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The Hemraude study was conducted to describe the profile of patients with HA, disease management, and economic burden in a collective perspective. This retrospective study was conducted using the French administrative healthcare claims database SNIIRAM/SNDS. Male patients treated for hemophilia A with a long-term illness (ALD) status or invalidity were included in the study between January 1, 2016 and December 31, 2017. Patients were classified in six treatment groups: no treatment, on-demand FVIII, prophylactic FVIII, FVIII in immune tolerance induction (ITI) protocol, on-demand bypassing agents, and prophylactic bypassing agents. Patients treated with FVIII in ITI protocol and those treated with bypassing agents are deemed to have developed inhibitors. HA patients were compared to a control population without coagulation disorder and matched (ratio 1:3) on age and sex. A total of 4172 patients were included in the analysis, aged on average 35.2 years, 5.3% had HIV infection, and 8.8% had hepatitis B or C. In 2017, half of the patients received no treatment for HA, 46.7% were treated with FVIII (25% on demand, 20.6% with prophylaxis, and 1.1% ITI), 1.5% with bypassing agents. Patients treated with prophylactic treatments, either inhibitor or non-inhibitor, were less likely to be hospitalized for severe bleeding compared to patients receiving on-demand treatments. The average annual costs for HA management per patient were 72,209.60 €. The highest costs were observed in patients treated with FVIII in ITI protocol and those receiving prophylactic bypassing agents. Direct costs of HA treatments for HA may be very high especially in the small percentage of patients developing inhibitors or treated with ITI protocol.

The Hemraude study was conducted to describe the profile of patients with HA, disease management, and economic burden in a collective perspective.This retrospective study was conducted using the French administrative healthcare claims database SNIIRAM/SNDS. Male patients treated for hemophilia A with a long-term illness (ALD) status or invalidity were included in the study between January 1, 2016 and December 31, 2017. Patients were classified in six treatment groups: no treatment, on-demand FVIII, prophylactic FVIII, FVIII in immune tolerance induction (ITI) protocol, on-demand bypassing agents, and prophylactic bypassing agents. Patients treated with FVIII in ITI protocol and those treated with bypassing agents are deemed to have developed inhibitors. HA patients were compared to a control population without coagulation disorder and matched (ratio 1:3) on age and sex.A total of 4172 patients were included in the analysis, aged on average 35.2 years, 5.3% had HIV infection, and 8.8% had hepatitis B or C. In 2017, half of the patients received no treatment for HA, 46.7% were treated with FVIII (25% on demand, 20.6% with prophylaxis, and 1.1% ITI), 1.5% with bypassing agents. Patients treated with prophylactic treatments, either inhibitor or non-inhibitor, were less likely to be hospitalized for severe bleeding compared to patients receiving on-demand treatments. The average annual costs for HA management per patient were 72,209.60 €. The highest costs were observed in patients treated with FVIII in ITI protocol and those receiving prophylactic bypassing agents.Direct costs of HA treatments for HA may be very high especially in the small percentage of patients developing inhibitors or treated with ITI protocol.

Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39–33.47) months in 2007 to 0.77 (IQR, 0.37–1.60) months in 2017. A decrease in PHI (−35.1%) and PRHI (−25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8–2014.4) and 2013.1 (95% CI, 2011.3–2014.8), respectively. Conclusions Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. Clinical Trials Registration NCT02898987.

