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Purpose Studies performed in spontaneously breathing patients with mild to moderate respiratory failure suggested that prone position (PP) in COVID-19 could be beneficial. Materials and methods Consecutive critically ill patients with COVID-19 were enrolled in four ICUs. PP sessions lasted at least 3 h each and were performed twice daily. A Cox proportional hazard model identified factors associated with the need of intubation. A propensity score overlap weighting analysis was performed to assess the association between spontaneous breathing PP (SBPP) and intubation. Results Among 379 patients, 40 underwent SBPP. Oxygenation was achieved by high flow nasal canula in all but three patients. Duration of proning was 2.5 [1.6;3.4] days. SBPP was well tolerated hemodynamically, increased PaO2/FiO2 (78 [68;96] versus 63 [53;77] mm Hg, p = 0.004) and PaCO2 (38 [34;43] versus 35 [32;38] mm Hg, p = 0.005). Neither day-28 survival (HR 0.51, 95% CI 0.16–1.16] nor risk of invasive ventilation [sHR 0.96; 95% CI 0.49;1.88] differed between patients who underwent PP and others. Conclusions SBPP in COVID-19 is feasible and well tolerated in severely hypoxemic patients. It did not induce any effect on risk of intubation and day-28 mortality.

STUDY QUESTIONCan whole-exome sequencing (WES) reveal a shared pathogenic variant responsible for primary gonadal failure in both male and female patients from a consanguineous family?SUMMARY ANSWERPatients with primary ovarian insufficiency (POI) and non-obstructive azoospermia (NOA) were homozygous for the rare missense variant p. S754L located in the highly conserved MSH4 MutS signature motif of the ATPase domain. An oligozoospermic patient was heterozygous for the variant.WHAT IS KNOWN ALREADYMSH4 is a meiosis-specific protein expressed at a certain level in the testes and ovaries. Along with its heterodimer partner MSH5, it is responsible for double-strand Holliday junction recognition and stabilization, to ensure accurate chromosome segregation during meiosis. Knockout male and female mice for Msh4 and Msh5 are reportedly infertile due to meiotic arrest. In humans, MSH4 is associated with male and female gonadal failure, with distinct variations in the MutS domain V.STUDY DESIGN, SIZE, DURATIONThis was a retrospective genetics study of a consanguineous family with multiple cases of gonadal failure in both genders. The subject family was recruited in Iran, in 2018.PARTICIPANTS/MATERIALS, SETTING, METHODSThe proband who is affected by POI, an NOA brother, a fertile sister and their parents were subjected to WES. The discovered variant was validated in these individuals, and the rest of the family was also genotyped by Sanger sequencing. The variant was not detected in 800 healthy Iranian individuals from the Iranome database nor in 30 sporadic NOA and 30 sporadic POI patients. Suggested effect in aberrant splicing was studied by RT-PCR. Moreover, protein homology modeling was used to further investigate the amino acid substitution in silico.MAIN RESULTS AND THE ROLE OF CHANCEThe discovered variant is very rare and has never been reported in the homozygous state. It occurs in the ATPase domain at Serine 754, the first residue within the highly conserved MutS signature motif, substituting it with a Leucine. All variant effect prediction tools indicated this variant as deleterious. Since the substitution occurs immediately before the Walker B motif at position 755, further investigations based on protein homology were conducted. Considering the modeling results, the nature of the substituted amino acid residue and the distances between p. S754L variation and the residues of the Walker B motif suggested the possibility of conformational changes affecting the ATPase activity of the protein.LARGE SCALE DATAWe have submitted dbSNP entry rs377712900 to ClinVar under SCV001169709, SCV001169708 and SCV001142647 for oligozoospermia, NOA and POI, respectively.LIMITATIONS, REASONS FOR CAUTIONStudies in model organisms can shed more light on the role of this variant as our results were obtained by variant effect prediction tools and protein homology modeling.WIDER IMPLICATIONS OF THE FINDINGSIdentification of variants in meiotic genes should improve genetic counseling for both male and female infertility. Also, as two of our NOA patients underwent testicular sperm extraction (TESE) with no success, ruling out the existence of pathogenic variants in meiotic genes in such patients prior to TESE could prove useful.STUDY FUNDING/COMPETING INTEREST(S)This study was financially supported by Royan Institute in Tehran, Iran, and Institut Pasteur in Paris, France. The authors declare no competing interests.TRIAL REGISTRATION NUMBERN/A

International audience; In 2020, research entities at the Institut Pasteur (IP) in Paris, as elsewhere around the world, were closed because of the coronavirus disease 2019 (COVID-19) pandemic. However, IP core facilities, laboratories, services, and departments working on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and priority projects were authorized to continue working both on site and remotely. Given the importance of its role in SARS-CoV-2 genome-sequencing initiatives, the IP Biomics core facility was fully functional during the first (i.e., March-June 2020) and second (i.e., November-December 2020) national lockdowns. We describe here how Biomics successfully implemented an emergency management plan to deal with this health crisis. We highlight the internal deployment of the institutional business continuity plan (BCP) through a series of actions. We also address the impact of the COVID-19 crisis on Biomics staff and collaborators. The added value of quality management and the limitations of risk management systems are discussed. Finally, we suggest that the Biomics infrastructure and the BCP described here could be used for benchmarking purposes, for other next-generation sequencing core facilities wishing to implement/improve their processes, and for future major crisis management.

