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Objective Estimate the effect of lifestyle adjustment activities in patients with metabolic syndrome treated by prescribed balneotherapy. Methods Observational pilot cohort study with 12-month follow-up after multidimensional lifestyle training (physical, dietary, educational) during 3-week standard stay in the spa town of Eugenie-les-Bains. Results Of 145 eligible patients, 97 were included; 63 were followed and analysable. At inclusion all had ≥ 3 National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) criteria defining metabolic syndrome, 76.2% were female, mean age was 61.2 years. At the end of follow-up (median:10.4 months, Inter-Quartile Range: [6.7;11.4]), 48 of these 63 patients (76.2%) no longer had metabolic syndrome (95%CI [65.7;86.7]). These 48 patients without metabolic syndrome at the end of follow-up represented 49.5% of the 97 included (95%CI [39.5;59.4]). Conclusions Future studies of lifestyle interventions taking advantage of the spa environment can be expected to find least one third of patients free of metabolic syndrome at the end of 12-month follow-up in the intervention group.

The aim of the present study was to describe the real-life usage patterns of paracetamol.The Echantillon Généraliste de Bénéficiaires (EGB) database, the permanent 1/97 representative sample from the French national healthcare insurance system, was searched in 2011 to identify usage patterns, concomitant chronic diseases and use of cardiovascular medication in users prescribed single-ingredient (SP) and combination (CP) paracetamol, representing 85% of all sales.Of 526 108 subjects aged ≥15 years in the EGB, 268 725 (51%) had paracetamol dispensed on ≥1 occasion; of these, 207 707 (77%) were dispensed only SP and 61 018 (23%) received CP with or without SP. SP users were younger (48.3 years vs. 50.5 years), and 57% of SP users vs. 58% of CP users were female. Chronic comorbidities were more common in CP than SP users. SP users had, on average, 3.4 dispensings per year vs. 5.0 for CP users, for 36 defined daily doses (DDD, 3 g) of SP vs. 53 DDD per year for CP; 49% SP users bought 14 DDD or fewer; 15% bought60 DDD. Use of paracetamol increased with age from about 16 DDD per year in 15-30-year-olds to over 90 DDD per year in patients above the age of 75; 53% of patients ≤60 years bought fewer than 14 DDD per year, whereas 55% of those60 bought more than 30 DDD per year. More than half the dispensings exceeded the legal per-box limit of 8 g.Over 50% of the French adult population were dispensed paracetamol at least once over the course of a year, generally for short-term use. Considering recent misgivings on the real efficacy and safety of paracetamol, such widespread use might have important public health consequences.

Purpose To determine healthcare claim patterns associated using nonsteroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis (RA). Methods The CADEUS study randomly identified NSAID users within the French health insurance database. One-year claims data were extracted, and NSAID indication was obtained from prescribers. Logistic regression was used in a development sample to identify claim patterns predictive of RA and models applied to a validation sample. Analyses were stratified on the dispensation of immunosuppressive agents or specific antirheumatism treatment, and the area under the receiver operating characteristic curve was used to estimate discriminant power. Results NSAID indication was provided for 26 259 of the 45 217 patients included in the CADEUS cohort; it was RA for 956 patients. Two models were constructed using the development sample (n = 13 143), stratifying on the dispensation of an immunosuppressive agent or specific antirheumatism treatment. Discriminant power was high for both models (AUC > 0.80) and was not statistically different from that found when applied to the validation sample (n = 13 116). Conclusions The models derived from this study may help to identify patients prescribed NSAIDs who are likely to have RA in claims databases without medical data such as treatment indication. Copyright © 2012 John Wiley & Sons, Ltd.

Aims/hypothesis Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010. Methods We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin, and adjusted for insulin, biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant (≥80% use time) users of insulin glargine compared with equivalent human insulin users. Results Only type 2 diabetic patients were studied. Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin, respectively, to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin, respectively. All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 (95% CI 0.28, 1.25) in incident exclusive users to 0.58 (95% CI 0.34, 1.01) in all predominant users. Cancer risk increased with exposure to insulin or sulfonylureas in these patients. Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 (95% CI 0.32, 1.06) to 0.56 (95% CI 0.36, 0.87). Conclusions/interpretation There was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone. The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin, thereby excluding a competitive risk bias.

Background Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST. Patients and methods Advanced GIST patients (n = 96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively. Results Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p = 0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p = 0.0256) and for both stomach (p = 0.043) and small bowel (p = 0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p = 0.0271) in the whole population independently of the anatomical localisation. Conclusion Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.

