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Little is known about psychoactive substance use in students, apart from tobacco, alcohol, and cannabis. This study investigated the prevalence of substance use and overlap between various psychoactive substances in students. This cross-sectional study was conducted in 10 066 students included in the i-Share cohort between January 1, 2015, and December 31, 2017. The baseline questionnaire was the key source of information. Psychoactive substances of interest (PSI) were cannabis, cocaine, amphetamines, nitrous oxide, poppers, and MDMA. Their patterns of use were categorized as lifetime, past year, and current use. The use of other psychoactive substances including alcohol and tobacco was described in PSI users and non-users. Most participants were female (75%), and their average age was 21 years. Lifetime use of at least one PSI was reported by 65.5% of participants. Cannabis was the most frequently used substance both over lifetime (57% of students) and past year (35%), followed by poppers and nitrous oxide (28% and 26% of students over lifetime, respectively). Among polydrug users (n = 1242), 65% used only nitrous oxide and poppers, showing a strong link between these two substances. Regular alcohol use, binge drinking, and current tobacco use were higher in PSI users than in non-users. Substance use was higher than previously found in both French and European studies in young people. Nitrous oxide use was particularly high. Regular alcohol use, binge drinking, and tobacco use could be used as markers to identify students at risk of PSI use to be targeted by prevention programs.

Summary Aim To describe the ambulatory changes in drug prescriptions 3 months after hospital discharge among elderly patients aged 75 and over, and to identify the reasons for these changes. Methods A prospective cohort study was conducted on subjects, discharged between 09/2016 and 01/2017 from the Bordeaux University Hospital. Prescription forms were collected from patients’ pharmacists. The main outcome was the occurrence of at least one significant change (SC) defined as an initiation, a discontinuation, a switch or change in drug daily dosage as regards the drugs prescribed upon hospital discharge and those prescribed 3 months after. Whenever drug SC occurred, general practitioners were requested to elicit reasons for such changes. Results Among the 126 patients included in our study, 73 underwent a 3-month follow-up period, without death or being re-hospitalised. 87.7% of them had at least one SC 3 months after discharge, with an average of 3.1 ± 2.5 SC per patient. Main changes involved: discontinuation or dose decrease of anxiolytics, hypnotics, antalgics, betablockers and calcium channel blockers; start or dose increase of diuretics, ACE inhibitors and angiotensin receptor blockers. In patients with a 3-month follow-up period, 27.4% underwent at least one ADR-induced SC. Conclusion Most elderly patients experience drug prescription changes after discharge. Some, according to drug iatrogenic, could be avoided through better cooperation between hospital and ambulatory prescribers.

Background: In Nigeria, reporting pharmacovigilance issues including adverse drug reactions (ADRs) from health facilities is encouraged especially by health care professionals (HCPs). Objectives: This study assessed the knowledge, attitude and practice of HCPs regarding pharmacovigilance in teaching hospitals in the South-South geo-political zone of Nigeria. Methodology: A cross-sectional study was conducted in six selected teaching hospitals in the South-South zone of Nigeria. A semi-structured questionnaire was self-administered to 1200 HCPs (doctors, pharmacists and nurses). Information sought included demographics, knowledge, attitude and practice of pharmacovigilance especially ADRs reporting. The data was analysed using descriptive and inferential statistics. Results: The 796 adequately completed questionnaires were used for the analysis. The mean age (standard deviation, SD) of the participants was 39.0 (8.0) years and the mean duration of practice (SD) was 12.7 (8.2) years. Two hundred and forty-one (30.3 %) of HCPs had ever documented or reported ADRs, of which only 97 (40.2 %) had ever used the national ADRs reporting form. Most respondents 746 (93.7 %) knew they could submit ADRs reports relating to new medicines and submit reports of new and unexpected ADRs 683 (85.8 %). Fewer respondents 540 (67.3 %) would submit reports relating to herbal medicines, and 256 (32.2 %) mild ADRs. Four hundred and fifty-six (57.3 %) had no difficulty in determining whether to report ADRs. Overall, nurses appeared the least knowledgeable about reporting ADRs. On improving reports, 278 (34.9 %) respondents advocated increased awareness and education on ADRs reporting. Conclusion: The HCPs in tertiary hospitals in the South-South zone had a modest knowledge, positive attitude but poor reporting practices in pharmacovigilance which may be improved with education and easier reporting processes.

AIMS Poor efficacy has been reported for patients with BRAF mutations for metastatic colorectal cancer (mCRC). METHODS EREBUS is a French cohort study of wild-type (wt) KRAS unresectable mCRC patients initiating a first-line treatment with cetuximab from 2009 to 2010, followed for two years (five years for vital status). Molecular genetics platforms have provided additional RAS and BRAF mutation testing results. Progression-free survival (PFS) and overall survival (OS) were assessed according to tumour mutation (mt) status: RASmt/BRAFany, RASwt/BRAFmt and RASwt/BRAFwt. Multivariate Cox analyses were used to evaluate association between mutation status and death or progression. RESULTS A total of 389 patients were included in 65 centres and with a known tumour mutation status: 64 RASmt/BRAFany (21%), 33 RASwt/BRAFmt (13%) and 213 RASwt/BRAFwt (87%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, Eastern Cooperative Oncology Group performance status ≤ 1 75%, 76% and 79%, and liver-only metastases 39%, 33% and 40%. Median progression-free survival was 8.0 months [5.9-9.3] for patients with RASmt/BRAFany, 6.0 months [2.3-7.2] for patients with RASwt/BRAFmt, and 10.4 months [9.5-11.0] for patients with RASwt/BRAFwt. Respectively, median overall survival was 18.4 months [10.9-23.3], 9.7 months [6.9-16.6] and 29.3 months [26.3-36.1]. In multivariate analyses, progression (HR = 2.71 [1.79-4.10]) and death (HR = 2.79 [1.81-4.30]) were more likely for RASwt/BRAFmt vs RASwt/BRAFwt patients. CONCLUSIONS BRAF mutations were associated with markedly poorer outcomes in initially unresectable RASwt mCRC patients treated by cetuximab in first-line treatment.

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs. Suspected cotrimoxazole-induced ADRs cases reported to the Bordeaux regional pharmacovigilance centre (France) during a five-year period were described. Seriousness was assessed according to international criteria. Quality of prescription was assessed by compliance with the Summary of Product Characteristics (SPC) and relevance of cotrimoxazole indication. Then, an ADR was considered as preventable if the cotrimoxazole indication was not relevant, or potentially preventable if indication was relevant but the prescription was not compliant with the SPC. A total of 96 cases were analyzed: median age was 60.5 years (range: 4-94); 59.4% of patients were male. ADRs were mostly cutaneous disorders (n = 46) and hematological disorders (n = 25). A total of 60 serious ADRs occurred in 55 patients. Prescribers complied with all SPC recommandations in 21.9% of cases. Indication of cotrimoxazole was relevant or highly relevant in 41 cases. In 58% of cases, the occurrence of a cotrimoxazole-induced ADR would have been preventable or potentially preventable. In a context of increasing interest for this antibiotic to treat infections due to resistant bacteria, physicians should be more aware of the potential consequences of inappropriate prescribing cotrimoxazole and reserve its use when there is no alternative and under suitable monitoring.

