Objectives/Goals: Obesity has been classified as a global epidemic and origin of numerous health issues. The central hypothesis of this study is that psychological measures, DNA methylation, and gene transcription will predict obesity-related outcomes after lifestyle interventions, and such interventions may alter DNA methylation profiles. Methods/Study Population: This study consisted of a randomized-controlled trial examining the effects of lifestyle +/- stress reduction interventions in 285 highly stressed parents with obesity, followed for 2 years. Full participants received nutrition and activity counseling, and were randomized to either a stress reduction intervention or a contact control. Those who otherwise qualified for the study but unable to fully participate were included in a no intervention control group. The intervention consisted of 12 weeks of nutrition and activity counseling +/- 2-hour weekly stress reduction interventions using MBSR and CBT-based strategies. DNA methylation was assessed using Illumina EPIC arrays. Results/Anticipated Results: Using linear mixed models (LMMs), this study will first examine the hypothesis that baseline psychological measures and pre-existing methylation sites associated with obesity and glycemic control (e.g., ABCG1, ATP10A, TXNIP, SREBF1, RNF39, and SOCS3) predict changes in BMI, HOMA-IR, and HgbA1C post-intervention and at 1 and 2 year follow-ups. Using sites that demonstrate statistical significance, we will develop a polymethylation risk score predictor of change in BMI. Next, we will examine the hypothesis that interventions which reduce obesity may also lead to improvements in epigenetic aging using LMMs to determine if changes in BMI or HOMA-IR predict changes in epigenetic age acceleration over the course of the study. Discussion/Significance of Impact: This work examines whether psychological factors and/or epigenetic markers may be used in patient stratification at initiation of treatment, enabling improved treatment selection, fewer years of obesity and decreased risk of comorbidities. This proposal also asks whether lifestyle interventions impact the aging process itself.

OBJECTIVES/SPECIFIC AIMS: The study aims to measure the associations between nonclinical factors and the likelihood of electing contralateral prophylactic mastectomy [(CPM) i.e. bilateral mastectomy for unilateral cancer] among women with breast cancer, with a focus on the roles of race, relationship status, and geographic location. The outcome of interest is a dichotomized surgery type variable (i.e. CPM versus other surgery). METHODS/STUDY POPULATION:. The Surveillance, Epidemiology, and End Results registry was queried to identify female breast cancer patients diagnosed at stage IA through IIIC from 2010 through 2015 and received surgery as part of their primary treatment (n=174,776). A multilevel logistic regression was used to model likelihood of CPM versus less aggressive surgical treatment (i.e. breast conserving surgery or unilateral mastectomy). Fixed-effects included age at diagnosis, race, relationship status, insurance type, county-level median income, county-level population density, stage at diagnosis (low-stage, IA-IIB; advanced-stage, IIIA-IIIC), an interaction term between race and stage at diagnosis, and breast tumor subtype. County of residence was used as a random-effect. RESULTS/ANTICIPATED RESULTS: Among women with low-stage cancer, compared to the reference class of white women, black women had 0.57 times lower odds of CPM (p<0.0001), Hispanic women had 0.69 times lower odds of CPM (p<0.0001), and Asian women had 0.60 times lower odds of CPM (p<0.0001). Among women with advanced-stage cancer, compared to white women, black women had 0.42 times lower odds of CPM (p<0.0001), Hispanic women had 0.51 times lower odds of CPM (p<0.0001), and Asian women had 0.45 times lower odds of CPM (p<0.0001). Compared to the reference class of single, never-married women, divorced/separated women had 1.25 times greater odds of CPM (p<0.0001), widowed women had 1.11 times greater odds of CPM (p=0.009), and married/partnered women had 1.18 times greater odds of CPM (p<0.0001). County-level variation from the random-effect (MOR, 1.49; p<0.001) had a greater influence on CPM election than fixed-effects for insurance class, breast tumor subtype, county median income, county population density, and year of surgery. DISCUSSION/SIGNIFICANCE OF IMPACT: The nonclinical factors associated with variation in breast cancer surgical decision-making suggest patients and providers both may benefit from further education about surgical treatment options. Providers may also benefit from educational materials that highlight treatment selection disparities within specific contexts, such as surgery for primary unilateral breast cancer. To more narrowly tailor future policy interventions, an additional mixed-methods exploration is recommended to clarify how relationship status and location serve as mechanisms for breast cancer decision-making.