International audience; The emergence of SARS-CoV-2 variant 20I/501Y.V1 (VOC-202012/1 or GR/501Y.V1) is concerning given its increased transmissibility. We reanalysed 11,916 PCR-positive tests (41% of all positive tests) performed on 7-8 January 2021 in France. The prevalence of 20I/501Y.V1 was 3.3% among positive tests nationwide and 6.9% in the Paris region. Analysing the recent rise in the prevalence of 20I/501Y.V1, we estimate that, in the French context, 20I/501Y.V1 is 52-69% more transmissible than the previously circulating lineages, depending on modelling assumptions.

International audience; Background: The humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the hemodialysis population, including its dynamics over time, remains poorly understood.Methods: To analyze initial and long-term humoral responses against SARS-CoV-2 in a hemodialysis population, we retrospectively evaluated findings from SARS-CoV-2 IgG serologic assays targeting the nucleocapsid antigen or spike antigen up to 6 months of follow-up in patients on hemodialysis in the Paris, France, region who had recovered from coronavirus disease 2019 (COVID-19).Results: Our analysis included 83 patients (median age 65 years); 59 (71%) were male and 28 (34%) had presented with severe COVID-19. We observed positive initial SARS-CoV-2 IgG antinucleocapsid serology in 74 patients (89%) at a median of 67 days postdiagnosis. By multivariable analysis, immunocompromised status was the only factor significantly associated with lack of an IgG antinucleocapsid antibody response. Follow-up data were available at 6 months postdiagnosis for 60 of 74 patients (81%) with positive initial antinucleocapsid serology, and 15 (25%) of them had negative antinucleocapsid serology at month 6. In total, 14 of 15 sera were tested for antispike antibodies, 3 of 14 (21%) of which were also negative. Overall, 97% of antinucleocapsid-antibody-positive specimens were also antispike-antibody positive. Female sex, age >70 years, and nonsevere clinical presentation were independently associated with faster IgG antinucleocapsid titer decay in multivariable analysis. After adjustment for sex and age >70 years, nonsevere clinical presentation was the only factor associated with faster decay of IgG antispike antibodies.Conclusions: This study characterizes evolution of the SARS-CoV-2 antibody response in patients on hemodialysis and identifies factors that are associated with lack of seroconversion and with IgG titer decay.

International audience; Background Although the COVID-19 pandemic peaked in March/April 2020 in France, the prevalence of infection is barely known. Herein, we assessed the serological response against the SARS-CoV-2 virus in a large population working in one institution of the Paris conurbation. We set up two high-throughput and sensitive methods to assess SARS CoV-2 Nucleoprotein and Spike protein-specific IgG response along with a pseudo-neutralization assay in sera. We studied 1847 participants who also answered a web-based survey on clinical symptoms.Methods and Results In May-July 2020, 11% (95% CI: 9.7-12.6) of serums were positive for IgG against the SARS-CoV-2 N and S protein and 9.5% (CI:8.2-11.0) were pseudo-neutralizer. The prevalence of immunization was 11.6% (CI:10.2-13.2) considering positivity in at least one assays. In 5% (CI:3.9-7.1) of RT-qPCR positive individuals, no systemic IgGs were detected. Among immune individuals, 21% had been asymptomatic.Anosmia and ageusia occurred in 52% of the IgG-positive individuals and in 3% of the negative ones. In contrast, 30% of the anosmia-ageusia cases were seronegative suggesting that the true prevalence of infection may reach 16.6%. In sera obtained 4-8 weeks after the first sampling anti-N and anti-S IgG titers and pseudo-neutralization activity declined by 31%, 17% and 53%, respectively with half-life of 35, 87 and 28 days, respectively.Conclusions The population studied being not particularly exposed to SARS-CoV-2 infection is representative of active workers in the Paris conurbation, suggesting that the current epidemiological models may underestimate the true prevalence of infection. The short lifespan of the serological systemic responses hinders retrospective assessment of the epidemic extent.

International audience; In a matter of months, COVID-19 has escalated from a cluster of cases in Wuhan, China, to a global pandemic. As the number of patients with COVID-19 grew, solutions for the home monitoring of infected patients became critical. This viewpoint presents a telesurveillance solution-Covidom-deployed in the greater Paris area to monitor patients with COVID-19 in their homes. The system was rapidly developed and is being used on a large scale with more than 65,000 registered patients to date. The Covidom solution combines an easy-to-use and free web application for patients (through which patients fill out short questionnaires on their health status) with a regional control center that monitors and manages alerts (triggered by questionnaire responses) from patients whose health may be deteriorating. This innovative solution could alleviate the burden of health care professionals and systems while allowing for rapid response when patients trigger an alert.

