Feasibility of pharmacy-initiated pharmacogenetic screening for CYP2D6 and CYP2C19

PURPOSE: Our purpose was to investigate the feasibility of pharmacy-initiated pharmacogenetic (PGt) screening in primary care with respect to patient willingness to participate, quality of DNA collection with saliva kits, genotyping, and dispensing data retrieved from the pharmacy. METHODS: Polypharmacy patients aged >60 years who used at least one drug with Anatomical Therapeutic Chemical (ATC) code N06AA01-N06AX19 (antidepressants), A02BC01-A02BC05 (proton-pump inhibitors), N05AA01-N05AH04 (antipsychotics), or C07AB02 (metoprolol) in the preceding 2 years were randomly selected. DNA was collected with saliva kits and genotyped for CYP2D6 and CYP2C19 with the AmpliChip. Pharmacy dispensing records were retrieved and screened for drugs interacting with the patient's CYP2D6 and CYP2C19 genotype by using the evidence-based PGt guidelines from the Dutch Pharmacogenetics Working Group. RESULTS: Out of the 93 invited patients, 54 (58.1%) provided informed consent. Nine saliva samples (16.7%) contained too little DNA. Call rates for CYP2D6 and CYP2C19 were 93.3% and 100%, respectively. Frequencies of genotype-predicted phenotype were 2.4%, 38.1%, 54.8%, and 4.8% for CYP2D6 poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), and ultrarapid metabolizers (UM) respectively. For CYP2C19 genotype-predicted phenotype, frequencies were 2.2%, 15.6%, and 82.2% for PM, IM, and EM, respectively. CONCLUSIONS: This study shows that pharmacy-initiated PGt screening is feasible for a primary care setting

Laser annealing of amorphous NiTi shape memory alloy thin films to locally induce shape memory properties

We present the results of a crystallization study on NiTi shape memory thin films in which amorphous films are annealed by ascanning laser. This technique has the advantage that shape memory properties can be spatially distributed as required by the application.A kinetics study shows that nucleation of the crystalline phase occurs homogenously in the films. Consequently, the laserannealing process produces polycrystalline films with a random crystallographic texture. The crystallized films have a uniformmicrostructure across the annealed areas. The material in the crystalline regions transforms reversibly to martensite on cooling fromelevated temperature and stress measurements show that a significant recovery stress is achieved in the films upon transformation

Global digital image correlation for pressure deflected membranes

Bulge testing is known for its ability to quantify the mechanical behavior of homogeneous thin membranes. In this method the measured quantities are related to the averaged stress and strain using bulge equations that only exist for a very limited set of membrane geometries. A novel 3D Digital Image Correlation (DIC) method is proposed to directly measure the strain and curvature elds without using any closed form approximation of the deformation kinematics. Importantly, for membranes under pressure, the stress is directly related to the curvature

Full-field bulge testing using global digital image correlation

The miniature bulge test is an acknowledged method for characterizing freestanding thin films. Nevertheless, some discrepancies in the quantitative results from such tests can be found in literature, explained in part by erroneous assumptions in the analytical description used to compute the global stress and strain from the membrane pressure and deflection. In this research, a new method is presented which renders the analytical description obsolete. A specialized Global Digital Image Correlation technique on high resolution, confocal microscopy, surface height maps of bulged membranes, has been developed. This method is able to capture full-field continuous deformation maps, from which local strain maps are computed. Additionally, local stress maps are derived from full-field curvature maps and the applied pressure. The local stress-strain maps allow the method to be used on inhomogeneous, anisotropic membranes as well as on exotic membrane shapes