OBJECTIVES/GOALS: The goal of the CTSA consortium is to move scientific discoveries to clinical application. Translational science (TS) focuses on the process by which this happens, and NCATS supports pilot projects that propose TS questions. We are developing a rubric to guide program managers’ability to discriminate between TS and translational research (TR). METHODS/STUDY POPULATION: The CTSA External Review Exchange Consortium (CEREC) and CEREC II are reciprocal review collaborations between CTSA hubs that identify reviewers for each other’s pilot grant applications. CEREC and CEREC II partners developed a 31-item rubric, based on NIH’s Translational Science Principles, for discriminating pilot TS grant applications from those proposing TR. The hubs contributed proposals pre-selected as either TS or TR projects. Then, experienced reviewers and/or program administrators from the hubs used the rubric to score each of the proposals. Reliability of the rubric will be assessed using inter-rater reliability (% agreement and kappa). To identify which of the items in the rubric best discriminate between TS and TR, Item Response Theory analysis will be employed. RESULTS/ANTICIPATED RESULTS: Ten CEREC participating hubs submitted 30 applications: 20 TS proposals and 10 TR proposals. Twenty-two reviewers from 12 CEREC hubs evaluated the applications by using the scoring rubric; at least two reviewers evaluated each proposal. The results of the analyses will describe the reliability of the rubric and identify which of the seven TS Principles are most useful for distinguishing between TS and TR pilot grant proposals. Ultimately, this work will yield a scoring rubric that will be disseminated throughout the CTSA network to facilitate the screening of TS applications. DISCUSSION/SIGNIFICANCE: Optimizing research processes is critical to ensure that scientific discoveries are integrated into clinical practice and public health policy as rapidly, efficiently, and equitably as possible. By appropriately identifying and funding TS projects, CTSA hubs can accelerate the impact of clinical and translational research.

OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for patients with chronic back pain. Technological advances have led to renewed optimism in the field, but mechanisms of action in the brain remain poorly understood. We hypothesize that SCS outcomes will be associated with changes in neural oscillations. METHODS/STUDY POPULATION: The goal of our team project is to test patients who receive SCS at 3 times points: baseline, at day 7 during the trial period, and day 180 after a permanent system has been implanted. At each time point participants will complete 10 minutes of eyes closed, resting electroencephalography (EEG). EEG will be collected with the ActiveTwo system, a 128-electrode cap, and a 256 channel AD box from BioSemi. Traditional machine learning methods such as support vector machine and more complex models including deep learning will be used to generate interpretable features within resting EEG signals. RESULTS/ANTICIPATED RESULTS: Through machine learning, we anticipate that SCS will have a significant effect on resting alpha and beta power in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF IMPACT: This collaborative project will further the application of machine learning in cognitive neuroscience and allow us to better understand how therapies for chronic pain alter resting brain activity.

ABSTRACT IMPACT: This study has implications for understanding early developmental mechanisms of ADHD and for guidelines regarding safe use of acetaminophen during pregnancy. OBJECTIVES/GOALS: Prenatal acetaminophen exposure has been associated with childhood attention-deficit hyperactivity disorder (ADHD), but the underlying mechanism is unknown. This prospective birth cohort study aims to identify linkages between specific metabolites in umbilical cord plasma and the association of prenatal acetaminophen exposure and ADHD. METHODS/STUDY POPULATION: The sample was a subset of the Boston Birth Cohort that included 583 mother-newborn dyads followed at Boston Medical Center from 1998 to 2018. Metabolites were measured from cord plasma collected at birth. Based on existing literature, the analyses focused on candidate metabolites involved in neuroendocrine, inflammation, and oxidative stress pathways. The outcome was physician-diagnosed ADHD between the ages of 3 and 16 years. Exploratory analyses and multiple logistic regressions were used to examine the association of these candidate metabolites with both unmetabolized cord plasma acetaminophen levels and with incident risk of ADHD, adjusting for covariates of maternal and child characteristics. RESULTS/ANTICIPATED RESULTS: Of the 583 children, 257 had ADHD and 326 had neurotypical development. Two promising results have been found thus far. 5-methoxytryptophol (5-MTX), a neuroendocrine molecule which also has antioxidant and immunomodulatory properties, was inversely associated with acetaminophen and ADHD risk. For children below the median cord 5-MTX level, the odds of ADHD were 3.29 (95% CI [1.56, 7.16], p=0.002) for the third tertile of acetaminophen compared to the first tertile. This association attenuated among those above the median 5-MTX level: 2.23 (95% CI [0.98, 5.21], p=0.059), suggesting a protective effect. Tryptophan, an essential amino acid and precursor of serotonin, was positively associated with acetaminophen and ADHD. Next steps include mediation analysis with tryptophan and analyses for other metabolites. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study identifies cord plasma metabolites as possible modifiers or mediators linking prenatal acetaminophen exposure and childhood ADHD, which may offer insight into a mechanistic pathway. The study findings have implications for FDA, clinical, and public health guidelines regarding safe use of acetaminophen during pregnancy.

