Impact of an Educational Intervention on Adverse Drug Reaction reporting in Tertiary Hospitals in South-South Nigeria.

BACKGROUND: Nigeria is yet to achieve the internationally recommended number of Adverse Drug Reactions (ADRs) reports. OBJECTIVE: This study evaluated the impact of an educational lecture followed by repeated text messages via the Short Messaging System (SMS) on ADR reporting. METHODS: Six teaching hospitals in the South-South zone of Nigeria were randomized in 1:1 ratio into intervention and non-intervention hospitals. The intervention hospitals received an educational lecture followed by monthly SMS reinforcements over 12 months. The number and quality of ADR reports from the local pharmacovigilance centers of each teaching hospital over the 12 months before and after the intervention were described. RESULTS: A total of 4912 healthcare professionals were working in the 6 hospitals at the time of the study (3099 in the intervention and 1813 in the control) and the educational intervention was conducted between January and March 2016. In the intervention hospitals, the number of ADR reports increased from 57 in the pre-intervention period (from January 1st 2015) to 75 in the post- intervention period. However, the proportion of serious ADRs decreased slightly from 26(45.6%) to 33(44%). Post-intervention, the report of suspected drug details in the ADR report form also improved. CONCLUSION: There was a trend to increased absolute number and quality of reports following educational intervention and SMS reminders.

CONTEXTE: Le Nigéria n'a pas encore atteint le nombre recommandé au niveau international de rapports sur les effets indésirables des médicaments (EIM). OBJECTIF: Cette étude a évalué l'impact d'une conférence éducative suivie par les messages texte répétés via le système de messagerie courte (SMS) sur les rapports d'ADR. MÉTHODES: Six hôpitaux universitaires de la zone Sud-Sud du Nigeria ont été randomisés dans un rapport 1:1 en hôpitaux d'intervention et de non-intervention. Les hôpitaux d'intervention ont reçu une conférence pédagogique suivie de renforcements SMS mensuels sur 12 mois. Le nombre et la qualité des rapports d'EIM des centres locaux de pharmacovigilance de chaque hôpital universitaire au cours des 12 mois avant et après l'intervention ont été décrits. RÉSULTATS: Au total, 4912 professionnels de santé travaillaient dans les 6 hôpitaux au moment de l'étude (3099 dans l'intervention et 1813 dans le contrôle) et l'intervention éducative a été menée entre janvier et mars 2016. Dans les hôpitaux d'intervention, le nombre des notifications d'EIM sont passés de 57 dans la période pré-intervention (à partir du 1er janvier 2015) à 75 dans la période post-intervention. Cependant, la proportion d'effets indésirables graves a légèrement diminué, passant de 26 (45,6 %) à 33 (44 %). Après l'intervention, le rapport des détails sur les médicaments suspects dans le formulaire de rapport d'EIM s'est également amélioré. CONCLUSION: Il y avait une tendance à l'augmentation du nombre absolu et de la qualité des rapports après une intervention éducative et des rappels par SMS. MOTS CLÉS: Effet indésirable médicamenteux, Intervention éducative, Professionnels de santé, Rappels SMS, Hôpitaux universitaires, Nigéria.

Agreement between hospital discharge diagnosis codes and medical records to identify metastatic colorectal cancer and associated comorbidities in elderly patients.

BACKGROUND: Quality of coding to identify cancers and comorbidities through the French hospital diagnosis database (Programme de médicalisation des systèmes 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≥65years 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.

Patterns of selective serotonin reuptake inhibitor use and risk of falls and fractures in community-dwelling elderly people: the Three-City cohort.

