bluuebunny/crossref_metadata_2025 huggingface dataset:
21771 HIV Prevention among HIV-Negative Latino Males: Identifying Sociocultural Factors Associated with Pre-exposure Prophylaxis
Authors: Zapata Juan Pablo , de St. Aubin Ed
Published: March 2021

ABSTRACT IMPACT: The broad goal of this investigation is to inform the development of culturally sensitive HIV prevention strategies to reduce specific challenges pertaining to PrEP uptake and utilization for Latino men. OBJECTIVES/GOALS: HIV is a significant public health concern affecting Latinos in the U.S. Daily use of pre-exposure prophylaxis (PrEP) effectively prevents HIV infection and has the potential to curb HIV epidemics. The objective of this study is to examine how sociocultural variables impact PrEP-related services among HIV-negative Latinxs. METHODS/STUDY POPULATION: The current study is a mixed-method investigation. Participants will include Latinx adult patients seeking services at an HIV community clinic. Approximately 150 participants will be recruited for the study. Participants who are eligible will complete sociocultural, mental health and PrEP-related measures. For the applied aim, community stakeholders will be recruited who serve the Latinx community. Upon completion of data collection, the data analytic plan is as follows: Aim 1, to establish the relationship between each sociocultural variable and PrEP uptake/utilization, preliminary analyses (i.e., correlations and regression analyses considering co-variates) will be conducted. Aim 2, grounded theory techniques will be conducted to establish community-informed practices to increase the use of PrEP. RESULTS/ANTICIPATED RESULTS: Relatively little is known about cultural factors that may impede PrEP uptake among Latinx MSM. Several researchers have identified specific factors such as language, acculturation, familismo, and similar cultural norms as significant barriers to care (Page et al., 2017). It is expected that each of these variables will contribute significant variance to willingness to use PrEP. Specifically, negative relationships are expected between fatalism and machismo and lower stages on the PrEP Contemplation Ladder. Comparably, a negative relationship is expected between the Hispanic acculturation subscale and lower stages on the PrEP Contemplation Ladder. It is however, hypothesized that there will be a positive relationship between familism and the non-Hispanic acculturation sub-scale. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite important advances in health to prevent HIV infection, HIV rates among Latinx MSM continue to rise. This investigation will have the potential to inform the development of culturally sensitive prevention strategies. By collecting qualitative data from key community stakeholders, this project will also directly inform a CBPR prevention.
55484 Dual activation of CAR and Nrf2 improves the efficacy: toxicity ratio of cyclophosphamide and doxorubicin-based treatment of TNBC
Authors: Stern Sydney , Liang Dongdong , Li Linhao , Kurian Ritika , Lynch Caitlin , Heyward Scott , Kareem Ajoke , Chun Young , Hong Charles , Xue Fengtian , Wang Hongbing
Published: March 2021

ABSTRACT IMPACT: Triple negative breast cancer (TNBC) affects 10-20% of women with breast cancer and is biologically more aggressive than other subtypes. The novel compound we have developed, DL7076, would give clinicians a vital strategy to improve the commonly used cyclophosphamide (CPA) and doxorubicin (DOX) regimen in the treatment of TNBC. OBJECTIVES/GOALS: The objective of this research project is to develop a novel compound which can activate both 1) the constitutive androstane receptor (CAR) and subsequently enhance the CYP2B6-mediated activation of CPA, and 2) the nuclear factor erythroid- related factor-2 (Nrf2) leading to the cardiomyocyte protection from DOX-associated cardiotoxicity. METHODS/STUDY POPULATION: Following the identification of the compound candidate, DL7076 was evaluated for tissue specific induction of CAR and Nrf2 using qPCR, western blot analysis, and luciferase reporter assays.

Further, we have developed a multicellular coculture model incorporating human primary hepatocytes for metabolism, TNBC spheroids as the target, and cardiomyocytes as a side target of DOX. We have investigated the anticancer effects of CPA/DOX on TNBC cells and the toxic effects on cardiomyocytes with/without a CAR-Nrf2 activator, in a multicellular environment where hepatic metabolism is well-retained. RESULTS/ANTICIPATED RESULTS: We found that our dual activator of CAR and Nrf2, DL7076, exhibits tissue specific induction of CAR and Nrf2. Inclusion of DL7076 in combination with the CPA/DOX regimen improves anticancer efficacy, through the subsequent increase in the formation of the active CPA metabolite. With the addition of DL7076, DOX-mediated off-target cardiotoxicity was markedly reduced.

