Translational Science Institute Research Articles

Environmental Pollutant Risk Factors for Worse COVID-19 Related Clinical Outcomes in Predominately Hispanic and Latino Populations

BackgroundPer- and poly-fluorinated compounds (PFAS) and heavy metals constitute two classes of environmental exposures with known immunotoxicant effects. In this pilot study, we aimed to evaluate the impact of exposure to heavy metals and PFAS on COVID-19 severity. We hypothesized that elevated plasma-PFAS concentrations and urinary heavy metal concentrations would be associated with increased odds of ICU admission in COVID-19 hospitalized individuals. MethodsUsing the University of Southern California Clinical Translational Sciences Institute (SC-CTSI) biorepository of hospitalized COVID-19 patients, urinary concentrations of 15 heavy metals and urinary creatinine were measured in n=101 patients and plasma concentrations of 13 PFAS were measured in n=126 patients. COVID-19 severity was determined based on whether a patient was admitted to the ICU during hospitalization. Associations of metals and PFAS with ICU admission were assessed using logistic regression models, controlling for age, sex, ethnicity, smoking status, and for metals, urinary dilution. ResultsThe average age of patients was 55±14.2 years. Among SC-CTSI participants with urinary measurement of heavy metals and blood measures of PFAS, 54.5% (n=61) and 54.8% (n=80) were admitted to the ICU, respectively. For heavy metals, we observed higher levels of Cd, Cr, and Cu in ICU patients. The strongest associations were with Cadmium (Cd). After accounting for covariates, each 1 SD increase in Cd resulted in a 2.00 (95% CI: 1.10-3.60; p=0.03) times higher odds of admission to the ICU. When including only Hispanic or Latino participants, the effect estimates between cadmium and ICU admission remained similar. Results for PFAS were less consistent, with perfluorodecanesulfonic acid (PFDS) exhibiting a positive but non-significant association with ICU admission (Odds ratio, 95% CI: 1.50, 0.97-2.20) and perfluorodecanoic acid (PFDA) exhibiting a negative association with ICU admission (0.53, 0.31-0.88). ConclusionsThis study supports the hypothesis that environmental exposures may impact COVID-19 severity.

Abstract LB139: Disparities in oral precancerous lesion surveillance in the United States upper Midwest

Abstract Objective: To determine whether geographic representation and race of patients in a regional oral cancer surveillance program (University of Minnesota Cancer Active Surveillance Population (UMN CASP)) mirror characteristics in the corresponding National Cancer Institute (NCI) designated comprehensive cancer center catchment. Introduction: Oral cancer poses a significant public health concern that may be mitigated through lesion surveillance. Representation of patients for clinical trials throughout an NCI cancer center catchment area is a crucial goal to promote improved health outcomes. This study investigates the demographic landscape of patients with preneoplastic oral lesions seen at the CASP. Methods: Through the UMN Clinical and Translational Sciences Institute, we queried 30 International Classification of Disease (ICD) 9 and 10 codes corresponding to 120 unique mucosal oral precancerous lesion descriptors of CASP patients. Automated extraction of electronic medical record (EMR) data for 4,496 patients treated by the senior author between 2011 and 2023 identified 1,375 patients with preneoplastic lesions. The proportion of patients residing in three-digit zip code regions of Minnesota were compared to 2021 American Community Survey state population data. Additionally, race data were compared between CASP patients and the UMN Masonic Cancer Center (MCC) patient catchment data. Results: CASP patients were over-represented relative to state population distributions within the Minneapolis-St. Paul metropolitan area and surrounding suburbs (region 554 p<0.0001 and region 551 p<0.0001). Under-representation of CASP patients was observed in all western and southern border regions (regions 559 p<0.0001, 560 p<0.0001, 561 p<0.0001, 562 p=0.0037, 565 p<0.0001, and 567 p=0.0006) as well as portions of central (563 p<0.0001), northern (566 p=0.0015), and north-eastern (558 p<0.0001) Minnesota. Proportional representation was observed in several regions of central (553 and 564), eastern (550), and north-eastern (557 and 556) Minnesota. Comparisons of CASP race data revealed a higher proportion of black patients (CASP 8.59% [95% CI 7.17-10.27%] vs. MCC 7.16% [95% CI 7.14-7.17%]) and a lower proportion of Asian/Pacific Islander patients (CASP 3.74% [95% CI 2.82-4.94%] vs. MCC 5.32% [95% CI 5.30-5.34%]) relative to MCC catchment patients. White, American Indian/Alaskan Native, and mixed-race groups were proportionally represented in both data sets. Conclusions: These data show that system wide EMR searches can be implemented to identify patients in an NCI cancer center catchment area with precancerous or other at-risk conditions for cancer. Importantly, Native patients were proportionally represented in the screening program while several rural locations were under-represented. This information can instruct the expenditure of additional resources for under-represented groups and permit streamlined enrollment of patients for cancer prevention clinical trials. Citation Format: Alexander J. Dwyer, Lindsey Mortensen, Beverly R. Wuertz, Frank G. Ondrey. Disparities in oral precancerous lesion surveillance in the United States upper Midwest [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB139.

