Stigmatization towards electro convulsive therapy: Impact of practical teaching on medical and nursing students.

BACKGROUND: This study explored the impact of theoretical and practical teaching on electro convulsive therapy (ECT) on medical and nursing students' stigmatizing attitudes towards ECT and representations of it. METHOD: Fourth-year medical students and nursing students answered questions from the Questionnaire on Attitudes and Knowledge of ECT (QuAKE) and from the Mental Illness: Clinicians' Attitudes version 2 (MICA v2) scale. The questionnaires were completed before and after observing a 3-hour practical training session in the ECT unit. The endpoint was the impact of practical training as assessed by MICA and QuAKE scores. Multivariate analyses were used to explore the impact of practical training on MICA and QuAKE total scores. RESULTS: Stigmatizing attitudes and representations of both medical and nursing students towards ECT were reduced after practical training (ß=-4.43 [95% CI -6.15; -2.70] p=0.0001). The impact was greater in medical students (ß=-8.03; 95% CI [-10.71; -5.43], P=0.0001) than in nursing students (ß=-2.77; 95% CI [-4.98; to 0.44], P=0.02). Gender, psychiatric history in close persons, and having already followed a psychiatric/ECT course had no independent impact on stigmatizing attitudes towards ECT and representations of it. CONCLUSION: Practical training in ECT should be given to all health professionals to improve access to it.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

"It's possible": reducing the coercion in care for adults living with neurodevelopmental disorders: a mixed-methods study / « C'est possible ¼, réduire la coercition dans les soins pour les personnes adultes vivant avec des troubles neurodéveloppementaux : une étude à devis mixte

Introduction: Adults living with a neurodevelopmental disorder may present episodes of aggression, which may lead to the use of seclusion or restraint. The aim of the study was to assess the effect of an intervention aimed at reducing the use of coercive measures in a long-term care unit for adults suffering from a neurodevelopmental disorder with or without psychiatric co-morbidities. Method: The single-center study used a sequential mixed-methods explanatory design. Retrospective data on periods of seclusion, with and without physical restraint, were collected for the ten-month pre-intervention and post-intervention periods. A qualitative survey was conducted at the end of the intervention period among the health professionals working in the unit to review the implementation and the efficiency of the approach. Results: A significant decrease was observed between the pre- and post-intervention period in the number of seclusion and restraint sequences, the number of patients experiencing seclusion and restraint, and the duration of seclusion and restraint sequences. The efficiency of the approach was confirmed by the health care professionals and was attributed to leadership focused on limiting coercive measures, better adherence to legal obligations, team cohesion, and the implementation of alternative tools and methods. Discussion: Reducing the use of coercive measures with adults with neurodevelopmental disorders is possible. Further studies are needed to confirm the effectiveness of alternative strategies to seclusion and restraint.

Introduction: Les personnes adultes vivant avec un trouble neurodéveloppemental peuvent présenter des épisodes d'agressivité, susceptibles d'entrainer le recours à l'isolement à la contention. Le but de l'étude a été d'évaluer et d'explorer l'effet d'une démarche de moindre recours aux mesures coercitives dans une unité d'accueil au long cours de personnes adultes souffrant d'un trouble neurodéveloppemental, avec ou sans comorbidités psychiatriques. Méthode: L'étude monocentrique a utilisé un devis mixte séquentiel explicatif. Des données rétrospectives sur les données mensuelles agrégées des séquences d'isolement avec et sans contention ont été recueillies sur une période de 10 mois précédant l'intervention et une période de 10 mois postintervention. Une enquête qualitative a ensuite été réalisée auprès des professionnels de santé intervenant dans l'unité afin d'appréhender la mise en œuvre et l'efficience des interventions de moindre recours. Résultats: La comparaison des périodes pré- et postintervention met en évidence une diminution significative du nombre de séquences d'isolement et de contention, du nombre de patients exposés à une mesure d'isolement et de contention, et de la durée des séquences d'isolement et de contention. L'efficience de la démarche est confirmée par les soignants et expliquée par un leadership tourné vers la limitation des mesures coercitives, l'obligation légale, la cohésion d'équipe, et la mise en place d'outils et de méthodes alternatives. Discussion: La diminution de la coercition auprès des personnes adultes souffrant d'un trouble neurodéveloppemental est possible. D'autres études sont nécessaires pour confirmer l'efficience de stratégies alternatives à l'isolement et à la contention.

