[Pulmonary nocardiosis with cerebral abscesses mimicking metastatic lung cancer: Three cases and a review of literature]. / Nocardiose pulmonaire avec abcès cérébraux mimant un cancer bronchique métastatique : trois cas et revue de la littérature.

Nocardiosis is an infectious disease with wide range of clinical features, which can eventually lead to death. The agent responsible belongs to the genus Nocardia that includes about fifty different species. Nocardiosis occurs mainly in immunocompromised hosts. We report here three cases of disseminated nocardiosis misdiagnosed initially as cerebral metastatic lung cancer. These patients, including two immunocompetent hosts, presented with both pulmonary and cerebral lesions. In all three patients, the diagnosis was based on magnetic resonance imaging with diffusion sequence, apparent diffusion coefficient reconstruction and neurosurgical cerebral biopsies. Treatment with an appropriate antibiotic regimen was prolonged for several months. Progress was favorable with full resolution of the neurological symptoms and the radiological abnormalities. These three cases emphasize the diagnostic challenge of nocardiosis, especially in disseminated disease.

Determinants of glycopeptides consumption in hospitals.

The aim of this study was to describe consumption of glycopeptides and to study factors associated with their use in 47 French hospitals. Consumption of glycopeptides for systemic use (defined daily doses per 1,000 patient-days: DDD/1,000 PD and per 100 admissions), number of methicillin-resistant Staphylococcus aureus (MRSA) (percentage and incidence per 1,000 patient-days), and number of venous central lines and hospital characteristics (size, length of stay, number of beds: total and for each hospital inpatient areas and antibiotic policies) were recorded from January, 2002, through December, 2002. Multiple linear regression was performed to check for hospital characteristics. The median rate of total consumption of glycopeptides was 4.11(range 0.21-27.22) DDD per 1,000 PD with higher consumption in large public hospitals and in intensive care areas (median 46.51; range 7.19-134) than in surgery areas (median 4.5; range 0.17-24.76). The consumption of glycopeptides correlated with MRSA incidence, but not with the proportion of MRSA. In the multivariate analysis, the incidence of MRSA and the number of beds in surgery areas were independent predictors of total glycopeptides use in the hospital, expressed in DDD per 1,000 PD (R2 adjusted, 0.39). The incidence of MRSA, the number of venous central lines, and the number of beds in the medicine areas were significant determinants associated with higher consumption of glycopeptides expressed in DDD per 100 admissions (R2 adjusted, 0.73). To reduce glycopeptides use in hospitals, the first effort required is that hospitals focus increased attention on the prevention of cross transmission for MRSA between patients but also on the use of the venous central line. Furthermore, hospitals have to compare their data with others to identify overuse of glycopeptides and to plan control interventions.

Hepatitis B vaccination and first central nervous system demyelinating events: reanalysis of a case-control study using the self-controlled case series method.

The hypothesis that hepatitis B vaccination is a risk factor for multiple sclerosis has been discussed at length. The data from an earlier case-control study were reanalyzed using the self-controlled case series method. Using the matched cases from the case-control study, we found a relative incidence of 1.68, 95% CI (0.77-3.68) for the 0-60-day post-vaccination risk period; this compares to an odds ratio of 1.8, 95% CI (0.7-4.6). When an additional 53 unmatched cases not used in the case-control study were included, the relative incidence was 1.35, 95% CI (0.66-2.79). Our results throw further light on the methodological aspects of the case series method. We recommend that, when case-control studies of vaccination and adverse events are planned, case series analyses based on the cases are also undertaken when appropriate.

Channelling of COX-2 inhibitors to patients at higher gastrointestinal risk but not at lower cardiovascular risk: the Cox2 inhibitors and tNSAIDs description of users (CADEUS) study.

