Maryse Lapeyre-Mestre

Anxious and Depressive Symptoms in Parkinson's Disease: The French Cross-Sectionnal DoPAMiP Study

Anxiety has been less extensively studied than depression in Parkinsons disease (PD). The DoPaMiP survey allowed assessing simultaneously anxiety and depressive symptoms in PD and comparing correlations of both symptoms with clinical and therapeutic features of the disease. Cross sectional survey conducted prospectively in 450 ambulatory nondemented PD patients and 98 patients with other disorders than PD. Anxiety and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), parkinsonism using the Unified Parkinsons Disease Rating Scale (UPDRS). Other clinical factors were measured using a structured standardized examination/questionnaire. The mean HADS‐A (anxiety) subscore was higher in PD patients than in the others (8.2 ± 3.9 vs. 6.5 ± 3.2, P < 10−4) as was the HADS‐D (depressive) subscore (6.6 ± 3.8 vs. 3.9 ± 3.2, P < 10−4). Patients with possible/probable anxious signs (HADS‐A ≥ 8) were more prevalent in PD (51% vs. 29%, P < 10−4) as were those with depressive symptoms (40% vs. 10%, P < 10−4). Conversely, anxiolytic and antidepressant medications consumption was not different between the 2 groups. Patients with anxious symptoms were more frequently female and younger than those without such symptoms, while those with depressive symptoms had more severe indices of parkinsonism, more comorbidities and lower cognitive function (Mini Mental State Exam). The logistic regression model revealed that patients with depressive symptoms received more frequently levodopa and less frequently a dopamine agonist. Anxiety and depressive symptoms were more frequent in PD patients than in medical control group. Both symptoms were commonly associated in the same PD patients, but were correlated with different clinical/therapeutic features, suggesting different underlying pathophysiological mechanisms.

Cannabis Use: Signal of Increasing Risk of Serious Cardiovascular Disorders

Background Cannabis is known to be associated with neuropsychiatric problems, but less is known about complications affecting other specified body systems. We report and analyze 35 recent remarkable cardiovascular complications following cannabis use. Methods and Results In France, serious cases of abuse and dependence in response to the use of psychoactive substances must be reported to the national system of the French Addictovigilance Network. We identified all spontaneous reports of cardiovascular complications related to cannabis use collected by the French Addictovigilance Network from 2006 to 2010. We described the clinical characteristics of these cases and their evolution: 1.8% of all cannabis‐related reports (35/1979) were cardiovascular complications, with patients being mostly men (85.7%) and of an average age of 34.3 years. There were 22 cardiac complications (20 acute coronary syndromes), 10 peripheral complications (lower limb or juvenile arteriopathies and Buerger‐like diseases), and 3 cerebral complications (acute cerebral angiopathy, transient cortical blindness, and spasm of cerebral artery). In 9 cases, the event led to patient death. Conclusions Increased reporting of cardiovascular complications related to cannabis and their extreme seriousness (with a death rate of 25.6%) indicate cannabis as a possible risk factor for cardiovascular disease in young adults, in line with previous findings. Given that cannabis is perceived to be harmless by the general public and that legalization of its use is debated, data concerning its danger must be widely disseminated. Practitioners should be aware that cannabis may be a potential triggering factor for cardiovascular complications in young people.

Hospitalizations because of Adverse Drug Reactions in Elderly Patients Admitted through the Emergency Department