Objective To assess the effectiveness and costs associated with contraceptive methods based on real-world data in France. Study design A cross-sectional cohort study based on data from a representative sample of the French National Healthcare Insurance Database (Echantillon Generalistes des Beneficiaires (EGB)) was performed between January 1st 2006 and December 31st 2012. Women aged 15 years or older and users of at least one reimbursed contraceptive method between January 1st 2012 and December 31st 2012 were selected. The outcome of interest was unintended pregnancy, defined as pregnancies occurring after at least one month since the dispensation of a contraceptive method. The mean annual costs of contraceptive methods (in 2012 Euros) were collected in the database from a health system perspective. Costs were expressed for the first year of use, considering the next years of use and taking into account or not the cost of unplanned pregnancies. Results A population of 48,090 women representative of the 4,664,730 French women with a reimbursed contraceptive method was identified in the EGB in 2012: 68.6% used at least one reimbursed oral contraception (OC), 30.2% used at least one intrauterine devices (IUD) (LGN-IUS 52 mg, 17.6%; copper, 13.1%) and 5.1% used at least one etonogestrel implant. Unplanned pregnancies rates ranged from 0.6% with LNG-IUS 52 mg and 0.8% with the etonogestrel implant to 4.8% with 1st and 2nd generation combined OCs. The mean annual costs of contraception for the first year of use ranged from €145 for 1st-2nd generation combined oral contraceptions (COCs) to €308 for LNG-IUS 52 mg taking into account the next years of use, the etonogestrel implant was associated with the lowest mean annual cost (€88). When costs of unplanned pregnancies were taken into account, the mean annual cost of contraception for the first year of use was lower for progestin-only OC (€251) and copper IUD (€257) compared to etonogestrel implant (€300) and LNG-IUS 52 mg(€323). Conclusion This real-world study suggests that Long-acting reversible contraceptives (LARCs) (i.e. implant and IUDs) should be considered for a broader use to prevent unplanned pregnancies and related abortions in France both from a public health and economic perspective.

Christos Chouaid,1 Delphine Loirat,2 Emilie Clay,3 Aurélie Millier,3 Chloé Godard,4 Amira Fannan,4 Laurie Lévy-Bachelot,4 Eric Angevin5 1Chest Department, Centre Hospitalier Intercommunal Créteil, Créteil, France; 2Institut Curie, Paris, France; 3Creativ-Ceutical, Paris, France; 4MSD France, Courbevoie, France; 5Institut Gustave Roussy, Villejuif, France Background: Adverse events (AEs) related to medical treatments in non-small cell lung cancer (NSCLC) are frequent and need an appropriate costing in health economic models. Nevertheless, data on costs associated with AEs in NSCLC are scarce, particularly since the development of immunotherapy with specific immune-related AEs.Objective: To estimate the costs of grades 3 and 4 AEs related to NSCLC treatments including immunotherapy in France.Methods: Grades 3 and 4 AEs related to treatment and reported in at least 1% of patients in Phase III clinical trials for erlotinib, ramucirumab plus docetaxel, docetaxel, pemetrexed plus carboplatin plus bevacizumab, platinum-based chemotherapies, nivolumab and pembrolizumab were identified. When no cost evaluation was reported in literature, estimates on standard treatments and medical resource use for each AE were obtained thanks to an expert panel. Total cost per AE was calculated from a French national health insurance perspective and updated in 2017 Euros. Hospital stay costs were estimated based on public and private weighted tariffs and data from the French Medical Information System (Programme de Médicalisation des Systèmes d’Information). Costs of tests, consultations and treatments were calculated based on national reimbursement tariffs.Results: Overall, costs of grades 3 and 4 AEs related to treatment ranged from €46 per event to €7,742 per year. Fourteen out of 24 AEs identified had a mean estimated cost over €2,000. The highest mean costs were related to type 1 diabetes (€7,742 per year) followed by pneumonitis (€5,786 per event), anemia (€5,752 per event), dehydration (€5,207 per event) and anorexia (€4,349 per event). Costs were mostly driven by hospitalization costs.Conclusion: Among the AEs identified, a majority appeared to have an important economic impact, with a management cost of at least €2,000 per event mainly driven by hospitalization costs. This study may be of interest for economic evaluations of new interventions in NSCLC. Keywords: non-small cell lung cancer, adverse events, cost analysis, chemotherapy, immunotherapy

