Background: Benzodiazepines (BZD) and nonbenzodiazepines hypnotics (z-drugs) are recognized as one of the most widely prescribed medications in the world. Objectives: The purpose of the study was to ...assess the BZD and z-drugs dependence in young to middle-aged outpatients who were taking BZD/z-drugs on a chronic basis, and to characterize their profile. Methods: This is a forward-looking cross-sectional epidemiological study. Data were collected through a semi-structured interview within a network of partner pharmacies from the Nantes area, in France. All data were obtained exclusively through patients' declarations. 212 patients (19-64 years old) were included: they were considered dependent when they answered positively to at least three items of the DSM IV. A multivariate logistic regression and a principal component analysis (PCA) were carried out to determine their profile. Results: Almost half of the patients met criteria for BZD/z-drugs dependence. The risk to develop BZD/z-drugs dependence is significantly associated with psychiatric history and with the quantity of BZD/z-drugs that is taken. A two factor concept of dependence could be identified according to the PCA: one axis with items of "tolerance" and "long term administration or higher doses", and a second axis with "concerned by treatment" and "somatic consequences". Conclusions/Importance: Among this BZD/z-drug dependent population, the two axes identified in the PCA represent two profiles of dependence: being in positive conditioning or suffering from negative consequences. Clinicians need to know them: these two clinical profiles may have an influence in terms of decision-making, especially to manage discontinuation.
Background: The pediatric population displays its own pharmacological characteristics, making children vulnerable to adverse drug reactions (ADRs). Objective: To determine the incidence of ADRs among ...the pediatric emergency department (PED) population. Methods: This is a descriptive, noncontrolled, prospective, and single-center study, during 4 consecutive months in the PED of Nantes University Hospital. Results: Setting up active gathering of data on ADRs enabled 121 reports of 11 095 consultations at the emergency department, which corresponds to an ADR incidence of 1.09%. Digestive and cutaneous reactions made up the majority of reactions judged as being nonserious (53%) and were mainly found in children between 2 -11 years old. Of the serious ADRs, 25% were found in the 12-15-year-old age range because of the drug overdose. The main medications administered, which were responsible for the majority of the ADRs, were an equimolar mix of oxygen and nitrogen monoxide, amoxicillin, and acetaminophen. Three means of collecting data were possible: collecting files data, oral communication, or filling a form, the last being the most used method. Conclusions: This active data gathering shows the incidence and nature of the adverse effects as well as the age distribution in the PED population. It highlights the considerable misuse of medications among young teenagers and the high incidence of overmedication in the younger age group. This work also revealed the need for a better reporting system. Future joint studies should be carried out between clinical and pharmacological departments to optimize communication and the correct use of medications in children.
To our knowledge, no studies have been conducted in France on benzodiazepine (BZD) dependence among outpatients with alcohol use disorders (AUD). Some international studies have been conducted on the ...consumption of BZD in this specific population, but the comparisons among them are difficult. We aimed to assess the current prevalence of probable benzodiazepine and BZD-like hypnotics (Z-drugs) dependence among outpatients seeking treatment for AUD.
Participants were patients seeking treatment for AUD for the first time or repeating treatment after more than twelve months. Recruitment took place in seven addiction centres between January and December 2013 in the Nantes region (France). BZD/Z-drug dependence was assessed according to the DSM-IV diagnostic criteria for dependence. This information was gathered through a self-report questionnaire.
Among the 1005 patients included in this study, 413 were BZD/Z-drug users (41.1%). Among the 413 patients, 217 were probably dependent on at least one substance, which represents 21.6% of the total population and 52.5% of BZD/Z-drug users.
BZD/Z-drug dependence represents a public health concern. Prescribers should take the risks into account and keep treatment courses to a minimum.
We have compared two groups of chronic benzodiazepines (or zolpidem/zopiclone) users: "Seniors," aged 65 years or more, and "Adults," aged less than 65 years. The study took place in the Pays de ...Loire region. The questionnaire assesses dependence based on items from the DSM-IV. The analysis was based on 176 Senior questionnaires and 212 Adult questionnaires. Whereas Senior patients take benzodiazepines routinely with little negative consequences, Adults suffer from underlying psychological trouble, mention a higher consumption than planned, which causes negative consequences. 35.2% of Seniors are dependent on benzodiazepines versus 49.8% of Adults.
The metabolic pathways of dolutegravir and nevirapine suggest a potential pharmacokinetic interaction between these drugs. The objective of this study was to investigate the influence of nevirapine ...administration on the pharmacokinetics of dolutegravir in patients infected with HIV-1.
This study was an investigator-initiated trial registered at ClinicalTrials.gov under identifier NCT02067767. Dolutegravir (50 mg once daily) was added to the antiretroviral regimen (400 mg of nevirapine once daily + 600/300 mg of abacavir/lamivudine once daily) in 10 adult patients for 5 days. After discontinuation of nevirapine, the combination of dolutegravir + abacavir/lamivudine was continued. Full pharmacokinetic profiles were assessed on the day of nevirapine discontinuation and 2 weeks after discontinuation of nevirapine. The pharmacokinetic parameters of dolutegravir were calculated by non-compartmental analysis. The log-transformed values of these parameters were compared between periods with and without nevirapine co-administration.
