E. Samuels, Carol Scott, M. Gravelin, Ellen Champagne
OBJECTIVES/GOALS: The objective of this initiative was to promote MICHR staff’s production of Clinical and Translational Science publications. MICHR leadership approved this initiative, including an evaluation plan with measurable outcomes goals, and contracted with an experienced scientific writing coach with over 20 years of experience working with CTSAs. METHODS/STUDY POPULATION: A sequential mixed methods program evaluation designs was used. Pre- and post-surveys were used to measure participating staff’s gain in skill, understanding & satisfaction. An interview with the instructor was then conducted to characterize staff performance, and identify possible areas of programmatic improvement. This initial phase of the program evaluation was conducted in the Summer of 2023. The results were used to inform an expansion of the program to include more staff in the the Fall of 2023. Pre- and post-program surveys of the participants were conducted and interviews with each program participant were conducted. Finally, interviews with non-participating staff were conducted to assess their need for writing support and the challenges and facilitators of their scientific writing. RESULTS/ANTICIPATED RESULTS: Preliminary evaluation results obtained in the summer of 2023 were positive. All participants completed the course, and spent an average of 3.3 hours working between sessions. Six manuscripts were developed, five of which are being readied for submission and one submitted as of August 2023. Analysis of the pre-and post-program surveys indicated that all participants gained writing skill and authorship knowledge. Specifically, they gained confidence in 7 writing skills and 6 first-author roles evaluated during the course. All participants were satisfied with their experience and recommended the course to their colleagues, and the course instructor was also satisfied with the course. However, the participants noted that competing work demands and variable preparation hindered their work in the course. DISCUSSION/SIGNIFICANCE: With the increasing focus on Clinical and Translational Science taking place across the CTSA Consortium it is important to involve research staff in paper writing teams, including in first-author roles. Professional development in scientific writing can support Clinical and Translational Research staff contributing to this emerging science.
{"title":"185 A Clinical and Translational Science manuscript writing support program for research staff","authors":"E. Samuels, Carol Scott, M. Gravelin, Ellen Champagne","doi":"10.1017/cts.2024.175","DOIUrl":"https://doi.org/10.1017/cts.2024.175","url":null,"abstract":"OBJECTIVES/GOALS: The objective of this initiative was to promote MICHR staff’s production of Clinical and Translational Science publications. MICHR leadership approved this initiative, including an evaluation plan with measurable outcomes goals, and contracted with an experienced scientific writing coach with over 20 years of experience working with CTSAs. METHODS/STUDY POPULATION: A sequential mixed methods program evaluation designs was used. Pre- and post-surveys were used to measure participating staff’s gain in skill, understanding & satisfaction. An interview with the instructor was then conducted to characterize staff performance, and identify possible areas of programmatic improvement. This initial phase of the program evaluation was conducted in the Summer of 2023. The results were used to inform an expansion of the program to include more staff in the the Fall of 2023. Pre- and post-program surveys of the participants were conducted and interviews with each program participant were conducted. Finally, interviews with non-participating staff were conducted to assess their need for writing support and the challenges and facilitators of their scientific writing. RESULTS/ANTICIPATED RESULTS: Preliminary evaluation results obtained in the summer of 2023 were positive. All participants completed the course, and spent an average of 3.3 hours working between sessions. Six manuscripts were developed, five of which are being readied for submission and one submitted as of August 2023. Analysis of the pre-and post-program surveys indicated that all participants gained writing skill and authorship knowledge. Specifically, they gained confidence in 7 writing skills and 6 first-author roles evaluated during the course. All participants were satisfied with their experience and recommended the course to their colleagues, and the course instructor was also satisfied with the course. However, the participants noted that competing work demands and variable preparation hindered their work in the course. DISCUSSION/SIGNIFICANCE: With the increasing focus on Clinical and Translational Science taking place across the CTSA Consortium it is important to involve research staff in paper writing teams, including in first-author roles. Professional development in scientific writing can support Clinical and Translational Research staff contributing to this emerging science.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"53 2","pages":"55 - 56"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140795961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVES/GOALS: To identify empiric neuropsychiatric symptom (NPS) clusters in behavioral variant frontotemporal dementia and to determine the role of early anxiety/depression on functional progression. METHODS/STUDY POPULATION: Analyses were conducted using data from the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, an established consortium with an ongoing cohort study of FTD patients across 18 clinical sites which includes comprehensive cognitive, neuropsychiatric, and structural neuroimaging data. A polychoric cluster analysis was performed on subjects from the ALLFTD cohort [applewebdata%3A//044E463E-34DA-4677-9EDC-B8309D14C337#_msocom_1] with early-stage disease (N=145, male 61%, median age 62 years) in order to identify empiric NPS clusters. Cox proportional hazard regression was then used to examine the association between early affective symptoms in bvFTD and subsequent functional disabilities adjusted for age, sex, level of education, and FTLD CDR global score. RESULTS/ANTICIPATED RESULTS: We identified a four-factor model as the best fit for the data: (1) an affective cluster with prominent depression, anxiety, agitation, and irritability, (2) a disinhibited symptom cluster with prominent elation and disinhibition, (3) an obsessive symptom cluster with prominent obsessive/ritualistic behavior and hyperorality, and (4) a psychotic symptom cluster with prominent delusions and hallucinations. The hazard of developing impairments in transactions, language, self-care, meal preparation, and incontinence was significantly elevated in those with early affective symptoms (depression/anxiety). DISCUSSION/SIGNIFICANCE: In this study we show that, NPS cluster into four discrete groups: (1) affective symptoms, (2) disinhibited symptoms, (3) obsessive symptoms, and (4) psychotic symptoms. Anxiety and depression are prominent within the affective symptom cluster and are associated with accelerated functional decline in a number of domains.