Lastly, utilizing the novel coculture system with human primary hepatocytes, TNBC spheroids, and cardiomyocytes, the inclusion of DL7076 to the CPA/DOX regimen shows decreased spheroid viability and improved cardiomyocyte viability and function. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that DL7076 can facilitate DOX/CPA containing regimens by increasing CAR-mediated metabolism and subsequent CPA bioactivation while selectively protecting cardiomyocytes from DOX-induced toxicity. This research is expected to translate our basic scientific findings into therapeutic interventions for women with TNBC.
86583 The role of creatine in developmental myelination and remyelination
Authors: Rosko Lauren , Gentile Tyler , Smith Victoria , Huang Jeffrey K.
Published: March 2021

ABSTRACT IMPACT: This study highlights the importance of creatine in developmental myelination and remyelination to investigate whether creatine provides a therapeutic value during a central nervous system (CNS) demyelinating insult with a potential value in patients with Multiple Sclerosis. OBJECTIVES/GOALS: Creatine is vital for ATP buffering in the brain. Interestingly, the cells that generate myelin express the main enzyme for creatine synthesis, Gamt. Patients with Gamt mutations display intellectual delays and impaired myelination. Therefore, we hypothesize that creatine is essential for developmental myelination and improves remyelination. METHODS/STUDY POPULATION: To investigate these hypotheses, we developed a new transgenic mouse model with LoxP sites flanking exons 2-6 of the guanidinoacetate methyltransferase (Gamt) gene where excision leads to expression of a green fluorescent tag allowing us to track the cells normally expressing Gamt. We used immunohistochemistry techniques to look at the corpus callosum, the main white matter tract in the brain, and evaluate the number of oligodendrocytes (OL), glial cells responsible for generating myelin. We also used the cuprizone model of toxic demyelination to investigate whether dietary creatine and cyclocreatine, a planar analog of creatine that more efficiently crosses the blood-brain barrier, can enhance remyelination. RESULTS/ANTICIPATED RESULTS: In this mouse model, we show a 95% (+/-0.47%, n=3) co-localization of Gamt within mature OL during postnatal (P) day P14 with no co-localization in neurons or other glial cells. This suggests that mature OL are the main cells making creatine in the CNS. Next, we show that knocking out Gamt leads to a significant reduction in OL in the developing corpus callosum, at P14 and P21 (P14: 0.007, n=3; P21: 0.04, n=3). We also show that creatine supplementation causes a trending increase in mature OL density in the corpus callosum following cuprizone demyelination (2% creatine; p=0.052; n=4). Interestingly, cyclocreatine supplementation significantly increased mature OL density in the corpus callosum following cuprizone demyelination (0.1% cyclocreatine; p=0.034; n=4). DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies highlight the important role creatine plays in developmental myelination and remyelination to investigate whether creatine and cyclocreatine provide a therapeutic value during a CNS demyelinating insult. This work investigates a potential therapeutic value of creatine to patients with Multiple Sclerosis.
27416 DNA Methylation Age Acceleration and Depressive Symptoms in African American Women with Cardiometabolic Conditions
Authors: Perez Nicole , Vorderstrasse Allison , Yu Gary , Taylor Jacquelyn
Published: March 2021

ABSTRACT IMPACT: This study deepens knowledge with respect to the associations between depression, cardiometabolic conditions, and accelerated aging with a clinically accessible marker in a population with disproportionate risk for comorbidity. OBJECTIVES/GOALS: The aim of this secondary analysis is to examine associations between DNA methylation age acceleration (DNAm AA) and depressive symptoms in African American women (AAW) considering the presence of cardiometabolic conditions (CMCs) including hypertension, diabetes, obesity. METHODS/STUDY POPULATION: Genomic and longitudinal clinical data (collected 2015-2020) from the Intergenerational Impact of Genetic and Psychosocial Factors on Blood Pressure Study (InterGEN) cohort (n=227) were utilized for this analysis. DNA methylation age (estimated by the Horvath method) incorporates DNA methylation status at 353 CpG sites. DNAm AA is the residual of DNA methylation age regressed on chronological age in a linear model. Spearman’s correlations and linear regression examine the relationship between DNAm AA and depressive symptoms (Beck Depression Inventory) and cardiometabolic status. The potential association and impact of SES, trauma, substance use, and stress were also considered. RESULTS/ANTICIPATED RESULTS: Contrary to our hypothesis, DNAm AA did not associate with the severity of depressive symptoms. Correlation between DNAm AA and affective symptom subscore (BDI) approached significance (p = 0.06). We observed significant correlations between DNAm AA and specific depressive symptoms including participants’ reported disappointment, disgust, or hatred toward themselves (p < 0.05), difficulty with making decisions (p < 0.05), and worry about their physical health (p < 0.05). DNAm AA was also significantly correlated with BMI (p > 0.001). Significant relationships were not evident in the subsequent regression analysis examining potential relationships between DNAm AA and depression. To our knowledge, this is the first study to examine associations between DNAm AA and depressive symptoms in AAW. DISCUSSION/SIGNIFICANCE OF FINDINGS: Depression limits life quality and quantity and is highly comorbid in CMCs. AAW have a high risk of comorbidity. This study deepens knowledge with respect to the associations between depression, CMCs, and aging with a clinically accessible marker in a population with disproportionate risk.
92811 Implementation of the Fitness, Lifestyle, and Optimal Wellness (FLOW) Program and Its Associated Health Outcomes
Authors: Brake Daniel , Asif Irfan , Cohen Caroline , McKeag Ian , Crockett Kaylee , Wiederman Michael
Published: March 2021

