bluuebunny/crossref_metadata_2025 huggingface dataset:
74325 Vast sex-specific differences in transcriptional landscapes of pancreatic neuroendocrine tumors
Authors: Ivanov Nikolay A. , Fahey Thomas J. , Mason Christopher E. , Min Irene M.
Published: March 2021

ABSTRACT IMPACT: Here, we describe extensive sex-specific differences in the transcriptomes of pancreatic neuroendocrine tumors (PNETs). Given that the clinical course of PNETs differs by sex (female sex is associated with better survival), achieving a greater understanding of the specific molecular sexual dimorphisms is invaluable for advancing personalized treatment. OBJECTIVES/GOALS: Epidemiologic studies demonstrate that pancreatic neuroendocrine tumors (PNETs) exhibit sexual dimorphisms with regards to prognosis, disease recurrence, and complication rates. We sought to compare the transcription and DNA methylation landscapes of PNETs by sex, to elucidate molecular differences that may underlie this sex disparity. METHODS/STUDY POPULATION: RNAseq data was generated from PNETs surgically resected at our institution (9 Female; 12 Male patients). RNA was extracted with the RNeasy Mini Kit, stranded sequencing libraries were prepared with TruSeq, and paired end sequencing was done on the HiSeq 2500/4000 systems. Transcript-level quantification was performed with salmon, and DESeq2 was used for differential expression analysis. To account for significant variation due to covariates other than sex, surrogate variables were computed with the SVA package and adjusted for. The goseq package was used for gene set over representation analysis. Matched DNA methylation (DNAm) and RNAseq data was downloaded from GEO (16 F; 16 M). Raw DNAm data was processed with minfi. Differential methylation analysis was done with limma and bumphunter. Analysis was done in R. RESULTS/ANTICIPATED RESULTS: We found that 826 autosomal genes were differentially expressed (DE) by sex in PNETs (at FDR ≤0.1). Gene set over representation analysis performed on the DE genes revealed significant enrichment for several processes, including ‘ascorbate & aldarate metabolism’ and ‘positive regulation of ERK1 & ERK2 cascade’ (all FDR ≤0.1). When we compared DNAm profiles between sexes, we found 8 CpGs which were differentially methylated by sex (at FDR ≤0.1), 7 of which were proximal to genes. Methylation of one of the sex-associated CpGs, overlapping the gene TIMM8B, was found to be negatively correlated with gene expression (rho=-0.41; p-value=0.02). Interestingly, TIMM8B deletion has been previously reported in other non-pancreatic neuroendocrine tumors. There were no differentially methylated regions between sexes. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings demonstrate that PNETs exhibit extensive sexual dimorphisms with regards to gene expression profiles but have largely congruent methylomes by sex. These molecular differences may contribute to the variability in clinical course between men and women, and their characterization is vital for the advancement of personalized medicine.
97856 Implementation of DPYD and UGT1A1 pharmacogenetic testing to guide chemotherapy dosing
Authors: Varughese Lisa A. , Lau-Min Kelsey S. , Teitelbaum Ursina , Osei-Akoto AnnaClaire , Reddy Nandi , Damjanov Nevena , Massa Ryan , Tuteja Sony
Published: March 2021

ABSTRACT IMPACT: The implementation of DPYD and UGT1A1 pharmacogenetic testing, a promising tool of precision medicine, translates evidence-based research into clinical oncology practice with personalized dosing to better predict interpatient variability in chemotherapy tolerability. OBJECTIVES/GOALS: Patients with DPYD and UGT1A1 genetic variants are at risk for severe toxicity from fluoropyrimidines and irinotecan, respectively. We propose that providing clinicians with the option to order a pharmacogenetic (PGx) test with relevant dose recommendations will increase test uptake to guide pharmacotherapy decisions and improve safety outcomes. METHODS/STUDY POPULATION: We plan to conduct a non-randomized, pragmatic, open-label study in 600 adult patients with gastrointestinal (GI) cancers initiating a fluoropyrimidine- and/or irinotecan-based regimen at three cancer centers within a health system. Implementation metrics of a new, in-house laboratory developed PGx test will be measured, including feasibility of returning results within one week, fidelity of providers following dose recommendations, and penetrance via test ordering rates. Clinical aims will include assessing severe toxicity during the first six months of chemotherapy. Outcomes will be compared to a historical control of GI cancer patients enrolled in a biobank and treated with standard dose chemotherapy. RESULTS/ANTICIPATED RESULTS: We anticipate that there will be an increase in PGx test uptake given its shorter turnaround time to facilitate clinical decision-making prior to the first dose of chemotherapy. Through integration of test results in the electronic health record (EHR) and clinical decision support tools for patients with actionable genotypes, we also expect that providers will have a high level of agreement to the recommended dose adjustments. We anticipate a decreased incidence of severe (Grade >3) toxicity among prospectively genotyped patients in the first six months of chemotherapy compared to DPYD and UGT1A1 variant carriers in the historical control group. Exploratory clinical utility data on costs of hospitalizations, chemotherapy treatment, PGx test, and medical services will also be reported. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study aims to address barriers identified by key stakeholders to implementing PGx testing to better tailor chemotherapy dosing to the genetic profiles to patients. This may prevent adverse event-related hospitalizations, improve quality of life for patients, and reduce health system resource utilization costs.
66942 Metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure
Authors: Langley Raymond J. , Migaud Marie M. , Files D. Clark , Morris Peter
Published: March 2021

