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ABSTRACT IMPACT: This research takes a transcriptomic approach to parse genes and molecular pathways that underlie the fear memory circuitry and, in doing so, identifies therapeutic targets that can further be developed into treatments for fear disorders, such as post-traumatic stress disorder. OBJECTIVES/GOALS: Normal fear learning produces avoidance behavior that promotes survival, but excessive and persistent fear after trauma can lead to development of phobias and post-traumatic stress disorder (PTSD). Our goal is to understand the mechanism and identify novel genetic targets underlying fear responses. METHODS/STUDY POPULATION: Involvement of the basolateral amygdala (BLA) in fear acquisition is well established and requires activation of N-methyl-D-aspartic acid receptors (NMDARs). At a cellular level, NMDAR activation leads to production of nitric oxide (NO) by a process mediated by interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS). To elucidate mechanisms underlying the role of the PSD95-nNOS-NO pathway in conditioned fear, here we use rodent behavioral paradigms, pharmacological treatment with a small molecule PSD95-nNOS inhibitor, RNA-sequencing, and an AAV-mediated knockdown of the nNOS gene in the BLA. RESULTS/ANTICIPATED RESULTS: We show that treatment with ZL006 attenuates rodent cued-fear consolidation. Additionally, with RNA-sequencing, expression of 516 genes was altered in the BLA following fear expression; of these genes, 83 were restored with systemic ZL006 treatment. Network data and gene ontology enrichment analyses further revealed that cGMP effects, insulin-like growth factor binding, and cognition-related pathways were significantly altered. Finally, we show that a BLA-specific knockdown of nNOS attenuates cued fear consolidation, without adverse effects on other memory and motor behaviors. DISCUSSION/SIGNIFICANCE OF FINDINGS: Via a model of NMDAR-mediated fear consolidation, our results reveal novel pathways and genetic targets that underlie plasticity of fear memory circuitry. Importantly, these results will inform future therapeutic strategies for targeting fear related disorders like PTSD.
ABSTRACT IMPACT: This study will provide the essential characterization of intrinsic neural activity in human brain organoids, both at the single cell and network levels, to harness for translational purposes. OBJECTIVES/GOALS: Brain organoids are 3D, stem cell-derived neural tissues that recapitulate neurodevelopment. However, to levy their full translational potential, a deeper understanding of their intrinsic neural activity is essential. Here, we present our preliminary analysis of maturing neural activity in human forebrain organoids. METHODS/STUDY POPULATION: Forebrain organoids were generated from human iPSC lines derived from healthy volunteers. Linear microelectrode probes were employed to record spontaneous electrical activity from day 77, 100, and 130 organoids. Single unit recordings were collected during hour-long recordings, involving baseline recordings followed by glutamatergic blockade. Subsequently, tetrodotoxin, was used to abolish action potential firing. Single units were identified via spike sorting, and the spatiotemporal evolution of baseline neural properties and network dynamics was characterized. RESULTS/ANTICIPATED RESULTS: Nine organoids were recorded successfully (n=3 per timepoint). A significant difference in number of units was seen across age groups (F (2,6) = 6.4178, p = 0.0323). Post hoc comparisons by the Tukey HSD test showed significantly more units in day 130 (51.67 ±14.15) than day 77 (16.33 ±14.98) organoids. Mean firing rates were significantly different in organoids based on age, with drug condition also trending toward significance (F (6,12) = 9.97; p = 0.0028 and p = 0.08 respectively). Post hoc comparisons showed a higher baseline firing rate in day 130 (0.99Hz ±0.30) organoids than their day 77 counterparts at baseline (0.31Hz ±0.066) and glutamate blockade (0.31Hz ±0.045). Preliminary network analysis showed no modularity or small-world features; however, these features are expected to emerge as organoids mature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial analysis of brain organoid activity demonstrates changes in single unit properties as they mature. Additional work in this area, as well as further network analyses, will confer better sense of how to rationally utilize brain organoids for translational purposes.
ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.
