Pharmacogenomics of anti-platelet therapy: how much evidence is enough for clinical implementation?

Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function (LOF) variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Patients given clopidogrel after percutaneous coronary intervention who carry LOF variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will clinicians be able to use pharmacogenetic information in conjunction with the history, physical examination and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient.

Pharmacogenomics of anti-platelet and anti-coagulation therapy.

Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with new diagnostic targets and therapeutic strategies hold promise for more effective individualized anti-coagulation and anti-platelet therapy.

Are Patients with Psychogenic Movement Disorders More Likely to be Healthcare Workers?

BACKGROUND: Reported risk factors for the development of a psychogenic movement disorder (PMD) include young age, female gender, history of abuse, current or past psychiatric disorder, lower levels of education and socioeconomic status, and employment as a healthcare worker. Although employment in healthcare is included in several diagnostic criteria for PMD, as well as in many case series, this association has never been validated. METHODS: Using the University of Maryland Movement Disorder Database (UMMDD), we identified PMD cases, as well as patients with isolated focal dystonia as controls. An experienced movement disorder specialist diagnosed all patients, and all cases met criteria for clinically established PMD. Demographic and occupational histories were obtained from medical records and were supplemented by telephone interviews. PMD cases and controls were compared using t tests/χ2 tests. RESULTS: Controls (n = 148) were older than PMD cases (n = 132), with an average age of 61.4 and 52.1 years, respectively (P < 0.001); there were no significant differences between groups with respect to gender, education level, and ethnicity. The proportion of healthcare workers was not significantly different between PMD cases and controls (25% of PMD cases vs. 20% of controls; P = 0.28). CONCLUSIONS: In contrast to traditional teaching, this investigation demonstrates that in our patient population, patients with a PMD were no more likely to be employed as healthcare workers than patients with isolated focal dystonia. This study calls into question the use of employment in healthcare as a reliable criterion to support the diagnosis of PMD.