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OBJECTIVES/GOALS: Biliary tract cancer is an uncommon, aggressive malignancy. Incidence varies geographically and is highest in East Asia and South America and lowest in Western countries. Previous dietary risk evaluations have primarily been case-control studies. We evaluated associations of dietary intakes with BTC risk in three cohort studies in two countries. METHODS/STUDY POPULATION: We evaluated 638,860 adults in China and the United Kingdom enrolled in the Shanghai Women’s Health Study (SWHS), Shanghai Men’s Health Study (SMHS), or UK Biobank (UKB). Dietary intake information was obtained from study participants at baseline using food frequency questionnaires previously validated for these studies. Dietary intakes of major food groups and macronutrients were divided into low, middle, and high intake tertiles. Cox regression was used to estimate hazard ratios and 95% CIs for biliary tract cancer risk associated with major food groups in all three cohorts and macronutrients in the SWHS and SMHS. Participants were excluded if, at enrollment, they had a history of cancer, CHD, stroke, a total daily Kcal count below 500 or exceeding 3500, or developed cancer or died within one year after enrollment. RESULTS/ANTICIPATED RESULTS: The analyzed cohort includes 558,372 participants: 66,945 SWHS, 55,750 SMHS, and 435,677 UKB participants with median enrollment ages of 49, 52, and 57 years old and median follow-up times of 18.1, 12.3, and 10.3 years, respectively. The SWHS observed 205 eligible BTC cases, SMHS 97, and UKB 366. SWHS and SMHS participants were combined for dietary evaluation and the highest tertile of fruit intake showed an inverse association with biliary tract cancer risk when compared to the lowest tertile: HR 0.74 (95% CI, 0.55-0.99); p-trend 0.044. In UKB, the highest tertile of fish intake was associated with a reduced risk when compared to the lowest tertile: HR 0.76 (95% CI, 0.59-0.98); p-trend 0.034. DISCUSSION/SIGNIFICANCE: High dietary fruit intake was associated with a reduced risk of biliary tract cancer only in SWHS and SMHS. High fish intake was associated with a reduced risk of biliary tract cancer only in UKB. Our findings reflect geographic-based BTC risk variation which we will further explore in our next model accounting for population-specific risk factors.
OBJECTIVES/GOALS: Analysis and modeling of large, complex clinical data remain challenging despite modern advances in biomedical informatics. We aim to explore the potential of topological data analysis (TDA) to address such challenges in the context of COVID-19 outcomes using electronic health records (EHRs). METHODS/STUDY POPULATION: In this work, we develop TDA approaches to characterize subtypes and predict outcomes in patients with COVID-19 infection. First, data for >70,000 COVID-19 patients were extracted from the OneFlorida EHR database. Next, enhancements to the TDA algorithm Mapper were designed and implemented to adapt the technique to this type of data. Clinical variables, including patient demographics, vital signs, and lab values, were then used as input to conduct a population-level exploratory analysis with an emphasis on identifying phenotypic subtypes at increased risk of adverse outcomes such as major adverse cardiovascular events (MACE), mechanical ventilation, and death. RESULTS/ANTICIPATED RESULTS: Preliminary Mapper experiments have produced visual representations of the COVID-19 patient population that are well-suited to exploratory analysis. Such visualizations facilitate easy identification of phenotypic subnetworks that differ from the general population in terms of baseline variables or clinical outcomes. In this and subsequent work, we aim to fully characterize and quantify differences between these subnetworks to identify factors that may confer increased risk (or protection from) adverse outcomes. We also plan to validate and rigorously compare the efficacy of this TDA-based approach to common alternatives such as clustering, principal component analysis, and machine learning. DISCUSSION/SIGNIFICANCE: This work demonstrates the potential utility of TDA for the characterization of complex biomedical data. Mapper provides a novel means of exploring EHR data, which are otherwise difficult to visualize and can aid in identifying or characterizing patient subtypes in diseases such as COVID-19.
