Browsing by Author "Ross, David"

Now showing 1 - 3 of 3
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    Core implementation strategies for improving cirrhosis care in the Veterans Health Administration
    (Wolters Kluwer, 2022) Yakovchenko, Vera; Morgan, Timothy R.; Miech, Edward J.; Neely, Brittney; Lamorte, Carolyn; Gibson, Sandra; Beste, Lauren A.; McCurdy, Heather; Scott, Dawn; Gonzalez, Rachel; Park, Angela; Powell, Byron J.; Bajaj, Jasmohan S.; Dominitz, Jason A.; Chartier, Maggie; Ross, David; Chinman, Matthew J.; Rogal, Shari S.; Emergency Medicine, School of Medicine
    Background and aims: The Veterans Health Administration (VHA) provides care for more than 80,000 veterans with cirrhosis. This longitudinal, multimethod evaluation of a cirrhosis care quality improvement program aimed to (1) identify implementation strategies associated with evidence-based, guideline-concordant cirrhosis care over time, and (2) use qualitative interviews to operationalize strategies for a manualized intervention. Approach and results: VHA providers were surveyed annually about the use of 73 implementation strategies to improve cirrhosis care in fiscal years 2018 (FY18) and 2019 (FY19). Implementation strategies linked to guideline-concordant cirrhosis care were identified using bivariate statistics and comparative configurational methods. Semistructured interviews were conducted with 12 facilities in the highest quartile of cirrhosis care to specify the successful implementation strategies and their mechanisms of change. A total of 106 VHA facilities (82%) responded at least once over the 2-year period (FY18, n = 63; FY19, n = 100). Facilities reported using a median of 12 (interquartile range [IQR] 20) implementation strategies in FY18 and 10 (IQR 19) in FY19. Of the 73 strategies, 35 (48%) were positively correlated with provision of evidence-based cirrhosis care. Configurational analysis identified multiple strategy pathways directly linked to more guideline-concordant cirrhosis care. Across both methods, a subset of eight strategies was determined to be core to cirrhosis care improvement and specified using qualitative interviews. Conclusions: In a national cirrhosis care improvement initiative, a multimethod approach identified a core subset of successful implementation strategy combinations. This process of empirically identifying and specifying implementation strategies may be applicable to other implementation challenges in hepatology.
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    Discovery and characterization of small molecules that target the Ral GTPase
    (Nature Publishing Group, 2014-11-20) Yan, Chao; Liu, Degang; Li, Liwei; Wempe, Michael F.; Guin, Sunny; Khanna, May; Meier, Jeremy; Hoffman, Brenton; Owens, Charles; Wysoczynski, Christina L.; Nitz, Matthew D.; Knabe, Eric W.; Brautigan, David L.; Paschal, Bryce M.; Schwartz, Martin A.; Jones, David; Ross, David; Meroueh, Samy O.; Theodorescu, Dan; Department of Biochemistry & Molecular Biology, IU School of Medicine
    The Ras-like GTPases RalA and B are important drivers of tumor growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here, we used protein structure analysis and virtual screening to identify drug-like molecules that bind a site on the GDP-form of Ral. Compounds RBC6, RBC8 and RBC10 inhibited Ral binding to its effector RalBP1, Ral-mediated cell spreading in murine fibroblasts and anchorage-independent growth of human cancer cell lines. Binding of RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasma resonance and 15N-HSQC NMR. RBC8 and BQU57 show selectivity for Ral relative to Ras or Rho and inhibit xenograft tumor growth similar to depletion of Ral by siRNA. Our results show the utility of structure-based discovery for development of therapeutics for Ral-dependent cancers.
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    Variation in statin prescription among veterans with HIV and known atherosclerotic cardiovascular disease
    (Elsevier, 2022) Erqou, Sebhat; Papaila, Alexa; Halladay, Christopher; Ge, Augustus; Liu, Michael A.; Jiang, Lan; Lally, Michelle; Menon, Anupama; Shah, Nishant R.; Miech, Edward; Virani, Salim S.; Zullo, Andrew R.; Shireman, Theresa I.; Longenecker, Christopher T.; Ross, David; Sullivan, Jennifer L.; Wu, Wen-Chih; Rudolph, James L.; Emergency Medicine, School of Medicine
    Background: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. Objective: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. Methods: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. Results: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. Conclusion: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.