OBJECTIVES/GOALS: Neonatal hypoglycemia is seen in 65% of maternally diabetic pregnancies, and can lead to severe neurological damage. Neonatal glycemia may also be an indicator of placental function in these pregnancies. The purpose of this study is to identify patterns of neonatal glycemia, and associated endothelial dysfunction, by maternal diabetes subtype. METHODS/STUDY POPULATION: Pregnancies with maternal Type 1 (T1DM), Type 2 (T2DM), and gestational diabetes mellitus (GDM) are being enrolled. Maternal hemoglobin A1c (HbA1c) and umbilical cord insulin/glucose are being collected from 20 pregnancies in each group, 10 of which also undergo placental/umbilical cord tissue collection. Following delivery, neonatal blood glucose levels are also collected every 3-4 hours (4+ measurements) to determine rate of glycemic change. Linear regression modeling will be used to determine associations with placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic subtype and between normoglycemic and hypoglycemic neonates. Endothelial gene expression will be compared using paired t-tests with Benjamini-Hochberg correction. RESULTS/ANTICIPATED RESULTS: Thus far, 5 T1DM, 10 T2DM, and 13 GDM samples have been collected. Gestational age at delivery and birth weight were similar between groups (38.1 ± 1.05 weeks; 3.6 ± 0.59 kilograms) and delivery method is evenly distributed (Cesarean section or vaginal delivery). Currently, with limited cohort size, no association is evident between maternal HbA1c and umbilical cord glucose/insulin (p=0.114) or neonatal hypoglycemia diagnosis (p=0.674) when controlled for gestational age and infant birthweight. We hypothesize that, with pending analyses, maternal HbA1c and umbilical cord insulin levels will correlate negatively with the rate of neonatal glycemic change, and positively with the level of inflammatory and angiogenic transcription identified in placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Characterization of postnatal glucose control is key to prognosis and risk stratification of infants of diabetic mothers. Understanding placental response to glucose, as well as sequela in the fetal endothelium, is also critical to understanding the pathogenesis of neonatal hypoglycemia and other adverse outcomes of diabetic pregnancy.

ABSTRACT IMPACT: Understanding dietary patterns and nutrient intakes of the aging population may help address concerns and dietary guidelines regarding their nutritional needs. OBJECTIVES/GOALS: The objective of this study is to test the hypothesis that a healthy dietary pattern in the oldest old (aged 80 years and older) is related to greater compliance with dietary recommendations and better nutrient intake profiles. METHODS/STUDY POPULATION: We conducted a cross-sectional study of 122 participants aged 82 to 97 years old from the Geisinger Rural Aging Study (GRAS) cohort in rural Pennsylvania (n = 56 men and 66 women). The main outcome measures of the investigation were the daily nutrient intakes and food group intakes evaluated from the average of three 24-hour dietary recalls. The dietary patterns were determined by cluster analysis from 28 food groups. Diet quality and adherence to the Dietary Guidelines for Americans was assessed by the Healthy Eating Index (HEI)-2015 and the Dietary Screening Tool (DST). Recommended intakes were determined by the Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs). RESULTS/ANTICIPATED RESULTS: Less than 50% of participants met the dietary recommended intakes for vitamins D, E, K, B6, dietary fiber, zinc, potassium, and calcium. The more-nutrient-dense cluster was characterized by higher intakes of fruits and vegetables. The less-nutrient-dense cluster was characterized by higher intakes of foods including desserts and sweets. After adjusting for age, sex, and energy intake, participants in the more-nutrient-dense dietary pattern had a higher intake of vitamins A, D, K, C, fiber, and potassium (p < 0.05 for all). After adjusting for age and sex, participants in the more-nutrient-dense pattern had better diet quality assessed by the (HEI)-2015 (p < 0.001) and DST (p = 0.006). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among the oldest old, many participants were found to have nutrient intakes lower than the recommended levels for fundamental nutrients suggesting that dietary guidance in addition to a dietary pattern more aligned with dietary guidelines may be beneficial for supporting healthy aging.

