Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial

Analysis of virological and clinical outcomes from a randomized trial that was terminated early suggest that combined treatment of seasonal influenza in adult outpatients with oseltamivir plus zanamivir is no more effective than either oseltamivir or zanamivir monotherapy

Routine HIV Screening in France: Clinical Impact and Cost-Effectiveness

BACKGROUND. In France, roughly 40,000 HIV-infected persons are unaware of their HIV infection. Although previous studies have evaluated the cost-effectiveness of routine HIV screening in the United States, differences in both the epidemiology of infection and HIV testing behaviors warrant a setting-specific analysis for France. METHODS/PRINCIPAL FINDINGS. We estimated the life expectancy (LE), cost and cost-effectiveness of alternative HIV screening strategies in the French general population and high-risk sub-populations using a computer model of HIV detection and treatment, coupled with French national clinical and economic data. We compared risk-factor-based HIV testing ("current practice") to universal routine, voluntary HIV screening in adults aged 18-69. Screening frequencies ranged from once to annually. Input data included mean age (42 years), undiagnosed HIV prevalence (0.10%), annual HIV incidence (0.01%), test acceptance (79%), linkage to care (75%) and cost/test (€43). We performed sensitivity analyses on HIV prevalence and incidence, cost estimates, and the transmission benefits of ART. "Current practice" produced LEs of 242.82 quality-adjusted life months (QALM) among HIV-infected persons and 268.77 QALM in the general population. Adding a one-time HIV screen increased LE by 0.01 QALM in the general population and increased costs by €50/person, for a cost-effectiveness ratio (CER) of €57,400 per quality-adjusted life year (QALY). More frequent screening in the general population increased survival, costs and CERs. Among injection drug users (prevalence 6.17%; incidence 0.17%/year) and in French Guyana (prevalence 0.41%; incidence 0.35%/year), annual screening compared to every five years produced CERs of €51,200 and €46,500/QALY. CONCLUSIONS/SIGNIFICANCE. One-time routine HIV screening in France improves survival compared to "current practice" and compares favorably to other screening interventions recommended in Western Europe. In higher-risk groups, more frequent screening is economically justifiable.Haute Autorite de Sante; the Institut de Veille Sanitaire; Sidaction; the Agence Nationale de Recherches sur le SIDA et les hepatites virales; the National Institute of Allergy and Infectious Diseases (R01 AI042006, K24 AI062476, P30 AI42851); the National Institute of Mental Health (R01 MH65869); the National Institute on Drug Abuse (R01 DA015612

Les services réseaux pour les systèmes X-by-Wire

Rapport interne.L'implantation dans les automobiles de systèmes de direction et de freinage à liaison numérique (X-by-Wire) sans redondance mécanique pose des problèmes nouveaux en terme de Sûreté de Fonctionnement. En effet, si l'aéronautique a aujourd'hui expérimenté beaucoup de systèmes distribués à liaison numérique critiques, les critères de coûts et d'espace sont tout à fait différents de ceux des constructeurs d'automobiles. C'est pourquoi les protocoles de communication sont devenus des points clés du respect des exigences de sûreté de fonctionnement. L'objectif de ce document est par conséquent de partir des exigences que doivent respecter les systèmes X-by-Wire pour en déduire les services dits " réseaux ", c'est à dire les services remplis par le protocole de communication. Par ailleurs, l'analyse des protocoles de communication étant le but final de l'étude, une méthode de comparaison construite sur un modèle en couche est proposé