PURPOSE: To describe the characteristics of users of cyclo-oxygenase (COX)-2 inhibitors and traditional nonselective non-steroidal anti-inflammatory drugs (tNSAIDs) in France. METHODS: Between 1 August 2003 and 31 July 2004, patients who received at least one dispensing of celecoxib, rofecoxib or tNSAIDs were randomly sampled with a 1:1:2 target ratio within the French National Healthcare Insurance database. Patients and prescribers were asked to fill a questionnaire on socio-demographic characteristics, NSAID indication and use and previous medical history. For each respondent, healthcare resources used in the 6 months before inclusion were extracted from the database. Multivariate logistic regression was used to study the determinants of a first COX-2 inhibitor dispensing. RESULTS: Of the 45 217 patients included, 13 065 COX-2 inhibitors and 13 553 tNSAID users had prescriber data. Ninety seven per cent of COX-2 inhibitor prescriptions were for 'rheumatological' indications, whereas 37% of tNSAIDs use was for benign diseases (n = 2643) or analgesia (n = 2318). Among patients with rheumatological indications (n = 4730) and a first COX-2 inhibitor (n = 2427) or tNSAID (n = 2303) dispensing, multivariate analysis of factors associated with COX-2 inhibitors dispensing showed that, compared to new tNSAID users, new COX-2 inhibitor users were older, more often female, on sick leave or unemployed. COX-2 use was also associated with previous gastrointestinal history and previous gastroprotective agent dispensing, but not with previous cardiovascular (CV) history. CONCLUSION: The choice of NSAID depended largely on indication and on previous gastrointestinal history, in line with the recommendations of the French health authorities. Possible knowledge of CV risk associated with COX-2 inhibitors did not influence prescribing.

[Relationship between antibiotic policies and antibiotic consumption in hospitals]. / Relation entre politique de bon usage et consommation des antibiotiques dans les établissements de santé.

OBJECTIVE: The authors had for aim to study the relationship between antibiotic policies and antibiotic consumption in hospitals. DESIGN: A component analysis was used to summarize the various measures of the antibiotic policies developed by hospitals. Antibiotics consumption was expressed as a number of Daily Defined Doses per 1,000 patient-days. The relation was studied by a multiple linear regression model with adjustment on hospital activity. RESULTS: The first component illustrated an active program of antibiotic policies associating: a local antibiotic committee, an infectious diseases consultant, written local guidelines for prescriptions and restrictive measures before dispensing. The highest antibiotic consumption was associated with active policies, especially for carbapenems, glycopeptides, and aminoglycosides. However the relationship differed according to the type of hospital, with lower antibiotic consumption, especially for penicillins, in private hospitals that had more active policies. CONCLUSION: The difference between public and private hospitals could be explained by the type of institution but also by the unit used to measure antibiotic consumption.

The CADEUS study: methods and logistics.

PURPOSE: At the request of the French Health authorities, a study called CADEUS (COX-2 inhibitors and NSAIDs: description of users) aimed to describe the users of cyclo-oxygenase (COX)-2 inhibitors and traditional non-selective non-steroidal anti-inflammatory drugs (tNSAIDs). We report here the methodology, logistics and study design performances. METHODS: CADEUS is a cohort study designed to include 40,000 patients randomly sampled monthly in the French National Healthcare Insurance database, who received at least one dispensation of celecoxib, rofecoxib or tNSAIDs (1:1:2), from September 2003 to August 2004. Patients and prescribers were asked to fill a questionnaire on indication, medical history, risk factors and hospitalizations since drug acquisition. There was no reminder. For each respondent, healthcare resources used for the 6 months before and after inclusion were extracted from the database. Response rate, response delay, responders and non-responders characteristics were assessed. RESULTS: Of the 222,879 patients and their prescribers contacted, 20.8% patients and 32.6% prescribers responded. Median response delay was 16 days for patients and 17 days for physicians. Factors associated with patient response were age, cohort, type of prescriber and period of inclusion. CONCLUSION: This is the first study of this design in France, combining data from a claims database and direct patient and prescriber questionnaires.

[Psychotropic drug use and mental psychiatric disorders in France; results of the general population ESEMeD/MHEDEA 2000 epidemiological study]. / Usage des psychotropes et troubles psychiatriques en France: résultats de l'étude épidémiologique ESEMeD/MHEDEA 2000/ (ESEMeD) en population générale.