The co-administration of nevirapine led to a significant decrease (P < 0.05) in the area under the plasma concentration-time curve for dolutegravir from the time the dose was administered until the end of the dosing interval (-19%, P = 0.011), as well as decreases in trough plasma concentration (-34%, P = 0.018) and terminal half-life (-15%, P = 0.039), and a significant increase (P < 0.05) in apparent oral clearance for dolutegravir (+23%, P = 0.011).
The decrease in dolutegravir exposure in combination with nevirapine suggests that the metabolism of dolutegravir is induced by nevirapine. According to therapeutic drug monitoring for dolutegravir, some patients may need a higher dose than 50 mg of dolutegravir once daily to maintain the therapeutic plasma concentration throughout the dosing interval.
Objectives
Assess the stability of several antibiotics in peritoneal dialysis (PD) solutions under common conditions of use in pediatrics, particularly in automated PD.
Methods
Amoxicillin, ...cefazolin, cefepime, ceftazidime, imipenem, cotrimoxazole, tobramycin, vancomycin, and the association of ceftazidime + vancomycin and ceftazidime + tobramycin, were tested in 3 different PD solutions: bicarbonate/lactate solution with 2 glucose concentrations (Physioneal 1.36 and 3.86%; Baxter Healthcare Corporation, Deerfield, IL, USA) and an icodextrin-containing solution (Extraneal; Baxter Healthcare Corporation, Deerfield, IL, USA). Concentrations were those recommended in guidelines for the treatment of peritonitis in pediatrics. Physioneal bags were incubated at 37°C for 24 hours, whereas Extraneal bags were stored 12 hours at room temperature (22 ± 2°C) and then 12 hours at 37°C. Drug concentrations were determined using high performance liquid chromatography (HPLC). Each measure was taken in triplicate. Stability of antibiotics was defined as less than 10% degradation of the drug over time.
Results
Cefazolin, cotrimoxazole, tobramycin, and vancomycin were stable under studied conditions. Ceftazidime was stable 24 hours in icodextrin, 12 hours in Physioneal 1.36% and 6 hours in Physioneal 3.86%. The association of tobramycin or vancomycin did not influence the stability of ceftazidime. Cefepime and amoxicillin were stable 6 h, 4 h, and 8 h in Physioneal 1.36%, 3.86% and Extraneal, respectively. The stability of imipenem was very low: 2 h in Physioneal and 6 h in Extraneal. Moreover, an increasingly yellow coloration was observed with the use of imipenem, whereas no color change or precipitation occurred in other bags.
Conclusion
Cefazolin, tobramycin, cotrimoxazole, and vancomycin are stable in PD solutions up to 24 hours and can be administered in the PD bag for the treatment of peritonitis, even in automated PD under studied conditions. However, amoxicillin, cefepime, ceftazidime, and imipenem must be used with caution due to their lack of stability.
The principal outcome was to identify which hypnotics substances, medicated (benzodiazepines, antihistamine, antidepressant…) or not medicated (herbal medicine, homeopathy, melatonin…), were consumed ...by community pharmacy patients who reported taking something for sleep disorder, and which factors can influence the consumption of medicated substance rather than nonmedicated substance. Data were collected via a network of 73 partner pharmacies around Nantes, France. Patients who reported taking a substance to sleep completed a questionnaire that collected data relative to the different substances consumed by that person for sleep, and the desired effect. Substances were classified in Hypnotic Drug Substances and nonmedicated hypnotic substances. A logistical regression was done in order to highlight the factors associated with the consumption of Hypnotic Drug Substance rather than nonmedicated hypnotic substances. Six hundred and forty‐seven patients were included, with an average age of 58 years and 74% female. The principal strategy employed to combat sleep disorder was the consumption of Hypnotic Drug Substance (54%), followed by herbal medicine (32%) and homeopathy (19%). The factors positively associated with the consumption of a Hypnotic Drug Substance are age, living alone, being out of work, or in the process of looking for a job and being a parent. In our survey, the use of Hypnotic Drug Substance to help patients with sleep is far from systematic. On the other hand, among patients who consume HDS, misuse is still significant, particularly in terms of the duration of consumption.
The authors aimed at developing a liquid chromatography tandem mass spectrometry (LC-MS/MS) method with online extraction to determine (R)- and (S)- methadone enantiomers and its main metabolite ...2-ethylidine-1,5-dimethyl-3,3 diphenylpyrrolidine (EDDP) in plasma.
The analysis combined straightforward sample preparation, consisting of protein precipitation with acetonitrile, and an online enrichment by a flush/back-flush cycle before the second dimension chromatography.
Using D3-deuterated internal standards allows overcoming significant relative matrix effect. Our method was linear up to 2000ng/mL. This simple sample preparation provides sensitive (the limit of quantitation is 25ng/mL for (R,S)-methadone and EDDP and 12.5ng/mL for (R)- and (S)- methadone), accurate and precise (the intra-day and inter-day imprecision and inaccuracy are lower than 15%) quantification of the plasma concentration of these drugs.
We have developed a reliable LC-MS/MS method for both routine therapeutic drug monitoring and pharmacokinetics studies and for toxicology analysis in the setting of methadone treatment or intoxication
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•An enantiomeric separation of methadone is purposed.•A chiral column was used to separate (R), (S) methadone and EDDP.•An online SPE – LC-MS/MS system was used.•We report a complete method validation in accordance with the FDA and EMA guidelines.
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