Objective To quantify benzodiazepine use non-compliant with guidelines in patients with psychiatric and non-psychiatric chronic diseases and assess the risk of non-recommended use associated with these diseases. Method A cohort study was conducted in the French health insurance databases, including 254,488 new benzodiazepine users between 2007 and 2014. Psychiatric, cardiovascular, cancer, diabetes and inflammatory diseases were identified. Patients were followed for 2 years. Non-recommended use was defined as excessive treatment duration, use of long half-life drugs in older patients and concomitant use of several benzodiazepines. Cox models identified the factors associated with non-recommended use. Results Non-recommended use was frequent, ranging from 44.9% to 68.1%. It was independently associated with each chronic disease, with a slight increase in patients with chronic inflammatory disease (HR = 1.07; 95%CI 1.03–1.13) or diabetes (HR = 1.09; 1.06–1.12), a higher risk in those with chronic cardiovascular disease (HR = 1.34; 1.31–1.37) or cancer (HR = 1.30; 1.25–1.35) and the highest risk in those with psychiatric disease (HR = 2.04; 2.00–2.09). Conclusion Patients with chronic disease have a high risk of benzodiazepine use leading to a higher exposure than recommended. Prescribers should be aware of the need to comply with the recommendations, especially in these patients who are the most frail and vulnerable to adverse events.

Background: The association between multimorbidities and polypharmacy among elderly individuals is well documented, and polypharmacy has been shown to increase the risk of adverse drug events (ADEs). However, little information is available about the risks associated with the lifelong use of medications to treat chronic multimorbidities. Objective: To determine the prevalence and nature of high-risk prescriptions among primary-care patients with chronic multimorbidities. Methods: We studied a weighted stratified random sample of 105 prescriptions for different patients with chronic multimorbidities taken from the Polychrome database established using information from the French primary-care record database (Observatoire de la MedecineGenerale). A medication review was conducted to identify contra-indications and potential drug-drug interactions for each prescription. Results: Contra-indications were identified for 60 (57.1%) prescriptions, potential drug-drug interactions for 70 (66.7%), absolute contra-indications for 9 (8.6%), and inadvisable drug combinations for 11 (10.5%). In all, 19 (18.1%) different patients were at risk for major ADEs. Cardiovascular and nervous-system drugs contributed 66.2% of contra-indications and 69.3% of potential drug-drug interactions. Conclusions: This exploratory study confirms the high prevalence and potential seriousness of prescriptions at risk for ADEs in a population of primary-care patients with chronic multimorbidities. The high prevalence of interactions involving the cardiovascular and nervous systems indicates that efforts to improve prescription practices should target these two categories of conditions and drugs in patients with chronic multimorbidities.

Benzodiazepines and z-drugs are primarily indicated for the treatment of sleep disorders and anxiety symptoms. Their frequent long-term use contrasts with the international guidelines that limit treatment duration to a maximum of 4 weeks. The objective of this study was to assess the frequency of their use that was not in accordance with guidelines in the French general population between 2007 and 2012 and associated characteristics. A cohort of 67,550 benzodiazepine new users was set up in an exhaustive database for health-care reimbursements and representative of the French population. Benzodiazepine use not in accordance with guidelines was defined as the concomitant dispensation of several benzodiazepines, the dispensation of treatment over a period longer than recommended, or a new dispensing within the 2 months following the end of a previous treatment of maximum recommended duration, considering that French recommendations distinguish between hypnotic (4 weeks) and anxiolytic benzodiazepines (12 weeks). Benzodiazepine use not in accordance with guidelines was high, in about 30% of new hypnotic users and 20% of new anxiolytic users. Its frequency was stable over the study period. Associated characteristics were similar for new hypnotic or anxiolytic users, i.e.. older age, treatment initiation by a psychiatrist, presence of a chronic disease, hospitalization, or another psychotropic treatment. These findings provide a solid basis for establishing a public health policy to reduce benzodiazepine use not compliant with guidelines. They should be further explored in patients most at risk in the present study, e.g., patients treated by a psychiatrist.

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.

Aims To investigate the association between the use of anxiolytic/hypnotic drugs and suicidal thoughts and/or behavior (STB) in students. Methods 12,112 participants who completed the baseline questionnaire in the i-Share cohort between April 2013 and March 2017 were included. STB were defined at inclusion as suicidal thoughts over the previous year and/or a lifetime suicide attempt. The use of prescribed anxiolytic/hypnotic drugs over the previous 3 months was measured at baseline and follow-up time points (in 2,919 students). Psychiatric disorders were assessed through validated scales. Multivariate logistic regression models were run using disease risk score. Results At inclusion, 25.2% of students had STB and 10.3% used anxiolytics/hypnotics. STB at baseline were associated with a more frequent use of anxiolytics/hypnotics in the previous 3 months, after adjustment for covariates including anxiety, depression, sleep, impulsivity, and substance use. The use of anxiolytics/hypnotics at baseline was not associated with the occurrence, persistence or remission of STB one year later. STB at baseline were associated with a new anxiolytic/hypnotic treatment one year later. Conclusions Anxiolytic/hypnotic drug use was associated with STB in students independently of many risk factors of suicide and most psychiatric disorders that require such treatment, which raises drug safety concerns.

The results of national safety studies are essential for decision-making at the regulatory level and have also educational implications for prescribing patterns. The aim of this study was to analyze the adverse drug reactions (ADRs) of analgesic medicines spontaneously reported to Pharmacovigilance and Risk Management Service of the Romanian National Agency for Medicines and Medical Devices between 2011 and 2015. For the 71 reports, patients had a mean age of 39.8 years; 60.6% of patients were female, and 38% male and 1.4% were unknown. Reporters were mainly physicians (74.7%), and 52.1% of ADR reports were transmitted through marketing authorization holders. Of the serious ADRs (32.4%), 34.7% led to hospitalization or prolonged hospitalization. The most frequent ADRs reported were skin and subcutaneous tissue disorders (25.8%) and general disorders and administration site conditions (19.2%). Metamizole, alone or in combination, was the main analgesic suspected in almost 15.5% of the cases and remains one of the most popular analgesics in Romania. Ten cases were assessed as preventable or potentially preventable (14%), of which two cases were serious. Even if the level of reporting is still low, this study conducted on ADRs of analgesics reported to the national pharmacovigilance center represents an essential step toward promoting the rational use of analgesics in Romania.

Background Quality of coding to identify cancers and comorbidities through the French hospital diagnosis database (Programme de medicalisation des systemes d’information, PMSI) has been little investigated. Agreement between medical records and PMSI database was evaluated regarding metastatic colorectal cancer (mCRC) and comorbidities. Methods From 01/01/2013 to 06/30/2014, 74 patients aged ≥ 65 years at mCRC diagnosis were identified in Bordeaux teaching hospital. Data on mCRC and comorbidities were collected from medical records. All diagnosis codes (main, related and associated) registered into the PMSI were extracted. Agreement between sources was evaluated using the percent agreement for mCRC and the kappa (κ) statistic for comorbidities. Results Agreement for primary CRC and mCRC was higher using all types of diagnosis codes instead of the main one exclusively (respectively 95% vs. 53% for primary CRC and 91% vs. 24% for mCRC). Agreement was substantial (κ 0.65) for cardiovascular diseases, notably atrial fibrillation (κ 0.77) and hypertension (κ 0.68). It was moderate for psychiatric disorders (κ 0.49) and respiratory diseases (κ 0.48), although chronic obstructive pulmonary disease had a good agreement (κ 0.75). Within the class of endocrine, nutritional and metabolic diseases (κ 0.55), agreement was substantial for diabetes (κ 0.91), obesity (κ 0.82) and hypothyroidism (κ 0.72) and moderate for hypercholesterolemia (κ 0.51) and malnutrition (κ 0.42). Conclusion These results are reassuring with regard to detection through PMSI of mCRC if all types of diagnosis codes are considered and useful to better choose comorbidities in elderly mCRC patients that could be well identified through hospital diagnosis codes.

