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). In addition, an Environmental Risk Assessment (ERA) allowed prioritizing API based on predicted concentrations and environmental toxicity data found in the literature for 71 compounds. Both prioritization approaches were compared. OPBT prioritization results highlight the high concern of some non steroidal anti-inflammatory drugs and antiviral drugs, whereas antibiotics are revealed by ERA as potentially problematic to the aquatic ecosystems. Nevertheless, according to the predicted risk quotient, only the hospital fraction of ciprofloxacin represents a risk to the aquatic organisms. Some compounds were highlighted as high-priority with both methods: ibuprofen, trimethoprim, sulfamethoxazole, ritonavir, gabapentin, amoxicillin, ciprofloxacin, raltegravir, propofol, etc. Analyzing consumption data and building prioritization lists helped choosing about 15 API to be monitored in hospital wastewaters. The API ranking approach adopted in this study can be easily transposed to any other hospitals, which have the will to look at the contamination of their effluents.

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. In particular, the difficulties and the benefits of this specific position were evaluated according to volunteers' own perceptions and words. METHOD: We employed a qualitative method. Various aspects of the volunteer's role were explored by means of semistructured questions, addressing their activity, their motivations, and their feelings. Participants were volunteers (n = 19) trained in palliative care and working at a university hospital. After giving written consent, they completed the semistructured questionnaire at home. Content analysis was used to identify the main categories of answers and the principal themes reported by the volunteers. RESULTS: The main difficulties were related to uncertainty of the context. As every situation is different, volunteers could not define their role once and for all. However, they derived great satisfaction from their activity. A supporting frame and a good balance between constraints and autonomy were facilitating factors. Besides, the complexity related to the context contributed to make the position valuable and challenging. SIGNIFICANCE OF RESULTS: Integrating a voluntary service in a primary care hospital is partly based on active participation of the volunteers in developing their position in a more adequate way. In return, this relative autonomy implies a rigorous and supportive attitude from the institution.

[Clinical pharmacology of medical cannabinoids in chronic pain]. / Cannabinoïdes médicaux dans les douleurs chroniques: aspects pharmacologiques.

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. Cytochromes P450 (CYP) 2C9 and 3A4 are involved in the metabolism of tetrahydrocannabinol and cannabidiol, which implies possible DDI with CYP450 inhibitor and inducer, such as anticonvulsivants and HIV protease inhibitors, which may be prescribed in patients with neuropathic pain.

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"). METHODS AND FINDINGS: We used hospital and community pharmacy invoice office data in the Swiss canton of Geneva to calculate utilisation of eight follow-on drugs in defined daily doses between 2000 and 2008. "Extra costs" were calculated for three different scenarios assuming replacement with the corresponding generic equivalent for prescriptions of (1) all brand (i.e., initially patented) drugs, (2) all follow-on drugs, or (3) brand and follow-on drugs. To examine the financial spillover effect we calculated a monthly follow-on drug market share in defined daily doses for medications prescribed by hospital physicians but dispensed in community pharmacies, in comparison to drugs prescribed by non-hospital physicians in the community. Estimated "extra costs" over the study period were €15.9 (95% CI 15.5; 16.2) million for scenario 1, €14.4 (95% CI 14.1; 14.7) million for scenario 2, and €30.3 (95% CI 29.8; 30.8) million for scenario 3. The impact of strictly switching all patients using proton-pump inhibitors to esomeprazole at admission resulted in a spillover "extra cost" of €330,300 (95% CI 276,100; 383,800), whereas strictly switching to generic cetirizine resulted in savings of €7,700 (95% CI 4,100; 11,100). Overall we estimated that the RDF resulted in "extra costs" of €503,600 (95% CI 444,500; 563,100). CONCLUSIONS: Evergreening strategies have been successful in maintaining market share in Geneva, offsetting competition by generics and cost containment policies. Hospitals may be contributing to increased overall healthcare costs by listing follow-on drugs in their RDF. Therefore, healthcare providers and policy makers should be aware of the impact of evergreening strategies.