Background: Anti-tumour necrosis factor (TNF) agents, through their intense immunoregulatory effect, have been suspected to increase the risk of malignant lymphoma. However, the classical epidemiological approaches conducted over about the last 10 years have not totally succeeded in addressing the question of a causal or artifactual association. Therefore, the analysis of a substantial set of case reports, although usually considered as poorly generalizable to the general population, could be particularly informative. Two main sources of case reports in postmarketing settings are available; publications in medical journals and reports to pharmacovigilance systems. Objective: The aim of the study was to compare the characteristics of case reports from both these sources in order to understand whether they provided the same information for the investigation of the causal link between lymphoma and anti-TNF agents. Methods: All case reports of malignant lymphoma in patients treated with an anti-TNF agent published in MEDLINE and all reports to the French pharmacovigilance system up to 1 February 2010 were identified. Cases of malignant lymphoma identified in postmarketing surveillance from both sources were compared regarding the following variables: age, sex, anti-TNF agent involved, indication for use, type of lymphoma, prior or concomitant immunosuppressive drugs and time to onset of lymphoma. Results: A total of 81 published case reports and 61 cases reported to the French pharmacovigilance system were compared. In published reports, patients were younger (p = 0.03) and more frequently receiving a first anti-TNF treatment (p = 0.03), particularly infliximab (p = 0.03). Conversely, in the pharmacovigilance system reports, a succession of different anti-TNFs (p = 0.03) and adalimumab (p< 0.0001) were more frequently reported. Lymphomas in patients treated with anti-TNF agents for Crohn’s disease were more prevalent in published cases than in pharmacovigilance reports (p< 0.0001), and in particular involved hepatosplenic T-cell lymphoma. Conversely, rheumatoid arthritis was the main indication for anti-TNF agents in pharmacovigilance reports (p = 0.01). Time to onset was markedly shorter in published cases (median 12 months) than in pharmacovigilance reports (median 30 months; p = 0.0001). Conclusions: Characteristics of published cases and those reported to the French pharmacovigilance system differed markedly for all characteristics tested, except sex and the use of prior or concomitant immunosuppressive drugs. Published case reports favoured convincing arguments for drug causation whereas cases reported to the pharmacovigilance system were more disparate but could describe more accurately the reality of lymphoma occurrence in this particular population. These results argue for the use of the pharmacovigilance reports when case reports are used to investigate the causal link between lymphoma and anti-TNF agents at the population level. Data from cases notified to the French pharmacovigilance system did not indicate an increased risk of lymphoma during the early phase of anti-TNF treatment. To confirm this hypothesis, a study combining pharmacovigilance reports from several countries, or, if feasible, a cohort study both with a large sample size and a long duration of follow-up would be required.

Objectif Evaluer les ressources de sante consommees et leurs couts associes chez les patients debutant un traitement par anticoagulant oral direct (AOD) ou antivitamine K (AVK) dans la fibrillation auriculaire non valvulaire (FANV). Methode Etude de cohorte de patients debutant un traitement par AOD (Pradaxa® ou Xarelto®) ou AVK dans la FANV au cours du premier semestre 2013, identifies et suivis dans l’EGB, echantillon aleatoire permanent de la base nationale du Sniiram et du PMSI. Les patients etaient suivis six mois apres la date index ; la date index etant definie comme la date de premiere delivrance du traitement d’interet avec trois ans d’historique dans la base de donnees. Deux populations FANV ont ete definies : (i) une population specifique incluant les patients avec une information diagnostique de FANV dans l’EGB (ALD ou hospitalisation pour fibrillation auriculaire sans antecedent de pathologie valvulaire), et sans autre indication probable ; (ii) une population sensible composee de la population precedente avec en plus, les patients ayant une information probabilistique de FANV, et sans autre indication probable. Les ressources consommees et leurs couts associes, couts totaux et specifiques de la maladie, ont ete estimes selon la perspective de l’assurance maladie. Resultats Parmi les 1 750 patients debutant un traitement par AOD (Pradaxa® ou Xarelto®) ou AVK durant la periode d’etude, 282 correspondaient a la definition de la population FANV specifique (AOD : 152 patients, AVK : 130 patients). Le sex-ratio etait proche de 1, l’âge moyen a la date index etait de 77 ans (AOD : 75 ans, AVK : 78 ans), avec un score CHA2DS2-VASc ≥ 2 pour 89 % des patients (AOD : 86 %, AVK : 93 %), et un score HAS-BLED ≥ 3 pour 47 % (AOD : 38 %, AVK : 58 %). Au cours des six mois de suivi, le nombre median de delivrances du traitement d’interet par patient etait de 6 (AOD : 7, AVK : 5), et 47 % ont ete hospitalises au moins une fois (AOD : 38 %, AVK : 58 %). Le cout total moyen par patient sur les six mois de suivi etait de 6 289 € (AOD : 4 232 €, AVK : 8 693 €), dont 28 % pour les hospitalisations non cardiovasculaires, 13 % pour les hospitalisations cardiovasculaires, 5 % pour les medicaments cardiovasculaires et antidiabetiques. Le cout medical total moyen specifique de la FANV par patient etait de 875 € (AOD : 824 €, AVK : 933 €), dont 45 % pour les hospitalisations, et 28 % pour les medicaments. Les resultats dans la population FANV sensible (n = 505, 285 AOD, 220 VKA) etaient similaires. Conclusion Cette etude montre que les couts specifiques de la maladie representent moins de 15 % des couts totaux et suggere des couts totaux et specifiques differents entre les AOD et les AVK dans la FANV. Toutefois, en l’absence d’ajustement du fait d’un nombre trop faible de sujets, ceci pourrait correspondre a des differences de caracteristiques entre les deux groupes et sera evalue de facon adequate sur l’ensemble du Sniiram avec des analyses appariees et ajustees.

