Evaluation of a Potential Interaction Between New Regimens to Treat Hepatitis C and Warfarin.

OBJECTIVE: New regimens to treat hepatitis C virus infection have expanded the eligible patient population to include more patients receiving concurrent warfarin. The primary objective of this study was to assess whether a drug interaction occurs when these regimens are added to warfarin therapy. METHODS: This was a retrospective cohort design using a nationwide database of the Veterans Affairs Health System. Patients on warfarin therapy treated with sofosbuvir or ombitasvir, paritaprevir-ritonavir, and dasabuvir (OBV-PTV/r-DSV) from March 2014 through October 2015 were identified. The warfarin dose response was calculated using a warfarin sensitivity index (WSI) defined as the steady-state INR divided by the mean daily warfarin dose. The primary outcome was the change in WSI from hepatitis C treatment initiation to completion. RESULTS: The final sample consisted of 271 patients. The WSI decreased 23% from a mean baseline value of 0.53 to 0.39 (decrease of 0.14; 95% CI = 0.11 to 0.16; P < 0.001). OBV-PTV/r-DSV produced a significantly greater decrease than any sofosbuvir regimen. Concurrent ribavirin accounted for an additional decrease in warfarin sensitivity of -0.09 (95% CI = -0.06 to -0.12; P < 0.001). The percentage of subtherapeutic INR results increased from 26% prior to hepatitis C treatment to 58% during treatment. CONCLUSIONS: Results indicate a clinically significant reduction in warfarin dose-response when hepatitis C treatment regimens were added to warfarin. They were most profound with OBV-PTV/r-DSV. Ribavirin was associated with an additive effect. Clinicians should be aware of this potential drug interaction to closely monitor and minimize subtherapeutic levels of anticoagulation.

Suitability of computed tomography-guided biopsy specimens for subtyping and genotyping of non-small-cell lung cancer.

INTRODUCTION: Recent advances in the treatment of NSCLC highlight the importance of distinguishing NSCLC subtypes and genotypes. We aimed to determine whether histological specimens obtained from computed tomography (CT)-guided biopsy are suitable for specific subtyping and epidermal growth factor receptor (EGFR) analyses of NSCLC. PATIENTS AND METHODS: The clinicohistological data of 332 consecutive patients undergoing 352 CT-guided biopsies for lung lesions between January 2007 and December 2011 were retrospectively analyzed. Additionally, NSCLC specimens were examined for the suitability of EGFR mutational testing. RESULTS: Of 209 specimens diagnosed as NSCLC, 197 (94.3%) were specifically subtyped into adenocarcinoma (n = 164; 78.5%), squamous cell carcinoma (n = 27; 12.9%) and other subtypes (n = 6; 2.9%). The rate of NSCLC not otherwise specified (NOS) was 5.7%, and the diagnosis of NSCLC-NOS was significantly associated with the poor differentiation of cancer (adjusted odds ratio, 6.17; 95% confidence interval, 1.62-23.55; P = .008). Of 134 histological tumor specimens submitted for EGFR molecular testing, 132 (98.5%) were suitable for analyses, and 130 of them (98.5%) showed conclusive results, revealing 59.8% (n = 79) with EGFR exon mutation(s). The sensitivity, specificity, and positive and negative predictive values of CT-guided biopsy in patients with malignancy were 92.2%, 100%, 100%, and 74.1%, respectively. Six percent (n = 21) of total lung biopsies led to pneumothorax requiring chest drainage, and no procedure-related fatality was observed. CONCLUSION: Small tumor specimens obtained with CT-guided needle lung biopsy are suitable for specific subtyping and EGFR analyses of NSCLC, thus providing critical information for personalized therapy.