{"title":"480 Neuropsychiatric Symptom Clusters in behavioral variant frontotemporal dementia: The Role of Early Anxiety/Depression on Functional Progression","authors":"C. Morrow","doi":"10.1017/cts.2024.406","DOIUrl":"https://doi.org/10.1017/cts.2024.406","url":null,"abstract":"OBJECTIVES/GOALS: To identify empiric neuropsychiatric symptom (NPS) clusters in behavioral variant frontotemporal dementia and to determine the role of early anxiety/depression on functional progression. METHODS/STUDY POPULATION: Analyses were conducted using data from the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, an established consortium with an ongoing cohort study of FTD patients across 18 clinical sites which includes comprehensive cognitive, neuropsychiatric, and structural neuroimaging data. A polychoric cluster analysis was performed on subjects from the ALLFTD cohort [applewebdata%3A//044E463E-34DA-4677-9EDC-B8309D14C337#_msocom_1] with early-stage disease (N=145, male 61%, median age 62 years) in order to identify empiric NPS clusters. Cox proportional hazard regression was then used to examine the association between early affective symptoms in bvFTD and subsequent functional disabilities adjusted for age, sex, level of education, and FTLD CDR global score. RESULTS/ANTICIPATED RESULTS: We identified a four-factor model as the best fit for the data: (1) an affective cluster with prominent depression, anxiety, agitation, and irritability, (2) a disinhibited symptom cluster with prominent elation and disinhibition, (3) an obsessive symptom cluster with prominent obsessive/ritualistic behavior and hyperorality, and (4) a psychotic symptom cluster with prominent delusions and hallucinations. The hazard of developing impairments in transactions, language, self-care, meal preparation, and incontinence was significantly elevated in those with early affective symptoms (depression/anxiety). DISCUSSION/SIGNIFICANCE: In this study we show that, NPS cluster into four discrete groups: (1) affective symptoms, (2) disinhibited symptoms, (3) obsessive symptoms, and (4) psychotic symptoms. Anxiety and depression are prominent within the affective symptom cluster and are associated with accelerated functional decline in a number of domains.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"40 2","pages":"141 - 141"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140769002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ameer Mansur, Moozhan Nikpanah, Johnathan McConathy, Erica Stringer-Reasor, Gabrielle Rocque, Ahmed Elkhanany, Katia Khoury, Nusrat Jahan, Suzanne E. Lapi, A. Sorace
OBJECTIVES/GOALS: This study was performed to explore the capabilities of simultaneous [89 Zr]trastuzumab-PET/MRI acquisition in a cohort of metastatic HER2+ breast cancer. The insights derived provide additional noninvasive characterization and precise intratumoral analysis tools for healthcare providers. METHODS/STUDY POPULATION: A total of 13 patients, aged between 40 and 70, diagnosed with HER2-positive breast cancer, were selected to participate in this study. Whole-body [89 Zr]trastuzumab-PET/MR imaging was performed 5 ± 1 days post-injection of the radiopharmaceutical during ongoing HER2-directed therapy. Concurrently acquired T1-weighted MRI facilitated the identification of normal organ and tumor regions of interest, which were further analyzed for mean ADC and mean standardized uptake value. Multiparametric intratumoral habitat analysis was performed. Utilizing the median metric values, tumors were evaluated for heterogeneity, specifically assessing high and low HER2 expression through an image processing framework in conjunction with ADC metrics. Long-term treatment response evaluation is ongoing. RESULTS/ANTICIPATED RESULTS: Initial analysis indicate all tumors exhibited higher overall uptake of [89 Zr]trastuzumab across various sites including the bone (p=0.019), brain (p=0.014), and breast (p=0.069), when compared to corresponding normal organs. Additionally, increased ADCmean values were observed in all regions besides brain tumors (bone: p=0.002, brain: p=0.5, breast: p=0.03, juxtapulmonary: p=0.037), indicating distinct patterns of cellularity. Notably, one of five patients with a breast lesion, who exhibited a complete response to HER2-targeted therapy, exhibited the highest breast lesion SUVmean. Brain and lymph node lesions demonstrated intratumoral heterogeneity of HER2 expression. Qualification of multi parametric maps is anticipated to inform on intratumoral heterogeneity DISCUSSION/SIGNIFICANCE: Despite limitation in clinical applications of quantitative approaches due to lack of standardization of processing, initial investigations, in combining molecular imaging of HER2 and quantitative MRI demonstrate potential in characterizing metastatic HER2+ breast cancer for intratumoral classification and therapeutic stratification.
{"title":"472 Utility of [89Zr]Trastuzumab-PET/MRI Imaging for Quantitative Assessment of Tumor Heterogeneity In HER2+ Breast Cancer","authors":"Ameer Mansur, Moozhan Nikpanah, Johnathan McConathy, Erica Stringer-Reasor, Gabrielle Rocque, Ahmed Elkhanany, Katia Khoury, Nusrat Jahan, Suzanne E. Lapi, A. Sorace","doi":"10.1017/cts.2024.400","DOIUrl":"https://doi.org/10.1017/cts.2024.400","url":null,"abstract":"OBJECTIVES/GOALS: This study was performed to explore the capabilities of simultaneous [89 Zr]trastuzumab-PET/MRI acquisition in a cohort of metastatic HER2+ breast cancer. The insights derived provide additional noninvasive characterization and precise intratumoral analysis tools for healthcare providers. METHODS/STUDY POPULATION: A total of 13 patients, aged between 40 and 70, diagnosed with HER2-positive breast cancer, were selected to participate in this study. Whole-body [89 Zr]trastuzumab-PET/MR imaging was performed 5 ± 1 days post-injection of the radiopharmaceutical during ongoing HER2-directed therapy. Concurrently acquired T1-weighted MRI facilitated the identification of normal organ and tumor regions of interest, which were further analyzed for mean ADC and mean standardized uptake value. Multiparametric intratumoral habitat analysis was performed. Utilizing the median metric values, tumors were evaluated for heterogeneity, specifically assessing high and low HER2 expression through an image processing framework in conjunction with ADC metrics. Long-term treatment response evaluation is ongoing. RESULTS/ANTICIPATED RESULTS: Initial analysis indicate all tumors exhibited higher overall uptake of [89 Zr]trastuzumab across various sites including the bone (p=0.019), brain (p=0.014), and breast (p=0.069), when compared to corresponding normal organs. Additionally, increased ADCmean values were observed in all regions besides brain tumors (bone: p=0.002, brain: p=0.5, breast: p=0.03, juxtapulmonary: p=0.037), indicating distinct patterns of cellularity. Notably, one of five patients with a breast lesion, who exhibited a complete response to HER2-targeted therapy, exhibited the highest breast lesion SUVmean. Brain and lymph node lesions demonstrated intratumoral heterogeneity of HER2 expression. Qualification of multi parametric maps is anticipated to inform on intratumoral heterogeneity DISCUSSION/SIGNIFICANCE: Despite limitation in clinical applications of quantitative approaches due to lack of standardization of processing, initial investigations, in combining molecular imaging of HER2 and quantitative MRI demonstrate potential in characterizing metastatic HER2+ breast cancer for intratumoral classification and therapeutic stratification.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"10 ","pages":"139 - 139"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140772701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVES/GOALS: The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research. METHODS/STUDY POPULATION: An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams' perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: There was a total of 63 responses. A majority of respondents have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts. Approximately half of the respondents believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues, distrust in doctors and/or researchers, fear of unknown side effects, and unavailability of medical interpreters. Respondents report that they are not discouraged from enrolling URGs and would utilize resources related to encouraging the inclusion of URGs DISCUSSION/SIGNIFICANCE: Language appears more influential than ethnicity or race when it comes to enrolling and retaining URGs. Additionally, it appears that enrolling is a bigger challenge than retaining. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation.