INTRODUCTION: The use of psychotropic drugs is high in France and has increased over the last two decades. To date, no national study evaluating psychotropic drug use in the context of the diagnosis of psychiatric disorders has been performed. Such data has now been generated in the ESEMeD/MHEDEA 2000 study, which has allowed comparison of the situation in France with that in five other European countries (Germany, Belgium, Spain, the Netherlands and Italy). OBJECTIVES: 1) To describe the declared use of psychotropic drugs (globally and by therapeutic class) in order to evaluate annual prevalence, treatment duration and demographic factors associated with use. 2) To estimate the proportion of subjects with an anxiety disorder, mood disorder or alcohol-related disorder (abuse or dependence) that have been appropriately treated with an antidepressant or anxiolytic drug. 3) to evaluate the proportion of psychotropic drug users who fulfil diagnostic criteria for these three classes of psychiatric disorder. METHODS: This was a transversal survey carried out between 2001 and 2003 of non-institutionalised subjects aged 18 or over in the general population of Germany (n = 3,555), Belgium (n = 2,419), Spain (n = 5,473), France (n = 2,894), the Netherlands (n = 2,372) and Italy (n = 4,712). In France, the sampling source used was a randomly generated list of telephone numbers. Subjects were interviewed at home by professional interviewers. The WMH-CIDI questionnaire was used. RESULTS: In France, 21% of subjects interviewed (n = 580) had taken at least one psychotropic drug during the year. For 19%, this was an anxiolytic or hypnotic (AX-HY), for 6.0% an antidepressant (AD), for 0.8% an antipsychotic (AP) and for 0.4% a mood regulating drug (TY). The distribution of users of AX-HY according to treatment duration was the following: 44% (1 to 15 days), 13% (16 to 30 days), 14% (1 to 3 months), 6.7% (3 to 6 months) and 23% (> 6 months). For users of ADs, the distribution was: 21% (1 to 15 days), 7.8% (16 to 30 days), 18% (1 to 3 months), 12% (3 to 6 months) and 42% (> 6 months). For subjects fulfilling diagnostic criteria for a mood disorder in the previous year or over their lifetime, 43% and 29% respectively had taken an AX-HY in the last twelve months and 29% and 16% an AD. For those who fulfilled diagnostic criteria for an anxiety disorder in the previous year or over their lifetime, the use of an AX-HY, in the last twelve months, concerned 43% and 30% of subjects respectively, whilst that of AD concerned 16% and 14%. For previous year or lifetime alcohol-related disorders, AX-HY use, in the last twelve months, concerned 63% and 22% of subjects respectively and use of ADs 9.3% and 7.2%. Amongst users of AX-HY in the last twelve months, a previous year or lifetime diagnosis of mood disorders was made for 16% and 39% of subjects respectively. Amongst users of ADs, the respective prevalence was 31% and 64%. A twelve-month and lifetime diagnosis of anxiety disorders was identified in 22% and 37% of users of AX-HY and among 27% and 50% of users of AD respectively. A twelve-month and lifetime diagnosis of alcohol-related disorders was found in 2.5% and 6.6% of users of AX-HY and among 1.1% and 7.8% of users of AD respectively. 68% of users of AX-HY had fulfilled none of these diagnostic criteria in the previous 12 months and 46% had never fulfilled them in their lifetime. With respect to AD users, the proportion who did not meet these diagnostic criteria in the previous 12 months was 56%, compared to 20% over their lifetime. Comparison of the French data from the study with those of the entire European sample showed that the annual prevalence of AX-HY and AD use was higher in France with mean treatment durations that were shorter. For antipsychotics and mood regulators, no clear differences were observed between France and the six countries of the study taken together. DISCUSSION: Over the last two decades, use of AX-HY seems to have decreased in France, even though it remains higher than that observed in the other European countries participating in this study. This high use can be explained in part by the observation that, in around half the cases, it corresponds to occasional use. In contrast, the use of antidepressants has increased. In subjects with recent mood disorders or anxiety disorders, the use of AX-HY remains higher than that of antidepressants. Finally among users of AX-HY, only half of them had presented a mood disorder, anxiety disorder or alcohol use disorder during their lifetime, whereas this proportion rose to 80% for users of antidepressants.

Accuracy of self-report and toxicological assays to detect substance misuse disorders in parasuicide patients.