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. Concentrations in plasma and aqueous humour were fitted using a two-compartment model (NONMEM software). Inter-individual and intra-individual variabilities were quantified and the influence of demographics and physiopathological and environmental variables on penciclovir pharmacokinetics was explored. RESULTS: Drug concentrations were fitted using a two-compartment, open model with first-order transfer rates between plasma and aqueous humour compartments. Among tested covariates, creatinine clearance, co-intake of angiotensin-converting enzyme inhibitors and body weight significantly influenced penciclovir pharmacokinetics. Plasma clearance was 22.8±9.1 L/h and clearance from the aqueous humour was 8.2×10(-5) L/h. AUCs were 25.4±10.2 and 6.6±1.8 µg·h/mL in plasma and aqueous humour, respectively, yielding a penetration ratio of 0.28±0.06. Simulated concentrations in the aqueous humour after administration of 500 mg of famciclovir three times daily were in the range of values required for 50% growth inhibition of non-resistant strains of the herpes zoster virus family. CONCLUSIONS: Plasma and aqueous penciclovir concentrations showed significant variability that could only be partially explained by renal function, body weight and comedication. Concentrations in the aqueous humour were much lower than in plasma, suggesting that factors in the blood-aqueous humour barrier might prevent its ocular penetration or that redistribution occurs in other ocular compartments.

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. Simultaneous drug-drug interactions through uptake and efflux transport systems in hepatocytes according to the cellular concentrations of competing drugs were never investigated. In perfused rat liver preparations, we demonstrate how the drug-drug interactions through transporters determine cellular concentrations of the competing drugs BOPTA and RIF, and we show that the cellular concentrations by modulating transport through membranes regulate the rat Oatp-Mrp2 interplay. Moreover, drug interactions through transporters change greatly over time.

A simplified method for busulfan monitoring using dried blood spot in combination with liquid chromatography/tandem mass spectrometry.

RATIONALE: Busulfan (Bu) is an important component of the myeloablative conditioning regimen prior to hematopoietic stem cell transplantation (HSCT) especially in children. Intravenously administered Bu exhibits a therapeutic window phenomenon requiring therapeutic drug monitoring. Analytical methods developed for Bu routine monitoring were aimed at using low volumes of biological fluids and development of simple procedures to facilitate the dosage adjustment. In this report, we describe a simple, rapid method for Bu measurement using dried blood spots (DBS) from only 5 µL of whole blood. METHODS: Bu extracted from DBS with methanol was measured by high-performance liquid chromatography with electrospray ionization and tandem mass spectrometry in multiple reaction monitoring mode using D8-Bu as an internal standard. The method was in-house validated evaluating trueness, repeatability, within-laboratory reproducibility, specificity and the lower limit of quantification (LLOQ). RESULTS: The method was linear in the calibration range of 100-2000 ng mL(-1) (r(2)>0.99) encompassing the therapeutic concentrations of Bu. A good trueness (<14%), precision (<10%), and recovery (100%) were observed during validation of the method with quality controls of 300, 600 and 1400 ng mL(-1). The LLOQ was determined as 50 ng mL(-1) and no matrix or carryover effects were observed. The validated method was applied to measure Bu levels in four children receiving infusion of Bu prior to HSCT. A good correlation was observed between the Bu levels measured by DBS and dried plasma spot (DPS) (r(2) =0.96) and between DPS and the GC/MS method (r(2) =0.92). Bu was found to be stable in DBS up to 6 h at room temperature and for 24 h at 4 °C. CONCLUSIONS: The new DBS method facilitates earlier dosage adjustment during Bu therapy by its specific and simple procedure using 5 µL of whole blood.

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) 46.9 ± 1.1 °C to 40.1 ± 1.7 °C (p <0.001) and of the mechanical pain threshold (62% decrease). A small intra- and inter-individual variability was observed as well as consistent intra-day stability for the heat pain threshold. The UVB irradiation also resulted in the development of an area of secondary hyperalgesia of 21.3 ± 11.3 cm(2). The mechanical pain threshold and area of secondary hyperalgesia showed small intra-individual variability and consistent intra-day stability. However, a greater variability was observed between subjects, which suggests that a crossover design would allow limiting the number of subjects.

[Atypical femoral fracture associated with the use of bisphosphonates, an adverse drug reaction not to be missed]. / Fracture atypique du fémur sous bisphosphonates, un effet indésirable a ne pas manquer.

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. They occur after minor or no trauma, include a thickening of the lateral femoral cortex, a delayed consolidation time and prodromal symptoms. In this context, the risk/benefit ratio of bisphosphonates remains favorable if the indication is adequate. In case of fracture, indication to treatment should be reevaluated. Pain or discomfort in the thigh in a patient receiving bisphosphonate should lead to radiological investigations in order to detect the possible occurrence of a stress fracture.

[Social marketing: applying commercial strategies to the prevention of nosocomial infections]. / Le marketing social: un regard nouveau sur la prévention des infections nosocomiales.

