Admission to intensive care: A qualitative study of triage and its determinants.

Objective: To examine physicians' decision making and its determinants about admission to intensive care.

Data Sources/study Setting: ICU physicians (n = 12) and internists (n = 12) working in a Swiss tertiary care hospital.

Study Design: We conducted in-depth interviews.

[Clinical pharmacology of medical cannabinoids in chronic pain].

In Switzerland, medical cannabinoids can be prescribed under compassionate use after special authorization in justified indications such as refractory pain. Evidence of efficacy in pain is limited and the clinical benefit seems to be modest. Their drug-drug interactions (DDI) profile is poorly documented.

Prioritization methodology for the monitoring of active pharmaceutical ingredients in hospital effluents.

The important number of active pharmaceutical ingredients (API) available on the market along with their potential adverse effects in the aquatic ecosystems, lead to the development of prioritization methods, which allow choosing priority molecules to monitor based on a set of selected criteria. Due to the large volumes of API used in hospitals, an increasing attention has been recently paid to their effluents as a source of environmental pollution. Based on the consumption data of a Swiss university hospital, about hundred of API has been prioritized following an OPBT approach (Occurrence, Persistence, Bioaccumulation and Toxicity).

Drug-related problems identification in general internal medicine: The impact and role of the clinical pharmacist and pharmacologist.

Background: Patients admitted to general internal medicine wards might receive a large number of drugs and be at risk for drug-related problems (DRPs) associated with increased morbidity and mortality. This study aimed to detect suboptimal drug use in internal medicine by a pharmacotherapy evaluation, to suggest treatment optimizations and to assess the acceptance and satisfaction of the prescribers.

Methods: This was a 6-month prospective study conducted in two internal medicine wards.

Providing Quality Therapeutics in Switzerland: Role of the Stakeholders and Recent Incentives for Further Improvements.

Quality therapeutics play an important role in Switzerland's health care and economy. Switzerland holds a key position in the world of research and development, as well as in drug production. Recently, new emphasis has been placed on promoting clinical research and maintaining Switzerland's position as a center of excellence in the field.

P-glycoprotein: a clue to vitamin K antagonist stabilization.

Background: Acenocoumarol is a vitamin K antagonist used in some European countries. As warfarin, this drug is characterized by a narrow therapeutic index and a large interindividual variability.

Aim: The objective of this study was to assess the involvement of ABCB1 polymorphisms on acenocoumarol treatment.

Doctors' decisions when faced with contradictory patient advance directives and health care proxy opinion: a randomized vignette-based study.

Context: Sometimes a written advance directive contradicts the opinion of a health care proxy. How this affects doctors' decision making is unknown.

Objectives: To quantify the influence of contradictory instructions on doctors' decisions.

Monitoring white blood cell count in adult patients with schizophrenia who are taking clozapine: a cost-effectiveness analysis.

Background: Long-term monitoring of white blood cell count is compulsory in patients taking clozapine, although the incidence of drug-induced agranulocytosis is lower than previously expected. The cost-effectiveness of this monitoring is unknown. We aimed to assess the cost-effectiveness of various strategies to monitor white blood cell count in adult patients with schizophrenia taking clozapine.

Volunteers trained in palliative care at the hospital: an original and dynamic resource.

Objective: Volunteers trained in palliative care are increasingly present in acute care units in general hospitals. Nevertheless, there still are few available data on this topic, especially concerning the integration of volunteers outside the palliative structures. Our present study aimed to describe the experience of volunteers trained in palliative care in the context of a primary care hospital.

Central pain sensitization, COMT Val158Met polymorphism, and emotional factors in fibromyalgia.

Unlabelled: Neurobiological evidence points to altered central nervous system processing of nociceptive stimuli in fibromyalgia. Enzymes like catechol-O-methyl-transferase (COMT) are involved in the elimination of catecholamines playing a possible role in central sensitization and pain. We used quantitative sensory testing to evidence central sensitization in fibromyalgia patients and test whether COMTVal158Met polymorphism, associated with a reduction in enzyme activity, plays a role in sensitized patients.

Drug-induced long QT in adult psychiatric inpatients: the 5-year cross-sectional ECG Screening Outcome in Psychiatry study.

Objective: The authors aimed to determine the prevalence of drug-induced long QT at admission to a public psychiatric hospital and to document the associated factors using a cross-sectional approach.

Method: All ECG recordings over a 5-year period were reviewed for drug-induced long QT (heart-rate corrected QT ≥500 ms and certain or probable drug imputability) and associated conditions. Patients with drug-induced long QT (N=62) were compared with a sample of patients with normal ECG (N=143).

Dual reuptake inhibitor milnacipran and spinal pain pathways in fibromyalgia patients: a randomized, double-blind, placebo-controlled trial.

Background: Investigations based on quantitative sensory testing have consistently shown evidence of allodynia in fibromyalgia syndrome (FMS) patients involving both the spinal and supraspinal pain regulatory systems. Functional imaging studies have demonstrated enhanced neural activities in pain-related brain areas as well as impairment of pain inhibition in the descending nociceptive regulatory system. A higher state of excitability of spinal nociceptive neurons as evidenced by lowered nociceptive flexion reflex R-III (NFR) threshold was reported for FMS patients.