In this population-based elderly cohort, participants using selective serotonin reuptake inhibitor (SSRI) antidepressants have an increased risk of falls and fractures notably when the treatment was continued over 4 years. Among the various SSRI types, citalopram only was at significant risk for falls and fluoxetine for fractures. INTRODUCTION: Increased risk of falls and fractures has been reported in elderly users of SSRIs. However, biases were insufficiently addressed notably temporality between exposure and outcome and confounding by residual depression. Our objective was to examine the associations between SSRIs and fall or fracture incidence focusing on their chronic use and different types of SSRIs. METHODS: The population-based cohort included participants aged 65 years and above, who had not fallen before inclusion (n = 6599) or were free of recent fracture (n = 6823) and were followed up twice over 4 years. New fall and fracture events were self-reported and defined as at least two falls and one fracture, respectively, during the previous 2 years. SSRI users were compared with those taking no antidepressants. Hazard ratios (HRs) were estimated using Cox models with delayed entry and adjusted for many confounders including residual depressive symptoms. RESULTS: Incidence of falls was 19.3 % over 4 years and that of fractures 9.5 %. After multi-adjustment, SSRI intake was significantly associated with a higher risk of falls (HR, 95 % CI = 1.58, 1.23-2.03) and fractures (HR, 95 % CI = 1.61, 1.16-2.24). The risks were significantly increased by 80 % in those continuing the treatment over 4 years. Citalopram intake only was at significant risk for falls and fluoxetine for fractures. CONCLUSIONS: In this large community-dwelling elderly sample, SSRI users were at higher risk of falls and fractures. This association was not due to reverse causality or residual depressive symptoms. Different SSRI drugs may have specific adverse effects on falls and fractures.

Sudden cardiac and sudden unexpected death related to antipsychotics: A meta-analysis of observational studies.

To estimate the risk of sudden cardiac death (SCD) or sudden unexpected death (SUD) related to individual antipsychotics, a meta-analysis of observational studies was performed. Adjusted odds ratio (OR) of SCD/SUD with 95% confidence intervals (CI) were extracted and pooled; heterogeneity was studied using Q statistic and I(2) index, and its potential causes (e.g., hERG blockade potency) explored using meta-regression. Two cohort (740,306 person-years) and four case-control (2,557 cases; 17,670 controls) studies, investigating nine antipsychotics, were included. Compared with nonusers, the risk was increased for quetiapine (OR = 1.72, 95% CI: 1.33-2.23), olanzapine (OR = 2.04, 1.52-2.74), risperidone (OR = 3.04, 2.39-3.86), haloperidol (OR = 2.97, 1.59-5.54), clozapine (OR = 3.67, 1.94-6.94), and thioridazine (OR = 4.58, 2.09-10.05). Heterogeneity was found (Q = 20.0, P = 0.01; I(2) = 60.0%), and the increasing mean hERG blockade potency (P = 0.01) accounted for 43% of this. The SCD/SUD risk differed between individual antipsychotics, and mean hERG blockade potency could be an explanatory factor. This should be considered when initiating antipsychotic treatment.

Use of the recommended drug combination for secondary prevention after a first occurrence of acute coronary syndrome in France.

PURPOSE: The recommended pharmacotherapy for secondary prevention of acute coronary syndrome (ACS) is long-term treatment with a combination of four therapeutic classes: beta-blockers, antiplatelet agents (including aspirin), statins or other lipid-lowering agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The aim of this study was to describe use and persistence of the recommended drug combination after the first occurrence of ACS in France. METHODS: This was a database cohort study of patients with first registration for ACS between 2004 and 2007 in a representative sample of the French healthcare insurance database (Echantillon Généraliste de Bénéficiaires, EGB). The drugs of interest were those recommended. Persistence was assessed for patients dispensed three or all four drug classes within 2 months following ACS. Discontinuation was defined by a gap of more than 6 weeks between two dispensations. The follow-up period was 24 months after ACS occurrence. RESULTS: Of 2,057 patients with incident ACS, 872 (42.4 %) had at least one dispensation of each of the four recommended drug classes, and 684 (33.3 %) had three of the four classes. Persistence to treatment at 24 months was 57.4 % (95 % CI [54.0-60.6]) for patients with four classes, and 55.5 % (95 % CI [51.6-59.1]) with three classes. Discontinuation of initial combination was higher in patients aged ≥ 65 years at ACS occurrence, those with associated ongoing chronic disease, and in those who did not suffer myocardial infarction. CONCLUSIONS: Post-ACS secondary prevention in France is not optimal, especially in patients who did not have myocardial infarction.