{"title":"104 Perceived Barriers to the Recruitment and Retention of Underrepresented Racial and Ethnic Groups (URGs) in Clinical Research","authors":"Victoria H. McNamara, Elise Smith, E. Tumilty","doi":"10.1017/cts.2024.102","DOIUrl":"https://doi.org/10.1017/cts.2024.102","url":null,"abstract":"OBJECTIVES/GOALS: The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research. METHODS/STUDY POPULATION: An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams' perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: There was a total of 63 responses. A majority of respondents have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts. Approximately half of the respondents believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues, distrust in doctors and/or researchers, fear of unknown side effects, and unavailability of medical interpreters. Respondents report that they are not discouraged from enrolling URGs and would utilize resources related to encouraging the inclusion of URGs DISCUSSION/SIGNIFICANCE: Language appears more influential than ethnicity or race when it comes to enrolling and retaining URGs. Additionally, it appears that enrolling is a bigger challenge than retaining. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"242 3","pages":"29 - 29"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chin Chin Lee, D. Ransford, Carlos A. Canales, Maria Alcaide, Patricia Wahl, Rosalina Das, Carl I Schulman
OBJECTIVES/GOALS: The objectives are 1) to describe the creation and implementation of a Clinical Research Feasibility Program at the University of Miami Miller School of Medicine (UMMSOM), and 2) to share early findings demonstrating its effectiveness in improving research operations which may be helpful for other academic medical centers. METHODS/STUDY POPULATION: Many clinical trials are closed prematurely because of low accrual or not being able to meet the target enrollment. The Miami CTSI and UMMSOM Executive Dean for Research office collaborated to establish the Research Feasibility Committee (RFC) focusing on clinical trial selection with upfront feasibility and recruitment planning. Program implementation included: 1) selecting faculty with successful clinical trial track records as committee members; 2) developing processes, tools, and governance; 3) feasibility pilot testing; and 4) feasibility program roll out and refinement. The feasibility review process starts with the PI/Designee completing a REDCap study intake form, followed by an administrative review to ensure completeness of the form. The RFC chair assigns reviewers for the studies. RESULTS/ANTICIPATED RESULTS: The RFC went live on September 1, 2022 reviewing industry sponsor clinical research studies. The RFC conducts a systematic feasibility assessment of the study protocol, operational requirements, enrollment barriers, institutional resources, and study budget (if available) for all applicable research studies prior to IRB submission and contract negotiation at the UMMSOM. To date, the RFC has received over 270 submissions. Based on feedback from users, the committee has made changes to improve the comprehension of questions and added questions to ensure capturing of critical information to assess study feasibility. Initial metrics suggest simply implementing the review process has decreased the number of clinical trial submissions: average number of studies per quarter was 41 pre-RFC vs 24 post RFC. DISCUSSION/SIGNIFICANCE: The development and implementation of the RFC involved many stakeholders from the research enterprise. Clear and frequent communication to the research community was a key factor in the program’s success. The next phase is assessing the impact of the RFC, such as preserving vital resources for trials more likely to be successful.
{"title":"529 Implementation of a Clinical Research Feasibility Program at an Academic Medical Center","authors":"Chin Chin Lee, D. Ransford, Carlos A. Canales, Maria Alcaide, Patricia Wahl, Rosalina Das, Carl I Schulman","doi":"10.1017/cts.2024.451","DOIUrl":"https://doi.org/10.1017/cts.2024.451","url":null,"abstract":"OBJECTIVES/GOALS: The objectives are 1) to describe the creation and implementation of a Clinical Research Feasibility Program at the University of Miami Miller School of Medicine (UMMSOM), and 2) to share early findings demonstrating its effectiveness in improving research operations which may be helpful for other academic medical centers. METHODS/STUDY POPULATION: Many clinical trials are closed prematurely because of low accrual or not being able to meet the target enrollment. The Miami CTSI and UMMSOM Executive Dean for Research office collaborated to establish the Research Feasibility Committee (RFC) focusing on clinical trial selection with upfront feasibility and recruitment planning. Program implementation included: 1) selecting faculty with successful clinical trial track records as committee members; 2) developing processes, tools, and governance; 3) feasibility pilot testing; and 4) feasibility program roll out and refinement. The feasibility review process starts with the PI/Designee completing a REDCap study intake form, followed by an administrative review to ensure completeness of the form. The RFC chair assigns reviewers for the studies. RESULTS/ANTICIPATED RESULTS: The RFC went live on September 1, 2022 reviewing industry sponsor clinical research studies. The RFC conducts a systematic feasibility assessment of the study protocol, operational requirements, enrollment barriers, institutional resources, and study budget (if available) for all applicable research studies prior to IRB submission and contract negotiation at the UMMSOM. To date, the RFC has received over 270 submissions. Based on feedback from users, the committee has made changes to improve the comprehension of questions and added questions to ensure capturing of critical information to assess study feasibility. Initial metrics suggest simply implementing the review process has decreased the number of clinical trial submissions: average number of studies per quarter was 41 pre-RFC vs 24 post RFC. DISCUSSION/SIGNIFICANCE: The development and implementation of the RFC involved many stakeholders from the research enterprise. Clear and frequent communication to the research community was a key factor in the program’s success. The next phase is assessing the impact of the RFC, such as preserving vital resources for trials more likely to be successful.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"111 8","pages":"157 - 157"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dennis Savaiano, Sarah Wiehe, G. Claxton, K. Hinshaw
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.
