Using risk analysis to anticipate and mitigate failures during a hospital pharmacy relocation.

Objectives: Documented experiences of relocating hospital pharmacies are rare, but adequate preparation is vital to ensuring smooth pharmacy operation and patient safety. In the autumn of 2019, the Pharmacy of Eastern Vaud Hospitals, composed of four units (Logistics, Manufacturing, Clinical Pharmacy, and Nursing Home Supply), was relocated to a new hospital in just a few days. In this context, a failure modes, effects and criticality analysis (FMECA) was carried out before the relocation in order to anticipate any failure modes likely to affect the pharmacy's missions or patient safety during the move.

Influence of body weight and UGT2B7 polymorphism on varenicline exposure in a cohort of smokers from the general population.

Purpose: The abstinence rate to tobacco after varenicline treatment is moderate and might be partially affected by variability in varenicline concentrations. This study aimed at characterizing the sources of variability in varenicline pharmacokinetics and to relate varenicline exposure to abstinence.

Methods: The population pharmacokinetic analysis (NONMEM®) included 121 varenicline concentrations from 82 individuals and tested the influence of genetic and non-genetic characteristics on apparent clearance (CL/F) and volume of distribution (V/F).

Association of nicotine metabolism and sex with relapse following varenicline and nicotine replacement therapy.

Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine, mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of varenicline in women and in nicotine normal metabolizers phenotypically determined by nicotine-metabolite ratio. Our objective was to study the influence of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine replacement therapy and varenicline.

Prescription of Sedative Drugs During Hospital Stay: A Swiss Prospective Study.

Background: In recent years, the number of prescriptions for sedative drugs has increased significantly, as has their long-term use. Moreover, sedative use is frequently initiated during hospital stays.

Objectives: This study aimed to describe new prescriptions of sedative drugs during hospital stays and evaluate their maintenance as discharge medication.

Transition of care: A set of pharmaceutical interventions improves hospital discharge prescriptions from an internal medicine ward.

Background: Continuity of care between hospitals and community pharmacies needs to be improved to ensure medication safety. This study aimed to evaluate whether a set of pharmaceutical interventions to prepare hospital discharge facilitates the transition of care.

Methods: This study took place in the internal medicine ward and in surrounding community pharmacies.

Clinical pharmacist's role in implementing a smoking cessation intervention in a Swiss regional hospital: an exploratory study.

Background: Smoking cessation represents one of the best means of preventing smoking-related complications. In recent years, a majority of hospitals have implemented smoke-free policies, making support for smoker patients a necessary and indispensable task. The clinical pharmacist is well-positioned to provide this kind of support, given a good understanding of the medical condition and pharmacotherapy of hospitalized patients and the possibility to acquire specific smoking cessation training.

Influence of CRTC1 polymorphisms on body mass index and fat mass in psychiatric patients and the general adult population.

Importance: There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown.

Objective: To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population.

Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers.

Background: There is a high interindividual variability in cytochrome P4501A2 (CYP1A2) activity and in its inducibility by smoking, only poorly explained by known CYP1A2 polymorphisms. We aimed to study the contribution of other regulatory pathways, including transcription factors and nuclear receptors, toward this variability.

Methods: CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of them who were abstinent for 4 weeks.

Contribution of CYP2B6 alleles in explaining extreme (S)-methadone plasma levels: a CYP2B6 gene resequencing study.

Background: (S)-Methadone, metabolized mainly by CYP2B6, shows a wide interindividual variability in its pharmacokinetics and pharmacodynamics.

Methods: Resequencing of the CYP2B6 gene was performed in 12 and 35 selected individuals with high (S)-methadone plasma exposure and low (S)-methadone plasma exposure, respectively, from a previously described cohort of 276 patients undergoing methadone maintenance treatment. Selected genetic polymorphisms were then analyzed in the complete cohort.

Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension.

The 15q24.1 locus, including CYP1A2, is associated with blood pressure (BP). The CYP1A2 rs762551 C allele is associated with lower CYP1A2 enzyme activity.

Simultaneous determination of antidementia drugs in human plasma: procedure transfer from HPLC-MS to UPLC-MS/MS.

A previously developed high performance liquid chromatography mass spectrometry (HPLC-MS) procedure for the simultaneous determination of antidementia drugs, including donepezil, galantamine, memantine, rivastigmine and its metabolite NAP 226-90, was transferred to an ultra performance liquid chromatography system coupled to a tandem mass spectrometer (UPLC-MS/MS). The drugs and their internal standards ([(2)H(7)]-donepezil, [(13)C,(2)H(3)]-galantamine, [(13)C(2),(2)H(6)]-memantine, [(2)H(6)]-rivastigmine) were extracted from 250 μL human plasma by protein precipitation with acetonitrile. Chromatographic separation was achieved on a reverse phase column (BEH C18 2.

Influence of cytochrome P450 oxidoreductase genetic polymorphisms on CYP1A2 activity and inducibility by smoking.

Background: Cytochrome P4501A2 (CYP1A2) presents a high interindividual variability in its activity and also in its inducibility by smoking. Cytochrome P450 oxidoreductase (POR) is an electron transfer protein that catalyzes the activity of several cytochromes P450. We aimed to study the influence of POR genetic polymorphisms on CYP1A2 activity while smoking and after smoking cessation, as well as on CYP1A2 inducibility.

Quantification of nicotine, cotinine, trans-3'-hydroxycotinine and varenicline in human plasma by a sensitive and specific UPLC-tandem mass-spectrometry procedure for a clinical study on smoking cessation.

A sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, its metabolites cotinine and trans-3'-hydroxycotinine and varenicline in human plasma was developed and validated. Sample preparation was realized by solid phase extraction of the target compounds and of the internal standards (nicotine-d4, cotinine-d3, trans-3'-hydroxycotinine-d3 and CP-533,633, a structural analog of varenicline) from 0.5 mL of plasma, using a mixed-mode cation exchange support.

The permeability P-glycoprotein: a focus on enantioselectivity and brain distribution.

Importance Of The Field: The permeability glycoprotein (P-gp) is an important protein transporter involved in the disposition of many drugs with different chemical structures, but few studies have examined a possible stereoselectivity in its activity. P-gp can have a major impact on the distribution of drugs in selected organs, including the brain. Polymorphisms of the ABCB1 gene, which encodes for P-gp, can influence the kinetics of several drugs.