Drug use and suicide attempts: the role of personality factors.

This study on suicide attempts is part of a large research project on dependent behavior in adolescents and young adults. 228 subjects aged 14-25 (107 "drug abusers," 121 controls) from the French speaking part of Switzerland were evaluated on the basis of a semi-structured interview (Mini International Neuropsychiatric Interview), enabling a DSM-IV diagnosis, and self-reports (SSS by Zuckermann, MMPI-2, IDI by Hirschfeld). 31.5% of "drug abuser" males and 41.2% of "drug abuser" females committed one or more suicide attempts. The results of a logistic regression show that the significant factor explaining suicide attempts in drug users is emotional reliance for males and experience-seeking for females.

Current trends in illegal drug use and drug related health problems in Switzerland.

As part of the evaluation of the Confederation's measures to reduce drug related problems, a review of available data on drug use and drug related problems in Switzerland has been conducted. Source of data included: population surveys (adults and teenagers), surveys among drug users, health statistics (drug related and AIDS related deaths, HIV case reporting, drug treatments) police statistics (denunciations for consumption). The aims of reducing the number of dependent hard drug users have been achieved where heroin is concerned. In particular, there seems to have been a decrease in the number of people becoming addicted to this substance. For all other illegal substances, especially cannabis, the trend is towards an increased use, as in many European countries. As regards dependent drug users, especially injecting drug users, progress has been made in the area of harm reduction and treatment coverage. This epidemiological assessment can be used in the discussions currently engaged about the revision of the Law governing narcotics and will be a baseline for future follow up of the situation.

First nationwide study on driving under the influence of drugs in Switzerland.

In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Delta(9)-tetrahydrocannabinol THC is >or=1.5ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are >or=15ng/ml in whole blood (confidence interval+/-30%). For all other psychoactive substances, impairment must be proven in applying the so-called "three pillars expertise". At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31+/-12 years (range 14-92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% (N=530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.

Traitement médicamenteux actuel de l'épiepsie [Current drug treatment for epilepsy]

If one patient is diagnosed with epilepsy, the first treatment line is represented by medications, which allow a seizure control in at least 2/3 of patients. Following the steady development of new compounds, there are currently more than 20 antiepileptic agents on the market, and several more will appear in the near future. This review, focusing on the indications and pitfalls of the most used drugs, with a particular attention to the new ones, aims at improving the orientation among this multitude of options. Since there is almost no difference regarding the efficacy on seizures, it is rather the profile of comorbidities and possible (positive and negative) side effects that will allow to select the best antiepileptic drug for each specific clinical situation, permitting a patient-tailored approach.

Evaluation of the Adolescent Drug Abuse Diagnosis instrument in a Swiss sample of drug abusers.

OBJECTIVE: The aim of this study was to evaluate a French language version of the Adolescent Drug Abuse Diagnosis (ADAD) instrument in a Swiss sample of adolescent illicit drug and/or alcohol users. PARTICIPANTS AND SETTING: The participants in the study were 102 French-speaking adolescents aged 13-19 years who fitted the criteria of illicit drug or alcohol use (at least one substance--except tobacco--once a week during the last 3 months). They were recruited in hospitals, institutions and leisure places. Procedure. The ADAD was administered individually by trained psychologists. It was integrated into a broader protocol including alcohol and drug abuse DSM-IV diagnoses, the BDI-13 (Beck Depression Inventory), life events and treatment trajectories. RESULTS: The ADAD appears to show good inter-rater reliability; the subscales showed good internal coherence and the correlations between the composite scores and the severity ratings were moderate to high. Finally, the results confirmed good concurrent validity for three out of eight ADAD dimensions. CONCLUSIONS: The French language version of the ADAD appears to be an adequate instrument for assessing drug use and associated problems in adolescents. Despite its complexity, the instrument has acceptable validity, reliability and usefulness criteria, enabling international and transcultural comparisons.

Neuropathies périphériques d'origine médicamenteuse [Drug-induced peripheral neuropathy].

Drug-induced peripheral neuropathies are common, secondary to multiple drug classes, in particular chemotherapeutic agents. They have an important impact on patients' quality of life. In recent years, significant progress has been made in the understanding of some pathophysiological mechanisms. The use of more objective assessment tools should allow the development of individualized and more effective therapeutic strategies.

Pharmacovigilance in pregnancy: adverse drug reactions associated with fetal disorders.

Abstract Objective: To provide the first update on drug safety profiles and adverse drug reactions (ADRs) associated with fetal disorders from the Swiss national ADR database. Methods: We conducted a retrospective study using data from 202 pharmacovigilance reports on drug-associated fetal disorders from the Swiss national ADR database from 1990 to 2009. Evaluated aspects included administrative information on the report, drug exposure, and disorders. Results: The ADR reporting frequency on the topic of fetal disorders has increased during the last 20 years, from only 1 report in 1991 to a maximum of 31 reports in 2008. Nervous system drugs were the most frequently reported drug group (40.2%) above all antidepressants and antiepileptics. The highest level of overall drug intake could be observed for the 1st trimester (85.4%), especially for the first 6 weeks of pregnancy. The most frequently reported types of fetal disorders were malformations (68.8%), especially those of the musculoskeletal and circulatory systems. A positive association was discovered between antiepileptics and malformations in general and in particular of the circulatory system and the eye, ear, face, and neck. Conclusions: The results suggest that the nervous system drug group bears an especially high risk for malformations. The most commonly identified drug exposures can help focus pharmacoepidemiologic efforts in drug-induced birth defects.

Stage of change of cigarette smoking in drug dependent patients.