International audience; Background:Patients with terminal complement pathway deficiency (TPD) are susceptible to recurrent invasive meningococcal disease (IMD). Neisseria meningitidis (Nm) strains infecting these patients are poorly documented in the literature.Methods:We identified patients with TPD and available Nm strains isolated during IMD. We investigated the genetic basis of the different TPDs and the characteristics of the Nm strains.Results:We included 56 patients with C5 (n = 8), C6 (n = 20), C7 (n = 18), C8 (n = 9), or C9 (n = 1) deficiency. Genetic study was performed in 47 patients and 30 pathogenic variants were identified in the genes coding for C5 (n = 4), C6 (n = 5), C7 (n = 12), C8 (n = 7), and C9 (n = 2). We characterized 61 Nm strains responsible for IMD in the 56 patients with TPD. The most frequent strains belonged to groups Y (n = 27 [44%]), B (n = 18 [30%]), and W (n = 8 [13%]). Hyperinvasive clonal complexes (CC11, CC32, CC41/44, and CC269) were responsible for 21% of IMD cases. The CC23 predominates and represented 26% of all invasive isolates. Eleven of the 15 clonal complexes identified fit to 12 different clonal complexes belonging to carriage strains.Conclusions:Unusual meningococcal strains with low level of virulence similar to carriage strains are most frequently responsible for IMD in patients with TPD.

International audience; Between February and May 2017, two cases of invasive meningococcal disease caused by a new, rapidly expanding serogroup W meningococci variant were reported among students of an international university in Paris. Bacteriological investigations showed that isolates shared identical genotypic formula (W:P1.5,2:F1–1:cc11) and belonged to the South American/UK lineage. A vaccination campaign was organised that aimed at preventing new cases linked to potential persistence of the circulation of the bacteria in the students.

International audience; On Friday November 13th at 9:20 pm, three kamikaze bombs went off around the Stade de France a stadium in Saint-Denis just outside Paris, 4 different shootings took place and bombings in Paris and hundreds of people were held hostage in a theater.This multi-site terrorist attack was the first of this magnitude in France. Drawing the lessons of these attacks and those which occurred in other countries from a health perspective is essential to continuously adapt and improve the French response to possible future attacks. Several issues would need to be further explored: Management of uncertainties: When to trigger the plans: after the 1st attack, the 2nd? When do attacks end and when to release mobilized resources? Management of victims: How to ensure that all victims are secured or taken care of? How to provide assistance when attacks are ongoing? Management of teams: Proper follow-up of persons involved in the response: health professionals, police and firemen, emergency call centers but also civil servants within administration that contributed to the response. Communication: Reactivity of all is a key element to secure appropriate resource is mobilized for the response. All actors have to be able to communicate quickly in a secured way.

International audience; Time series studies assessing the effect of temperature on mortality generally use temperatures measured by a single weather station. In the Paris region, there is a substantial measurement network, and a variety of exposure indicators created from multiple stations can be tested. The aim of this study is to test the influence of exposure indicators on the temperature-mortality relationship in the Paris region. The relationship between temperature and non-accidental mortality was assessed based on a time series analysis using Poisson regression and a generalised additive model. Twenty-five stations in Paris and its three neighbouring departments were used to create four exposure indicators. These indicators were (1) the temperature recorded by one reference station, (2) a simple average of the temperatures of all stations, (3) an average weighted on the departmental population and (4) a classification of the stations based on land use and an average weighted on the population in each class. The relative risks and the Akaike criteria were similar for all the exposure indicators. The estimated temperature-mortality relationship therefore did not appear to be significantly affected by the indicator used, regardless of study zone (departments or region) or age group. The increase in temperatures from the 90(th) to the 99(th) percentile of the temperature distribution led to a significant increase in mortality over 75 years (RR = 1.10 [95% CI, 1.07; 1.14]). Conversely, the decrease in temperature between the 10(th) and 1(st) percentile had a significant effect on the mortality under 75 years (RR = 1.04 [95% CI, 1.01; 1.06]). In the Paris area, there is no added value in taking multiple climatic stations into account when estimating exposure in time series studies. Methods to better represent the subtle temperature variations in densely populated areas in epidemiological studies are needed.

International audience; In France, HIV prevention within Maghrebi or French of Maghrebi origin has been seldom studied. The purpose of this study is to compare the recourse to HIV test according to nationality and origin. Data were from the 2010 SIRS cohort, which included 3,006 households representative of the Paris metropolitan area. Results of the study show comparatively low HIV testing rate among Maghrebi and French of Maghrebi origin compared to French with French parents.