Background and objectivesSeveral studies have been conducted to determine the frequency and characteristics of adverse drug reactions (ADRs) in elderly populations, focusing on those leading to hospital admission. However, most of these studies have been limited in their ability to assess risk factors, particularly the renal status of patients. Thus, the aim of this prospective study was to assess the incidence of ADRs and associated factors leading to hospital admissions in the elderly population.MethodsAll patients aged ≥65 years admitted to the Toulouse University Hospital through the Emergency Department during four non-consecutive weeks in 2002–3 were included in this study except for patients in ambulatory care or admitted for intentional overdoses. The characteristics of patients admitted for a suspected ADR were compared with those of patients admitted for other reasons.ResultsThe incidence of hospital admissions for ADRs was 8.37 per 100 admissions (95% CI 6.52, 10.52), corresponding to 66 patients with ADRs among 789 admissions. The most important factors associated with ADRs were the number of drugs being taken (odds ratio [OR] 1.18; 95% CI 1.08, 1.29), self-medication (OR 2.34; 95% CI 1.18, 4.66), use of antithrombotics (Anatomic Therapeutic and Chemical [ATC] classification B01; OR 2.26; 95% CI 1.33, 3.88) and use of antibacterial drugs (ATC J01; OR 4.04; 95% CI 1.50, 10.83). Surprisingly, exposure to drugs for acid-related disorders was associated with a low risk of ADRs (OR 0.26; 95% CI 0.09, 0.76).ConclusionA significant incidence of ADRs leading to hospital admissions was found among elderly people. Our study showed that there is a need to increase the availability of information for the general public concerning potential ADRs due to self-medication and for prescribers concerning ADRs due to drug-drug interactions and polypharmacy.

Sleep attacks and antiparkinsonian drugs: a pilot prospective pharmacoepidemiologic study.

A prospective survey was performed to characterize the prevalence of sleep attacks and to evaluate precipitating factors in a group of 236 patients with idiopathic Parkinsons disease. Sleep attacks were reported by 72 patients (30.5%). Multivariate analysis showed a marked association between the occurrence of sudden sleep episodes and first autonomic failure, followed by treatment with ropinirole and bromocriptine. The present work underlines the major contributing role of autonomic failure followed by dopamine agonists in the occurrence of such an event. Because a relationship between sleep attacks and not only ropinirole but also bromocriptine treatment was described, the present work suggests that sleep attacks are a common side effect of all dopamine agonists.

Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database.

Adverse drug reactions (ADRs) represent an important medical issue: they result in 3–7% of all hospital admissions and are associated with a substantial increase in morbidity and mortality. Numerous methods can be used to investigate ADRs. Each has its strengths and weakness. The insufficiencies of basic (experimental) pharmacology as well as clinical trials for studying ADRs are well known. Animal physiology often differs from that of humans. Clinical trials, although necessary, do not allow definite conclusions, because they are built to evaluate efficacy more than safety. Thus, spontaneous notifications remain the cornerstone for ADRs despite their mandatory limitations (under-reporting, selective reporting, lack of denominator etc.). Intensive studies could allow quantification of a specific problem of drug safety (i.e. drug admission into hospital for ADRs). For some years, several pharmacoepidemiological methods have been used to identify and also to quantify ADRs. Among thesse methods, case–control or cohort studies are most widely used. However, their setting up requires specific organization, delay, money and also use of large databases, which are not often specifically built for evaluation of ADRs. In the present issue of the journal, clinical pharmacologists and pharmacoepidemiologists from Poitiers University Hospital (France) have used another method, working from the French PharmacoVigilance database. They used disproportionality analysis for identification of memory disorders associated with drugs [1]. The present paper discusses the benefits and strengths of this method.

Utilisation and safety of low molecular weight heparins: prospective observational study in medical inpatients.