OBJECTIVES/GOALS: In 2017, new guidelines recommended multi-step algorithms for CDI diagnosis, and clinical centers rapidly implemented changes despite limited pediatric data. We assessed a multi-step algorithm using NAAT followed by EIA for ability to differentiate symptomatic CDI from colonization in children. METHODS/STUDY POPULATION: We prospectively enrolled pediatric patients with cancer, cystic fibrosis, or inflammatory bowel disease who were not being tested or treated for CDI and obtained a stool sample for NAAT. If positive by NAAT (colonized), EIA was performed. Children with symptomatic CDI who tested positive by NAAT via the clinical laboratory were also enrolled and EIA performed on residual stool. A functional cell cytotoxicity neutralization assay (CCNA) was performed in addition. RESULTS/ANTICIPATED RESULTS: Of the 138 asymptomatic children enrolled, 24 (17%) were colonized. An additional 37 children with symptomatic CDI were enrolled. Neither EIA positivity (41% versus 21%, P = 0.11) or CCNA positivity (49% versus 46%, P = 0.84) were significantly different between symptomatic versus colonized children. When both EIA and CCNA were positive, children were more commonly symptomatic than colonized (33% versus 13%, P = 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: A multi-step testing algorithm with NAAT and EIA failed to differentiate symptomatic CDI from colonization in our pediatric cohort. As multi-step algorithms are moved into clinical care, pediatric providers will need to be aware of the continued limitations in diagnostic testing.

OBJECTIVES/SPECIFIC AIMS: Examine data from PNID patients to evaluation the strength of associations between pre-operative and post-operative levels of pain, quality of life, and emotional reactions to pain to determine if one or more can serve as better predictors of surgical success than pain. METHODS/STUDY POPULATION: In our preliminary study, we gathered data from a pre-existing database of 464 PNID patients that contains self-reported visual analog scale scores (VAS) of pain intensity, QoL, and depression. We measured these variables at three time points: pre-operatively, post-operatively, and at the final visit. We used the Wilcoxon signed rank test to determine if each of these three variables differed significantly between the pre-operative visit and the post-operative visit period and from the pre-operative visit to the final visit. RESULTS/ANTICIPATED RESULTS: Median time from the pre-operative visit to surgery was 9 weeks; median time from surgery to the post-operative visit was 4 weeks; and median time from the post-operative visit to the final visit was 23.5 weeks. There was a clinically meaningful difference in pain scores between the pre-operative and post-operative visits (median difference 1.15; 95% CI 0.75-1.55). In the period between the post-operative visit and the final visit there was also a decrease in pain (0.90; 95% CI 0.55-1.30). The magnitude of change in median difference of 1.85 (95% CI 1.50-2.20) between the pre-operative visit and the final visit was larger than the change in median difference of 0.90 (95% CI 0.55-1.30) between the post-operative visit and the final visit. The pre-operative visit median QoL score was higher than the median score at the post-operative visit (1.65; 95% CI 1.25-2.10). The smallest median difference in QoL of occurred between the post-operative and the final visit (1.10; 95% CI 0.60-1.45). As seen with the pain scores, the magnitude of change in median difference of 2.50 (95% CI 2.20-2.85) for QoL was greatest between the pre-operative and the final visit. Depression scores showed the least amount of change amongst all the variables, between the pre-operative and the post-operative visit (1.00; 95% CI (0.70-1.40), and similarly between the post-operative visit and the final visit (0.15; 95% CI (0-.40). The median differences between the pre-operative and final visit were greatest in QoL (2.50; 95% CI 2.20-2.85), followed by pain scores (1.85; 95% CI 1.50-2.20), and finally, depression (1.05; 95% CI 0.70-1.40). DISCUSSION/SIGNIFICANCE OF IMPACT: Our results show that all three variables measured improve with surgery and continue to improve over the post-operative course to the final visit. This suggest that the relationships between pain, QoL, and depression should be further investigated. We are hopeful that elucidating how these variables interact in the PNID patient population, will encourage peripheral nerve surgeons to use these parameters in conjunction with pain intensity to measure outcomes. A follow-up study expanding on these results and including measures of anger and frustration in a larger sample is underway.