The aim of this study was to evaluate the continuation rates of reimbursed contraceptive methods in French real-world conditions.A retrospective cohort study using a representative sample of the national health insurance database, the General Sample of Beneficiaries (Echantillon Généralistes des Bénéficiaires [EGB]), was performed between 2006 and 2012. Selected women were ≥15 years of age and had started a reimbursed contraceptive method between 2009 and 2012 without prior reimbursement for an implant or an intrauterine contraceptive method between 2006 and 2008. The outcome of interest was the continuation rates, defined as the probability of women initiating a contraceptive method and continuing to use the same method over time. Continuation rates were assessed for up to 2 years. Only the first contraceptive method used during the study period was considered in the analysis. Non-parametric Kaplan-Meier survival analysis was used to assess continuation rates.A population of 42,365 women representative of the 4,109,405 French women initiating any reimbursed method between 2009 and 2012 was identified in the EGB: 74.5% of women used oral contraceptives, 12.8% the levonorgestrel-releasing intrauterine system (LNG-IUS), 9.2% the copper intrauterine device (Cu-IUD) and 3.5% the subdermal etonogestrel (ENG) implant. The 2 year continuation rates varied from 9.1% for progestin-only oral contraceptives, 27.6% for first to second generation combined oral contraceptives (COCs) and 33.4% for third generation COCs to 83.6% for the ENG implant, 88.1% for the Cu-IUD and 91.1% for the LNG-IUS.This study conducted in real-world conditions showed that long-acting reversible contraceptive (LARC) methods remain rarely used in France despite high continuation rates over 2 years. Increasing the use of LARC methods is therefore a public health priority.

Introduction Le projet national “Parcours Sante des aines” (PAERPA) a ete mis en place pour optimiser le parcours de sante des personnes âgees de plus de 75 ans. Il s’agit d’une experimentation de type recherche-action dediee aux personnes fragiles portee par les agences regionales de sante (ARS). Dans les Hauts-de-France, l’intervention incluait un acte de revision de la medication. Cet acte etait realise par une equipe mobile de geriatrie (EMG) et un plan personnalise de sante permettait d’assurer la continuite ville-hopital. Afin de suivre le parcours de soins du patient, une extraction des donnees medico-administratives a ete effectuee dans la base du Systeme national des donnees de sante (SNDS). L’objectif est de comparer la proportion de similitude entre les ordonnances a l’entree d’hospitalisation et les donnees de facturation ainsi que la proportion de prescriptions potentiellement inappropriees (PPI). Materiel et methodes Etude de cohorte observationnelle retrospective incluant les patients hospitalises aux urgences et vus par l’EMG entre 2015 et 2017. Ils presentent au moins trois pathologies chroniques dont une en rapport avec le motif d’hospitalisation, ou sont sous anticoagulants oraux ou diuretiques. Les ordonnances sont retranscrites des dossiers de l’EMG puis sont encodees par code ATC grâce au logiciel R®. Ces ordonnances sont comparees aux donnees de facturation extraites du SNDS. Les PPI sont determinees grâce aux criteres de Laroche. Pour un meme patient, les codes ATC (niveau 5) et les PPI sont compares entre les deux sources de donnees. Resultats Au total, 220 patients ont eu l’intervention par l’EMG, et 188 patients avaient un traitement facture dans le SNDS. Toutes les mesures ont ete effectuees sur les 188 patients. La comparaison des codes ATC (niveau 5) entre les donnees du centre hospitalier de Denain et celles du SNDS a fourni un rappel egal a 61 %, une precision a 81 % et une F-mesure egale a 0,70. La comparaison des PPI entre la conciliation medicamenteuse d’entree selon les donnees de l’EMG et le traitement facture selon les donnees du SNDS permet d’obtenir un Kappa de Cohen egal a 0,62 [0,5 ; 0,74]. Conclusion La concordance entre les deux sources de donnees est correcte puisque le kappa est compris entre 0,6 et 0,8. Les donnees du SNDS ne prennent pas en compte des potentiels stocks a domicile des patients. Les donnees des conciliations medicamenteuses de l’EMG ne comptabilisent pas les medicaments OTC (« Over-The-Counter ») presents dans les donnees de facturation. Les donnees des conciliations medicamenteuses de l’EMG ne comptabilisent pas les medicaments delivres pour diverses pathologies aigues anterieures a l’hospitalisation.