Nicotine cessation programmes in Switzerland, which are commonly based on the stage of change model of Prochaska and DiClemente (1983), are rarely offered to patients with illicit drug dependence. This stands in contrast to the high smoking rates and the heavy burden of tobacco-related problems in these patients. The stage of change was therefore assessed by self-administered questionnaire in 100 inpatients attending an illegal drug withdrawal programme. Only 15% of the patients were in the contemplation or decision stage. 93% considered smoking cessation to be difficult or very difficult. These data show a discrepancy between the motivation to change illegal drug consumption habits and the motivation for smoking cessation. The high proportion of patients remaining in the precontemplation stage for smoking cessation, in spite of their motivation for illicit drug detoxification, may be due to the perception that cessation of smoking is more difficult than illicit drug abuse cessation.

HIV-1 co/super-infection in intravenous drug users.

BACKGROUND: The frequency of HIV-1 co/super-infection is unknown despite their implications for public health and vaccine development. This issue was addressed during an epidemic of both CRF11 and B subtype among intravenous drug users (IVDUs). METHODS: Bulk sequencing of reverse transcriptase, protease and C2V3 regions and subtype-specific nested polymerase chain reaction (PCR) in plasma and proviral DNA were performed using baseline and follow-up samples collected in recently infected IVDUs between 1998-2002 and in IVDUs with chronic infection living in the same area and presenting an unexpected rise of viremia (> 1 log10). RESULTS: In 58 recently infected patients, three B/CRF-11 co-infections, 25 B, 28 CRF-11 and two other subtypes were detected at baseline. In the three co-infected patients, both CRF-11 and B were detected in plasma and proviral DNA and persisted during follow-up. B- and CFR-11-specific PCR performed on follow-up samples of 40 of 58 recently infected patients (median follow-up, 14.5 months) revealed a transient B super-infection in a patient initially infected by CRF-11. Five of 156 chronic IVDUs (total follow-up: 346 years) had an unexpected rise of viremia. In two of them, aviremic without treatment for years after an initial B infection, a symptomatic CRF-11 super-infection occurred and was associated with high viral load and a fall of CD4 cell count. CONCLUSIONS: In recently infected IVDUs, co-infection B/CRF-11 is relatively frequent (5%). In chronically infected IVDUs super-infection may be transient and may occur in patients controlling efficiently HIV infection by the initial strain.

Antiretroviral drug toxicity in relation to pharmacokinetics, metabolic profile and pharmacogenetics.

Introduction: Besides therapeutic effectiveness, drug tolerability is a key issue for treatments that must be taken indefinitely. Given the high prevalence of toxicity in HIV therapy, the factors implicated in drug-induced morbidities should be identified in order to improve the safety, tolerability and adherence to the treatments. Current approaches have focused almost exclusively on parent drug concentrations; whereas recent evidence suggests that drug metabolites resulting from complex genetic and environmental influences can also contribute to treatment outcome. Pharmacogenetic variations have shown to play a relevant role in the variability observed in antiretroviral drug exposure, clinical response and sometimes toxicity. The integration of pharmacokinetic, pharmacogenetic and metabolic determinants will more probably address current therapeutic needs in patients. Areas covered: This review offers a concise description of three classes of antiretroviral drugs. The review looks at the metabolic profile of these drugs and gives a comprehensive summary of the existing literature on the influence of pharmacogenetics on their pharmacokinetics and metabolic pathways, and the associated drug or metabolite toxicity. Expert opinion: Due to the high prevalence of toxicity and the related risk of low adherence to the treatments, association of kinetic, genetic and metabolic markers predictive of therapeutic or toxicity outcomes could represent a more complete approach for optimizing antiretroviral therapy.

Therapeutic Drug Monitoring (TDM) of Imatinib: Effectiveness of Bayesian dose adjustment for CML patients enrolled in the Imatinib Concentration Monitoring (I-COME) study

Introduction: As imatinib pharmacokinetics are highly variable, plasma levels differ largely between patients under the same dosage. Retrospective studies in chronic myeloid leukemia (CML) patients showed significant correlations between low levels and suboptimal response, as well as between high levels and poor tolerability. Monitoring of trough plasma levels, targeting 1000 μg/L and above, is thus increasingly advised. Our study was launched to assess prospectively the clinical usefulness of systematic imatinib TDM in CML patients. This preliminary analysis addresses the appropriateness of the dosage adjustment approach applied in this study, which targets the recommended trough level and allows an interval of 4-24 h after last drug intake for blood sampling. Methods: Blood samples from the first 15 patients undergoing 1st TDM were obtained 1.5-25 h after last dose. Imatinib plasma levels were measured by LC-MS/MS and the concentrations were extrapolated to trough based on a Bayesian approach using a population pharmacokinetic model. Trough levels were predicted to differ significantly from the target in 12 patients (10 <750 μg/L; 2 >1500 μg/L along with poor tolerance) and individual dose adjustments were proposed. 8 patients underwent a 2nd TDM cycle. Trough levels of 1st and 2nd TDM were compared, the sample drawn 1.5 h after last dose (during distribution phase) was excluded from the analysis. Results: Individual dose adjustments were applied in 6 patients. Observed concentrations extrapolated to trough ranged from 360 to 1832 μg/L (median 725; mean 810, CV 52%) on 1st TDM and from 720 to 1187 μg/L (median 950; mean 940, CV 18%) on 2nd TDM cycle. Conclusions: These preliminary results suggest that TDM of imatinib using a Bayesian interpretation is able to target the recommended trough level of 1000 μg/L and to reduce the considerable differences in trough level exposure between patients (with CV decreasing from 52% to 18%). While this may simplify blood collection in daily practice, as samples do not have to be drawn exactly at trough, the largest possible interval to last drug intake yet remains preferable to avoid sampling during distribution phase leading to biased extrapolation. This encourages the evaluation of the clinical benefit of a routine TDM intervention in CML patients, which the randomized Swiss I-COME trial aims to.