Validation of a novel direct method to determine reduced adherence to atorvastatin therapy.

AIMS: Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut-off values based on the sum of atorvastatin and its major metabolites in the blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values. METHODS AND RESULTS: The pharmacokinetic study included 60 participants treated with atorvastatin 20 mg (N = 20), 40 mg (N = 20), and 80 mg (N = 20). Atorvastatin was then stopped and blood samples collected from day zero to day four. Quantification of the parent drug and its metabolites in blood plasma was performed with a liquid chromatography-tandem mass spectrometry assay. The cut-off values for reduced adherence were validated and optimized by calculating diagnostic sensitivity and specificity. Our candidate cut-off value of dose-normalized six-component sum of atorvastatin plus metabolites <0.10 nM/mg provided a sensitivity of 97% and a specificity of 93% for detecting ≥2 omitted doses. An optimized cut-off <0.062 nM/mg provided a sensitivity of 90% and a specificity of 100%. An alternative simplified two-component metabolite sum with a cut-off value <0.05 nM/mg provided a sensitivity of 98% and a specificity of 76%. An optimized cut-off <0.02 nM/mg provided a sensitivity of 97% and a specificity of 98%. CONCLUSION: This validation study confirms that our direct method discriminates reduced adherence from adherence to atorvastatin therapy with high diagnostic accuracy. The method may improve lipid management in clinical practice and serve as a useful tool in future studies.

The comparison of 2-dimensional with 3-dimensional hepatic visualization in the clinical hepatic anatomy education.

OBJECTIVE: To determine whether 2-dimensional or 3-dimensional hepatic visualization is better for the medical students to be used while studying the clinical hepatic anatomy. MATERIAL AND METHODS: Twenty-nine patients who underwent surgical intervention due to focal hepatic pathology at the Department of General Surgery, University of Heidelberg, and at Clinics of Santariskes, Vilnius University Hospital were included in the retrospective cohort study. Before the surgical intervention, the computed tomography (CT) liver scan and 3-dimensional (3D) hepatic visualization were performed. A total of 58 2-dimensional and 3-dimensional digital liver images, mixed up in random sequence not to follow each other with a specially designed questionnaire, were presented to the students of Faculty of Medicine, Vilnius University. Their aim was to determine tumor-affected liver segments, to plan which liver segments should be resected, and to predict anatomical difficulties for liver resection. Results were compared with the data of real operation. RESULTS: The students achieved better results for tumor localization analyzing 3D liver images vs. CT scans. This was especially evident determining the localization of tumor in segments 5, 6, 7, and 8 (P<0.05). Furthermore, the results of proposed extent of liver resection have been found to be better with 3D visualization (mean+/-SD - 0.794+/-0.175) in comparison with CT scans (mean+/-SD - 0.670+/-0.200), (P<0.001). CONCLUSIONS: Computer-generated 3D visualizations of the liver images helped the medical students to determine the tumor localization and to plan the prospective liver resection operations more precisely comparing with 2D visualizations. Computer-generated 3D visualization should be used as a means of studying liver anatomy.