OBJECTIVES/GOALS: The purpose of this study is to determine critical recovery support factors (SDOH, postpartum and post-discharge continuity of care), to optimize continuity of recovery and to determine the best intervention among postpartum and parenting women for treatment retention. METHODS/STUDY POPULATION: Through a mixed methods approach, we will review retrospective hospital discharge data to identify hospital-based gaps in treatment. We will conduct key informant interviews with postpartum women, treatment providers and stakeholders to broaden understanding of critical recovery factors from lived experiences and test a parent-centered evidence-based intervention for a comprehensive and targeted approach to recovery. RESULTS/ANTICIPATED RESULTS: This research will lead to new understanding of critical maternal recovery support factors for sustaining treatment retention for 6-12 months after childbirth and to improve long term maternal health outcomes. DISCUSSION/SIGNIFICANCE: The recovery journey and postpartum period are challenging and lack specific recovery support evidence. Recovery support and continuity of care protocols are unclear after childbirth. Maternal opioid-related overdose deaths occur 6-12 months after childbirth. Therefore, this study will impact and inform recovery retention strategies.
OBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism of toxicity. METHODS/STUDY POPULATION: The epidemiological aim of this study characterizes mitochondrial outcomes in samples of umbilical cord tissue and blood from two Manhattan based birth cohorts. Prenatal PAH exposure is quantified using silicone wristbands worn for 48 hours during the third trimester of pregnancy. Experimentally, we are applying a PAH mixture designed to emulate the exposure profile of the human cohorts to mouse preimplantation embryos on various dosing schedules and quantifying the same mitochondrial outcomes. mtDNAcn is quantified using rtPCR while superoxide production and membrane potential are measured using fluorescence microscopy. The goal of this study design is to leverage the strengths of each approach to draw more robust conclusions than could be derived from either alone. RESULTS/ANTICIPATED RESULTS: Preliminary results of this study have found associations between higher levels of PAH exposure and increased mitochondrial superoxide production and hyperpolarization of the mitochondrial membrane potential in mouse preimplantation embryos. We anticipate these findings to persist across dosing schedules. We furthermore expect a decrease in mtDNAcn in association with higher PAH exposure in umbilical cord tissue samples and decreased mtDNAcn with exposure to the PAH mixture in mouse embryos. DISCUSSION/SIGNIFICANCE: Characterizing the effect of prenatal PAH exposure on the mitochondria is a critical step in understanding the mechanisms that underlie the toxicity of this exposure. By employing a similar exposure mixture and mitochondrial outcomes across epidemiological and experimental approaches, we offer a model of true interdisciplinary research design.
OBJECTIVES/GOALS: Non-alcoholic fatty liver disease increases with aging and may be associated with MCI. Thus, adults >65 years with NAFLD have a greater risk of MCI. Our objective is to associate NAFLD with MCI and, therefore, optimize the management of MCI through prevention strategies and early interventions. METHODS/STUDY POPULATION: We will recruit 100 patients >65 of all sexes from the GI and Geriatrics clinics of the University of Puerto Rico (UPR). NAFLD prevalence in aging adults will be estimated via ICD-10 codes and definition will be liver fat accumulation or steatosis (AASLD) without secondary causes. We will exclude patients RESULTS/ANTICIPATED RESULTS: We expect to find a higher NAFLD prevalence in aging adults >65 years old compared to younger ones. Furthermore, we aim to elucidate an association of NAFLD with MCI in aging adults. Besides, as the literature has shown, we anticipate that the main cognitive domains affected by NAFLD will be the visuospatial and executive functions. As the population ages, this study will help identify future targets for early interventions in people diagnosed with NAFLD that could have a greater risk for cognitive impairment. DISCUSSION/SIGNIFICANCE: To our knowledge, no study has determined the association of NAFLD with MCI in Hispanics >65 in PR. Raising awareness of NAFLD as a possible treatable or preventable risk factor for MCI by screening NAFLD patients for MCI may improve not only their global health but their quality of life as well.