OBJECTIVES/SPECIFIC AIMS: Treatment of breast cancer surgery can be classified into two overall groups: Breast-Conserving Therapy (BCT) (including partial mastectomy (PM) and oncoplastic surgery (OS)) and MAST (including mastectomy (M) and M with breast reconstruction (M+R)). Breast reconstruction (OS or M+R) offers patients an improved quality of life by aesthetically symmetric breast, higher patient satisfaction and reduced re-excision rates. Furthermore, subgroups of M+R, mastectomy with implant placement (M+I) has doubled to 21%, meanwhile mastectomy with muscular flap reconstruction (M+MF) has declined to only 2% of overall breast cancer intervention. Furthermore, in patients with with ductal carcinoma in situ (DCIS), published national guidelines recommend that sentinel lymph node biopsy (SLNB) should be offered when treated with M and should not be offered when treated with BCS. Overall complication rates for breast cancer surgery vary depending on short-term or long term outcome but are approximately 2-40%. Mortality and overall morbidity are overall low in less than 5% of cases. Known wound or infectious complications have been associated with smoking, radiation, obesity and diabetes. Nevertheless, other patient comorbidities and surgical predictors influencing acute postoperative complications are contentious. Single institutional studies or reviews compared single or two groups of breast cancer interventions for post-operative complication rates. Few studies with large enough patient cohort to analyze all possible variables influencing post-operative acute complications following all breast cancer surgeries. Understanding surgical complications is crucial to patient safety and improving health outcomes. Therefore, this study examines the 30-day postoperative complication rates in breast cancer patients who underwent a PM, M, M+R, or OS. Using the NSQIP database, we aim to elucidate these surgical trends and complications trends, while expanding our understanding of predictive surgical factors. We also examined appropriate axillary management associated with surgical interventions between 2005 and 2016. METHODS/STUDY POPULATION: A retrospective cohort analysis was conducted using the ACS-NSQIP database from 2005 to 2017. All participant user files (PUF) were obtained and approved by ACS NSQIP. The Tufts Medical Center Institutional Review Board deemed this study exempt from institutional review, given ACS NSQIP database is a de-identified data set. Inclusion criteria for this study were women with classified post-operative diagnosis of invasive breast cancer (IBC) or ductal carcinoma in-situ (DCIS) breast cancer who underwent either any BCT or any MAST procedure. Post-operative diagnosis was classified according International Classification of Diseases Ninth/Tenth Revision (ICD-9/10) code for IBC or DCIS. Surgical (M, PM, OS, M+R) and axillary lymph node categorization were done using CPT codes known for each intervention. Exclusion criteria included males, benign breast surgery, surgery for benign breast disease, lobular carcinoma, patients undergoing breast cancer surgery with 2 CPT codes with ambiguous category placement and septic patients at time of surgery. For each intervention, a total of 16 complications were clustered into 8 groups and examined over the 13-year period. ALN management was categorized as follows: no intervention on ALNs, or ALN surgery (SLNB or ALN dissection (ALND)). Chi-square tests were performed for demographic and complication rate analysis. Smoothed linear regression and non-parametric Mann- Kendall test assessed complication trends. Uni-variate and multivariate logistical regression were computed to associate odd’s ratio for comorbidities, surgical predictors and patients demographics. RESULTS/ANTICIPATED RESULTS: A total of 226,899 patients met the inclusion criteria. Annual breast surgery trends changed as follows: PM 45.6% to 45.9 (p=0.21), M 36.8% to 25.5% (p=0.001), M+R 15.7% to 23.6% (p=0.03) and OS 1.8% to 5.0% (p=0.001). Analyzing the patient cohort who underwent breast conservation, categorical analysis showed a decreased use of PM alone (96% to 90%) with an increased use of OS (4% to 10%). For the patient cohort undergoing mastectomy, M alone decreased (69% to 52%); M+R with muscular flap decreased (9% to 2%); and M+R with implant placement increased (20% to 41%) – all 3 trends p<0.0001. The rate of ALN management has changed as follows: SNLB or ALND significantly increased in mastectomy patients from 53.6% to 69.5% (SS 1.5%, R2 0.69, p < 0.01), while it changed little in the BCS population: 22.5% to 26.4% (SS 0.4%, R2 0.18, p = 0.09). Complication rates have steadily increased in all mastectomy groups (p< 0.05) but not in BCT. Cumulative complication rates between surgical categories were significantly different in each complication cluster (all p<0.0001). Overall complication rates were: PM: 2.25%, OS: 3.2%, M: 6.56%, M+MF: 13.04% and M+I: 5.68%. The most common predictive risk factors were mastectomy interventions, increasing operative time, ASA class and BMI, smoking, recent weight loss, history of CHF, COPD and bleeding disorders (all p<0.001). Patients who were non-diabetic, younger (<60) and treated as outpatient all had protective OR for an acute complication (p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: The modern era of breast surgery is identified by the increasing use of reconstruction for patients undergoing breast conservation (in the form of OS) and mastectomy (in the form of M+R). Despite national recommendations for the management of axillary lymph nodes in patients undergoing breast surgery for DCIS, nearly 30% of cases continue to be mismanaged: more than 30% of patients with DCIS undergoing mastectomy fail to receive SLNB, and more than 26% of DCIS patients undergoing BCS are still receiving axillary lymph node surgery. Our study provides data showing significant trends that will impact the future of both breast cancer surgery and breast training programs. We also provide data comparing nationwide acute complication rates following different breast cancer surgeries that can be used to inform patients during surgical decision making.

