics expertise affiliated with the Nelson lab. Colonic transit time will be measured with the previously validated method using radio-opaque markers. Generalized linear models will be used as the analysis framework for comparing study endpoints among groups. RESULTS/ANTICIPATED RESULTS: This study seeks to examine the innovative concept that specific microbial signatures are associated with increased fecal excretion of organic acids to provide unique insights on a potential mechanistic link between altered intraluminal organic acids and fecal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: Results may lead to development of targets for novel therapies and diagnostic biomarkers for IBS, emphasizing the role of the fecal metabolome.

OBJECTIVES/GOALS: Commercial health insurance payers invest in disease management programs (DM) to coordinate care for complex patients. To overcome gaps in connecting patients hospitalized with heart failure to DM, we implemented a novel warm handoff referral between hospital providers and payer DM using the Implementation Research Logic Model (IRLM). METHODS/STUDY POPULATION: A research and quality improvement team collaborated with champions from one hospital and three payers to build and pilot an inpatient-based referral for hospitalized patients with heart failure who were beneficiaries of one of three payers. The standard process of payers initiating contact with patients by phone was restructured to enable inpatient teams to initiate referrals by screening eligible patients prior to discharge. Between August 2020 and October 2021, 285 patients were hospitalized and eligible for screening. Patient registries were built to track patient referral, eligibility, and enrollment status. Monthly stakeholder meetings were used to collect referral rates and review barriers and facilitators related to implementation. RESULTS/ANTICIPATED RESULTS: Of the 63.6% (N=168) patients screened, 31.4% (N=83) were referred, 17.4% (N=46) declined referral, and 14.8% (N=39) were deemed ineligible by payers. Inpatient screenings were challenged by variability across five units with incomplete/missed referrals, primarily attributed to COVID-19-related staff shortages. Payers were challenged by delayed/incomplete referrals and varying access to the hospitals EHRs. Building patient registries helped inpatient champions track eligibility and referral status, and centralizing screening to one champion improved screening rates and reduced incomplete referrals. Additional challenges being addressed include clarifying each payers unique eligibility requirements, refining payers review of referral emails, and creating descriptions of DM for patients. DISCUSSION/SIGNIFICANCE: Implementing inpatient-based DM referrals requires patient and staff engagement, real-time data sharing, and iterative process improvement. Referrals using robust health IT systems could improve patient engagement by connecting payers, providers, and patients; and improve evaluation efforts with real-time process and outcome data.

OBJECTIVES/GOALS: The goal of this project was to create a professional network for the Rutgers Clinical Research Management master’s program to foster relationships between potential and current clinical research professional workforce members. A professional network provides an opportunity for its members to stay continuously engaged in the community. METHODS/STUDY POPULATION: Two Qualtrics surveys were created after researching the social presence of the Rutgers SHP community, similar master-level programs, clinical research professional networks, and general social landscapes. The surveys were sent through LinkedIn and email with telephone reminders to the Rutgers SHP CRM community to gather demographic information, preferred method of engagement, and desired network content. In addition, six alumni and two faculty SHP CRM members were interviewed via Zoom for further feedback. The data from these surveys was analyzed on excel and supported the creation of content and structure for the CRM Network. RESULTS/ANTICIPATED RESULTS: Survey results indicated 70% (n=20) of respondents preferred engagement through email or LinkedIn. Engagement topics included alumni/faculty news, workforce opportunities, and networking events. A LinkedIn page and website were created to highlight members’accomplishments and activities. An electronic quarterly newsletter was developed to expand the content with alumni and faculty editorials and future opportunities to engage with the Rutgers CRM program. Further data analysis revealed that 73% (n=16) preferred in-person vs remote events. A Facebook page was created to provide a forum for casual interactions that may lead to in-person opportunities. Seven participants volunteered to join the newly formed CRM Network Advisory Committee that will develop future content and manage the CRM Network. DISCUSSION/SIGNIFICANCE: The CRM Network was well received by the Rutgers CRM community as a tool to foster relationships between current and future clinical research professionals. Despite data limitations (small sample size and incomplete responses), the CRM Network was created and transferred to the Advisory committee for implementation and future expansion.

