ScholarWorks shares over 40,000 articles, working papers, chapters, presentations, posters, theses, historical documents and other items submitted by members of the IU Indianapolis campus community.
Get started! Login with your IU credentials to share freely with 2 million readers per year.
Communities in ScholarWorks
Select a community to browse its collections.
Recent Submissions
Implicit Racial Bias and Unintentional Harm in Vascular Care
(American Medical Association, 2025-02-26) Kalbaugh, Corey A.; Beidelman, Erika T.; Howard, Kerry A.; Witrick, Brian; Clark, Ashley; McGinigle, Katharine L.; Minc, Samantha; Alabi, Olamide; Hicks, Caitlin W.; Gonzalez, Andrew A.; Cené, Crystal W.; Cykert, Samuel; Surgery, School of Medicine
Importance: Implicit bias may influence physician treatment decisions and contribute to Black-White health disparities. There are limited data linking implicit bias with actual care delivery and outcomes.
Objective: To determine whether implicit racial bias is associated with potentially harmful surgical treatment selection for a cohort of patients with peripheral artery disease-related claudication.
Design, setting, and participants: This survey study, linked with observational registry data, included eligible clinicians who participate in the Vascular Quality Initiative (VQI) among 960 centers. The VQI includes academic medical centers, teaching hospitals, community hospitals, and private practices. Eligible participants included all vascular specialist VQI members (N = 2512), of whom 218 completed the race implicit association test (IAT) and were linkable to procedure-level data. The study was conducted between October 2021 and October 2022.
Exposure: Race IAT.
Main outcomes and measures: Clinician-level implicit bias results were linked to patient-level registry data of peripheral revascularization procedures performed for claudication. The adjusted odds of performance of any infrapopliteal procedure by specialist implicit bias and patient race were measured via mixed-effects logistic regression models. Implicit bias as a moderator of the association of infrapopliteal procedures for claudication and patient race with 1-year amputation was assessed as a secondary outcome.
Results: Among 218 vascular specialists (mean [SD] age, 46 [9] years; 160 [73%] male), 157 (72%) had a pro-White bias. Black patients treated by a physician with pro-White bias had a significant increase in the odds of receiving an infrapopliteal procedure compared with the total sample (adjusted odds ratio [AOR], 1.67; 95% CI, 1.12-2.48). When treated by a specialist with pro-White bias, Black patients had increased odds of 1-year amputation, regardless of anatomic location treated, compared with White patients (AOR, 2.34; 95% CI, 1.20-4.55). Conversely, Black patients treated by a specialist with no bias had similar odds of an infrapopliteal procedure (AOR, 0.93; 95% CI, 0.68-1.26) as the full patient sample and similar odds of 1-year amputation (AOR, 1.29; 95% CI, 0.33-4.99) as White patients.
Conclusions and relevance: These findings indicate that implicit bias is associated with potentially harmful infrapopliteal procedures for Black patients and contributes to Black-White outcome disparities in the US. These results suggest the need for system-level interventions that transparently identify and warn of procedures not aligned with best practices to reduce the negative influence of implicit bias.
Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial
(Oxford University Press, 2025) Heerspink, Hiddo J. L.; Agarwal, Rajiv; Bakris, George L.; Cherney, David Z. I.; Lam, Carolyn S. P.; Neuen, Brendon L.; Sarafidis, Pantelis A.; Tuttle, Katherine R.; Wanner, Christoph; Brinker, Meike D.; Dizayee, Sara; Kolkhof, Peter; Schloemer, Patrick; Vesterinen, Paula; Perkovic, Vlado; FIND-CKD investigators; Medicine, School of Medicine
Background: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes in two phase 3 outcome trials. The Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) study investigates the effect of finerenone in adults with CKD without diabetes.
Methods: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin:creatinine ratio (UACR) ≥200-≤3500 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<90 ml/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin system inhibitor were randomized 1:1 to once-daily placebo or finerenone 10 or 20 mg depending on eGFR >60 or <60 ml/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety.
Results: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 ml/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%) and calcium channel blockers by 794 (50.1%). Sodium-glucose co-transporter 2 (SGLT2) inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 versus 46.8 ml/min/1.73 m2) and a slightly higher median UACR (871.9 versus 808.3 mg/g) compared with those not using SGLT2 inhibitors at baseline.
Conclusions: FIND-CKD is the first phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.
Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment in Adults With Early Syphilis: Secondary Analysis of a Randomized Clinical Trial
(American Medical Association, 2025-02-03) Dionne, Jodie A.; Zhu, Chunming; Mejia-Galvis, Jorge; Workowski, Kimberly; Batteiger, Teresa A.; Dombrowski, Julia C.; Mayer, Kenneth H.; McNeil, Candice J.; Seña, Arlene C.; Taylor, Stephanie; Wiesenfeld, Harold C.; Hamill, Matthew M.; Perlowski, Charlotte; Hook, Edward W., III; Medicine, School of Medicine
Importance: Syphilis rates have been increasing in the US for the past decade. The incidence of the Jarisch-Herxheimer reaction (JHR) after penicillin treatment for early syphilis is reported to range from 8% to 56%.
Objectives: To prospectively assess the incidence of JHR signs and symptoms among adults with early syphilis treated with benzathine penicillin G and to document factors associated with JHR and benzathine penicillin G treatment response outcomes.
Design, setting, and participants: The main study was designed as a phase 4 randomized clinical trial to compare the treatment efficacy of 1 vs 3 doses of benzathine penicillin G in adults with early syphilis, measured as serologic response at 6 months. A total of 249 adults with or without HIV were screened and enrolled between October 31, 2018, and March 3, 2020. Participants were screened and enrolled at 10 US study sites in the Sexually Transmitted Infections Clinical Trials Group. Statistical analysis for this secondary analysis took place between March 2023 and August 2024.
Intervention: Participants received a first dose of benzathine penicillin G, 2.4 million units intramuscularly, at the enrollment visit. The JHR assessment window was day 1 to day 7 after the first dose of benzathine penicillin G.
Main outcomes and measures: Primary outcomes in this study were the incidence of symptoms consistent with JHR within 7 days after benzathine penicillin G treatment. Unelicited and elicited symptoms were assessed by participant self-report using a standardized checklist during contact made by a study clinician. Factors associated with JHR were collected at baseline, and serologic treatment response was assessed at 6 months. Posttreatment incident JHR symptoms were captured as safety outcomes for this trial. Analysis was performed on an intention-to-treat basis.
Results: Of 249 participants, the median age was 32 years (IQR, 27-41 years), 242 (97.2%) were men, and 153 (61.4%) were living with HIV. One or more JHR symptoms occurred in 59 participants (23.7%) treated for early syphilis, with a median symptom onset at 4.9 hours (IQR, 3.0-9.2 hours) and a median duration of 12.8 hours (IQR, 5.0-24.0 hours). Symptom onset was within 12 hours of treatment for 49 of 57 participants (86.0%). Among 59 symptomatic participants, myalgias (30 [50.8%]), chills (27 [45.8%]), weakness (23 [39.0%]), and feverishness (21 [35.6%]) were most common. In adjusted models, JHR was associated with secondary syphilis (adjusted odds ratio [AOR], 2.91 [95% CI, 1.51-5.61]) and the absence of HIV (AOR for living with HIV, 0.49 [95% CI, 0.26-0.94]). The proportion of participants with a serologic treatment response to benzathine penicillin G at 6 months was higher among participants with JHR (84.7% [50 of 59] vs 68.9% [131 of 190] without JHR).
Conclusions and relevance: In this prespecified secondary analysis of a randomized clinical trial of early syphilis treatment wtih benzathine penicillin G in adults, approximately 1 in 4 participants experienced short-lived JHR symptoms, which were associated with secondary syphilis stage, lack of HIV, and successful treatment outcomes at 6 months. These messages could be used in patient counseling.
Racial and Ethnic Survival Disparities Among Children With High-Risk Neuroblastoma: A Children's Oncology Group Report
(American Medical Association, 2025-02-03) Umaretiya, Puja J.; Naranjo, Arlene; Zhang, Fan F.; Park, Julie R.; Weiss, Brian D.; Granger, Meaghan; Desai, Ami V.; Ozkaynak, M. Fevzi; Yu, Alice L.; Aziz-Bose, Rahela; Pruitt, Sandi L.; DuBois, Steven G.; Bagatell, Rochelle; Bona, Kira; Pediatrics, School of Medicine
Importance: Whether population-based racial and ethnic survival disparities for children with high-risk neuroblastoma persist in the clinical trial setting is unknown.
Objective: To investigate racial and ethnic survival disparities among children with high-risk neuroblastoma treated on frontline clinical trials.
Design, setting, and participants: This retrospective cohort study used data from Children's Oncology Group (COG) high-risk neuroblastoma trials from January 1, 2007, to December 31, 2016, with a data freeze on June 30, 2021. Children with high-risk neuroblastoma were analyzed in 2 cohorts: induction/consolidation trial participants and post-consolidation trial participants. Statistical analyses were performed from September 2, 2021, to December 30, 2024.