286 Partnering and engaging in Indiana Communities through listening sessions and data sharing: successes of Connection IN Health

OBJECTIVES/GOALS: Participants will be able to identify how partnering with state health departments for a CTSA initiative assists in meeting shared goals by building infrastructure and sharing resources and list key components of a successful county engagement process that can be replicated. METHODS/STUDY POPULATION: Connections IN Health is a collaborative project with the Indiana Clinical and Translational Sciences Institute, Indiana Department of Health, Indiana University Simon Comprehensive Cancer Center, and community partners. We address chronic disease in Indiana with coalition-based engagement at the grassroots level, and partnering to provide technical assistance, resources, connections and evidence-based strategies to address the health challenges. Our methods of county engagement include surveying the broad community, conducting listening sessions with key community stakeholders, compiling, analyzing and sharing data, collaborating with existing local coalitions, assessing community readiness and suggesting evidence-based practices to implement. RESULTS/ANTICIPATED RESULTS: As a result of county engagement, local coalitions have current, local data to drive their efforts in improving local health rankings and outcomes. Community partners in eight counties have selected and implemented evidence-based strategies to manage and/or prevent diabetes, cardiovascular disease and/or stroke. Some examples include: starting a community garden with cooking classes in a food desert to provide fresh produce and nutrition/cooking knowledge, creating a mobile kitchen on hand for organizations to use to provide education and cooking skills, providing a passport for wellness at existing community events with food samples and health screenings and offering evidence-based educational programming such as Dining with Diabetes and Be Heart Smart. DISCUSSION/SIGNIFICANCE: Moving county health coalitions to evidence-based programming that has the greatest likelihood for success is a critical translational sciences challenge. Our rigorous and well defined approach yields significant improvement in local health coalition activities, sustaining their activities through long-term trusted relationships.

194 Increasing COVID-19 vaccine uptake through community engagement: collaborative efforts among Cooperative Extension and Clinical and Translational Science Institutes

OBJECTIVES/GOALS: The CDC-funded Program to Alleviate National Disparities in Ethnic and Minority Immunizations in the Community intersects two national networks that transform building trust in communities: Cooperative Extension Systems and Clinical and Translational Science Awardees, with the goal of reducing vaccine hesitancy and increasing vaccine uptake. METHODS/STUDY POPULATION: PANDEMIC included North Central Florida; Greater Sacramento, California; Bronx, New York; St. Louis and the Ozarks, Missouri; rural Kentucky; and Minnesota. Our 10 Promising Practices (PPs) focus on the equitable distribution of COVID-19 vaccines and health information, with two detailing collaborative efforts to better achieve health equity: PP3) Bringing Services and Vaccines to People Where They Are & PP5) Creating Coalitions with Trusted Neighborhood Partners. CHWs and Extension Educators, trusted community members, work together to deliver culturally/linguistically diverse health messages in plain language in areas of high vaccine hesitancy and bring vaccines to people where they are. All outreach activities are tracked and categorized by PP affiliation. RESULTS/ANTICIPATED RESULTS: From November 2021 – August 2023, PANDEMIC has administered nearly 11,000 COVID-19 vaccines at over 2,500 outreach events. At events, Community Health Workers (CHWs) listen to community members to assess vaccine perceptions and health needs/concerns. We adapt messaging and outreach initiatives to promote vaccination through data analyses that help us understand perceptions. Responses are calculated for the populations of focus (PoF)–Latino/Hispanic, African American/Black, American Indian/Alaskan Native, Asian, Native Hawaiian/Other Pacific Islander) compared to others (Non-Latino/Hispanic White or unspecified race). Over 16,000 surveys were collected from November 2021 – August 2023 with 60% coming from the PoF. Key differences in perceptions will be shown along with other cross-site metrics. DISCUSSION/SIGNIFICANCE: PANDEMIC offers an innovative model for collaboration among CTSAs and Cooperative Extension Systems to better understand community perceptions and support vaccination efforts and overall health promotion in communities of greatest need, with a focus on racial and ethnic minority communities and underinsured/uninsured populations.

