Anne Castot

The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies

To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area.

Benzodiazepine-like hypnotics and the associated risk of road traffic accidents.

The aim of the study was to investigate the association between the use of benzodiazepine or benzodiazepine‐like hypnotics and the risk of road traffic accidents. Data from three French national databases were matched: the health‐care insurance database, police reports, and the police database of injury‐related traffic accidents. A total of 72,685 drivers involved in injury‐related road traffic accidents in France, from 2005 to 2008, were included in the study. The risk of being responsible for a traffic accident was higher in users of benzodiazepine hypnotics (odds ratio (OR) = 1.39 (1.08–1.79)) and in the 155 drivers to whom a dosage of more than one pill of zolpidem a day had been dispensed during the 5 months before the collision (OR = 2.46 (1.70–3.56)). No association was found between the use of zopiclone and risk of traffic accidents. Although this study did not find any association between the use of zolpidem as recommended and causation of traffic accidents, the potential risk related to possible abuse of the drug and risky driving behaviors should be further investigated. The results related to benzodiazepine hypnotics are consistent with those of previous studies.

Road traffic crashes and prescribed methadone and buprenorphine: A french registry-based case–control study

BACKGROUND Opioids have been shown to impair psychomotor and cognitive functioning in healthy volunteers with no history of opioid abuse. Few or no significant effects have been found in opioid-dependant patients in experimental or driving simulation studies. The risk of road traffic crash among patients under buprenorphine or methadone has not been subject to epidemiological investigation so far. The objective was to investigate the association between the risk of being responsible for a road traffic crash and the use of buprenorphine and methadone. METHODS Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes. Case-control analysis comparing responsible versus non responsible drivers was conducted. RESULTS 72,685 drivers involved in an injurious crash in France over the July 2005-May 2008 period, were identified by their national health care number. The 196 drivers exposed to buprenorphine or methadone on the day of crash were young, essentially males, with an important co-consumption of other substances (alcohol and benzodiazepines). Injured drivers exposed to buprenorphine or methadone on the day of crash, had an increased risk of being responsible for the crash (odds ratio (OR)=2.02, 95% confidence interval (CI): 1.40 and 2.91). CONCLUSIONS Users of methadone and buprenorphine were at increased risk of being responsible for injurious road traffic crashes. The increased risk could be explained by the combined effect of risky behaviors and treatments.

Adverse drug events

The exceptional heat wave in 2003 led to excess mortality, particularly in elderly people1—in France about 14 800 deaths, mainly among people over 70.2 We evaluated adverse drug reactions reported to …

First French Experience of ADR Reporting by Patients After a Mass Immunization Campaign with Influenza A (H1N1) Pandemic Vaccines

AbstractBackground: Available data concerning the contribution of patient adverse drug reaction (ADR) reporting in practice are scarce. Few studies have compared patients’ reports with reports from healthcare professionals (HCPs). During the 2009–10 mass immunization campaign with A (H1N1)v2009 pandemic influenza vaccines, a reinforced pharmacovigilance plan was introduced in France according to European Medicines Agency recommendations. For the first time, patients were offered the opportunity to report suspected ADRs to pandemic vaccines directly to regional pharmacovigilance centres. Objective: The aim of the study was to compare the characteristics of patient and HCP ADR reports in order to assess the qualitative and quantitative contribution of patient reporting to the French Pharmacovigilance System. Methods: All spontaneous ADRs registered into the French Pharmacovigilance Database from 21 October 2009 to 15 June 2010, in which either one of the most frequently administered pandemic vaccines (i.e. Panenza® or Pandemrix®) was involved, were analysed. ADRs were classified as ‘serious’, ‘medically serious’ and ‘non-serious’. This study focused on ‘serious’ and ‘medically serious’ ADRs. An ADR was ranked as ‘medically serious’ when it required medical intervention or hospitalization within less than 24 hours. In each level of seriousness, frequency of ‘unlabelled’ ADRs, ADRs of ‘special interest’, imputability scores and category of ADRs according to Medical Dictionary for Regulatory Activitives (MedDRA®) primary System Organ Class were compared between patient and professional reports. Results: Among the 4746 reports received during the study period, 1006 (21.2%) originated from patients. HCPs reported significantly more ‘medically serious’ or ‘serious’ ADRs than patients (15.1% [565/3740] vs 8.4% [85/1006], respectively; p < 0.001). No difference was found in ‘unlabelled, serious’ ADRs between patients and HCPs (56.5% [n= 13] vs 56.7% [n= 136], respectively). Conclusions: In this first French experience of formal patient participation to ADR reporting, patient contribution to the total number of ADRs reached 21.2%. This study revealed no major qualitative difference between patient and HCP reports. ADR profiles reported by patients appeared to be consistent with those from professionals. Further investigations are necessary to assess the intrinsic quality of notification forms coming from non-professional reporters. However, this study is of particular interest in the context of publication of the first governmental decree that will formally integrate patient participation to the current French ADR reporting scheme.