To overcome the inherent issue of catalyst recycling in homogeneous catalysis, much effort has been devoted to the heterogenization of catalysts onto solid supports and to the separation of the reactants (and/or products) and the catalyst using immiscible liquid phases (liquid multiphase catalysis). For these latter systems, solvents such as water, alcohols, ionic liquids, fluorous media, supercritical fluids, and gas-expanded liquids have been employed successfully as the catalyst phase. In this chapter, the most relevant biphasic catalytic systems involving NHC complexes are discussed. Particular attention is devoted to alkene metathesis, which is considered to be one of the most important processes that uses complexes with carbene ligands. Sulfonated or related water-soluble carbene ligands are also described for biphasic reactions, such as cyclization, C–C bond formation, and hydroformylation.

This paper presents the results of the application of a cold spray technique for structuring metallic surfaces with microparticles. The resulting changes in surface properties were characterized to observe their influences on the tribological behavior of the structured surface. The spray technique was applied to a technical component, a 16MnCr5 steel chain pin, designed to be mounted in a linear reciprocating tribometer. TiO 2 microparticles were used to structure the surface with a homogeneous distribution of singly dispersed particles, rather than a homogeneous closed coating on the surface. Tribometer tests were performed to directly compare structured and unstructured chain pins, and a significantly reduced sliding friction coefficient was observed for the structured pin. The pins were characterized in detail by surface analysis prior to and after application of the tribological load to set the surface parameters and surface chemistry, even on the microscale. It was confirmed that the particle structuring induced changes in the surface properties, and the durability of the changes after tribological loading was evaluated.

Background Since 2011, the management of advanced melanoma has radically changed with the availability of new therapies (immunotherapy and BRAF targeted therapy), and with BRAF testing. Objectives Following the introduction of these new therapies, the objectives of this AMEL study were to describe treatment patterns and evaluate overall survival (OS) among unresectable stage III/IV melanoma patients, in a real-life setting in France. Methods The AMEL study is a multicentre retrospective record review study. 33 physicians working in 33 unique treatment centres participated in the study. 264 patients diagnosed between January 1st 2012 and October 31st 2012 with unresectable stage III/IV melanoma were included in the study. Results 94.7% of the patients received a 1st line anti-tumour drug treatment, 62.5% a 2nd line treatment while 26.9% received a 3rd line treatment with no significant differences between patients with a BRAF mutation (50.4%) and BRAF wild-type (47.0%). 1st line treatment differs according to the BRAF status: 74.8% of patients with a BRAF mutation received a BRAF inhibitor while 79.3% of the BRAF wild-type patients were treated with conventional chemotherapy. In 2nd line and over, the treatment patterns were more heterogeneous, depending on the BRAF mutation, the treatment received previously, the speed of progression of the disease and the availability of immunotherapy at the time the treatment was initiated. Conclusion Regardless of the BRAF mutation status, the median OS of patients was 16 months (95% CI= 14-18). Compared to a similar study conducted in 2007 (MELODY) a gain of 4 months is observed. The gain seems to be higher for patients with a BRAF mutation (18 months) than for those without a BRAF mutation (14 months). The OS of patients who sequentially received both a BRAF inhibitor and ipilimumab (28 months) highlights the benefit of this treatment sequence. This article is protected by copyright. All rights reserved.

International audience; While the management of apple orchards is intensifying through high tree density, heavy input use and short lifespan, growers in some traditional production areas keep on planting semi-extensive orchards. We assessed the environmental impacts of those two contrasted production systems using the last methodological recommendations for Life Cycle Assessments (LCA) in perennial crops. The use of such framework permitted to assess the weight of the unproductive stages in the orchard lifespan impacts, and the contribution of fertiliser direct field emissions to the total impacts. Mainly due to fertilisation, the intensive orchard displayed the higher environmental impacts over the orchard lifespan for all calculated impact categories except energy demand. Fertilisation, including fertiliser production and application, represented half or more of the calculated impact categories in the intensive orchard, attesting to the importance of taking these field emissions into account and to include the N-tree requirements in the calculation. Methodological considerations are discussed and the necessity to explicit the approach used to account for the duration of perennial cropping systems is also outlined. Unproductive stages weighted from 9 to 21% of the studied impact categories in the semiextensive orchard and from 13 to 28% in the intensive orchard, with little contribution of the nursery stage (from 0.2 to 2.6%). This study outlines that orchard strategies (management and design) perform differently according to the context that constrains tree water need and pest and disease control.