Effective community engagement in T3–T4 research is widespread, however, similar stakeholder involvement is missing in T1–T2 research. As part of an effort to embed community stakeholders in T1–T2 research, an academic community partnered team conducted discussion groups with researchers to assess perspectives on (1) barriers/challenges to including community stakeholders in basic science, (2) skills/training required for stakeholders and researchers, and (3) potential benefits of these activities. Engaging community in basic science research was perceived as challenging but with exciting potential to incorporate “real-life” community health priorities into basic research, resulting in a new full-spectrum translational research model.

OBJECTIVES/GOALS: Decision-making impairments in addiction can arise from dysfunction in distinct neural circuits. Such processes can be dissociated by measuring complex, computationally distinct behaviors within an economic framework. We aim to characterize computational changes conserved across models of addiction. METHODS/STUDY POPULATION: We used neuroeconomic tasks capable of dissociating neurally separable decision processes using behavioral analyses equally applicable to humans and rodents. We tested 12 human cocaine-users and 9 healthy controls on the Web-Surf task designed to match the rodent Restaurant Row task on which 27 mice were trained and then exposed to saline (n = 10), cocaine (n = 7), or morphine (n = 10). All subjects foraged for rewards (humans: entertaining videos; mice: food) of varying costs (1-30s delays) and subjective value (humans: genres; mice: flavors) by making serial accept or reject decisions while on a limited time budget, balancing the utility of wanting desirable rewards despite conflicting costs. RESULTS/ANTICIPATED RESULTS: When encountering unique offers for rewards with a delay above one’s willingness to wait, cocaine-treated mice like cocaine-exposed humans were less likely to appropriately reject economically disadvantageous offers. Furthermore, these mice and humans did so despite spending more time deliberating between future options. In contrast, morphine-treated mice displayed distinct impairments when given the opportunity to correct past mistakes, a process we previously demonstrated was uniquely sensitive to alterations in strength of synaptic connectivity of the infralimbic-accumbens shell circuit in mice. We anticipate human opioid-users will mirror these latter, computationally distinct findings. DISCUSSION/SIGNIFICANCE OF IMPACT: These data elucidate facets of addiction shared across species yet fundamentally distinct between disease subtypes. Our translational approach can help shed light on conserved pathophysiological mechanisms in order to identify novel diagnostic parameters and computational targets for intervention.