ABSTRACT IMPACT: This work investigates C. difficile strains in soil as a potential exposure for gut colonization and community-acquired infection of C. difficile. OBJECTIVES/GOALS: Identifying environmental sources of C. difficile can inform how non-hospital reservoirs can potentially contribute to C. difficile exposure and subsequent gastrointestinal colonization. The objective of the study was to identify C. difficile and toxin genes across various soil sources. METHODS/STUDY POPULATION: This was a cross-sectional study utilizing soil samples obtained throughout Texas, USA. All samples were collected between August and November of 2019 and 2020. Samples were taken from human and animal high contact areas, such as recreational parks. Samples were stored at -80oC until processing. DNA extractions were performed using the DNeasy Powersoil Pro Kit (Qiagen) per manufacturer’s instructions. Real-time PCR was also performed on extracted DNA using the Microbial DNA qPCR Multi-Assay Kit for Clostridium difficile Pathogenicity (Qiagen) for the identification of C. difficile, toxin A (TcdA), and toxin B (TcdB) genes. RESULTS/ANTICIPATED RESULTS: A total of 137 soil samples including dry dirt, sand, and wet soil near water sources were collected and processed for the presence of C. difficile. These included samples from parks and trails (42.3%), water sources (36.5%), and other public spaces (21.2%). C. difficile was identified in 59 (43.1%) soil samples: 6 (4.4%) with Toxin A and 2 (1.5%) with toxin B production. C. difficile was most prevalent among samples taken from parks and trails (50.0%), followed by other public spaces (48.3%), and water sources (32.0%). The median (IQR) Cq value for the C. difficile gene was 39.24 (33.45-40.47) among samples that tested positive. DISCUSSION/SIGNIFICANCE OF FINDINGS: We identified a high prevalence of Clostridioides difficile in soil samples, though toxin gene detection prevalence was low. Future studies will analyze other sources, including water and varying surface samples to obtain a comprehensive view of C. difficile in the environment.
ABSTRACT IMPACT: By demonstrating the feasibility of a multimodal, interdisciplinary intervention for prediabetes, the current project aims to provide a template for the prevention of diabetes and associate comorbid conditions. OBJECTIVES/GOALS: To determine if a multi-modal, interdisciplinary intervention delivered to a group of prediabetic patients will result in reduced rates of diabetes progression. This project is a retrospective evaluation that will exam the feasibility and possibly efficacy of this intervention. METHODS/STUDY POPULATION: We will enroll 50 participants for the clinic, aged 21-60 inclusive. Patients will have a Body Mass Index >27kg/m2 with a diagnosis of prediabetes. Patients must be non-pregnant, using approved contraception, and agree to not become pregnant for 1 year after enrollment. After enrollment, the initial treatment period is for 1 year and includes a 12 week low calorie diet plan, a 6-month intensive behavioral and lifestyle modification plan followed by a 6 month behavior reinforcement extension. Weight management medications may be used if appropriate for the patient from a clinical perspective during the 6-month intensive behavioral/lifestyle modification. RESULTS/ANTICIPATED RESULTS: It is anticipated that there will be decreased weight with a mean weight loss goal of approximately >10%. Furthermore, it is expect that there will be improvement of other markers of metabolic disease. These include improvement of lipid values (LDL-C, HDL-C, Triglycerides, Total Cholesterol) as well as blood pressure with expected blood pressures of below 130/80 in greater than 50% of participants. Finally, It is expected that 50% or greater participants will have improvement of glycemic control. It is anticipated that greater than 50% of participants will have improvement of glycemic control and achieve normoglycemia. These values will be determined based upon fasting glucose or A1c. DISCUSSION/SIGNIFICANCE OF FINDINGS: The significance of this intervention is enormous. By demonstrating feasibility in this trial, we can work toward both assessing efficacy and possibly dissemination of this model program. If these interventions provide durable changes at scale, this could help slow the epidemic of obesity and obesity related comorbid conditions.