"It's possible", reducing the coercion in care for adults living with neurodevelopmental disorders: A mixed-methods study / « C'est possible ¼, réduire la coercition dans les soins pour les personnes adultes vivant avec des troubles neurodéveloppementaux : une étude à devis mixte

INTRODUCTION: Adults living with a neurodevelopmental disorder may present episodes of aggression, which may lead to the use of seclusion or restraint. The aim of the study was to assess the effect of an intervention aimed at reducing the use of coercive measures in a long-term care unit for adults suffering from a neurodevelopmental disorder with or without psychiatric co-morbidities. METHOD: The single-center study used a sequential mixed-methods explanatory design. Retrospective data on periods of seclusion, with and without physical restraint, were collected for the ten-month pre-intervention and post-intervention periods. A qualitative survey was conducted at the end of the intervention period among the health professionals working in the unit to review the implementation and the efficiency of the approach. RESULTS: A significant decrease was observed between the pre- and post-intervention period in the number of seclusion and restraint sequences, the number of patients experiencing seclusion and restraint, and the duration of seclusion and restraint sequences. The efficiency of the approach was confirmed by the health care professionals and was attributed to leadership focused on limiting coercive measures, better adherence to legal obligations, team cohesion, and the implementation of alternative tools and methods. DISCUSSION: Reducing the use of coercive measures with adults with neurodevelopmental disorders is possible. Further studies are needed to confirm the effectiveness of alternative strategies to seclusion and restraint.

Introduction: Les personnes adultes vivant avec un trouble neurodéveloppemental peuvent présenter des épisodes d'agressivité, susceptibles d'entrainer le recours à l'isolement à la contention. Le but de l'étude a été d'évaluer et d'explorer l'effet d'une démarche de moindre recours aux mesures coercitives dans une unité d'accueil au long cours de personnes adultes souffrant d'un trouble neurodéveloppemental, avec ou sans comorbidités psychiatriques. Méthode: L'étude monocentrique a utilisé un devis mixte séquentiel explicatif. Des données rétrospectives sur les données mensuelles agrégées des séquences d'isolement avec et sans contention ont été recueillies sur une période de 10 mois précédant l'intervention et une période de 10 mois postintervention. Une enquête qualitative a ensuite été réalisée auprès des professionnels de santé intervenant dans l'unité afin d'appréhender la mise en œuvre et l'efficience des interventions de moindre recours. Résultats: La comparaison des périodes pré- et postintervention met en évidence une diminution significative du nombre de séquences d'isolement et de contention, du nombre de patients exposés à une mesure d'isolement et de contention, et de la durée des séquences d'isolement et de contention. L'efficience de la démarche est confirmée par les soignants et expliquée par un leadership tourné vers la limitation des mesures coercitives, l'obligation légale, la cohésion d'équipe, et la mise en place d'outils et de méthodes alternatives. Discussion: La diminution de la coercition auprès des personnes adultes souffrant d'un trouble neurodéveloppemental est possible. D'autres études sont nécessaires pour confirmer l'efficience de stratégies alternatives à l'isolement et à la contention.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

The risk of dementia in patients using psychotropic drugs: Antidepressants, mood stabilizers or antipsychotics.

OBJECTIVE: The risk of dementia associated with the use of psychotropic drugs is not fully understood. A nested case-control study was carried out to assess the risk of dementia broadly defined or Alzheimer's disease associated with antidepressants, mood stabilizers or antipsychotics. METHODS: A cohort was formed from healthcare claim databases including all patients aged 50 and over with a first dispensing of the psychotropic drugs concerned between 2006 and 2017. Patients who developed dementia over the study period were considered as cases. The association between drug exposure prior to a five-year lag time and diagnosis of dementia was assessed by conditional logistic regression models. RESULTS: No association was found between dementia, either broadly defined or Alzheimer disease, and antidepressant or mood stabilizers. Findings were conflicting with regard to antipsychotics. First- and second-generation antipsychotics (FGA and SGA) were not associated with Alzheimer disease. SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (Odds ratio [OR] 2.00; 95%CI 1.06-3.79; p = 0.03). In a sensitivity analysis using a lag time of 3 years, ever use of SGA and SGA treatments of more than 3 months were associated with a higher risk of dementia broadly defined than no use of antipsychotics (OR 1.71; 1.10-2.67; p = 0.02 and OR 1.84; 1.03-3.32; p = 0.04, respectively). CONCLUSION: The association between antipsychotics and dementia should be further investigated to establish patients, specific drugs, and patterns of treatment at risk. Prescribers should remain cautious when prescribing them.

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Contrasting the Social Cognitive and Metacognitive Capacities Among Patients With Schizophrenia and Autism Spectrum Disorders Enrolled in Psychiatric Rehabilitation.

ABSTRACT: Unique deficits in synthetic metacognition have been found in schizophrenia when compared with other psychiatric conditions and community controls. Although persons with autism spectrum disorders (ASD) display similar deficits in social cognition relative to those with schizophrenia, to date no study has compared metacognitive function between these groups. We aimed to compare the metacognitive capacities of persons with schizophrenia and ASD and their associations with other outcomes (neurocognition, social cognition, depression, and quality of life). Fifty-six outpatients with schizophrenia or ASD (mean age, 32.50 [9.05]; 67.9% male) were recruited from two French Centers of Reference for Psychiatric Rehabilitation of the REHABase cohort. Evaluation included the Indiana Psychiatric Illness Interview, Metacognition Assessment Scale-Abbreviated, Movie for the Assessment of Social Cognition, and a large cognitive battery. Compared with those with schizophrenia, participants with ASD had higher self-reflectivity ( p = 0.025; odds ratio, 1.38 [1.05-1.86]) in univariable analyses. Metacognitive deficits may be found in ASD with a profile that varies from what is found in schizophrenia. It is possible that methods for enhancing metacognitive abilities during psychiatric rehabilitation may be refined to assist adults with ASD to better manage their own recovery.

Impact of anticholinergic load on functioning and cognitive performances of persons with psychosis referred to psychosocial rehabilitation centers.

BACKGROUND: Few studies have explored whether high-anticholinergic load may hamper rehabilitation in persons with schizophrenia. We aim to explore the associations between anticholinergic load of psychotropic treatment and functioning or cognitive performances of persons with psychosis engaged in psychosocial rehabilitation. METHODS: The study was performed using data collected at baseline assessment in the REHABase cohort including persons referred to a French network of psychosocial rehabilitation centers. The composite-rating scale developed by Salahudeen et al. was used to rate the anticholinergic load of psychotropic drugs prescribed at baseline assessment. The associations between total anticholinergic load score (categorized as 'low' <3 v. 'high' ⩾3) and functioning or cognitive characteristics were explored using multivariate analyses. RESULTS: Of the 1012 participants with schizophrenia spectrum disorders identified in the REHABase, half used at least two psychotropic drugs with anticholinergic activity and one out of three was prescribed at least one psychotropic drug with high-anticholinergic activity. High-anticholinergic load was significantly associated with lower stage of recovery [odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.05-2.76, p = 0.03], poor mental well-being (OR = 1.55, 95% CI 1.02-2.33, p = 0.04) and poor self-rated medication adherence (OR = 2.14, 95% CI 1.29-3.53, p = 0.003). Regarding cognition, a high-anticholinergic score was associated with poorer delayed-episodic memory (OR = 1.69, 95% CI 1.01-2.85, p = 0.05) and at the trend level with faster completion time on the test exploring executive performance (OR = 0.67, 95% CI 0.43-1.04, p = 0.07). CONCLUSIONS: The psychosocial rehabilitation plan of persons with psychosis should integrate optimization of psychotropic treatment in order to lessen the functional and cognitive impact of high-anticholinergic load.

Characteristics associated with self-reported medication adherence in persons with psychosis referred to psychosocial rehabilitation centers.

The aim of the present study was to explore the characteristics of psychotropic treatment and of psychosocial functioning associated with self-reported medication adherence in persons with psychosis engaged in rehabilitation. The study was performed in the REHABase cohort including persons referred to a French network of psychosocial rehabilitation centers. Treatment adherence was assessed using the Medication Adherence Rating Scale (MARS). The associations between MARS score (categorized as "low" < 7 vs. "high" ≥ 7) and functioning or psychotropic treatment characteristics were explored using multivariate analyses in 326 participants with schizophrenia spectrum disorders. Regarding psychotropic treatment, high anticholinergic load was the only characteristic associated with poor medication adherence (adjusted OR, aOR 1.98, 95% CI 1.07-3.66). Regarding functioning measures, participants with poor medication adherence were more likely to present with lower stage of recovery (aOR 2.38, 95% CI 1.31-4.32), poor quality of life (aOR 2.17, 95% CI 1.27-3.71), mental well-being (aOR 1.68, 95% CI 1.03-2.72) and self-esteem (aOR 1.74, 95% CI 1.05-2.87), and higher internalized stigma (aOR 1.88, 95% CI 1.09-3.23). Self-reported poor medication adherence is a marker of poor functioning in persons with psychosis. The MARS is a quick and simple measure of adherence that may be helpful in clinical and rehabilitation settings to identify persons with specific rehabilitation needs.

Long-term risk of hip or forearm fractures in older occasional users of benzodiazepines.

AIMS: This article sought to study the association between patterns of benzodiazepine (BZD) use and the risk of hip and forearm fractures in people aged 50 and 75 years or more. METHODS: In a representative cohort of the French National Health Insurance Fund of individuals aged 50 years or older (n = 106 437), we followed up BZD dispensing (reflecting their patterns of use) and the most frequent fall-related fractures (hip and forearm) for 8 years. We used joint latent class models to simultaneously identify BZD dispensing trajectories and the risk of fractures in the entire cohort and in those 75 years or older). We used a survival model to estimate the adjusted hazard ratios (aHRs) between these trajectories and the risk of fractures. RESULTS: In the entire cohort, we identified 5 BZD trajectories: non-users (76.7% of the cohort); occasional users (15.2%); decreasing users (2.6%); late increasing users (3.0%); and early increasing users (2.4%). Compared with non-users, fracture risk was not increased in either occasional users (aHR = 0.99, 95% confidence interval [CI] 0.99-1.00) or in decreasing users (aHR = 0.90, 95% CI 0.74-1.08). It was significantly higher in early increasing users (aHR = 1.86, 95% CI 1.62-2.14) and in late increasing users (aHR = 1.39, 95% CI 1.15-1.60). We observed similar trajectories and risk levels in the people older than 75 years. CONCLUSION: Occasional BZD use, which is compatible with current recommendations, was not associated with an excess risk of the most frequent fall-related fractures in people older than 50 or 75 years.

Misuse of benzodiazepines: Prevalence and impact in an inpatient population with psychiatric disorders.

AIMS: Use and misuse of benzodiazepine might be very prevalent in patients with acute psychiatric symptoms, whereas they might be associated with specific adverse events in this population. The study investigated their prevalence in these patients. Secondary objectives were to identify risk factors for misuse of benzodiazepines, and its impact. METHODS: A cohort study was based on the hospital's electronic patient records and conducted in patients aged 18 years and over and admitted to a psychiatric hospital. They were followed up for 84 days or until the end of hospitalisation. Four variables of misuse were built: excessive duration of treatment, type of product, excessive dosage and concomitant benzodiazepines. Backward stepwise multivariate logistic regression analysis was used to assess risk factors for each misuse criterion, on the 1 hand, and impact of benzodiazepine misuse, on the other. RESULTS: In total, 511 psychiatric inpatients were included with 89.0% of them exposed to benzodiazepine. Discharge prescription included no benzodiazepine or a dosage lower than the maximum dosage prescribed during hospitalisation for 78.2% of patients exposed to benzodiazepine during their stay. Of benzodiazepine treatments, 31.4% were associated with at least 1 misuse criterion. Excessive dosage was associated with age ≥65 years (OR 11.57; 95% confidence interval 4.92-27.17), substance/alcohol use disorders (3.35; 95% confidence interval 1.70-6.62) and parenthood (0.49; 0.25-0.97). Some criteria of benzodiazepine misuse were associated with a higher frequency of adverse events occurring after treatment initiation. CONCLUSIONS: Misuse of benzodiazepines is very common in inpatients with psychiatric disorders. These findings should alert clinicians to comply with clinical recommendations.

Trajectories of Antipsychotic Drug Use Over 10 Years in a French Community-Based Sample of Persons Aged 50 and Older.

OBJECTIVE: To identify the temporal prescribing patterns of antipsychotics among persons aged 50 and older and to explore the demographic and clinical characteristics associated with each trajectory of antipsychotic drug use. METHODS: This was a historical fixed cohort study on a community-based sample of persons affiliated with the French Insurance Healthcare system. Data from community drug reimbursement claims were collected by the French Insurance Healthcare system over the period 2006-2015. The study included 160,853 persons aged 50 and older. Trajectories of antipsychotic drug use were identified by examining the distribution of antipsychotic use within consecutive 3-month periods over the entire follow-up period. Latent class analyses were used to identify distinct trajectories. Multivariate polynomial logistic regression models were used to explore the characteristics independently associated with trajectories. RESULTS: Five trajectories of antipsychotic use were identified: null or very low use (93.8%), occasional use (2%), decreasing use (1.6%), chronic use (1.5%), and increasing use (1.1%). Occasional users were older and had a lower use of other psychotropic drugs and a high use of health resources. Chronic users had the highest frequency of chronic psychiatric diseases and were less likely to present with dementia or Parkinson disease. Persons with increasing use of antipsychotics were more frequently males and had a high frequency of dementia; half of them died over the follow-up period compared with 20% in the total sample. CONCLUSION: Further studies should explore whether the benefit-risk ratio of antipsychotic drugs in older adults differs according to trajectories of use.

Trends in patterns of antidepressant use in older general population between 2006 and 2012 following publication of practice guidelines.

OBJECTIVE: The French regulatory agency published in 2006 practice guidelines related to the management of depressive and anxiety disorders. The main objective of the study was to assess their impact regarding use and monitoring of antidepressant drug treatment in older patients. The secondary objective was to identify factors associated with compliance with practice guidelines. METHODS: A historical fixed cohort study with dynamic follow-up time was conducted in 16,144 subjects aged 65 years and over, initiating antidepressant treatment and registered in the National Health Insurance Database between 2006 and 2012. Compliance with guidelines was assessed from year to year using segmented regression analysis. Multiple logistic regressions were used to identify factors associated with compliance with guidelines. RESULTS: Duration of antidepressant treatment was compliant with guidelines in 13.0% of patients aged 65-74 years and 18.5% of patients aged 75 years and over. Biological monitoring was performed in 12.6% of patients aged 65-74 years and 18.5% of patients aged 75 years and over. No significant change of rate of compliance with guidelines was observed over the study period. Compliance of prescriptions with guidelines was associated with patient's age, specialty of the prescriber, presence of chronic disease, year of treatment initiation, and presence of a university hospital in the area of residence. CONCLUSION: While treatment duration and biological monitoring were often inadequate in older patients, the publication of guidelines by the French health regulatory authorities did not lead to any significant and sustained improvement in their patterns of antidepressant use. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of pharmacy-based and diagnosis-based comorbidity measures from medical administrative data.

PURPOSE: Health status is sometimes quantified by chronic condition (CC) scores calculated from medical administrative data. We sought to modify two pharmacy-based comorbidity measures and compare their performance in predicting hospitalization and/or death. The reference was a diagnosis-based score. METHODS: One of the two measures applied an updated approach linking specific ATC codes of dispensed drugs to 22 CCs; the other used a list of 37 drug categories, without linking them to specific CCs. Using logistic regressions that took repeated measures into account and hospitalization and/or death the following year as the outcome, we assigned weights to each CC/drug category. Comorbidity scores were calculated as the weighted sum of the 22 CCs/37 drug categories. We compared the performance of both measures in predicting hospitalization and/or death with that of a diagnosis-based score based on 30 groups of long-term illnesses (LTIs), a status granted in France to exempt beneficiaries with chronic diseases from copayments. We assessed the predictive performance of the scores with the quasi-likelihood under the independence model criterion (QIC), the c statistic and the Brier score. RESULTS: The two pharmacy-based scores performed better than the LTI score, with lower QIC and Brier scores and higher c statistics. Their predictive performance was very similar. CONCLUSIONS: While there is no clear consensus or recommendations about the optimal choice of comorbidity measure, both pharmacy-based scores may be useful for limiting confounding in observational studies among general populations of adults from health insurance databases. Copyright © 2016 John Wiley & Sons, Ltd.

Trends in incident use of benzodiazepines and Z-drugs in France from 2006 to 2012: a population-based study.