Tolérance aux fautes dans les architectures X-by-Wire

Rapport interne.L'implantation dans les automobiles de systèmes de direction et de freinage à transmission numérique (X-by-Wire) sans redondance mécanique pose des problèmes nouveaux en terme de Sûreté de Fonctionnement. En effet, si l'aéronautique a aujourd'hui expérimenté beaucoup de systèmes distribués à transmission numérique critiques, les critères de coûts et d'espace sont tout à fait différents de ceux des constructeurs d'automobiles. La sécurité du conducteur étant directement mise en cause, les hypothèses faites lors de l'évaluation de la sûreté de fonctionnement des architectures utilisées doivent être exhaustives et réalistes. Dans ce papier, partant d'un exemple d'une architecture de freinage, nous démontrons l'importance de la couverture des hypothèses des fautes (de conception, Byzantines, physiques, ?) et le besoin de décliner les exigences (disponibilité, sécurité et performance temps réel) sur trois niveaux (système - fonction/service - composant) lors de l'évaluation. Quant aux méthodes d'analyse d'architectures embarquées spécifiques dans l'automobile, un état de l'art est donné montrant le besoin d'un effort d'intégration des outils existants. || Introduction of electronic steering and braking systems (X-by-Wire) without mechanical redundancy in motor vehicles arises new problems in terms of dependability. If a lot of similar critical numerical systems are experienced in aeronautic industry, crit

Impact of Fault Tolerance Mechanisms on X-by-Wire system dependability

Colloque avec actes et comité de lecture. nationale.National audienceMany fault-tolerant mechanisms have been proposed by software and hardware designers based on the communication protocol to ensure Steer-by-Wire system safety. The objective of this paper is to evaluate the impact of two fault-tolerance services mainly used for X-by-Wire systems, Fail-Silent Electronic Control Units and Membership Agreement, as to X-by-Wire system dependability. By creating a Failure Model adapted to X-by-Wire systems and fault tolerance properties, we give an analytical method which quantifies the impact of Fail Silent Property on the probability of an undesired event, and the impact of Membership Agreement on the probability of vehicle immobilizatio

Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn’s Disease

International audienceUstekinumab is approved for treatment of Crohn's disease (CD).1,2 Few data are available to assess the usefulness of monitoring inflammatory biomarkers and therapeutic drug monitoring to predict response to ustekinumab. We conducted a prospective study to assess the relationships between these parameters and the clinical outcome at week 16 in active CD patients receiving ustekinumab

IBD-INFO Questionnaire: A Multicenter French Up-to-Date Survey of Patient Knowledge in Inflammatory Bowel Disease

International audienceBackground: It has been demonstrated in many chronic conditions, including inflammatory bowel disease (IBD), that better patient knowledge about pathology and treatment improves the course and management of disease. The aim of this study was to develop an updated self-questionnaire to assess patients' level of knowledge of IBD. Methods: The IBD-INFO included 3 parts: an original part (Q1) and 2 parts from the translation of the preexisting questionnaires Crohn's and Colitis Knowledge score (CCKNOW) (Q2) and Crohn's and Colitis Pregnancy Knowledge score (CCPKNOW) (Q3). The reliability and discriminatory ability of the questionnaire were validated in 3 groups of non-IBD volunteers with various theoretical knowledge levels. The final questionnaire (64 validated questions) was then tested on 364 in- and out- IBD patients from 4 French university hospitals. The score for each part of the questionnaire was calculated, and factors associated with low scores were identified by univariate and multivariate logistic regression analyses. Results: The scores obtained by the 3 non-IBD volunteer groups differed significantly (P \textless 0.0001), and the IBD-INFO questionnaire showed excellent internal reliability and consistency (α = 0.98). The median total score obtained by the IBD patients was 27/64 (range, 0-59), and scores for Q1, Q2, and Q3 were, respectively, 10/23 (range, 0-21), 11/24 (range, 0-23), and 4/17 (range, 0-16). In multivariate analysis, lack of a university degree, not being a member of a patient association, not receiving anti-tumor necrosis factor alpha (anti-TNFα) treatment, duration of IBD <=3 years, male sex, and age \textgreater38 years were independent risk factors of a poor IBD-INFO knowledge score. The areas of knowledge least mastered were vaccination, IBD-related cancers, treatments, and pregnancy. Conclusions: Using the IBD-INFO, an updated self-administered questionnaire built to assess IBD patients' knowledge, several risk factors have been highlighted that allow better targeting of patients and areas requiring an improvement in the level of information