OBJECTIVE: To assess the accuracy of self-reported substance use and toxicological assays in subjects admitted for Intentional Drug Overdose (IDO), using as a reference diagnosis of substance use disorder. METHOD: Self-reported substance use was collected and toxicological assays were carried out in urine samples in 507 patients with IDO. A standardized psychiatric evaluation was performed in 100 randomly selected subjects. RESULTS: In routine practice, the emergency department staff did not investigate substance use in nearly one of two patients. Patients' statements and toxicological assays were more specific than sensitive, with lower scores for toxicological assays. Patients' statements made it possible to detect nearly 80% of subjects with substance use disorder. CONCLUSION: Identification of substance use disorder in subjects with IDO has strong clinical consequences regarding treatment and prevention of suicidal behaviour. Thus, emergency department staff should be made aware of the value of more systematically exploring self-reported substance use.

[Benzodiazepine use in the elderly: the EVA Study]. / Utilisation de benzodiazépines chez le sujet âgé: données de la cohorte EVA.

BACKGROUND: The objectives of this study were to describe the use of benzodiazepines in the elderly and to identify socio-demographic and medical factors associated with this use. METHODS: Data on the use of sedative and sleeping drugs were collected from a self-reported questionnaire, in a sample of 1265 elderly subjects (aged 60 to 70 years) interviewed at the first follow-up examination of the EVA Study (Epidemiology of Vascular Aging Study). RESULTS: Use of sedative or sleeping drugs was reported by 28.7% of the participants and use of benzodiazepines by 23%. Most of the benzodiazepines used (71%) had anxiolytic indications, 48% were long-acting compounds (elimination half-life>=20 h.). Among benzodiazepine users, 71% reported using benzodiazepines daily and 77% reported they had been taking benzodiazepines for at least 2 years. Nearly two third of the benzodiazepine users reported taking their medications as prescribed. When they were not compliant, they took benzodiazepines less often and/or at slighter doses than prescribed. Use of benzodiazepines was associated with symptoms of depression or anxiety (women: odds-ratio=2.6 [1.7-4.1]; men: odds-ratio=4.4 [2.4-7.8]) and with regular use of at least three non-psychotropic drugs (women: odds-ratio=2.0 [1.4-2.9]; men: odds-ratio=1.8 [1.1-3.1]). Women with a high educational level or with moderate alcohol consumption were less likely to take benzodiazepines; these associations were not found in men. CONCLUSIONS: The present study shows that benzodiazepines are the sedative and sleeping drugs most widely used by the elderly. Nearly three quarters of benzodiazepine users were chronic users.

Benzodiazepine use in an elderly community-dwelling population. Characteristics of users and factors associated with subsequent use.

OBJECTIVES: The objective of this study was to describe determinants of current and subsequent benzodiazepine use in an elderly population, the Paquid cohort. METHODS: The study was conducted on a cohort of 2,792 community-dwelling subjects 65 years of age or more living in the Gironde department, southwestern France. Benzodiazepine use and its correlates were studied with data collected at inclusion in the cohort. Longitudinal analysis over a 5-year period of follow-up was done to identify baseline predictors of subsequent use. RESULTS: At baseline, prevalence rate of benzodiazepine use was 31.9%. It was associated with female gender [odds ratio (OR) = 2.0; 95% confidence interval (CI): 1.66, 2.46], previous psychiatric disease (OR = 2.87; 95% CI: 2.31, 3.56), concomitant antidepressant use (OR = 2.45; 95% CI: 1.59, 3.78), depressive symptomatology (OR = 1.70; 95% CI: 1.28, 2.26), multiple drug use (OR = 1.82; 95% CI: 1.50, 2.21), multiple chronic diseases (OR = 1.37; 95% CI: 1.12, 1.67) and poor self-perceived health (OR = 1.63; 95% CI: 1.33, 2.0). For the 1926 benzodiazepine non-users at inclusion and followed during 5 years, incidence rate of subsequent use was 5.37 per 100 person-years (95% CI: 4.76, 5.98). In multivariate Cox proportional hazards regression analysis, previous psychiatric diseases, poor self-perceived life satisfaction and polymorbidity were significantly associated with subsequent benzodiazepine use. CONCLUSIONS: Elderly people are heavy users of benzodiazepines. Independently from mental health status, those in poor health were most at risk of benzodiazepine use.

[Drug evaluation in France: comparison of two approaches]. / L'évaluation des médicaments en France: comparaison de deux approches.