OBJECTIVES/GOALS: The goal of this presentation is to highlight the role of and challenges to the Biostatistics, Epidemiology and Research Design (BERD) Core as it transitions into (i) the resources and services module (ii) and also possibly a regional center of translational science. METHODS/STUDY POPULATION: BERD cores play key roles in translational research missions, often in the form of long-term collaborative relationships focusing on project conception and design, interim monitoring and review, analysis and dissemination. The resources and services module encourages consolidation of all resources and services under the single modular umbrella, which can pose challenges to BERD autonomy and function. CTSAs transitioning from local to regional centers can also threaten to overwhelm BERD workloads and resources. Our CTSA planned an outsource-insource model to make the BERD a central feature of the new module and transplant its functionality to partner institutions. RESULTS/ANTICIPATED RESULTS: The team has planned a centralized, web-based entry-point for both self-guided inquiry and electronic requests of all resources and services, which aides project database creation and provides notification for review. The review process adds two new approval types: guided assistance to help navigate connections to relevant resources, and triaged referrals to training modules for remediation and skills development. Our BERD has added a Consulting Laboratory for projects of sufficient but non-priority merit that would otherwise be waitlisted, and established connections with regional partner institutions to whom they can refer investigators. DISCUSSION/SIGNIFICANCE: We have consolidated all resources and services into a single, accessible location, emphasizing tailored guidance to maximize limited resources. We also planned a transportable regional model that accounts for local resources and capacity to keep from overstretching the BERD and other hubs.
OBJECTIVES/GOALS: While the current management of single ventricle repairs has drastically prolonged life expectancy, the repair fails over time primarily through pathologic inflammation and fibrosis. Our goal is to demonstrate that cardio-omentopexy can decrease inflammation and fibrosis in swine after cryoinjury. METHODS/STUDY POPULATION: A cryoinjury is created using a liquid nitrogen cooled probe to the right ventricle of 20kg swine. In half the groups the omentum is attached to the heart over the area of the injury. The swine are recovered and monitored for 4 or 8 weeks at which time they are euthanized. The injured area is evaluated via histological and immunohistochemical testing for markers of inflammation and scarring including collagen type, scar area, macrophage activity. RESULTS/ANTICIPATED RESULTS: We anticipate that the addition of omentopexy to cryoinjury will decrease scar area, fibrosis and markers of chronic inflammation. Additionally, we expect an increase in myocytes in the area of injury. We expect that this will occur through the anti-inflammatory and protective mechanism of the omentum. DISCUSSION/SIGNIFICANCE: Cardio-omentopexy, if able to decrease fibrosis and preserve myocytes, may provide a useful adjunct to the treatment of single ventricle repair by prolonging the longevity of the repair. Additionally, as these repairs often require a ventriculotomy, decreasing the operative scar may preserve myocardial function.
OBJECTIVES/GOALS: Cadmium is a widespread neurotoxic metal pollutant; however prior study results of Cd and later-life cognition are mixed. We investigated association of urinary cadmium on Alzheimer’s Disease (AD) mortality risk, accounting for key co-pollutants smoking and lead, in the presence of competing risks. METHODS/STUDY POPULATION: We included 5692 persons, 60 years old from the 1998-2018 National Health and Nutrition Examination Survey. Underlying cause of death was determined via linked 1999-2019 National Death Index data. Urinary cadmium (UCD) reflects prolonged exposure and was adjusted for creatinine. We used multiple imputation (5 iterations) to recapture substantial model observation drop-out (N=782). We used three Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence interval (CI) per unit increase in UCD and time to AD mortality: a competing risks model, a survey-weighted model, and a baseline model including neither, all adjusted for demographic characteristics, lead, and smoking. RESULTS/ANTICIPATED RESULTS: Follow-up ranged from 0 to 20.8 years (mean 8.2 years), with a total of 1,987 individuals deceased (14,232 person-years at-risk), including 88 individuals dying from AD. Mean UCD was 0.50 μg/g creatinine (standard error=0.01). In baseline and survey-weighted models fully adjusted for NHANES cycle, poverty income ratio, age, race/ethnicity, sex, marital status, education, smoking status, and blood lead levels, a per unit increase in UCD was associated with approximately twice the rate of AD mortality (baseline model HR: 1.92, 95% CI: 1.28, 2.89; survey-weighted model HR: 2.08, 95% CI: 1.42, 3.06). In the competing risks model, this association was attenuated (HR: 1.58, 95% CI 1.06 2.36). DISCUSSION/SIGNIFICANCE: Our study finds chronic cadmium exposure associated with AD mortality even after accounting for competing risks of AD mortality and confounding effects of cigarette smoking and lead exposure, strengthening the evidence that long-term cadmium exposure adversely affects later-life cognitive health.