Objectives/Goals: Sexual minority populations (SMPs), including lesbian, gay, and bisexual groups, disproportionately encounter discriminatory experiences due to bi/homonegativity and systemic inequities across various social domains. We aim to understand how the neighborhood-level stressors and resilience sources differed across specific groups in SMPs. Methods/Study Population: Utilizing the NIH All of Us’ cloud-based platform, we selected cohorts self-identifying as gay (n  =  9,454), bisexual (n  =  15,284), lesbian (n = 5267), or straight (n  =  349,748). We explored multiple key measures of neighborhood-level stressors (e.g., neighborhood disorder, neighborhood cohesion, and environment index) and resilience sources (e.g., neighbor cohesion, social support), and other factors (e.g., food insecurity, housing insecurity, and housing instability) by their sexual orientations using analysis of variance or Chi-square analyses. Results/Anticipated Results: Our sample comprised 60.8% females and 37.5% males identifying as non-binary or transgender, with an average age of 55.6 years (SD  =  17.1). The racial composition was 56.0% White, 19.4% Black, 18.7% Hispanic, and 5.9% others (e.g., Asian, multiracial). Compared to straight individuals, SMPs reported high neighborhood stressors (e.g., disorder, worse environment) but lower neighborhood-level resilience sources (e.g., social support, cohesion). In addition, bisexual groups reported highest prevalence of housing insecurity (6.7% vs. 2.3%), housing instability (36.0% vs. 19.6%), and food insecurity (26.57% vs. 12.21%). Discussion/Significance of Impact: SMPs, particularly bisexual individuals, face greater neighborhood stressors and fewer resilience sources than their straight counterparts. These findings call for targeted interventions to address these disparities and promote health equity, using large-scale datasets to inform community-based solutions.

Objectives/Goals: This study examines prevalence of complete sample size justifications in publications in the top five clinical neurology journals. Secondary goals include comparing study designs and clinical populations to explore whether some may be more likely to include inadequate sample size considerations. Methods/Study Population: Recent studies (n  =  125) in Lancet Neurology, Alzheimer’s and Dementia, JAMA Neurology, Acta Neuropathology, and Brain will be evaluated. For each journal, the 25 most recent empirical articles between 2022 and 2023 will be examined for their inclusion of a justification and reproducible sample size calculation. Inclusion of components of an ideal sample size justification will be evaluated: effect size to be detected (standardized or unstandardized), alpha, power, and from where values were derived. Prevalence and completeness will be compared among study designs, clinical populations, and with regard to journal reporting requirements. Results/Anticipated Results: At the pilot review stage, 17 of 25 included studies had any kind of sample size justification, and only 3 studies had enough information to reproduce their sample size calculations. Retrospective studies included a sample size justification more frequently (81.8% vs. 57.1%), but prospective studies had more complete sample size justifications, when present. We hypothesize that sample size calculations will be more complete in reports of clinical trials and prospective cohort studies, compared to retrospective and cross-sectional designs. Based on our previous research, we do not expect that journal reporting requirements will affect completeness of sample size justifications. Discussion/Significance of Impact: Translational decision-making is informed in part by the robustness of current research. Transparency of sample size considerations in publications can contribute to the formation of less biased opinions of translational readiness and, subsequently, more efficient and effective translation.

OBJECTIVES/SPECIFIC AIMS: The development of new anti-cancer agents for children requires an inherently longer timeline than in adults. The 3+3 study design for Phase 1 dose escalation trials is commonly used to estimate the maximum tolerated dose and assess safety. The Rolling 6 study design was developed to shorten the study conduct timeline. METHODS/STUDY POPULATION: This study compares twenty Phase 1 COG Pilot and Phase 1 Consortium trials that employed the Rolling 6 design with hypothetical results under the assumption that a 3+3 design had been executed. The number of evaluable patients required to complete the study, number of DLTs, number of inevaluable patients, overall study duration, time suspended to enrollment (i.e., waiting for DLT evaluation), and DLT risk are compared between study designs using Wilcoxon’s signed rank test. RESULTS/ANTICIPATED RESULTS: The Rolling 6 study design required less time to complete the studies compared with 3+3 design (median 273 vs. 297 days, P = 0.01). In general, the Rolling 6 study design required more patients, had more inevaluable patients, and there were more dose limiting toxicity (DLT) events. However, there was no significant difference in DLT risk (median 0.15 vs. 0.17, P = 0.72). DISCUSSION/SIGNIFICANCE OF IMPACT: The Rolling 6 study design effectively shortens the study conduct timeline compared with the traditional 3+3 design for Phase 1 COG Pilot and Phase 1 Consortium trials without increasing the risk of toxicity.