Objectif Les scores de propension ont ete developpes pour resumer des variables qui predisent le fait de recevoir une intervention A ou B dans une etude non randomisee et ainsi reduire le risque de confusion dans la comparaison de l’impact de ces deux interventions sur un outcome. Les scores de propension haute dimension (hdPS) permettent de prendre en compte un tres grand nombre de variables, qui de plus peuvent collectivement etre des proxy de facteurs de confusion non disponibles dans les donnees. L’objectif de cette analyse etait d’estimer l’impact d’un hdPS avec les donnees du SNDS, sur les differences initiales entre les patients initiant un traitement par dabigatran (150 mg ou 110 mg) et les AVK pour une fibrillation auriculaire non valvulaire (FANV) ; le dabigatran 150 mg etant le dosage standard et le 110 mg recommande chez le sujet âge et/ou a risque hemorragique eleve, ou en cas d’insuffisance renale moderee. Methode Cohorte de tous les patients initiant un traitement par dabigatran ou un AVK en 2013 pour une FANV dans le SNDS. Pour chaque comparaison (150 mg versus AVK, 110 mg versus AVK), un hdPS a ete defini avec un modele de regression logistique prenant en compte le sexe, l’âge, les facteurs de risque thromboembolique et hemorragique, ainsi que 500 indicatrices selectionnees automatiquement pour maximiser le biais entre exposition et outcome etudie (algorithme de Bross), parmi plus de 2000 variables de soins reparties en quatre dimensions : ALD, diagnostics CIM10 d’hospitalisation (trois ans d’historique), medicaments (ATC niveau 7), actes medicaux avec la specialite, actes paramedicaux et examens biologiques (un an d’historique). L’impact du hdPS a ete evalue avec les courbes de distribution du hdPS brute et apres appariement, ainsi que les differences standardisees brutes, ajustees sur le hdPS et pour les patients apparies 1 :1 sur le hdPS (methode Greedy avec caliper 0,05). Resultats En 2013, 103 101 patients FANV initiant un traitement anticoagulant ont ete identifies : 10 847 traites par dabigatran 150 mg, 15 532 par le 110 mg et 44 653 par AVK avec des distributions de hdPS et des caracteristiques nettement differentes. Parmi eux, 77 % des patients dabigatran 150 mg (n = 8389) et 93 % des patients dabigatran 110 mg (n = 14 442) ont ete apparies a un patient AVK avec des distributions de hdPS tout a fait superposables, un âge moyen de 67,3 ans, 67 % d’hommes et 65 % de CHA2DS2-VASc ≥ 2 pour les patients dabigatran 150 mg et VKA apparies, 78,6 ans, 49 % d’hommes et 91 % de CHA2DS2-VASc ≥ 2 pour les patients dabigatran 110 mg et AVK apparies, et des differences standardisees ≤ 5 % pour 500 variables descriptives etudiees, voire ≤ 2 % pour la plupart, et par ailleurs non necessairement selectionnees parmi les indicatrices du hdPS. Conclusion Cette etude montre des differences importantes entre les patients FANV traites par dabigatran 150 mg ou 110 mg et les AVK en pratique courante, avec une utilisation preferentielle du 110 mg chez les patients les plus âges. La methode du hdPS a permis de construire une variable d’appariement performante pour constituer des groupes tres comparables pour la comparaison de deux traitements dans le SNDS.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • To our knowledge, no study has ever described the intensity of nonsteroidal anti-inflammatory drug (NSAID) utilization in an employed population by occupation. • As the use of NSAIDs carries a well-known risk of adverse effects, this risk adds to the burden of musculoskeletal disorders in employed populations. • Information on utilization of NSAIDs in this context will help to better characterize and prevent this risk. WHAT THIS STUDY ADDS • In spite of a previous history of dyspepsia, blue collar workers had the highest rate of chronic and continuous utilization of nonselective NSAIDs. • No clustering of cyclooxygenase-2 selective NSAID utilization according to a previous history of dyspepsia was observed among blue collar workers. • The association between chronicity of NSAID utilization and occupation was independent of medical indication for the prescription and other lifestyle factors. AIM The aim of this study was to compare patterns of utilization of NSAIDs for musculoskeletal disorders (MSD) by occupation in a general employed population. METHODS This was a secondary analysis of the CADEUS cohort study on 5651 actively employed patients, who submitted at least one claim for the reimbursement of a NSAID dispensation for a MSD between August 2003 and July 2004, in the French National Healthcare Insurance database. Questionnaires were sent to prescribing physicians to obtain diagnoses and the medical history, and to patients for their occupation, height and weight and smoking status. Multivariate logistic regression was used to study the determinants of a heavy use of NSAIDs defined as ‘over four dispensations in one year with less than two months between any two’. RESULTS Factors associated with heavy use of NSAIDs were age (Odds ratio (OR): 1.8 (ten years), 95% confidence interval (CI): 1.6–1.9), osteoarthritis (versus back pain) (OR: 1.8, 95% CI: 1.5–2.1), body mass index (superior to 30) (OR: 1.8, 95% CI: 1.5–2.2), and occupation (blue collar versus white collar workers) (OR: 1.4, 95% CI: 1.2–1.6). Blue collar workers also had a 20% higher prevalence of 5-year history of dyspepsia. No difference was observed between sexes or in the use of COX-2 selective inhibitors between occupations. CONCLUSION Factors associated with occupational constraints that contribute to the severity of MSDs, may explain the heavier use of NSAIDs among blue collar workers in spite of a concurrent and past medical history of adverse reactions to this type of medication.