139 Adapting Center for Improvement of Mentored Experiences in Research (CIMER) Mentor Training for Clinical Research Professionals: A Process Description

OBJECTIVES/GOALS: Learn how the National Organization of Research Development Professionals (NORDP) adapted the Center for Improvement of Mentored Experiences in Research (CIMER) NIH-funded evidenced-based mentor training curriculum for research development professionals and how the curriculum will be further adapted for clinical research professionals. METHODS/STUDY POPULATION: NORDP pioneered the adaptation of the CIMER curriculum for professional research staff. In addition to revamping the case studies and ensuring the curriculum was appropriately staff-centric, the NORDP team developed best practices for adapting the curriculum. This approach included four phases: (1) developing expertise in mentor training, (2) adapting curriculum for staff, (3) creating role-specific case studies, and (4) integrating mentor training with institutional or professional association-based mentoring programs. In collaboration with CIMER and units at the University of Minnesota (UMN), the mentor training model for research development will be further adapted for clinical research staff, i.e. coordinators, regulators, facilitators. RESULTS/ANTICIPATED RESULTS: This poster will discuss the preliminary work of adapting the curriculum for clinical research professionals by the UMN’s Departments of Family Medicine and Community Health and Clinical and Translational Science Institute’s Translational Workforce Development team. The anticipated short to mid-term outcomes of this work include: (1) improved research professionals mentoring knowledge and skills, (2) diversity addressed across research roles, (3) reduced staff turnover and associated costs, (4) increased staff job satisfaction and moral, and (5) research culture changed to value mentoring excellence across the academic enterprise. DISCUSSION/SIGNIFICANCE: Research mentoring has traditionally been focused on faculty and trainees. Given the unique skill sets and increasing complexity of research staff roles, mentoring can increase job satisfaction and reduce the overall costs related to turnover, i.e. research productivity, loss of institutional knowledge, hiring costs, etc.

99 Using LGBTQ+ Community Expertise to Co-Develop Inclusive Sexual Orientation and Gender Identity (SOGI) Screening for Research Studies

OBJECTIVES/GOALS: To promote diverse research engagement and address health disparities by creating an inclusive tool to collect sexual orientation and gender identity (SOGI) data from potential participants #_msoanchor_1 METHODS/STUDY POPULATION: The Penn State Community Health Equity & Engagement in Research (CHEER) team, part of our Clinical and Translational Science Institute (CTSI), developed inclusive screening guidance to collect SOGI data from potential research participants to fill an identified gap in the literature. Guidance was developed through an iterative feedback process, leveraging expertise from local, regional, and national organizations, healthcare systems, and leaders throughout Clinical & Translational Science Award hubs. By eliciting expert feedback, CHEER co-developed a comprehensive SOGI data collection form, filling an important gap of inclusivity in the consenting process. Training of this new tool was delivered to CHEER’s far-reaching listserv researchers (internal and external) and community partners. RESULTS/ANTICIPATED RESULTS: Feedback collected from our LGBTQ+ expert partners resulted in a total of five inclusive SOGI screening questions; two ‘Gender Identity’ questions, one ‘Sexual Orientation’ question, and two ‘Sex’ questions, with “prefer not to answer” and “another option not listed” provided. The goal of this effort is to equip research teams with a tool that integrates SOGI characteristics that may be particularly important to determine study eligibility respective to a person’s identity or orientation. Additionally, collecting SOGI data in an inclusive way may increase trust worthiness in research from potential research participants, particularly among the LGBTQ+ community, who have been underrepresented yet experience several inequities and disparities across multiple health outcomes. DISCUSSION/SIGNIFICANCE: CHEER’s goal is to reduce health disparities in underrepresented populations, including the LGBTQ+ community, by promoting inclusivity and engagement in research. Developing a community-driven screening that addresses the unique needs of the LGBTQ+ community successfully bridges a gap in equity across all research participants.

552 Substance Abuse Research: Bench to Community (SARB2C) as a Model for Team Science

OBJECTIVES/GOALS: To present Substance Abuse Research: Bench to Community (SARB2C) as a model for team science both within and between institutions. Emerging from targeted efforts by the NIH to engage translational scientists in prominent public health issues, the initiative illustrates the benefits of bringing together researchers and trainees to share ideas. METHODS/STUDY POPULATION: In 2019 a group was formed at University of Florida to discuss ongoing translational research in the area of substance abuse, including faculty, staff, and trainees from across the campus. The group was expanded in February 2022 to include domestic colleagues at the University of Kentucky as well as international collaborators at Chulalongkorn University in Bangkok, Thailand. One-hour monthly meetings began in person but now take place virtually. Larger projects are discussed individually, focusing on opportunities for collaboration. Attendees also provide updates on their work, including proposals in development and manuscripts in process. This facilitates dialogue around the science, from the bench to the community, and connects people to advance team science. RESULTS/ANTICIPATED RESULTS: In light of the ongoing opioid epidemic and the public health threat of other emerging substances, collaboration among researchers in this area is essential to advance the science and explore real-world solutions. SARB2C demonstrates the benefit of connecting researchers across T0 to T4, and that of including trainees for invaluable experience. This environment fosters open discussion and creativity and helps break down the silos that impede science. A highlight from early in the group’s history was a visit from the Program Officer for the UF Clinical and Translational Science Institute in February 2020. Since that time, multiple collaborations have resulted in grants submitted, such as P30 center grants and an innovative R61/R33, as well as numerous publications. DISCUSSION/SIGNIFICANCE: A complex public health emergency like the opioid epidemic requires creativity and collaboration, from laboratory science to interventions in the community, putting it squarely within the sights of translational research. SARB2C will soon enter its fifth year of linking researchers and training the next generation of scientists.