OBJECTIVES/SPECIFIC AIMS: To describe the use of primary debulking surgery and neoadjuvant chemotherapy in advanced-stage ovarian cancer patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) over the period of 1 year. Specifically, identify a subset of patients that are medically eligible to be considered for surgery. Examine the ultimate treatment designation for those patients, assessing the application of the MSKCC resectability algorithm and its utility in guiding treatment choice. METHODS/STUDY POPULATION: Using the prospectively maintained Ovarian Cancer Database at MSKCC, we queried patients who presented for initial management of ovarian cancer from July 1, 2015 to June 30, 2016. All patients with stage IIIB-IV disease who received their primary treatment at MSKCC were included in our study. Patients needed to have pathology-confirmed ovarian cancer and all histological subtypes were included. Data were collected and analyzed in Excel. RESULTS/ANTICIPATED RESULTS: There were a total of 173 patients treated for stage IIIB-IVB ovarian cancer at MSKCC during the study period. Of those 98 patients received PDS, whereas 75 were directed to NACT, making MSKCC’s overall NACT rate 43.4% for the year we studied. Of the patients who received NACT, 19 met full Aletti Criteria at diagnosis, precluding them from being considered for surgery. In addition, 21 patients had medical contraindications to surgery, meaning that a total of 40 patients who were given NACT were not able to be considered for PDS. If we then take into account only the patients who were medically eligible for PDS, the rate of NACT at MSKCC drops to 23.1%, almost half of the original value. These medically eligible patients are the population that should be receiving an MSKCC resectability score. Of the 98 patients who underwent PDS, 73.5% had a preoperative resectability score calculated. Based on the algorithm, 81.3% of those patients were deemed to be “low risk” and 15.2% were deemed to be “high risk” of a suboptimal debulking. The algorithm dictates that all “high risk” patients who go on to PDS should undergo a laparoscopy first to assess for resectability and potentially avoid an unnecessary open procedure. Hundered percent of the “high risk” cases that were taken to the OR had an initial laparoscopy before proceeding with PDS. Overall, 93.1% of patients that underwent PDS had an optimal cytoreduction, or ≤1 cm residual disease at the conclusion of surgery. Of the 6 patients throughout the year that had a suboptimal outcome, or >1 cm residual disease, 3 were initially scored as “low risk,” 1 was scored as “high risk,” and 2 did not receive an MSKCC resectability score prior to their procedure. Of note, 3 of the suboptimal cases had unresectable disease in an anatomical location not accounted for in the resectability algorithm. DISCUSSION/SIGNIFICANCE OF IMPACT: The rates of PDS Versus NACT vary widely between institutions, and it is not always clear how calculations are made. High-volume centers likely see a higher percentage of sicker patients with more advanced disease, which could increase their rates of NACT as many of these patients are not eligible for surgery. It is important to standardize the way our field quotes NACT rates, and to understand how treatment decisions are being made at a given institution. PDS has a demonstrated survival benefit, and while we would ideally use this modality for all of our patients, there will always be a baseline percentage of patients who cannot be considered for the surgery. Since we will never be able to offer those patients PDS, our objective should be to identify patients who can be considered for the procedure and to work toward optimizing their outcomes. In this study we identified the population of patients who are truly the PDS Versus NACT cohort as they were eligible for both modalities. We then examined the application and utility of the MSKCC resectability algorithm in an attempt to further optimize treatment allocation. This scoring system was implemented at our hospital over the past year with the goal that 100% patients going on to PDS would receive a preoperative score. Unfortunately, 26.5% of PDS patients were not scored prior to their procedure. This makes it more difficult to evaluate the efficacy of the scoring system, especially considering 1/3 of the suboptimal cases were not scored. Had these patients received a score, they might have been deemed “high risk” and could have avoided a lengthy operation with a significant chance of a suboptimal outcome. In addition, it is important to note that 3 of the suboptimal PDS outcomes were initially scored as “low risk,” and 3 of the suboptimal outcomes were due to disease locations not accounted for in the original resectability algorithm. We will continue logging disease locations of suboptimal cases, it is possible that a certain disease location not in the scoring system is responsible for a significant portion of suboptimal outcomes. The resectability score model had an overall predictive accuracy of 0.756 when it was initially published, and we must continue tracking scores and outcomes to determine its validity when applied prospectively in our population. In order to accurately do so however, an emphasis should be made to ensure 100% of patients being considered for PDS receive a score going forward.

