Cholesterol reduction from statin therapy has been one of the greatest public health successes in modern medicine. Simvastatin is among the most commonly used prescription medications. A non‐synonymous coding single‐nucleotide polymorphism (SNP), rs4149056, in SLCO1B1 markedly increases systemic exposure to simvastatin and the risk of muscle toxicity. This guideline explores the relationship between rs4149056 (c.521T>C, p.V174A) and clinical outcome for all statins. The strength of the evidence is high for myopathy with simvastatin. We limit our recommendations accordingly. Clinical Pharmacology & Therapeutics (2012); 92 1, 112–117. doi:10.1038/clpt.2012.57

Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% [95% confidence interval (CI), 72 to 98%], and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR–based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting.

Cytochrome P-450 2C9 (CYP2C9) polymorphisms (CYP2C9*2 and CYP2C9*3) reduce the clearance of warfarin, increase the risk of bleeding, and prolong the time to stable dosing. Whether prospective use of a retrospectively developed algorithm that incorporates CYP2C9 genotype and nongenetic factors can ameliorate the propensity to bleeding and delay in achieving a stable warfarin dose is unknown. We initiated warfarin therapy in 48 orthopedic patients tailored to the following variables: CYP2C9 genotype, age, weight, height, gender, race, and use of simvastatin or amiodarone. By using pharmacogenetics-based dosing, patients with a CYP2C9 variant achieved a stable, therapeutic warfarin dose without excessive delay. However compared to those without a CYP2C9 variant, patients with a variant continued to be at increased risk (hazard ratio 3.6, 95% confidence interval 1.4–9.5, p = 0.01) for an adverse outcome (principally INR > 4), despite pharmacogenetics-based dosing. There was a linear relationship (R² = 0.42, p < 0.001) between the pharmacogenetics-predicted warfarin doses and the warfarin maintenance doses, prospectively validating the dosing algorithm. Prospective, perioperative pharmacogenetics-based dosing of warfarin is feasible; however, further evaluation in a randomized, controlled study is recommended.