OBJECTIVES/GOALS: The preclinical stage of Alzheimer disease (AD) is a clinically silent period that can be detected through neuroimaging and biofluid biomarkers. The goal of this study was to determine whether performance of complex daily tasks is associated with plasma biomarkers of brain amyloidosis or neuroaxonal injury in cognitively normal (CN) older adults. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing longitudinal cohort study. CN older adults performed three complex daily tasks (shopping, checkbook balancing, medication management) from the Performance Assessment of Self-Care Skills in their home. Tasks were scored for independence, with more assistance required indicating worse performance. Participants had a plasma sample obtained within two years of completing the tasks. Plasma amyloid (Aβ42 and Aβ40) were evaluated by high precision immunoprecipitation mass spectrometry assays and neurofilament light (NfL) was measured with single molecule array (Simoa) assays. Nonparametric partial correlations were used to quantify the associations between task performance and plasma AD biomarkers, controlling for age and gender. RESULTS/ANTICIPATED RESULTS: 105 CN participants (mean age 74.7 years, 55% female, 88% white) were included. After controlling for age and gender, worse performance of complex daily tasks (more assistance required) was associated with increased plasma NfL (Spearman’s: 0.23, p=0.04) but not plasma Aβ42/Aβ40. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks in CN older adults may be associated with increased plasma NfL a marker of neuroaxonal injury, but not with plasma amyloid. These findings could lead to a better understanding of clinical changes that may occur prior to the onset of noticeable memory symptoms in AD or related dementias.
OBJECTIVES/GOALS: Multiple induction agents can facilitate rapid sequence intubation (RSI) in management of refractory status epilepticus (rSE), many which have anti-seizure properties. We examine the anti-seizure efficacy and safety of induction agents used during RSI in the management of rSE. METHODS/STUDY POPULATION: We conducted a single-center retrospective review of patients admitted to the neuro-ICU intubated for management of rSE. Propofol, ketamine and benzodiazepines were considered anti-seizure medication (ASMs), etomidate was not. Patients were treated with propofol or midazolam following intubation. Our primary outcome was clinical or electrographic recurrence of SE within 12 hours of intubation. Exploratory outcomes included time to recover command following, duration of mechanical ventilation (MV) and complications related to intubation. We used multivariable logistical regression to evaluate outcomes between patients induced with ASMs and etomidate. A Fisher exact test was used to compare rSE cessation in a subset of patients with continuous electroencephalography (cEEG) at the time of intubation. RESULTS/ANTICIPATED RESULTS: We identified 149 induced for RSI in management of rSE: 88 patients intubated using ASMs (propofol,n=56; ketamine,n=14; benzodiazepines,n=18) and 61 patients intubated with etomidate. Forty-one patients had recurrence (29.9% ASMS, 24.6% etomidate). The induction agent was not associated with recurrence of SE, time to command following, or duration of MV. Twenty-seven patients had cEEG monitoring at the time of intubation. Sixteen of the 22 patients induced with ASMs had cessation of rSE with induction, while 1 of 5 intubated with etomidate had cessation (Fisher exact test, p=0.047). There were 34 patients with post-induction hypotension (22.9% ASMs, 22.9% etomidate (Fisher exact test, p=1)). DISCUSSION/SIGNIFICANCE: Induction with an anti-seizure medication during intubation was more likely to halt rSE, but did not decrease the likelihood of clinical or electrographic recurrence of rSE and may not affect time to recovery of command following or duration of MV.