ABSTRACT IMPACT: This study provides public health and K-12 school districts with a pragmatic, flexible, adaptable model showing COVID-19 transmission dynamics, using local data and program elements that are modifiable and with an online model for easy use, to enable safe and equitable re-opening and maintenance of in-person learning. OBJECTIVES/GOALS: School closures resulting from the COVID-19 pandemic disrupt student education and health and exacerbate inequities. Public health agencies and school districts currently lack pragmatic models to assess the effects of potential strategies for resuming and maintaining in-person learning on outcomes such as transmission and attendance. METHODS/STUDY POPULATION: This study explored how various combinations of transmission-mitigating interventions affect health and learning outcomes in a range of underlying epidemiological conditions. The CTSA science team developed a conceptual framework and an agent-based simulation model with parameters including prevalence, transmission, testing, preventive and responsive actions, infection control, population behavior and awareness, and the potential impact of vaccine adoption and exemption policies. The team partnered with a large school district to ensure relevance of the program components to decision-making. RESULTS/ANTICIPATED RESULTS: The model shows that no single program element or condition ensures safety. Combining interventions can result in synergy in the mitigation efforts. Even without testing, an efficient health screening process with forthcoming risk reporting, combined with on-campus infection control, can reduce on-campus transmission. The resulting model is accessible online to enable exploration of likely scenarios. It is adaptable as COVID-19 science evolves, including for testing and vaccines. DISCUSSION/SIGNIFICANCE OF FINDINGS: This research provides public health agencies and school districts with a model that couples local conditions with programmatic elements to help inform the local COVID-19 response, recognizing that decisions about the school community are often complex politically, technically, and operationally when it comes to addressing a health crisis.
ABSTRACT IMPACT: We developed a novel semi-automated computational platform to quantify spatial characteristics of preserved peripheral visual field loci in retinitis pigmentosa. This work may inform future research on therapies to prevent visual field loss in retinitis pigmentosa and related diseases. OBJECTIVES/GOALS: Retinitis pigmentosa (RP) causes progressive and severe peripheral visual field (pVF) loss in some but not all patients. The characteristics of pVF in RP are incompletely understood. We developed a novel semi-automated computational platform to quantify the spatial characteristics of pVF. METHODS/STUDY POPULATION: We analyzed preserved pVF size and location in both eyes of RP patients using the Goldmann V4e isopter. We developed a custom algorithm in MATLAB to align and average the binary V4e isopter segmentations, and generated a two-dimensional probability map of the spatial distribution of preserved pVF loci along the radial and circumferential dimensions. To adjust for disease duration, cases were categorized by the time from self-reported symptom onset. Probability maps of pVF preservation were generated for categories of disease duration using unsupervised K-means clustering. Analyzing cases with longitudinal data, we identified loci of stable pVF over time. RESULTS/ANTICIPATED RESULTS: A total of 152 patients were included (N=304 eyes). The mean age was 46.7 years and 49.3% were male. Disease duration was categorized as <20 years (N=72, 47.4%), 20-40 years (N=60, 39.5%), or >40 years (N=20, 13.2%). Longitudinal data (3.2 -5.7 years of follow-up) were available in 65 patients (42.8%). Probability plots of preserved pVF loci in the cross-sectional dataset showed that the median percentage of preserved pVF loci were located between 50 ºand 80 ºeccentricity and between the 30 ºto 50 ºmeridians, with highly concordant inter-ocular symmetry. Probability plots in the longitudinal dataset showed that inferotemporal pVF loci were most likely to be preserved over time. DISCUSSION/SIGNIFICANCE OF FINDINGS: Semi-automated quantification of pVF loci is a useful platform to analyze spatial characteristics of the visual field in RP. Certain portions of the pVF may be relatively resistant to functional decline. Understanding the molecular basis of pVF resilience will inform further research on RP therapy.