ABSTRACT IMPACT: The pathophysiologic features of a metabolomic endotype that predicts patient outcomes due to sepsis have the potential to direct new therapies that target immune dysregulation and bioenergetic insufficiency. OBJECTIVES/GOALS: Acute respiratory failure (ARF) requiring mechanical ventilation is a frequent complication of sepsis and other disorders. It is associated with high morbidity and mortality. Despite its severity and prevalence, little is known about metabolic and bioenergetic changes that accompanying ARF. METHODS/STUDY POPULATION: In this study, semiquantitative and quantitative ultrahigh performance liquid chromatography mass spectrometry (UHPLC MS) analysis was performed on patient serum collected from the Trial with Acute Respiratory failure patients: evaluation of Global Exercise Therapies (TARGET). Serum from survivors (n=15) and nonsurvivors (n=15) was collected at day 1 and day 3 after admission to the medical intensive care unit as well as at discharge in survivors. Pathway analysis of the biochemical changes was performed to determine whether the disruption in specific metabolic pathways can identify the bioenergetic and metabolomic profile of these patients. RESULTS/ANTICIPATED RESULTS: Significant metabolomic differences were related to biosynthetic intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, and decreased acyl-glycerophosphocholines in nonsurvivors compared to survivors. The metabolites associated with poor outcomes are substrates of enzymatic processes dependent on NAD(P), while the abundance of NAD cofactors rely on the bioavailability of dietary vitamins B1, B2 and B6. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with an alteration of the glutathione-dependent drug metabolism as characterized by the substantial differences observed in the acetaminophen metabolome. DISCUSSION/SIGNIFICANCE OF FINDINGS: This metabolomic endotype represents a previously unappreciated association between severity of outcomes and micronutrient deficiency, thus pointing to new pharmacologic targets and highlighting the need for nutritional remediation upon hospitalization to improve patient outcomes due to ARF.
81007 Training Biomedical Engineers in Regulatory Science: Critical Role of Experts from Industry and FDA
Authors: Lottes Aaron E. , Brightman Andrew O.
Published: March 2021

ABSTRACT IMPACT: Lack of regulatory knowledge and education is a key barrier to the translation of medical devices and we describe the design and results for a university graduate-level course providing training on medical device regulatory submissions for approval that can help fill this unmet need and improve and accelerate translational success. OBJECTIVES/GOALS: Within the Indiana CTSI, the Medical Technology Advance Program (MTAP) in the Purdue University Weldon School of Biomedical Engineering (BME) offers three courses in regulatory science and regulatory affairs for medical devices. One course is focused on regulatory submissions for approval, and this report details the course design and evaluation. METHODS/STUDY POPULATION: For Fall 2020, the Regulatory Submissions for Approval course was enhanced to increase participation from regulatory professionals in US FDA and industry, with the core content, curriculum and course design led by BME faculty. The course was taught two days per week and included both in-person and remote (synchronous or asynchronous) attendance options. During the first class session each week a topic was covered in standard lecture format by BME faculty with industry regulatory experience. During the second class session, guests from both industry and FDA were invited to provide in-depth discussion on the topic, share perspectives and viewpoints, present real-world examples, experiences, and case studies, and answer student questions. An end of semester survey evaluated the effectiveness of the course design. RESULTS/ANTICIPATED RESULTS: Medical Device regulatory submissions and related activities were taught including product classification, presubmissions and meetings, 510(k), de novo, EUA, PMA, HDE, and advisory panels. FDA history, regulatory careers, regulatory science, and EU, China, and Japan regulations were also discussed. Overall, 29 speakers from FDA and industry participated live via video calls. A survey completed by 21/23 studentsrevealed overall satisfaction: all reported increased regulatory understanding and 20/21 learned ‘a lot’ or ‘an incredible amount’. The weekly lecture was the top factor contributing to learning, and guest speakers were the next most important factors. Nearly all students indicated FDA and industry speakers were ‘very’ or ‘extremely’ valuable/helpful. Additional results will be presented. DISCUSSION/SIGNIFICANCE OF FINDINGS: The three courses are designed to improve medical device translation by training students to better understand regulatory processes and pathways. Survey results and feedback indicated this course was successful. Continued participation from FDA and industry is critical to the learning. Additional case studies will also help enhance learning.
39901 Breaking down silos to synergize clinical trial development and initiation: The Clinical Research Support Center, University of Minnesota
Authors: Odlaug Brian L. , Crevel Francoise , Tosun Nicole , Lee Ryan , McKenzie Carrie , Bellin Melena , Prich Brenda , Weisdorf Daniel
Published: March 2021