Two independent expert groups assess new medicines in France: that of the journal Prescrire (P), and the official Transparency Commission (CT). Each uses its own 5-level scale to assess its contribution to therapeutics (P: (1) bravoi, (2) interesting, (3) adds something, (4) possibly useful, (5) nothing new; CT: (1) major, (2) important, (3) moderate, (4) modest, (5) none). We have compared the gradings for new drugs in P from 1993 to 1998 (except vaccines, generics and items for exclusive hospital use) to those of CT. Of 414 P gradings, 14 were without opinion, 54 were not found in CT (old or unexamined products), and 82 had been examined but not graded. The 264 graded pairs were 99 new substances (NS), 17 new combinations (NA), 50 new indications (NI), 56 new formulations (NF), 27 new dosages (ND), 10 new forms of packaging (NC), and 5 late gradings or reregardings (CR). For NS and NA, there were 21 discordances (2 degrees difference or more) between P and CT. When P is shifted one point to the left (better gradings), the number of discordances decreases to 2. NI, NF, ND, NC were less often graded by CT (respectively 63 per cent, 67 per cent, 54 per cent, 31 per cent of gradings). For NI, high CT grading results in 15 discordances (30 per cent). For NF, ND, NC the concordance is good (respectively 3, 1, 0 discordances). For CR, 13 of 18 products (72 per cent) are downgraded for P, and are discordant with the 5 initial CT grades. In 3 per cent of cases, P emits no opinion, CT gives a high grading in 2/3, never null (these are for severe diseases). In conclusion, the two groups of experts come to similar conclusions considering different objectives (use or not a new drug vs. give indications for reimbursement) and the time distortion. Discrepancies can also be explained thus, but some can result from differences in appreciation of the data.

Benzodiazepines and hip fractures in elderly people: case-control study.

OBJECTIVE: To determine whether benzodiazepines are associated with an increased risk of hip fracture. DESIGN: Case-control study. PARTICIPANTS: All incident cases of hip fracture not related to traffic accidents or cancer in patients over 65 years of age. 245 cases were matched to 817 controls. SETTING: Emergency department of a university hospital. MAIN OUTCOME MEASURES: Exposure to benzodiazepines and other potential risk or protective factors or lifestyle items. RESULTS: The use of benzodiazepines as determined from questionnaires, medical records, or plasma samples at admission to hospital was not associated with an increased risk of hip fracture (odds ratio 0.9, 95% confidence interval 0.5 to 1.5). Hip fracture was, however, associated with the use of two or more benzodiazepines, as determined from questionnaires or medical records but not from plasma samples. Of the individual drugs, only lorazepam was significantly associated with an increased risk of hip fracture (1.8, 1.1 to 3.1). CONCLUSION: Except for lorazepam, the presence of benzodiazepines in plasma was not associated with an increased risk of hip fracture. The method used to ascertain exposure could influence the results of case-control studies.

Incidence and predictors of drug-treated diabetes in elderly French subjects. The PAQUID Epidemiological Survey.

AIMS: To estimate the incidence and predictors of drug-treated diabetes in elderly subjects. METHODS: The PAQUID epidemiological survey, a population-based study, has followed up 3,777 subjects older than 65 years since 1988. At each visit (baseline, 1, 3, 5 and 8 years), treatment regimen was used to identify new drug-treated diabetic subjects. Potential predictors of drug-treated diabetes were collected during the baseline visit (body mass index (BMI), educational level, cigarette smoking and wine consumption, physical activity, depressive symptomatology, subjective health, treatment, and hypertension) and analysed by using a multivariate backward stepwise regression Cox model with delayed entry. RESULTS: The prevalence rate of drug-treated diabetes was 7.5% at baseline and 7.1% after 8 years' follow-up. The incidence rate of drug-treated diabetes was 3.8/1,000 person-years, 5.9/1,000 person-years in men and 2.4/1,000 person-years in women, with no significant variation according to age group. Male sex (relative risk (RR) 2.4, 95% confidence interval (CI) 1.4-4.0, P < 0.001, attributable risk (AR) 0.36), elevated BMI (for one point increase, RR 1.1, 95% CI 1.1-1.1, P < 0.001, > or = 25 vs. < 25, RR 2.1, 95% CI 1.2-3.5, AR 0.33), thiazide diuretics used alone (RR 5.9, 95% CI 1.8-19.6, P = 0.02), and poorer subjective health ('the same' vs. 'better' RR 1.8, 95% CI 1.0-3.1, P = 0.04; 'worse' vs. 'better' RR 2.3, 95% CI 0.9-5.7, P = 0.06) were independent predictors of drug-treated diabetes in this population. CONCLUSIONS: In older French individuals, men seem to be particularly exposed to drug-treated diabetes although being overweight was found to be a strong predictor as in younger populations.