Factors associated with non-persistence to oral and inhaled antiviral therapies for seasonal influenza: a secondary analysis of a double-blind, multicentre, randomised clinical trial

International audienceOBJECTIVES:We aimed to evaluate and compare non-adherence to oral and inhaled antiviral therapies prescribed of a randomised clinical trial in outpatients with influenza A infection.DESIGN:A parallel, three-arm, double-blinded trial randomly allocated antiviral therapies twice daily for 5 days: (1) oral oseltamivir plus inhaled zanamivir (arm OZ); (2) oseltamivir plus inhaled placebo (arm Opz); or (3) oral placebo plus inhaled zanamivir (arm poZ). Analysis of non-adherence was a secondary objective of the trial.SETTINGS:Outpatients were enrolled by 145 general practitioners throughout France during the 2008-2009 seasonal influenza epidemics.PARTICIPANTS:A total of 541 adults presenting with influenza-like illness for less than 36 hours.PRIMARY OUTCOMES:Non-persistence, the time between inclusion and the last dose treated as a failure time, was used as the primary endpoint.RESULTS:The proportions of patients who persisted on treatment until the end of prescription were estimated at 85.73% (±3.28%) for the oral route and 82.73% (±3.44%) for the inhaled route. Based on multivariable models, non-persistence was associated with a PCR confirmation of influenza for both the oral (HR=0.54, p=0.010) and inhaled (HR=0.59, p=0.018) drugs and antibiotic coprescriptions (HR=2.07, p=0.007; and HR=1.88, p=0.017, respectively) and active combination treatment (HR=1.71, p=0.035; and HR=1.58, p=0.035, respectively). The hazard of non-persistence of the inhaled therapy was increased compared with that of the oral therapy (HR=1.23, p=0.043).CONCLUSION:In addition to the clinical and virological profiles of influenza infection, non-persistence may have been influenced by an active combination and the route of administration

Effectiveness of hepatitis B rapid tests toward linkage-to-care: results of a randomized, multicenter study

International audienceObjectives: Worldwide, many infected individuals are unaware of their hepatitis B virus (HBV) status. We evaluated the effectiveness of HBV rapid testing in promoting linkage-to-care.Methods: In 2012, volunteers were recruited from five Parisian centers. Participants were randomized 1 : 1 to receive standard serology (S) or rapid testing (VIKIA-HBsAg/Quick Profile anti-HBsAb) with confirmatory serology (R+S). The primary endpoint was percentage of individuals with appropriate linkage-to-care (nonimmunized individuals starting vaccination or HBsAg-positive individuals receiving medical evaluation). The secondary outcomes were percentage receiving HBV-test results and performance of HBV rapid tests.Results: In total, 995 individuals were screened. Among the HBV-infection groups included in the primary endpoint (n=409), 20 (4.9%) received appropriate linkage-to-care, with no difference between S and R+S groups (5.7 vs. 4.1%, P=0.5). Two of eight HBsAg-positive participants had a medical visit (1/6 and 1/2 in the S and R+S groups, respectively) and 18/401 (4.5%) nonimmunized participants initiated HBV-vaccination (11/205 and 7/196). Factors that tended to be associated with linkage-to-care were female sex, birth country of high HBV prevalence, and extended medical stay. Test results were not obtained in 4.7% of participants, which was significantly higher in the S arm (P=0.02). Both sensitivity and specificity were 100% for the VIKIA-HBsAg rapid test and 94.4 and 80.8%, respectively, for the anti-HBsAb Quick Profile rapid test.Conclusion: Despite a higher proportion of participants obtaining their results in the R+S arm and better performance of anti-HBsAb rapid tests than described previously, we found no evidence that HBV screening based initially on rapid tests leads to increased HBV-vaccination rates or medical evaluation. This strategy should be evaluated in more hard-to-reach population