Use of the French National Health Data System (SNDS) in pharmacoepidemiology: A systematic review in its maturation phase.

AIM OF THE STUDY: The French National Health Data System (SNDS) comprises healthcare data that cover 99% of the population (over 67 million individuals) in France. The aim of this study was to present an overview of published pharmacoepidemiological studies using the SNDS in its maturation phase. METHODS: We conducted a systematic literature review of original research articles in the Pubmed and EMBASE databases from January 2012 until August 2018. RESULTS: A total of 316 full-text articles were included, with an annual increase over the study period. Only 16 records were excluded after screening because they did not involve the SNDS but other French healthcare databases. The study design was clearly reported in only 66% of studies of which 57% were retrospective cohorts and 22% cross-sectional studies. The reported study objectives were drug utilization (65%), safety (22%) and effectiveness (9%). Almost all ATC groups were studied but the most frequent ones concerned the nervous system in 149 studies (49%), cardiovascular system drugs in 104 studies (34%) and anti-infectives for systemic use in 50 studies (16%). CONCLUSION: The SNDS is of growing interest for studies on drug use and safety, which could be conducted more in specific populations, including children, pregnant women and the elderly, as these populations are often not included in clinical trials.

Psychoactive substance use among students: A cross-sectional analysis.

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.

Overview of the European post-authorisation study register post-authorization studies performed in Europe from September 2010 to December 2018.

BACKGROUND: The European post-authorisation study (EU PAS) register is a repository launched in 2010 by the European Medicines Agency (EMA). All EMA-requested PAS, commonly observational studies, must be recorded in this register. Multi-database studies (MDS) leveraging secondary data have become an important strategy to conduct PAS in recent years, as reflected by the type of studies registered in the EU PAS register. OBJECTIVES: To analyse and describe PAS in the EU PAS register, with focus on MDS. METHODS: Studies in the EU PAS register from inception to 31st December 2018 were described concerning transparency, regulatory obligations, scope, study type (e.g., observational study, clinical trial, survey, systematic review/meta-analysis), study design, type of data collection and target population. MDS were defined as studies conducted through secondary use of >1 data source not linked at patient-level. Data extraction was carried out independently by 14 centres with expertise in pharmacoepidemiology, using publicly available information in the EU PAS register including study protocol, whenever available, using a standardised data collection form. For validation purposes, a second revision of key fields for a 15% random sample of studies was carried out by a different centre. The inter-rater reliability (IRR) was then calculated. Finally, to identify predictors of primary data collection-based studies/versus those based on secondary use of healthcare databases) or MDS (vs. non-MDS), odds ratios (OR) and 95% confidence intervals (CI) were calculated fitting univariate logistic regression models. RESULTS: Overall, 1426 studies were identified. Clinical trials (N = 30; 2%), systematic reviews/meta-analyses (N = 16; 1%) and miscellaneous study designs (N = 46; 3%) were much less common than observational studies (N = 1227; 86%). The protocol was available for 63% (N = 360) of 572 observational studies requested by a competent authority. Overall, 36% (N = 446) of observational studies were based fully or partially on primary data collection. Of 757 observational studies based on secondary use of data alone, 282 (37%) were MDS. Drug utilisation was significantly more common as a study scope in MDS compared to non-MDS studies. The overall percentage agreement among collaborating centres that collected the data concerning study variables was highest for study type (93.5%) and lowest for type of secondary data (67.8%). CONCLUSIONS: Observational studies were the most common type of studies in the EU PAS register, but 30% used primary data, which is more resource-intensive. Almost half of observational studies using secondary data were MDS. Data recording in the EU PAS register may be improved further, including more widespread availability of study protocols to improve transparency.

Adverse drug reactions induced by cotrimoxazole: Still a lot of preventable harm.

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 center (France) during a 5-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 recommendations 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.

Ambulatory drug changes in the elderly after hospital discharge: A cohort study.

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.

Effectiveness of first-line cetuximab in wild-type RAS metastatic colorectal cancer according to tumour BRAF mutation status from the EREBUS cohort.

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.

Association between anxiolytic/hypnotic drugs and suicidal thoughts or behaviors in a population-based cohort of students.

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.

Use of benzodiazepines non-compliant with guidelines in patients with psychiatric and non-psychiatric chronic disorders.

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.

Quality of Life and Pain During Treatment of Metastatic Castration-resistant Prostate Cancer With Cabazitaxel In Routine Clinical Practice.

BACKGROUND: This prospective study collected quality of life (QoL) and pain data during cabazitaxel treatment in patients with advanced metastatic or castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Functional Assessment of Cancer Therapy-Prostate (QoL) and Brief Pain Inventory-Short Form (pain) questionnaires were collected over 6 months. RESULTS: In 61 patients with mCRPC (median age, 72 years) from 22 centers, metastatic sites were bones (97%), lymph nodes (36%), and visceral (20%); 25% received cabazitaxel in the second line, 29% in the third line, and 46% in the fourth line or beyond. All had been previously treated with docetaxel, except one with paclitaxel, and 75% also with abiraterone, enzalutamide, or both. The median cabazitaxel duration was 3.4 months. Forty-nine patients were evaluable for QoL and 44 for pain. QoL was improved in 37%, maintained in 35%, and deteriorated in 37%. In 27%, pain decreased ≥ 1 level and remained stable in 52%. A total of 34% lowered analgesic drug level. Prostate-specific antigen response ≥ 50% was observed in 11 (32.6%) patients, of whom 7 improved QoL and 1 was stable. At 6 months, 83.6% survived (95% confidence interval, 71.7%-90.8%). A total of 46% had ≥ 1 grade ≥ 3 adverse events, mainly anemia and neutropenia. CONCLUSION: Although cabazitaxel was given as the third line and beyond for three-quarters of patients, over one-third had improved QoL and/or decreased pain during treatment.

Use of benzodiazepines and z-drugs not compliant with guidelines and associated factors: a population-based study.

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.

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

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

Overall and progression-free survival with cabazitaxel in metastatic castration-resistant prostate cancer in routine clinical practice: the FUJI cohort.

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.

Treatment Modalities and Survival in Older Adults with Metastatic Colorectal Cancer in Real Life.

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.

Monitoring of drug misuse or potential misuse in a nationwide healthcare insurance database: A cross-sectional study in France.

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.

The value of a health insurance database to conduct pharmacoepidemiological studies in oncology.

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.

Educational intervention to improve the knowledge, attitude and practice of healthcare professionals regarding pharmacovigilance in South-South Nigeria.

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.

[Use and misuse of benzodiazepines in patients with psychiatric disorders]. / Usages et mésusages des benzodiazépines chez les patients souffrant de troubles psychiatriques.

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.

Assessment of the state of pharmacovigilance in the South-South zone of Nigeria using WHO pharmacovigilance indicators.

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.

Impact of cancer diagnosis on persistence of oral antidiabetic drugs.

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 Généraliste de Bénéficiaires, 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.

Effectiveness of Cetuximab as First-Line Therapy for Patients With Wild-Type KRAS and Unresectable Metastatic Colorectal Cancer in Real-Life Practice: Results of the EREBUS Cohort.

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.