International audience; Estimates from multilevel regression of 1768 women living in the Paris metropolitan area showed that women who reported concentrating their daily activities in their perceived neighbourhood of residence had a statistically greater likelihood of not having undergone cervical screening during the previous 2 years. Furthermore, the characteristics of the administrative neighbourhood of residence (such as the practitioner density or the proportion of residents with a recent preventive consultation) had a statistically greater impact in terms of delayed cervical screening on women who concentrated the vast majority of their daily activities within their perceived neighbourhood of residence than among those who did not. The residential environment might promote or damage, to a greater extent, the health behaviour of people whose daily activities are concentrated within their perceived neighbourhood, since we can assume that their exposure to their neighbourhood characteristics is stronger. It could thus be useful to study more often the combined effects of activity space and neighbourhood of residence on participation in preventive health-care activities.

International audience; AIMS: To investigate for the first time the short-term effects of airborne pollen counts on general practitioner (GP) consultations for asthma attacks in the Greater Paris area between 2003-2007. METHODS: Counts were available for common pollens (Betula, Cupressa, Fraxinus and Poaceae). Weekly data on GP visits for asthma attacks were obtained from the French GP Sentinel Network. A quasi-Poisson regression with generalised additive models was implemented. Short-term effects of pollen counts were assessed using single and multi-pollen models after adjustment for air pollution and influenza. RESULTS: A mean weekly incidence rate of 25.4 cases of asthma attacks per 100,000 inhabitants was estimated during the study period. The strongest significant association between asthma attacks and pollen counts was registered for grass (Poaceae) in the same week of asthma attacks, with a slight reduction of the effect observed in the multi-pollen model. Adjusted relative risk for Poaceae was 1.54 (95% CI: 1.33-1.79) with an inter-quartile range increase of 17.6 grains/m3 during the pollen season. CONCLUSIONS: For the first time, a significant short-term association was observed between Poaceae pollen counts and consultations for asthma attacks as seen by GPs. These findings need to be confirmed by more consistent time-series and investigations on a daily basis.

International audience; BACKGROUND/OBJECTIVES: Observational studies document the inverse relationship between cardiovascular disease (CVD) and moderate alcohol intake. However, the causal role for alcohol in cardioprotection remains uncertain as such protection may be caused by confounders and misclassification. The aim of our study was to evaluate potential confounders, which may contribute to putative cardioprotection by alcohol. SUBJECTS/METHODS: We evaluated clinical and biological characteristics, including cardiovascular (CV) risk factors and health status, of 149,773 subjects undergoing examination at our Center for CVD Prevention (The Urban Paris-Ile-de-France Cohort). The subjects were divided into four groups according to alcohol consumption: never, low (30 g/day); former drinkers were analyzed as a separate group. RESULTS: After adjustment for age, moderate male drinkers were more likely to display clinical and biological characteristics associated with lower CV risk, including low body mass index, heart rate, pulse pressure, fasting triglycerides, fasting glucose, stress and depression scores together with superior subjective health status, respiratory function, social status and physical activity. Moderate female drinkers equally displayed low waist circumference, blood pressure and fasting triglycerides and low-density lipoprotein-cholesterol. Alcohol intake was strongly associated with plasma high-density lipoprotein-cholesterol in both sexes. Multivariate analysis confirmed that moderate and low drinkers displayed better health status than did never drinkers. Importantly, few factors were causally related to alcohol intake. CONCLUSIONS: Moderate alcohol drinkers display a more favorable clinical and biological profile, consistent with lower CV risk as compared with nondrinkers and heavy drinkers. Therefore, moderate alcohol consumption may represent a marker of higher social level, superior health status and lower CV risk.

Aims: We performed a preliminary assessment of the eukaryotic 18S rDNA diversity present in finished drinking water samples from three different surface water treatment plants supplying water to the city of Paris (France). Methods and Results: A molecular analysis was performed on a sample from each site based on sequencing of PCR amplified and cloned 18S ribosomal RNA genes. Overall, the 18S rDNA sequences combined from all samples could be affiliated to the Amoebozoa (20·8% of the phylotypes), Ciliophora (25%), Metazoa (33·3%), Fungi (8·3%), Cercozoa (4·2%) and unclassified eukaryotes (8·3%) groups. Conclusions: The 18S rDNA sequences affiliated to the Amoebozoa, Ciliophora and Metazoa lineages were found to be the most abundant phylotypes observed in the drinking water samples. Phylotypes found to be present in two, or all three, samples (41·7% of the total) may represent groups with members adapted to drinking water treatment plant (DWTP) ecosystem conditions. Significance and Impact of the Study: This study shows that finished drinking water can contain 18S rDNA sequences representing a variety of eukaryotic taxa. Further research is needed to better characterize the eukaryotic biodiversity of DWTPs and the effects of the finished drinking water diversity on the downstream water distribution network.