ABSTRACT IMPACT: This change will improve primary care physicians and pediatrics ability to identify, intervene and prevent obesity related renal damage in the vulnerable population of young adults OBJECTIVES/GOALS: Obesity related glomerulopathy has a reversible stage manifested as hyperfiltration. Early intervention depends on the ability to identify hyperfiltration. Hyperfiltration prevalence is underestimated using the currently recommended formula We investigated whether calculating BSA-adjusted GFR will more readily identify hyperfiltration. METHODS/STUDY POPULATION: We extracted data from a large urban, multi-institutional Electronic Health Records (EHR) clinical data research network to construct an EHR data base of 60,549 women and girls ages 12-21 years from the New York metropolitan area. EGFR was calculated in two ways, 1) according to age appropriate formula, and 2) according to age appropriate formula and adjusted to body surface area (BSA). BMI-for-age values were classified according to the World Health Organization schema and grouped according to the CDC definitions. BSA was calculated according to the Du-Bois formula. Hyperfiltration was defined by a threshold of 135ml/min. The Bland Altman method assessed the agreement between formulas across the different BMI groups. RESULTS/ANTICIPATED RESULTS: Serum creatinine values were similar across different BMI groups. Comparing eGFR values, hyperfiltration rates were similar across BMI groups, ranging between 4%-6.6%. BSA-adjusted GFR was different across BMI groups: hyperfiltration rates were 0.81% for the underweight group, 2.56% for the normal weight, 12.18% for the overweight and 39% in the obese group. This trend of hyperfiltration paralleled the the rise in urine creatinine across BMI groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: BSA-adjusted GFR more sensitively detects hyperfiltration due to obesity than does eGFR. Calculating BSA-adjusted GFR will improve primary care and pediatric physicians’ ability to identify, intervene and prevent early ORG. Changes in body composition may account for the increasing discordance between BSA-adjusted and eGFR as BMI rises.
ABSTRACT IMPACT: Given the association between lower time to treatment and better clinical outcomes in stroke patients, identifying factors correlated with reduced proximity and thus greater time to stroke care can aid efforts to reduce disparities in stroke outcomes. OBJECTIVES/GOALS: The objective of this study is to quantify the relationship between distance to the nearest certified stroke hospital and census-derived demographics of age, race/ethnicity, income, and insurance status. METHODS/STUDY POPULATION: This is a cross-sectional study. Population data for all census tracts in the contiguous United States were obtained from the US Census Bureau’s 2014-2018 American Community Survey. Stroke hospitals were identified from national or state level certification databases and were required to offer at least IV tPA. The main outcome is driving distance in kilometers from each census tract to the nearest certified stroke center, which was calculated using OSMnx, a Python package to retrieve, model and analyze real-world street networks. Quantile regression analysis was used to compare relationships between distances and tract-level demographics of age, race/ethnicity, income, and insurance status. RESULTS/ANTICIPATED RESULTS: 2,423 stroke centers and 71,929 census tracts containing 316,995,649 individuals were included. 49,918 (69%) tracts were urban. Demographic disparities in proximity to certified stroke care were greater in non-urban areas than in urban areas. Higher representation of individuals with age ≤65 years were associated with increased median distance to a certified stroke center in non-urban areas, but not urban areas. Median distance was greater with greater representation of American Indian or uninsured populations in urban and non-urban census tracts. Higher median income was associated with decreased median distance in non-urban census tracts and greater median distance in urban census tracts. DISCUSSION/SIGNIFICANCE OF FINDINGS: Reduced proximity to stroke care exists in areas with greater representation of elderly, American Indian, or uninsured persons; and low median income. These disparities are magnified in non-urban settings. Such knowledge can aid efforts to address and reduce disparities in stroke outcomes.
ABSTRACT IMPACT: Our work helps show universities that embedding dedicated sexual health clinics within university health and wellness clinics may expand the amount of students they see for sexual health screenings during a time of increased sexual behavior and exploration. OBJECTIVES/GOALS: The National College Health Association reports that college students have frequent, condomless sex. Student health and wellness clinics (SHWC) offer sexual health services, but few have dedicated sexual health clinics (SHC). We evaluated sexual health service use at a university SHWC after implementation of a dedicated SHC two half-days per week. METHODS/STUDY POPULATION: This was a retrospective analysis of data collected from patients receiving sexual health screening at the University of Alabama at Birmingham (UAB) SHWC between January 2015 and June 2019. Demographic variables, sexual behaviors, reason for testing, and rates of STIs were extracted from the electronic medical record and were compared by clinic (SHC vs. SHWC). Data on screening visits of patients over 18 were included in the final analysis. Variables were summarized with frequencies and percentages. Univariate models were fit, and multi-variable models will be fit, selecting variables with p values of 0.1 or less. Odds ratios with corresponding 95% confidence intervals for univariate analysis are presented. The study was approved by the UAB Institutional Review Board. RESULTS/ANTICIPATED RESULTS: A total of 5025 STI screenings were performed. Males (OR 4.13; 3.61-4.72), undergraduates (OR 1.33; 1.15-1.54), and persons reporting sex with the same sex (OR 1.88; 1.56-2.28), were significantly more likely to seek care at the SHC. Students with symptoms were more likely to seek care at the SHWC (OR 0.53; 0.47-0.61), while persons who reported contact with STIs were more likely to seek care at the SHC (OR 2.88; 2.22-3.74). The overall percentage of positive screenings was 9.3% for chlamydia (CT), 3.0% for gonorrhea (GC), 0.8% for trichomoniasis (TV), 0.7% for syphilis, and 0.3% for HIV with higher percentages of positive for CT (OR 1.60; 1.30-1.96) and GC (OR 2.02; 1.44-2.85) in the SHC. A greater percentage of positives for TV (OR 0.37; 0.14-0.96) was found in the SHWC. DISCUSSION/SIGNIFICANCE OF FINDINGS: Based on demographics of persons utilizing services, embedding a dedicated SHC within a university SHWC may expand populations reached for STI screening. With higher percentages of patients testing positive for CT and GC, a SHC may allow for greater diagnosis and treatment of STIs in general screening and persons presenting as contacts.