[Evolution of drug treatments in the aged living at home]. / Evolution des traitements médicamenteux des personnes âgées vivant à domicile.

PURPOSE: Although overprescription and overconsumption of drugs are common in the elderly, their features are still not well known since retrospective data on drug intake in this population is very limited. This study was therefore aimed at assessing the evolution of drug intake in the elderly. METHODS: In a study undertaken in the context of the PAQUID project, drug intake was assessed in a group of elderly subjects living at home in either Gironde or Dordogne in south-western France. Each subject was visited by an investigator in successively 1988-89, 1991-92, 1993-94, and 1996-97. Three thousand seven hundred and seventy-seven subjects were included in the study since 1988. Their mean age was 75.4 years (CI 95%: 75.2-75.6 years) and the sex ratio was 0.72. RESULTS: Eighty-nine percent of the subjects took at least one drug per day; 49% took one to four drugs per day; and 40% took more then five drugs per day. The total drug consumption showed an increase in drug intake during the 8-year follow-up, whether the subjects were or not dependent according to their IADL score. CONCLUSION: Analysis of drug intake evolution according to age, sex and daily drug intake at inclusion in the study showed that during follow-up drug intake increased in younger people who had no treatment at study inclusion, while it decreased in older subjects receiving multiple medications. This decrease might be due to either adverse side-effects, drug interactions, or repeated episodes of hospitalization.

Patterns of neuroleptic drug prescription: a national cross-sectional survey of a random sample of French psychiatrists.

AIMS: To describe the psychiatric indications of neuroleptics (especially the relative share of schizophrenic and other psychotic disorders) and the usage patterns of these drugs (dose, duration, coprescriptions). METHODS: A one-day national cross-sectional survey in a random sample of 723 French psychiatrists was carried out in 1996. Each psychiatrist was asked to complete a standardized questionnaire for the first three patients seen the day of the survey to whom at least one neuroleptic was prescribed (initiated or renewed). RESULTS: One thousand seven hundred and fifty-four questionnaires were returned. Three quarters of the patients (74%) were psychotic (664 with schizophrenia, and 636 other psychosis), 19. 3% were depressive and 6.7% had other psychiatric disorders. Phenothiazines were the most often prescribed (40.8%), followed by butyrophenones (22.5%), benzamides (15.8%), other neuroleptics (14. 8%) and thioxanthenes (6.1%). Among schizophrenic subjects, an average number of 1.54 (95% CI: 1.50-1.60) neuroleptics were prescribed per patient, compared with 1.4 (95% CI: 1.32-1.41) and 1. 2 (95% CI: 1.14-1.23) in other psychotic and depressive subjects, respectively. Regardless of the indication, non-neuroleptic psychotropic drugs were coprescribed in 75.4%, mainly benzodiazepines (75.7%). Adjuvant drugs used in prevention or treatment of side-effects were coprescribed in 46.7%, mostly anticholinergic antiparkinsonians (86.1%). CONCLUSIONS: Neuroleptics are mainly prescribed for psychotic disorders and especially schizophrenia. However, current recommendations are not always followed.

Risk factors for fractures in the elderly.

We report the results of a 5-year prospective cohort study of risk factors for fractures, including drinking fluoridated water, in a cohort of 3,216 men and women aged 65 years and older. We studied risk factors for hip fracture and fractures at other locations separately. We found a higher risk of hip fractures for subjects exposed to fluorine concentrations over 0.11 mg per liter but without a dose-effect relation (odds ratio (OR) = 3.25 for a concentration of 0.11-0.25 mg per liter; OR = 2.43 for > or = 0.25 mg per liter]. For higher thresholds (0.7 and 1 mg per liter), however, the OR was less than 1. We found no association between fluorine and non-hip fractures. Non-hip fractures were associated with polymedication rather than with specific drug use, whereas fracture was associated with polymedication and use of anxiolytic and antidepressive drugs. Subjects drinking spirits every day were more likely to have hip fractures. Tobacco consumption increased the risk for non-hip fractures.