Although a large proportion of healthcare-associated infections are avoidable, healthcare workers do not always practice evidence-based preventive strategies. Marketing technologies might help to improve patient safety. This article presents the basic principles of marketing and its potential use to promote good infection control practices. The marketing mix (Product, Price, Place, and Promotion) should be taken into account to induce behaviour change. By placing the emphasis on the perceived "profits" for healthcare workers the approach might lose its moral aspect and gain in effectiveness. VigiGerme, a non-commercial registered trademark, applies social marketing techniques to infection control and prevention.

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. DATA COLLECTION/EXTRACTION METHODS: Interviews were analyzed using an inductive thematic approach. PRINCIPAL FINDINGS: Admission decisions regarding seriously ill or elderly patients with comorbidities are complex. Nonmedical factors such as ICU beds availability, health care resources on the ward, information about patient preferences, and family behavior determine the decision. Code status and the quality of interaction between physicians are key determinants. The absence of code status or poor documentation of code status discussions makes decisions more difficult and laden emotionally, as physicians feel they are making a life-death decision. Mutual respect and collaborative decision making facilitate the decision. Tensions arise due to ICU physicians' postponing the decision because of lack of beds, ICU physicians' dismissive attitudes, perceived shortcomings in the other physician's completion of expected tasks, and preconceptions about the other physician. CONCLUSIONS: Systematic documentation of code status, and fostering collaboration between ICU physicians and internists would facilitate ICU admission decisions in complex clinical situations.

[Off-label prescribing]. / La prescription "off-label".

Prescribing a medication for a condition not described in the label approved by national regulatory bodies (in Switzerland, Swissmedic) is called "off-label" prescribing. Unlicensed drug use is common in all fields of medicine and may be encountered in therapeutic guidelines. The term does not imply improper nor illegal use, and may provide the only available treatment for "orphan" conditions, or for certain populations (children, pregnant women, very old patients). Off-label drug use should be based on sound scientific evidence of efficacy and safety. In Switzerland, patients need to be informed that health insurance coverage is not guaranteed with off-label use. The prescribing physician bears the responsibility of off-label use with the possibility of unanticipated risks, and should therefore be prepared for possible malpractice suits.

Codeine intoxication associated with ultrarapid CYP2D6 metabolism.

Life-threatening opioid intoxication developed in a patient after he was given small doses of codeine for the treatment of a cough associated with bilateral pneumonia. Codeine is bioactivated by CYP2D6 into morphine, which then undergoes further glucuronidation. CYP2D6 genotyping showed that the patient had three or more functional alleles, a finding consistent with ultrarapid metabolism of codeine. We attribute the toxicity to this genotype, in combination with inhibition of CYP3A4 activity by other medications and a transient reduction in renal function.

Pharmacokinetic and pharmacodynamic properties of buprenorphine after a single intravenous administration in healthy volunteers: a randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Buprenorphine is used as an analgesic for postoperative and chronic pain. The usual sublingual dose is 0.2 to 0.8 mg, and the usual parenteral dose is 0.3 mg for acute postoperative pain. The pharmacokinetic and related pharmacodynamic properties of buprenorphine at these doses have not been characterized. OBJECTIVE: The aim of this study was to assess the pharmacokinetic properties of buprenorphine 0.002 mg/kg IV (0.15 mg/70 kg) and its antinociceptive and psychomotor effects. METHODS: Healthy male volunteers received 0.002 mg/kg buprenorphine IV in a randomized, double-blind, placebo-controlled, crossover design. Blood samples were collected at 0.5, 1, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, and 8 hours for the determination of plasma concentrations. Pharmacokinetic parameters were estimated by a compartmental model using specialized software. Antinociceptive and psychomotor effects were determined for 8 hours. Quantitative sensory testing with thermal and electrical (nociceptive flexion RIII reflex) stimulations was performed. The cold pressor test was used to assess pain tolerance to a tonic, intense pain stimulation. Psychomotor performance was assessed by the digit symbol substitution test (DSST). Participants also rated sedation on an 11-point numeric scale (0 = none to 10 = severe). A selective liquid chromatography-tandem mass spectrometry assay was developed for the determination of buprenorphine; the limit of quantification was 0.05 ng/mL using a 0.25-mL plasma aliquot. Participants were instructed to report adverse effects, which were recorded for type, time of onset, seriousness, and duration. RESULTS: The study enrolled 12 participants, all of whom were white. Mean (SD) age was 26 (3.5) years, and mean weight was 67 (9) kg. None of the participants had a history of opiate abuse. Buprenorphine significantly increased the objective (nociceptive flexion RIII reflex) and subjective pain thresholds for >4 hours and pain tolerance (cold pressor test) for 2 hours. The mean (SD) RIII reflex threshold and subjective threshold at baseline were 31.6 (9.5) mA and 45.5 (22.3) mA, respectively. The maximum increases (mean [SD]) were +14.1 (17.5) mA for the RIII reflex (P = 0.02) and +24.2 (21.7) mA for the subjective threshold (P = 0.02), corresponding to mean (SEM) percentages of 53.7% (20.2%) and 74.7% (20.4%) of the baseline values, respectively. The maximum increases were observed at 120 minutes for both measures. The effect of buprenorphine on pain tolerance peaked at 30 minutes. Mean (SEM) latency before withdrawal of the hand was 69 (10) seconds, corresponding to a mean increase of 63.8% (14.4%) from baseline (P = 0.003). Buprenorphine had a significant effect on the DSST. The mean maximum decrease in the total number of symbols drawn was -6 (14.5%; P = 0.005) at 1 hour. The participants reported high levels of sedation: at peak effect (120 minutes), mean scores increased from 2.9 to 6.4 (SEM 0.7) (P = 0.005). Levels returned to baseline values by the end of the session, unlike for the nociceptive tests. The onset of effects occurred during the distribution phase for all the measures, and their duration was observed across a wide range of concentrations during the elimination phase. The most likely explanation for this finding is the high affinity of buprenorphine at mu-opioid receptors, and possibly distribution to the brain. Buprenorphine t(l/2) was 2.75 hours. A secondary peak in concentration was observed at 90 minutes, suggesting enterohepatic circulation of buprenorphine. A 2-compartment model adequately described buprenorphine pharmacokinetics. CONCLUSIONS: A clinically relevant analgesic dose of 0.002 mg/kg (0.15 mg/70 kg) of buprenorphine had a significant effect on nociception and psychomotor performance in these healthy male volunteers. A 2-compartment model satisfactorily characterized buprenorphine pharmacokinetics, and we found evidence of enterohepatic circulation.