Purpose To investigate sunitinib in the real-life first-line treatment of metastatic renal cell carcinoma (mRCC). Methods SANTORIN is a French observational multicentre cohort. Patients initiating sunitinib in first-line mRCC therapy were included (January 2008 to April 2010) and followed for 24 months. Data were collected from medical files. The outcomes were 24-month overall survival (OS) and progression-free survival (PFS), response and safety. Results Three hundred two patients were included: median age, 64.8 years; male, 73.2%; clear cell mRCC, 83.1%; prior nephrectomy, 85.4%; >1 metastatic sites, 64.2%; brain metastases, 6.3%; ECOG-PS ≥ 2, 9.9%. Median duration of first-line therapy with sunitinib was 10.7 months. Initial sunitinib dose was 50 mg/day for 83.4% of patients; dose reduction occurred in 65.2%. Sunitinib was discontinued in 73.2% of the patients: for progression (61.1%), death (31.2%) or adverse events (6.8%). More than half (58.3%) had grade ≥3 adverse events, mainly hypertension (12.6%) and hand–foot syndrome (12.3%). The 24-month OS and PFS rates [95%CI] were 49.5% [43.7;55.0] and 16.4% [12.5;20.9], respectively. Median OS was 23.6 months [20.2;–] and median PFS 8.4 months [7.6;9.9]. Overall best response rate was 31.1%. Conclusions Results from this large observational study suggest that effectiveness of sunitinib in first-line mRCC as predicted by clinical trials is maintained in real-life clinical practice. The expected benefit in poor-prognosis patients that were not evaluated in the pivotal clinical trial remains; however, questionable and long-term safety monitoring is still warranted. Copyright © 2017 John Wiley & Sons, Ltd.

Summary Background In February 2013, a retired French professor of medicine published a book denying the benefits of statins for cardiovascular prevention. The book was the subject of extensive media coverage and multiple public discussions and debate. Aims To investigate the impact of this media event on use of statins among regular users. Methods This repeated cohort study used the French claims database sample Echantillon generaliste des beneficiaires to identify regular statin users and quantify the number who discontinued statins after February 2013, compared to discontinuation patterns in previous years (2011 and 2012). Discontinuation was defined as a gap of at least 2 months without statin exposure. Results In 2013, 30,725 regular statin users were identified; 29,517 in 2012 and 28,272 in 2011. Statin discontinuation at 9-month follow-up in 2013 was 11.9% (95% confidence interval [CI] 11.5–12.2), compared with 8.5% (95% CI 8.2–8.8) in 2012 and 8.5% (95% CI 8.2–8.8) in 2011. Discontinuation varied according to cardiovascular risk: 19.4% (95% CI 18.2–20.6) in low risk, 11.6% (95% CI 11.1–12.0) in moderate risk, and 7.4% (95% CI 6.8–8.1) in high risk for the 2013 cohort. These discontinuation rates were, respectively, 1.53 (95% CI 1.36–1.72), 1.40 (95% CI 1.31–1.49), and 1.25 (95% CI 1.08–1.46) times higher in 2013 than in 2012 for low risk, moderate risk, or high risk patients. Conclusions The rate of statin discontinuation, overall and in each cardiovascular risk group, was greater in 2013 after the media event than in previous years. The clinical impact of the increased discontinuation could be important.

Contexte Les benzodiazepines sont souvent prescrites de maniere non conforme aux recommandations de bonne pratique, notamment chez les patients hospitalises en service de psychiatrie. Ce mesusage est associe a un risque accru d’evenements indesirables. Cette etude avait pour objectif de distinguer les traitements par benzodiazepine inities avant (traitement prevalent) ou pendant une hospitalisation (traitement incident) pour evaluer la frequence du mesusage et le risque d’evenement indesirable. Methodologie Une etude de cohorte a inclus des patients hospitalises en fevrier et juin 2016 au centre hospitalier Charles-Perrens. Quatre criteres de mesusage des benzodiazepines ont ete definies : posologie excessive, prescription concomitante de plusieurs molecules, duree de traitement excessive et type de produit. Les associations entre d’une part le caractere prevalent ou incident du traitement par benzodiazepine et, d’autre part, le mesusage de ces medicaments et les evenements indesirables qui pourraient leur etre attribues ont ete evalues par des modeles de regression logistique multivariee. Resultats Au total 454 patients hospitalises (88,9 %) etaient utilisateurs de benzodiazepines, 270 de maniere incidente et 184 prevalente. Pres d’un tiers remplissaient au moins un critere de mesusage et un quart un evenement indesirable sous traitement. Le fait qu’un traitement par benzodiazepine soit incident ou prevalent n’influait pas significativement sur le mesusage hormis la duree d’utilisation chez les patients avec une duree d’hospitalisation courte. Un traitement incident etait alors associe a un moindre risque de traitement long (RC 0,31 [0,10 ; 0,92]). Le caractere prevalent ou incident du traitement par benzodiazepine n’etait pas associe au risque d’evenement indesirable sous traitement. Conclusion Le mesusage de benzodiazepines est frequemment retrouve chez les patients hospitalises en psychiatrie, meme lorsque ce traitement a ete initie au cours de l’hospitalisation.

Background Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to confirm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel. Methods Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months. Results Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1–12.9]. In multivariate analyses, grade ≥ 3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade ≥ 3 adverse events were haematological with 8% febrile neutropenia. Conclusion Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25 mg/m2, median OS, respectively, 13.4 and 14.5 months). There was no effect of treatment-line on survival. No unexpected adverse concerns were identified. Study registration It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu, as EUPAS10391. It has been approved as an ENCEPP SEAL study.

Summary Aim of the study To provide a tool for drug misuse or potential misuse monitoring by using a healthcare insurance database. Methods A cross-sectional study repeated quarterly from 2007 to 2014 was conducted using data from a 1/97th random sample of the French national healthcare reimbursement system. For each drug studied, ad hoc indicators were designed to assess drug misuse, defined as prescriptions that did not comply with the label stipulated in the summary of product characteristics, in terms of the drug (e.g., interactions) or the patient (age, medical history). We focused on specifically identified situations of drug misuse involving non-steroidal anti-inflammatory drugs (NSAIDs), antiemetics in patients with Parkinson's disease and antipsychotics in pediatrics; we also focused on direct anticoagulants, asthma and oral antidiabetic drugs but results for these latter are only shown in supplementary materials. Results At-risk prescribing of NSAIDs in patients treated by diuretics or renin-angiotensin system inhibitors always remained higher than 14% over the study (maximum: 19%; 2014 quarter 4: 15.4%). Off-label prescribing of contraindicated anti-dopaminergic antiemetics with dopaminergic antiparkinson drugs was marginal (maximum: 2.2%; 2014 quarter 4: 0.5%) but represented at least 5.5% of antiemetic prescriptions. Despite the rise in antipsychotic prescriptions in pediatrics, no dramatic increase in misuse related to age was observed during the study period (2007 quarter 1: 16.1%; 2014 quarter 4: 11.1%). The highest degree of misuse was observed for aripiprazole and for second-generation antipsychotics other than risperidone and aripiprazole. Conclusion This study provides a simple tool to monitor drug misuse or potential misuse using information from a health insurance database. The results highlight the need for the Regulator to rethink risk management information campaigns and to modify the official information on products.