SUMMARYIn Belgium, non-typhoidal salmonellosis and campylobacteriosis are the two most frequently reported foodborne illnesses. During 2005, a 71% decrease of Salmonella Enteritidis infections compared with the average annual number cases in the period 2000–2004 was recorded by the Belgian National Reference Centre for Salmonella and Shigella. After the peak of 1999, the total number of salmonellosis cases decreased gradually, with the exception of 2003 when an increase was again recorded due to the rise of isolates belonging to the serotype Enteritidis. PT4, the predominant phage type of serotype Enteriditis over recent years (except in 2003), became the second most prevalent phage type in 2005 after PT21. We present in this paper the epidemiology (incidence and trends) of human salmonellosis in Belgium and assess the role of the vaccination programme in layer flocks on the decline of the incidence of human salmonellosis and foodborne outbreaks due to S. Enteritidis.

ResumenObjetivosEl estudio trataba de determinar si una intervención organizada de promoción de la salud durante las consultas médicas mejora la evolución para los pacientes que cumplen los criterios de la CIE-10 para trastornos de ansiedad o depresivos.MétodosEn 2001, los médicos utilizaron la MINI para la detección selectiva de 9.743 empleados de baja por enfermedad y médicos especialistas en 21 centros médicos de una gran compañía. Se llevó a efecto una intervención de promoción de salud en ocho centros “activos”. Esta intervención tenía lugar inmediatamente después del diagnóstico y consistía en explicar los trastornos, proporcionar los resultados de la prueba y folletos basados en las recomendaciones de la OMS, y aconsejar a los pacientes que consultaran a su médico personal, psiquiatra o médico laboral, si era necesario. La eficacia de la intervención, evaluada por la gravedad de los síntomas y la evolución al año, se valoró comparando los ocho centros activos con 13 centros de control (sin intervención).ResultadosSe detectaron trastornos entre 10,6% de los sujetos, 29,4% de los cuales no tenían diagnóstico anterior de trastorno de ansiedad o depresivo. La intervención se asoció con un efecto positivo en las puntuaciones de la HAD a las 6 semanas y a los 6 meses. La ausencia total de trastornos al año se asociaba con la edad, el sexo y la intervención, entre todos los casos identificados (RV = 1,53), entre aquellos con un trastorno de ansiedad al menos (RV = 1,45) y entre aquellos con trastorno depresivo al menos (RV = 1,40).ConclusiónCombinar la detección con la provisión organizada de información, incluyendo material impreso, mejora la evolución de los pacientes y las capacidades diagnósticas de los médicos.

Background Studies devoted to the detection and treatment of anxiety and depression in adult populations show that at least 10% meet ICD10 criteria for an anxiety or a depressive disorder, but only half are diagnosed as such and only one third of those receive appropriate treatment. The goal of the APRAND program was to explore the possibility of improving management strategies via health education during doctors' visits. Methods In 2001, EDF-GDF conducted an experimental program in which 21 physicians from its in-house health insurance program used the MINI mental state examination to screen for ICD10 criteria for anxiety and depressive disorders in 9743 employees on sick leave. A “here-elsewhere” epidemiologic study evaluated the program, recording the initial diagnoses and studying a year later the outcome of the persons identified with these disorders in 8 active centers (with prevention activities) and in 13 control centers (without prevention activities). The activities consisted of explanations of the disorders identified, delivery of the test results, delivery of leaflets based on the WHO guidelines, and strong recommendations to see a general practitioner, or a psychiatrist, or the occupational physician, if necessary. Logistic regressions compared the two groups, taking into account sex, age, geographic region, comorbidity, and medical care at screening. Results Preventive activities were significantly associated with the disappearance at 1 year of depressive episodes (OR = 1.93; CI 95%; 1.3–2.84) and of phobic or panic disorders (OR = 1.98; CI 95%; 1.14–3.44). The only other variables affecting prognosis were age and sex. The probability of recovery or remission increased by 10 to 20% at active centers, according to age, sex and disorder. Moreover, the physicians reported that they learned a great deal from the program, which thus also improved their practices. Conclusion Diagnosis and prognosis of depressive episodes and phobic and panic disorders in adult populations can be improved by a preventive diagnostic and educational approach of the type used by APRAND during doctor's visits.