OBJECTIVES/GOALS: Physicians can request the clinical use of investigational products for their patients through an FDA pathway called Expanded Access (EA). Most evaluations of EA focus on the FDA submission only. We sought to evaluate these requests through the full academic medical center process. METHODS/STUDY POPULATION: Through the Transforming Expanded Access to Maximize Support and Study grant, we reviewed regulatory records for single-patient EA requests at four institutions (Duke University, University of Rochester, University of Michigan, and University of Texas Southwestern) which occurred between June 1, 2021 and February 28, 2023. Key data was collected, including the investigational product requested, submission and approval dates, urgency of request, and indication for treatment. Descriptive statistics were performed with Microsoft Excel. RESULTS/ANTICIPATED RESULTS: A total of 405 EA requests were identified, of which 319 (78.8%) were for drugs, 59 (14.6%) for biologics, and 27 (6.7%) for medical devices. The majority were characterized as non-emergency (60.7%), but the proportion of emergency to non-emergency cases varied considerably when stratified by year, with a peak in emergency cases in 2020. The most common products included therapies for COVID-19 and Mpox. Median time to obtain all approvals for treatment was 7 days for emergency cases and 28 days for non-emergency. The FDA review took the least time, with a median of 1 day in non-emergency cases. Full board approval from an institutional review board in non-emergency cases was 7 days. DISCUSSION/SIGNIFICANCE: These results generally align with previous reports on EA submissions received by the FDA. The timelines for the EA process represent an important benchmark both for treatment planning and institutional improvement.

Objectives/Goals: This review examined if sleep duration is associated with established Alzheimer’s disease (AD) fluid biomarkers, such as amyloid-β peptides (Aβ40 and Aβ42), total-tau (t-tau), phosphorylated tau (p-tau181 and p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Methods/Study Population: We searched PubMed, CINAHL, and SCOPUS through September 15, 2024, using keywords and appropriate subject headings related to AD, fluid biomarkers, and sleep. The search was developed and conducted in collaboration with a medical librarian. We also searched Google Scholar and screened the reference lists of relevant reviews. Two independent reviewers screened 1,657 peer-reviewed articles, of which 21 met the inclusion criteria (14 with biomarkers measured in cerebrospinal fluid [CSF] and 7 in blood). Two review authors independently extracted study details from included articles using a standardized data extraction template. Results/Anticipated Results: Sample sizes ranged from 18 to 4,712 participants. Sleep duration was assessed using self-reported measures in 8 studies and objective measures in 13. For the 14 studies using CSF biomarkers, lower Aβ42 (3/14), Aβ40 (1/14), or the ratio (1/14) were associated with either short or long sleep duration; t-tau (3/14) and p-tau181 (4/14) levels were mostly associated with short sleep. For the 7 blood-based biomarker studies, Aβ42 (2/7), Aβ40 (2/7), and the ratio (3/7) had mixed results with either short or long sleep. T-tau (1/7) and p-tau181 (1/7) levels were associated with long sleep; NfL (2/7) was associated with both short and long sleep. Six studies reported nonlinear relationships, with both short and long sleep associated with unfavorable biomarker profiles. None of the studies investigated p-tau 217 or GFAP. Discussion/Significance of Impact: Our results suggest that the relationship between sleep duration and AD fluid biomarkers is very complex, and it highlights the importance of sleep in AD risk assessment and prevention. The inconsistency in findings stresses the need for standardized study design and measurement methods to clarify causality and inform clinical guidelines.