{"title":"286 Partnering and engaging in Indiana Communities through listening sessions and data sharing: successes of Connection IN Health","authors":"Dennis Savaiano, Sarah Wiehe, G. Claxton, K. Hinshaw","doi":"10.1017/cts.2024.262","DOIUrl":"https://doi.org/10.1017/cts.2024.262","url":null,"abstract":"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.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"37 20","pages":"88 - 88"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ronald C. Eldridge, Nabil F. Saba, Andrew Miller, E. Wommack, Jennifer Felger, Deborah W. Bruner, C. Xiao
OBJECTIVES/GOALS: Cachexia is the involuntary and irreversible loss of muscle and fat and is a major cause of morbidity and mortality in head and neck cancer (HNC). It remains a poorly understood disease diagnosed by weight loss and a confluence of symptoms. We explored the metabolic and inflammatory mechanisms of cachexia symptoms via an multiomics network algorithm. METHODS/STUDY POPULATION: Prior to chemoradiotherapy, HNC subjects completed questionnaires and donated blood for untargeted (metabolites) and targeted (lipids and cytokines) assays. Metabolites and lipids were measured by liquid chromatography mass spectrometry. Cytokines were measured by multiplex assays. We plotted a multiomics network graph by estimating partial least squares correlations amongst metabolites, lipids, cytokines, and common cachexia symptoms—max percent weight loss over 1 year, baseline BMI, fatigue, performance, albumin, hemoglobin, and white blood cell count. To interpret the network, an algorithm identified highly correlated clusters of metabolites-lipids-cytokines-symptoms representing possible biological relatedness, which were functionally annotated via metabolic enrichment analysis. RESULTS/ANTICIPATED RESULTS: In 123 subjects (59 years of age, 72% male, 84% white, avg weight loss of 13%), we analyzed 186 metabolites, 54 lipids, 7 cytokines and 7 cachexia symptoms. We required a correlation >0.25 and P-value <.05 to be included in the network graph, resulting in 323 connections and 3 identified clusters. Max weight loss and baseline BMI were in a cluster enriched by unsaturated fatty acid biosynthesis (P<.0001) and arachidonic acid (P=.01) metabolic pathways but not linked to inflammation cytokines. The five other cachexia symptoms were in a cluster with 4 cytokines (C-reactive protein, interleukin 6, IL10, IL1, Tumor necrosis factor receptor 2) and enriched by aminoacyl tRNA (P<.01) and valine biosynthesis (P=.02). We observed no meaningful differences when we stratified the analysis by human papillomavirus. DISCUSSION/SIGNIFICANCE: Cachexia symptoms in head and neck cancer may be linked to specific metabolic dysregulation—weight loss and BMI were linked to fatty acids; fatigue, anemia and others were linked to amino acids and inflammation. This information may allow for the recognition of a cachexic-metabolic subtype or provide novel targets for metabolic intervention.