ABSTRACT IMPACT: Through its interdisciplinary, tailored approach, the FLOW program could change the way that we approach promoting healthy lifestyle changes in the primary care field. OBJECTIVES/GOALS: The goal of this project is to assess patient outcomes associated with the implementation of the Fitness, Lifestyle, and Optimal Wellness (FLOW) Program. The ultimate aim of this program is two-fold: increasing patient-reported wellness and improving objective health measurements. METHODS/STUDY POPULATION: The FLOW program consists of a multidisciplinary team of sports medicine physicians, nutritionists, fitness trainers, and clinical psychologists. Patients who choose to participate in the program undergo a comprehensive physician-guided assessment, including lifestyle and metabolic evaluation, biomarker profile, and body composition analysis. Based on the patient’s goals and results of evaluation, he/she is then connected with other members of the FLOW team to develop a comprehensive plan and offer resources for potential improvements in physical activity, nutrition, and/or behavior. The patient will undergo follow-up assessments and questionnaires at three and six months to track their objective measurements and reported progress. RESULTS/ANTICIPATED RESULTS: The anticipated results of the FLOW program are an overall improvement in patient health and wellbeing. More specifically, we anticipate seeing increased levels of exercise from initial reported levels, as well as better nutrition habits. We expect to see improvements in follow-up body composition assessments, with gains in fat-free mass and decreased body fat, in addition to patient-reported improvements in behavioral health as measured by PHQ-9, GAD-2, and the Perceived Stress Scale. We will also assess reported sleep health with the hopes to see improvement in follow-up assessments. DISCUSSION/SIGNIFICANCE OF FINDINGS: The FLOW program is designed to address health inequities that disproportionately affect the Deep South. Through this program, we propose a new role of the primary care team in promoting healthy lifestyle habits and disease prevention through exercise, nutrition, and behavioral health services.

Regulatory Science
70274 TL1 team approach to investigating the adhesin gene fimH in adherent invasive E. coli induced inflammation and colorectal cancer development
Authors: Newsome Rachel C , Yu Qin , Murota Yoshitaka , Hood Derek , Nguyen Duy , Smolchek Ryan A , Uruena Juan M , Sawyer W Gregory , Jobin Christian
Published: March 2021

ABSTRACT IMPACT: We are developing the 3D perfusion system for use with patient-derived bacteria to further characterize the mechanism behind bacterial-induced inflammation and cancer. OBJECTIVES/GOALS: We previously reported the adherent invasive E. coli NC101 promote colorectal cancer (CRC) in mice. FimH, a mannose-specific adhesin on type 1 fimbriae, is involved in bacterial surface adhesion. Herein, we investigated the role of FimH in E. coli NC101-induced adherence and carcinogenesis in a novel 3D perfusion culture imaging plate. METHODS/STUDY POPULATION: E. coli NC101 gene fimH was deleted byï ŲRed Recombinase System. Biofilm formation was assessed by crystal violet and congo red staining. 5 dpf (wild-type strain) zebrafish embryos were infected in 6x107 cfu/ml wild type (WT) or fimH-deleted (ï ,,fimH) E. coli NC101 for 24hr and gut dissected for bacterial culture. A 2D/3D infection culture system for IEC-6 and HT-29 cells was infected for 4 hr and imaged and then DNA damage examined by comet assay, cell cycle andÎ3H2AX accumulation. Germ-free (GF) Il10-/- (colitis) mice were orally gavaged with 108 cfu WT orï ,,fimH E. coli NC101 for 16 weeks. E. coli colonization were quantified by plate culture and qPCR. Lipocalin2 was quantified by ELISA. PCNA and β-catenin were evaluated by immunohistochemistry (IHC). RESULTS/ANTICIPATED RESULTS: Biofilm formation was reduced by more than 40% (p<0.05) in E. coli NC101ï ,,fimH compared to WT strain. Zebrafish larvae showed a 41% decrease in intestinal colonization ofï ,,fimH compared to WT (p<0.05). E. coli NC101-induced DNA damage was reduced by 67% (p<0.0001) in HT-29 cells infected withï ,,fimH compared to WT strain. Using the 3D infection system, a 46% decrease in yH2AX (p<0.05) and 42% decrease in G2 cell cycle arrest (p<0.05) was observed inï ,,fimH infected IEC-6 cells compared to WT strain. Furthermore, ï ,,fimH infected Il10-/- mice showed decreased colonization (p<0.01), decreased intestinal inflammation (p<0.05), decreased stool lipocalin2 level (p<0.01), and reduction of PCNA positive cells in the intestine (p<0.05) compared to mice infected with WT strain. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adhesin protein FimH is required by E. coli NC101 to colonize and promote colitis and carcinogenesis both in a 3D perfusion culture and in mice and may serve as potential therapeutic target.
16506 Recognizing Interdisciplinary Collaborative Research in Promotion and Tenure Processes
Authors: Zierler Brenda K. , Summerside Nicole , Sprecher Jennifer , Blakeney Erin , Vogel Mia , Chu Frances , Posner Jonathan D.
Published: March 2021