Purpose We describe drug–drug interactions (DDIs) encountered with antifungals in clinical practice. Methods Retrospective observational study of hospitalized adults receiving systemic antifungal treatment in the intensive care unit (ICU) and in the infectious diseases unit (IDU) of the University Hospital of Bordeaux, France between 1996 and 2001. All treatment episodes with antifungal agent were examined and all prescribed concomitant medication identified for potential drug–drug interactions (PDDI)-serious events occurring during treatment were adjudicated for clinical DDI. Results There were 150 treatment episodes with antifungal agent in 105 patients. Fluconazole was used in 48% of the treatment episodes, amphotericin B in 46%, itraconazole in 4.7% and flucytosine in 1.3%. One hundred and sixteen PDDIs were identified related to the use of amphotericin B (81.0%), fluconazole (17.2%) or itraconazole (1.7%). Of these, 22 were associated with a clinical evidence of adverse interaction (hypokalemia, increased creatininemia or nephrotoxicity). All these clinical drug–drug interactions (CDDIs) were with amphotericin B. They were due to furosemide (36.4%), cyclosporine (31.8%) and hydrocortisone (18.2%). PDDIs were mostly associated with leukaemia (40.4%), HIV infection (24.6%) and cancer (10.5%). Conclusions In ICU and IDU, systemic antifungal treatments lead to many PDDIs, mainly related to the type of antifungal used and to the pathology treated. Clinical DDI seem more common with amphotericin. Copyright © 2007 John Wiley & Sons, Ltd.

To evaluate the prevalence of nocturnal symptoms in a large sample of asthmatic patients, and to assess the agreement between patients' complaints and general practitioners' (GPs') reports in primary care.Cross-sectional survey involved 3,526 GPs and 751 specialists (pulmonologists and allergists) and included 13,493 patients with persistent asthma. Symptoms, treatment, and social and medical data were collected in real time by the patients and their GPs.France.Prevalence of nocturnal symptoms was 60%. A total of 7,989 patients with nocturnal symptoms had complete data for both patients and GPs; 3,849 (48.1%) had perfect agreement between GP and their complaints for nocturnal symptoms (agreement group; [kappa = 1]); 3,376(42.2%) declared having no symptoms during the night, but these were detected by the GP during the visit (underestimated by patients and detected by GPs); 773(9.6%) declared having nocturnal symptoms, but these were not detected by GPs. Patients with a good agreement with their GP's opinion were significantly more frequently followed-up by a specialist than other patients (p = 0.002).Nocturnal symptoms appear to be underdeclared by patients. GPs should therefore systematically ask their patients about nocturnal symptoms to increase control of asthma and to adequately manage its treatment.

To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrenees atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

Objective: To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). Method: Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. Results: Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3–2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. Conclusion: Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings.

Reviewing available data shows that most of antipsychotic drugs are associated with arrhythmia and sudden death. Experimental studies have shown a HERG channel blockade, a dose-dependent increase in duration of action potential or of QT interval, with various degrees of indicators of serious arrhythmogenicity. However, it seems difficult to relate these in vitro and in vivo preclinical models to clinical findings, in part, because the relationship between concentrations used and in vivo tissue concentrations during treatment in man is not known. Consequently, we established the myocardium to plasma concentration ratios for a series of antipsychotic drugs by intraperitoneal administration of different level doses to the guinea pig. Then, we compared these values to their ability to induce arrhythmia or torsade de pointes in clinical practice. The myocardium to plasma concentration ratios were 2.2 for clozapine, 2.7 for olanzapine, 3.1 for sertindole, 4.5 for risperidone, and 6.4 for haloperidol. These data suggest that when the ratio is higher than 4, arrhythmia and sudden death may be expected. On the contrary, when the ratio is less than 3, little effect may be predicted. These results underscore the importance of interpreting HERG channel data and electrophysiological data in the context of other pharmacokinetic parameters such as myocardium to plasma distribution.