Some concerns have emerged about the evidence of benefits on survival outcomes or quality of life of new anticancer drugs. In parallel, the decreased cancer mortality leads to an increased number of patients exposed to cancer treatment-related consequences. In this context, pharmacoepidemiology is crucial to assess anticancer drug use, effectiveness and safety in real life conditions. We aimed to describe strengths, limitations and considerations associated with the use of the French national health insurance database (système national des données de santé [SNDS]) to conduct pharmacoepidemiological studies in oncology. The SNDS represents a powerful tool in pharmacoepidemiology owing to its extensive coverage, accurate description and quantification of drug exposure and individual data on patients. The main limitations of this database ensue from the administrative nature resulting in technical difficulties in its management and gaps in availability of data. Another limitation is the lack of accurate identification of diseases, comorbidities or outcomes and potential confounding with notably the lack of data regarding cancer stage, prognosis or risk factors. Finally, the accurate identification of the nature of chemotherapy received by patients is sometimes complex. To minimize these limitations, several approaches and statistical methods could be used as highlighted by national or international initiatives. First, the SNDS may be linked with cancer registry or clinical data. Then, several data sources could be combined using meta-analytical methods. The development of methodological tools and the use of standardized methods are crucial to enhance the quality of studies that can impact clinical practice and guide public decision. Pharmacoepidemiological approaches and pharmacovigilance represent an important cornerstone in oncology for signal detection or long-term follow up of cancer patients. In this context, validated methods to identify cancer patients and to describe chemotherapy regimens within these data should be promoted and remain too scarce despite international guidelines. Moreover, limits and strength of each data sources should be systematically discussed according to the research question. Optimized and framed use of claims database represents a future challenge in onco-pharmacoepidemiology.

Metastatic colorectal cancer (mCRC) is frequent among elderly patients. However, in the era of new targeted therapies, little is known about real-life mCRC treatment in this population. This study aimed to describe elderly mCRC patients and the current real-life treatment practices. mCRC patients aged ≥65 years were identified using the registry of multidisciplinary team meetings, mandatory for all cancer patients, held between January 1, 2013 and June 30, 2014 at the Bordeaux University Hospital. Data were collected from medical records using a standardized questionnaire. Treatment type was defined as follows: at least one anticancer medication administered vs. best supportive care (BSC). A total of 78 patients were included; median age was 74 years and the M/F sex ratio 1.6. Eleven patients (14.1%) were referred to a geriatric oncology consultation. One patient died before treatment initiation, 28 (35.9%) had BSC, and 49 (62.8%) were treated with anticancer medications: 20 (25.6%) had chemotherapy combined with a targeted therapy, and 28 (35.9%) chemotherapy alone (one missing data for treatment). Compared to patients treated with anticancer medications, BSC patients were older (P < 0.0001) and had more often metachronous metastases (P = 0.01), more comorbidities (P = 0.05), and a greater number of concomitant medications (P = 0.004). This study is one of the rare investigations providing insight to treatment practices in all elderly mCRC patients, not just those who receive anticancer medications. Our results suggest that efforts must be pursued to better integrate geriatric oncology in daily clinical practice.

Background: Non-persistence to oral hormonal therapy (HT) in breast cancer (BC) is an emerging health issue, and estimations vary according to the population selected and/or the statistical method applied. This study aimed to estimate non-persistence over 5 years to HT in an unselected sample of women with BC using a French national population-based database and accounting for competing risks. Methods: A retrospective cohort of 600 women initiating a HT between 2006 and 2007 was constituted using a representative sample of the French national healthcare insurance system database. The Cumulative Incidence Function method was used to estimate the probability of first treatment discontinuation of at least 90 days accounting for competing risk of death from any cause over the theoretical 5-year period of treatment. Results: Thirty one percent of patients who initiated a HT were identified as non-persistent at the fifth year of follow-up. Patients who switched to another HT (HR 3.10, 95% CI (2.20; 4.36)) or had metastatic BC (HR 3.07, 95% CI (1.73; 5.46)) were more likely to be non-persistent. Women who initiated aromatase inhibitors as compared with tamoxifen (HR 0.62, 95% CI (0.46; 0.83)), had administrative registration for BC (HR 0.21, 95% CI (0.13; 0.32)), or had received an adjuvant chemotherapy (HR 0.65, 95% CI (0.48; 0.89)) were less likely to discontinue. Conclusions: The estimate of long-term non-persistence in an unselected sample of women treated in France by oral hormonal therapy is substantial, even accounting for competing risks.

Nigeria was admitted into the WHO International Drug Monitoring Programme in 2004. That marked a new era of pharmacovigilance in Nigeria. Nigeria is a large country in sub-Saharan Africa with essentially a homogenous black population of over 170 million people, a significant disease burden (communicable and non-communicable) and consequent medication use. Inevitably, the need for medicine safety is becoming increasingly appreciated by the government, health-care workers and patients. Pharmacovigilance activities in Nigeria are coordinated by the National Pharmacovigilance Centre (NPC) situated in the National Agency for Food and Drug Administration and Control (NAFDAC—the drug regulatory agency in Nigeria). NPC serves as a repository for reported adverse drug reactions from health workers and also liaises with other international groups such as the WHO, US Food and Drug Administration and the European Medicines Agency in improving drug safety in Nigeria. Increasing participation of the public in drug safety is also a major thrust of the NPC and the contributions of public-health programmes in this resource-poor setting to pharmacovigilance cannot be overemphasised. The provisions of a unique policy to define the responsibilities of the stakeholders in pharmacovigilance, as well as training of the health-care workers, are a few of the achievements of the agency in charge of pharmacovigilance in Nigeria.

Introduction: Public health programs (PHPs) provide unique opportunities for addressing health issues in resource-limited settings. A major challenge to the implementation of existing PHPs in Nigeria is the absence of effective monitoring of the safety of medicines and vaccines. The introduction of the World Health Organization (WHO) pharmacovigilance (PV) indicators provides a useful tool to address this challenge. Objective: The objective is to assess the structures, processes, and outcomes of PV activities in three selected PHPs (the National Malaria, tuberculosis [TB], and HIV/AIDS) in Nigeria using the WHO PV indicators and identify possible challenges to achieving the outcomes. Materials and Methods: A cross-sectional mixed method study of the PV system in selected PHPs. Data sources were from the Federal Ministry of Health, the National PV Center (NPC), the National Malaria/TB, and HIV/AIDS Control Programs and official documents were reviewed. Data were collected quantitatively using the WHO PV and PHP indicator questionnaires and qualitatively using key informant interviews. Results: The basic structures and tools for carrying out PV activities in the PHPs were in existence but optimal implementation was lacking. Of the 790 adverse drug reaction (ADR) reports from the PHPs to the NPC ADR database, 77% were from the HIV/AIDS Control Programs, 14% from the malaria control program, and 9% from TB program. The interview with representatives of the different programs revealed a consensus of opinion around lack of adequate human resource for PV, poor funding, poor stakeholders' coordination to improve PV reporting across all three programs as well as in the NPC. Conclusion: This study highlighted the magnitude of suboptimal implementation of PV activities evident by the number of reports as against the expected.