ABSTRACT IMPACT: The model of the Clinical Research Support Center at the University of Minnesota of streamlining clinical trial infrastructure can be leveraged by the larger clinical trial community to create valuable efficiencies and facilitate faster initiation of research activities by supporting researchers from concept to dissemination. OBJECTIVES/GOALS: Substantial time, energy, and money are spent bridging disparate resources in research. We describe how the University of Minnesota’s (UMN) Clinical Research Support Center (CRSC) streamlines trial infrastructure, creating valuable efficiencies to support researchers from concept to dissemination. METHODS/STUDY POPULATION: The CRSC, established in 2018 through the Clinical and Translational Science Award (CTSA) program, brings resources together in a single, centralized, and convenient location to help researchers navigate the UMN clinical research startup process and specifically to assist with the development and initiation of a research study from feasibility assessment to project opening. Diverse expertise in components of human subject research is available to support the broad scope of projects at a large institution like the UMN. We present how CRSC services, when coordinated by Clinical Research Specialists, have been used to improve access to clinical research resources during the start up process. RESULTS/ANTICIPATED RESULTS: Since inception in 2018, the CRSC has provided support to over 1700 studies with 437 research projects referred to a Clinical Research Specialist within the CRSC. Of those projects, 97 (22.2%) received comprehensive support from the following expert groups: regulatory guidance (n=74), biostatistics (n=68), clinical (hospital or clinic) partners (n=60), recruitment (n=36), budget development assistance (n=30), and (bio)informatics (n=27). Successful examples of synergies to streamlining study start up include shortening the window between protocol development support from Clinical Research Specialists and IRB submission preparation through to Regulatory Specialists to 3 days. DISCUSSION/SIGNIFICANCE OF FINDINGS: Providing cross-functional support to research teams through the CRSC increases the likelihood of quicker and successful execution and completion of research initiation and subsequently impacts the dissemination of that research to patients and the broader community.
87842 The Effects of Head Impact Exposure on Changes in Neurocognitive and Oculomotor Function Across a High School American Football Season: A Pilot Study
Authors: Huibregtse Megan E. , Macy Jonathan T. , Steinfeldt Jesse A. , Kawata Keisuke
Published: March 2021

ABSTRACT IMPACT: This work reveals the influence of a season of American football-related head impact exposure on two functional outcome measures in a cohort of adolescent boys, shedding light on the chronic effects of 'subconcussive head impacts.' OBJECTIVES/GOALS: To examine the influence of a season of exposure to head impacts in American football on changes in neurocognitive and oculomotor function in adolescent male athletes. METHODS/STUDY POPULATION: Participants were recruited from a local high school: the football group (FB; n = 26) was instrumented with sensor-installed mouthguards to track impact exposure during games and practices, and members of the men’s cross-country team were recruited to the control group (CON; n = 9). All participants were administered Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) and were assessed for near point of convergence (NPC) at pre- and post-season. Linear models will be fit for changes in the five ImPACT composite scores and NPC values, with group and one of the head impact variables as predictors for each model. In a secondary within-group analysis, correlation coefficients will be calculated for the relationships between the head impact variables and the functional change scores for the FB group. RESULTS/ANTICIPATED RESULTS: The two groups did not differ significantly on age or number of previous concussions; the CON group had significantly lower BMI. Group assignment was significantly associated with change in NPC (p < 0.05 for all three models); no significant associations were observed for any of the head impact variables with change in NPC. Group and each of the head impact variables (total impacts, sum of peak linear acceleration [PLA], and sum of peak rotational acceleration [PRA]) were not significantly associated with change in any of the five ImPACT composite scores. Change in visual memory composite score was negatively correlated with total impacts (r = -0.37, p = 0.034) and sum of PRA (r = -0.36, p = 0.040). DISCUSSION/SIGNIFICANCE OF FINDINGS: Significant, albeit relatively weak, correlations between change in visual memory composite score and two head impact kinematic variables, coupled with significant increases in NPC in the FB group compared to the CON group, suggest that a season of exposure to football-related head impacts has the potential to elicit minor functional impairments.
00004 Accuracy of the PREP2 algorithm for predicting Three Month Upper Limb Functional Capacity within a United States population of Persons with Stroke
Authors: Barth Jessica , Waddell Kimberly , Bland Marghuretta D. , Lang Catherine E.
Published: March 2021

ABSTRACT IMPACT: Evaluate the accuracy of applying a predictive algorithm using clinical measures only in persons with stroke in the US. OBJECTIVES/GOALS: PREP2 is an algorithm, that predicts UL functional capacity at 3 months post stroke from measures taken within the first week.(1, 2) Despite its accuracy and ease of use, challenges arise of applying PREP2 in the US. The objective of this study was to evaluate the accuracy of PREP2 using only clinical measures in persons with stroke in the US. METHODS/STUDY POPULATION: Individuals with first-ever stroke were recruited from a local hospital and followed longitudinally, as part of an ongoing observational cohort. Variables captured within two weeks of stroke and entered into the algorithm were: age, SAFE score(1-3) and NIH Stroke Scale(4) total score. The algorithm classifies individuals into one of four expected categories: excellent, good, limited, or poor. The dependent variable was the predicted category of UL functional capacity as defined by ranges of the 3-month Action Research Arm Test score.(5) Accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the algorithm, were calculated using a 4x4 contingency table. Other statistics analyzed include demographic characteristics and a weighted kappa for the algorithm. RESULTS/ANTICIPATED RESULTS: Data from 49 individuals were analyzed (57% male, 88% ischemic stroke, age = 65±8.56 years). Expected categorization matched observed categorization in 29/49 subjects, with the overall accuracy of the algorithm of 59% (95% CI = 0.44-0.73). The sensitivity of the algorithm was low except for the excellent category (0.95). Specificity was moderate to high for good (0.81), limited (0.98), and poor (0.95) categories. PPV was low for all categories and NPV was high for all categories except the good category. Additional results including weighted kappa and inaccuracy of predictions to be presented. DISCUSSION/SIGNIFICANCE OF FINDINGS: PREP2 algorithm, with clinical measures only, is better than chance (chance = 25% for each of the 4 categories) alone at predicting a category of UL capacity at 3 months post stroke. PREP2 is a simple tool that facilitates evaluation of eventual UL outcome from measures routinely captured after a stroke within most healthcare settings in the US.
47149 Imaging Tools for Early Detection of Kidney Disease.
Authors: Baldelomar Edwin J. , Reichert David , Shoghi Kooresh , Bennett Kevin M.
Published: March 2021