OBJECTIVES/GOALS: There are two objectives: 1) To identify healthcare providers’ (HCP) barriers and potential solutions towards rural adolescents’ access to mental healthcare. Healthcare providers include pharmacists, physicians, and mental healthcare providers (MHPs). 2) To identify rural high schoolers’ barriers and potential solutions towards access to mental healthcare. METHODS/STUDY POPULATION: Fifteen HCPs will be recruited via email listserv and the snowball method. Perceived barriers of rural adolescents, personal barriers, current practices to address mental health in adolescents, and preferred solutions will be discussed. Twenty student and parent dyads will be recruited using fliers in school systems and will be interviewed individually outside of class time on school grounds or over the phone. Barriers to care and preferred solutions will be discussed. All interviews will be semi-structured, recorded, conducted in person or over the phone, and last for 30 minutes to an hour. Compensation will be $25 for students and parents each, $50 for pharmacists and mental health providers and $100 for physicians. Thematic qualitative data analysis will be performed using Atlas.ti software. RESULTS/ANTICIPATED RESULTS: Data collection is ongoing. Anticipated results for barriers include absence of mental healthcare providers in rural areas, inability to access mental healthcare providers further away, stigma towards mental healthcare, and lack of knowledge of mental health conditions and treatment. Anticipated results for potential solutions may include promoting mobile applications to assist with telehealth and self-care. Other solutions may be collaboration among rural healthcare providers for adolescents with mental health conditions. Preferred solutions may also include pharmacists disseminating knowledge to rural adolescents and their parents or referrals to mental healthcare providers. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will identify barriers and solutions to access to mental healthcare among rural adolescents. These solutions can then be applied towards the creation of programs that address salient issues within rural communities with a greater chance of uptake and use so that rates of depression and suicide will decrease. CONFLICT OF INTEREST DESCRIPTION: Funding through UAB TL1 award.

The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public–private partnership value are shared to inform responses to future pandemics.

The Science Writing Initiative for Trainees is a science communications internship program for biomedical graduate students and postdoctoral fellows at the Medical University of South Carolina. Interns serve as an amateur press corps, writing news stories and press releases about recent high-impact research articles. Since 2016, 25 interns have written more than 100 EurekAlert! press releases that have received more than a half million views. Interns learn to explain science across the translational spectrum and to convey findings in plain language to a lay audience, serving as ambassadors for science.

Through a series of example research studies, we illustrate processes in translating case report forms to increase language diversity in study populations while simultaneously highlighting implications for data collection and analyses. The Northwestern University Data Analysis and Coordinating Center manages the translation of participant-facing study documents into languages other than English through a process that has been refined over several years, adjusting for changes in technical capabilities in electronic case report forms. This approach to manage, examine for context, and implement certified case report form translations offers an efficient workflow to streamline data capture in multiple languages.

OBJECTIVES/SPECIFIC AIMS: The accurate and efficient serial measurement of patient centered outcomes is a priority in the clinical care of systemic lupus erythematosus (SLE). Patient-Reported Outcomes Measurement Information Systems (PROMIS®) Global Health Short Form (PROMIS10) is a 10-item universal patient reported outcome measure of global physical and mental health with construct validity in SLE. The longitudinal responsiveness (sensitivity to change) of PROMIS10 in SLE patients is unknown. We aimed to evaluate the responsiveness of PROMIS10 in SLE outpatients using patient and physician-derived anchors. METHODS/STUDY POPULATION: Adults meeting SLE classification criteria were recruited from an SLE Center of Excellence. Subjects completed PROMIS10 at two visits a minimum of one month apart. SLE disease activity was measured with a patient global assessment of change, a physician global assessment and the physician-derived SELENA-SLEDAI. Responsiveness over time of PROMIS10 scores was evaluated using known-groups validity. Effect sizes of changes in PROMIS global physical health and global mental health scores from baseline to follow up were compared across groups of patients who differed in their patient global assessment of change, physician global assessment, and SELENA-SLEDAI using Kruskal-Wallis tests. RESULTS/ANTICIPATED RESULTS: A diverse cohort of 228 SLE patients completed baseline surveys (Table 1), with 190 (83%) completing a follow up survey. Using the patient-based anchor, PROMIS10 demonstrated mild to moderate responsiveness to improvement (effect size 0.29) and worsening (effect sizes −0.27 and −0.54) of health status for both global physical health and global mental health (Table 2). Using the physician global assessment and SELENA-SLEDAI as anchors, there were no statistically significant differences in effect sizes across groups. DISCUSSION/SIGNIFICANCE OF IMPACT: PROMIS10 showed responsiveness over time to patient-reported, but not physician-derived changes in lupus health status. These data suggest that PROMIS10 can be used to efficiently measure and monitor important aspects of the patient experience of lupus not captured by physician-derived metrics. Further studies are needed to evaluate the role of PROMIS in optimizing longitudinal disease management in SLE.

OBJECTIVES/SPECIFIC AIMS: Objective: Identify barriers and facilitators of positive patient-provider interactions for AAN patients. METHODS/STUDY POPULATION: Methods: Using a mixed-methods, longitudinal, patient-interview design, N = 29 (to date) women with a history of AAN have been enrolled. Each patient completed a diagnostic interview and standardized surveys to establish ED diagnosis, severity, and associated psychopathology. Transcribed, semi-structured qualitative interviews are assessed for common themes using content analysis methods. RESULTS/ANTICIPATED RESULTS: Anticipated Results: Patients aged 18 to 74 (M = 36.3, SD = 12.0), with mean BMI = 39.8 (22.7-61.1; SD = 11.3), and mean weight suppression (lbs) during their illness = 119.41 (SD = 69.3). Women reported a mean=12.75 years (0-37 years, SD = 10.5) treatment delay. Qualitative analysis revealed the following barriers in healthcare provider interactions: 1) experiences of provider weight-bias, 2) low specificity in ED screening questions, 3) lack of indicated screening procedures/diagnostic tests (orthostatic screening, EKG, food log, labs), and 4) provider praise of ED behaviors. Facilitators: 1) lower BMI at presentation, 2) provider education in EDs, 3) community-provider collaboration, and 4) patient self- and family- advocacy. DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: Unfortunately, while early intervention best predicts positive outcomes, higher-weight patients in this study experienced significant treatment delay. Translationally, it is taking too long for AAN patients to receive the right treatment at the right time. However, findings indicate that interventions at the provider level (increasing ED education, building community partnerships, increased adherence to screening protocols) could improve screening, diagnostic, and referral practices—and ultimately long-term outcomes for this unique patient population.

Objectives/Goals: Neuromodulation strategies like transcranial magnetic stimulation (TMS) can target specific neural circuits underlying particular psychiatric symptoms, potentially 1) enhancing understanding of mechanisms of illness and recovery and 2) acting as novel therapeutics. These feasibility studies lay foundation for a study of major depression. Methods/Study Population: Four healthy volunteers completed structural and functional MRI (fMRI). fMRI included a trait-adjective task, a negative self-referential processing task known to activate VMPFC, which is known to be abnormal in major depression. During the task, participants respond on a task pad whether they feel that each of a series of displayed adjectives (positive, negative, or neutral) applies to them. Three participants then participated in a simulated image-guided TMS session using their MRI data to target their VMPFC. Three-dimensional tracking of the participant’s head and the TMS coil was used to position the coil for peak stimulation of the targeted brain region. Results/Anticipated Results: Our team collected quality neural and behavioral data on the fMRI task; participants reported a tolerable experience. Simulated neuronavigated TMS showed feasibility and tolerability of positioning the device to stimulate VMPFC. The fMRI task activated the VMPFC as predicted. The MRI and TMS protocols were replicable and tolerable. These procedures can now be used experimentally by our team with confidence to test our hypothesis that targeting the VMPFC within the brain’s default-mode network may normalize aberrant VMPFC activity seen in major depression, thereby improving excessive negative self-referential processing. Discussion/Significance of Impact: This project lays essential groundwork for my K12 project, “Targeting Negative-Self Referential Processing in Depression with TMS,” a longitudinal neuroimaging and behavioral study using these methods in the study population of people with major depression.