ABSTRACT IMPACT: This study will be the first to explore the relationship between preeclampsia and breast cancer risk using the largest cohort of Black women in the US, and it will guide future research and potentially inform clinical practice to reduce breast cancer disparities in this population. OBJECTIVES/GOALS: Black women are disproportionately impacted by preeclampsia. This disorder induces hormonal changes that may contribute to diseases such as breast cancer. However, there is a lack of clear data on the relationship between preeclampsia and breast cancer, and few previous studies included Black women. This study will work to fill this knowledge gap. METHODS/STUDY POPULATION: We prospectively assessed the association between preeclampsia during pregnancy and risk of breast cancer in 43,040 parous women in the Black Women’s Health Study, a nationwide cohort of Black women who were ages 21 -69 at enrollment in 1995. Through 2017, we confirmed 1,968 incident diagnoses of invasive breast cancer. Approximately 6% of parous women reported a diagnosis of preeclampsia; characteristics of the population at baseline are shown in Table 1. We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of breast cancer overall. We used age as the time scale and adjusted for breast cancer risk factors including parity, age at first birth, age at menarche, and body mass index (BMI) at age 18. RESULTS/ANTICIPATED RESULTS: : Compared to parous women without a history of preeclampsia, women with a history of preeclampsia in any pregnancy were not at an increased risk of breast cancer overall (HR 0.98; 95% CI 0.81, 1.18). These preliminary results suggest that history of preeclampsia is not an important risk factor for breast cancer overall in Black women. Our analyses are ongoing to evaluate whether the association may vary by estrogen receptor status or within subgroups of the population defined by age, menopausal status, BMI, and time since last pregnancy. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will provide unprecedented knowledge on the association between hypertensive diseases during pregnancy and incidence of breast cancer in the largest cohort of Black women in the U.S.
ABSTRACT IMPACT: Identifying differential COVID-19 progression across the disease continuum may help policymakers and service providers better identify or predict gaps in services and resources and develop precision strategies to support COVID-19 patients where the need is mostly needed. OBJECTIVES/GOALS: Single institution studies have documented COVID-19 disproportionally affected US racial and ethnic minority groups compared to Whites. However, few population-wide data studied severity and death in multiracial populations. We aim to examine the current disparity in the COVID-19 continuum, including hospitalizations, severity, and death. METHODS/STUDY POPULATION: Data on 67,094 laboratory documented COVID-19 cases nested from the state-wide ‘OneFlorida’ research consortium through August 3, 2020, were assessed to decide differences and disparities in COVID-19 outcomes. A COVID-19 outcome continuum outlining the proportions of cases transitioning from diagnosis to death was constructed (Figure 1). OneFlorida partners provide health care to more than 40% of Floridians in the nation’s third-largest and very diverse state. OneFlorida partners encompass hospitals, practice/clinic settings, and physicians, which provide care for 15 million patients across all of Florida’s 67 counties. It is part of the Patient-Centered Outcomes Research Institute (PCORI). RESULTS/ANTICIPATED RESULTS: Among cases, 25,443 (37.9%) were non-Hispanic Whites, 11,709 (17.5%) were non-Hispanic Blacks, and 16,119 (24.0%) were Hispanics. Among COVID-19 patients, Blacks and Hispanics had a higher frequency of emergency department (ED) visits (45.7% and 46.0%, respectively), whereas admission rates were higher in Blacks (15.6%) and Whites (15.9%) than in Hispanics (11.5%). Blacks had the highest rates of intubation (3.6%) and in-hospital deaths (2.7%) compared to Whites (2.5% and 2.3%, respectively) and Hispanics (1.3% and 1.4%, respectively), Figure 1. When rates were indexed to the state census data, Blacks had the worst rates across the disease continuum (infection to death). In comparison, Hispanics had higher rates of ED visits but lower rates of intubation and death, Table 1. DISCUSSION/SIGNIFICANCE OF FINDINGS: Outcomes continuum is a useful tool at an individual-level to assess care outcomes and at population-level as a framework to analyze the proportion of population with COVID-19 that progress to each successive disease stage. This will help policymakers to better identify gaps in services and develop precision strategies to support COVID-19 patients.