OBJECTIVES/SPECIFIC AIMS: To evaluate gaps in knowledge for women who are cancer survivors regarding the impact of comorbidities and lifestyle behaviors on endometrial and cervical cancer risk, and to assess prevalence of established care with a primary care physician (PCP) among patients and evaluate acceptability of referral to a PCP METHODS/STUDY POPULATION: Single institution cross-sectional study examining all women aged 18 or older with a diagnosis of cervical or endometrial cancer who present for care by a gynecologic oncologist at Barnes-Jewish Hospital/Washington University in St. Louis School of Medicine. Patients will be invited to complete a survey specific to cancer diagnosis that includes questions on participant background and sociodemographic information, knowledge of risk factors for their specific cancer site, and whether or not the patient has a primary care provider and the acceptability of referring RESULTS/ANTICIPATED RESULTS: Majority of women will be unaware of how comorbidities affect cancer risk and treatment outcomes. For women without a PCP, we anticipate that they will be accepting towards the notion of being referred to one for establishing care. DISCUSSION/SIGNIFICANCE OF IMPACT: Pilot information from this study will 1. Allow providers to improve cancer survivorship care plans by increasing collaboration between PCPs and oncologists to provide ongoing care, and 2. Afford information for providers on where gaps in knowledge exist so as to better education patients.

OBJECTIVES/GOALS: The goal of this project is to develop a strategy to collect and extract published evidence in real time and to house and model these data for efficient downstream application to Program activities such as targeted reviews, grant evaluation and partner engagement. METHODS/STUDY POPULATION: We created the World Trade Center Health Effects Library in 2016. Today, this living review is ongoing and is fueled by daily systematic searches of online publication databases. Each day we screen new references for health effects of 9/11. The publication must include measurements, reports, or discussion of 9/11 health effects. If a publication meets these criteria, it is categorized by outcome and funding category. Primary outcome category data, reference metadata, and funding data are then made immediately available for programmatic analysis. All reference data are entered into a data pipeline and modelled for targeted reviews. RESULTS/ANTICIPATED RESULTS: The WTC Health Effects Library curates 1932 references and adds an average of 60 new references each year on a wide range of study populations, exposures, and conditions. The completeness of the library has been verified by comprehensive literature searches for 9/11 health outcomes conducted externally and by CDC Library staff. As a result, the curated library is a proven alternative to a lengthy literature search and allows the Program and stakeholders to explore the data and engage immediately in targeted reviews on curated topics. The data that are collected in the screening and categorization process are merged with publication metadata and funding data to inform a data pipeline that supports outputs such as interactive visuals, charts, reports, and curated bibliographies for structured review. DISCUSSION/SIGNIFICANCE: This living review allows the Program to rapidly conduct focused reviews, to evaluate grants, and to communicate accurate data to partners. By using the curated data, we have reduced the time required to perform mandated evidence reviews by weeks, have conducted two structured reviews, and defined gaps in research maturity and health equity.

OBJECTIVES/GOALS: Peri-implantitis is the inflammation of peri-implant mucosa and subsequent loss of supporting bone. Its treatment is only <40% successful mainly due to persistent bacterial infection. The goal of this project is to increase success rates by developing a robust antibiofilm multi-biomolecular membrane that can be placed around implant surfaces. METHODS/STUDY POPULATION: A collagen membrane was soaked in the antimicrobial peptide GL13K solution overnight to form an interpenetrating fibrillary network. The nanostructure of the membrane was imaged with scanning electron microscope (SEM). The hydrophobicity of the membrane was analyzed by water contact angle (WCA) measurements. The biodegradability was tested in a 0.01 mg/mL Type I collagenase solution for up to 5 weeks. The antimicrobial activity of the membrane was assessed with Gram-positive oral bacteria Streptococcus gordonii. The cytotoxicity was evaluated by culturing human gingival fibroblasts (HGF), and the osteogenesis was assessed using preosteoblasts MC3T3. Pure collagen membrane was used as the control. Statistical significance (p<0.05) was determined by one-way ANOVA with Tukey’s HSD test. RESULTS/ANTICIPATED RESULTS: The antimicrobial peptide GL13K self-assembled to short fibrils (< 1 µm long), which entangled with the larger collagen fibers (around 200 nm in diameter). The collagen fibers presented characteristic periodic banding structures, which provided biomimetic cues for cell behavior as extracellular matrix. The interpenetrated GL13K fibrils turned the highly hydrophilic collagen membrane to a hydrophobic membrane (WCA = 135 °) and significantly reduced the rate of degradation by collagenases. The developed membrane was efficient in preventing the attachment of S. gordonii. A large portion of the attached bacteria was killed on the surface of the membrane. The incorporation of GL13K did not affect the cytocompatibility of the membrane for HGF. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed an antibiofilm membrane with interpenetrating collagen and antimicrobial peptide fibrils. The strong antimicrobial activity and low cytotoxicity support its further translational evaluation as scaffolds for increasing success rate in treating peri-implantitis.

