Browsing by Author "Szatrowski, Austin"

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    Computational integration and meta-analysis of abandoned cardio-(vascular/renal/metabolic) therapeutics discontinued during clinical trials from 2011 to 2022
    (Frontiers, 2023-02) Zeng, Carisa; Lee, Yoon Seo; Szatrowski, Austin; Mero, Deniel; Khomtchouk, Bohdan B.; Biohealth Informatics, School of Informatics and Computing
    Cardiovascular/renal/metabolic (CVRM) diseases collectively comprise the leading cause of death worldwide and disproportionally affect older demographics and historically underrepresented minority populations. Despite these critical unmet needs, pharmaceutical research and development (R&D) efforts have historically struggled with high drug failure rates, low approval rates, and other challenges. Drug repurposing is one approach to recovering R&D costs and meeting unmet demands in therapeutic markets. While there are multiple approaches to conducting drug repurposing, we recognize the importance of bringing together and consolidating discontinued drug information to help identify prospective repurposing candidates. In this study, we have harmonized and integrated information on all relevant CVRM drug assets from U.S. Securities and Exchange Commission (SEC) filings, clinical trial records, PharmGKB, Open Targets, and other platforms. A list of existing therapeutics discontinued or shelved by pharmaceutical/biotechnology companies in 2011-2022 were manually curated and interpreted for insights using information on each drug's genetic target, mechanism of action (MOA), clinical indication, and R&D information including highest phase of clinical development, year of discontinuation, previous repurposing attempts (if any), and other actionable metadata. This study also summarizes the profiles of CVRM drugs discontinued within the past decade and identifies the limitations of publicly available information on discontinued drug assets. The constructed database could serve as a tool for identifying candidates for drug repurposing and developing query methods for collecting R&D information.
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    HDL Cholesterol Is Remarkably Cardioprotective Against Coronary Artery Disease in Native Hawaiians and Pacific Islanders
    (Elsevier, 2025-05-02) Szatrowski, Austin; Maggio, Zane; Khomtchouk, Bohdan; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and Engineering
    Background: High-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiometabolic risk and exhibits nonlinear effects at extreme levels. Cardiometabolic diseases are a leading cause of death and are particularly prevalent among Native Hawaiian and Pacific Islanders (NHPIs). Objectives: This study characterizes HDL-C's association with coronary artery disease (CAD), major adverse cardiovascular events (MACE), and type 2 diabetes (T2D) in NHPIs compared to the general population. Methods: Using electronic health record data from the National Institutes of Health All of Us Research Program, we applied Cox proportional hazards models to compare HDL-C's protective effects on CAD, MACE, and T2D between 261 NHPIs and the remaining cohort (n = 188,802). Models were adjusted for key confounders, and restricted cubic splines were used to assess nonlinear risk dynamics. Results: Tracking individuals across 10,534,661 person-years (mean age 55.7 ± 15.8 years, 38% male), HDL-C was more strongly associated with reduced CAD risk in NHPIs (HR: 0.32; 95% CI: 0.19-0.54) than in the general cohort (HR: 0.57; 95% CI: 0.56-0.58). A marginally stronger association was observed for MACE (NHPI HR: 0.40; 95% CI: 0.23-0.71 vs general HR: = 0.54; 95% CI: 0.53-0.56), while T2D associations were similar. Spline analysis indicated that low HDL-C increases risk for both CAD and T2D in NHPIs. Conclusions: HDL-C's protective role against cardiometabolic diseases is more pronounced in NHPIs, particularly for CAD. These findings support further investigation into tailored clinical assessments for this population.
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    The Molecular-Social-Genetic Determinants of Cardiovascular Health in Pacific Islanders
    (Elsevier, 2024-06-18) Lee, Yoon Seo; Lord, George; Szatrowski, Austin; Maggio, Zane A.; Knutson, Andrew Kekūpaʻa; Hedges, Jerris R.; Khomtchouk, Bohdan B.; Medicine, School of Medicine