247 Virtual community and partner-engaged panels - We can do them, but should we?

OBJECTIVES/GOALS: We describe the transition of ShAred Resource Panels (ShARPs) within the Center for Community Health (CCH) at Northwestern University’s Clinical and Translational Sciences (NUCATS) Institute to virtual sessions and explore ongoing practices. METHODS/STUDY POPULATION: Restrictions placed during the COVID-19 pandemic led to changes in community-engaged health equity research, such as the transition of community and partner-engaged panels from in-person to virtual. ShARPs have occurred since December 2015. The model includes research team members, community members, community co-facilitator, and CCH staff. These custom panels bring together 8-10 community members familiar with a research topic or community of focus, offering feedback on adaptations that can improve research relevance and feasibility. Until the COVID-19 pandemic, all ShARPs were conducted in person. From March 2020 to January 2023, panels occurred virtually. From 2023, the option of virtual or in-person ShARPs has been available. Count data and informal interview data were reviewed. RESULTS/ANTICIPATED RESULTS: The number of ShARPs peaked in 2019 and has remained stable. The first virtual ShARP occurred on April 22, 2020, and all subsequent sessions have been virtual. As of October 2023, 6 ShARPs have occurred, with no research teams pursuing an in-person session despite its availability. Participants described virtual ShARPs as convenient and accessible. Academic teams cited concern about low community member participation should they opt for an in-person session. DISCUSSION/SIGNIFICANCE: It is feasible to conduct ShARPs virtually and is the current preferred modality. Whether virtual ShARPs enhance, neutralize, or detract from the effectiveness of the session is unknown and guides our future work. More research is needed, including discussion, and learning from our CTSA colleagues.

273 Evaluating a Newly Formed Community and Patient Advisory Board to Promote Equity and Inclusivity in Clinical and Translational Research

OBJECTIVES/GOALS: At UNC-Chapel Hill’s CTSA hub – the NC Translational and Clinical Sciences Institute (NC TraCS) – we conducted a participatory evaluation of a new community and patient advisory board (CPAB) to assess member experiences, and the outcomes and early impacts of their work on institutional programming related to equity and inclusivity in research. METHODS/STUDY POPULATION: NC TraCS staff conducted informal interviews with CPAB members to discuss how they envision success in their work, ideas for measuring progress towards their goals, and how they have seen similar work measured by others. These conversations guided the development of outcomes, indicators, and data collection methods for the CPAB evaluation plan. CPAB member satisfaction, experiences, and perceptions of accomplishments were assessed via an online survey. Concurrently, an Outcome Harvesting approach was used, through which NC TraCS staff retrospectively identified key outcomes of the CPAB’s work through team discussion of programmatic changes and review of internal documents and data. RESULTS/ANTICIPATED RESULTS: CPAB members (n=10) were highly satisfied with meetings, group dynamics, activities and accomplishments, and 90% of members felt that NC TraCS was very responsive to their feedback. Key outcomes included: 1) co-creating a shared vision, goals, and operational policies for the CPAB; 2) co-developing a training series for research teams about patient and community engagement; 3) disseminating best practices for co-developing advisory boards; 4) providing guidance to improve NC TraCS consultations, services, and resources related to enhancing equitable participation in research (e.g., developing an Equity in Research Framework); and 5) contributing to institutional initiatives related to diversity, equity, and inclusion (e.g., improving compensation processes for research participants and partners). DISCUSSION/SIGNIFICANCE: Evaluations of CPABs often focus on process measures, while assessments of outcomes and impacts are lacking. Our evaluation data highlight the early outcomes and value of a newly formed CPAB. Furthermore, our approach can inform the creation and evaluation of equity-focused advisory boards within other research institutions.