OBJECTIVES/GOALS: The purpose of this study is to compare the mental health of African Americans to Whites during 2019 and 2020 using the a National Survey on Drug Use and Mental Health (NSDUMH). METHODS/STUDY POPULATION: Secondary data analysis from the National Survey on Drug Use and Health. The data consisted of 55,772 observations, 3,090 variables. This study will consist of the United State adult data population from 2019 and 2020 using the National Survey on Drug Use and Mental Health (NSDUMH). RESULTS/ANTICIPATED RESULTS: The results of this research will be produced from the following analysis. The analysis will consist of a secondary data analysis from the National Survey on Drug Use and Mental Health (NSDUMH). The primary independent variable of interest is race. All the indicator (race, sex, insurance, etc). Dependent variable is the mental health of African Americans and Whites. This is the variable in the NSDUMH labeled as the Major Depressive Episodes (MDE). The data analysis will be conducted using univariate analysis describing the study population. Bivariate analysis will be performed using chi-square. Since our dependent variable will be dichotomous we will be using several logistic regressions. DISCUSSION/SIGNIFICANCE: Strengthen mental health and psychosocial support services as part of strengthening preparedness, response and resilience to COVID-19 and future public health emergencies. Also adopt the updated Comprehensive Mental Health Action Plan for the future.
OBJECTIVES/GOALS: The purpose of our study was to assess the knowledge, attitudes and practices of nursing students during the COVID-19 pandemic. METHODS/STUDY POPULATION: Data were collected using an online questionnaire consisted of demographic characteristics and 24 items about COVID-19-related knowledge, attitudes and practices. RESULTS/ANTICIPATED RESULTS: A total of 1,216 nursing students participated in this study. About 82% of the participants reported that the COVID-19 virus spreads via respiratory droplets of infected individuals. The most clinical symptoms of COVID-19 correctly identified by participants were fever (97.6%), dry cough (92.4%), dyspnoea (82%) and fatigue (74.9%). More than 56.6% of the participants were afraid of being affected by COVID-19. Almost all participants reported that they avoid crowded places frequently. About 93.4% of the participants declared frequently wearing face mask when leaving home, and 85.5% maintained social distancing frequently. However, only 47.4% reported that they frequently washed their hands. About 51% stated that coronavirus outbreak has considerably changed their daily routines. DISCUSSION/SIGNIFICANCE: Sensitization and education campaigns are needed to improve their preventative practices, such as hand hygiene and wearing face mask. In addition, it may be of importance to incorporate competences into curricula to improve knowledge, attitudes and practices of future health professionals and to prepare them for emergencies and outbreaks.
OBJECTIVES/GOALS: Preeclampsia (PE) is a hypertensive disorder of pregnancy, affecting 5 - 7% of pregnancies worldwide. A major cause of morbidity and mortality, PE is also associated with subsequent adverse health outcomes, including long-term increased risk of cardiovascular disease. The genetics conferring increased risk for PE are incompletely understood. METHODS/STUDY POPULATION: We performed a cross-ancestry, fixed-effects meta-analysis, incorporating both published and unpublished genome-wide association study (GWAS) summary statistics. In addition to publicly available summary statistics from two prior studies, we generated GWAS data from three electronic health record biobanks (BioVU, eMERGE, and PMBB). In total, we utilized data from 359,378 individuals (4,411 cases and 354,967 controls). Leveraging this large-scale biobank data importantly allows for detection of complex factors contributing to the diverse etiology of PE. Cases across cohorts were defined using PE-specific ICD-9/ICD-10 codes and phecodes. Cohorts included pregnant individuals of self-identified non-Hispanic Black, non-Hispanic White, and East Asian ancestry. RESULTS/ANTICIPATED RESULTS: 2 of 20,204,625 loci achieved genome-wide significance (p < 5 × 10–8) when minor allele frequency was limited to common variants (>0.01). The most significant locus was rs138180605 (p = 1.77 × 10–8), located in an intergenic region between FGFR2 and ATE1, both previously associated with breast cancer. The other significant locus was rs137895377 (p = 2.33 × 10–8), located in an intronic region of PLEKHO1. Another 225 loci achieved suggestive significance (p < 1 × 10–5). 203 loci could be mapped to 109 unique genes, some previously associated with related phenotypes such as hypertension. Next steps will focus on functional analyses, including genetically predicted gene expression incorporating placental tissue, followed by construction of a PE polygenic risk score to demonstrate predictive utility of results. DISCUSSION/SIGNIFICANCE: This work has contributed to the limited body of knowledge surrounding maternal genetic susceptibility to PE by identifying several loci warranting further investigation. Further work will expand on these results to improve understanding of genetic factors and clarify clinical risk of disease.