International audience; OBJECTIVES: This study aims to (1) evaluate the probability and timing of termination of pregnancy for fetal anomaly (TOPFA) for all congenital heart defects (CHD) and categories of CHD and (2) assess clinical and socioeconomic predictors of TOPFA for isolated CHD excluding ventricular septal defects (VSD). METHODS: Using population-based data from the Paris Registry of Congenital Malformations, we assessed the probability of TOPFA and gestational age at TOPFA. We used logistic regression to estimate the adjusted effects of maternal characteristics, clinical factors (CHD type, fetal growth restriction, nuchal translucency measurement and gestational age at prenatal diagnosis) on the odds of TOPFA. RESULTS: The proportion of TOPFA for prenatally diagnosed CHD was 46% for all CHD combined, 82% for CHD associated with chromosomal anomalies and 27% for isolated CHD-VSD excluded. Isolated CHD-VSD excluded diagnosed before 22 weeks of gestational age had a 3.2-fold higher odds of TOPFA (adjusted OR 3.2, 95%CI 1.4-7.1). Maternal occupation was not associated with the odds of TOPFA. Women of African origin had a tenfold lower odds of TOPFA than women of French origin (adjusted OR 0.1, 95%CI 0.02-0.4). CONCLUSION: In addition to severity of CHD, early prenatal diagnosis and maternal characteristics were highly associated with the probability of TOPFA for CHD.

International audience; OBJECTIVES: This study aims to (1) evaluate the probability and timing of termination of pregnancy for fetal anomaly (TOPFA) for all congenital heart defects (CHD) and categories of CHD and (2) assess clinical and socioeconomic predictors of TOPFA for isolated CHD excluding ventricular septal defects (VSD). METHODS: Using population-based data from the Paris Registry of Congenital Malformations, we assessed the probability of TOPFA and gestational age at TOPFA. We used logistic regression to estimate the adjusted effects of maternal characteristics, clinical factors (CHD type, fetal growth restriction, nuchal translucency measurement and gestational age at prenatal diagnosis) on the odds of TOPFA. RESULTS: The proportion of TOPFA for prenatally diagnosed CHD was 46% for all CHD combined, 82% for CHD associated with chromosomal anomalies and 27% for isolated CHD-VSD excluded. Isolated CHD-VSD excluded diagnosed before 22 weeks of gestational age had a 3.2-fold higher odds of TOPFA (adjusted OR 3.2, 95%CI 1.4-7.1). Maternal occupation was not associated with the odds of TOPFA. Women of African origin had a tenfold lower odds of TOPFA than women of French origin (adjusted OR 0.1, 95%CI 0.02-0.4). CONCLUSION: In addition to severity of CHD, early prenatal diagnosis and maternal characteristics were highly associated with the probability of TOPFA for CHD.

Background For the first time in France in a population-based survey, this study sought to investigate the potential impact of migration origin and the proportion of lifetime spent in mainland France on body mass index (BMI) and overweight in adults living in the Paris metropolitan area. Methods A representative, population-based, random sample of the adult, French speaking population of the Paris metropolitan area was interviewed in 2005. Self-reported BMI (BMI = weight/height2) and overweight (BMI ≥ 25) were our 2 outcomes of interest. Two variables were constructed to estimate individuals’ migration origin: parental nationality and the proportion of lifetime spent in mainland France, as declared by the participants. We performed multilevel regression models among different gender and age groups, adjusted for demographics and socioeconomic status. Results In women, a parental origin in the Middle East or North Africa (MENA) was associated with a higher risk of being overweight (especially before the age of 55) and a higher BMI (between 35 and 54 years of age), and so were women of Sub-Sahara African parental origin in the middle age category. Only in the youngest men (< 35 years of age) did we observe any association with parental nationality, with a higher BMI when having a MENA parentage. Regarding the association between the proportion of lifetime spent in France and overweight, we observed that, in women, a proportion of 50% to 99% appeared to be associated with overweight, especially after the age of 35. In men, having spent more than half of one’s lifetime in France was associated with a higher risk of overweight among oldest men. Conclusions Our results plea for potential cultural determinants of overweight in the migrant and migrants-born populations in the French context of the capital region. Taking into account the people’ family and personal migration histories may be an important issue in public health research and policies on overweight and obesity prevention.

Background Family social support, as a form of social capital, contributes to social health disparities at different age of life. In a life-course epidemiological perspective, the aims of our study were to examine the association between self-reported family social environment during childhood and self-reported health in young adulthood and to assess the role of family functioning during childhood as a potential mediating factor in explaining the association between family breakup in childhood and self-reported health in young adulthood. Methods We analyzed data from the first wave of the Health, Inequalities and Social Ruptures Survey (SIRS), a longitudinal health and socio-epidemiological survey of a random sample of 3000 households initiated in the Paris metropolitan area in 2005. Sample-weighted logistic regression analyses were performed to determine the association between the quality of family social environment in childhood and self-rated health (overall health, physical health and psychological well-being) in young adults (n = 1006). We used structural equation model to explore the mediating role of the quality of family functioning in childhood in the association between family breakup in childhood and self-rated health in young adulthood. Results The multivariate results support an association between a negative family social environment in childhood and poor self-perceived health in adulthood. The association found between parental separation or divorce in childhood and poor self-perceived health in adulthood was mediated by parent-child relationships and by having witnessed interparental violence during childhood. Conclusion These results argue for interventions that enhance family cohesion, particularly after family disruptions during childhood, to promote health in young adulthood.