ABSTRACT IMPACT: Chronic kidney disease (CKD) affects ˜15% of the US population and the majority of patients are diagnosed too late to benefit from early intervention. We are developing a new diagnostic imaging tool (RadioCF-PET) for the kidney to enable early detection of diseases and to monitor overall kidney health. OBJECTIVES/GOALS: Nephron mass, or the number of functioning nephrons, is a measure of the functional capacity of the kidney. RadioCF-PET may enable early detection of nephron loss in patients with or at risk of CKD before changes are clinically detectable, facilitating early interventions to improve outcomes in these patients. METHODS/STUDY POPULATION: RadioCF-PET, labeled with Cu-64, has the advantage of using sub pharmacological doses for imaging, carrying low risk and can be used with the FDA’s exploratory IND (eIND) mechanism for early in human testing. We are developing the technology to be used in pre-eIND toxicology and pharmacology studies. We are also developing other aspects of translational science to propel this technology toward translation, including: market analysis, critical path to market, customer discovery, and commercialization strategy. RESULTS/ANTICIPATED RESULTS: Milestone 1: Apply technology in mouse model study and in human kidneys rejected for transplant. Anticipated Result 1: PET signal from RadioCF-PET correlates with glomerular density in healthy and diseased model male mice (R2 = 0.98). RadioCF-PET signal correlates with glomerular number in a donated human kidney (R2= 0.78). Milestone 2: Application to federal funding (STTR) and gap funding mechanisms to enable pre-eIND studies. Anticipated Result 1: Application for funding will aid to clarify and validate our market analysis and commercialization strategy. Milestone 3: Continued research and development with the technology in new studies. Other Anticipated Results: Future work with RadioCF-PET will enhance technology performance in preparation for pre-eIND studies. DISCUSSION/SIGNIFICANCE OF FINDINGS: We foresee a large clinical and commercial potential for RadioCF-PET to provide precise, early monitoring in patients at risk for or with CKD. The two biggest hurdles for clinical translation are validating safety and proving efficacy. This work targets both issues to facilitate RadioCF-PET toward clinical translation.
38351 Immune-related adverse events in cancer patients receiving immune checkpoint inhibitors
Authors: Lucas Margaret Byrnethew , Pai Lori , Breeze Janis , Parsons Susan
Published: March 2021

ABSTRACT IMPACT: The existing literature describing immune-related adverse events (irAE) has predominantly focused on clinical trial populations, which may not be representative of the broader population receiving immune checkpoint inhibitors (ICI), so we sought to perform a comprehensive evaluation of irAE in a real-world population of cancer patients being treated with ICI. OBJECTIVES/GOALS: With a cohort of patients with malignancy treated with ICI, we characterized incidence, severity, timecourse of ir-AE. We sought to inform providers who prescribe ICI to recognize the clinical burden of irAE in an effort to more effectively communicate the benefits and risks of ICI with patients. METHODS/STUDY POPULATION: After obtaining approval from the institutional review board, we used a pharmacy database to identify adult cancer patients treated with an ICI between January 2014 and October 2018. We used electronic medical records to obtain baseline variables. Each patient was followed at each clinic visit for 12 months for development of a physician-reported irAE.

For irAE, site and grade were recorded as documented by the provider. At diagnosis and each follow-up visit, we collected: 1) adjustments to ICI, immunosuppression, and hormone therapy.

Continuous variables were summarized using mean and standard deviation (SD) or median and interquartile range (IQR). Categorical variables were summarized using frequencies and percentages. Time to development and resolution of irAE were calculated using Kaplan-Meier curves. RESULTS/ANTICIPATED RESULTS: Among 131 patients, two-thirds were men, and 60% were Caucasian with a mean age was 65 years. Nearly 40% had an Eastern Cooperative Oncology Group performance score of 2 or higher. A small proportion (3.1%) had an autoimmune disorder. Nearly half had lung cancer (49.6%), and several had received radiation (33.6%). Over 70% were former or current smokers. In total, 57 patients (43.5%) developed an irAE, resultng in a total of 95 irAE, at a median of 208 days (126 days, not reached). The most common irAE included dermatitis, thyroiditis, pneumonitis, and hepatitis. Of 95 irAE, half were grade 1, 30% were grade 2, and nearly 20% were grade 3 or higher. Median time to resolution was 85 days (56-183 days). DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that irAE are clinically impactful in this relatively unfit, medically complex population, which may be a more accurate reflection of patients receiving ICI in everyday practice. This study showcases that this population is susceptible to irAE, although this needs to be examined in larger, prospective trials.
55715 Quantification of Neonatal THC Exposure Following Prenatal Marijuana Use
Authors: Kennon-McGill Stefanie , Moody Heather , Moran Jeff , James Laura
Published: March 2021