The psychiatric patients are not only particularly exposed to benzodiazepines; they may also be more vulnerable to their side effects than general population. Benzodiazepines are frequently misused in psychiatric patients in terms of duration, dose and number of concomitant medications. There is no evidence that benzodiazepines are effective against most psychiatric disorders, including depression and suicidal risk. Several studies have shown associations between benzodiazepine use and depression worsening, increased disinhibition, suicide risk, anxiety, aggression, and even mortality in patients with psychiatric disorders. Despite the common use of benzodiazepine drugs by clinicians, large and methodologically sound studies are lacking to document the patterns of benzodiazepine use in populations with psychiatric disorders and their specific risks in these patients. It is not known whether it is legitimate to apply the good practice recommendations for benzodiazepines in patients with severe psychiatric disorders.

The psychiatric patients are not only particularly exposed to benzodiazepines; they may also be more vulnerable to their side effects than general population. Benzodiazepines are frequently misused in psychiatric patients in terms of duration, dose and number of concomitant medications. There is no evidence that benzodiazepines are effective against most psychiatric disorders, including depression and suicidal risk. Several studies have shown associations between benzodiazepine use and depression worsening, increased disinhibition, suicide risk, anxiety, aggression, and even mortality in patients with psychiatric disorders. Despite the common use of benzodiazepine drugs by clinicians, large and methodologically sound studies are lacking to document the patterns of benzodiazepine use in populations with psychiatric disorders and their specific risks in these patients. It is not known whether it is legitimate to apply the good practice recommendations for benzodiazepines in patients with severe psychiatric disorders.

Objectives Metastatic colorectal cancer (mCRC) is increasingly treated with targeted therapies, but little is known about real-life mCRC treatment in older adults. The aims were to describe the real-life first-line treatment modalities in older adult mCRC patients, to identify factors associated with treatment modalities, and to evaluate survival with regard to treatment modalities. Patients and methods A cohort of mCRC patients aged 65 years and older at diagnosis was identified between 2009 and 2013 using French national healthcare insurance system claims data. Treatment modalities were: treatment with one or more anticancer medication vs best supportive care and, among treated patients, treatment with targeted therapy vs conventional chemotherapy alone. Multivariate logistic regression was used to identify factors associated with treatment by anticancer medication and by targeted therapy. Cox proportional hazards models were used to assess the independent effect of treatment modalities on overall survival while adjusting for baseline covariates identified with logistic regression. Results A total of 503 patients were included with a median age of 78 years (54% were men). Of these, 299 (59%) were treated with anticancer medications. Among treated patients, 131 (44%) received targeted therapy. In multivariate analysis, age 75 years or older, renal failure, malnutrition, and five or more concomitant medications were associated with a lower likelihood of treatment with anticancer medications. Among treated patients, age 75 years or older, history of cancer, lymph node metastases, and a single metastatic site were associated with a lower likelihood of treatment with targeted therapy. Multivariate Cox proportional hazards models found that treatment with any anticancer medication tended to be associated with a lower risk of death; treatment with targeted therapy was not significantly associated. Conclusion A more appropriate prescription of anticancer medications in the older adult will require the definition of more explicit criteria to avoid undertreatment. The real benefit of targeted therapies vs conventional chemotherapy alone needs to be confirmed in this population. J Am Geriatr Soc 67:913-919, 2019.

International audience; Background: Our aim in this study was to evaluate the effect of a combined educational intervention and year-long monthly text message reinforcements via the Short Messaging System (SMS) on the knowledge, attitude and practice (KAP) of healthcare professionals (HCPs) towards pharmacovigilance.Methods: Six randomly selected teaching hospitals in the South-South zone of Nigeria were randomized in 1:1 ratio into intervention and control groups. The educational intervention consisted of delivering a seminar followed by sending monthly texts message reinforcements via SMS over 12 months. Then a semi-structured questionnaire regarding the KAP of pharmacovigilance was completed by HCPs working in the hospitals after the intervention. Data was analysed descriptively and inferentially.Results: A total of 931 HCPs participated in the post intervention study (596 in the intervention and 335 in the control). The M:F ratio was 1:1.5. According to the KAP questionnaire, a significant difference was observed between the intervention and control groups, regarding knowledge of the types of adverse drug reactions (ADRs). ADR resulting from pharmacological action of the drug (85.6% versus 77%, p = 0.001), the fact that ADRs can persist for a long time; (60.1% versus 53.4%, p = 0.024) and a higher awareness of the ADR reporting form (48.7% versus 18.8%, p < 0.001). Most respondents in the intervention group (68.5% versus 60.6%, p = 0.001) believed they should report ADRs even if they were unsure an ADR has occurred, a greater proportion of HCPs from the intervention group had significantly observed an ADR (82% versus 73.4%, p = 0.001). Furthermore, of the 188 who had ever reported an ADR, 41% from the intervention group used the national ADR reporting form compared with 19.8% from the controls (p < 0.001). Conclusion: This educational intervention and the use of SMS as a reinforcement tool appeared to have positively impacted on the knowledge and practice of pharmacovigilance in South-South Nigeria with a less-than-impressive change in attitude. Continuous medical education may be required to effect long-lasting changes.

Background WHO pharmacovigilance indicators have been recommended as a useful tool towards improving pharmacovigilance activities. Nigeria with a myriad of medicines related issues is encouraging the growth of pharmacovigilance at peripheral centres. This study evaluated the status of pharmacovigilance in tertiary hospitals in the South-South zone of Nigeria with a view towards improving the pharmacovigilance system in the zone. Methods A cross-sectional descriptive survey was conducted in six randomly selected tertiary hospitals in the South-South zone of the country. The data was collected using the WHO core pharmacovigilance indicators. The language of assessment was phrased and adapted in this study for use in a tertiary hospital setting. Data is presented quantitatively and qualitatively. Results A total of six hospitals were visited and all institutions had a pharmacovigilance centre, only three could however be described as functional or partially functional. Only one centre had a financial provision for pharmacovigilance activities. Of note was the absence of the national adverse drug reaction reporting form in one of the hospitals. The number of adverse drug reaction reports found in the databases of the centres ranged from none to 26 for the previous year and only one centre had fully committed their reports to the National Pharmacovigilance Centre. There were few documented medicines related admissions ranging from 0.0985/1000 to 1.67/1000 and poor documentation of pharmacovigilance activities characterised all centres. Conclusion This study has shown an urgent need to strengthen the pharmacovigilance systems in the South-South zone of Nigeria. Improvement in medical record documentation as well as increased institutionalization of pharmacovigilance may be the first steps to improve pharmacovigilance activities in the tertiary hospitals. Electronic supplementary material The online version of this article (10.1186/s40360-018-0217-2) contains supplementary material, which is available to authorized users.

Aims The purpose of this study was to determine the effects of cancer occurrence on persistence of oral antidiabetic drugs (OAD) in France. Methods A retrospective cohort including incident OAD users between 2006 and 2011 was set up using a permanent sample of health insurance beneficiaries (Echantillon Generaliste de Beneficiaires, EGB). A Cox model was used to assess the association between cancer occurrence and OAD persistence. Non-persistence was defined as a gap in OAD treatment coverage between the end of a given prescription and a new one greater than or equal to 90 days. Cancer occurrence was studied as a time-dependent variable. Results The study included 13,943 OAD users. Median follow-up was 760 days. After adjustment for age, sex, first OAD used, type of prescriber and polypharmacy, non-persistence risk was higher after a diagnosis of cancer: (HR: 1.93 and IC 95% 1.69; 2.21). Subgroup analyses according to cancer localization found a higher risk of non-persistence for lung cancer (HR: 2.66 and IC 95% 1.68; 4.23) and colorectal cancer (HR: 2.02 and IC 95% 1.40; 2.91). Conclusions Our findings indicate there is an association between cancer diagnosis and OAD non-persistence. Additional studies of this type would be useful to evaluate the association between cancer diagnosis and persistence of treatment of other chronic diseases.