International audience; The aims of this network group were to collect epidemiological data of PcP cases in 14 hospitals in the Paris area and to determine the Di-Hydro Pteroate Synthase (DHPS) genotypes, genetic markers for possible sulfamide resistance. From January 1, 2003 to December 31, 2008, 993 (mean 166/year) PcP cases have been reported. Sixty-five percent of patients were HIV-positive. The median count of CD4 lymphocytes was 32/mm(3) (30 in HIV-positive patients, 152 in HIV-negative patients). In HIV-positive patients, PcP revealed the HIV infection in 39%. Among 304 PcP occurring in HIV known infected patients, no prophylaxis was prescribed for 64%; cotrimoxazole prophylaxis had been prescribed to 47 patients but only one of them had the right compliance. In HIV-negative patients (264), corticosteroids were prescribed in 59% and cytotoxic chemotherapies in 34%; 78% did not receive prophylaxis. One hundred sixty nine tumoral pathologies and 116 transplantations were notified. The mortality rate was 16% at day 14 (13% in HIV-positive patients, 26% in HIV-negative patients). Mutations in DHPS genes were detected in 18.5% of samples; 12.5% of patients were infected with several strains. The total annual number of cases has been stable for five years but the proportion of HIV-negative patients increased from 25% to 43%.

Wednesday, 4 pm. At the beginning of December, I was in a meeting inside Paris, my assistant called me: roads were blocked from an exceptional snowstorm and she was stuck in our hospital, which is a part of Paris hospital complex, localized in the West Paris suburb. Hopefully, trains were still working and I could go back to it. Between the train station and the hospital, it looked like a “war scene”: at nightfall, street lamps lighted the bright white desolated boulevard; some cars were in the middle of the sloping road without anybody inside; some people were standing next to their car, without moving, waiting for release. The sudden snow falls immobilize everybody. In front of the hospital, few ambulances are trying to get out without any success. At 6pm, the pre-hospital emergency system decided to dispatch paramedics all around in our district and to refuse hospitals transfers (except in case of life threatening which can’t be managed in some hospitals). Disable patients (major specialty of our hospital) and families of patients were stuck, such as health staff. The night shift was not be able to come. An emergency committee was set up at 3pm by the director. Considering I was the referent of the disaster plan of the hospital, I joined the committee. It included managers and head nurses. They already applied different decisions: leave the staff nursery open and ask the technical staff to stay (restaurant, technical support and gardeners to clear the road inside hospital). It has been asked to all the nurses and health staff to stay until relief teams could come. However, every nurses, auxiliary nurses, technicians, doctors, managers, physicians assistants, paramedics proposed themselves to stay, considering nursery and restaurants staid opened. All people of the hospital staff (2000 workers) cooperated together to great patients, family, colleagues who could not go home. The head nurses were the link between managers and nursing staff. The emergency committee had to ask people who were not essential in actual care and who could go home to leave, considering the very unusual circumstances could last some days. Communications by phone were also disturbed from a technical problem. At 8pm, the situation was more clear: no car could come and leave the hospital. Nursing staff was asked to stay at their shift the night if they had not any relief team. Everybody was invited to eat at the restaurant at this time. At 9pm30, the emergency committee numbers around 100 extra people who had to spend the night at hospital, including patients who could not be transferred, family of patients, and staff. The problem was then to find extra blankets and beds, and a solution was found with the help of the Red Cross. Breakfast was organized and the relief in the morning was made with workers who work around. We considered at this time that everything was under control and those who could go home, should do, with a morning point. During the night, snow had stop and roads were cleared; the meeting point was short. A final meeting at the end of the day was decided to debrief. Two weeks later, with a long period a snow, nursing staff, supports, are now accustomed to manage this situation, without activating a formal emergency committee. Only regular points were made. In conclusion, this experience feedback was very interesting. For instance, one major though about future improvement in our hospital organization was to elaborate an intermediate continuity activity plan. Actually, such as many hospitals, we have disaster plans to face heat wave, terrorist attack, pandemic flu and more, with an increase of the number of patients where we could bring back many health workers. However, no plan was elaborated in case of isolation situation and without necessity of disaster care. This event highlights the need of an intermediate procedure. It also a good example of collaboration in all units, unfortunate unusual between managers, nursing care (including doctors), technical support in this era of reengineering process of French hospitals. It showed that we must protect the unique richness of our hospital, I mean our workers.

