Core implementation strategies for improving cirrhosis care in the Veterans Health Administration.

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.

Hepatitis C Care in the Department of Veterans Affairs: Building a Foundation for Success.

The Department of Veterans Affairs (VA) has made significant progress in treating hepatitis C virus, experiencing more than a 75% reduction in veterans remaining to be treated since the availability of oral direct-acting antivirals. Hepatitis C Innovation Teams use lean process improvement and system redesign, resulting in practice models that address gaps in care. The key to success is creative improvements in veteran access to providers, including expanded use of nonphysician providers, video telehealth, and electronic technologies. Population health management tools monitor and identify trends in care, helping the VA tailor care and address barriers.

Disulfiram induces apoptosis in human melanoma cells: a redox-related process.

Melanoma is highly resistant to conventional chemotherapy. We have demonstrated that redox regulation in melanoma cells is aberrant, and redox-modulating agents can induce cell apoptosis. We have currently explored the effect of disulfiram (DSF), a member of the dithiocarbamate family, on apoptosis of melanoma cells in vitro. Human metastatic melanoma cells c81-46A, c81-61, and c83-2C were treated with DSF and apoptosis measured. DSF, at a dose of 25-50 ng/ml, consistently caused a 4-6-fold increase in apoptosis. The same dose of DSF did not significantly affect apoptosis in melanocytes. Coincubation of N-acetyl-cysteine reversed the DSF-induced apoptosis. Buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl-cysteine synthetase, as a single agent caused a approximately 2-fold increase in apoptosis when incubated with melanoma cells for 4 days. BSO slightly enhanced the level of apoptosis induced by DSF (4-10% higher than DSF alone). Intracellular glutathione was remarkably depleted with BSO treatment. DSF did not cause glutathione depletion; however, the ratio of reduced and oxidized glutathione was significantly decreased (14% of control), and N-acetyl-cysteine partially restored the ratio to 30% of control. There was a transient (2-fold) elevation of intracellular superoxide level after 24 h of DSF treatment (before the overt apoptosis). The intracellular H2O2 level progressively decreased with time. DSF decreased the mitochondrial membrane polarization in a time-dependent manner, and there was a significant inverse correlation between apoptosis and mitochondrial membrane polarization. We propose that DSF-induced apoptosis is redox related but involves a different mechanism from BSO-induced apoptosis in tumor cells. Our findings have provided new data for additional understanding of drug-induced apoptosis in melanoma cells and suggests an alternative therapeutic approach to melanoma.