Evaluation of risk perception related to drug use during pregnancy: a Swiss survey

Introduction Health care professionals' perception of risk mayimpact on therapeutic management of women during pregnancy.Since the thalidomide tragedy, the use of drugs during pregnancygenerates fear. This concern might affect the estimation of the riskassociated with drug intake during pregnancy, leading to prematurediscontinuation of a required treatment, superfluous anxiety orpointless termination of a desired pregnancy. Although data regardingthe security of drugs during pregnancy are still scarce, a few specializedinformation sources exist providing reliable recommendationsfor daily practice. This study aimed at characterizing therisk perception associated with drugs during pregnancy in a sample ofSwiss health care professionals.Materials & Methods An online French and German survey was sentby email to the Swiss professional societies of Pharmacists, Gynecologists,Mid-wives and Pediatricians. The questionnaire wasconstructed to assess (a) the characteristics of the population and theopinion of the professionals regarding the medication use pattern intheir pregnant patients, (b) to evaluate the sources of information usedduring their practice and finally (c) to assess their risk perceptionassociated with drugs during pregnancy. Results were analyzed bydescriptive statistics.Results A total of 1,310 questionnaires were collected (18% responserate). Most health care professionals believe that 30-60% of theirpregnant patients are taking at least one treatment during their pregnancyand that 80% are adherent to it. A large majority think,however, that women are anxious when they must take their medication.More than 80% of health professionals commonly use theSwiss Drug Reference Book (Compendium) to assess the risk associatedwith drugs during pregnancy, despite the uniformly low levelof credibility and utility they express about this reference. Except forsome gynecologists, the majority of professionals are not aware of ordo not use specialized books. The majority of participants thinkwrongly that more than 30% of drugs are teratogenic. About 20% ofthem are not aware of the risk associated with paracetamol intakeduring pregnancy. More than 70% agree that phytotherapeutic mixturesare not safer than conventional drugs, with the exception of midwiveswho tend to overestimate the safety of such drugs. With thenotable exception of gynecologists, the risk related to drug intake wasoverall overestimated.Discussion & Conclusion Swiss professionals differ in their perceptionof the risk associated with drugs during pregnancy and tend tooverestimate it. The differences might be attributed to the level oftraining and awareness of specialized sources offering a realisticestimation of the risk. Further efforts are needed to expand thetraining and the tools for health care professionals to optimize druguse during pregnancy.

2012 Iowa Drug Control Strategy

Drug use is a preventable behavior; drug addiction is a treatable disease; and a balanced approach of proven and promising prevention, treatment and enforcement is required to protect Iowans from drugs now and in the future. Drug abuse itself is a two-faceted problem, affected by both the available supply of and the demand for illegal drugs and other substances of abuse. Any strategy dealing with both the supply of and demand for drugs of abuse must be three-fold and involve these coordinated components: 1) Prevention strategies to discourage the initial human demand for drugs, 2) Treatment for those who already abuse or are addicted to drugs, in order to halt their drug-seeking behavior, and 3) Law enforcement actions to decrease the supply of illegal drugs and bring to treatment those who otherwise would not seek help. It is with these three approaches in mind that the Governor’s Office of Drug Control Policy presents the 2012 Iowa Drug Control Strategy. Mark J. Schouten Director, Governor’s Office of Drug Control Policy

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.

Oral pregabalin as an add-on treatment for status epilepticus.

Oral antiepileptic drugs (AEDs) represent possible add-on options in refractory status epilepticus (SE). In this setting, pregabalin (PGB) has not been reported before. Over the last 42 months, we identified 11 SE episodes (10 patients) treated with PGB in our hospital. Its use was prompted by the favorable pharmacokinetic profile, devoid of drug-drug interactions. The patients mostly had refractory, partial SE. Only two patients were managed in the intensive care unit (ICU). We found a definite electroclinical response in 5 of 11, already evident 24 h after PGB introduction, and a possible response (concomitantly with other AEDs) in 3 of 11 of the episodes; 3/11 did not respond. The treatment was well tolerated. Partial SE appeared to better respond than generalized convulsive SE. PGB appears to be an interesting option as add-on treatment in refractory partial SE.

Efficacy of levofloxacin in the treatment of experimental endocarditis caused by viridans group streptococci.