OBJECTIVES/GOALS: The primary purpose of the QA/QC Project Manager (PM), appointed under the NCATS UL1 administrative supplement award, is to facilitate quality and timely NCATS prior approval submissions preventing study start delays. Other goals include supporting these projects’ IRB applications and monitoring to ensure data quality and compliance. METHODS/STUDY POPULATION: At the Indiana CTSI, the QA/QC PM is assigned to the Regulatory Knowledge and Support program (RKS) and functions as a unique regulatory service provider. Through monitoring, auditing, and personalized consultations, the IN CTSI QA/QC PM provides study teams with regulatory, GCP, and other compliant study conduct insights while managing NCATS prior approval and RPPR submission quality and timeliness. In contrast to many CTSAs, this role is uniquely situated within RKS and provides QA/QC support through a regulatory lens. The Indiana CTSI QA/QC PM serves on the CTSA QA/QC Lead Team collaborating with NCATS and other CTSA QA/QC personnel. The Lead Team engages with NCATS to host monthly/quarterly meetings and participate in a discussion forum of NCATS and other CTSA QA/QC personnel. RESULTS/ANTICIPATED RESULTS: Not all CTSAs employ the QA/QC PM as regulatory support and the role and skill sets at each CTSA vary, yet the collaborative nature of these individuals across the CTSAs facilitates sharing of resources and knowledge. While prior approval and RPPR submissions vary widely, the QA/QC PMs can rely on their counterparts for guidance complying with the same regulations and policies within unique research settings and institutional nuances. The IN CTSI QA/QC PM, in collaboration with the QA/QC Lead Team, provided quality assurance revisions to the NCATS prior approval instructions which were adopted and published by NCATS January 2022 for implementation at all CTSAs. Ongoing, quality control efforts are accomplished through education, monitoring, and regulatory consultations. DISCUSSION/SIGNIFICANCE: As the research environment evolves, the QA/QC PM responsibilities shift in response to needs within RKS and NCATS. The versatility of the position enables QA/QC to occur at all stages of a study. QA/QC strategies aim to facilitate communication, quality NCATS prior approval and RPPR submissions, and compliance with proposed study conduct.

OBJECTIVES/GOALS: To identify challenges faced by academic researchers in accessing online regulatory information and/or tools to advance their research work to develop a free, publicly accessible, interactive web portal that provides regulatory support. METHODS/STUDY POPULATION: The Regulatory Knowledge and Support core of the Southern California Clinical and Translational Science Institute interviewed five local research professionals. These interviews guided the development of a Qualtrics survey, consisting of multiple responses and open-ended questions, submitted to our local institutional review board (IRB). After receiving IRB approval, the survey was disseminated via email, newsletters, flyers, and presentations targeting researchers at academic institutions and members of clinical and translational science hubs. Survey data will be used to identify the challenges academic researchers face in finding regulatory resources and to compile the types of regulatory information or tools they would find helpful for their research. RESULTS/ANTICIPATED RESULTS: According to the interviews, researchers with extensive involvement in clinical trials found regulatory resources easily accessible compared to those with less experience. Additionally, they all stated having a colleague or regulatory specialist whom they can consult about regulatory requirements. Insights from these initial interviews confirmed the need to obtain a comprehensive view across research professionals. Anticipated results will show the challenges in accessibility, source, and type of regulatory resources researchers typically encounter. It is also anticipated that researchers will share what kinds of resources they would find most useful for their work. Ultimately, the information and tools identified as essential by survey takers will be collected and incorporated into the web portal. DISCUSSION/SIGNIFICANCE: Academic researchers find navigating through regulatory hurdles persistently challenging when translating their work from bench to clinic, especially since academia is typically resource-constrained. Findings from this study will allow the creation of a web portal for researchers that is broadly accessible and meets their regulatory needs.