ObjectiveThe study sought to determine whether an organized health promotion intervention during medical consultations improves the outcome for patients who meet the ICD10 criteria for anxiety or depressive disorders.MethodsIn 2001, physicians used the MINI to screen 9743 employees on sick leave and consulting physicians in 21 medical centres of a large company. A health promotion intervention was implemented in eight “active” centres. It took place immediately after diagnosis and consisted of explaining the disorders, delivering the test results and leaflets based on WHO recommendations, and advising patients to consult their personal physician, psychiatrist or occupational physician, if necessary. Its effectiveness, evaluated by symptom severity and outcome over 1 year, was assessed by comparing the eight active centres to 13 control centres (without the intervention).ResultsDisorders were detected among 10.6% of the subjects, 29.4% of whom had no previous diagnosis of anxiety or depressive disorder. The intervention was associated with a positive effect on the 6-week and 6-month HAD scores. Total absence of disorders at 1 year was associated with age, sex, and intervention, among all identified cases (OR = 1.53), among those with at least one anxiety disorder (OR = 1.45), and among those with at least one depressive disorder (OR = 1.40).ConclusionCombining detection with organized provision of information including printed material improves patients' outcome and physicians' diagnostic abilities.

Antibiotic treatment is not required in cases of Salmonella enterica gastroenteritis but is essential in cases of enteric fever or invasive salmonellosis or in immunocompromised patients. Although fluoroquinolones and extended-spectrum cephalosporins are the drugs of choice to treat invasive Salmonella , resistance to these antibiotics is increasing worldwide. During the period 2000 to 2003, 90 Salmonella enterica serovar Virchow poultry and poultry product isolates and 11 serovar Virchow human isolates were found to produce an extended-spectrum β-lactamase, CTX-M-2, concomitantly with a TEM-1 β-lactamase. The bla CTX-M-2 gene was located on a large conjugative plasmid (>100 kb). Pulsed-field gel electrophoresis indicated a clonal relationship between the poultry and human isolates. All these isolates displayed additional resistance to trimethoprim-sulfamethoxazole and tetracycline as well as a reduced susceptibility to ciprofloxacin (MICs of between 0.5 and 1 μg/ml). CTX-M-2-producing Salmonella with a reduced susceptibility to fluoroquinolones constitutes a major concern, since such strains could disseminate on a large scale and jeopardize classical antibiotic therapy in immunocompromised patients.

Gradual changes have been observed in the phage-types of methicillin-resistant Staphylococcus aureus (MRSA) isolates from Belgian hospitals. A total of 6551 isolates, collected in 93 Belgian hospitals over 10 years (1992-2001), was examined. A decreasing incidence of the main early Belgian epidemic phage-types ([A], [B], [H]*, Jo*) was observed. Since 1997 and 2000, a new series of phage-types ([Hv]*, [J]*, [O]*), which were likely related to the previous group [H]*, have been noted. The general trends were confirmed in two particular hospitals. Local epidemic and/or endemic phage-types were also encountered.

Suite a des enquetes epidemiologiques sur les accidents domestiques, de loisirs et sportifs des employes beneficiaires du Regime Particulier de Securite Sociale des Industries Electriques et Gazieres en 1996 et 1997, cet article degage des accidents evitables et frequents, susceptibles d’etre cibles par des actions d’education pour la sante. Il s’appuie aussi sur les demandes d’information exprimees par la population pour conseiller des themes d’actions d’information. Il propose une suite a l’« enquete-action » impulsee en 1996, en tenant compte du contexte et des contraintes professionnelles : messages de prevention, actions internes de promotion de la sante experimentales et evaluees, relais de campagnes externes visant les accidents qui pourraient etre evites chez les adultes. Les accidents evitables identifies dans cette etude ne sont pas specifiques de la population active etudiee. Ils pourraient etre cibles par des programmes plus generaux de promotion de la sante.