ABSTRACT IMPACT: This research study will provide evidence for public policy, systemic changes, and other interventions to address the adverse impacts of prolonged stress exposure experienced by young Black men. OBJECTIVES/GOALS: Previous studies have demonstrated a strong association between allostatic load (i.e., stress-induced cumulative biological risk) and mortality in the Black American population. The aim of this study is to examine the association between allostatic load and mortality in Black men and to determine if the relation varies by age. METHODS/STUDY POPULATION: Data from the third National Health and Nutritional Examination Survey (NHANES III, 1988-1994), linked to the 2015 National Death Index Public Release File, will be used for Black male adults 18 years or older. Allostatic load score includes nine biomarkers: albumin, C-reactive protein, total cholesterol, high-density lipoprotein, hemoglobin A1C, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, and pulse rate. The number of variables for which the participant’s scores fall in the quartile of highest clinical risk are added together to create a summary score. Cox proportional-hazard analyses is employed to estimate the associations between allostatic load and all-cause mortality for the total sample and stratified by age, adjusting for selected characteristics. RESULTS/ANTICIPATED RESULTS: We hypothesize that the association of allostatic load with mortality will be greater among younger, compared to older, Black men. Young Black men (ages 25-44) are at particular risk of adverse impacts of chronic stress and allostatic load, due to their experience of chronic discrimination, systemic racism, racial battle fatigue, and mundane, extreme, environmental stress. Furthermore, the allostatic load-mortality association may be attenuated for older Black men due to a survival effect. DISCUSSION/SIGNIFICANCE OF FINDINGS: If the association between allostatic load score and mortality is stronger in young Black men, it would provide evidence for early identification of a group with high risk of premature mortality, and for public policy, systemic changes, and other interventions to address the adverse impacts of prolonged stress exposure experienced by young Black men.

OBJECTIVES/GOALS: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by dysregulated collagen accumulation in the lung parenchyma. Our goal is to investigate the role of O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in pulmonary fibrosis to ultimately discover novel therapies for fibrosis resolution. METHODS/STUDY POPULATION: Lung tissue from IPF and non-IPF donors was subjected to immunohistochemistry (IHC) to assess O-GlcNAc levels. Primary human lung fibroblasts were treated with OGT or O-GlcNAcase (OGA) inhibitors followed by transforming growth factor-beta 1 (TGF-β1) stimulation to assess O-GlcNAc regulation of fibroblast-to-myofibroblast transition (FMT) markers [alpha smooth muscle actin (α-SMA) and type 1 and type 3 collagen (COL1α1, COL3α1)] In Drosophila melanogaster, OGT knockdown (KD)/overexpression (OE) was conditionally induced to assess pericardin, a type IV collagen-like protein, regulation by immunofluorescence. Lastly, a mouse model of bleomycin-induced pulmonary fibrosis was examined following OGT KD and assessed for fibrosis resolution via histology, hydroxyproline assay, and western blotting. RESULTS/ANTICIPATED RESULTS: O-GlcNAc staining was increased in IPF lung tissue compared to non-IPF control lungs. In primary human lung fibroblasts, TGF-α1 administration resulted in increased FMT markers (α-SMA, COL1α1, and COL3α1), which were reduced or increased by OGT or OGA inhibition, respectively. Genetic manipulation in the Drosophila models showed decreased pericardin expression with OGT KD compared to the wild-type, whereas OGT OE increased pericardin compared to control. Additionally, OGT KD in bleomycin treated aged mice resulted in reduced collagen levels at the transcript and protein level and concurrent fibrosis resolution as assessed by Masson’s trichrome staining and total hydroxyproline analysis. Collectively, showing OGT/O-GlcNAc regulating collagen in fibrosis resolution. DISCUSSION/SIGNIFICANCE: These data suggest that the OGT/O-GlcNAc axis regulates collagen deposition in pulmonary fibrosis, and we show that O-GlcNAc is implicated in the pathogenesis of IPF. We identified OGT as a therapeutic target to overcome current drug limitations, opening new horizons for biomedical treatment.