OBJECTIVES/GOALS: Although their 5-year survival >90%, young patients with HL face tradeoffs between near-term disease control and risk of treatment-related adverse effects decades later, so we seek to understand what patients and clinicians value in HL treatment decisions. METHODS/STUDY POPULATION: Leveraging our access to large cohorts of physicians, HL patients/survivors, and caregivers, we will use adaptive choice-based conjoint analysis (ACBC) to elicit treatment preferences when offered scenarios that incorporate tradeoffs, e.g., would a patient rather live 20 years with 10% risk of second malignancy or live 40 years with 30% of second malignancy. To reduce survey fatigue, prior choice responses limit subsequent scenarios. Through ACBC, we will identify variations in preferences and the importance of disease outcomes, treatment characteristics, and late effects for HL by respondent type. RESULTS/ANTICIPATED RESULTS: The goal is a final sample of 200 physicians and 200 patients/caregivers. We will collect demographics from physicians (age, type of physician, years practicing, type of practice, gender, and geography) and patients/caregivers (age at diagnosis, time since treatment, race, gender, smoker, education). We will ask questions about values of disease outcomes, late effects (second cancers, cardiac disease, chronic fatigue and neuropathy), and treatment characteristics (uncertainty of late effects, salvageability). Results will include utilities about participants views on disease-control and late effects. We anticipate participants to value disease control over late effects. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study will elicit how physicians and patients/caregivers value treatment tradeoffs for HL. In an era of multiple treatment choices with varying short- and long-term benefits and harms, identifying values and preferences become critical for patient-centered treatment decisions.

Objectives/Goals: Increased follicle-stimulating hormone (FSH) is linked to declines in ovarian and metabolic function in older women. Obesity is both a manifestation and a driver of aging pathologies. In animal models, FSH and insulin resistance (IR) were reduced after 6 mos. of a nutritional therapeutic (GLYLO). Our goal was to translate preclinical evidence to humans. Methods/Study Population: An integrated, precision medicine approach identified a unique phenotype of aging-related debility relative to older females. A non-comparer pilot study was conducted to translate GLYLO preclinical findings to postmenopausal women with obesity (n = 85; >55 years; body mass index [BMI]  = 35.0±4.35; range: 30.3–42.8). Participants meeting the inclusion and exclusion criteria (n = 13) were enrolled and received two capsules of GLYLO (vitamins and natural products) daily for 6 mos. Assessments for FSH, estradiol (E2), IR (homeostatic model [HOMA-IR]), total cholesterol (TC), low- (LDL), high-density lipoproteins (HDL), safety biomarkers (e.g., red cell distribution width [RDW%], mean corpuscular volume [MCV]), and depression (Center for Epidemiologic Studies Depression Scale) were conducted prior to and after 6 mos. Results/Anticipated Results: Mixed-effect models with intent-to-treat analysis were applied to compare outcomes prior to (n = 13) and following (n = 7) the intervention. Significant reductions in FSH were observed (-13.1 [2.47] ∆/SD; p = 0.002)) following the 6-month intervention. Interestingly, BMI, E2 (p = 0.412), HOMA-IR (p = 0.885), TC (p = 0.363), and LDL (p = 0.145) were unchanged, while HDL decreased significantly (-9.7 [3.82] ∆/SD; p = 0.044). Other biomarkers, RDW% (-0.2 [0.05] ∆/SD; p = 0.009) and MCV (-2.3 [0.33] ∆/SD; p = 0004), were significantly reduced. All other safety parameters were not altered. Six participants reported mild to moderate adverse events (acid indigestion) and were lost to follow-up. Depression scores significantly increased (+4.0 [0.75] ∆/SD; p = 0.002)). Results were similar with and without intent to treat analysis. Discussion/Significance of Impact: Decreased FSH, but not IR, was observed following six months of GLYLO in postmenopausal women with obesity. Significant alterations in HDL, depression, RDW%, and MCV warrant further investigation. Findings are limited by the small sample size and loss to follow-up. Randomized, controlled trials are needed to confirm these results.