Resection of metastases after chemotherapy improves survival outcomes of patients with initially inoperable metastatic colorectal cancer (mCRC), yet little data is available for those treated in the first-line setting with bevacizumab plus irinotecan. To provide data on this, the present study described the subgroup of the ETNA cohort who underwent metastases surgery. The population of operated patients was described according to metastatic site (exclusively hepatic, non-exclusively hepatic, and non-hepatic). Factors associated with overall survival (OS) and progression-free survival (PFS) were evaluated using multivariable Cox analysis. A total of 76 patients (21.1 % of the ETNA cohort) underwent metastases resection: 50 % male, median age 61.9 years, 85.5 % ECOG ≤ 1, and median duration of bevacizumab use 7.2 months. No surgery-related deaths were observed and 30.6 % of patients had at least one post-operative complication, mainly infections (11.8 % of resections), bleeding complications (3.5 %), or delayed wound healing (2.4 %). Complete remission was higher for those with exclusively hepatic metastases (22/32, 68.8 %) than those with non-exclusively hepatic metastases (12/24, 50.0 %), or non-hepatic metastases (12/20, 60.0 %). Among operated patients, 52.6 % had died after 5 years of follow-up. In multivariable analysis at 2 years of follow-up, death (HR 0.09 [95 % CI 0.02-0.35]) and progression (HR 0.35 [95 % CI 0.23-0.56]) were less likely for patients with complete remission (CR) after surgery R0-R1 or radiofrequency ablation (RFA) [CR RFA] compared with those who were not resected or with R2 resection. In real-life practice, bevacizumab with irinotecan in first-line therapy for mCRC allows secondary resection of metastases and survival is more favourable in those with complete remission (R0-R1/CR RFA).

The aims of this study were to determine the patterns of analgesic adverse drug reactions (ADRs) and to assess their preventability and contributing factors. This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported to the Bordeaux pharmacovigilance center from January 2011 to June 2012. The 141 cases selected for the analysis included 16 cases of medication errors (11.3 %) and 15 addiction cases (10.6 %). In total, 214 ADRs were registered, for which 173 analgesic medicines were suspected. The most frequent ADRs reported were nervous system disorders (26.6 %), psychiatric disorders (15.0 %), and skin and subcutaneous tissue disorders (12.1 %). Tramadol alone or in combination (17.3 %), followed by morphine (15 %), fentanyl (9.8 %), and paracetamol (8.7 %) were the most frequently involved analgesics. More than half of the cases (54.6 %) were serious and led to hospitalization or prolonged hospitalization. Preventability was determined for 134 cases (95 %): 51.5 % were considered as preventable, 26.1 % not preventable, and 22.4 % not assessable. The main contributing factors for the preventable cases included negligence of recommendations for analgesic use and failure to consider patients’ risk factors when prescribing. A significant number of analgesic ADRs could be prevented, and being aware of their contributing factors promotes efficient analgesia with minimum risks to the patients.

Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly. This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life. An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and

Treatment of metastatic colorectal cancer (mCRC) has been modified since the launching of targeted therapies. Colorectal cancer (CRC) is common in elderly patients; their representation in randomized controlled trials (RCTs) is thus crucial. This study aimed to evaluate and quantify the inclusion of elderly/frail patients in RCTs of targeted therapies in mCRC. A systematic review using Medline, Scopus, Cochrane Database and ISI Web of Science was performed to identify all phase II/III RCTs of bevacizumab, cetuximab, panitumumab, regorafenib and aflibercept in mCRC until January 2015. Two reviewers independently performed studies selection, and data extraction. The protocol was registered in Prospero (CRD42015016163). Among 1,369, identified publications, 54 RCTs were selected. Nine RCTs (17%) excluded elderly patients; median age of the included population was

Introduction Few real-life data are available on cetuximab benefit. The EREBUS cohort was performed to assess metastases resection rate, use, safety, and survival outcomes in wild-type KRAS (Kirsten rat sarcoma viral oncogene) patients with initially unresectable metastatic colorectal cancer (mCRC) treated by cetuximab in real practice. Patients and Methods The study cohort comprised patients initiating cetuximab between January 2009 and December 2010 in 65 French centers, with initially unresectable mCRC and wild-type KRAS . Kaplan-Meier analysis estimated 24-month probability of metastases resection and progression-free survival, and 36-month overall survival (OS). Cox proportional hazards models investigated factors associated with survival outcomes. Results Among the 389 patients included, median age was 64 years, 67.4% were male, 77.9% had Eastern Cooperative Oncology Group performance status ≤ 1, and hepatic metastases were most frequent at baseline (n = 146 exclusively, n = 149 not exclusively, n = 94 nonliver only). Median duration of cetuximab use was 4.8 months. Metastases resection was performed in 106 patients (27.2%) (n = 60 liver exclusively, n = 33 not exclusively, n = 13 nonliver only). The 24-month probability (95% confidence interval) of metastases resection occurrence was 33.6% (28.5-39.3). Median progression-free survival was 9.2 (8.5-9.8) months for the total cohort and 13.0 (11.6-15.1) for those resected; median OS was 23.0 (20.6-26.3) months for the total cohort and was not reached after 36 months for those who were resected. The strongest factor associated with higher OS was metastases resection with complete remission (hazard ratio, 0.41; 95% confidence interval, 0.19-0.88). Conclusion This cohort study highlights in French real-life practice the benefit of cetuximab in first-line mCRC therapy, notably in case of metastases resection with complete remission.

Purpose During the last decade, many oral anticancer drugs (OAcDs) have been marketed, providing interesting but potentially costly pharmaceutical alternatives to intravenous treatments. This study aims to provide updated information on their use and costs. Methods A cross-sectional yearly repeated study was conducted from 2006 to 2014 using the representative sample of the French national health care insurance system claims database (EGB). OAcD use was described for each year, among prevalent (ie, patients with at least 1 OAcD reimbursement) and incident users (ie, patients with no OAcD reimbursement within the prior year) and according to their pharmacological classes (Hormone Therapy [HT], Cytotoxic Therapy [CT], Targeted Therapy [TT], and others). Demographic characteristics were described for both users; comorbidities and direct medical costs were described for incident users only. Results The yearly prevalence and incidence of OAcD use, mainly represented by HT, remained stable from 2006 to 2014 (1.2%; 0.4%). Compared with users of other OAcD classes, the proportion of TT users substantially increased over the 8-year study period (+9.3%), and TT incident users had more severe comorbidities at treatment initiation. The health expenditures were the most important in TT users with median monthly medical direct costs varying from 2995€ to 4968€ per patient between 2006 and 2014. Conclusion With the development of new OAcDs, the TTs use reaches a wider population of patients but is responsible for increasing health expenditures.

Resume Les crises recentes qui ont secoue le monde du medicament ont mis en exergue la complexite, les benefices et les risques de la communication sur le medicament. La difficulte de cette communication trouve son origine dans la diversite des sources d’information et des audiences, la credibilite des communicants, la difficulte a communiquer l’incertitude scientifique et le principe de precaution. Ce dernier est influence par des perceptions et des tolerances variables au risque. On observe globalement un manque de formation au risque et un refus de la societe actuelle de tout risque. La communication sur le medicament est soumise a des contraintes legales ou reglementaires, utilise souvent des outils et des messages non adaptes a l’audience et meconnait souvent les methodes de communication. Pour sortir de cette spirale, il convient de coordonner l’information disponible en renforcant le portail unique d’information sur les medicaments et coordonner la communication entre les autorites avec un porte parole unique. Un effort particulier doit etre fait sur la formation au bon usage et au risque des medicaments que ce soit a l’intention de la population generale et des patients mais aussi a l’intention des professionnels de sante avec la mise en place d’une plateforme d’enseignement en ligne academique unifiee de formation continue au medicament et a son bon usage.