ABSTRACT IMPACT: Recognizing Interdisciplinary Collaborative Research in Promotion and Tenure Processes OBJECTIVES/GOALS: Academic institutions have traditionally focused on individual achievements for promotion. We present our effort on identifying and measuring attitudes on promotion and tenure (PT) criteria that values and rewards interdisciplinary research (IR). We have developed a toolkit to facilitate the recognition of IR in PT processes. METHODS/STUDY POPULATION: Our group reviewed appointment, promotion and tenure (APT) policies from each of the six Health Science Schools and the College of Engineering at the University of Washington (UW) to assess language of objective criteria and attributes of IR to guide APT committees in the evaluation of interdisciplinary researchers. We surveyed faculty about their attitudes relating to IR within the context of promotion and tenure. Interviews of department chairs and administrators about institutional policies and infrastructure that supports or inhibits IR, and current best practices, were conducted. We have developed toolkits for junior faculty, department chairs, external reviewers, and APT committees to facilitate rewarding IR at promotion. RESULTS/ANTICIPATED RESULTS: Review of APT policies found criteria that recognizes IR for APT in three schools. 118 faculty responded to the survey (44% Professor, 26% Associate, and 37% eligible for APT committees). The majority of faculty reported they were currently conducting IR (95%), considered IR important (98%), and believed the UW faculty code should encourage IR (85%). Although a vast majority considered their units supportive of IR (>80%), less than half (43%) reported that their APT criteria provided examples that included participation in IR. Our survey also found that APT committees were challenged about best practices to reward IR, APT external reviewers struggle to evaluate individual vs team contributions, and individual faculty are challenged to describe contributions for APT within context of an interdisciplinary team. DISCUSSION/SIGNIFICANCE OF FINDINGS: IR is conducted and valued by UW faculty; however, current structures, policies, and APT code do not facilitate IR for promotion and tenure. We have developed a toolkit for promotion-eligible faculty, chairs, external reviewers, and APT committees to facilitate IR. Our goal is to modify UW faculty code and unit APT criteria to recognize and reward IR.
00006 Yield of routine PET/CT surveillance imaging after primary surgical treatment for asymptomatic patients with high-risk stage II/III melanoma
Authors: Jaeger Zachary J. , Reed Rachel E. , Barker Abigail R. , Mhlanga Joyce C. , Cornelius Lynn A. , Fields Ryan C.
Published: March 2021

ABSTRACT IMPACT: The results of this research may influence NCCN guidelines on PET/CT surveillance for this population of patients for whom the guidelines are currently vague. OBJECTIVES/GOALS: We aim to quantify and describe the yield of surveillance PET/CT for detecting asymptomatic recurrence of melanoma after primary surgical treatment for stages IIB, IIC, and IIIA. Our goal is to provide evidence to inform appropriate guidelines for scheduling surveillance PET/CT for this population. METHODS/STUDY POPULATION: This is a retrospective study of patients who have undergone a PET/CT at Barnes-Jewish Hospital. Data will be collected in our Research Electronic Data Capture (REDCap) database. The sample size is 158. Data analysis will be explanatory for the yield of imaging and description of false positives and additional unnecessary workup. Survival endpoints will be reported and multivariate analysis with subgroups will be performed for predictors of PET/CT results. Cost-efficiency analysis will be conducted in collaboration with the Center for Health Economics and Policy (CHEP), with emphasis on a patient-oriented perspective. RESULTS/ANTICIPATED RESULTS: To date, we have collected data for 158 patients, with approximately equal numbers of each stage (56 IIB, 54 IIC, 48 IIIA). Due to lack of clear guidelines for this population, there is significant variation of imaging schedules and results between similar patients or groups of patients. This makes it difficult to anticipate results. Based on clinical experience, literature review, and preliminary data, we may anticipate lower yield of routine PET/CT for the detection of asymptomatic recurrence, with frequent false negatives and occasional false positives, in addition to detection and further workup of benign processes. DISCUSSION/SIGNIFICANCE OF FINDINGS: The high-risk stages IIB, IIC, and IIIA currently occupy a gray area where surveillance PET/CT remains controversial. For this group of patients, it is important to weigh the benefits of early detection and risks of false positives, unnecessary workup and anxiety, and cost.
24780 Investigating the role of mycobacterial lipid antigens and CD1-restricted T cells in host-protective tuberculosis immunity using a guinea pig model
Authors: Harris Macallister , Dilisio James , Gary Hadley , Chan Edward , Moody D. Branch , Podell Brendan
Published: March 2021