ABSTRACT IMPACT: Quantification of neonatal THC exposure will allow for better insight into how THC exposure correlates with neurodevelopmental outcomes. OBJECTIVES/GOALS: Tetrahydrocannabinol (THC) use has become increasingly prevalent in recent years, including among pregnant women. However, few, if any, clinical studies have quantified precise in utero exposure levels of THC during pregnancy. Our study aims to fill this gap by using analytical methods to quantify THC in mother and baby following prenatal THC use. METHODS/STUDY POPULATION: Pregnant women were asked to give a self-report of all cannabis and cannabinoid use during pregnancy, including dose, frequency, and route of consumption. Upon arrival at the labor and delivery unit, maternal blood samples were collected. Immediately following birth and 24 hours after birth, umbilical cord and neonatal blood samples were collected, respectively. All blood samples were analyzed using tandem liquid chromatography-mass spectrometry (LC-MS) for the presence of THC, tetrahydrocannabinol carboxylic acid (THC-COOH), and hydroxy-tetrahydrocannabinol (THC-OH). Maternal THC and metabolite levels were compared to both cord and neonate samples. RESULTS/ANTICIPATED RESULTS: To date, we have collected 3 mother-infant sample dyads and 4 mother-infant control samples. We anticipate collecting a total of 20 mother-infant samples from each group. We will quantify levels of THC and its metabolites in maternal samples and compare these to cord and infant samples. We expect that THC/metabolite levels will vary as a function of dose and frequency of consumption. We also expect that THC/metabolites will be higher in umbilical cord blood relative to neonatal blood. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study is among the first to directly measure exposure in the neonate following prenatal cannabis use. Quantification of THC/metabolite concentrations will be supplemented with developmental evaluations of infants at 6 and 12 months of age in order to gain better insight into how THC exposure correlates with neurodevelopmental outcomes.
76644 Cognitive and Behavioral Outcomes in Adolescents with Sickle Cell Disease Before and After a Telehealth Cognitive Remediation Program to Prepare for Transition of Care
Authors: Murdaugh Donna , Tucker Tiffany , Seghatol-Eslami Victoria , Stewart Anne , Lebensburger Jeffery , Wallace Eric , Bhatia Smita
Published: March 2021

ABSTRACT IMPACT: This study is providing a telehealth intervention for the first time in patients with sickle cell disease with the goal of improving cognitive functioning and preparing adolescents for successful transition of care to adult healthcare providers. OBJECTIVES/GOALS: There is a high prevalence of cognitive impairment in adolescents with sickle cell disease (SCD). The purpose of this study is to test the efficacy of an individualized cognitive remediation program designed to promote not just cognitive function, but also adaptive and self-management skills necessary for successful transition to independence. METHODS/STUDY POPULATION: 12 participants with SCD (5 males, ages 10-16) participated in an individualized program, Cognitive-Remediation of Executive and Adaptive Deficits in Youth [C-READY], consisting of three main components: individual goal-based therapy, parent training sessions, and home skill practice. C-READY sessions occur one-on-one with a trained therapist for 8 sessions conducted over 4 weeks. Weekly parent training sessions are also conducted as part of the C-READY program. All of these sessions occurred via telehealth video-calling between the therapist and the adolescent/parent. Participants were evaluated before and after the C-READY program using neuropsychological assessment measures and transition readiness questionnaires. Parents also completed ratings on telehealth delivery, content, and timing. RESULTS/ANTICIPATED RESULTS: Repeated measures ANOVA indicated significant improvement in transition readiness behaviors as rated by parents, including improved independence in medication management (p = 0.029) and in talking with their healthcare providers (p = 0.019). Significant improvement was also demonstrated on a neuropsychological measure related to executive function skills, specifically inhibition and switching (p = 0.012). Results from telehealth surveys (rated on a 5-point Likert scale) indicated overall satisfaction with services (4.2/5), including visual (4/5) and voice quality (4.3/5) of telehealth equipment. Ratings also indicated feeling that their privacy was respected (4/5) and that their interactions with their therapist were appropriate and sensitive (4.5/5). DISCUSSION/SIGNIFICANCE OF FINDINGS: These results provide support for interventions that focus on cognitive skills to improve behaviors necessary for successful transition of care in youth with SCD. Results are also promising for delivery via telehealth in order to address barriers related to access to care. Future results will continue to be reported, as this study is currently ongoing.
77523 Prospective cohort study of predominantly immigrant people with chronic hepatitis B in the Baltimore-metropolitan Washington D.C. area
Authors: Tang Lydia
Published: March 2021