Patented drug extension strategies on healthcare spending: a cost-evaluation analysis.

Background: Drug manufacturers have developed "evergreening" strategies to compete with generic medication after patent termination. These include marketing of slightly modified follow-on drugs. We aimed to estimate the financial impact of these drugs on overall healthcare costs and also to examine the impact of listing these drugs in hospital restrictive drug formularies (RDFs) on the healthcare system as a whole ("spillover effect").

Impact of advance directives and a health care proxy on doctors' decisions: a randomized trial.

Context: Advance directives or proxy designations are widely recommended, but how they affect doctors' decision making is not well known.

Objectives: The aim of this study was to quantify the influence of advance directives and proxy opinions on doctors' decisions.

Methods: We mailed to all the generalists and internists in French-speaking Switzerland (N = 1962) three vignettes describing difficult decisions involving incapacitated patients.

Evidence of drug-drug interactions through uptake and efflux transport systems in rat hepatocytes: implications for cellular concentrations of competing drugs.

For drugs with hepatobiliary transport across hepatocytes, the interplay between uptake and efflux transporters determines hepatic concentrations of drugs, but the evolution over time of these concentrations is difficult to measure in humans other than with magnetic resonance imaging contrast agents in the liver. Gadobenate dimeglumine (BOPTA) is a contrast agent used in liver magnetic resonance imaging that enters into human hepatocytes through organic anion transporting polypeptides (OATP) and exits unchanged into bile through the multiple resistance-associated protein 2 (MRP2). Rifampicin (RIF) is transported by the same membrane proteins and may compete with BOPTA for hepatic uptake.

Role of P-glycoprotein in the uptake/efflux transport of oral vitamin K antagonists and rivaroxaban through the Caco-2 cell model.

Vitamin K antagonists (VKAs) are prescribed worldwide and remain the oral anticoagulant of choice. These drugs are characterized by a narrow therapeutic index and a large inter- and intra-individual variability. P-glycoprotein could contribute to this variability.

Impact of CYP2C9 polymorphisms on the vulnerability to pharmacokinetic drug-drug interactions during acenocoumarol treatment.

Aim: The objective of this study was to investigate the impact of CYP2C9 polymorphisms and drug-drug interactions on the risk of overanticoagulation in patients treated with acenocoumarol, a vitamin K antagonist.

Materials & Methods: A prospective observational study was performed on patients starting acenocoumarol (n = 115). CYP2C9 genotypes were assessed.

Intraocular penetration of penciclovir after oral administration of famciclovir: a population pharmacokinetic model.

Objectives: We developed a population model that describes the ocular penetration and pharmacokinetics of penciclovir in human aqueous humour and plasma after oral administration of famciclovir.

Methods: Fifty-three patients undergoing cataract surgery received a single oral dose of 500 mg of famciclovir prior to surgery. Concentrations of penciclovir in both plasma and aqueous humour were measured by HPLC with fluorescence detection.

Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain model in mice: a pharmacokinetic-pharmacodynamic study.

Facilitation of spinal GABAergic inhibition with benzodiazepines (BZDs) reverses pain sensitization in animals; however, the use of BZDs in man is limited by their sedative effect. The antihyperalgesic effects of GABA(A) agonists are mediated by GABA(A) receptors containing α2 subunits, whereas sedation is linked to α1 subunit-containing receptors. α2 and α3 selective GABA(A) receptor modulators have been tested in animals but are not yet available for use in human beings.

Pharmacokinetic interaction between prasugrel and ritonavir in healthy volunteers.

The new anti-aggregating agent prasugrel is bioactivated by cytochromes P450 (CYP) 3A and 2B6. Ritonavir is a potent CYP3A inhibitor and was shown in vitro as a CYP2B6 inhibitor. The aim of this open-label cross-over study was to assess the effect of ritonavir on prasugrel active metabolite (prasugrel AM) pharmacokinetics in healthy volunteers.

Validation of the simplified UVB model to assess the pharmacodynamics of analgesics in healthy human volunteers.

A pharmacokinetic/pharmacodynamic, randomized, crossover, placebo-controlled study was conducted in healthy human volunteers with the primary objective of exploring the existence of a positive interaction between paracetamol 1 g and ketorolac 20 mg intravenously on experimental pain models. Further, the simplified UVB model was validated as a screening tool for analgesics or a combination of analgesics in clinical drug development. It was observed that the UVB irradiation induced primary hyperalgesia, evidenced by significant decreases of the heat pain threshold from (mean ± SD) 46.

Transcriptional regulation of CYP2C19 and its role in altered enzyme activity.

Cytochrome P450 2C19 (CYP2C19) is involved in the metabolism of several drugs that are currently in clinical use. The gene encoding CYP2C19 is polymorphic with the existence of different alleles resulting in altered enzyme activity. In addition, CYP2C19 activity is also dependent on its basal expression levels determined by the transcriptional regulation.

[Atypical femoral fracture associated with the use of bisphosphonates, an adverse drug reaction not to be missed].

Atypical femur fractures represent a new disease entity associated with the use of oral bisphosphonates. This review summarizes the current understanding of this phenomenon. These fractures are usually transverse, affecting the proximal third of the femoral shaft.