An increased risk of cardiovascular thrombotic events in users of NSAIDs was first demonstrated for rofecoxib. This risk seems to be related to the COX-2 inhibitory potency and has been found with most NSAIDs except naproxen. Two main hypotheses have been advanced: an imbalance between COX-1-dependent platelet production of thromboxane and partly COX-2-dependent endothelial production of prostacyclin, and a COX-2-dependent increase in blood pressure.Clinical trials and observational studies providing information about cardiovascular risk associated with long-term use of NSAIDs were retrieved; 14 clinical trials and 16 observational studies mentioned a follow-up of at least 6 months.Results are ambiguous: long-term exposure seemed associated with an increased risk of myocardial infarction or stroke with high-dose rofecoxib, and perhaps diclofenac, but less with other NSAIDs. In other studies, little or no increase in risk was associated with exposures shorter than 30 days. Since most NSAIDs are rarely used long term, there is little information on risks associated with long-term use. The relative risks or odds ratios associated with most drugs are mostly well below 2.

PURPOSE: Data mining in spontaneous reporting databases generates large numbers of signals of disproportionate reporting (SDRs) that need to be prioritised for assessment. The pharmacological relevance of drug-event associations is not considered in SDR prioritisation algorithms. This aimed to propose and test a pharmacological score for SDR prioritisation. METHODS: The Pharmacological Score for SDRs Prioritisation (PS-SP) was developed using a Delphi approach. An expert group agreed that PS-SP should include general criteria concerning SDRs and criteria concerning pharmacological relevance, and that criteria should be weighted for their risk representation. Once defined, the PS-SP was tested for prioritisation of SDRs for extrapyramidal syndrome in the French Pharmacovigilance database; the SDR classification was compared to that obtained using a traditional disproportionality approach. RESULTS: For a given drug, the general criteria retained were the reporting rate of the adverse drug reaction (ADR) and value of the 95% confidence interval (CI) lower boundary of the Reporting Odds Ratio (ROR). Pharmacological criteria consisted of the ADR reporting rate without concomitant at-risk drugs or those indicated for ADR treatment, and the value of the ROR 95% CI lower boundary as estimated in the subset of reports concerning drugs from the same therapeutic and then pharmacological class. Compared with traditional disproportionality, PS-SP prioritised specific drugs within congeners: metoclopramide, indoramin, and trimetazidine appeared as outliers within their classes; conventional antipsychotics had higher prioritisation than atypical antipsychotics. CONCLUSION: The pilot evaluation of PS-SP performed in extrapyramidal syndrome advocates for the use of pharmacological criteria in SDR prioritisation algorithms.

Introduction Alors que les benzodiazepines et les medicaments apparentes (zolpidem et zopiclone) sont largement utilises chez les patients souffrant de pathologies psychiatriques, il existe peu de donnees sur les modes d’utilisation de ces medicaments dans cette population et leur bon usage. De plus, leur usage serait associe dans cette population a des risques specifiques: agressivite, suicide, sedation, ataxie, troubles cognitifs, anxiete, depression, manque d’efficacite. L’objectif de cette etude etait d’etudier l’usage et l’impact des benzodiazepines chez des patients hospitalises en psychiatrie. Methode Une etude de cohorte a ete menee a l’hopital Charles Perrens (Bordeaux, France), incluant tous les adultes admis en fevrier ou juin 2016. Ils ont ete suivis jusqu’a la fin de l’hospitalisation, ou pendant six mois s’ils etaient toujours hospitalises ou suivis par une structure dependant de l’hopital. Une situation de mesusage a ete identifiee selon quatre criteres des recommandations francaises : i/Une periode de traitement superieure a 28 jours pour les benzodiazepines hypnotiques et les apparentes, ou 84 jours pour les benzodiazepines anxiolytiques ; ii/Une prescription concomitante de deux benzodiazepines ou plus ; iii/Un dosage superieur a celui recommande dans le resume des caracteristiques du produit ; iv/Une prescription de benzodiazepines a longue demi-vie chez le sujet âge. Resultats 511 patients ont ete inclus, avec une moyenne d’âge de 43 ans, et 49,5 % de femmes. La plupart des patients hospitalises ont recu au moins une benzodiazepine (n = 454, 88,8 %). Parmi eux, presque tous ont utilise une benzodiazepine anxiolytique (n = 448, 98,7 %) et une petite proportion a recu une benzodiazepine hypnotique (n = 64, 14,1 %). Environ la moitie des utilisateurs de benzodiazepines avaient une duree de traitement trop longue (39,1 % pour les hypnotiques et 54,2 % pour les anxiolytiques), mais cette frequence est sous-estimee. Les trois quarts des utilisateurs d’hypnotiques (75,3 %) et moins d’un septieme des utilisateurs d’anxiolytiques (14,5 %) avaient au moins deux prescriptions concomitantes de benzodiazepines. Pres de la moitie des utilisateurs d’hypnotiques (53,1 %) et d’anxiolytiques (43,5 %) avaient au moins une ordonnance de benzodiazepine avec une posologie trop elevee. 21,6 % des 51 patients âges avaient une benzodiazepine a demi-vie longue. Conclusion Parmi les patients souffrant de troubles psychiatriques, le nombre d’utilisateurs de benzodiazepine et la proportion de mauvaise utilisation des benzodiazepines sont preoccupants. On peut s’interroger sur la pertinence des recommandations de bon usage dans cette population.

Introduction Les benzodiazepines et apparentees (zolpidem et zopiclone) sont principalement indiquees dans le traitement des troubles du sommeil et des troubles anxieux. Leur utilisation est largement repandue dans la population generale et associee a des risques certains ou potentiels (troubles cognitifs, psychomoteurs, chute, accidents de la route, demence, maladie de Parkinson, tolerance pharmacologique, difficultes de sevrage, dependance). De ce fait, elles ont une duree maximale de traitement recommandee de 4 semaines pour les hypnotiques, et 12 semaines pour les anxiolytiques, et il est deconseille d’associer plusieurs benzodiazepines. La Haute Autorite de Sante recommande egalement de ne pas utiliser de benzodiazepine a demi-vie d’elimination longue chez le sujet âge. Une utilisation ne respectant pas l’ensemble de ces recommandations de bon usage constitue un mesusage. La population psychiatrique est particulierement exposee aux benzodiazepines, elle pourrait etre aussi plus vulnerable vis a vis de leurs effets indesirables. Pourtant, il n’existe pas de recommandation francaise sur leur utilisation dans cette population particuliere. Cette revue narrative de la litterature a pour objet d’evaluer l’usage et le mesusage des benzodiazepines dans la population atteinte de pathologies psychiatriques, ainsi que les risques associes a leur utilisation dans cette population. Resultats Les benzodiazepines font l’objet d’un mesusage frequent chez les patients souffrant de troubles psychiatriques, en termes de duree, de dose et de nombre de medicaments concomitants prescrits, quel que soit le trouble traite. Pourtant, il n’existe pas de demonstration de leur efficacite sur la plupart des troubles psychiatriques, y compris depression et risque suicidaire. Parmi les donnees de securite de ces medicaments, plusieurs etudes ont montre des associations entre utilisation de benzodiazepines et aggravation de la depression, augmentation de la desinhibition, du risque suicidaire, de l’anxiete, de l’agressivite. Conclusion Malgre l’utilisation courante des benzodiazepines par les cliniciens, les etudes de grande taille et de bonne qualite methodologique manquent pour documenter les modes d’utilisation des benzodiazepines en population souffrant de troubles psychiatriques, ainsi que leurs risques specifiques chez ces patients. On ne peut conclure sur la legitimite d’appliquer les recommandations de bonne pratique concernant les benzodiazepines chez ces patients