Patients' representations of antidepressants: a clue to nonadherence?

OBJECTIVES: Antidepressants are prescribed frequently to chronic pain patients due to their pain relief effects. This medication raises major adherence issues. Despite the adverse effects, little is known about the factors that may jeopardize adherence in chronic pain patients. We carried out a qualitative study to investigate chronic pain patients' representations of antidepressants as compared with pain-free controls. METHODS: One hundred thirteen chronic pain patients recruited in a multidisciplinary pain clinic and 62 matched controls were questioned with standardized semistructured interviews. The interviews were submitted to content analysis. RESULTS: Ambivalence emerged as an important aspect of "patients" and controls' views about antidepressants. Antidepressants were described as potent chemicals acting in the brain, possibly causing effects on cognition, emotions, and personality, and inducing dependence and loss of control. Positive effects were mentioned, but when respondents related their own views and experiences, the statements became less favorable. Another key point was that neither the representations of the patients and nor those of the controls comprised the analgesic properties of antidepressants. DISCUSSION: Chronic pain patients' representations differed only little from those of controls. Antidepressants were not considered as addressing somatic problems. Thus, the prescription of antidepressants for chronic pain may be mistaken for a denial of the "reality" of pain. Although this study did not assess medication adherence, it is possible that patient representations have a bearing on adherence. Clinically, this suggests that these representations should be elicited and addressed, taking into account the patients' own models of pain.

Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors.

BACKGROUND: Drug-induced long QT syndrome is a serious adverse drug reaction. Methadone prolongs the QT interval in vitro in a dose-dependent manner. In the inpatient setting, the frequency of QT interval prolongation with methadone treatment, its dose dependence, and the importance of cofactors such as drug-drug interactions remain unknown. METHODS: We performed a systematic, retrospective study comparing active or former intravenous drug users receiving methadone and those not receiving methadone among all patients hospitalized over a 5-year period in a tertiary care hospital. A total of 167 patients receiving methadone fulfilled the inclusion criteria and were compared with a control group of 80 injection drug users not receiving methadone. In addition to methadone dose, 15 demographic, biological, and pharmacological variables were considered as potential risk factors for QT prolongation. RESULTS: Among 167 methadone maintenance patients, the prevalence of QTc prolongation to 0.50 second((1/2)) or longer was 16.2% compared with 0% in 80 control subjects. Six patients (3.6%) in the methadone group presented torsades de pointes. QTc length was weakly but significantly associated with methadone daily dose (Spearman rank correlation coefficient, 0.20; P<.01). Multivariate regression analysis allowed attribution of 31.8% of QTc variability to methadone dose, cytochrome P-450 3A4 drug-drug interactions, hypokalemia, and altered liver function. CONCLUSIONS: QT interval prolongation in methadone maintenance patients hospitalized in a tertiary care center is a frequent finding. Methadone dose, presence of cytochrome P-450 3A4 inhibitors, potassium level, and liver function contribute to QT prolongation. Long QT syndrome can occur with low doses of methadone.