199 Early expansion and outcomes of a multilingual Latine review board for inclusive science

OBJECTIVES/GOALS: The NC Translational and Clinical Sciences (NC TraCS) Institute’s Latine Community Review Board (CRB) provides expertise to researchers seeking to culturally adapt interventions and improve language access in clinical and translational science. Early efforts aimed to expand CRB membership, build member capacity, and assess CRB impact. METHODS/STUDY POPULATION: Founded in 2021, the NC TraCS Latine CRB is an advisory group of natively Spanish-speaking, Latine North Carolinians who contract with research teams (RTs) to review Latine community-facing study materials (e.g., decision aids, scales, recruitment scripts) and provide feedback for improving or validating materials’ linguistic accuracy and cultural relevance. Bilingual staff facilitate members’ review of materials, use focus group methods to solicit feedback, and report key findings and suggested revisions to RTs. In 2023, we recruited new age-, gender-, and racially diverse members; and implemented process and impact evaluation, via (1) post surveys of RTs and (2) assessment of members’ experiences and visions for growth utilizing the Focused Conversation Method (Top-network, 2021). RESULTS/ANTICIPATED RESULTS: Since 2021, NC TraCS has conducted 11 Latine CRB review sessions to support 7 research studies. Current CRB members (n=8) report that (1) their work effectively supports Latine inclusion in research; (2) increased group size and diversity help ensure study materials are comprehensible to heterogenous Latine populations; and (3) an hourly member compensation rate equal to the hourly rate of TraCS’ staff accurately represents member contributions. Members also cited that they value open communication, continuous improvement, communication via email and group chat, periodic programming meetings, and RT updates on study outcomes. Post-session RT surveys to date (n=3) show that RTs would recommend this program to other researchers (pending survey responses from RTs this year will provide additional impact data). DISCUSSION/SIGNIFICANCE: Early data highlight the value of fairly compensated, bilingually coordinated input from diverse Latine community members for improving studies’ inclusion of heterogeneous, multilingual communities. Our approach can inform the development, growth, and continuous improvement of multilingual review boards at other research institutions.

120 Impact of Undergraduate Clinical Research Experience: Highlighting the UCLA Clinical and Translational Science Institute Research Associates Program (CTSI-RAP)

OBJECTIVES/GOALS: CTSI-RAP is a professional development program that provides undergraduate students with clinical research exposure and training. Students support UCLA research faculty by assisting with all aspects of the research process, including recruiting participants, data management, and presentations. METHODS/STUDY POPULATION: CTSI-RAP onboards a 15-20 volunteer student cohort annually in a competitive application and interview process with less than a 10% acceptance rate. Since the inaugural cohort in 2013, over 160 students have participated. The program engages hundreds of students each year through the recruitment process, campus clinical research events, and student-led conference opportunities. Evaluation surveys developed through REDCap in 2022 sought to assess the program’s impact on undergraduate experiences, professional development, and post-graduate careers. Surveys distributed to investigators and their study teams evaluated the student’s clinical research knowledge and engaged student involvement. RESULTS/ANTICIPATED RESULTS: Based on evaluation surveys, the CTSI-RAP program received excellent reviews from both students and their assigned study teams. 100% of students and faculty would recommend the program to a friend or colleague. 30% of students present or publish annually, indicating a wealth of meaningful contributions made by students. 90% of students go on to attend medical school, health-related graduate school, or other health-related employment. Several students continue working in clinical research through gap-year employment. As demonstrated by the high caliber of student and faculty experiences, CTSI-RAP has created an esteemed and valued symbiotic infrastructure to support clinical research endeavors at UCLA. DISCUSSION/SIGNIFICANCE: Through clinical research career exploration and professional skill-building in undergraduate careers, the CTSI-RAP program produces highly-trained future leaders in the field and benefits the capacity of UCLA research. CTSI-RAP provides a model for similar programs to be funded and implemented in other institutions.

510 Addressing the Regulatory Needs and Challenges of Academic Researchers by Creating a One-Stop Shop Web Portal

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.

Engaging African American Faith Leaders as Partners in Ethical Research

This paper outlines an initiative to adapt the Community Partnered Research Ethics Training (CPRET) for the cultural context of the CHURCH (Congregation as Healers Uniting to Restore Community Health) project. The CHURCH project is a community-partnered participatory research project that seeks to promote the mental well-being of African American populations by developing, implementing, and evaluating a mental health training curriculum for faith leaders in Black churches. Participatory research, in which community stakeholders collaborate with researchers as equal partners to address problems impacting marginalized communities, has recently become more popular in academia. Training is necessary to equip community partners with the skills and knowledge required for full research participation. Community partners frequently encounter ethical issues in participatory research, but limited training resources are available to proactively prevent and address such issues. The CPRET was developed through a collaboration between the Clinical and Translational Science Institute and the Human Research Protection Office and Community Research Advisory Board at the University of Pittsburgh. It surveys research processes and core research ethics principles, and it stimulates discussion regarding best practices by engaging participants in scenario-based exercises in which they identify ethical and unethical research. By describing how we utilized the CPRET in the CHURCH project and presenting a summary of participant feedback, we aim to build resources for community-engaged scholars seeking to engage community members in ethical research.