OBJECTIVES/GOALS: The goal was to create and deploy an intuitive, easy-to-use tool that clinical investigators can apply to their data to identify erroneous or inconsistent data entries. Investigators can then correct any errors prior to sharing the data with their statistician for analysis. METHODS/STUDY POPULATION: We developed an interactive shiny app, the Data Loofah, using R Studio that researchers or data analysts can use to examine data. After an investigator uploads data, the app reports which variables are numeric or categorical. Means, standard deviation, median, 25th and 75th quantiles, range and number of missing values are reported for numeric variables. Counts and percentages of categorical variables are summarized. Graphical displays further enhance identification of errors. Access to the Data Loofah is through a secure, university-maintained website with access restricted to university personnel. Supporting materials consisting of instructional step-by-step handouts and videos were developed to assist investigators in the use of the app. RESULTS/ANTICIPATED RESULTS: We will integrate use of the Data Loofah into our Clinical and Translational Science Program’s biostatistics consultative practice. Investigators will use the Data Loofah to pre-screen their data prior to sending it to a statistician, identify errors and inconsistencies, and facilitate making necessary corrections. Statisticians will also use the Data Loofah to review data with investigators prior to starting analyses. Through use of this app, investigators are expected to develop a better understanding of their data specifically and more generally about requirements for preparing data for statistical analysis. Most significantly, regular use of the Data Loofah is expected to result in higher quality data and more efficient use of statistician resources due to reduced effort for data cleaning. DISCUSSION/SIGNIFICANCE: Data cleaning is a time-consuming task and finding data errors can be difficult for data analysts not familiar with clinical variables under study. Further, failure to identify data errors can lead to erroneous results. By facilitating identification of data errors by clinical investigators, the Data Loofah will improve and enhance research output.
OBJECTIVES/GOALS: To describe and compare clinical data and outcomes for patients with CNS tumors and tumor mimics in Puerto Rico who are undergoing surgical and nonsurgical management. Thus, increasing data from an underrepresented group which can serve as a foundation for investigating determinants of outcomes. METHODS/STUDY POPULATION: This proposal will examine patient charts, radiology and pathology reports, financial data, and treatment details from the electronic medical record of patients receiving surgical and nonsurgical treatment for CNS tumors and mimics in the University of Puerto Rico Medical Sciences Campus and all associated institutions. Data will be analyzed retrospectively between January 1, 2014 and June 30, 2022, and prospectively for ten years until December 31, 2032. Patients with primary and metastatic CNS tumors and tumor mimics in the brain, meninges, ventricles, spinal cord, cranial nerves, orbit, facial sinuses, bony skull, vasculature will be included. The registry will include patients from birth onward. RESULTS/ANTICIPATED RESULTS: We plan to compare different surgical and non-surgical techniques and devices in terms of technical and clinical outcomes after surgical interventions for CNS tumors. We are collaborating with the CNS Tumor Outcome Registry at Emory (CTORE) and plan to continue collaboration with other institutions. Combining our data, we aim to develop predictive models of patient outcomes after surgical and nonsurgical intervention for CNS pathologies using supervised and unsupervised machine learning strategies. DISCUSSION/SIGNIFICANCE: There is a significant lack of literature on CNS intervention outcomes in Puerto Rico. This registry will provide the platform for cost-analysis studies for techniques and clinical protocols applicable to pre-operative, intra-operative, post-operative, and conservative management of patients, in Puerto Rico and beyond.