ABSTRACT IMPACT: This study will help to characterize the root causes of racial and ethnic disparities in viral respiratory outbreaks and determine the extent to which this is unique to the COVID-19 pandemic, so that preventative interventions can be designed for future pandemics and epidemics. OBJECTIVES/GOALS: The causes of racial and ethnic disparities in COVID-19 clinical outcomes are multifactorial but include social inequity driven by structural racism. This study seeks to characterize the patterns of these disparities by linking patient-level EHR data with population-level sociodemographic measures. METHODS/STUDY POPULATION: This retrospective review of adult patients tested for SARS-CoV-2 in the UCHealth System will compare rates of COVID-19 infection, hospitalization, in-hospital mortality and 30-day mortality across racial and ethnic groups. Race and ethnicity are determined by patient self-report in the EHR. Univariable and multivariable regression analyses will be used to assess the association of these outcomes with sociodemographic factors. Potential confounders that will be adjusted for include Charlson Co-morbidity Index, disease severity and likelihood of readmission. Using chi-square tests, we will assess differences in the race/ethnicity distributions between this cohort and those from the 2009 H1N1 Pandemic and the 2018-19 influenza season. RESULTS/ANTICIPATED RESULTS: Of the first 459 patients hospitalized for COVID-19 in March and April 2020, race/ethnicity were: 194 Hispanic (42.3%), 104 non-Hispanic Black (22.6%), 83 non-Hispanic white (18.1%), 43 Asian (9.4%), and 35 other or unknown race (7.6%). There were significant differences in the race/ethnicity distribution compared to the cohort of patients hospitalized for viral respiratory infection during the 2018-19 influenza season (n=254, p <0.001): 58 Hispanic (22.8%), 52 non-Hispanic black (20.4%), 116 non-Hispanic white (45.7%), 15 Asian (6%), and 13 other or unknown race (5.1%). Our anticipated results include further adjusted analyses and comparisons to the 2009 pandemic. We will compare COVID-19 prevalence and outcomes by race/ethnicity with other viral infection outbreaks, adjusting for confounders. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial hospitalizations for COVID-19 at our institution are notable for a high proportion of Hispanic patients and smaller proportion of non-Hispanic whites, in contrast to the prior year. Our study will demonstrate the extent to which racial and ethnic disparities are typical in viral respiratory outbreaks, which can guide future interventions.
