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Item 4355 Impact of Demographic & Racial Differences on DNA Repair Capacity in Lung Cancer(Cambridge University Press, 2020-07-29) Duncan, Francesca Christina; Sears, Catherine; Al Narallah, Nawar; Al-Hader, Ahmad; Medicine, School of MedicineOBJECTIVES/GOALS: Lung cancer is the leading cause of cancer-related mortality in the United States for both men and women. African Americans are disproportionately affected with lung cancer, having higher incidence and mortality rates compared to Caucasian men and women. African American smokers are diagnosed with lung cancer at a lower age with lower cumulative smoking history. Differences in socioeconomic and environmental factors likely contribute to lung cancer disparities, but less is known about acquired biologic alterations that can promote initiation and progression of lung cancer, particularly in African Americans. This is of interest because there may be other biological, genetic, or environmental factors contributing to lung cancer outcomes as it relates to differences in gender and race. One potential biologic variable may be in the DNA repair capacity (DRC), which describes a cell’s ability to repair damage to DNA caused by carcinogens, oxidants, and radiation. Altered DNA repair is a hallmark of cancer, leading to mutations and malignant transformation. We hypothesize that DRC is decreased in African Americans with lung cancer compared to Caucasian Americans with lung cancer, contributing to the disparity that exists in this racial group. We will 1) perform a retrospective chart review to determine demographic differences between African Americans and Caucasians at three central Indiana hospitals and 2) determine the impact of race and lung cancer on DRC amongst African Americans and Caucasians with and without lung cancer. METHODS/STUDY POPULATION: Lung cancer patients are identified in 3 central Indiana hospitals with different payer source and patient populations using ICD codes. Collected demographics include age, gender, pack-years, lung cancer histology, treatment, and mortality. DRC is measured by host-cell reactivation (non-homologous end-joining and nucleotide excision repair pathways) by flow-cytometry. Measurement of DRC is performed on PBMCs obtained from 120 patients (male and female, African Americans and Caucasians with and without lung cancer). Correlation of DRC and lung cancer will be determined by comparing lung cancer diagnosis to quartile DRC, and adjusted for confounders (measured demographics). Correlative measures will include measures of DNA damage and genomic instability. RESULTS/ANTICIPATED RESULTS: 3450 lung cancer patients were diagnosed with lung cancer at Indiana University Hospital between 1/1/2000 – 5/31/2015. Of these, 48.2% were female and 92.7% smokers. African Americans, Caucasians and Other ethnicities represented 12%, 86% and 2%, respectively. Of smokers, 11.4% were African American. The primary payer source was Federal/Medicare. Retrospective review of lung cancer patients from two additional health systems (county and VA hospitals) will be performed as above with outcomes measured. DRC and additional correlative measures will be performed as in Methods. DISCUSSION/SIGNIFICANCE OF IMPACT: If present, altered DRC in African Americans compared to Caucasians may contribute to the disproportional impact of lung cancer on African Americans. If DRC is decreased in African Americans with lung cancer, future studies will focus on identifying potential genetic, epigenetic and environmental causes for this decrease.Item Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium(American Medical Association, 2022) Zanobetti, Antonella; Ryan, Patrick H.; Coull, Brent; Brokamp, Cole; Datta, Soma; Blossom, Jeffrey; Lothrop, Nathan; Miller, Rachel L.; Beamer, Paloma I.; Visness, Cynthia M.; Andrews, Howard; Bacharier, Leonard B.; Hartert, Tina; Johnson, Christine C.; Ownby, Dennis; Khurana Hershey, Gurjit K.; Joseph, Christine; Yiqiang, Song; Mendonça, Eneida A.; Jackson, Daniel J.; Luttmann-Gibson, Heike; Zoratti, Edward M.; Wright, Anne L.; Martinez, Fernando D.; Seroogy, Christine M.; Gern, James E.; Gold, Diane R.; Children’s Respiratory and Environmental Workgroup (CREW) Consortium; Epidemiology, School of Public HealthImportance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. Design, setting, and participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Main outcomes and measures: Prevalence of early and persistent childhood wheeze and asthma incidence. Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Conclusions and relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.Item DEI-05. Assessing Household Material Hardship in Children with Central Nervous System (CNS) Tumors(Oxford University Press, 2024-06-18) Coven, Scott L.; Tran, Yvette H.; Park, Seho; Mendonça, Eneida A.; Pediatrics, School of MedicineBACKGROUND: Household material hardship (HMH) is defined as unmet basic needs including food, heat, housing, or transportation. Researchers have documented higher rates of poor nutrition, injury, infectious disease, and hospitalization in healthy children living in families with household material hardship. Furthermore, targeted interventions exist to modify these health outcomes. However, little is known regarding the relationship between social determinants of health and their impact on overall and quality of survival for children with brain or spinal cord tumors. The current available information is based upon retrospective and secondary data sources, often limited to basic socioeconomic factors such as race and ethnicity. The objective was to describe the change in household material hardship through patient reported outcome measures from baseline to six-months and explore the association between social determinants of health, including prospective household material hardship data, and clinical outcomes among children with brain and spinal cord tumors. METHODS: We aimed to enroll 150 patients with a brain or spinal cord tumors who were followed by the Pediatric Neuro-Oncology Program at Riley Hospital for Children at IU Health. These participants were approached during their routinely scheduled clinic visits by a member of the study team. Written or verbal consent/assent was obtained, and their data was transcribed into a REDCap™ database. RESULTS: To date, we have enrolled 118 children onto this study, with 35/76 participants completing their six-month follow-up survey. In line with Kira Bona’s previous work, we have found that around 30% acknowledged one positive domain of household material hardship. Additionally, we have found that almost 40% of our cohort fall below the 200% Federal Poverty Level, which is often considered a cutpoint for lower socioeconomic status. CONCLUSIONS: We have shown that collecting prospective patient reported sociodemographic information is feasible in a busy clinical setting.Item Moving Beyond Gender Disparities: A Call to Action for Gender Parity and Equity(Elsevier, 2022) Jarman, Angela F.; Hobgood, Cherri D.; Madsen, Tracy E.; Emergency Medicine, School of MedicineItem Relationships Between 2018 UNOS Heart Policy and Transplant Outcomes In Metropolitan, Micropolitan, and Rural Settings(Elsevier, 2022) Breathett, Khadijah; Knapp, Shannon M.; Addison, Daniel; Johnson, Amber; Shah, Rashmee U.; Flint, Kelsey; Van Spall, Harriette G. C.; Sweitzer, Nancy K.; Mazimba, Sula; Medicine, School of MedicineBackground: In 2018, United Network for Organ Sharing (UNOS) extended the radius for which a heart transplant candidate can match with a donor, and outcomes across population densities are unknown. We sought to determine whether the policy change was associated with differences in heart transplant waitlist time or death post-transplant for patients from rural, micropolitan, and metropolitan settings. Methods: Using the Scientific Registry of Transplant Recipients, we evaluated U.S. adult patients listed for heart transplant from Janurary 2017 to September 2019 with follow-up through March 2020. Patients were stratified by home zip-codes to either metropolitan, micropolitan, or rural settings. Fine and Gray and Cox models were respectively used to estimate Sub-distribution hazard ratios (SHR) of heart transplant with death or removal from transplant list as a competing event, and HR of death post-transplant within population densities after versus before the UNOS policy change date, October 18, 2018. Analyses were adjusted for demographics, comorbidities, and labs. Results: Among 8,747 patients listed for heart transplant, 84.7% were from metropolitan, 8.6% micropolitan, and 6.6% rural settings. The 2018 UNOS policy was associated with earlier receipt of heart transplant for metropolitan [SHR 1.56 (95% CI: 1.46-1.66)] and micropolitan [SHR 1.48 (95% CI: 1.21-1.82)] populations, but not significantly for rural [SHR 1.20 (95% CI: 0.93-1.54)]; however, the interaction between policy and densities was not significant (p = .14). Policy changes were not associated with risk of death post-transplant [metropolitan: HR 1.04 (95% CI: 0.80-1.34); micropolitan: HR 1.10 (95% CI: 0.55-2.23); rural: HR 1.04 (95% CI: 0.52-2.08); interaction p = .99]. Conclusions: The 2018 UNOS heart transplant policy was associated with earlier receipt of heart transplant and no difference in post-transplant survival within population densities. Additional follow-up is needed to determine whether improvements are sustained.Item Treatment Needs for Dental Caries, Restorative Care Index, and Index of Extractions in Adolescents 12 and 15 Years Old(The University of the West Indies, 2013) Medina-Solís, CE; Pontigo-Loyola, AP; Mendoza-Rodríguez, M; Lucas-Rincón, SE; Márquez-Rodríguez, S; Navarrete-Hernandez, JJ; Maupomé, GerardoObjective: To determine the Treatment Needs Index (TNI) for dental caries, the restorative Care Index (CI), and to introduce a Tooth Extractions Index (TEI) to estimate past and current treatment needs among Mexican adolescents. Subjects and methods: A descriptive cross-sectional study was carried out on 1538 adolescents aged 12 and 15 years in the state of Hidalgo, Mexico, to collect decayed, missing, filled teeth (DMFT) data to describe TNI, CI and TEI indices. Results: Higher TNI was identified in younger male teenagers who had always lived in the same community, without dental visits in the last year, and who had poorer socio-economic markers. Higher CI was found in older, female subjects who had moved in their lifetimes to a new community in the area, with dental visits in the last year and who had better socio-economic markers. Higher TEI was found in older, female teenagers who had moved in their lifetimes to a new community in the area, without dental visits in the last year, and who had worse socio-economic markers. Conclusions: We observed high rates of treatment needs for dental caries and little experience of restorative treatment. While dental extractions due to advanced caries should ideally be zero, relatively few adolescents had this treatment experience. Despite the fact that the overall background of these adolescents is rather homogeneous, it was still possible to find that treatment needs' indices (past and present needs) appeared to be modified by sociodemographic and socio-economic variables.Item Under the influence of genetics: how transdisciplinarity leads us to rethink social pathways to illness(University of Chicago Press, 2008) Pescosolido, Bernice A.; Perry, Brea L.; Long, J. Scott; Martin, Jack K.; Department of Sociology, School of Liberal ArtsThis article describes both sociological and genetic theories of illness causation and derives propositions expected under each and under a transdisciplinary theoretical frame. The authors draw propositions from three theories -- fundamental causes, social stress processes, and social safety net theories -- and tailor hypotheses to the case of alcohol dependence. Analyses of a later wave of the Collaborative Study on the Genetics of Alcoholism reveal a complex interplay of the GABRA2 gene with social structural factors to produce cases meeting DSM/ICD diagnoses. Only modest evidence suggests that genetic influence works through social conditions and experiences. Further, women are largely unaffected in their risk for alcohol dependence by allele status at this candidate gene; family support attenuates genetic influence; and childhood deprivation exacerbates genetic predispositions. These findings highlight the essential intradisciplinary tension in the role of proximal and distal influences in social processes and point to the promise of focusing directly on dynamic, networked sequences that produce different pathways to health and illness.