Asymmetric hydroformylation is a very promising catalytic reaction that produces chiral aldehydes from inexpensive feedstocks (alkenes and syngas) in a single step under essentially neutral reaction conditions. Asymmetric hydroformylation offers a great potential for the fine chemical industry since enantiomerically pure or enriched aldehydes can be obtained through hydroformylation of a variety of substrates using the appropriate chiral-phosphorus-modified rhodium catalyst. This chapter presents the successful transformations of benchmark and specific substrates, organized according to the substitution pattern.

The purpose of this paper is to examine personal and health factors, both at the beginning of the study and thereafter, associated with participation in the GAZEL cohort, set up in 1989 in a large French company. The authors used logistic regression to analyze the associations between participation and data available for both participants (n = 20,093) and nonparticipants (n = 24,829). Higher participation was associated with male sex, marriage, children, managerial status, and residence in particular regions. Among men, lower participation was associated with sick leave in the year before recruitment and afterwards. During follow-up, participation was negatively associated with several groups of diseases, especially those associated with alcohol consumption. The risk of upper respiratory and digestive tract and lung cancer during follow-up was higher among nonparticipants. The same phenomenon occurred among women, but less markedly, for cancers of the breast and genital organs. During follow-up, mortality among men was higher among nonparticipants, especially for alcohol-related diseases. The association among women was less strong. Among men, but not among women, diseases caused by alcohol, smoking, or dangerous behavior were the primary reason for the health differences observed between participants and nonparticipants. Overall, the most important determinants of participation were cultural factors and lifestyle behaviors.

Human nontyphoidal Salmonella infections are the primary cause of foodborne disease in developed countries, resulting in considerable morbidity and occasionally death, especially in immunocompromised patients. Strains of Salmonella that are resistant to antimicrobial agents have become a world-wide health problem. Fluoroquinolones are drugs of choice for treatment of human invasive salmonellosis, and have been useful for the treatment of infections caused by multi-resistant strains. However, strains resistant to ciprofloxacin have been noted. A random sample of 378 Salmonella strains of human origin was collected during 1998. Their susceptibility to 11 antimicrobial agents was determined by the agar dilution method according to NCCLS standards. In total, 38 serotypes were represented of which S. Enteritidis (20.4%), S. Typhimurium (20.4%), S. Hadar (9.0%), S. Brandenburg (7.9%), S. Infantis (7.7%), and S. Virchow (5.3%) were the most common. All strains were susceptible to ceftriaxone and ciprofloxacin. For nalidixic acid the rate of resistance was 19.0%. Of the 72 strains resistant to nalidixic acid, 31 were S. Hadar, and thus 91.2% (31/34) of the S. Hadar isolates showed resistance to nalidixic acid. Most of the S. Hadar strains were also resistant to ampicillin, tetracycline and sulphamethoxazole, and an elevated MIC50 (0.25 microgram/ml) and MIC90 (1 microgram/ml) was observed for ciprofloxacin. The high rate of resistance to nalidixic acid can be a first step towards the development of resistance to ciprofloxacin.

FVB/N inbred mice have been widely used to generate a variety of transgenic lines, but their physiology and especially their immunological characteristics are poorly documented. We therefore studied the ultrastructure of the thymus and the distribution of thymocyte subpopulations in FVB/N mice at several ages. In young FVB/N mice the stromal microenvironment exhibits the three types of epithelial cells and the two types of bone-marrow derived cells (macrophages and interdigitated cells) previously described in other strains of mice. Moreover, in the thymic medulla of young FVB/N mice, a fourth cell type with the morphological characteristics of an immature epithelial cell was present in relatively high number. Furthermore, thymocyte subpopulations distribution shows an earlier thymocyte maturation than in other strains. Finally, changes associated with thymic involution were observed about 5 months earlier than in many other mouse strains. Our results demonstrated that the FVB/N strain has a specific immunological status.