OBJECTIVES/GOALS: The Learning Health System (LHS) framework at Columbia University Irving Medical Center (CUIMC) aims to optimize health system performance through enhancing the patient and care team experience, reducing inequities, costs and improving population health outcomes, through a collaborative, interdisciplinary and data driven approach. METHODS/STUDY POPULATION: In alignment with the Quintuple Aim, the LHS program at CUIMC is composed of five critical components: data integration (particularly using Epic EHR and real-time informatics data), utilization of evidence-based practices, a methodology for continuous improvement, and leadership commitment. Our methodology incorporates an iterative process improvement project cycle into an integrated infrastructure and governance of an academic medical center and its hospital partners to fulfill rapid project design and implementation. The LHS at CUIMC aims to bring a cultural shift through stakeholder engagement, symposia, training, accelerated pilot award opportunities, and building external partnership engagement. RESULTS/ANTICIPATED RESULTS: At CUIMC, our definition of a successful integration of a LHS framework is a cultural shift in thinking, method, and continuous improvement. The LHS program has developed multidisciplinary teams that are involved in defining and sharing data, design, and project management resources. In 2021, the first annual symposium was launched and brought together over 200 stakeholders from across the organization to support continuous education, training, and scaling of the framework. As a result of this foundation, two pilot initiatives have been funded and launched, the innovation accelerator model developed and is supporting over ten unique innovative and transformative clinical and operational programs, and several research grant applications have been submitted citing learning health system methodologies. DISCUSSION/SIGNIFICANCE: Our LHS framework has broken down silos and institutional barriers, creating a network of stakeholder groups. Our interdisciplinary approach has enabled us to create sustainable processes, resources and training on rapid, rigorous design, evaluation and implementation of interventions using real-time informatics data and digital health tools.

OBJECTIVES/GOALS: Patient-specific definition of extent of surgical excision is foundational to the safety offered by computer assisted interventions. Consequently, this study aims to develop a pipeline for automated segmentation of bone removed during cortical mastoidectomy, a technically complex otologic surgery. METHODS/STUDY POPULATION: A simulator, previously developed in our lab, allows fully immersive simulation of mastoidectomy using segmented temporal bones generated from CT data. Using the simulator, one attending surgeon will perform three trials of mastoidectomy on 20 different temporal bones. From the simulator we will obtain data on the volume of bone removed for a specific anatomy, averaged between trials. No new U-net (nnU-net), an open-source three-dimensional segmentation network, will then be trained to predict the volume of bone removed using segmented pre-operative CT imaging. Segmentation accuracy will be evaluated with the Dice coefficient, modified Hausdorff distance (mHD), sensitivity and specificity. RESULTS/ANTICIPATED RESULTS: We expect the mean pairwise Dice coefficient to be high indicating relative similarity of volume removed between trials. Moreover, we predict that following five-fold cross-validation the best model will result in a Dice coefficient, mHD, sensitivity, and specificity indicative of volume removed predictions consistent with surgeon-generated data. Finally, given that network training will penalize overlap of the predicted excised bone segment and previously segmented anatomic structures, we expect that no critical anatomical structures will be marked as tissue removed. DISCUSSION/SIGNIFICANCE: We hope to show that deep learning architectures can accurately predict bone removed during mastoidectomy. These predictions can be used for preoperative planning, as clinical endpoints in surgical simulators, or be used in conjunction with surgical robots, all ultimately improving patient safety.

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.