OBJECTIVES/SPECIFIC AIMS: (1) To evaluate clinical outcomes in mechanically ventilated patients with and without fever. We hypothesize that, after adjusting for confounding factors such as age and severity of illness: (a) In septic patients, fever will be associated with improved clinical outcomes. (b) In nonseptic patients, fever will be associated with worse clinical outcomes. (2) To examine the relationship between antipyretics and mortality in mechanically ventilated patients at risk for an acute lung injury. We hypothesize that antipyretics will have no effect on clinical outcomes in mechanically ventilated patients with and without sepsis. METHODS/STUDY POPULATION: This is a retrospective study of a “before and after” observational cohort of 1705 patients with acute initiation of mechanical ventilation in the Emergency Department from September 2009 to March 2016. Data were collected retrospectively on the first 72 hours of temperature and antipyretic medication from the EHR. Temperatures measurements were adjusted based on route of measurement. Patients intubated for cardiac arrest or brain injury were excluded from our primary analysis due to the known damage of hyperthermia in these subsets. Cox proportional hazard models and multivariable linear regression analyzed time-to-event and continuous outcomes, respectively. Predetermined patient demographics were entered into each multivariable model using backward and forward stepwise regression. Models were assessed for collinearity and residual plots were used to assure each model met assumptions. RESULTS/ANTICIPATED RESULTS: Antipyretic administration is currently undergoing analysis. Initial temperature results are reported here. In the overall group, presence of hypothermia or fever within 72 hours of intubation compared with normothermia conferred a hazard ratio (HR) of 1.95 (95% CI: 1.48–2.56) and 1.31 (95% CI: 0.97–1.78), respectively. Presence of hypothermia and fever reduced hospital free days by 3.29 (95% CI: 2.15–4.42) and 2.34 (95% CI: 1.21–3.46), respectively. In our subgroup analysis of patients with sepsis, HR for 28-day mortality 2.57 (95% CI: 1.68–3.93) for hypothermia. Fever had no effect on mortality (HR 1.11, 95% CI: 0.694–1.76). Both hypothermia and fever reduced hospital free days by 5.39 (95% CI: 4.33–7.54) and 3.98 (95% CI: 2.46–5.32) days, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: As expected, both hypothermia and fever increased 28-day mortality and decreased hospital free days. In our sepsis subgroup, hypothermia again resulted in higher mortality and fewer hospital free days, while fever did not have a survival benefit or cost, but reduced hospital free days. Antipyretic administration complicates these findings, as medication may mask fever or exert an effect on survival. Fever may also affect mechanically ventilated septic patients differently than septic patients not on mechanical ventilation. Continued analysis of this data including antipyretic administration, ventilator free days and progression to ARDS will address these questions.

OBJECTIVES/GOALS: Initiation of JUUL use by young adults is one of the most significant issues of concern within the debate on vaping. Despite the proliferation of products and the surge in prevalence, no studies have investigated individual-level interventions or prevention strategies for pod-mod use. METHODS/STUDY POPULATION: Participants (N = 947) were young adults (<30 years old) recruited from Amazon’s Mechanical Turk based on smoking (never, former, and current smokers) and JUUL use status (never and current users), resulting in 6 use groups. In a pre-post design, participants completed baseline assessments, were presented with a brief JUUL-specific educational intervention, and completed post-assessment measures. The one-page intervention provided basic information about JUUL and stated that JUUL is harmful to non-smokers but could be beneficial to smokers if they completely switch. Primary outcomes were changes in JUUL knowledge, perceived harmfulness, intentions for future use, and motivation to change. RESULTS/ANTICIPATED RESULTS: Participants (Mage = 26.1) were male (57%) and White (75%). Overall, the intervention increased JUUL-related knowledge, risk perceptions, commitment to quitting, and readiness to quit JUUL (ps<.01). Similarly, participants showed decreased interest in future JUUL use, interest in purchasing JUUL, and interest in future regular use (ps<.01). Non-JUUL users showed decreased interest in initiating JUUL use after viewing the intervention (p<.01). There were significant Time X Group interactions for JUUL-related knowledge (p<.001), with never JUUL/never smokers showing the greatest increase in product knowledge following the intervention. However, no other interaction effects were significant. DISCUSSION/SIGNIFICANCE OF IMPACT: The intervention was effective in increasing knowledge and risk perceptions while reducing intentions for future use. The intervention was most effective in increasing knowledge among non-users, suggesting that brief educational interventions may be useful tools for preventing pod-mod initiation. CONFLICT OF INTEREST DESCRIPTION: Dr. Carpenter has received consulting honoraria from Pfizer. All other authors have no conflicts to disclose.