Summary: Overwhelming post-splenectomy infection (OPSI) remains a long-term risk in asplenic patients, which may be reduced by appropriate preventive measures. Specific guidelines have been developed to lower its incidence. Aims: To assess the implementation of guidelines by specialized physicians of a university hospital and primary care physicians. Methods: A retrospective review of splenectomized patients’ medical files over a six year period was carried out. Patients’ general practitioners were contacted and a questionnaire was sent to them. Results: 154 individuals who underwent splenectomy between 2000 and 2005 were eligible (62 children and 92 adults): 70.8% received pneumococcal vaccine, 44% received vaccine against Haemophilus influenzae type b with a good cover of children population (88.7%), 24% received meningococcal vaccine. Prophylactic antibiotics were prescribed in 74% of patients. Septic events were found in 8.4%, and global mortality was 11.7% during a mean follow-up period of 4.5 years. Conclusions: Management of the infectious risk in asplenic patient has to be improved: some of the patients are not correctly identified as at risk of OPSI, and vaccination against Neisseria meningitidis is insufficient. Hospital specialists should improve the implementation of guidelines and give better information to general practitioners involved. Keywords: Prevention, Infection, Splenectomy, Immunization

A prospective multicenter surveillance program on yeast bloodstream infections was implemented in the Paris, France, area without restrictions on ward of hospitalization (intensive care unit, hematology, and surgery) or age (adults and children). The present analysis concerns 2,618 isolates collected over 7 years from 2,441 patients. Centralized species identification and antifungal susceptibility testing using the EUCAST methodology were performed. Almost 10% (232/2,441) of the patients had recently (≤30 days) been treated with antifungal drugs. We analyzed the effect of recent exposure to fluconazole ( n = 159) or caspofungin ( n = 61) on the proportions of the five major Candida species. For both drugs, preexposure was associated with a decreased prevalence of Candida albicans in favor of less drug-susceptible species ( C. glabrata and C. krusei for the former and C. parapsilosis and, to a lesser extent, C. glabrata and C. krusei for the latter; P = 0.001). In the multivariate analysis, the risk of being infected with an isolate with decreased susceptibility to fluconazole was independently associated with an age of ≥15 years (odds ratio [OR] = 2.45; 95% confidence interval [CI] = 1.39 to 4.31; P = 0.002) and with recent exposure to fluconazole (OR = 2.17; 95% CI = 1.51 to 3.13; P < 0.001), while the risk of being infected with an isolate with decreased susceptibility to caspofungin was independently associated with an age P = 0.001) and with recent exposure to caspofungin (OR = 4.79; 95% CI = 2.47 to 9.28; P < 0.001). These findings could influence future recommendations for the management of candidemia.

International audience; Two species of Listeria are pathogenic; L. monocytogenes infects humans and animals, and L. ivanovii has been considered to infect ruminants only. We report L. ivanovii–associated gastroenteritis and bacteremia in a man. This isolate was indistinguishable from prototypic ruminant strains. L. ivanovii is thus an enteric opportunistic human pathogen.The genus Listeria contains 2 pathogenic species, L. monocytogenes and L. ivanovii (1). They both invade host cells, replicate in the cytosol after phagosomal escape, and spread from cell to cell by polymerizing actin. These mechanisms correlate with the presence in each species of genetic determinants called the inlAB internalization locus, the LIPI-1 intracellular survival pathogenicity island, and the hpt intracellular growth locus (2). However, each species appears to infect different hosts: L. monocytogenes infects humans and ruminants, whereas L. ivanovii is thought to infect ruminants only (2). L. ivanovii have been previously isolated, although rarely, from infected humans, indicating pathogenic potential for humans (Table). We report a case of L. ivanovii infection in a man with a kidney transplant. The ecology of L. ivanovii suggests that the rarity of human listeriosis due to this species reflects not only host tropism factors but also the rare occurrence of this species in the environment, compared with L. monocytogenes.

Background Early detection of diastolic dysfunction is crucial for patients with incipient heart failure. Although this evaluation could be performed from phase-contrast (PC) cardiovascular magnetic resonance (CMR) data, its usefulness in clinical routine is not yet established, mainly because the interpretation of such data remains mostly based on manual post-processing. Accordingly, our goal was to develop a robust process to automatically estimate velocity and flow rate-related diastolic parameters from PC-CMR data and to test the consistency of these parameters against echocardiography as well as their ability to characterize left ventricular (LV) diastolic dysfunction. Results We studied 35 controls and 18 patients with severe aortic valve stenosis and preserved LV ejection fraction who had PC-CMR and Doppler echocardiography exams on the same day. PC-CMR mitral flow and myocardial velocity data were analyzed using custom software for semi-automated extraction of diastolic parameters. Inter-operator reproducibility of flow pattern segmentation and functional parameters was assessed on a sub-group of 30 subjects. The mean percentage of overlap between the transmitral flow segmentations performed by two independent operators was 99.7 ± 1.6%, resulting in a small variability ( 0.71) and receiver operating characteristic (ROC) analysis revealed their ability to separate patients from controls, with sensitivity > 0.80, specificity > 0.80 and accuracy > 0.85. Slight superiority in terms of correlation with echocardiography (r = 0.81) and accuracy to detect LV abnormalities (sensitivity > 0.83, specificity > 0.91 and accuracy > 0.89) was found for the PC-CMR flow-rate related parameters. Conclusions A fast and reproducible technique for flow and myocardial PC-CMR data analysis was successfully used on controls and patients to extract consistent velocity-related diastolic parameters, as well as flow rate-related parameters. This technique provides a valuable addition to established CMR tools in the evaluation and the management of patients with diastolic dysfunction.