Translational Science, Policy, & Health Outcomes Science
ABSTRACT IMPACT: Antibiotic stewardship guidelines should consider the barriers clinicians in low- and middle-income countries face due to limited biomarkers for determining the etiologic pathogen for viral infections like respiratory syncytial virus (RSV) that have a similar presentation to bacterial infections. OBJECTIVES/GOALS: We aimed to evaluate antibiotic administration practices in children who were hospitalized at a government-run hospital in Amman, Jordan, where point-of-care testing is limited. We hypothesized those with RSV are more likely to be administered antibiotics during their hospitalization than children without RSV. METHODS/STUDY POPULATION: We conducted a cross-sectional cohort study in Jordanian children hospitalized with history of acute respiratory symptoms and/or fever from 2010 to 2013. Admitting diagnoses were dichotomized into suspected viral- (e.g., bronchiolitis) and bacterial-like infection (e.g., sepsis, pneumonia). Stratifying by sex, we performed a polytomous logistic regression adjusting for age, underlying medical condition, maternal education, and region of residence to estimate prevalence odds ratios (PORs) and 95% confidence intervals for macrolides, broad-, and narrow-spectrum antibiotics during hospitalization. Sensitivity and specificity of admission diagnoses and laboratory results were compared. RESULTS/ANTICIPATED RESULTS: Children with a suspected viral-like admission diagnosis, compared to those with suspected bacterial-like, were 89% less likely to be administered a narrow-spectrum antibiotic (POR: 0.11; p<0.001). There were slight differences by sex with males having a lower prevalence than females of narrow-spectrum or broad-spectrum antibiotic administration; but they had a higher prevalence of macrolide administration. Overall, children with RSV had a 30% probability (sensitivity) of being assigned to a suspected viral infection; whereas RSV-negative children had an 85% probability (specificity) of being assigned to a suspected bacterial infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: Children with a suspected viral-like infection were less likely to receive an antibiotic; however, when evaluating the accuracy of admission diagnosis to RSV-laboratory results there were considerable misclassifications. These results highlight the need for developing antibiotic interventions for Jordan and the rest of the Middle East.
ABSTRACT IMPACT: This work seeks to improve the diagnostic accuracy of urinary tract infection among hospitalized older adults and mitigate antibiotic overuse in this population. OBJECTIVES/GOALS: Primary objective: To determine the diagnostic accuracy of serum procalcitonin (PCT) for the diagnosis of symptomatic urinary tract infection (UTI) in hospitalized older adults. Secondary objectives: (1) To develop a predictive model for the diagnosis of UTI; (2) To determine the ability of PCT in discriminating between lower and upper UTI. METHODS/STUDY POPULATION: We performed a prospective observational cohort study of 228 participants from a single institution. The study population included older adults (age 65 or older) who were hospitalized on the general medicine wards with a possible or suspected urinary tract infection (UTI). Upon obtaining informed consent, serum procalcitonin (PCT) was processed on remnant blood samples collected from the emergency department. We performed additional data collection through the electronic health record to obtain demographic information, clinical characteristics, and other laboratory and imaging results. Clinicians were surveyed for the diagnosis of UTI and charts were adjudicated by independent reviews of the medical record by infectious diseases experts to determine the primary endpoint of symptomatic UTI. RESULTS/ANTICIPATED RESULTS: We anticipate that serum procalcitonin predicts the presence of symptomatic urinary tract infection (UTI) by demonstrating an area under the receiver operating characteristic curve of at least 0.85. A predictive model developed in our cohort for the diagnosis of symptomatic UTI will be improved by the addition of serum PCT to the prediction model. Finally, we anticipate the serum PCT will accurately discriminate between upper and lower UTI. DISCUSSION/SIGNIFICANCE OF FINDINGS: Diagnosis of symptomatic UTI in hospitalized older adults is challenging and may lead to overuse of antibiotics and the development of antibiotic resistance in this vulnerable patient population. Serum procalcitonin offers a novel diagnostic strategy in the diagnosis of symptomatic UTI to enable more appropriate antibiotic therapy.