The Role of Sociogenomics on Chronic Wounds 

Background and Objective: 
 Chronic wounds affect almost 2.5% of the United States population. Along with substantial healthcare costs, other factors like reduced employment opportunities and social isolation further complicate the patient’s quality of life. Socioeconomic status (SES) has been shown to influence gene expression that can increase susceptibility and deterioration of chronic wounds. Our study looks to identify genes that have been impacted by SES in chronic wound patients. Exploring this association can enhance understanding of the relationship between SES and chronic wound outcomes. 
 Experimental Design: 
 A cohort of 72 chronic wound patients were recruited. Patient demographics and socioeconomic backgrounds were collected. Blood DNA isolation was performed and allotted for genetic analysis by Axiom™ Precision Medicine Diversity Array (PMDA). DNA genotyping data was obtained, and single nucleotide polymorphisms (SNP) markers pertaining to wound healing were studied. P < 0.05 were used to designate significant SNP marker mutations in the cohort. 
 Results: 
 To add strength to our project, we have chosen to further study the results obtained by our group (https://doi.org/10.18060/27205), which has previously found significant SNPs associations of the vitamin D receptor (VDR) and the methylenetetrahydrofolate reductase (MTHFR) genes in chronic wound patients. Using PMDA, our analysis showed polymorphisms in CYP24A1 (p = 0.0072), a gene involved in vitamin D metabolism, and MTHFR (p = 0.00625), a gene involved in folate and homocysteine metabolism. Modifications of these genes have been associated with pathogenesis to impaired wound healing. 
 Conclusion: 
 There is a need for further investigation into health outcomes and their association with SES. Our study aims to address the knowledge gap in this field by focusing on chronic wound healing in relation to socioeconomic status. With our results, we hope to emphasize the importance of sociogenomics, and how it can be utilized to advocate for improved patient outcomes across all socioeconomic backgrounds. 
  
 Acknowledgements: 
 This project was funded, in part, with support from the Indiana Clinical and Translational Sciences Institute funded, in part by UL1TR002529 from the National Institutes of Health (NIH). The presented work is also supported by NIH grants R01DK135447 and R01DK128845 to CKS. The laboratory of KS is supported by DoD grant W81XWH-22-1-0146. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.  

Spanish Translation and Cultural Adaptations of Physical Therapy Parent Educational Materials for Use in Neonatal Intensive Care.

A paucity of Spanish language, culturally relevant parent education materials in the healthcare setting results in suboptimal care for Latinx families and further perpetuates health disparities. The purpose of this article is to describe the process for Spanish translation and cultural adaptations to parent education materials of a parent-centered physical therapy program designed to support maternal mental health and infant development during Neonatal Intensive Care (NICU). Two bilingual physical therapy (PT) students translated educational materials from English to Spanish and were proofread by a professional translator. Next, we conducted a materials review with 5 members of the Latine Community Review Board (CRB), a "standing" advisory group of natively Spanish-speaking, Latine North Carolinians who contract with research teams under the coordination of the Inclusive Science Program (ISP) of the North Carolina Translational and Clinical Sciences Institute (NC TraCS). Review session recruitment, facilitation, and data analysis were conducted by bilingual NC TraCS project managers and the primary investigator for the main feasibility study. Readability analyses were performed at the final stage of translation and adaptation. Themes from CRB review sessions for improvement included to 1) use parent-friendly language, 2) use the plural masculine form of gendered language for caregivers to include all gender identities in this neonatal context, 3) address challenges with direct translation, and 4) use written education materials to supplement in-person, hands-on training with parents and their infants.All translated materials received a grade level of 5 on the Crawford grade-level index. Based on CRB feedback and readability analysis, the translation and cultural-adaptation process resulted in comprehensible written parent education materials for Spanish-speaking families. Review meetings with the CRB reinforced the need for Spanish materials in the healthcare setting. Further assessment of these materials with Spanish-speaking families in the NICU setting is needed.

RocHealthData.org: Development and usage of a publicly available, geographic source of social determinants of health data.

Access to local, population specific, and timely data is vital in understanding factors that impact population health. The impact of place (neighborhood, census tract, and city) is particularly important in understanding the Social Determinants of Health. The University of Rochester Medical Center's Clinical and Translational Science Institute created the web-based tool RocHealthData.org to provide access to thousands of geographically displayed publicly available health-related datasets. The site has also hosted a variety of locally curated datasets (eg., COVID-19 vaccination rates and community-derived health indicators), helping set community priorities and impacting outcomes. Usage statistics (available through Google Analytics) show returning visitors with a lower bounce rate (leaving a site after a single page access) and spent longer at the site than new visitors. Of the currently registered 1033 users, 51.7% were from within our host university, 20.1% were from another educational institution, and 28.2% identified as community members. Our assessments indicate that these data are useful and valued across a variety of domains. Continuing site improvement depends on new sources of locally relevant data, as well as increased usage of data beyond our local region.

