Value of Pharmacogenetic Testing Assessed with Real-World Drug Utilization and Genotype Data.

Implementation of pharmacogenetic testing in clinical care has been slow and with few exceptions is hindered by the lack of real-world evidence on how to best target testing. In this retrospective register-based study, we analyzed a nationwide cohort of 1,425,000 patients discharged from internal medicine or surgical wards and a cohort of 2,178 university hospital patients for purchases and prescriptions of pharmacogenetically actionable drugs. Pharmacogenetic variants were obtained from whole genome genotype data for a subset (n = 930) of the university hospital patients. We investigated factors associated with receiving pharmacogenetically actionable drugs and developed a literature-based cost-benefit model for pre-emptive pharmacogenetic panel testing. In a 2-year follow-up, 60.4% of the patients in the nationwide cohort purchased at least one pharmacogenetically actionable drug, most commonly ibuprofen (25.0%) and codeine (19.4%). Of the genotyped subset, 98.8% carried at least one actionable pharmacogenetic genotype and 23.3% had at least one actionable gene-drug pair. Patients suffering from musculoskeletal or cardiovascular diseases were more prone to receive pharmacogenetically actionable drugs during inpatient episode. The cost-benefit model included frequently dispensed drugs in the university hospital cohort, comprising ondansetron (19.4%), simvastatin (7.4%), clopidogrel (5.0%), warfarin (5.1%), (es)citalopram (5.3%), and azathioprine (0.5%). For untargeted pre-emptive pharmacogenetic testing of all university hospital patients, the model indicated saving €17.49 in direct healthcare system costs per patient in 2 years without accounting for the cost of the test itself. Therefore, it might be reasonable to target pre-emptive pharmacogenetic testing to patient groups most likely to receive pharmacogenetically actionable drugs.

A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants.

Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth.