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Aims: Although medicine misuse is a public health issue, it has multiple meanings in the medical literature. This study aimed to characterize, classify and identify the most appropriate definitions of medicine misuse. Methods: A systematic review was performed in Medline, ISI Web of Science, SocINDEX, PsycInfo, PsycArticles and Psychological and Behavioral Sciences Collection, using keywords related to "misuse", "appropriateness" and "medicine" between 1 November 2008 and 25 August 2020. Additional searches were conducted in websites of regulatory agencies and public health institutions. Two authors independently selected studies providing both definitions and examples of misuse, while a third resolved disagreements. Definitions were used to propose a hierarchical classification based on initiator, intent, purpose and context of medicine misuse. The study is registered on PROSPERO: CRD42018115789. Results: Of 3404 identified records, 51 were included. A total of 71 definitions and 74 examples of misuse were retrieved. When the prescriber is initiator and according to intent, potential medicine misuse referred to "intentional or unintentional prescribing not in line with clinical evidence". Based on context, they could prescribe medicines not clinically justified, i.e. overprescribing, or prescribe indicated medicines incorrectly, i.e. misprescribing. Among other groups of definitions, those overlapping with drug abuse or medication use errors were considered out‐of‐scope. Conclusion: This systematic review provides a comprehensive overview of the terms and definitions used to characterize medicine misuse and could serve as a basis for a terminology that makes clear distinctions between misuse, abuse and errors. [ABSTRACT FROM AUTHOR]

Considering their novelty and cost, post‐marketing evaluation is highly relevant for new anticancer drugs. Identify and characterize available and potentially useful databases for post‐marketing evaluation of these specific drugs is necessary. A review was conducted to identify available and accessible databases to study the post‐marketing evaluation of drugs in real‐life care setting. Databases identified have been classified into medico‐administrative databases, medical record databases, and databases resulting from ad hoc collections. Taking as examples databases available in France, each type was described as well as its strengths and limits for a potential use in the oncology field. Record linkage of medico‐administrative databases could cover almost the whole population and is now used to evaluate anticancer drugs (e.g., Système National des Données de Santé). Large medical record databases are still lacking, but efforts are currently made to give access to hospital data warehouses for research purposes. Finally, databases resulting from ad hoc collections are also available for some cancer localizations and allow to obtain highly valuable clinical and biological data. A range of important and valuable databases exist but, individually, none is enough to answer to all questions from health authorities, healthcare professionals, and patients. In order to obtain a complete overview on utilization, associated health outcomes and costs of these drugs, it seems necessary to better interlink available databases. [ABSTRACT FROM AUTHOR]

Using claims databases of a public healthcare program (Quebec) for the years 2010–2013, we conducted a cohort study of patients with acute ischemic stroke (AIS) to describe secondary prevention treatments and determine how they stood against practice guidelines. We compared the risk of death or AIS recurrence over 1 year in patients treated with anticoagulants, antiplatelets, and/or other cardiovascular drugs. In the month after discharge, 44.3% of the patients did not receive the recommended treatment and > 20% did not have any treatment. Untreated patients were younger, had less comorbidities, and a more severe AIS. Anticoagulants and antiplatelets were associated with a reduced risk of death or recurrence (hazard ratio (HR) 0.27; 95% confidence interval (CI) 0.20–0.36 and HR 0.25; 95% CI 0.16–0.38, respectively) compared with the untreated group. Effect size was similar for the other treatments. Findings confirm treatment benefits shown in clinical trials and emphasize the importance of AIS secondary prevention. [ABSTRACT FROM AUTHOR]

Eye lens membrane cells require high cholesterol concentrations that might be counteracted by lipid‐lowering drugs. Using a nationwide database, we conducted a nested case‐control study to evaluate the risk of cataract development associated with the use of lipid‐lowering drugs. Patients aged 45 years and over with first cataract surgery in 2014 (cases) and up to four controls matched on age, gender, diabetes, hypothyroidism, glucocorticoid use, cardiovascular risk, and area of residence were included in the study. Among the 2,811 cases and 11,106 matched controls included, analyses showed a significantly increased risk of cataract surgery for a cumulative exposure to fibrates exceeding 5 years (adjusted odds ratio (aOR) 1.58; 95% confidence interval (CI): 1.17–2.15), unlike cumulative exposure to statins, whatever the dose or duration of treatment (aORs from 1.00–1.08, none being significant). This study highlighted an increased risk of cataract surgery with prolonged use of fibrates but not of statins. [ABSTRACT FROM AUTHOR]

The article informs that bankruptcies and social plans expected in many sectors with correctness and courage of political choices and economic factors of the disaster. Topics include incredible concerns misuse of the drug and its consequences; and the domain of health, remember that the emergency plan for the public hospital of the hospital debt.

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. [ABSTRACT FROM AUTHOR]

Objective: To assess the characteristics of life-threatening adverse drug reactions in patients admitted to medical intensive care unit and to define those that could facilitate early identification.Design: A prospective 6-month observational study.Patients: Of the 436 admissions to the teaching hospital medical intensive care unit, all patients aged over 15 years and who had received documented drug treatment were included (n = 405).Measurements: Characteristics of patients [age, gender, underlying diseases, organ failure(s), drugs taken, Severity Acute Physiologic Score II, length of stay, outcome at discharge] were prospectively collected using a standardised questionnaire. A panel of experts assessed putative serious adverse drug reaction(s) for each drug taken and each organ failure at admission by using a standardised causality assessment method. Characteristics of patients with and without serious adverse drug reactions at admission were compared using univariate and then stepwise descending multivariate logistic regression.Results: Of the 405 patients included, 111 (27.4%) presented an adverse drug reaction leading to organ failure. In 48% of cases adverse drug reactions were preventable, 23% were undiagnosed and 19% contributed to death. Age over 75 years [odds ratio (OR) 2.25; 95% confidence interval (CI) 1.15-4.38; p = 0.02], having more than three drugs (OR 6.90; 95% CI 1.44-33.00; p = 0.02) and a diagnosis of haematological malignancy (OR 6.19; 95% CI 2.07-18.53; p = 0.001) were independently associated with serious adverse drug reactions.Conclusions: Preventable life-threatening adverse drug reactions were frequently involved in organ failure at admission to medical intensive care; many of them had not been identified. [ABSTRACT FROM AUTHOR]

Background: The French pharmacovigilance system is based on a network of 31 regional centres located in teaching hospitals and coordinated by the French Medicines Agency ("Agence Française de Sécurité Sanitaire des Produits de Santé" [Afssaps]). Since 1984, they have shared a common database of adverse drug reactions (ADRs) that are spontaneously reported by healthcare professionals. The objective of this study is to describe the characteristics of the reports and the reporting trends in the French pharmacovigilance spontaneous reporting database from 1986 to 2001.Methods: All the reports from January 1986 to December 2001 were included. Drugs and ADRs were translated to anatomical therapeutic chemical (ATC) codes and MedDRA classifications, respectively.Results: The total number of reports was 197 580 over the 16-year period, with linearly increase over time. The median (interquartile range [IQR]) age of the patients was 53 (34-70) and the male/female ratio was 0.82. The median (IQR) time between the date of occurrence of the ADR and the date of report was 73 days (34-166). The reporter was a specialist in 74% of the reports and a general practitioner in 17%. The annual rate of reporting according to medical demography strongly increased for the specialists, especially since 1994. At least one ADR was considered as serious in 44.8% of the reports. The ADRs were most frequently related to nervous system drugs (23%), followed by cardiovascular drugs (19%) and systemic anti-infectives (17%). The latter class had the fastest progression mostly due to antiretroviral therapy since 1996. According to the Medical Dictionary for Regulatory Activities (MedDRA) coding, the system organ most often reported was skin and subcutaneous tissue disorders (29%), followed by nervous system disorders (19%), gastrointestinal disorders (12%), blood and lymphatic system disorders (12%), vascular disorders (12%) and general disorders and administration site conditions (12%).Discussion: All spontaneous reporting systems are affected by under-reporting. One of their goals is to generate early signals, which might be more affected by reporting bias than by under-reporting. Some improvements should be made in the design of the French database, but data collected since 1986 constitute an essential tool for the routine work of the 31 pharmacovigilance centres.Conclusion: This first description of the data of the French pharmacovigilance database involving all drugs and ADRs shows an increasing tendency to reporting over time, especially in specialists and for systemic anti-infective drugs. The database that uses hierarchical international classifications for drugs and adverse reactions may be used for further studies and could be the basis for an automatic signal generation system. [ABSTRACT FROM AUTHOR]

Introduction: The case-population approach compares exposure among cases to that of their source population. By using aggregated data to estimate the denominator, this approach can provide a real-time estimate of an association that could be particularly valuable to explore urgent vaccine safety concerns and to generate signals during a vaccine campaign. Objective: Our objective was to present the vaccine case-population method, a method derived from the case-population approach and adapted for vaccine safety surveillance, and to test it using several published examples. Methods: For the vaccine case-population method, exposure in the population is estimated from the sum of at-risk periods using the number of vaccinated individuals, or data of vaccine sales, and the at-risk period considered for the vaccine-event pair. The vaccine case-population method was applied to data from published case-control studies retrieved from the MEDLINE database and having quantified risks associated with vaccines. Odds ratios derived from the vaccine case-population method were compared with those from published case-control studies. Results: A total of 20 vaccine-event pairs were retrieved in which the vaccine case-population method could be applied. For all identified vaccine-event pairs, when a significant association was found using the vaccine case-population method, a significant association was also found in the corresponding case-control study. Conversely, when no association was found by the vaccine case-population method, no association was found in the corresponding case-control study. Conclusion: These results suggest that the vaccine case-population method can produce coherent conclusions and may be used in the future for prospective investigation of urgent vaccine safety concerns or for the prospective generation of vaccine safety signals. This method could also be used to identify selection bias from cases excluded from the case-control study. [ABSTRACT FROM AUTHOR]

Introduction: Investigations have highlighted the lack of evidence regarding the likelihood of congenital malformations following exposure to antipsychotic drugs during pregnancy. To gain further knowledge regarding their safety, we evaluated signals of congenital malformations with antipsychotics using VigiBase(®), the World Health Organization (WHO) Global Individual Case Safety Report (ICSR) database.Method: A case/non-case study was conducted in VigiBase(®) between 1967 and 2014. Signals of disproportionate reporting (SDRs) were detected using the proportional reporting ratio (PRR), which defines SDRs as drug-report associations with a PRR ≥2, Chi square ≥4, and number of cases ≥3. SDR detection for antipsychotics was performed for congenital malformations after removing all reports related to drug competitors and reports of movement disorders from the database.Results: After removing reports related to drug competitors (antiepileptics, antidepressants, antivirals) and movement disorders, three signals were revealed: 'palate disorders congenital' (PRR 2.1, 95 % CI 1.6-2.9, Chi square = 30; n = 41), 'oesophageal disorders congenital' (PRR 2.5, 95 % CI 1.3-4.7, Chi square = 11; n = 10) and 'anorectal disorders congenital' (PRR 3.0, 95 % CI 1.6-5.6, Chi square = 13; n = 11). Among antipsychotics, phenothiazines with a piperazine side-chain, risperidone and aripiprazole appeared to be more suspect.Conclusion: Confirming a first signal from spontaneous reporting data, three SDRs for antipsychotics and gastrointestinal congenital abnormalities were unmasked in VigiBase(®). This signal should be further explored by ad hoc pharmacoepidemiologic studies in order to assess whether it is relevant for prescription and public health. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction Benzodiazepine use has been associated with increased risk of dementia. However, it remains unclear whether the risk relates to short or long half-life benzodiazepines and whether it extends to other psychotropic drugs. Methods Prospective cohort study among 8240 individuals ≥65, interviewed on medication use. Incident dementia confirmed by an end point committee after a multistep procedure. Results During a mean of 8 years of follow-up, 830 incident dementia cases were observed. Users of benzodiazepines at baseline had a 10% increased risk of dementia (adjusted hazard ratio [HR], 1.10; 95% confidence interval, 0.90–1.34). However, long half-life (>20 hours) benzodiazepine users had a marked increased risk of dementia (HR = 1.62; 1.11–2.37) compared with short half-life users (HR = 1.05; 0.85–1.30). Users of psychotropics had an increased risk of dementia (HR = 1.47; 1.16–1.86). Discussion Results of this large, prospective study show increased risk of dementia for long half-life benzodiazepine and psychotropic use. [ABSTRACT FROM AUTHOR]

Use of atropinic drugs remains controversial in Parkinson's disease (PD) because there is insufficient evidence about their efficacy and they can induce serious adverse drug reactions. Atropinic risk scales were developed to help to identify atropinic drugs in prescription forms and to evaluate their burden in clinical practice. In the present review, we discuss the few studies investigating atropinic burden in PD and present the results of our study indicating that atropinic drugs are still widely prescribed in PD (almost 3 of 5 prescriptions) with a clinically significant atropinic burden in around 1 of 6 PD patients. Drugs mainly responsible for high values of atropinic burden were those used for nonmotor symptoms. Clinically significant atropinic burdens were mainly induced by associations of several "low-risk" drugs. Physicians must be aware that in addition to classical atropinic antiparkinsonian drugs, many others (psychotropics) can contribute to increased atropinic burden in PD patients. © 2016 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Since adverse drug reactions are a major public health concern, early detection of drug safety signals has become a top priority for regulatory agencies and the pharmaceutical industry. Quantitative methods for analyzing spontaneous reporting material recorded in pharmacovigilance databases through data mining have been proposed in the last decades and are increasingly used to flag potential safety problems. While automated data mining is motivated by the usually huge size of pharmacovigilance databases, it does not systematically produce relevant alerts. Moreover, each detected signal requires appropriate assessment that may involve investigation of the whole therapeutic class. The goal of this article is to provide a methodology for comparing two detected signals. It is nested within the automated surveillance framework as (1) no extra information is required and (2) no simple inference on the actual risks can be extrapolated from spontaneous reporting data. We designed our methodology on the basis of two classical methods used for automated signal detection: the Bayesian Gamma Poisson Shrinker and the frequentist Proportional Reporting Ratio. A simulation study was conducted to assess the performances of both proposed methods. The latter were used to compare cardiovascular signals for two HIV treatments from the French pharmacovigilance database. [ABSTRACT FROM AUTHOR]