ABSTRACT IMPACT: Examining lipid immunity for Mycobacterium tuberculosis in a translatable Guinea pig model may serve as a critical foundation for the creation of an efficacious human lipid based vaccine against tuberculosis. OBJECTIVES/GOALS: CD1 is a group of glycoproteins on antigen-presenting cells (APCs) that present lipid antigens to T cells. Mycobacterium tuberculosis (Mtb) has a lipid-rich cell wall which is essential for the pathogenesis of tuberculosis. Our goal is to determine the frequency, phenotypes, and functionality of CD1 T cells against Mtb using the guinea pig model. METHODS/STUDY POPULATION: Guinea pigs serve as the best translational model for CD1 immunology as they have both group 1 and group 2 CD1 complexes, comparable to human CD1. We performed ex-vivo and in-vivo experiments to analyze lipid antigen-specific CD1 T cell responses with Mtb infection. Assays to detect lipid-specific CD1 T cell activation include cellular proliferation, cytotoxicity assays, and interferon-gamma (IFNγ) release assay (Elispot) using both synthetic and Mtb-derived lipids. We isolated and characterized CD1 T cells using tetramerized CD1 complexes loaded with specific Mtb lipids. Spatial interaction between lipid loaded CD1 APCs with CD1 T cells were demonstrated by immunohistochemistry (IHC). Lastly, we will investigate the impact of lipid-based immunology via knockdown and overexpression of CD1 complexes. RESULTS/ANTICIPATED RESULTS: The cytotoxicity assay demonstrated that the CD1b1 and CD1b3 complexes play roles in the presentation of Mtb lipids, specifically glucose monomycolate, and mycolic acid, as noted by T cell killing of fibroblasts that express specific CD1 complexes that can present Mtb lipids. Similarly, cellular proliferation exhibited lipid specific T cell proliferation. IFNγ production by the stimulated CD1-restricted T cells (Elispot) was weak indicating CD1 T cells may not produce IFNγ. IHC successfully showed CD1 APCs in lungs and spleens of infected guinea pigs. It is anticipated that knocking out CD1 expression will lead to impaired immunity, and increase severity of disease as noted by pathologic lesions/bacterial burden, and systemic spread; in contrast, CD1 enhancement will limit the severity of tuberculosis. DISCUSSION/SIGNIFICANCE OF FINDINGS: We characterized CD1 T cells in infected guinea pigs at the tissue level, demonstrating Mtb lipid immunology. As a result, we laid the groundwork for investigating whether augmenting lipid immunity in the guinea pig model will enhance immunity against tuberculosis. Fruition of such work may lead to the development of effective tuberculosis vaccines.
45698 Molecular Signatures of Cocaine Neurotoxicity in Human Brain Models
Authors: Mendez Emily , Stertz Laura , Fries Gabriel , Hu Ruifeng , Meyer Thomas , Zhao Zhongming , Walss-Bass Consuelo
Published: March 2021

ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.
28835 Describing Physical Symptoms among Patients with PTSD at an Anxiety Clinic in Puerto Rico
Authors: Torres-Valentin Marie , Martinez-Gonzalez Karen G. , Martinez-Taboas Alfonso
Published: March 2021

ABSTRACT IMPACT: Our work will provide valuable information about the associations between physical symptoms and PTSD in patients from a Spanish-speaking, evidence-based clinic. OBJECTIVES/GOALS: In this reserach study, we want to describe physical symptoms of patients with a preliminary PTSD diagnosis. We also want to explain associations between physical symptoms, and the presence, or absence of PTSD, and to evaluate findings in terms of prevention services, referrals, and alternatives for augmenting treatment-adherence. METHODS/STUDY POPULATION: This was a descriptive, secondary database analysis of the Center for the Study of Fear and Anxiety (by its Spanish acronym, CETMA). The database included information of the initial evaluation between 2012 and 2019. We aimed to describe sociodemographic and medical variables, and evaluate associations, in terms of the presence or absence of PTSD. RESULTS/ANTICIPATED RESULTS: Patients with PTSD were mostly women, single, with a completed bachelor’s degree. The majority had at least one neurological, or musculoskeletal condition. Respiratory conditions were the least represented. We found significant associations between musculoskeletal, neurological, and ear/nose/throat conditions, in terms of PTSD diagnosis. DISCUSSION/SIGNIFICANCE OF FINDINGS: Puerto Rico recently experienced two hurricanes, several earthquakes, and the pandemic. Findings provide data about the interface between mental and physical symptoms of patients with PTSD. We recommend a randomized population study with mental and physical variables, for understanding possible effects of cumulative stress in Puerto Ricans.
27646 Spinal Control Impairments During Two Clinical Tests of Lower Limb Movement in People with and without Low Back Pain
Authors: Chen Stacey , Hooker Quenten , Lanier Vanessa , Van Dillen Linda
Published: March 2021