PURPOSE: To study trends in incident use of benzodiazepines in France between 2006 and 2012. METHODS: A cross-sectional study repeated yearly was conducted using data from the French national healthcare insurance system. New benzodiazepine users were defined as users without any benzodiazepine dispensing in the year prior to the first dispensing of benzodiazepine in each year. Relative changes in incidence of use were calculated with the year 2006 as reference; confidence intervals for changes were estimated using the bootstrap method. RESULTS: Over the study period, the incident use of benzodiazepines decreased from 6.2% to 5.9%; this corresponded to a 5.1% decrease (95%CI: -6.8% to -4.2%) for 2012 compared to 2006. The decrease mainly concerned hypnotics (-15.5%; -21.2% to -15.3%) and appeared more pronounced in people aged 18-44 years. Incident use of anxiolytics remained stable overall during the period (4.0% of the population). Within anxiolytics, incident use of long half-life benzodiazepines (bromazepam, prazepam) decreased in favor of short half-life benzodiazepines (alprazolam, oxazepam). This change concerned patients aged 65-79 and patients aged 80 years and over. Nevertheless, in 2012, nearly one third of incident users aged 65 years and over started a treatment with a long half-life benzodiazepine, mostly bromazepam. CONCLUSIONS: A limited decrease in incident benzodiazepine use was observed in France between 2006 and 2012 that concerned only hypnotics. Although congruent with recommendations, this improvement appears insufficient with regard to the level of exposure to these drugs in France. New actions especially targeting anxiolytic benzodiazepine use should be undertaken to consolidate these results. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome: a national survey of DES daughters and unexposed controls.

To explore whether prenatal exposure to diethylstilbestrol (DES) is associated with increased risk of poor psychological outcome independently of the occurrence of major somatic complications related to DES exposure. Data on health outcome were collected in women prenatally exposed to DES (n = 2566) and unexposed women (n = 2967) recruited in a French national survey. Women prenatally exposed to DES were 1.7 times more likely to have consulted a mental health specialist compared to unexposed women (adjusted odds ratio = 1.69, 95% confidence interval 1.47-1.96), independently of demographic characteristics, poor gynecological or obstetrical outcome, or history of cancer. Frequency of consultation with a mental health specialist in persons with a history of gynecological complications or cancer was comparable in women prenatally exposed to DES and unexposed women. Findings regarding psychological outcome obtained in the high-risk group of women prenatally exposed to DES may contribute to improving identification of psychological needs of all women presenting with gynecological abnormalities.

Comorbidities and concurrent medications increasing the risk of adverse drug reactions: prevalence in French benzodiazepine users.

PURPOSE: To estimate benzodiazepine prevalence of use and to quantify, in benzodiazepine users, the prevalence of comorbidities and concurrent medications increasing the risk of adverse drug reactions (ADRs). METHODS: Cross-sectional study performed using data from the French national healthcare insurance system. The prevalence of use was estimated by considering as users, patients who had at least one benzodiazepine reimbursement during the year 2013. Patients at increased risk for benzodiazepine ADRs were those who had (i) drug-drug interactions at risk for central nervous system and respiratory depression and (ii) comorbidities at risk for adverse respiratory effects, or for falls or fractures. RESULTS: Overall, the prevalence of benzodiazepine use in 2013 was estimated to be 13.8 %; it was higher among women and increased with age. This prevalence was 10.6 % for anxiolytic benzodiazepines, and 6.1 % for hypnotic benzodiazepines. Approximately half of the benzodiazepine users (48.1 %) were at increased risk for benzodiazepine ADRs; this proportion increased with age. Drug-drug interactions represented the most prevalent condition (39.3 % of benzodiazepine users). The drugs most frequently involved were opioids: analgesics (15.9 %) and antitussives (6.8 %). Overall, 11.3 % of benzodiazepine users had comorbidities at increased risk for adverse respiratory effects (13.9 % in those aged 65-79), and 7.0 % comorbidities at increased risk for falls or fractures (13.4 % in those aged ≥80). CONCLUSIONS: This study found that benzodiazepine use remained high in France, and that roughly half of the users presented with comorbidities and concurrent medications increasing the risk of ADRs. These findings are of concern, given that benzodiazepines are frequently used, and especially among the elderly.