Exposures: Race and ethnicity were the primary exposures, categorized as Hispanic, non-Hispanic Black, non-Hispanic other (American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), or non-Hispanic White.
Main outcomes and measures: Primary outcomes included overall survival (OS) and event-free survival (EFS) from time of trial enrollment, estimated by Kaplan-Meier methods. Associations with race and ethnicity were evaluated by log-rank tests and Cox proportional hazards regression models. Secondary outcomes included induction delays, early trial withdrawal, relapse as first event, death as first event, postrelapse OS, and early phase trial enrollment.
Results: The induction/consolidation cohort (median follow-up, 8.3 years [IQR, 6.1-9.8 years]) included 696 patients (404 males [58.1%]; 79 Hispanic patients [11.4%], 109 non-Hispanic Black patients [15.7%], 27 patients of non-Hispanic other race [3.9%], and 481 non-Hispanic White patients [69.1%]). The post-consolidation cohort (median follow-up, 7.5 years [IQR, 5.8-9.4 years]) included 935 patients (567 males [60.6%]; 87 Hispanic patients [9.3%], 145 non-Hispanic Black patients [15.5%], 41 patients of non-Hispanic other race [4.4%], and 662 non-Hispanic White patients [70.8%]). In multivariable Cox proportional hazards regression models, Hispanic children experienced significantly inferior OS (hazard ratio [HR], 1.78; 95% CI, 1.25-2.53; P = .01) on induction/consolidation studies compared with non-Hispanic White children; EFS did not differ. Non-Hispanic Black (HR, 1.54; 95% CI, 1.13-2.11) and Hispanic children (HR, 1.63; 95% CI, 1.09-2.43) experienced inferior OS on post-consolidation studies compared with non-Hispanic White children (P = .009); Hispanic children in post-consolidation studies experienced inferior EFS (HR, 1.68; 95% CI, 1.14-2.47; P = .02). Death as first event and postrelapse OS also differed by race and ethnicity.
Conclusions and relevance: This study suggests that Black and Hispanic children with high-risk neuroblastoma experienced inferior OS despite uniform planned treatment on frontline COG clinical trials. Investigated mechanisms did not completely explain survival disparities. Future evaluation of disparate treatment-related toxicities and postrelapse care as explanatory mechanisms are key next steps to promote equity.
Increased mortality from alcohol use disorder, alcohol-associated liver disease, and liver cancer from alcohol among older adults in the United States: 2000 to 2021
(Wiley, 2025) Danpanichkul, Pojsakorn; Duangsonk, Kwanjit; Tham, Ethan Kai Jun; Tothanarungroj, Primrose; Auttapracha, Thanida; Prasitsumrit, Vitchapong; Sim, Benedix; Tung, Daniel; Barba, Romelia; Wong, Robert J.; Leggio, Lorenzo; Yang, Ju Dong; Chen, Vincent L.; Noureddin, Mazen; Díaz, Luis Antonio; Arab, Juan Pablo; Wijarnpreecha, Karn; Liangpunsakul, Suthat; Medicine, School of Medicine
Background: To investigate the trends in alcohol-associated liver disease (ALD), liver cancer from alcohol, and alcohol use disorder (AUD) burden among older adults in the United States (US).
Methods: We gathered the ALD, liver cancer from alcohol, and AUD prevalence, mortality, and age-standardized rates (ASRs) from the Global Burden of Disease (GBD) Study 2021 between 2010 and 2021. We estimated the annual percent change (APC) with confidence intervals (CIs) for the burden of ALD, liver cancer from alcohol, and AUD in older adults (>70 years) in the United States. The findings were contrasted with global estimates and categorized by sex and state.
Results: In 2021, there were approximately 512,340 cases of AUD, 56,990 cases of ALD, and 4490 cases of primary liver cancer from alcohol among older adults in the United States. In contrast to declining ASRs of prevalence and mortality in the global burden, these parameters were increased in older adults in the United States. From 2000 to 2021, prevalence from AUD (APC: 0.54%, 95% CI 0.43% to 0.65%), ALD (APC + 0.54%, 95% CI 0.22% to 0.86%), and primary liver cancer from alcohol (APC 2.93%, 95% CI 2.76% to 3.11%) increased. Forty states in the United States exhibited a rise in the prevalence rates of ALD in older adults.
Conclusion: Our findings highlighted the increased prevalence and mortality of AUD, ALD, and primary liver cancer from alcohol among older adults in the United Sates, contrasting with the decline in global trends. Public health strategies on ALD, AUD, and primary liver cancer from alcohol, which targets older adults, are urgently needed.