OBJECTIVES/GOALS: Examine the use of Patient-Reported Outcomes (PRO) in Huntington’s Disease (HD) clinical trials (CT) and compare across time and sponsor types. METHODS/STUDY POPULATION: Conduct literature review on 1. background of HD, 2. what symptoms and outcome measures are most important to patients, including the Patient-Focused Drug Development (PFDD) meeting for HD–led by the U.S. Food and Drug Administration (FDA), 3. what outcome measure tools currently exist and what they measure. Utilizing Clinicaltrials.gov, trials for HD were examined to assess the number of trials conducted, what COAs were used, and funding types. Trials were filtered by study type (keep Interventional) and status (filter out suspended, terminated, unknown, and withdrawn). The frequency of COAs will then be mapped based on the symptoms from the PFDD meeting. RESULTS/ANTICIPATED RESULTS: From the PFDD meeting for HD, symptoms that were important to patients include cognitive impairment, depression and anxiety, and motor symptoms. From the 139 interventional studies that were active, complete, recruiting, or not recruiting, 79 studies were conducted by Industry, 3 by NIH, 93 by Other (Academia/Community Organizations), and 1 by a U.S. Federal Agency (other than NIH). One of the most commonly used COA is the Unified Huntington’s Disease Rating Scale (UHDRS), which includes a motor, cognitive, and behavior assessment, and an assessment on functional capacity and independence. Of the 27 out of 139 trials analyzed to date, there were a total of 37 COAs. DISCUSSION/SIGNIFICANCE: The widespread use of UHDRS can be attributed to its standardization in 1999. It captures the symptoms of HD that are most important to patients. Because UHDRS is not sensitive to any one symptom, other COAs have been developed which focus on unique aspects of HD and allow for its earlier detection.

OBJECTIVES/SPECIFIC AIMS: According to Diffusion of Innovations Theory, an important predictor of successful implementation of a new intervention within an organization is perceived need for change (i.e. tension for change [TFC]). No research has examined factors influencing TFC in relation to human papillomavirus (HPV) vaccination. Providers who assume their clinic already performs well in HPV vaccination coverage may perceive a lower need for assistance for improvement. We assessed the association between perceived HPV vaccine completion compared to peer clinics and perceived support needed to increase HPV vaccination coverage. METHODS/STUDY POPULATION: All providers (physicians/nurse practitioners/physician assistants) and staff (clinical/non-clinical) from 21 pediatric clinics participating in an HPV vaccine quality improvement (QI) intervention study in Tennessee were invited to complete a baseline survey. Perceived comparative performance (i.e. perceived HPV vaccine completion compared to peer clinics) and TFC (i.e. perceived support needed to increase HPV vaccination coverage) were measured on continuous scales of 0-100. We used logistic regression to estimate odds of perceiving higher TFC (upper tertile, score of 51-100) for every unit increase in perceived comparative performance. Analyses controlled for age of respondent, perceived strength of evidence for HPV vaccine guidelines, and clinic factors, including culture/climate and available resources. RESULTS/ANTICIPATED RESULTS: Of 325 respondents, most were staff (61%), female (87%), and non-Hispanic White (83%). Respondents who perceived higher HPV vaccination coverage compared to peer clinics perceived lower clinic-level TFC (adjusted OR [aOR] = 0.98; 95% CI, 0.97-0.99). When stratifying by job role, this negative association was observed among providers (aOR = 0.95; 95% CI, 0.92-0.98), but not among staff (aOR = 1.00; 95% CI, 0.98-1.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Providers who perceived higher HPV vaccination coverage compared to peer clinics perceived lower need for support to improve vaccination outcomes. Our results suggest that QI efforts targeting pediatric clinics may find it useful to assess providers’ perceptions of their clinic’s performance, which could affect motivation to engage in QI efforts and successfully improve outcomes.