ABSTRACT IMPACT: This work examines the association between diabetes mellitus and latent tuberculosis infection among a cohort of household contacts exposed to active tuberculosis in Ethiopia, focusing attention on the need for further translational research to determine the mechanisms of susceptibility to Mycobacterium tuberculosis infection among individuals with diabetes and pre-diabetes. OBJECTIVES/GOALS: Diabetes mellitus (DM) is an established risk factor for active TB disease, but there is limited understanding of the relationship of DM and latent tuberculosis (LTBI). We sought to determine the relationship between DM or pre-DM with LTBI among household or close contacts (HHCs) of active TB cases in Ethiopia. METHODS/STUDY POPULATION: We conducted a cross-sectional study of the HHCs of index active TB cases enrolled in an ongoing TB Research Unit (TBRU) study in Addis Ababa, Ethiopia. HHCs of individuals with laboratory-confirmed TB had QuantiFERON ®-TB Gold Plus (QFT) and glycated hemoglobin (HbA1c) tests performed. LTBI was defined as a positive QFT and lack of symptoms. HbA1C results were used to define no DM (HbA1c <5.7), pre-DM (HbA1c 5.7-6.5%), and DM (HbA1c >6.5% or prior history of diabetes). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, sex and HIV status as potential confounders. RESULTS/ANTICIPATED RESULTS: Among 466 HHCs, the median age was 29 years (IQR 23-38), 58.8% were female, 3.4% were HIV-positive, and median BMI was 20.9 kg/m^2 (IQR 18.9-23.8). Overall, 329 HHCs (70.6%) had LTBI, 26 (5.6%) had DM and 73 (15.7%) had pre-DM. Compared to HHC without DM, the prevalence of LTBI was higher in those with pre-DM (68.9% vs. 72.6%; OR 1.19, 95% CI 0.69-2.13) and those with DM (88.5%; OR 3.45, 95% CI 1.17-14.77). In multivariable analysis, there was a trend towards increased LTBI risk among HHCs with DM vs. without DM (OR 2.16, 95% CI 0.67-9.70) but the difference was not statistically significant. Among HHCs with LTBI, the median IFN-? response to TB1 antigen was modestly greater in those with DM (5.3 IU/mL; IQR 3.0-7.8) and pre-DM (5.4 IU/mL; IQR 2.0-8.4) compared to HHCs without DM (4.3 IU/mL; IQR 1.4-7.7). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results suggest that DM may increase the risk of LTBI among HHCs recently exposed to active TB. Among those with LTBI, increased IFN-? antigen response in the presence of DM and pre-DM may indicate an exaggerated but ineffectual response to TB. Further investigation is needed to assess how dysglycemia impacts susceptibility to M. tuberculosis.

Clinical trials continue to disproportionately underrepresent people of color. Increasing representation of diverse backgrounds among clinical research personnel has the potential to yield greater representation in clinical trials and more efficacious medical interventions by addressing medical mistrust. In 2019, North Carolina Central University (NCCU), a Historically Black College and University with a more than 80% underrepresented student population, established the Clinical Research Sciences Program with support from the Clinical and Translational Science Awards (CTSA) program at neighboring Duke University. This program was designed to increase exposure of students from diverse educational, racial, and ethnic backgrounds to the field of clinical research, with a special focus on health equity education. In the first year, the program graduated 11 students from the two-semester certificate program, eight of whom now hold positions as clinical research professionals. This article describes how leveraging the CTSA program helped NCCU build a framework for producing a highly trained, competent, and diverse workforce in clinical research responsive to the call for increased diversity in clinical trial participation.