Neural connectivity moderators and mechanisms of ketamine treatment among treatment-resistant depressed patients: a randomized controlled trial

Intravenous (IV) ketamine has emerged as a rapid and effective treatment for TRD. However, the specific neural mechanisms of ketamine's effects in humans remains unclear. Although neuroplasticity is implicated as a mechanism of action in animal models, relatively few randomized controlled trials (RCTs) in TRD patients have examined ketamine's impact on functional connectivity, a posited functional marker of neuroplasticity-particularly in the context of a mood-induction paradigm (termed miFC). 152 adults with TRD (63% female; 37% male) were randomly allocated to receive a single infusion of ketamine or saline in a 2:1 ratio. We examined changes in connectivity (from baseline to 24-h post-infusion) that differed by treatment, and whether clinical treatment response at 24-h post-infusion was uniquely related (among patients allocated to ketamine relative to saline) to (1) pre-treatment connectivity and (2) changes in connectivity. We examined both miFC and rsFC, using prefrontal cortex and limbic seed regions. We also conducted a multiverse analysis to examine findings most robust against analytic decisions. Across both miFC and rsFC, ketamine was associated with greater in prefrontal/limbic connectivity compared to saline, and lower baseline connectivity of limbic and prefrontal regions predicted greater treatment response in patients receiving ketamine. Greater connectivity increases in participants receiving ketamine was uniquely related to greater treatment response. In addition, certain findings were identified as being reproducible against different analytic decisions in multiverse analyses. Our findings identify specific neural connectivity patterns impacted by ketamine and were uniquely related to outcomes following ketamine (relative to saline). These findings generally support prominent neuroplasticity models of ketamine's therapeutic efficacy. These findings lay new groundwork for understanding how to enhance and optimize ketamine treatments and develop novel rapid-acting treatments for depression. This research was supported by NIH grant R01MH113857 and by the Clinical and Translational Sciences Institute at the University of Pittsburgh (UL1-TR-001857).

The development of a clinical research educational training for community health workers using the joint task force for clinical trial competency framework.

Introduction: The NYU Clinical & Translational Science Institute, in collaboration with a number of community-engaged initiatives, developed a training for community health workers (CHWs) to enhance health literacy about clinical research. This innovative research training provides CHWs with a basic level of competency in clinical research to convey the importance of research to communities and better advocate for their health needs. CHWs are an underutilized resource to engage diverse populations in clinical research. The training also addresses the need to expand and diversify the clinical research workforce-integrating CHWs into research teams and connecting underserved populations with research opportunities to enhance quality of care. Methods: Structured individual interviews and focus group sessions were held with CHWs as well as clinical research faculty and staff to identify knowledge gaps in clinical research and identify best practices for educating community members on research. Using the Joint Task Force (JTF) for Clinical Trial Competency framework, an online course was developed consisting of 28 modules offered asynchronously for internal and external audiences. Topics include the fundamentals of clinical research, scientific concepts and research design, research ethics, study management, clinical study operations, communications, and teamwork, as well as the importance of diversity and equity in research and the barriers to participation. Results: Learning was evaluated using multiple choice questions after each module to ensure the fundamental level of knowledge was obtained. A separate survey, completed at the conclusion of the course, evaluated the quality of training. Discussion: The course aims to enhance the knowledge and skills of CHWs to help promote greater understanding of clinical research within the communities they serve, including the risks and benefits of clinical research and opportunities for participation. As members of the research team, community stakeholders can help design interventions tailored to the unique needs, culture, and context of their communities. In addition, this research training equips trainees with skills to engage the community actively, involving them in the research process and ensuring community priorities are represented in research through more community engaged processes.

HJKC3-007: Outcomes of Patients with Chronic Myeloid Leukemia in Chronic Phase Treated with Asciminib and Other Tyrosine Kinase Inhibitors in Routine Clinical Practice