Staphylococcus aureus was isolated from internal organs of 13 different psittacine birds submitted for necropsy over a period of 6 years. The birds all had lesions consistent with septicaemia. S. aureus isolates included three different phage types. In seven of the 13 birds, concurrent infections with Chlamydophila species, Enterococcus hirae, Candida species, unidentified streptococci and coagulasenegative staphylococci were detected. One bird also had lesions of lymphoid leucosis. Few indications were found that staphylococcosis associated problems may spread epidemically. The present studies suggest that S. aureus is pathogenic for psittacine birds, although it does not seem to be a frequent cause of disease.

To identify the pathways involved in HIV-1 modification of cellular gene expression, chronically infected U937 cells were screened by mRNA differential display. A chimeric transcript consisting of the 3' end of the LTR of a HIV-1 provirus, followed by 3.7 kb of cellular RNA was identified suggesting that long readthrough transcription might be one of the mechanisms by which gene expression could be modified in individual infected cells. Such a phenomenon may also be the first step towards the potential transduction of cellular sequences. Furthermore, the mRNA encoding for the transcription factor Egr-1 was detected as an over-represented transcript in infected cells. Northern blot analysis confirmed the increase of Egr-1 mRNA content in both HIV-1 infected promonocytic U937 cells and T cell lines such as Jurkat and CEM. Interestingly a similar increase of Egr-1 mRNA has previously been reported to occur in HTLV-1 and HTLV-2 infected T cell lines. Despite the consistent increase in the level of Egr-1 mRNA, the amount of the encoded protein did not appear to be modified in HIV-1 infected cells, suggesting an increased turn over of the protein in chronically infected cells.

In total, 150 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected during 2002 from a general Belgian hospital were phage-typed at routine test dilution × 100. The majority (45%) belonged to phage group (J)*, while 10% were classified as a new phage type 29/(42E) / 54/(D11)*. The isolates belonging to this new type carried the aac(6')-aph(2”) and the aph(3') aminoglycoside resistance genes and showed high-level resistance to oxacillin. Molecular typing revealed that they belonged to the multiresistant clonal pulsed-field gel electrophoresis (PFGE) type D8. PFGE group D, characterised as genotype ST228-MRSA-I, has been present in Belgian hospitals since 1999.

Testosterone (a strongly hydrophobic steroid) and testosterone hemisuccinate (a negatively charged derivative) were used as probes to investigate alterations in the outer membrane of Pseudomonas aeruginosa. Diffusion rates of the steroids across the lipid bilayer were measured by coupling the influx of these compounds to their subsequent oxidation by an intracellular delta1-dehydrogenase enzyme. Wild-type cells of P. aeruginosa (strain PAO1) were found to be 25 times more permeable to testosterone than to testosterone hemisuccinate. The uptake of the latter compound appeared to be partially dependent on the external pH, thus suggesting a preferential diffusion of the uncharged protonated form across the cell envelope. Using various PAO mutants, we showed that the permeation of steroids was not affected by overexpression of active efflux systems but was increased up to 5.5-fold when the outer membrane contained defective lipopolysaccharides or lacked the major porin OprF. Such alterations in the hydrophobic uptake pathway were not, however, associated with an enhanced permeability of the mutants to the small hydrophilic molecule N,N,N',N'-tetramethyl-p-phenylene diamine. Thirty-six agents were also assayed for their ability to damage the cell surface of strain PAO1, using testosterone as a probe. Polymyxins, rBPI23, chlorhexidine, and dibromopropamidine demonstrated the strongest permeabilizing activities on a molar basis in the presence of 1 mM MgCl2. These amphiphilic polycations increased the transmembrane diffusion of testosterone up to 50-fold and sensitized the PAO1 cells to hydrophobic antibiotics. All together, these data indicated that the steroid uptake assay provides a direct and accurate measurement of the hydrophobic uptake pathway in P. aeruginosa.