Effect of treatment gaps in elderly patients with dementia treated with cholinesterase inhibitors.

OBJECTIVE: To determine the effect of treatment gaps on the risk of institutionalization or death among community-dwelling elderly patients treated with cholinesterase inhibitors (ChIs). METHODS: A survival analysis was conducted among a cohort of community-dwelling elderly patients (age 66+) newly treated with ChIs identified in the Quebec drug claims databases (Régie de l'Assurance Maladie du Québec [RAMQ]) between January 1, 2000, and December 31, 2007. Treatment nonpersistence during the year following ChI initiation was defined as treatment discontinuation or gaps of at least 6 weeks. To account for reverse causality, Cox proportional hazard modeling was conducted only among patients who did not discontinue treatment, in order to assess the association between treatment nonpersistence and institutionalization or death. RESULTS: Among the 24,394 elderly ChI users, 4,108 (16.8) experienced a treatment gap during the year following ChI treatment initiation while 596 (2.4%) discontinued their treatment within the first 3 months (early stoppers) and 4,038 (16.6%) after 3 months of treatment (late stoppers). Of all treated patients, 4,409 (18.1%) were institutionalized or died during follow-up. In patients who did not stop their treatment, the risk of institutionalization or death appeared lower in patients who experienced a treatment gap (hazard ratio 0.91; 95% confidence interval 0.86-0.96). CONCLUSIONS: Our results suggest that, contrary to what was previously reported in clinical trials, treatment gaps do not compromise the outcome of patients treated with ChIs in a real-life setting.

Cardiovascular and gastrointestinal safety of NSAIDs: a systematic review of meta-analyses of randomized clinical trials.

As part of the Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project, we reviewed the incidence of cardiovascular (CV) and gastrointestinal (GI) events associated with the use of this category of drugs. We collected data from published meta-analyses (MAs) of clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs). The Medline, Cochrane, ISI, and SCOPUS databases were systematically searched for MAs of NSAID clinical trials that could potentially contain data on adverse incidents such as myocardial infarction (MI), cerebrovascular events (CeVs), stroke, thromboembolic events (ThEs), heart failure (HF), gastrointestinal bleeding (GIB), and perforation, ulcer, and bleeding (PUB). From 1,733 identified references, 29 MAs were selected for the review. This allowed 109 estimations of incidence rates of CV adverse events and 26 estimations of incidence rates for GI adverse events. No data were found on hemorrhagic stroke or LGIB. Coxibs were studied in more MAs than traditional NSAIDs were (21 MAs for coxibs vs. 7 for traditional NSAIDs; one meta-analysis studied both). Many NSAIDs were not considered in any of the MAs. Our systematic review of MAs included information on the incidence of CV and GI events and identified important knowledge gaps regarding, in particular, the CV safety of traditional NSAIDs.

Factors associated with the prevalence of antibiotic use for the treatment of hospital-acquired infections at 393 French hospitals: a regional variation analysis.

OBJECTIVE: The present study investigated regional variations in antibiotic use for the treatment of hospital-acquired infections (HAIs) in France by means of a multilevel analysis, to identify targets for quality improvement. METHODS: Data were obtained from the 2001 and 2006 French national point-prevalence surveys of HAIs and antibiotic use. The present study was conducted using data from 393 nonteaching public hospitals. Data included patient characteristics calculated at the hospital level (mean age and proportion of patients with the following: HAI, presence of a vascular catheter, presence of a urinary catheter, surgical procedure, and immunodeficiency) and hospital characteristics (size and presence of an intensive care unit). The regional effect was measured using a random intercept on a regional variable. RESULTS: Overall, the prevalence of antibiotic use was 5.35% for both study years. The most commonly used antibiotics for HAIs were fluoroquinolones (2001, 1.33%; 2006, 1.35%) and combinations of penicillins with a ß-lactamase inhibitor (2001, 0.92%; 2006, 1.02%). Mapping of antibiotic use showed wide variation between regions. The regional effect explained 3% of antibiotic variation in the unadjusted analysis. In the multivariable analysis, hospital size, high prevalence of patients with immunodeficiency, and infection characteristics explained 45% of the variability in antibiotic use. The regional effect was not retained in the final model. CONCLUSION: The pattern of antibiotic use for HAIs differed over time, and regional variations were mostly explained by patient characteristics; there was no regional effect. Models that take data hierarchy into account are essential to better approach antibiotic use and develop relevant strategies for improvement.