ABSTRACT IMPACT: Our work may be able to impact the examination and clinical decision making of a clinician to identify and target movement impairments to treat people with low back pain. OBJECTIVES/GOALS: Test if the magnitude of spinal control impairments is different in two clinical tests of lower limb movement in people with and without low back pain (LBP). The impairment is defined as the time difference between the start of limb to lumbopelvic motion. Also, test if the magnitude of impairments across tests is associated with LBP intensity and function. METHODS/STUDY POPULATION: 18 controls and 21 people with LBP (51.6% F, 34.5 ±11.5 yrs) participated in a cross-sectional, laboratory-based study. Subjects completed the modified Oswestry Disability Questionnaire (LBP-related functional limitation measure; 0-100%) and the Numeric Pain Rating Scale (LBP intensity; average pain prior 7 days; 0-10) self-report surveys and clinical tests of hip medial and lateral rotation performed in prone. A three-dimensional motion capture system was used to capture angular lumbopelvic and hip motion across time. A 2x2 mixed model ANOVA will be used to examine the effects of group, hip rotation test, and group x hip rotation test. Separate bivariate correlations will be used to quantify the association of magnitude of the impairment to (1) average LBP intensity and (2) LBP-related functional limitation. RESULTS/ANTICIPATED RESULTS: We hypothesize that, compared to healthy controls, people with LBP will display a greater magnitude of impairment across the hip medial and lateral rotation tests. In addition, we hypothesize that the magnitude of the difference in impairment between people with LBP vs controls will be larger during the hip lateral rotation test compared to the hip medial rotation test. Finally, we hypothesize that in people with LBP the magnitude of the impairments across tests will be associated with LBP intensity and LBP-related functional limitation. DISCUSSION/SIGNIFICANCE OF FINDINGS: If our hypotheses are supported, the hip rotation tests would further be recognized as a key part of a clinician’s examination and an important target for treatment of LBP.
35991 Towards a Novel Robotic Control Scheme to Improve Lower Extremity Movement Post-Stroke
Authors: Ruopp Tom , Schmit Brian , Schindler-Ivens Sheila
Published: March 2021

ABSTRACT IMPACT: Effective robotic pedaling therapy would allow stroke survivors a precision, customized, and adaptable therapy to help recover lower extremity function. OBJECTIVES/GOALS: It has been observed that people post-stroke can pedal each limb individually but not simultaneously when the bicycle is split-crank. This implies that lower extremity movement difficulties are affected more by interlimb rather than unilateral coordination deficits. This work seeks to further develop a robotic split-crank pedaling therapy device. METHODS/STUDY POPULATION: This work uses a robotic split-crank pedaling device to facilitate rehabilitation of interlimb coordination, measured by continuous relative phase (CRP) and paretic neuromuscular output. The effects of three control schemes were tested: assist, resist, and assist+resist. Each limb was strapped to a pedal which was connected to a motor. The participants were asked to pedal forward while keeping the pedals antiphase. The robot aided or resisted according to the activated control scheme. Control schemes were tested on two stroke participants. The control schemes respond proportionally to phasing deviation from 180 degrees. The assist scheme assisted the lagging limb while the resist scheme resisted the leading limb. The assist+resist did both control actions. RESULTS/ANTICIPATED RESULTS: For the assist scheme, CRP improved for participant 1 (P1) and declined for participant 2 (P2). P1 increased paretic velocity while P2 decreased. Rectus Femoris (RF) and Biceps Femoris (BF) activity of both limbs lowered for P1. RF and BF activity of both limbs remained about the same but shifted for P2. For the resist scheme, CRP improved for P1 and declined for P2. P1 increased paretic velocity while P2 decreased. P1 increased BF activity of both limbs while RF activity remained constant. P2 increased paretic BF activity and non-paretic RF activity. For the assist+resist scheme, CRP improved for both participants. Both participants increased paretic velocity. P1 increased paretic BF activity and decreased RF activity. P2 better modulated paretic BF and RF. DISCUSSION/SIGNIFICANCE OF FINDINGS: All control schemes augmented performance, however the assist+resist scheme showed the most promise in terms of CRP and muscle activity. More participants are needed to determine true effects of each control scheme. The control scheme selected will be the foundation for further improvements such as adaptive control and extrinsic feedback.
62541 Continuity of Care for Patients with Chronic Gastrointestinal Disease: A Latent Class Analysis of Patients With High-Intensity Specialty Care Needs
Authors: Cohen-Mekelburg Shirley , Greene Liberty , Waljee Akbar , Hofer Tim , Saini Sameer , Zulman Donna
Published: March 2021