ABSTRACT IMPACT: Building a patient cohort to support clinical-translational research in chronic hepatitis B OBJECTIVES/GOALS: The overall objective of my KL2 project is to delineate the effect of HIV coinfection, and CHB disease stage and hepatitis B (HBV) viremia on the ability of toll-like receptor 8 agonism to restore HBV-specific immune cell function. This abstract describes the characteristics of the cohort from which research blood samples for my KL2 are collected. METHODS/STUDY POPULATION: HOPE is a prospective cohort study enrolling people with CHB including HIV/CHB coinfection, and resolved CHB. Participants are enrolled at primary care clinics in Maryland, Washington D.C., and Virginia. Standard-of-care antiviral treatment with tenofovir alafenamide (TAF) is prescribed through the study if indicated. Patients receiving TAF from the study are either starting treatment, or switching to TAF from another antiviral medication. If receiving TAF, participants are seen every 3-6 months for medication refills, clinical and research blood draws, and adverse event evaluations. Liver fibrosis is measured by FibroScan and a minority undergo liver biopsy. RESULTS/ANTICIPATED RESULTS: So far, 204 people have been enrolled, 177 with CHB (23 HIV/CHB coinfection), and 22 with resolved HBV infection. To date, 45 patients who were viremic at baseline and initiated on TAF have been enrolled. CHB predominantly affects Asian and African immigrants in the U.S, and the majority (77%) of HOPE participants are immigrants from these countries. The majority are male (70%), mean age 51 years (SD ±14). So far, 86 people with CHB monoinfection have been prescribed TAF on-study. Thirty-five percent of these had significant (>F2) liver fibrosis at baseline and half had elevated ALT (mean 47.5, SD ±55 IU/ml). Forty-three percent switched to TAF from another oral antiviral. Most switched due to lack of coverage by health insurance. DISCUSSION/SIGNIFICANCE OF FINDINGS: HOPE is a CHB cohort dedicated to collecting research samples and providing antiviral treatment. It is the foundation for the CHB translational research program at the University of Maryland School of Medicine. The availability of paired viremic and virally suppressed, HIV/CHB, and resolved HBV research samples are strengths of HOPE.
49156 Effects of Race and Demographics on Use of Physical Restraints in the Emergency Department
Authors: Wong Ambrose H. , Whitfill Travis , Ohuabunwa Emmanuel C. , Ray Jessica M. , Dziura James D. , Bernstein Steven L. , Taylor Richard Andrew
Published: March 2021

ABSTRACT IMPACT: Within three EDs in a regional health system in Connecticut, African American race, male gender, non-Hispanic ethnicity, lack of private insurance, and homelessness were associated with significant odds of being physically restrained during a visit. OBJECTIVES/GOALS: Agitated patient encounters in the Emergency Department (ED) are on the rise, and physical restraints are used to protect staff and prevent self-harm. However, these are associated with safety risks and potential stigmatization of vulnerable individuals. We aim to determine factors that are associated with odds of being restrained in the ED. METHODS/STUDY POPULATION: We conducted a retrospective cohort analysis of all patients (≥18 yo) placed in restraints during an ED visit to three hospitals within a large tertiary health system from Jan 2013-Aug 2018. We undertook descriptive analysis of the data and created a generalized linear mixed model with a binary logistic identity link to model restraint use and determine odds ratios for various clinically significant demographic factors. These include gender, race, ethnicity, insurance status, alcohol use, illicit drug use, and homelessness. Our model accounted for patients nested across the three EDs and also accounted for multiple patient visits. RESULTS/ANTICIPATED RESULTS: In 726,417 total ED visits, 7,090 (1%) had associated restraint orders. Restrained patients had an average age of 45, with 64% male, 54% Caucasian and 29% African American. 17% had private insurance, 36% endorsed illicit substances, 51.4% endorsed alcohol use and 2.3% were homeless. African Americans had statistically significant odds of being restrained compared to Caucasians with adjusted odds ratio (AOR) of 1.14 (1.08,1.21). Females (AOR 0.75 [0.71, 0.79] had lower odds of being restrained compared to males while patients with Medicaid (AOR 1.57 [1.46, 1.68]) and Medicare (AOR 1.70 [1.57, 1.85]) had increased odds compared to the privately insured. Illicit substance use (AOR 1.55 [1.46, 1.64]), alcohol use (AOR 1.13 [1.07, 1.20] and homelessness (AOR 1.35 [1.14, 1.16]) had increased odds of restraint use. DISCUSSION/SIGNIFICANCE OF FINDINGS: We showed statistically significant effects of patient demographics on odds of restraint use in the ED. The increased odds based on race, insurance status, and substance use highlight the potential effects of implicit bias on the decision to physically restrain patients and underscores the importance of objective assessments of these patients.
57084 Combining artificial intelligence and robotics: a novel fully automated optical coherence tomography-based approach for eye disease screening
Authors: Song Ailin , Ortiz Pablo , Draelos Mark , Schuman Stefanie G. , Jaffe Glenn J. , Farsiu Sina , Izatt Joseph A. , McNabb Ryan P. , Kuo Anthony N.
Published: March 2021