When patients report diseases that prescribers seem unaware of: discordance between patient and physician reporting of risk-related previous history in NSAID users from the CADEUS study.

Prescribers are often unaware of possibly dangerous previous medical histories (PMHs) of their patients. Data from a study of nonsteroidal anti-inflammatory drug (NSAID) users served to identify factors associated with this lack of awareness. In this study, we analyzed the factors that may have led prescribers to report the absence of some PMHs that the patients reported as being present. Of 26,618 patients prescribed an NSAID, 469 (1.7%) reported a PMH of unstable angina, 648 (2.4%) reported heart failure, 2,244 (8.4%) reported gastric or duodenal ulcer, 489 (1.8%) reported upper gastrointestinal tract bleeding (UGIB), 5,343 (20.0%) reported gastroesophageal reflux disease (GERD), and 7,832 (29.4%) reported dyspepsia. Between 64 (GERD) and 92% (UGIB) of these patient-reported PMHs were absent in the corresponding prescribers' reports. This discordance was associated with the following factors: patients of younger age, female patients, less frequent patient-prescriber contact, prescription of NSAID by a specialist, no recent specialist consultation, hospitalization or surgery related to the PMH, and no dispensation of proton-pump inhibitors (PPIs) for digestive disorder-related PMHs. The study showed that a substantial proportion of prescribers seemed unaware of the presence of risk-related PMHs that the patient reported when asked.

Easily available adjustment criteria for the comparison of antibiotic consumption in a hospital setting: experience in France.

Hospitals in France are encouraged to monitor antibiotic consumption (AbC) and it is known that this differs among hospitals. The aim of the current study was to identify relevant and easily available adjustment criteria for the purpose of benchmarking. We analysed data from 34 public non-teaching hospitals and 43 private hospitals located in south-western France and overseas departments using retrospective data from 2005. This study investigated the relationship between AbC expressed as defined daily doses per 1000 patient-days (DDD/1000 PDs) or per 100 admissions (DDD/100 admissions) and the number of venous central lines, the number of episodes of bacteraemia and various hospital characteristics. The relationship was tested using multiple linear analyses. The median total AbC in public hospitals was 395 DDD/1000 PDs (range, 196-737) and 341 DDD/100 admissions (range, 180-792). In private hospitals this was 422 DDD/1000 PDs (range, 113-717) and 212 DDD/100 admissions (range, 38-510). The best model for public hospitals included the proportion of PDs in surgery, intensive care and medical wards and explained 84% of the variability in AbC expressed as DDD/1000 PDs. For private hospitals, the mean length of stay and the proportion of PDs in surgery and medical wards explained 68% of the variability in AbC expressed as DDD/100 admissions. Overall, this French experience shows that relevant adjustment criteria for the comparison among hospitals are easily available. It is important that each country establish its own model considering the intrinsic peculiarities of the hospital system and taking into account both indicators (DDD/1000 PDs or DDD/100 admissions) to design the best model.

[Pattern and evolution of the prescription of olanzapine during one year: Results of the cohort study ECOL]. / Modalités et évolution de la prescription d'olanzapine : résultats de l'étude de cohorte ECOL.