AbstractAims: Low molecular weight heparins (LMWHs) are widely used as curative or preventive treatments of thromboembolic diseases. The aim of our study was to: (i) investigate the pattern of prescription of LMWHs in different departments of French teaching hospitals; and (ii) estimate the incidence of adverse drug reactions (ADRs) induced by LMWHs and associated risk factors for the occurrence of bleeding events. Methods: This prospective study was performed in two teaching hospitals in Toulouse (south-western France) in March 1999 in different medical wards. All patients receiving a prescription for a LMWH were included in the survey. All data were prospectively recorded in each ward. Results: A total of 334 patients were included. Sex ratio (male/female) was 1.25 and mean age was 72.5 ± 16.3 years (extremes: 18–101). 450 prescriptions for LMWHs were collected (1.34 prescription per patient) and involved mainly enoxaparin (61%), which was more frequently used than tinzaparin in patients over 75 years old (71.7 vs 28.3%; p < 0.0001). Ninety-nine patients received a LMWH for curative treatment (corresponding to 127 prescriptions of which 99 were for enoxaparin and 28 were for tinzaparin [p < 0.0001]). Indications included therapy for deep venous thrombosis, pulmonary embolism, acute coronary syndrome, unstable angina pectoris, non-Q-wave myocardial infarction. Serious renal insufficiency was significantly more frequent in patients from the geriatrics department (p < 0.00001). Enoxaparin was prescribed more frequently in patients with serious or moderate renal insufficiency than tinzaparin (72 vs 61%, p < 0.05). The incidence of LMWHs-induced ADRs was 10.5% occurring in 22 cases during preventive treatment of deep venous thrombosis and in 13 cases during curative therapy. ADRs were classified as ‘serious’ in 11 cases (31.4%). Reported ADRs were bleeding events (n = 15), thrombocytosis (n = 13), thrombopenia (n = 4) and hepatic cytolysis (n = 1). The mean delay for the occurrence of bleeding effects was 8.0 ± 9.1 days (range 1–40). Multivariate analysis of the influence of several criteria on the occurrence of haemorrhagic effects showed that the decrease of creatinine clearance (10 ml/min) was associated with an increased haemorrhagic risk (relative risk [RR] = 1.34, 95% CI 1.12–1.65; p < 0.05). Moreover, the risk of adverse bleeding effects increased for patients with a creatinine clearance <20 ml/min (RR = 2.8; 95% CI 1.00–7.8). Conclusion: Our data firstly show a different pattern of LMWHs prescription in different clinical wards. Secondly, the risk of bleeding ADRs in patients treated by LMWHs increases significantly with renal function impairment for the two LMWH preparations studied. More pharmacoepidemiological studies are necessary in patients with several risk factors, particularly in elderly people who often have renal impairment, in order to determine the optimal pattern use of each LMWH.

Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France.

The epidemiology of immune thrombocytopenia (ITP) is not well known. The purpose of this study was to assess ITP incidence at a nationwide level (France) with recent data (mid-2009 to mid-2011; 129 248 543 person-years). The data source is the French health insurance database. We selected cases with diagnosis codes for in-hospital stays and long-term disease attributions, thus restricting our search to ITPs necessitating health care. We studied incidence by age, gender, calendar month, regions, and proportion of secondary ITPs, of ITPs becoming persistent or chronic, and of severe bleeding at disease onset. We identified 3771 incident ITP patients. Incidence was 2.9/100,000 person-years, with peaks among children and in those >60 years of age. ITP was more frequent among males in these subgroups. The incidence was lower in overseas Caribbean French departments, suggesting a lower incidence among Afro-American people. There was a north-south gradient in mainland France and seasonal variations (peak in winter and nadir in summer). Persistence or chronicity occurred in 36% of children compared with 67% of adults. Among adults, 18% of ITPs were secondary. Malignancy was the main cause (10.9%). Myelodysplastic syndromes were not rare (2.3%). Severe gastrointestinal or central nervous system bleeding at ITP onset was rare (<1%).