OBJECTIVES/GOALS: My research aims to discover African American breast cancer genetic risk factors. Interested in genetic predisposition, I search for inherited variants that could explain why African American women are disparately diagnosed at younger ages and with aggressive subtypes compared to other ethnicities. METHODS/STUDY POPULATION: Our study cohort, the Alabama Hereditary Cancer Cohort (AHCC), consists of African Americans that have had a breast cancer diagnosis indicative of hereditary breast cancer. Whole genome sequencing is conducted for AHCC breast cancer cases. Hypothesizing that African American-specific protein-truncating variants explain inherited risk, our control cohort consists of whole exome sequencing data of (~2500) African Americans from the Type 2 Diabetes Exome Sequencing Project on dbGAP. Single variant and gene-based association tests are being conducted to identify risk variants/genes. Prime editing is conducted to introduce risk variants into cancer cell lines for functional analyses. RESULTS/ANTICIPATED RESULTS: Preliminary studies, involving 60 breast cancer cases, have already revealed multiple African American-specific genetic variants in the nuclear and mitochondrial genome that are statistically linked to breast cancer risk. We are in the process of increasing our breast cancer sample size, aiming for significantly higher confidence. Prime editing for selected novel variants has begun in breast cancer cell lines. Functional assays will then be carried out to observe differences in cell proliferation, cell migration, and spheroid formation in the genetically edited compared to unedited cell lines. DISCUSSION/SIGNIFICANCE: African Americans are underrepresented in breast cancer research. This study reduces research participation gaps and identifies genetic risk variants, leading to better risk assessments and screening methods. Such discoveries can also lead to new therapeutic targets, reducing breast cancer deaths.
OBJECTIVES/GOALS: Infectious keratitis is a potentially sight-threatening disease. Its epidemiology has been considered on various national and regional levels, which demonstrates unique patterns in patient risk factors, causative organisms, antimicrobial resistance and clinical outcomes. This study will examine the patterns specific to the Rochester, NY area. METHODS/STUDY POPULATION: This project will be a ten-year retrospective study, examining all patients who were diagnosed with infectious keratitis at the University of Rochester Medical Center between 2011 and 2021. The study population is selected from a compiled list of those patients with an ICD diagnosis code including ’keratitis’ in the eRecord that falls within our chosen date range. Participants were excluded if the patient’s physician documented that the keratitis is most likely not infectious in etiology. If eligible for the study, there is documentation of patient demographics, clinical risk factors, clinical course, culture data from corneal scraping and antimicrobial resistance patterns, if available. Once data is collected, it will be analyzed and compared to pre-existing regional and national data. RESULTS/ANTICIPATED RESULTS: Between 2011 and 2021, there were 1652 patients with ICD diagnoses of keratitis at the University of Rochester Medical Center. Of these patients, we anticipate approximately 1,200 to meet our inclusion criteria. Some of the major risk factors for developing infectious keratitis in this population include contact lens use, immunocompromised state (elderly, diseased or iatrogenic) and corneal trauma. Clinical complications include progression to endophthalmitis, need for interventional surgery, or failure to improve on clinical exam after 2 weeks of antimicrobials. Causative organisms are most often bacterial. Certain organisms are associated with specific risk factors while other organisms predict greater risk of complications. We also anticipate patterns of antimicrobial resistance to emerge. DISCUSSION/SIGNIFICANCE: This study will provide insights into the risk factors and clinical course of infectious keratitis according to causative organisms in the Rochester, NY area. This can help us mitigate risk factors and help prognosticate for patients, once diagnosed. Also, patterns of antimicrobial resistance can inform empiric antimicrobial recommendations.
OBJECTIVES/GOALS: Flavored tobacco sales restrictions (FTSR) may reduce youth tobacco use, but may not be as effective in areas with greater tobacco retailer density (TRD), which is associated with greater tobacco access and more common in low-income areas. We examined the association between FTSRs and e-cigarette use for youth in high and low TRD cities. METHODS/STUDY POPULATION: We analyzed data from the California Healthy Kids Survey using a difference-in-differences (DID) strategy. We compared pre- and post-policy changes in ease of access to e-cigarettes, current use, and ever use one year after implementation among students (9th and 11th graders) attending school in a city with a FTSR (n=20,832) versus without (n=66,126). Separate analyses were conducted for students in cities with low and high TRD, with a median cutoff of 3.3 tobacco retailers per square mile. RESULTS/ANTICIPATED RESULTS: Students attending schools in cities with high TRD (compared with low TRD) had a higher percentage of parents with a high school education or less, and were more likely to identify as Hispanic or Non-Hispanic Asian/Pacific Islander. Among students with low TRD, FTSRs were associated with reduced ease of access to e-cigarettes (DID=0.76, 95% CI: 0.58, 0.99). However, among students with high TRD, FTSRs were associated with increased ease of access (DID: 1.25, 95% CI: 1.02, 1.56) and current use (DID=1.57, 95% CI: 1.31, 1.87). DISCUSSION/SIGNIFICANCE: FTSRs were associated with lower youth e-cigarette access in low, but not high TRD areas. Stronger policies or enforcement may be needed in high TRD areas.