OBJECTIVES/SPECIFIC AIMS: Research overview: Providing patient-centered care is increasingly a top priority in the U.S. healthcare system.1,2 Hospitals are required to publicly report patient-centered assessments, including results from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient satisfaction surveys.3 Furthermore, clinician and hospital reimbursements are partially determined by performance on patient satisfaction measures.3 Consequently, hospitals and clinicians may be incentivized to improve patient satisfaction scores over other important outcomes.4 Paradoxically then, the pursuit of patient-centered care may lead clinicians to fulfill patient requests for unnecessary and potentially harmful treatments.5 Opioid prescribing during hospitalizations may be particularly affected by clinicians’ seeking to optimize patient satisfaction scores.6,7 Satisfaction with pain care is an important predictor of overall patient satisfaction in the HCAHPS surveys,8,9 and clinicians report increased pressure to fulfill patient requests for immediate pain-relief.10,11 Therefore, clinicians may prescribe opioids to avoid receiving lower patient satisfaction scores.12,13 Furthermore, clinicians lack clear guidance on opioid prescribing for some populations, including non-surgical inpatients, who represent almost half of all hospitalizations.14 To reduce clinicians’ incentive to prescribe opioids as a means of achieving patient satisfaction, the Center for Medicare and Medicaid Services (CMS) temporarily removed questions related to patient satisfaction with pain care from the clinician and hospital reimbursement formulas beginning in 2018.15 Importantly, prior research16-20 has not rigorously tested the hypothesis implied by the CMS policy change: that certain opioid prescribing practices in inpatient pain care are associated with higher patient satisfaction. Objectives: The purpose of this study was to evaluate the association between the receipt/dose of opioids during non-surgical hospitalizations and patient satisfaction measured by the HCAHPS survey. METHODS/STUDY POPULATION: Methods/Study Population: We conducted a pooled cross-sectional study of adults (18 and older) with non-surgical hospitalizations within the 11-hospital healthcare system in a Midwestern state from 2011-2016. Data were extracted from electronic health records and linked to HCAHPS patient satisfaction surveys. We estimated the propensity score for receipt of any opioids during hospitalization and separately the receipt of high dose opioids (≥100 morphine milligram equivalent [MME]) based on patient, encounter, and facility characteristics for all hospitalizations with complete data. We used nearest neighbor matching to construct two matched samples to minimize selection bias and confounding by indication. We used a standardized difference threshold of < 0.1 as an indication of the balance between matched groups. Outcomes were compared with a test on the equality of proportions using large-sample statistics. All analysis was performed in STATA 14.0 analytical software. Main outcomes: We analyzed four dependent variables. Two pain-specific patient satisfaction variables were derived from the responses to the following survey questions: 1) “During this hospital stay, how often your pain was well controlled? (pain control)” and 2) “During this hospital stay, how often did the hospital staff do everything they could to help you with your pain? (pain help)”, with 4-point Likert scale responses ranging from “Never” to “Always.” We also used two global satisfaction measures derived from the responses to the following survey questions: 1) “Using any number from 0 to 10, where 0 is the worst hospital possible and 10 is the best hospital possible, what number would you use to rate this hospital during your stay (overall patient satisfaction)?” and 2) “Would you recommend this hospital to your friends and family (willingness to recommend a hospital)? (4-point scale of “Definitely Yes” to “Definitely No”). Because the responses are not normally distributed, and the response options are truncated, we dichotomized each of these questions following previously published approaches8 and CMS methodology3 (e.g. “always” vs. all other responses or “9 or 10 rating” vs. all others). RESULTS/ANTICIPATED RESULTS: Results: Among 17,691 patients who reported that they needed pain medications during hospitalization in their HCAHPS survey, 43.7% (n=7,735) received opioids. Among the matched sample (n=8,848), 55% were female, 90% were white, 9% were black, 74% were emergency admissions, 29% had a circulatory diagnosis, 92% were discharged home, and the average pain score ranged from 0.2 to 7.1 during the hospital stay. Compared to matched patients hospitalized but did not receiving opioids, those who received opioids did not significantly differ in their rating of pain help (75% of patients without opioids rated that they always received help for their pain versus 75% of patients with opioids; p=.78), pain control (55% of patients without opioids reported that their pain was well controlled versus 54% on opioids; p=.93), willingness to recommend the hospital (69% of patients without opioids reported that they would definitely recommend a hospital versus 71% with opioids; p=.16) and overall rating of their care (47% of patients without opioids rated their hospitalization as 10 versus 46% on opioids; p=.22). DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: We found no evidence that receipt of opioids is associated with patient satisfaction, including at doses. To our knowledge, this is the first study that used propensity score matching to examine the association between inpatient opioid prescribing practices and patient satisfaction. Furthermore, our sample is unique in the inclusion of patients hospitalized for non-surgical indicators over a five year period in the multi-hospital healthcare system in a Midwestern state. Our findings add to the existing literature which has shown contradictory associations between opioid prescribing and patient satisfaction.16-22 Specifically, few studies that looked at surgical inpatients showed a lack of association between patient satisfaction16,18 and opioid prescribing, whereas others showed that receipt of opioids was associated with lower patient satisfaction.17-20 Our findings may imply that satisfaction with pain care may be achieved without administering opioids to non-surgical inpatients. Alternatively, satisfaction with pain care may not be influenced by opioid prescribing for non-surgical inpatients. Future research should further examine the association between opioid prescribing and patient satisfaction among non-surgical inpatients on a national scale to get a better understanding of the relationship between certain pain care practices and patient satisfaction.