Levofloxacin was investigated against viridans group streptococci in vitro and in rats with experimental aortic endocarditis. The MIC(90)s of levofloxacin and ciprofloxacin for 20 independent isolates of such bacteria were 1 and 8 mg/L, respectively. Rats were infected with two types of organism: either fully susceptible to levofloxacin MIC < or = 0.5 mg/L) or borderline susceptible (MIC 1-2 mg/L). Fully levofloxacin-susceptible bacteria comprised one penicillin-susceptible (MIC 0.004 mg/L) Streptococcus gordonii, and one penicillin-tolerant as well as one intermediate penicillin-resistant (MIC 0.125 mg/L) isogenic strains. Borderline levofloxacin-susceptible bacteria comprised one penicillin-susceptible Streptococcus sanguis and one highly penicillin-resistant Streptococcus mitis (MIC 2 mg/L). Rats were treated for 5 days with drug dosages simulating the following treatments in humans: (i) levofloxacin 500 mg orally once a day (q24 h), (ii) levofloxacin 500 mg orally twice a day (q12 h), (iii) levofloxacin 1 g orally q24 h, (iv) ciprofloxacin 750 mg orally q12 h, and (v) ceftriaxone 2 g iv q24 h. Levofloxacin was equivalent or superior to ceftriaxone, and was successful in treating experimental endocarditis irrespective of penicillin resistance. Nevertheless, standard levofloxacin treatment equivalent to 500 mg q24 h in human was less effective than twice daily 500 mg or once daily 1 g doses against borderline-susceptible organisms. Ciprofloxacin, used as a negative control, was ineffective and selected for resistant isolates. This underlines the importance of MIC determinations when treating severe streptococcal infection with quinolones. In the case of borderline-susceptible pathogens, total daily doses of 1 g of levofloxacin should be considered.

Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer's disease.

With the aging population and its rapidly increasing prevalence, dementia has become an important public health concern in developed and developing countries. To date, the pharmacological treatment is symptomatic and based on the observed neurotransmitter disturbances. The four most commonly used drugs are donepezil, galantamine, rivastigmine and memantine. Donepezil, galantamine and rivastigmine are acetylcholinesterase inhibitors with different pharmacodynamic and pharmacokinetic profiles. Donepezil inhibits selectively the acetylcholinesterase and has a long elimination half-life (t½) of 70 h. Galantamine is also a selective acetylcholinesterase inhibitor, but also modulates presynaptic nicotinic receptors. It has a t½ of 6-8 h. Donepezil and galantamine are mainly metabolised by cytochrome P450 (CYP) 2D6 and CYP3A4 in the liver. Rivastigmine is a so-called 'pseudo-irreversible' inhibitor of acetylcholinesterase and butyrylcholinesterase. The t½ of the drug is very short (1-2 h), but the duration of action is longer as the enzymes are blocked for around 8.5 and 3.5 h, respectively. Rivastigmine is metabolised by esterases in liver and intestine. Memantine is a non-competitive low-affinity antagonist of the NMDA receptor with a t½ of 70 h. Its major route of elimination is unchanged via the kidneys. Addressing the issue of inter-patient variability in treatment response might be of special importance for the vulnerable population taking anti-dementia drugs. Pharmacogenetic considerations might help to avoid multiple medication changes due to non-response and/or adverse events. Some pharmacogenetic studies conducted on donepezil and galantamine reported an influence of the CYP2D6 genotype on the pharmacokinetics of the drugs and/or on the response to treatment. Moreover, polymorphisms in genes of the cholinergic markers acetylcholinesterase, butyrylcholinesterase, choline acetyltransferase and paraoxonase were found to be associated with better clinical response to acetylcholinesterase inhibitors. However, confirmation studies in larger populations are necessary to establish evidence of which subgroups of patients will most likely benefit from anti-dementia drugs. The aim of this review is to summarize the pharmacodynamics and pharmacokinetics of the four commonly used anti-dementia drugs and to give an overview on the current knowledge of pharmacogenetics in this field.

Use of duplex ultrasonography in the treatment of thromboangiitis obliterans with iloprost.

We present a 34-year-old patient with digital necrosis due to thromboangiitis obliterans. He was successfully treated with iloprost, a prostaglandin analogue. Duplex ultrasonography was performed during the perfusion of iloprost to optimize the doses and the treatment duration. A complete revascularization was observed after 10 days. Iloprost perfusions were stopped, and a slow regression of the necroses was observed in the subsequent days. With the use of duplex ultrasonography, unnecessary high doses of iloprost and long periods of treatment can be avoided reducing side effects and treatment costs.

Changes in protein turnover and resting energy expenditure after treatment of malaria in Gambian children.