{"title":"434 Investigating the metabolic-inflammatory mechanisms of cachexia symptoms in head and neck cancer patient plasma via multiomics integration of the metabolome, lipidome, and inflammation cytokines","authors":"Ronald C. Eldridge, Nabil F. Saba, Andrew Miller, E. Wommack, Jennifer Felger, Deborah W. Bruner, C. Xiao","doi":"10.1017/cts.2024.375","DOIUrl":"https://doi.org/10.1017/cts.2024.375","url":null,"abstract":"OBJECTIVES/GOALS: Cachexia is the involuntary and irreversible loss of muscle and fat and is a major cause of morbidity and mortality in head and neck cancer (HNC). It remains a poorly understood disease diagnosed by weight loss and a confluence of symptoms. We explored the metabolic and inflammatory mechanisms of cachexia symptoms via an multiomics network algorithm. METHODS/STUDY POPULATION: Prior to chemoradiotherapy, HNC subjects completed questionnaires and donated blood for untargeted (metabolites) and targeted (lipids and cytokines) assays. Metabolites and lipids were measured by liquid chromatography mass spectrometry. Cytokines were measured by multiplex assays. We plotted a multiomics network graph by estimating partial least squares correlations amongst metabolites, lipids, cytokines, and common cachexia symptoms—max percent weight loss over 1 year, baseline BMI, fatigue, performance, albumin, hemoglobin, and white blood cell count. To interpret the network, an algorithm identified highly correlated clusters of metabolites-lipids-cytokines-symptoms representing possible biological relatedness, which were functionally annotated via metabolic enrichment analysis. RESULTS/ANTICIPATED RESULTS: In 123 subjects (59 years of age, 72% male, 84% white, avg weight loss of 13%), we analyzed 186 metabolites, 54 lipids, 7 cytokines and 7 cachexia symptoms. We required a correlation >0.25 and P-value <.05 to be included in the network graph, resulting in 323 connections and 3 identified clusters. Max weight loss and baseline BMI were in a cluster enriched by unsaturated fatty acid biosynthesis (P<.0001) and arachidonic acid (P=.01) metabolic pathways but not linked to inflammation cytokines. The five other cachexia symptoms were in a cluster with 4 cytokines (C-reactive protein, interleukin 6, IL10, IL1, Tumor necrosis factor receptor 2) and enriched by aminoacyl tRNA (P<.01) and valine biosynthesis (P=.02). We observed no meaningful differences when we stratified the analysis by human papillomavirus. DISCUSSION/SIGNIFICANCE: Cachexia symptoms in head and neck cancer may be linked to specific metabolic dysregulation—weight loss and BMI were linked to fatty acids; fatigue, anemia and others were linked to amino acids and inflammation. This information may allow for the recognition of a cachexic-metabolic subtype or provide novel targets for metabolic intervention.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"96 ","pages":"129 - 130"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140771066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eva Furrow, Luca Rampoldi, Luca Jovine, Jeffrey A. Wesson, Amy E. Treeful, M. Jayachandran, John C. Lieske, Michael F. Romero, Jody P. Lulich
OBJECTIVES/GOALS: Using a natural canine model of kidney stone disease, we previously identified a pathogenic variant in the uromodulin gene (UMOD) that imparts a dramatic risk for calcium oxalate (CaOx) stones. This study was designed to characterize the effects of the pathogenic variant on uromodulin processing, specifically polymerization and peptide excretion. METHODS/STUDY POPULATION: Uromodulin polymerization status and peptides were measured in random urine samples from CaOx stone-forming dogs with the pathogenic UMOD variant and breed-, sex-, and age-matched healthy control dogs. Polymerization status was determined using an ultracentrifugation protocol and Western blotting in 6 CaOx cases and 3 controls; relative abundance of the polymerizing and nonpolymerizing forms was evaluated. Uromodulin peptide abundances were measured by LC-MS/MS with 4 dogs per group; results were summed to determine total uromodulin peptide excretion for each dog, and individual peptide abundances were calculated as a percentage of the total. Polymerization status and peptides were compared between groups. RESULTS/ANTICIPATED RESULTS: Dogs with the pathogenic UMOD variant had abnormalities in both uromodulin polymerization and peptide processing. The polymerization data showed that the polymerizing form of uromodulin was abundant in all healthy controls but absent or severely reduced in most dogs with the variant. In contrast, nonpolymerizing uromodulin was detected in all dogs with no observed difference between those with and without the variant. The peptidomics data showed that stone-forming dogs with the pathogenic UMOD variant lacked a peptide cleavage site, resulting in the loss of two common peptides that terminate at that site and the presence of longer peptides that span the site. DISCUSSION/SIGNIFICANCE: These findings implicate uromodulin polymerization and peptide processing defects in kidney stone risk. Future studies will define the mechanisms through which these defects affect stone formation, ultimately informing development of novel preventative therapies.