INTRODUCTION: The necessary evidence of new therapies of clinical interest extends beyond clinical trials in a less controlled population and closer to clinical practice justified since several years the need of conducting observational, noninterventional studies. Observational studies must include epidemiological (quantitative observational) data to define prevalence and natural history of the target conditions. Moreover, pharmacological interventions in "naturalistic" patients populations, selected by clinicians as per clinical judgment within the scope of the target disease will allow to generate data to complement clinical trials. Clinical trials designed to show robust data on efficacy and tolerability particularly during registration trials must be complemented by robust observational research to confirm and better describe clinical effectiveness in the target population. A noninterventional, observational trial is a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorization. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnosis or monitoring procedures shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data. Olanzapine is a new antipsychotic therapy registered in Europe for the treatment of schizophrenia since 1996. AIMS OF THE STUDY: The primary objective of this observational research was to study the evolution of the olanzapine dosage under naturalistic settings. Secondary objectives included patients characteristics, severity of disease, therapeutic evolution and coprescriptions, in a patient's cohort, suffering from schizophrenia, adult patients, diagnosis based on ICD-10; patients were followed during a total of 12 months. DESIGN OF THE STUDY: The cohort study was conducted in France. Between the period of June 2000 and February 2001, 407 psychiatrics randomized to participate in the study had consolidated the patient's cohort. RESULTS: A total of 1810 patients were included, 1093 (60, 4%) male, 717 (39, 6%) females. Age was recorded for a total of 1802 (99, 6%) patients, mean age was 37.8 years as per inclusion criteria and patients consent according to current regulations. Patients entered in the cohort as per clinicians decision underwent a treatment with olanzapine during an outpatient's consultation or at hospitalization. More than two thirds of the patients were followed up during 12 months after onset of this treatment. Clinical outcome was assessed at three, six, nine and 12 months following cohort inclusion using the following tools: CGI, PANSS, Calgary and GAF; as per CGI 78% of the patients cohort were severely ill, the mean PANSS score was 94.1. At second month of treatment clinicians were requested to very well document any changes in olanzapine dosage as well as reasons for the dosage modifications and potential coprescriptions. DISCUSSION: The daily mean dosage of olanzapine was 9.5mg at initiation of treatment, 10.5mg after one month and 11.2mg after 12 months of follow-up. The increase of the dosage after one month was associated with factors such as younger age, schizophrenia diagnosis and severity of the symptoms as measured by CGI and PANSS scores evolution, low initial dosage and hospitalization at treatment initiation. Within the 1810 participants included in the cohort, 1383 (76.5%) received a coprescrition of a psychotropic, for example, 811 (44.8%) a benzodiazepine, 506 (28.0%) an antidepressant. Among the patients cohort that were followed during 12 months, all the clinical and patient-functioning indicators progressed in the direction of a significant improvement.

Antidepressants: general practitioners' opinions and clinical practice.

OBJECTIVE: To describe and compare general practitioners' (GPs) opinions on antidepressant drugs and their prescriptions to depressed patients. METHOD: Between November 2000 and July 2001 a representative sample of French GPs was asked their opinion of the 15 most prescribed antidepressants, and then to describe the treatments of the current depressive episode of four depressive patients each, their changes and the reasons thereof. RESULTS: One hundred and eighty-one GPs and 778 patients participated. The best-ranked antidepressants by the GPs were paroxetine, fluoxetine, sertraline and clomipramine for efficacy, and paroxetine, tianeptine, sertraline and fluoxetine for tolerability. In patients, the drugs most often prescribed were fluoxetine, paroxetine, and sertraline. Those least often stopped for intolerance were moclobemide (0%), dosulepine (0%), venlafaxine (4.5%) and citalopram (5.0%), and maprotiline (0%), citalopram (1.7%) and venlafaxine (2.3%) for lack of efficacy. The best predictor for prescription of antidepressants was the GPs' overall ranking, itself depending on opinions of the tolerability and efficacy of the drug. However, opinions of tolerability and efficacy were not related to the rates of treatment discontinuation for intolerability or inefficacy. CONCLUSION: Prescriber opinion does not seem related to actual product performance.