ABSTRACT IMPACT: Despite its importance in systemic diseases such as diabetes, the eye is notably difficult to examine for non-specialists; this study introduces a fully automated approach for eye disease screening, coupling a deep learning algorithm with a robotically-aligned optical coherence tomography system to improve eye care in non-ophthalmology settings. OBJECTIVES/GOALS: This study aims to develop and test a deep learning (DL) method to classify images acquired from a robotically-aligned optical coherence tomography (OCT) system as normal vs. abnormal. The long-term goal of our study is to integrate artificial intelligence and robotic eye imaging to fully automate eye disease screening in diverse clinical settings. METHODS/STUDY POPULATION: Between August and October 2020, patients seen at the Duke Eye Center and healthy volunteers (age ≥18) were imaged with a custom, robotically-aligned OCT (RAOCT) system following routine eye exam. Using transfer learning, we adapted a preexisting convolutional neural network to train a DL algorithm to classify OCT images as normal vs. abnormal. The model was trained and validated on two publicly available OCT datasets and two of our own RAOCT volumes. For external testing, the top-performing model based on validation was applied to a representative averaged B-scan from each of the remaining RAOCT volumes. The model’s performance was evaluated against a reference standard of clinical diagnoses by retina specialists. Saliency maps were created to visualize the areas contributing most to the model predictions. RESULTS/ANTICIPATED RESULTS: The training and validation datasets included 87,697 OCT images, of which 59,743 were abnormal. The top-performing DL model had a training accuracy of 96% and a validation accuracy of 99%. For external testing, 43 eyes of 27 subjects were imaged with the robotically-aligned OCT system. Compared to clinical diagnoses, the model correctly labeled 18 out of 22 normal averaged B-scans and 18 out of 21 abnormal averaged B-scans. Overall, in the testing set, the model had an AUC for the detection of pathology of 0.92, an accuracy of 84%, a sensitivity of 86%, and a specificity of 82%. For the correctly predicted scans, saliency maps identified the areas contributing most to the DL algorithm’s predictions, which matched the regions of greatest clinical importance. DISCUSSION/SIGNIFICANCE OF FINDINGS: This is the first study to develop and apply a DL model to images acquired from a self-aligning OCT system, demonstrating the potential of integrating DL and robotic eye imaging to automate eye disease screening. We are working to translate this technology for use in emergency departments and primary care, where it will have the greatest impact.
69350 Using Control Charts to Inform Public Health and Community Engagement during the COVID-19 Pandemic
Authors: Inkelas Moira , Manuel Vladimir G. , Emerewa Iheanacho O. , Kuo Tony
Published: March 2021

ABSTRACT IMPACT: Demonstrate applicability of an underutilized method for showing variation that enables public health agencies to respond to the COVID-19 pandemic OBJECTIVES/GOALS: Enacting sensible public policies in the coronavirus disease 2019 (COVID-19) pandemic requires real-time data that civic and public health leaders can easily interpret and act on. This collaboration between a CTSA and a local health department sought a novel use of control charts to provide timely and interpretable data. METHODS/STUDY POPULATION: Healthcare and other industries use control charts to understand the behavior of processes and systems so they can intervene on them. The CTSA science team developed statistical process control charts at the neighborhood level to help illustrate their value for decision-making as the pandemic progresses. This method included accounting for congregate populations (skilled nursing facilities, correctional facilities) to produce data for the general public. RESULTS/ANTICIPATED RESULTS: Patterns in COVID-19 vary over time by neighborhood. Juxtaposing control charts with social characteristics of local areas in a dashboard format provides granularity for decision-makers and data for engaging communities in changing behavior. Annotating time series charts in real time connects events and local knowledge with observed data, which can help authorities and people to learn and act based on variations displayed by the control charts about disease outbreaks and cases. School districts are among those that could benefit from control charts with information about the school community and how COVID-19 spread is occurring. DISCUSSION/SIGNIFICANCE OF FINDINGS: Control charts have rarely been used in public health despite their ease of use and interpretability. This study demonstrates a novel approach to providing timely, accurate data that can support real-time decision-making of government and public health as well as school districts, businesses, and others.
78595 Assessing the influence of comorbidities in patients undergoing sternal reconstruction following cardiac surgery: a single institution's 15 year review
Authors: Soto Edgar , Kumbla Pallavi A. , Restrepo Ryan , Delay Thomas K. , Awad Shadi K , Collawn Sherry , de la Torre Jorge , Denney Brad , Fix Jobe R , Grant John H , Kilic Ali , King Timothy W , Patcha Prasanth , Davies James , Vasconez Luis O , Myers Rene P.
Published: March 2021