ABSTRACT IMPACT: Grouping patients with potentially high intensity specialty care needs based on their propensity for healthcare continuity patterns can inform the development of personalized care coordination and care navigation interventions OBJECTIVES/GOALS: To examine variation in healthcare continuity patterns across primary care, mental health care, and specialty care for a patient population with chronic gastrointestinal conditions and a high risk for healthcare utilization. METHODS/STUDY POPULATION: We analyzed data for Veterans Affairs patients with chronic gastrointestinal disease (cirrhosis, inflammatory bowel disease, chronic pancreatitis) whose 1-year hospitalization risk was ≥90th percentile in 2014, and who had a minimum of 4 office visits. To assess continuity, we examined frequency of office visits, number of outpatient providers, and two established continuity of care measures (the usual provider of care index and the Bice-Boxerman continuity of care index) over 12 months. We used latent class analysis to categorize patients into classes based on overall, primary care (PCP)-specific, gastroenterology (GI)-specific, and mental health specific-healthcare continuity patterns. RESULTS/ANTICIPATED RESULTS: The 26,751 Veterans in the analytic cohort had a mean of 13.3 (sd 8.63) office visits and 7.2 (sd 3.83) providers per patient. Patients were classified into five phenotypes: (1) moderate overall use and continuity; (2) low overall continuity of care; (3) high GI- and PCP-specific continuity of care; (4) low overall continuity of care with some mental health use; and (5) high utilization with substantial mental health use. In the subsequent year, 11,259 (42.1%) patients had a hospitalization and 16,167 (60.4%) had an emergency department visit. These groups varied in their sociodemographic and clinical characteristics, and in their risk for hospitalization and emergency department use. DISCUSSION/SIGNIFICANCE OF FINDINGS: Latent class analysis revealed five distinct primary and specialty care utilization patterns. Grouping patients with high intensity specialty care needs based on their propensity for healthcare continuity patterns can inform the development of personalized care navigation interventions.
98179 Identifying Low-Value Care Across A Statewide Health System: Collaboration Between Quality, Population Health, Informatics, and Health Services Research
Authors: Oronce Carlos Irwin A. , Mafi John N. , Pablo Ray , Sorensen Andrea , Patel Ayan , Dahm Lisa , Skootsky Samuel A. , Sak Rachael , Sarkisian Catherine
Published: March 2021

ABSTRACT IMPACT: This project demonstrates that addressing low-value care, which has the potential to cause patient harm, relies on novel data tools and collaboration between health system and research stakeholders. OBJECTIVES/GOALS: Reducing low-value care, or patient care that offers no net benefit in specific clinical scenarios, is an important approach to improving value as it can simultaneously lower health care spending and improve quality. We describe an initiative to identify such care in a large statewide employer. METHODS/STUDY POPULATION: Claims data for self-funded University of California (UC) Preferred Provider Organization (PPO) plan members during 2019 were abstracted from the University of California Health (UCH) Clinical Data Warehouse, a unique central database that includes electronic medical record data from >5 million patients across UC medical campuses and all claims from UC self-funded health plans. UCH spans six academic health systems across California. The Milliman MedInsight Health Waste Calculator, a proprietary algorithm-based software tool, was used to identify low-value care and estimate associated spending. The HWC measures 48 low-value services using recommendations from the Choosing Wisely Campaign, the US Preventive Services Task Force, and other clinical specialty guidelines. RESULTS/ANTICIPATED RESULTS: Of 43,882 members of the UC PPO, 11,174 (25.4%) received at least one low-value service. The HWC identified 50,103 eligible services and classified 35% as low-value. Total spending on low-value services ranged between $2,209,516 and $5,089,866, based on a more or less conservative estimate. Across the five sites, the proportion of low-value services ranged from 31% to 39%. Five services comprised 65% of costs from low-value care: annual EKGs, preoperative baseline labs for low-risk surgeries, vitamin D deficiency screening, imaging for eye disease, and headache imaging. The top five services by order frequency were annual EKGs, vitamin D tests, preoperative labs, antibiotics for upper respiratory infections, and imaging for eye disease. DISCUSSION/SIGNIFICANCE OF FINDINGS: Low-value care is prevalent and costly within a large statewide employer. Collaborative multidisciplinary partnerships between employers, health systems, informatics, and researchers can leverage existing data to identify opportunities for improving the value of care for covered populations.
97448 Biopsychosocial Determinants of Pain Assessment and Management - Medical and Surgical Trainees’ Perspective
Authors: Villwock Jennifer A , Polivka Barbara
Published: March 2021

ABSTRACT IMPACT: Better understanding how clinicians make decisions about pain management, particularly since our prior research has demonstrated that opioids prescribed at discharge is the strongest predictor of opioids taken, is critical to decrease high-risk medication prescribing while preserving high-quality care. OBJECTIVES/GOALS: (1) Identify major biological, psychological, and social determinants of medical and surgical residents’ pain management decisions; (2) Determine salient themes regarding the experience of residents in the management of acute and chronic pain METHODS/STUDY POPULATION: Focus groups of internal medicine and general surgery residents at an academic, tertiary care training hospital located in an urban setting were conducted. Due to the COVID-19 pandemic, all focus groups were conducted virtually and occurred during required didactic sessions to facilitate participation. All interviews were recorded and transcribed. Two reviewers independently reviewed and coded the data following the principles of constructivist grounded theory. RESULTS/ANTICIPATED RESULTS: 42 residents participated in ten focus groups ranging in size from two to five individuals. Six themes emerged demonstrating salient BPS factors in pain management decisions: (1) patient and clinician expectations determine what is considered normal/acceptable; (2) inability of pain scales to reliably capture patient pain; (3) desire for more objective methods of pain assessment, while simultaneously recognizing that pain is an inherently subjective experience; (4) difficulty in determine when pain is 'real’ or 'legitimate'; (5) lack of education and protocols regarding pain management; (6) the importance of engaging other services such as acute pain service or nurse educators in complicated situations. Junior residents often expressed doubt in the appropriateness of their approaches and decisions. DISCUSSION/SIGNIFICANCE OF FINDINGS: Surgical and medical trainees routinely treat pain and may struggle, particularly in the early phases of training, to determine if pain levels are appropriate. There is also a lack of education and/or best practices for assessing and managing pain. These areas represent high-value, clinician-focused targets for future interventions to improve care.
92438 Symptom Dynamics and Biomarkers of Disease Progression in Older Adult Patient-Caregiver Dyads During Care Transitions after Heart Failure Hospitalization: Study Design and Anticipated Results
Authors: Bidwell Julie T. , Ferrer Emilio , Lee Christopher S. , Cadeiras Martin , Lyons Karen S. , Young Heather M. , Hinton Ladson
Published: March 2021