ABSTRACT IMPACT: Younger patients receiving biologics for rheumatoid arthritis have higher medical expenditure. OBJECTIVES/GOALS: TNF inhibiting biologic disease modifying antirheumatic drugs are among the most highly regarded treatment options for rheumatoid arthritis (RA). We aimed at evaluating the medical and prescription costs associated with monoclonal antibody use vs. other RA treatment options in subjects diagnosed with RA. 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 identify all RA subjects (n=_____). Demographics and MEPS-provided flags for RA were abstracted from the medical condition files for all the subjects surveyed (2008-2018). Prescribed biologics were identified based on generic and brand names following a manual review to detect any misspellings. Total medical expenses and prescription expenses were abstracted for all identified RA subjects. Subject were surveyed for two consecutive years, thus expenses were assessed for each of the two surveyed years. Costs were adjusted for inflation and expressed in 2018 dollars. The relationship between biologics use, cost and age or gender was evaluated by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: Most RA subjects did not use biologics. RA was more prevalent in women than in men with no significant correlation between sex and the use of biologics in year 1, year 2, or the combined years (p=.44, p=.63, and p=.65, respectively). Biologics users were found to be significantly younger (p<.001), with a mean of 52.8 years compared to 59 years in those who did not use biologics. The 95% confidence interval was 3.7 to 8.6 years younger than non-users. Total medical and prescription costs were higher for biologics users (p<.001) in all analyses. The mean prescription cost difference was $24,038 more per year for biologics users, and $26,296 more total medical expenses, CI $20,502-$27,230 and CI $21,947-$30,646, respectively. There was a trend for biologics users to have higher non-prescription medical expenses (p=.05). DISCUSSION/SIGNIFICANCE OF FINDINGS: Interestingly, biologics non-users had some extreme outliers with expenses far higher than any biologics users, possibly due to poorly controlled RA due to age and/or comorbidities. Yet, our most interesting findings are the higher use of biologics among younger RA subjects and the elevated costs of care being driven mainly by prescriptions cost.
ABSTRACT IMPACT: The impact of this study is that the results may lead to the development of effective educational programs and a comprehensive cancer control program while verifying patients and medical care providers adherence and compliance with cancer clinical guidelines. OBJECTIVES/GOALS: The objective of this study is to assess risk factors, preventive measures, and screening practices for human papilloma virus (HPV) associated cancers in a sub-population in Central-Eastern Puerto Rico (PR). METHODS/STUDY POPULATION: This is a sub-analysis from an annual descriptive cross-sectional questionnaire of risk factors, preventive measures, and screening practices for cancer in PR administered at a private hospital campus using a convenience sample of healthy and non-healthy adults. RESULTS/ANTICIPATED RESULTS: Out of 345 enrolled subjects in 2019 for the questionnaire, 67 were enrolled by the first author, from which 66 (19%) subjects qualified for this sub-analysis for completing the study: 79% females. When analyzing HPV risk factors, 5% of the participants were smokers. Eleven percent of the subjects received the preventive HPV vaccine. Among those non-vaccinated and eligible for vaccination, 95% were willing to get it. Seventy one percent of females 21-29 years old and 97% of 30-65 years olds had age-appropriate cervical cancer screening. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite the low prevalence of HPV vaccination, almost all of the subjects within the age range for HPV vaccination were willing to get it. Also, there was a lower prevalence of cervical cancer screening in females 21-29 years old when compared with 30-45 years old. In conclusion, there is a need for more education about HPV associated cancers and vaccine.
ABSTRACT IMPACT: Despite their clinical benefits reported in patients with Parkinson’s, statin use is not associated with cost savings. OBJECTIVES/GOALS: Statins have unique lipid-lowering, anti-inflammatory and anti-oxidant benefits. Their pleiotropic benefits were shown to decrease risk of occurrene and progression of Parkinson’s disease (PD). In this study we explored whether or not statin use reflects medical or prescription cost savings. 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 identify all PD subjects (n=613). Demographics and PD ICD9/10 codes, 332/G20, were abstracted from the medical condition files for all the subjects (1996-2018). Prescribed cholesterol drugs were identified based on generic and brand names following a manual review to detect any misspellings. Total medical expenses and prescription expenses were abstracted for all identified PD subjects. Subject were surveyed for two consecutive years, thus expenses were assessed for each of the two surveyed years. Costs were adjusted for inflation and expressed in 2018 dollars. The relationship between cholesterol drug use, cost and age or gender was evaluated by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: Out of the 613 PD subjects identified, 421 received no cholesterol management, 15 received non-statins, 153 received a statin and 24 received a statin-based combo therapy. While the medical expenses in the general population receiving a statin are roughly three times higher than non-statin users, no significant cost difference was noticed between PD subjects receiving or not statins. However, after adjusting for age and gender, receiving statin vs. non-statin vs combo vs none was significantly associated with total expense (p=0.017) suggesting that cholesterol management decision may play a significant role. DISCUSSION/SIGNIFICANCE OF FINDINGS: Selection of specific cholesterol treatment may play a considerable role in the overall PD expenditure. Duration of statin treatment and type of statin are expected to play a role.
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.
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.