ABSTRACT IMPACT: Current practice guidelines offer a variety of treatment options for sternal reconstruction but complications and infections remain a serious surgical problem. This work seeks to provide a comprehensive picture of the com-morbidities and reconstructive methods that lead to success and improve patient outcomes. OBJECTIVES/GOALS: Patients that undergo cardiac surgery via the median sternotomy approach are at risk of wound complications that require repair. We seek to evaluate how outcomes of sternal reconstruction are influenced by patient comorbidities, flap usage and internal mammary artery grafts and methods of sternal closure. METHODS/STUDY POPULATION: We identified patients between 2005 and 2020 who underwent sternotomy followed by debridement and flap coverage at our institution. Comorbidities, method of reconstruction, demographic data, surgical history, and other factors pertaining to mortality and morbidity were collected. The data will then be analyzed to identify population characteristics using logistic regression variables to determine univariate and adjusted multivariable measures of association with mortality. We present the pre-liminary data analyzed using chi-square and one-way anova in R. RESULTS/ANTICIPATED RESULTS: In this study we present a preliminary characterization of one institution’s sternal reconstruction patient outcomes with a variety of reconstruction methods including pectoralis advancement flaps, omental flaps and latissumus dorsi flaps. Notable preoperative comorbidities include 50% of patients > age 60, 18% with diabetes mellitus, 18 % with diagnosed hypertension, 18% with COPD, and 9% with a smoking history DISCUSSION/SIGNIFICANCE OF FINDINGS: In an evolving cardiothoracic landscape, clinical characteristics of patients being treated for sternal reconstructive surgery present a moving target. Understanding current risk factors, preoperative management and timing for aggressive surgical treatment offers an opportunity to update treatment protocol and maximize successful outcomes.
38029 Helping Patients with Chronic Conditions Overcome the Challenges of High Deductible Health Plans
Authors: Hu Tiffany Y. , Ali Iman , Kullgren Jeffrey T.
Published: March 2021

ABSTRACT IMPACT: With a growing number of Americans enrolled in high-deductible health plans, patients, especially those with chronic conditions, face increasing cost-sharing burden. We aim to develop a novel behavioral intervention to help patients use consumer strategies to better manage their health care spending. OBJECTIVES/GOALS: To assess patient preferences to develop an intervention to encourage the use of cost-conscious strategies to manage out-of-pocket health care spending among high-deductible health plan (HDHP) enrollees with chronic conditions. METHODS/STUDY POPULATION: This mixed-methods study is first conducting semi-structured telephone interviews of up to 20 adults with one or more chronic conditions who are enrolled in an HDHP. Preliminary findings from these interviews are being used to inform the design of a national internet panel survey of at least 300 HDHP enrollees. Collectively, the interviews and survey will assess experiences of HDHP enrollees and their preferences for the content, design, format, and mode of an intervention to help them engage in cost-conscious health care behaviors. These findings will then be used to develop a novel behavioral intervention that will subsequently be pilot tested for acceptability, feasibility, and preliminary efficacy. RESULTS/ANTICIPATED RESULTS: Early interview data identified gaps in knowledge of health care consumer strategies among HDHP enrollees with low confidence in being able to engage in cost-conscious health care behaviors. Several participants indicated interest in an intervention to learn more about how to engage in cost-conscious strategies (e.g., putting aside money for anticipated health care expenses, comparing cost and quality for services at different places, and talking to providers about health care costs). Most early interview participants preferred an easily accessible technological intervention, such as a website or app. Interviews are continuing, and the national survey will be fielded in early 2021. DISCUSSION/SIGNIFICANCE OF FINDINGS: HDHP enrollees with chronic conditions could benefit from an intervention that helps them manage their high cost-sharing. Based on the results of interviews and a national survey, we will develop and pilot test a novel behavioral intervention to promote use of cost-conscious health care behaviors.
21083 Perceptions on the Role of Physical Therapy Providers for Falls Prevention: A Qualitative Investigation
Authors: Vincenzo Jennifer L. , Patton Susan Kane , Lefler Leanne L. , Falvey Jason R. , McElfish Pearl A. , Curran Geoffrey , Wei Jeanne
Published: March 2021

ABSTRACT IMPACT: Being explicit about the prevention of falls throughout an older adults’ episode of care may further help reinforce the role of physical therapy providers in falls prevention and improve dissemination of this knowledge. OBJECTIVES/GOALS: The purpose of this study was to determine older adults’ awareness of and perspectives about the role of physical therapy providers for falls prevention and determine potential barriers and facilitators to utilization of preventive rehabilitation services METHODS/STUDY POPULATION: We used a qualitative descriptive phenomenological approach to emphasize participants’ perceptions and lived experiences. Four focus groups were conducted with 27 community-dwelling older adults (average age = 78 years). Focus groups were recorded, transcribed, condensed, and coded using thematic analysis. RESULTS/ANTICIPATED RESULTS: Surveys indicated 37% of participants experienced a fall in the last year and 26% reported suffering an injury. Four main themes and six subthemes surrounding older adults’ perceptions of physical therapy providers’ roles for falls prevention emerged: (1) Awareness of Falls Prevention (subthemes: I Don’t Think About It, I Am More Careful); (2) Being Able to Get Up from the Floor; (3) Limited Knowledge about the Role of Physical Therapy Providers in Falls Prevention (subtheme: Physical Therapy Services are for After a Fall, Surgery, or for a Specific Problem); and 4). Barriers to Participating in Preventive Physical Therapy Services (subthemes: Perceived Need and Costs, Access Requires a Doctor’s Prescription). DISCUSSION/SIGNIFICANCE OF FINDINGS: Older adults lack awareness about the role of physical therapy services in falls prevention, perceiving services are only to treat a specific problem or after a fall. Physical therapists should be explicit about the role of physical therapy in falls prevention for all older adults undergoing rehabilitation, regardless of the reason.