Introduction Les donnees epidemiologiques sur la consommation de substances psychoactives (SPA) en France concernent majoritairement les adolescents et la population generale. Cette etude decrit les consommations de SPA dans une large cohorte etudiante. Methode La population d’etude comprenait les etudiants inclus dans la cohorte i-Share (grande etude sur la sante des etudiants) entre le 1er janvier 2015 et le 31 decembre 2017, les informations etaient extraites exclusivement du questionnaire d’inclusion. La consommation de SPA (cannabis, amphetamines, ecstasy, cocaine, protoxyde d’azote et poppers) a ete decrite. Pour chacune de ces substances, leurs modes de consommation et les substances associees (tabac, alcool, LSD, crack, heroine, champignons hallucinogenes, ketamine, GHB) ont egalement ete decrits ainsi que les couples de substances poly-consommees (usage non experimental d’au moins deux SPA). Resultats Au total, 10 066 etudiants ont ete inclus dans l’analyse, 75 % etaient des femmes et l’âge moyen etait de 21 ans et 63,0 % d’entre eux avaient un baccalaureat scientifique. Parmi eux 61,5 % avaient deja consomme une SPA. Le cannabis etait la substance la plus consommee avec 53,4 % de consommateurs au cours de la vie et 33,5 % la derniere annee suivi par le protoxyde d’azote et les poppers avec 24,1 % de consommateurs au cours de la vie. Une consommation experimentale etait declaree par 52,8 % des consommateurs de cannabis et ce taux s’elevait a 55,0 % parmi les consommateurs d’amphetamines. Au sein de la cohorte, 12,3 % des etudiants etait poly-consommateurs ; l’association poppers et protoxyde d’azote concernait 64,7 % des poly-consommateurs. Les consommateurs de SPA etaient plus concernes par le binge drinking que les consommateurs de tabac et d’alcool uniquement et etaient plus souvent des fumeurs actifs. Les consommateurs de SPA consommaient egalement des substances hallucinogenes avec dans l’ordre decroissant : champignons hallucinogenes, LSD et ketamine. Discussion Cette etude decrit les consommations de SPA chez les etudiants dans une large cohorte. L’importance de consommation du protoxyde d’azote et de la ketamine montre la necessite de prendre en compte ces substances dans les rapports nationaux et europeens sur la consommation de SPA.

In response to a regulatory request for real-life data on patterns of use and survival outcomes, 793 patients initiating bortezomib for multiple myeloma in France (May 2004-April 2006) were included in this observational study. Data were collected from medical files and patients were followed for 2 years, with vital status collected after 3 years. In total 779 patients were analyzed: 83.1% had immunoglobulin G (IgG) or IgA M-component, mean age was 65.7 years and 46.5% were female. Bortezomib was initiated as third-or-later line in 82.0%. For 75.9%, the starting dose was 1.3 mg/m(2); 42.6% had bortezomib alone, 54.0% with dexamethasone. The mean number of bortezomib cycles was 5.0. Three-year overall survival from bortezomib initiation was 31.4% (95% confidence interval, CI [28.1; 34.7]) and median overall survival was 19.6 months. Two-year progression-free survival was 12.0% (95% CI [9.8; 14.4]), and median progression-free survival was 7.2 months. Overall best response was 44.0%. Survival outcomes during real-life use of bortezomib were within the range of those reported in clinical trials.

Purpose To test an automated method to decrease the number of false-positive (FP) signals of disproportionate reportings (SDRs) generated by co-prescription. Methods Automated backward stepwise removal of reports concerning the drug associated with the highest ranked SDR for an event was tested for gastric and oesophageal haemorrhages (GOH), central nervous system haemorrhages and cerebrovascular accidents (CNSH), ischaemic coronary artery disorders and muscle pains (MP) using the reporting odds ratio in the French spontaneous reporting research database. After ranking SDRs detected in the complete dataset on the lower limit of the reporting odds ratio 95% confidence interval, reports concerning the drug with the highest ranked SDR were removed. In the dataset thus generated, SDRs were again identified, ranked and reports related to the drug involved in the newly highest ranked SDR removed. The process was repeated until no signal was detected. Initially detected SDRs eliminated using this technique were assessed regarding the summary of products characteristics and the literature to determine their FP nature. Results Seventeen SDRs were successively eliminated for GOH, 37 for CNSH, 15 for ischaemic coronary artery disorders, and 36 for MP. Four were FP for GOH, 29 for CNSH, 7 for ACI and none were FP for MP. The positive predictive value of the backward stepwise removal procedure in identifying FP SDRs ranged from 0% (MP) to 78.4% (CNSH). Conclusions Although further adjustment is needed to improve the method presented herein, our results suggest that numerous FP signals because of co-prescription bias could be eliminated using an automated method. Copyright © 2013 John Wiley & Sons, Ltd. key words—pharmacovigilance; spontaneous reporting; adverse reaction; signal detection; bias; methods; pharmacoepidemiology

National audience; Initié en 2013, par l’institut de santé publique de l’Inserm et le réseau des centres d’investigation clinique (CIC, structures conjointes Inserm–CHU) pour coordonner les recherches des CIC-EC (modules épidémiologie clinique), le réseau national RECaP de Recherche en épidémiologie clinique et en santé publique a pour but de mutualiser des projets de recherche originaux et de produire des innovations en épidémiologie clinique et en santé publique. Financé par l’Inserm, ce réseau regroupe à ce jour l’ensemble des CIC-EC et quatre CIC-P (plurithématique) répartis à travers la France. Ses missions sont de : – promouvoir la recherche française en épidémiologie clinique, biostatistique et en santé publique, et favoriser l’émergence d’une recherche collaborative dans ces thématiques ; – mutualiser des outils pour la recherche et des réflexions méthodologiques pour améliorer les différents types d’études et contribuer ainsi à les porter à un niveau de compétitivité internationale ; – contribuer à l’animation scientifique dans le domaine de la recherche en épidémiologie clinique et en santé publique. Le réseau mène des projets de recherche transversaux et interdisciplinaires en santé publique et en épidémiologie clinique. Il est impliqué dans des projets collaboratifs et soutient plusieurs projets en attente de financements. De plus, afin de permettre l’émergence de nouveaux projets collaboratifs, le réseau met en place des groupes de travail thématiques tels que « recherche sur la recherche », « évaluation des interventions complexes » ou « pharmaco-épidémiologie ». Ces groupes permettent le transfert de savoir-faire d’une équipe à l’autre et d’une thématique à une autre, pour l’accélération de la recherche en France, à un niveau de compétitivité internationale. Enfin, le réseau participe à l’animation scientifique en épidémiologie clinique et en santé publique via la conférence annuelle EPICLIN/Journées des statisticiens des centres de luttes contre le cancer. Il soutient la conférence financièrement et logistiquement par la création d’un manuel d’organisation pour la transmission d’une équipe organisatrice à l’autre