Objectif Estimer l’incidence en vie reelle des evenements hemorragiques, evenements arteriels thrombotiques (EAT), syndromes coronaires aigus (SCA), et deces chez les patients debutant un traitement par anti-vitamines K (AVK) dans la fibrillation auriculaire (FA), avant l’arrivee des anticoagulants oraux directs (AOD). Methode Etude de cohorte de patients debutant un traitement par AVK entre le 01/01/2007 et le 31/12/2011, identifies et suivis dans une base de donnees de remboursement de soins et d’hospitalisation, l’EGB, echantillon aleatoire permanent de la base nationale du SNIIRAM et du PMSI. Les patients etaient suivis trois ans maximums apres la date index, avec une censure au 31/12/2012 ; la date index etant definie comme la date de premiere delivrance d’AVK, avec deux ans d’historique dans la base de donnees. Les patients FA etaient ceux presentant soit une information diagnostique (ALD ou hospitalisation), soit une information probabilistique d’apres les donnees de l’EGB, et sans autre indication probable des AVK. La population FANV etait definie par les patients de la population FA sans antecedent de pathologie valvulaire. Le taux d’incidence etait estime durant l’exposition aux AVK pour les evenements hospitalises : hemorragie, EAT, SCA, ainsi que pour le deces. Resultats Parmi les 8894 patients debutant un traitement par AVK durant la periode d’etude, 3345 correspondaient a la definition de la population FA avec 3977 personnes-annee (PA) suivies. La moitie des patients etaient des hommes (52 %), l’âge moyen etait de 75 ans, 87 % presentaient un score CHA2DS2-VASc ≥2, et 12 % un score HAS-BLED > 3. Le taux d’incidence des hemorragies pour 1000 PA exposees aux AVK etait de 28 patients (IC 95 % [23–34]), incluant 6 [3–8] hemorragies cerebrales, 10 [7–13] digestives, et 14 [10–17] autres hemorragies. Le taux d’incidence des autres evenements pour 1000 PA exposees aux AVK etaient de 16 [12–20] pour les SCA, 15 [11–18] pour les EAT, et 38 [32–44] pour les deces. Les resultats etaient identiques lorsque seuls les patients avec une information diagnostique (ALD ou hospitalisation) etaient pris en compte. Les caracteristiques des patients et les taux d’incidence estimes dans la population FANV ( n = 2818) etaient egalement tres similaires : 28 [22–34] pour les hemorragies, 16 [12–20] pour les SCA, 15 [11–19] pour les EAT, et 35 [29–41] pour les deces pour 1000 PA exposees aux AVK. L’incidence annuelle en France a ete estimee entre 12 200–19 200 cas d’hospitalisation pour hemorragie (IC 95 %), 6300–11 400 cas de SCA hospitalises, 5900–10 800 cas d’EAT hospitalises, et 15 700–23 700 deces durant une exposition aux AVK pour une FANV. Conclusion Cette etude apporte des valeurs de reference en termes de risques hemorragiques, de risques thrombotiques arteriels et de deces, avant l’arrivee des AOD dans la FANV, avec des taux d’incidence de meme ordre avec ou sans antecedent de pathologie valvulaire.

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.

The correct use of inhalation devices is an inclusion criterion in many comparative studies. However, patients can make errors, thus compromising the effectiveness of their own inhaler. The aim of the study is to evaluate inhaler use by patients with chronic obstructive pulmonary disease (COPD) [n = 984]. General practitioners assessed inhalation technique, using a specific checklist previously established for each inhaler model (Aerolizer, Autohaler, Diskus, a pressurised metered-dose inhaler (pMDI) or a Turbuhaler). A total of 24% of the patients using a pMDI did not make an error compared with 34-40% of those using breath-actuated devices. The frequency of critical errors varied according to the device: 11.5-14.9% of the subjects using an Aerolizer, Autohaler or Diskus versus 37.4% and 38.1% of the patients using a pMDI and a Turbuhaler, respectively. The proper use of the Turbuhaler is often overestimated (24.7%) compared with the pMDI (2.1%). The development of educational programmes for patients and prescribers is needed to improve the management of COPD.

Objectif Comparer les risques d’hemorragies, d’evenements arteriels thrombotiques, de syndromes coronaires aigus et de deces a un an chez les patients initiant un traitement anticoagulant pour une fibrillation auriculaire non valvulaire (FANV) : dabigatran (D) versus antivitamine K (AVK) et rivaroxaban (R) versus AVK. Methode Cohorte de patients avec une FANV debutant un premier traitement par D, R ou AVK en 2013 en France, identifies et suivis pendant un an dans le Sniiram. Deux populations FANV ont ete definies : – specifique : –patients avec un diagnostic de FA sans antecedent de pathologie valvulaire (ALD/hospitalisation) ; – sensible : –patients de la population specifique plus ceux avec une FANV probable basee sur un score de pathologie. Pour chaque comparaison, les patients etaient apparies 1:1 sur le sexe, l’âge, la date de premiere delivrance d’anticoagulant et un score de propension haute dimension incluant les facteurs de risque arteriel thrombotique et hemorragique. L’incidence cumulee a un an du premier evenement pendant l’exposition au traitement a ete estimee par la methode de Kaplan-Meier et les risques compares avec un modele de Cox pour le deces et de Fine et Gray pour les evenements cliniques, definis par un diagnostic principal d’hospitalisation. Resultats En 2013, 103 101 patients (27 060 D, 31 388 R, 44 653 AVK) ont ete identifies dans le Sniiram pour la population specifique et 144 220 (37 222 D, 46 882 R, 60 116 AVK) pour la population sensible. Pour la population specifique, les patients etaient âges en moyenne de 75 (± 12) ans avec 54 % d’hommes, un score CHA 2 DS 2 -VASc ≥ 2 pour 83 %, un score HAS-BLED > 3 pour 10 %, avec des differences standardisees importantes pour chacune des comparaisons et des differences standardisees normalisees ou nulles apres appariement. Le nombre de patients apparies de la population specifique pour chaque comparaison et leurs resultats sont presentes dans le Tableau S1 . La population sensible presentait des caracteristiques similaires et des resultats superposables. Conclusion Cette etude de plus de 100 000 patients montre un meilleur benefice–risque des anticoagulants oraux directs comparativement aux AVK dans la FANV, incluant moins de deces et d’hemorragies intracrâniennes, sans augmentation des hemorragies gastro-intestinales.