Assessment of abuse potential of benzodiazepines from a prescription database using ‘doctor shopping’ as an indicator

AbstractBackground: Benzodiazepines are widely used for different purposes because of their pharmacological properties, but their abuse potential may represent a limitation to their use. Data suggest that this abuse potential may vary between products and available dosages. Doctor shopping (the simultaneous use of several physicians by a patient) is one of the most important ways in which prescription drugs, in particular benzodiazepines, are diverted. Objective: To assess the potential for abuse of several benzodiazepines using doctor shopping in a French administrative area as a proxy for abuse. Methods: All prescriptions reimbursed during the year 2003 in Haute-Garonne, France (one million inhabitants) for benzodiazepines that were available in ambulatory care through community pharmacies as solid oral forms were extracted from a reimbursement database. The benzodiazepines were alprazolam (0.25 mg, 0.50 mg), bromazepam 6 mg, clonazepam 2mg, clorazepate (5mg, 10 mg, 50 mg), diazepam (1 mg, 5 mg, 10 mg), flunitrazepam 1 mg, lorazepam (1 mg, 2.5 mg) and tetrazepam 50 mg. For each patient, the quantities prescribed, dispensed and obtained by doctor shopping (i.e. overlap between prescriptions from different prescribers) were computed. Benzodiazepines were compared using their ‘doctor shopping indicator’ (DSI, the percentage of each drug obtained through doctor shopping among the total reimbursed quantity). Results: About 128 000 patients received at least one benzodiazepine during the year. Four groups of benzodiazepines were identified according to their abuse potential: very high abuse potential (flunitrazepam, DSI = 42.8%); high abuse potential (diazepam 10 mg, DSI = 3.2%; clorazepate 50 mg, DSI = 2.7%); intermediate abuse potential (alprazolam 0.50 mg, bromazepam, clonazepam, DSI ranging from 1.8% to 1.9%); and low abuse potential (other benzodiazepines and dosages, DSI ranging from 0.3% to 1.1%). Conclusion: The DSI can be used to assess the relative abuse liability of benzodiazepines and to detect signals of new patterns of abuse in settings where centralized records of prescription or deliveries are available for the great majority of patients.

Pharmacological and clinical evidences on the potential for abuse and dependence of propofol: a review of the literature.

Propofol (2,6‐diisopropylphenol) is an intravenous short‐acting anaesthetic widely used for inducing and maintaining anaesthesia. Propofol is also being increasingly used for sedation. Beside medical use, propofol is abused for recreational purpose, mostly in medical professionals who are not informed of the risk of dependence to this compound. The aim of this review was to provide an overview of molecular, animal and clinical pharmacological data of the literature evidencing the potential for abuse and dependence of propofol.

Assessing the feasibility of using an adverse drug reaction preventability scale in clinical practice: a study in a French emergency department.

AbstractObjective: To assess the preventability of adverse drug reactions (ADRs) leading to hospital admissions and to investigate the feasibility of the use of a standardised preventability scale in clinical practice. Design: The study was a prospective pharmacovigilance study. All patients more than 15 years old admitted to an emergency department during a period of 4 weeks were included. Characteristics of patients admitted for a suspected ADR (cases) were compared to those admitted for other reasons (controls). Preventability was assessed in two different ways: (i) by using a standardised preventability scale; and (ii) by the assessment of four reviewers without the scale. Results of the two methods were compared. Patients: In total, 671 patients were admitted to an emergency department during the study period. Results: Overall, 44 ADRs were identified involving 41 patients. The incidence of hospital admissions for ADRs was 6.1 per 100 admissions (95% CI 4.4–8.3). According to the French causality assessment method, 71% of ADRs were ‘possible’, 18% were ‘plausible’ and 11% were ‘likely’. Using the standardised preventability scale, one-third of all ADRs were considered as being preventable (9% ‘definitely’ and 25% ‘potentially’ preventable). Reviewers found that 54.5% of ADRs were ‘preventable’. Discrepancies between the two methods concerned mainly cases defined as not preventable by the scale. In general, reviewers overestimated the preventability of ADR compared with the scale. Conclusions: These results emphasise that ADRs leading to hospitalisation are frequent, with one-third of them likely to be preventable. Moreover, the risk of ADRs mainly involved a small number of drugs. Our experience suggests that there is a need for further studies to validate the French standardised scale of preventability assessment.