OBJECTIVES/GOALS: Lung Ultrasound Congestion Score (LUS-CS) is a proposed measure for guiding treatment in acute heart failure (AHF). An emergency department (ED) pilot trial of LUS-guided diuresis showed reduced LUS-CS at 48 hours but no difference at hospital discharge or for clinical outcomes. We hypothesized total change in LUS-CS would predict adverse outcomes. METHODS/STUDY POPULATION: This was a post-hoc secondary analysis of the BLUSHED-AHF trial. BLUSHED-AHF was a pilot trial in which AHF patients were randomized to a LUS-guided diuresis strategy vs. usual care in the ED. The intervention was stopped after the ED course (i.e. during hospitalization). BLUSHED-AHF was designed for the intervention to target absolute values of LUS-CS over time, rather than change in LUS-CS from each patient’s baseline. We fit a cox regression model for a primary outcome of death or AHF rehospitalization, with total (ED to Hospital Discharge) change in LUS-CS as the primary predictor, adjusted for the Get-With-The-Guidelines heart failure risk score (GWTG). Survival curves were plotted, and hazard ratios calculated. RESULTS/ANTICIPATED RESULTS: 128 patients in BLUSHED-AHF were analyzed. Greater reduction in LUS-CS from ED to hospital discharge predicted event-free survival (HR = 0.74 for each 20 unit reduction in LUS-CS, 95%CI 0.56-0.99). This effect did not vary by hospitalization length or ED disposition. There was a significant interaction between change in LUS-CS and GWTG score (p DISCUSSION/SIGNIFICANCE: LUS-CS total change, and not absolute values, predict adverse events in LUS-guided diuresis. Post-ED cessation of the intervention in BLUSHED-AHF may have precluded opportunity for clinical benefit. Future trials should run the entire hospital course, target change from baseline, and consider patient selection by AHF severity and initial LUS-CS.
OBJECTIVES/GOALS: The primary aim is to evaluate the efficacy of a Mandibular Advancement Device (MAD) vs conservative treatment for adults with non-apneic snoring, as measured by the sleeping partner. The secondary aim is to evaluate the effectiveness of treatment of snoring on the sleeping partner’s sleep quality. METHODS/STUDY POPULATION: We plan to enroll 60 pairs of primary snorers and their sleeping partners in our randomized clinical trial. Snorers will be randomized to either 4 weeks of conservative therapy, consisting of nightly Mometasone nasal rinse, breathe-rite strips, mouth taping, and lateral positional therapy, or 4 weeks of Mandibular Advancement Device therapy (MAD). 30 pairs of snorers and their partners will be in each arm. At follow up the primary outcome measure, the Clinical Global Impression of Improvement Scale (CGI-I), will be assessed by the sleeping partner to evaluate the response to snoring treatment. RESULTS/ANTICIPATED RESULTS: To date, there is no study reporting the rate of response in participants using MAD in Primary Snoring. Due to lack of preliminary data and effect size, we hypothesize that the rate of the responders in the MAD group will be 20% higher than the rate of responders in the active control group based on literature studies and preliminary results. A responder will be classified as someone whose sleeping partner rates on the CGI-I scale that the snoring was much improved or very much improved. MAD has been shown previously to be an effective therapy at treating sleep apnea and reducing snoring, and we anticipate it will continue to be so for patients who do not have sleep apnea. DISCUSSION/SIGNIFICANCE: Snoring is a nearly ubiquitous problem that prevents restful sleep for spouses of snorers, which is known to have detrimental health effects. Yet it does not have scientifically proven treatments. Our study will evaluate these treatments in an effort to improve the health of the sleeping partners.