Objectif principal Evaluer le mesusage du Pylera® en France. Objectifs secondaires Decrire les caracteristiques des patients consommant du Pylera® ; decrire les nouvelles prescriptions d’un traitement specifique pour eradiquer Helicobacter pylori (H. pylori) (indicateur ou proxy pour evaluer l’echec au traitement). Methodes Etude de cohorte de patients avec une 1re delivrance de Pylera® (date index) entre le 1er avril 2013 et le 30 avril 2014 dans l’EGB (echantillon generaliste des beneficiaires), un echantillon permanent representatif au 1/97e de la base nationale de l’assurance maladie et du programme de medicalisation des systemes d’information (PMSI), avec un historique et un suivi de 12 mois a partir de la date index. Le critere de mesusage etait defini par la delivrance de plus d’une boite de Pylera® a la date index ou d’une delivrance de Pylera® sans test diagnostique specifique dans l’annee precedant la date index. Resultats Un total de 540 patients a eu au moins une delivrance de Pylera® dont les caracteristiques generales etaient : âge moyen de 53 ans (15 % de plus de 70 ans, 1 % d’adolescents entre 12 et 18 ans), 44 % d’hommes, 30 % avec au moins une affection longue-duree (ALD) et 18 % deja traites dans les 12 mois precedents pour une eradication de H. pylori. Les principaux prescripteurs de Pylera® etaient les gastro-enterologues ou medecins hospitaliers (61 %), suivis par les medecins generalistes (30 %). Un inhibiteur de la pompe a protons etait codelivre dans 93 % des cas, principalement l’omeprazole (65 %), suivi de l’esomeprazole (17 %). Neuf patients (2 %) avaient une insuffisance hepatique ou renale et une patiente etait enceinte. Cinquante-neuf patients (11 %) avaient au moins un critere de mesusage : 10 patients (2 %) avec une delivrance le meme jour de plus d’une boite de Pylera® (7 patients avec 2 boites, 2 avec 3 boites, et 1 avec 4 boites) et 49 patients (9 %) sans test a l’uree ou une endoscopie dans l’annee precedente. En tenant compte de la serologie comme test diagnostique, le nombre de patients avec un critere de mesusage diminue de 59 patients (11 %) a 51 patients (9 %). Pendant les 12 mois de suivi, 45 patients (8 %) ont eu une nouvelle delivrance de traitements pour eradiquer H. pylori, dont 17 patients dans les 3 mois suivant la date index. Conclusion Cette etude basee sur les donnees de remboursement de soins en France, montre un mesusage du Pylera® pour un peu plus de 10 % des patients, essentiellement une absence de test de diagnostic avant l’initiation du traitement, et la delivrance de plusieurs boites de Pylera® pour 2 % des patients. A cela s’ajoute quelques patients avec des contre-indications mentionnees dans le resume des caracteristiques du produit, insuffisance renale, insuffisance hepatique et grossesse. Les 8 % de patients qui ont eu une nouvelle delivrance dans l’annee d’un traitement pour eradiquer H. pylori sont dans la borne basse des 10 % et 30 % de taux d’echec d’eradication de l’infection a H. pylori decrit dans la litterature en France.

Background: The real-life benefits and risks of the direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) have been disputed. This study aimed to compare the 1-year risk of major events for new users of dabigatran (D) or rivaroxaban (R) vs. vitamin K antagonists (VKA) in NVAF

Introduction Les scores de propension haute dimension (hdPS) ont ete developpes pour estimer l’effet d’une intervention en tenant compte d’un tres grand nombre de variables pour predire le fait de recevoir l’une ou l’autre des interventions, et egalement etre collectivement un proxy de facteurs de confusion non disponibles dans les donnees. L’objectif de cette analyse etait d’estimer l’impact d’un hdPS sur les differences initiales entre les patients initiant un traitement par anticoagulant oral direct (AOD) ou anti-vitamine K (AVK) pour une fibrillation auriculaire non-valvulaire (FANV) d’apres les donnees du Sniiram. Methodes Identification de tous les sujets initiant un AOD (dabigatran n = 27 060) ou un AVK ( n = 44 653) pour une FANV en 2013 dans le Sniiram. Definition d’un hdPS AOD versus AVK avec un modele de regression logistique prenant en compte des variables forcees (caracteristiques socio-demographiques, facteurs de risque thromboembolique et hemorragique) et 500 variables sur trois ans d’historique de soins reparties en quatre dimensions (ALD, diagnostics d’hospitalisation, medicaments, consultations medicales/paramedicales/biologie), selectionnees pour minimiser le biais entre exposition et evenement etudie (algorithme de Bross). L’impact du hdPS a ete evalue avec les differences standardisees (DS) entre AOD et AVK : brutes, ajustees sur le hdPS et apres appariement 1 : 1 sur le hdPS, ainsi que sur la courbe de distribution du hdPS brute et apres appariement. Resultats Les deux groupes presentaient des distributions de hdPS brutes nettement differentes, decalees a droite pour AOD et a gauche pour AVK (mediane hdPS 0,5 et 0,3 respectivement) avec une zone de recouvrement importante, et tout a fait superposables apres appariement, tout en conservant 76 % des patients du groupe le plus faible ( n = 20 489 par groupe). Une DS brute >10 % concernait 34 % des variables et aucune DS > 10 % apres ajustement ou appariement. Discussion/Conclusion Le hdPS permet de construire une variable d’ajustement ou d’appariement performante pour comparer l’effet et/ou le risque d’un traitement entre deux groupes dans le Sniiram.