Background and significance: There are typically high response rates to first line TKI therapies in chronic phase chronic myeloid leukemia (CP-CML). However, responses in later lines (second line and beyond) are diminished and highly dependent on the specific tyrosine kinase inhibitors (TKIs) used. Asciminib received FDA approval in October 2021 for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) CML-CP who were previously treated with two or more TKIs, and in patients with Ph+ CML-CP with the T315I mutation. Our goal in this study is to evaluate the role of asciminib therapy for patients with CML beyond clinical studies, in routine clinical practice. Study Design and methods: Data for this study will be abstracted from the HJKC3 (H. Jean Khoury Cure CML Consortium) CML registry project (HJKC3-0005); the HJKC3 CML Registry is a collaborative academic multi-site registry. Patients will be consented to allow collection of both retrospective and prospective data for the HJKC3 CML Registry. The data forms and surveys will be built and managed through the Research Electronic Data Capture (REDCap), a secure web application managed by the Clinical & Translational Science Institute. Participating sites include members of the HJKC3 (curecml.org). This study will be an opportunity to evaluate asciminib usage in ‘real-world’ academic practices across the United States. This observational study will include cohorts of patients diagnosed with CP-CML previously treated with two or more tyrosine kinase inhibitors and/or receiving asciminib and/or those with a T315I mutation, not currently enrolled in a randomized controlled trial. The HJKC3 CML Registry intends to collect clinical and patient reported outcome (PRO) data. After obtaining patient consent, patients will be invited to complete PRO assessments. The study will attempt to collect PRO data regardless of disease or treatment status. PRO assessments will be primarily administered online, though study staff will offer alternatives (e.g., phone) for participants without internet access. Study subjects will be emailed a link to access a secure platform hosted by one of the study sites, Medical College of Wisconsin (MCW), using the REDCap platform. Study Objectives: The primary objective of the study is to describe characteristics of patients who were previously treated with two or more TKIs and treated with asciminib or with any other TKIs. The secondary objectives are to describe the clinical outcomes and PRO of those patients. Exploratory objectives include description of characteristics, treatment outcome and PRO for patients with T315I mutation. Statistical plan: The sample size of approximately 225 participants during the 5-year recruitment period is based on the available clinical expertise and ongoing recruitment data in the HJKC3 CML registry in lieu of statistical power analysis. We estimate that 150 patients in the HJKC3 CML registry will be treated with other TKI and 75 treated with asciminib. Among a total of 225 patients, we estimate that 75 patients with the T315I mutation will be enrolled in the registry. No formal statistical inference will be drawn to compare the outcomes between these two groups. Bayesian predictive probability (PP) will be utilized for the exploratory analysis of Major Molecular Response (MMR). Survival probabilities will be computed using the Kaplan-Meier method, and the p-values from the log-rank test will be provided. Different PRO domains of the patient's symptoms and functioning will be analyzed separately (e.g., depression separate from fatigue, separate from GI symptoms, etc.) since combining them into a summary score may dilute the effects of the individual (and not necessarily related) components and mask actual change. The main objective for the analyses of PRO data from the registry is to describe any differences by treatment type in patients treated with asciminib and other TKIs.

Abstract PO-010: Operationalizing the health care system electronic medical record to create head and neck cancer research and screening databases

Abstract Introduction: A “living” prospective database for tracking patient outcomes and creating clinical trial screening populations would be useful for head and neck multidisciplinary teams and can be translated to innumerable populations of interest. The database should be rapidly accessible, economical, accurate, and transcend the typical 5-year length of grants. We hypothesized we could construct such a database and piloted the concept using patients within our head and neck cancer active surveillance population. This population consists of patients at high risk for the development of primary and secondary oral carcinoma over 20 years. A second goal was identifying subjects for oral leukoplakia studies and construction of genomic atlases. Methods: Through the University of Minnesota Clinical and Translational Sciences Institute (CTSI), we performed an IRB interrogation of our patient population in the EPIC electronic medical record (EMR) of 4,496 unique patients seen by the senior author and identified 1,375 unique deidentified patient records representing individuals with likely preneoplastic lesions. Our approach included 30 International Classification of Disease (ICD) 9 and 10 codes corresponding to 120 unique mucosal head and neck precancerous lesion descriptors. Information included typical demographic and risk data, laboratory, pathology, and possible staging data. All curated data were stored on CTSI servers with direct access to data analysis software. Results: The ICD 9 and 10 codes queried encompass 36 low risk, 16 moderate/low risk, 8 moderate/high risk, and 55 high risk lesion codes. 25/30 of the queried ICD 9 and 10 codes (>12,000 instances) were identified in the 4,496 patients queried, encompassing 1,375 unique patients, with most patients harboring multiple ICD codes. We identified 464 patients with diagnosed high risk lesions, 346 with moderate/high risk lesions, 692 with moderate/low risk lesions, and 728 with low-risk lesions. Several research functions in the EMR were identified to construct screening lists. From IRB approval to obtaining the data set from the CTSI, this process requires fewer than 24 hours of combined labor, minimal cost, and did not require manual chart abstraction. Conclusions: From our preliminary success in curating a dataset of patients diagnosed with high-risk oral lesions, we conclude that utilization of ICD 9 and 10 codes as inclusion criteria represents an efficient and simple way for busy practitioners to screen large amounts of clinical data for study populations of interest (>1 × 106 EMR). We will develop quality assurance and improvement measures to audit data accuracy. Further expansion of this work will apply similar algorithmic dataset curation to medical records acquired from clinicians beyond the current study population. Critically, this process could be used for a variety of conditions to develop comprehensive longitudinal databases to examine both retrospective and prospective outcomes, provided an ICD 9 or 10 code exists for the condition and coding is accurate and consistent. Citation Format: Lindsey Mortensen, Alexander J. Dwyer, Beverly R. Wuertz, Frank G. Ondrey. Operationalizing the health care system electronic medical record to create head and neck cancer research and screening databases [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-010.