Numerical and asymptotic solutions of generalised Burgers’ equation

The generalised Burgers’ equation has been subject to a considerable amount of research on how the equation should behave according to asymptotic analysis, however there has been limited research verifying the asymptotic analysis. In order to verify the asymptotic analysis, this paper aims to run long time and detailed numerical simulations of Burgers’ equation by employing suitable rescalings of Burgers’ equation. It is hoped that this technique will make it possible to notice subtle changes in the shock structure which would otherwise be impossible to observe. The main aim of this paper is to validate the numerical methods used in order to allow further research into shock evolution where further relaxation effects will be included

Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model

Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model.Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective.Both baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit

Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands

Aims: to investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands. Materials & methods: A decision-analytic Markov model was used to analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and acenocoumarol versus clinical dosing. Results: Pharmacogenetic dosing increased costs by €33 and QALYs by 0.001. The incremental cost-effectiveness ratios (ICERs) were €28,349 and €24,427 per QALY gained for phenprocoumon and acenocoumarol respectively. At a willingness to pay threshold of €20,000 per QALY, the pharmacogenetic dosing algorithm was not likely to be cost-effective compared to the clinical dosing algorithm. Conclusions: Pharmacogenetic dosing improves health only slightly when compared with clinical dosing. However, availability of low-cost genotyping would make it a cost-effective option