[Oral anticoagulation and pharmacogenetics: importance in the clinical setting]. / Anticoagulation orate et pharmacogénetique: perspectives pour la pratique clinique.

Single nucleotide polymorphisms (SNPs) in genes encoding cytochrome P450 enzyme 2C9 (CYP2C9) and Vitamin K epoxide reductase subunit I (VKORC1) make a significant contribution to the inter-individual variability in the maintenance dose of vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon). Doses requirements in CYP2C9*2 and CYP2C9*3 heterozygotes are reduced by 8-16% and 20-36%, respectively. SNP g-1639a in VKORC1 is also associated with vitamin K antagonists dosage since heterozygotes ga and homozygotes aa require respectively 21-28% and 27-56% less warfarin or acenocoumarol than homozygotes gg. CYP2C9 and VKORC1 account for up to half the variability in vitamin K antagonists requirements and incorporating genotying data for these two genes into dosing algorithms could lead to a safer anticoagulation therapy.

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. METHODS: All the generalists and internists in French-speaking Switzerland were mailed the questionnaire. Respondents (43.5%) evaluated three vignettes that described medical decisions for incapacitated patients. Each vignette was produced in four versions: one with an advance directive, one with a proxy opinion, one with both, and one with neither (control). In the first vignette, the directive and proxy agreed on the recommendation to forgo a medical intervention; in the second, the advance directive opposed, but the proxy favored the intervention; and in the third, the roles were reversed. Each doctor received one version of each vignette, attributed at random. The outcome variables were the doctor's decision to forgo the medical intervention and the rating of the decision as difficult. RESULTS: Written advance directives and proxy opinions significantly influenced doctors' decision making. When both were available and concordant, they reinforced each other (odds ratio [OR] of forgoing intervention 35.7, P < 0.001 compared with no instruction). When the directive and proxy disagreed, the resulting effect was to forgo the intervention (ORs 2.1 and 2.2 for the two discordant vignettes, both P < 0.001). Discordance between instructions was associated with increased odds of doctors rating the decision as difficult (both ORs 2.0, P ≤ 0.001). CONCLUSION: Contradictions between advance directives and proxy opinions result in a weak preference for abstention from treatment and increase the difficulty of the decision.

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. Recent revisions to the law regarding medical trials in human research allow for better allocation of regulatory resources and simplified procedures for drugs already authorized in Switzerland. The country has its own regulatory agency, the Swiss Agency for Therapeutic Products (Swissmedic), which is a public institution of the Swiss government. Swissmedic is responsible for ensuring safety in medicines, particularly regarding authorizations and market surveillance in the sector of medicinal products and medical devices. Although the centralized authorization procedure of the European Union for medicines does not apply to Switzerland, there are mutual recognition mechanisms between the Swiss medicine regulatory authority and the European Medicines Agency. Swissmedic is also in charge of postmarketing safety and oversees the national pharmacovigilance center, which collaborates closely with the World Health Organization center in Uppsala. In addition, university hospital-based clinical pharmacologists, who are involved in basic science and clinical research, regulatory affairs, ethics committees, and pharmacovigilance, promote quality therapeutics. This article discusses the role of the various stakeholders and the recent efforts made to provide a better allocation of resources aimed at further improving quality therapeutics in Switzerland.

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. Physician rounds were attended by a pharmacist and a pharmacologist. An assessment grid was used to detect the DRPs in electronic prescriptions 24h in advance. One of the following interventions was selected, depending on the relevance and complexity of the DRPs: no intervention, verbal advice of treatment optimization, or written consultation. The acceptance rate and satisfaction of prescribers were measured. RESULTS: In total, 145 patients were included, and 383 DRPs were identified (mean: 2.6 DRPs per patient). The most frequent DRPs were drug interactions (21%), untreated indications (18%), overdosages (16%) and drugs used without a valid indication (10%). The drugs or drug classes most frequently involved were tramadol, antidepressants, acenocoumarol, calcium-vitamin D, statins, aspirin, proton pump inhibitors and paracetamol. The following interventions were selected: no intervention (51%), verbal advice of treatment optimization (42%), and written consultation (7%). The acceptance rate of prescribers was 84% and their satisfaction was high. CONCLUSION: Pharmacotherapy expertise during medical rounds was useful and well accepted by prescribers. Because of the modest allocation of pharmacists and pharmacologists in Swiss hospitals, complementary strategies would be required.