ABSTRACT IMPACT: This study is designed to address a critical gap in our understanding of how aging patients and caregivers recognize and respond to clinically important changes in heart failure symptoms during vulnerable transitions. OBJECTIVES/GOALS: Research on family involvement in heart failure (HF) symptom response is limited. Our objective is to examine HF symptom monitoring processes in couples after HF hospitalization, and quantify how coupled symptom assessments predict symptom response, patient clinical events, care strain, and dyad health during the high-risk post-discharge period. METHODS/STUDY POPULATION: This is an ongoing T2 translational study that employs an intensive longitudinal design. Adults aged ≥65 years hospitalized for HF and their caregiving spouse/partner are enrolled. The target n is 48 dyads. Over 5 weeks of follow-up, dyads complete daily diaries assessing patient HF symptoms. Clinical biomarkers of HF severity (NTproBNP, ST2) are also collected. Primary study endpoints are dyads’ HF symptom response behaviors and caregiver strain; secondary endpoints are dyads’ health status and patient clinical events. Dyadic dynamics of symptom assessment will first be characterized using dyadic autoregressive time series models. Subsequently, we will extract cross-partner effect parameters from the time series models and test whether dyadic effects predict the trajectories of each of our endpoints. RESULTS/ANTICIPATED RESULTS: This study is currently underway. In line with our study hypotheses, we anticipate that couples who assess patient symptoms similarly (dyadic agreement), and whose symptom assessments accurately reflect clinical severity, will be more likely to respond to symptoms appropriately with lower stress to the caregiving partner, and have better trajectories of health (self-reported and clinical). Characterizing dyadic symptom dynamics will provide important insight into the day-to-day process of symptom recognition in couples. Further, quantifying dyadic symptom dynamics in relation to our endpoints will provide information on the clinical value of dyadic symptom agreement, and whether it might be a target for future interventions to support better symptom response and health outcomes for both dyad members. DISCUSSION/SIGNIFICANCE OF FINDINGS: This project innovates on existing paradigms by applying family-level theory and techniques to better understand and support interventions for couples during post-discharge HF transitions - a vulnerable period for older adults that has traditionally been studied almost exclusively at the patient-level, with marginal success.
33764 Cost-effectiveness of Initial Treatment Strategies for Localized Prostate Cancer: A Systematic Review
Authors: Wahba B. Malik , Phillips Tarik , Sands Kenneth , Lieu Judith , Chow Alexander K. , Pickersgill Nicholas , Doering Michelle , Kim Eric H
Published: March 2021

ABSTRACT IMPACT: We compare the cost-effectiveness of treatments for early prostate cancer, and propose how to maximize the value of care within an increasingly cost-constrained healthcare climate. OBJECTIVES/GOALS: Each year 192,000 men in the United States are diagnosed with prostate cancer. With various treatment options available, there is a growing role for cost-effectiveness analyses which may help maximize the value of care to the patient. In this review we compare the cost-effectiveness of primary treatments for clinically localized prostate cancer. METHODS/STUDY POPULATION: In this systematic review we aim to compare the cost-effectiveness or cost-utility of primary treatment strategies for clinically localized prostate cancer. This review, which adheres to 2009 PRISMA guidelines, included studies of men with clinically localized prostate cancer comparing at least two treatment strategies using the incremental cost-effectiveness ratio (ICER). We included analyses only of the United States healthcare system with at least 10 years of follow-up. These studies were published from 2006 to 2019 and generally included men with low or low to intermediate risk prostate cancer. Most studies reported outcomes for men age 65-70. All studies were prospective simulated trials and used a Markov model to simulate patient outcomes. RESULTS/ANTICIPATED RESULTS: Ten articles were included in the analysis. All studies used a Markov model to simulate a randomized trial. Six studies primarily compared radiation modalities, and four compared observation with immediate treatment. There was substantial heterogeneity in treatment protocols and the patients being simulated. Sensitivity analyses showed these models to be influenced by utility values and length of follow-up. A meta-analysis was not possible as no studies reported the variance of the primary outcome. Heterogeneity in study design limited comparisons of treatments across studies. However, these models were sensitive to patient-specific clinical factors, including life expectancy and the utility during and after each treatment. DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies indicate collectively that the cost-effectiveness of prostate cancer treatment for similarly staged men may be heavily impacted by comorbidities and personal preferences. As the US moves towards value-based care, patient preferences may continue to drive the preferred treatment for newly diagnosed prostate cancer.