Objectif : Estimer l’effet attendu d’une prise en charge multidisciplinaire mise en place lors d’une cure thermale chez des patients présentant un syndrome métabolique. Méthodologie : Cohorte observationnelle avec 12 mois de suivi après intervention multidimensionnelle durant une cure thermale à Eugénie-les-Bains. Résultats : Parmi 145 patients éligibles, 97 ont été inclus, 63 ont été suivis et analysés : à l’inclusion tous avaient ≥ 3 critères National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) définissant le syndrome métabolique, 76,2 % étaient des femmes, l’âge moyen était de 61,2 ans. À la fin du suivi (médiane : 10,4 mois, interquartile : [6,7 ; 11,4]), 48 de ces 63 patients (76,2 %) ne présentaient plus de syndrome métabolique (95 % CI [65,7 ; 86,7]. Ces 48 patients sans syndrome métabolique à la fin du suivi représentent 49,5 % des 97 inclus (95 % CI [39,5 ; 59,4]). Conclusion : Des études d’interventions comportementales durant une cure thermale peuvent s’attendre à trouver au moins un tiers des patients sans le syndrome métabolique à la fin de 12 mois de suivi dans le groupe intervention., Objective. Estimate the effect of lifestyle adjustment activities in patients with metabolic syndrome treated by prescribed balneotherapy. Methods. Observational pilot cohort study with 12-month follow-up after multidimensional lifestyle training (physical, dietary, educational) during 3-week standard stay in the spa town of Eugénie-les-Bains. Results. Of 145 eligible patients, 97 were included; 63 were followed and analysable. At inclusion all had ≥3 National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) criteria defining metabolic syndrome, 76.2 % were female, mean age was 61.2 years. At the end of follow-up (median:10.4 months, Inter-Quartile Range: [6.7;11.4]), 48 of these 63 patients (76.2 %) no longer had metabolic syndrome (95 %CI [65.7;86.7]). These 48 patients without metabolic syndrome at the end of follow-up represented 49.5 % of the 97 included (95 %CI [39.5;59.4]). Conclusions. Future studies of lifestyle interventions taking advantage of the spa environment can be expected to find at least one third of patients free of metabolic syndrome at the end of 12-month follow-up in the intervention group.

Introduction Le paracetamol est le produit le plus prescrit en France mais presque rien n’est connu de son risque cardiovasculaire ou digestif eventuel en vie reelle. Nous avons donc mis en place une etude visant a mesurer le risque de survenue d’infarctus du myocarde, de syndrome coronaire aigu, d’accident vasculaire cerebral ou d’hemorragie digestive haute apres dispensation de paracetamol en France. Methode Il s’agit d’une etude de cohorte autocontrolee dans l’EGB, l’echantillon 1/97 permanent representatif du Sniiram, base couvrant plus de 98 % de la population francaise. Toutes les dispensations de paracetamol entre 2009 et 2012 ont ete identifiees dans l’EGB. Seuls ont ete conserves les episodes d’utilisation exclusive du paracetamol (sans AINS), chez les sujets âges de plus de 15 ans. Chaque episode comportant une periode a risque, de trois mois apres la dispensation, et une periode controle, symetrique avant la dispensation. Les evenements d’interet etaient les hospitalisations identifiees dans le PMSI, en rapport avec un infarctus du myocarde (I21, IdM), un angor instable (I20,0), les deux etant regroupes sous le terme de syndrome coronaire aigu (SCA) ; d’accident vasculaire cerebral (AVC, I63) ; d’hemorragie digestive haute (UGIB, K250, K254, K260, K270, K290, K920, K921 ou K922). Les analyses ont ete faites sur la population totale des episodes inclus, puis en stratifiant sur la presence d’aspirine a faible dose (AFD), selon l’âge, la quantite dispensee de paracetamol, le niveau de risque cardiovasculaire. Resultats Il y avait 1 025 877 episodes d’exposition au paracetamol chez 342 494 patients (âge moyen 47,2 ans ; 55,8 % feminins). Les risques relatifs globaux ajustes de survenue d’IDM, SCA, AVC et UGIB [IC 95 %] etaient de 1,01 [0,85–1,21], 0,91 [0,82–1,01], 0,85 [0,73–0,98] et 1,34 [1,08–1,66]. Chez les utilisateurs d’AFD (5 % des episodes), le risque d’IdM, de SCA ou d’AVC etaient reduits (0,29 [0,20–0,42], 0,39 [0,32–0,47], 0,35 [0,26–0,48]. Chez les non-utilisateurs d’AFD ayant plus de 60 ans, les risques etaient notablement eleves (IdM 1,91 [1,43–2,54], SCA 1,38 [1,19–161] ; AVC 1,13 [093–1,37], UGIB 1,45 [1,08–1,95]). Conclusions La prescription de paracetamol s’accompagne d’un risque diminue d’evenement cardiovasculaire chez les patients co-utilisateurs d’aspirine a faible dose. En revanche, chez les non-utilisateurs d’aspirine, l’accroissement notable des risques cardiovasculaires et digestifs devrait faire rediscuter de l’utilite reelle d’encourager l’utilisation de paracetamol, en particulier chez le sujet âge de plus de 60 ans.