{"title":"431 Defective uromodulin polymerization and peptide excretion in a natural canine model of kidney stones","authors":"Eva Furrow, Luca Rampoldi, Luca Jovine, Jeffrey A. Wesson, Amy E. Treeful, M. Jayachandran, John C. Lieske, Michael F. Romero, Jody P. Lulich","doi":"10.1017/cts.2024.373","DOIUrl":"https://doi.org/10.1017/cts.2024.373","url":null,"abstract":"OBJECTIVES/GOALS: Using a natural canine model of kidney stone disease, we previously identified a pathogenic variant in the uromodulin gene (UMOD) that imparts a dramatic risk for calcium oxalate (CaOx) stones. This study was designed to characterize the effects of the pathogenic variant on uromodulin processing, specifically polymerization and peptide excretion. METHODS/STUDY POPULATION: Uromodulin polymerization status and peptides were measured in random urine samples from CaOx stone-forming dogs with the pathogenic UMOD variant and breed-, sex-, and age-matched healthy control dogs. Polymerization status was determined using an ultracentrifugation protocol and Western blotting in 6 CaOx cases and 3 controls; relative abundance of the polymerizing and nonpolymerizing forms was evaluated. Uromodulin peptide abundances were measured by LC-MS/MS with 4 dogs per group; results were summed to determine total uromodulin peptide excretion for each dog, and individual peptide abundances were calculated as a percentage of the total. Polymerization status and peptides were compared between groups. RESULTS/ANTICIPATED RESULTS: Dogs with the pathogenic UMOD variant had abnormalities in both uromodulin polymerization and peptide processing. The polymerization data showed that the polymerizing form of uromodulin was abundant in all healthy controls but absent or severely reduced in most dogs with the variant. In contrast, nonpolymerizing uromodulin was detected in all dogs with no observed difference between those with and without the variant. The peptidomics data showed that stone-forming dogs with the pathogenic UMOD variant lacked a peptide cleavage site, resulting in the loss of two common peptides that terminate at that site and the presence of longer peptides that span the site. DISCUSSION/SIGNIFICANCE: These findings implicate uromodulin polymerization and peptide processing defects in kidney stone risk. Future studies will define the mechanisms through which these defects affect stone formation, ultimately informing development of novel preventative therapies.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"382 1","pages":"129 - 129"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140788111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVES/GOALS: The objective of this project was to evaluate the factors that contribute to LGBTQIA2+ patient comfortability. This information was then used to understand how best to create a comfortable space for LGBTQIA2+ patients. METHODS/STUDY POPULATION: This survey was focused on underinsured and uninsured patients seen at the Rainbow Clinic - a free student-run LGBTQIA2+ clinic. Surveys were distributed by undergraduate volunteers on tablets as a qualtrics survey. Surveys collected demographic information in addition to 5 questions that assessed patient comfortability. These questions included evaluating the patient’s comfort with sharing information with the provider and the patient’s comfort of coming into clinical spaces. These surveys were distributed before and after clinic appointments to capture any changes in comfortability that could have occurred as a result of the appointment. RESULTS/ANTICIPATED RESULTS: Up to May of 2023, 49 patients were seen in Rainbow Clinic. 33 patients filled out the intake survey and 31 patients filled out the check-out survey resulting in a 67% and 63% response rate respectively. Questions were asked on a likert scale (1-5) from Strongly Disagree to Strongly Agree. Questions evaluating patient comfort in sharing information with their provider yielded an average score that was statistically significant, suggesting patients felt comfortable at the Rainbow Clinic. Additionally, patients indicated that the LGBTQIA2+ specific labeling of the Rainbow Clinic made them significantly more comfortable coming into the clinic. DISCUSSION/SIGNIFICANCE: This project suggests that patient comfortability can be improved by training and intentional LGBTQIA2+ labeling. Considering the hesitancy of this community towards healthcare, improving comfortability not only benefits clinical care and outcomes but can also bolster the body of research on this community.
{"title":"111 Evaluating Patient Influences on Comfortability for LGBTQIA2+ Patients in Clinical Spaces (EPIC)","authors":"G. Lee, Bashar Shihabuddin, C. Shihabuddin","doi":"10.1017/cts.2024.109","DOIUrl":"https://doi.org/10.1017/cts.2024.109","url":null,"abstract":"OBJECTIVES/GOALS: The objective of this project was to evaluate the factors that contribute to LGBTQIA2+ patient comfortability. This information was then used to understand how best to create a comfortable space for LGBTQIA2+ patients. METHODS/STUDY POPULATION: This survey was focused on underinsured and uninsured patients seen at the Rainbow Clinic - a free student-run LGBTQIA2+ clinic. Surveys were distributed by undergraduate volunteers on tablets as a qualtrics survey. Surveys collected demographic information in addition to 5 questions that assessed patient comfortability. These questions included evaluating the patient’s comfort with sharing information with the provider and the patient’s comfort of coming into clinical spaces. These surveys were distributed before and after clinic appointments to capture any changes in comfortability that could have occurred as a result of the appointment. RESULTS/ANTICIPATED RESULTS: Up to May of 2023, 49 patients were seen in Rainbow Clinic. 