To explore the changes in resting energy expenditure (REE) and whole body protein turnover induced by malaria, 23 children aged 6 to 14 y (23.9 +/- 1.0 kg, 1.3 +/- 0.02 m) were studied on three separate days after treatment (d 1, d 2, and 15 d later). REE was assessed by indirect calorimetry (hood), whereas whole body protein turnover was estimated using a single dose of [15N]glycine administered p.o. by measuring the isotopic enrichment of [15N]ammonia in urine over 12 h. Within the first 3.5 h after treatment, the body temperature dropped from 39.8 +/- 0.1 to 37.8 +/- 0.1 degrees C (p < 0.0001), and REE followed the same pattern, decreasing rapidly from 223 +/- 6 to 187 +/- 4 kJ/kg/d (p < 0.0001). Whole body protein synthesis and breakdown were significantly higher during the 1st day (5.65 +/- 0.38 and 6.21 +/- 0.43 g/kg/d, respectively) than at d 15 (2.95 +/- 0.17 and 2.77 +/- 0.2 g/kg/d). It is concluded that Gambian children suffering from an acute episode of malaria have an increased REE averaging 37% of the control value (d 15) and that this was associated with a substantial increase (by a factor of 2) in whole body protein turnover. A rapid normalization of the hypermetabolism and protein hypercatabolism states after treatment was observed.

Simultaneous quantification of selective serotonin reuptake inhibitors and metabolites in human plasma by liquid chromatography-electrospray mass spectrometry for therapeutic drug monitoring.

A simple and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed for the simultaneous quantification in human plasma of all selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their main active metabolites (desmethyl-citalopram and norfluoxetine). A stable isotope-labeled internal standard was used for each analyte to compensate for the global method variability, including extraction and ionization variations. After sample (250μl) pre-treatment with acetonitrile (500μl) to precipitate proteins, a fast solid-phase extraction procedure was performed using mixed mode Oasis MCX 96-well plate. Chromatographic separation was achieved in less than 9.0min on a XBridge C18 column (2.1×100mm; 3.5μm) using a gradient of ammonium acetate (pH 8.1; 50mM) and acetonitrile as mobile phase at a flow rate of 0.3ml/min. The method was fully validated according to Société Française des Sciences et Techniques Pharmaceutiques protocols and the latest Food and Drug Administration guidelines. Six point calibration curves were used to cover a large concentration range of 1-500ng/ml for citalopram, desmethyl-citalopram, paroxetine and sertraline, 1-1000ng/ml for fluoxetine and fluvoxamine, and 2-1000ng/ml for norfluoxetine. Good quantitative performances were achieved in terms of trueness (84.2-109.6%), repeatability (0.9-14.6%) and intermediate precision (1.8-18.0%) in the entire assay range including the lower limit of quantification. Internal standard-normalized matrix effects were lower than 13%. The accuracy profiles (total error) were mainly included in the acceptance limits of ±30% for biological samples. The method was successfully applied for routine therapeutic drug monitoring of more than 1600 patient plasma samples over 9 months. The β-expectation tolerance intervals determined during the validation phase were coherent with the results of quality control samples analyzed during routine use. This method is therefore precise and suitable both for therapeutic drug monitoring and pharmacokinetic studies in most clinical laboratories.

Self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predicts treatment failure in virologically suppressed patients.

BACKGROUND: The aim of this study was to explore the predictive value of longitudinal self-reported adherence data on viral rebound. METHODS: Individuals in the Swiss HIV Cohort Study on combined antiretroviral therapy (cART) with RNA <50 copies/ml over the previous 3 months and who were interviewed about adherence at least once prior to 1 March 2007 were eligible. Adherence was defined in terms of missed doses of cART (0, 1, 2 or >2) in the previous 28 days. Viral rebound was defined as RNA >500 copies/ml. Cox regression models with time-independent and -dependent covariates were used to evaluate time to viral rebound. RESULTS: A total of 2,664 individuals and 15,530 visits were included. Across all visits, missing doses were reported as follows: 1 dose 14.7%, 2 doses 5.1%, >2 doses 3.8% taking <95% of doses 4.5% and missing > or =2 consecutive doses 3.2%. In total, 308 (11.6%) patients experienced viral rebound. After controlling for confounding variables, self-reported non-adherence remained significantly associated with the rate of occurrence of viral rebound (compared with zero missed doses: 1 dose, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.72-1.48; 2 doses, HR 2.17, 95% CI 1.46-3.25; >2 doses, HR 3.66, 95% CI 2.50-5.34). Several variables significantly associated with an increased risk of viral rebound irrespective of adherence were identified: being on a protease inhibitor or triple nucleoside regimen (compared with a non-nucleoside reverse transcriptase inhibitor), >5 previous cART regimens, seeing a less-experienced physician, taking co-medication, and a shorter time virally suppressed. CONCLUSIONS: A simple self-report adherence questionnaire repeatedly administered provides a sensitive measure of non-adherence that predicts viral rebound.

Intratympanic application of an antiviral agent for the treatment of Ménière's disease.