Safety surveillance of influenza A(H1N1)v monovalent vaccines during the 2009–2010 mass vaccination campaign in France

In June 2009, the World Health Organization declared a pandemic due to A(H1N1)v 2009 influenza virus. In France, a mass vaccination campaign started following European Medicines Agency (EMA) recommendations, and a Pharmacovigilance plan was launched. The aim of this study was to describe safety data collected from 21 October 2009 to 15 June 2010 for Pandemrix® (ASO3 adjuvant vaccine, indicated in adults and children >9 years) and Panenza® (a nonadjuvant vaccine primarily administered to children <9 years old and pregnant women), the two most frequently used vaccines in France. The French Pharmacovigilance system consists of a network of 31 regional centres and is based on mandatory spontaneous reports of “serious” and/or “unexpected” adverse events (AEs) [1]. However, it is well known that spontaneous notifications suffer from underreporting, the magnitude of which varies between 82% and 98% [2]. For the 2009–2010 vaccination campaign, French health authorities heightened awareness to extensive notifications with online health practitioner and patient reports via the regional centre concerned. All

Médicaments et chaleur : étude SIRIUS cas-témoins multicentrique chez les sujets de plus de 65 ans durant l’été 2007 en France

OBJECTIVE To evaluate in real conditions the role of drugs in heat-related adverse effects. METHODS We performed a multicentric case-control study in 3 university hospitals in France, including 36 cases (patients older than 65 years hospitalized with hyperthermia or dehydration between 1st July and 31st August 2007) and 51 controls. We compared drugs and changes in drug dosage according to the values of renal function. RESULTS At inclusion, clearance creatinine was available for only 12 patients (mean = 31.6 ml/min), and three-fold higher in controls (p < 0.001). Cases took more drugs than controls (4.3 vs. 3.9; p < 0.001), particularly neuroleptic drugs (3.6% vs. 0.5%; p = 0.007). CONCLUSION Despite its small size, our study shows that patients suffering from dehydration in summer are those with more severe renal impairment, taking more drugs (particularly neuroleptics). This pilot work could allow to improve methodology of further studies on drugs during heat waves.

Adverse drug effects in patients with Alzheimer's disease or another dementia: PEIMA study

was predictive of acetylcholinesterase inhibitors (AChEI) response in patients with Alzheimer’s disease (AD), but few examined the effect of education level. This study was aimed to identify whether the effect of baseline cognition on AChEI response was modified by education level. Methods: A total of 257 mild to moderate AD patients, who received AChEI, were recruited from the neurology clinics of three teaching hospitals in northern Taiwan from 2007 to 2010. Mini-mental status examination (MMSE) was performed at baseline and at months 6 and 12 after the initiation of AChEI. The education level was classified as lower education ( 6 years) or higher education (> 6 years). Responders to AChEI treatment were defined as the improvement of MMSE score equaled to two points or greater between baseline and 6 months. Logistic regression was used to explore the association between baseline MMSE and AChEI response by education level (higher and lower). Results: About 90% patients completed 6 months while 72% completed 12 months of AChEI treatment. A significant improvement was observed at the 6 months in both AD patients with low and high education (mean MMSE change 1⁄4 0.9 6 2.6, 0.5 6 2.6, respectively). At the 12 months, a sustained improvement in MMSE score was observed among those with low education (12 month MMSE-baseline MMSE 1⁄4 0.99 6 3.12, p 1⁄4 0.0014). In contrast, among those with higher education, MMSE increased at 6 month and then decreased to slightly lower than baseline at 12 month (12 month MMSE-baseline MMSE 1⁄4 0.35 6 3.8, p 1⁄4 0.415). A lower baseline MMSE score was associated with better response to AChEI in those with higher education, after adjustment for age, gender, and apolipoprotein E (APOE) e4 status [odds ratio (OR) 1⁄4 0.82, 95% confidence interval (CI) 1⁄4 0.72-0.92]. Patients with the lowest quartile of baseline MMSE were 7 times more likely to be responders as compared with those in the highest quartile (95% CI 1⁄4 2.36-20.5). Education level alone was not predictive of AChEI response. Conclusions: AD patients with low education level have more sustained response to AChEI. Baseline MMSE is a useful predictor of AChEI treatment, especially in those with high education.