33 patients filled out the intake survey and 31 patients filled out the check-out survey resulting in a 67% and 63% response rate respectively. Questions were asked on a likert scale (1-5) from Strongly Disagree to Strongly Agree. Questions evaluating patient comfort in sharing information with their provider yielded an average score that was statistically significant, suggesting patients felt comfortable at the Rainbow Clinic. Additionally, patients indicated that the LGBTQIA2+ specific labeling of the Rainbow Clinic made them significantly more comfortable coming into the clinic. DISCUSSION/SIGNIFICANCE: This project suggests that patient comfortability can be improved by training and intentional LGBTQIA2+ labeling. Considering the hesitancy of this community towards healthcare, improving comfortability not only benefits clinical care and outcomes but can also bolster the body of research on this community.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"36 6","pages":"32 - 32"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140771552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Lopez Medina, Alessandra M. Campos-Staffico, Choudhary Anwar A Chahal, Isabella Volkers, Juliet P. Jacoby, Mohammed Saeed, Omer Berenfeld, Jasmine A. Luzum
OBJECTIVES/GOALS: The objective of this research was to determine the associations of candidate genetic variants withdrug-induced long QT syndrome (diLQTS) risk, an adverse effect of over 150 FDA-approved drugsthat can lead to cardiac arrhythmias and sudden cardiac death. METHODS/STUDY POPULATION: This was a retrospective observational study of the genomic biobank at the University of Michigan Health System. Patients treated with a high-risk QT-prolonging drug and ECG measurements were included. The primary outcome was exaggerated prolongation of the QTc interval (i.e., >60 ms change from baseline and/or >500 ms absolute value) corrected using Bazett. We analyzed 3 genetic variants: KCNE1-D85N (rs1805128), SCN5A-G615E (rs12720452) and KCNE2-I57T (rs7415448) in the dominant genetic model. A Bonferroni-corrected p-value of 0.017 was considered statistically significant using logistic regression adjusted for clinical covariates. RESULTS/ANTICIPATED RESULTS: In total 6,083 self-reported white patients were included (12% event rate). The adjusted odd ratio for KCNE1-D85N was 2.24 (95%CI: 1.35-3.57; p=0.0011). The adjusted odds ratio forKCNE2-I57T was 1.40 (95%CI: 0.26-5.78, p=0.662). Only 4 total patients carried the SCN5A-G615E variant, and none of the carriers had prolonged QTc. DISCUSSION/SIGNIFICANCE: This is the largest study of candidate genetic variants in cardiac ion channels associated with the diLQTS risk. KCNE1-D85N was associated with diLQTS risk, while KCNE2-I57T was suggestive of a potential association. KCNE1-D85N should be considered in clinical guidelines as a risk factor of diLQTS.
{"title":"475 Genetic risk factors for drug-induced long QT syndrome: Findings from a large real-world clinical cohort.","authors":"Ana Lopez Medina, Alessandra M. Campos-Staffico, Choudhary Anwar A Chahal, Isabella Volkers, Juliet P. Jacoby, Mohammed Saeed, Omer Berenfeld, Jasmine A. Luzum","doi":"10.1017/cts.2024.403","DOIUrl":"https://doi.org/10.1017/cts.2024.403","url":null,"abstract":"OBJECTIVES/GOALS: The objective of this research was to determine the associations of candidate genetic variants withdrug-induced long QT syndrome (diLQTS) risk, an adverse effect of over 150 FDA-approved drugsthat can lead to cardiac arrhythmias and sudden cardiac death. METHODS/STUDY POPULATION: This was a retrospective observational study of the genomic biobank at the University of Michigan Health System. Patients treated with a high-risk QT-prolonging drug and ECG measurements were included. The primary outcome was exaggerated prolongation of the QTc interval (i.e., >60 ms change from baseline and/or >500 ms absolute value) corrected using Bazett. We analyzed 3 genetic variants: KCNE1-D85N (rs1805128), SCN5A-G615E (rs12720452) and KCNE2-I57T (rs7415448) in the dominant genetic model. A Bonferroni-corrected p-value of 0.017 was considered statistically significant using logistic regression adjusted for clinical covariates. RESULTS/ANTICIPATED RESULTS: In total 6,083 self-reported white patients were included (12% event rate). The adjusted odd ratio for KCNE1-D85N was 2.24 (95%CI: 1.35-3.57; p=0.0011). The adjusted odds ratio forKCNE2-I57T was 1.40 (95%CI: 0.26-5.78, p=0.662). Only 4 total patients carried the SCN5A-G615E variant, and none of the carriers had prolonged QTc. DISCUSSION/SIGNIFICANCE: This is the largest study of candidate genetic variants in cardiac ion channels associated with the diLQTS risk. KCNE1-D85N was associated with diLQTS risk, while KCNE2-I57T was suggestive of a potential association. KCNE1-D85N should be considered in clinical guidelines as a risk factor of diLQTS.","PeriodicalId":508693,"journal":{"name":"Journal of Clinical and Translational Science","volume":"483 1","pages":"140 - 140"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140773522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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