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.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.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.Post-ACS secondary prevention in France is not optimal, especially in patients who did not have myocardial infarction.

Dans le cadre des cures thermales dans l'indication "maladies métaboliques" à Eugénie-les-Bains, une prise en charge multifactorielle du syndrome métabolique est proposée aux curistes (démarche éducative orientée vers une prise en charge nutritionnelle et physique). Afin d’éva- luer cette approche, une étude pilote a été menée pour déterminer l’effet maximal observé de l’intervention sur le moyen terme. Dans le présent article, les résultats portant sur les trois semaines de la cure sont rapportés. Entre juillet et novembre 2008, les médecins thermaux ont inclus des patients présentant un syndrome métabolique selon les critères du NCEP-ATP III. Au total, 145 patients ont été consi- dérés (femmes : 74,5 %, âge moyen : 58,9 ans), 53,1 % ont pratiqué une activité physique dans les six mois précédant la cure. Pendant la cure, la majorité des patients ont suivi les recomman- dations diététiques, 32,4 % ont participé à une activité physique encadrée et 89,7 % à une acti- vité physique libre, 66,2 % ont participé à un atelier éducatif. En fin de cure, 62,8 % des patients présentaient une diminution d’au moins 0,5 de l’IMC et 68,3 % des patients avaient une tension artérielle inférieure à 130/85 mmHg. Pour 6,2 % des patients, le tour de taille est devenu inférieur à 102 cm pour les hommes ou à 88 cm pour les femmes. Les résultats de cette étude pilote suggèrent que l’approche multifactorielle dans le cadre d’une cure thermale est bénéfique en fin de cure pour les patients présentant un syndrome métabo- lique et ouvre la voie à des études réalisées à plus grande échelle., In the context of spa therapy for “metabolic diseases” at Eugénie-les-Bains, a multifactorial treatment of metabolic syndrome, according to an educational approach aimed at nutrition and physical activities, is made available to patients. To evaluate this approach, a pilot study was conducted to determine the maximal observed effect of the intervention over the medium term. In the present paper only results concerning the three-week stay at the spa centre are reported. Between July and November 2008 spa centre physicians prospectively included patients with metabolic syndrome according to the NCEP-ATP III criteria. A total of 145 patients were consi- dered (female: 74.5 %, mean age: 58.9 years), and 53.1 % engaged in a physical activity during the six months preceding inclusion. During their stay at the spa centre, the majority of patients followed the dietary recommendations, 32.4 % participated in an organised physical activity, 89.7 % in a freely available physical activity, and 66.2 % participated in an educational course or discussion group. At the end of their stay, 62.8 % of patients had a reduction in BMI of at least 0.5 and the blood pressure of 68.3 % of patients passed below the threshold of 130/85 mmHg. For 6.2 % of patients, the umbilical waist circumference became less than 102 cm for men or 88 cm for women. The results of this pilot study suggest that the multifactorial approach in the context of hydro- therapy at a spa centre is beneficial at end of stay for patients with metabolic syndrome and opens the way for further investigation in wider studies.

To determine healthcare claim patterns associated using nonsteroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis (RA).The CADEUS study randomly identified NSAID users within the French health insurance database. One-year claims data were extracted, and NSAID indication was obtained from prescribers. Logistic regression was used in a development sample to identify claim patterns predictive of RA and models applied to a validation sample. Analyses were stratified on the dispensation of immunosuppressive agents or specific antirheumatism treatment, and the area under the receiver operating characteristic curve was used to estimate discriminant power.NSAID indication was provided for 26,259 of the 45,217 patients included in the CADEUS cohort; it was RA for 956 patients. Two models were constructed using the development sample (n = 13,143), stratifying on the dispensation of an immunosuppressive agent or specific antirheumatism treatment. Discriminant power was high for both models (AUC 0.80) and was not statistically different from that found when applied to the validation sample (n = 13,116).The models derived from this study may help to identify patients prescribed NSAIDs who are likely to have RA in claims databases without medical data such as treatment indication.

A retrospective, observational, cohort study in primary care. To determine the total direct medical and non-medical cost of chronic low back pain (LBP) in France and its associated factors. Chronic LBP affects 5-10% of the population its burden in France is unknown. Ninety-eight randomly selected general practitioners included 796 adult patients with chronic LBP between October 2001 and December 2002. Direct costs due to physician visits, investigations, medications, hospitalizations, and other medical and non-medical resource use were collected for the 6 months prior to study visit. Costs both reimbursed and not by the French health insurance system were considered. Quality of life (QoL) and disease severity were measured using Short Form (SF)-8 and Roland-Morris disability questionnaire (RMDQ), respectively. Costs were updated to represent 2007 prices. Men represented 50.6% of the 796 patients, mean age was 53 +/- 11.3 years, and the duration of LBP was more than 1 year in 80.9% of patients. The total mean cost per patient over six months was 715.6 euro (95% CI: 644.2-797.8). Of these costs, 22.9% related to care provided by physiotherapists and allied specialists, 19.5% to medications, 17.4% to hospitalizations, 9.6% to investigations, and 12.5% to physician fees. In multivariate analysis, the factors associated with the cost of chronic LBP were disease severity (RMDQ score) and age of the patients. LBP is a disease that is both common and costly.

To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.