It has been suggested that Ménière's disease is part of a polyganglionitis in which symptoms result from the reactivation of neurotropic virus within the internal auditory canal, and that intratympanic applications of an antiviral agent might be an efficient therapy. In 2002, we performed a pilot study ending with encouraging results. Control of vertigo was achieved in 80% of the 17 patients included. We present here a prospective, double-blind study, with a 2-year follow-up, in 29 patients referred by ENT practitioners for a surgical treatment after failure of a medical therapy. The participation in the study was offered to patients prior to surgery. A solution of ganciclovir 50 mg/ml or of NaCl 9% was delivered for 10 consecutive days via a microwick inserted into the tympanic membrane in the direction of the round window or through a ventilation tube. One patient was withdrawn from the study immediately after the end of the injections. He could not complete the follow-up period, because of persisting vertigo. As he had received the placebo, he was then treated with the solution of ganciclovir. Symptoms persisted and he underwent a vestibular neurectomy. Among the remaining 28 patients, surgery could be postponed in 22 (81%). Surgery remained necessary to control vertigo in 3 patients from the group that received the antiviral agent, and in 3 from the control group. Using an analogical scale, patients of both groups indicated a similar improvement of their health immediately after the intratympanic injections. The scores obtained with a 36-item short-form health survey quality of life questionnaire and the Dizziness Handicap Inventory were also similar for both groups. In conclusion, most patients were improved after the intratympanic injections, but there was no obvious difference between the treated and control groups. The benefit might be due to the middle ear ventilation or reflect an improvement in the patients' emotional state.

Iowa’s Drug Control Strategy, 2008

The 2011 Iowa Drug Control Strategy is submitted in satisfaction of Chapter 80E.1 of the Code of Iowa which directs the Drug Policy Coordinator to monitor and coordinate all drug prevention, enforcement and treatment activities in the state. Further, it requires the Coordinator to submit an annual report to the Governor and Legislature concerning the activities and programs of the Coordinator, the Governor’s Office of Drug Control Policy and all other state departments with drug enforcement, substance abuse treatment, and prevention programs. Chapter 80E.2 establishes the Drug Policy Advisory Council (DPAC), chaired by the Coordinator, and consisting of a prosecuting attorney, substance abuse treatment specialist, law enforcement officer, prevention specialist, judge and representatives from the departments of corrections, education, public health, human services, public safety and human rights. This report and strategy was developed in consultation with the DPAC.

Iowa’s Drug Control Strategy, 2010

The 2011 Iowa Drug Control Strategy is submitted in satisfaction of Chapter 80E.1 of the Code of Iowa which directs the Drug Policy Coordinator to monitor and coordinate all drug prevention, enforcement and treatment activities in the state. Further, it requires the Coordinator to submit an annual report to the Governor and Legislature concerning the activities and programs of the Coordinator, the Governor’s Office of Drug Control Policy and all other state departments with drug enforcement, substance abuse treatment, and prevention programs. Chapter 80E.2 establishes the Drug Policy Advisory Council (DPAC), chaired by the Coordinator, and consisting of a prosecuting attorney, substance abuse treatment specialist, law enforcement officer, prevention specialist, judge and representatives from the departments of corrections, education, public health, human services, public safety and human rights. This report and strategy was developed in consultation with the DPAC.

Iowa’s Drug Control Strategy, 2012

The 2011 Iowa Drug Control Strategy is submitted in satisfaction of Chapter 80E.1 of the Code of Iowa which directs the Drug Policy Coordinator to monitor and coordinate all drug prevention, enforcement and treatment activities in the state. Further, it requires the Coordinator to submit an annual report to the Governor and Legislature concerning the activities and programs of the Coordinator, the Governor’s Office of Drug Control Policy and all other state departments with drug enforcement, substance abuse treatment, and prevention programs. Chapter 80E.2 establishes the Drug Policy Advisory Council (DPAC), chaired by the Coordinator, and consisting of a prosecuting attorney, substance abuse treatment specialist, law enforcement officer, prevention specialist, judge and representatives from the departments of corrections, education, public health, human services, public safety and human rights. This report and strategy was developed in consultation with the DPAC.

Iowa’s Drug Control Strategy, 2009

The 2011 Iowa Drug Control Strategy is submitted in satisfaction of Chapter 80E.1 of the Code of Iowa which directs the Drug Policy Coordinator to monitor and coordinate all drug prevention, enforcement and treatment activities in the state. Further, it requires the Coordinator to submit an annual report to the Governor and Legislature concerning the activities and programs of the Coordinator, the Governor’s Office of Drug Control Policy and all other state departments with drug enforcement, substance abuse treatment, and prevention programs. Chapter 80E.2 establishes the Drug Policy Advisory Council (DPAC), chaired by the Coordinator, and consisting of a prosecuting attorney, substance abuse treatment specialist, law enforcement officer, prevention specialist, judge and representatives from the departments of corrections, education, public health, human services, public safety and human rights. This report and strategy was developed in consultation with the DPAC.