A pilot study of the implementation of pharmacogenomic pharmacist initiated pre-emptive testing in primary care.

Despite the nationwide availability of pharmacogenomic (PGx) guidelines in electronic medication surveillance systems in The Netherlands, PGx guided prescribing is still uncommon in primary care. We set out to investigate the adoption of pharmacist initiated PGx testing in primary care. Community pharmacists were offered a free PGx test covering 40 variants in 8 genes to test patients receiving an incident prescription (IRx) of a selection of 10 drugs. Results of the PGx test along with predicted phenotypes and a therapeutic recommendation based on the Dutch Pharmacogenetics Working Group (DPWG) guidelines were transferred to the pharmacist and physician. Adoption was defined as the percentage of eligible patients that received genotyping. From November 2014-July 2016, 200 patients were included with an adoption of 18.0%. Of the included patients 57.5% received an IRx for atorvastatin, 14.5% started with simvastatin and 28.0% received an IRx for amitriptyline, (es)citalopram, nortriptyline, or venlafaxine. 90% of the patients carried at least one actionable PGx test result in the selected PGx-panel. In 31.0% of the incident prescriptions a combination between a drug with a known gene-drug interaction and an actionable genotype was present and a therapeutic recommendation was provided. The provided recommendations were accepted by the clinicians in 88.7% of the patients. Pharmacist initiated implementation of PGx in primary care is feasible, and the frequency of actionable gene-drug interactions for the selected drugs is high.

Stronger T-Cell Alloreactivity and Diminished Suppressive Capacity of Peripheral Regulatory T Cells in Infertile Women Undergoing In Vitro Fertilization.

PROBLEM: Increasing evidence suggests modulation of the maternal immune response to be essential for successful pregnancy. We studied the immunophenotypic profile and function of peripheral blood T lymphocytes in infertile women undergoing in vitro fertilization (IVF) and fertile control population. METHOD: We collected peripheral blood mononuclear cells (PBMC) from infertile patients with recurrent implantation failure (RIF), infertile patients with successful IVF (IVFs), and normal fertile women. Cells were phenotypically analyzed, and the proliferative response and cytokine production were studied in mixed lymphocyte cultures (MLC), using lymphocytes of the own partner, or a third-party male as stimulators cells. To examine the suppressive capacity of regulatory regulatory T cells (Tregs), we performed MLC studies with a CD45(+) fraction depleted for CD4(+) CD25(bright) T cells. RESULTS: No significant differences in proportions of subsets of circulating T lymphocytes were observed. The proliferative allo-immune response of PBMC of IVF women (RIF and IVFs) was significantly higher, with higher production of T-helper cells (Th1) and Th2 cytokines, compared to the fertile women. This difference in proliferation and cytokine production was associated with a diminished suppressive capacity of Tregs in these women. CONCLUSION: The higher allo-immune response of the IVF women compared to fertile women might be the result of a diminished suppressive capacity of Tregs and emphasizes the important role of Tregs during conception.