Background Few data are available on prescriber adherence to tuberculosis (TB) treatment guidelines. In particular, excessively long treatment carries a risk of avoidable adverse effects and represents a waste of healthcare resources. We examined factors potentially associated with excessively long treatment. Methods We reviewed the medical records of patients diagnosed with TB in 2004 in the eastern Paris region. Sociodemographic and clinical factors associated with excessively long treatment were identified by logistic regression analyses. Based on contemporary guidelines, excessively long treatment was defined as more than 6 months of a four-drug regimen for thoracic TB with full sensitive strains, and more than 12 months for patients with extrathoracic TB. Results Analyses concerned 478 patients with a median age of 36.0 ± 13.5 years, of whom 48% were living in precarious conditions (i.e. poor living conditions and/or no health insurance), 80% were born abroad, and 17% were HIV-seropositive. TB was restricted to the chest in 279 patients (isolated pulmonary, pleuropulmonary, and isolated pleural TB in 245, 13, and 21 patients, respectively), exclusively extrathoracic in 115 patients, and mixed in the remaining 84 patients. Treatment was prescribed by a chest specialist in 211 cases (44.1%) and 295 patients (61.7%) were managed in a single institution. The treatment duration complied with contemporary guidelines in 316 cases (66.1%) and was excessively long in 162 cases (33.9%). The median duration of excessively long treatment was 313 days (IQR: 272-412). In multivariate analysis, isolated thoracic TB, previous TB, HIV infection, a prescriber other than a chest specialist, and management in more than one healthcare center during treatment were independently associated with excessively lengthy treatment. Conclusion One-third of TB patients received excessively long treatment, reflecting inadequate awareness of management guidelines or unwillingness to implement them.

International audience; INTRODUCTION: Our objective was to describe self-sufficiency and quality of life one year after intensive care unit (ICU) discharge of patients aged 80 years or over. METHODS: We performed a prospective observational study in a medical-surgical ICU in a tertiary non-university hospital. We included patients aged 80 or over at ICU admission in 2005 or 2006 and we recorded age, admission diagnosis, intensity of care, and severity of acute and chronic illnesses, as well as ICU, hospital, and one-year mortality rates. Self-sufficiency (Katz Index of Activities of Daily Living) was assessed at ICU admission and one year after ICU discharge. Quality of life (WHO-QOL OLD and WHO-QOL BREF) was assessed one year after ICU discharge. RESULTS: Of the 115 consecutive patients aged 80 or over (18.2% of admitted patients), 106 were included. Mean age was 84 +/- 3 years (range, 80 to 92). Mortality was 40/106 (37%) at ICU discharge, 48/106 (45.2%) at hospital discharge, and 73/106 (68.9%) one year after ICU discharge. In the 23 patients evaluated after one year, self-sufficiency was unchanged compared to the pre-admission status. Quality of life evaluations after one year showed that physical health, sensory abilities, self-sufficiency, and social participation had slightly worse ratings than the other domains, whereas social relationships, environment, and fear of death and dying had the best ratings. Compared to an age- and sex-matched sample of the general population, our cohort had better ratings for psychological health, social relationships, and environment, less fear of death and dying, better expectations about past, present, and future activities and better intimacy (friendship and love). CONCLUSIONS: Among patients aged 80 or over who were selected at ICU admission, 80% were self-sufficient for activities of daily living one year after ICU discharge, 31% were alive, with no change in self-sufficiency and with similar quality of life to that of the general population matched on age and sex. However, these results must be interpreted cautiously due to the small sample of survivors.

International audience; We examined the variations of bacterial populations in treated drinking water prior to and after the final chlorine disinfection step at two different surface water treatment plants. For this purpose, the bacterial communities present in treated water were sampled after granular activated carbon (GAC) filtration and chlorine disinfection from two drinking water treatment plants supplying the city of Paris (France). Samples were analyzed after genomic DNA extraction, polymerase chain reaction (PCR) amplification, cloning, and sequencing of a number of 16S ribosomal RNA (rRNA) genes. The 16S rDNA sequences were clustered into operational taxonomic units (OTUs) and the OTU abundance patterns were obtained for each sample. The observed differences suggest that the chlorine disinfection step markedly affects the bacterial community structure and composition present in GAC water. Members of the Alphaproteobacteria and Betaproteobacteria were found to be predominant in the GAC water samples after phylogenetic analyses of the OTUs. Following the chlorine disinfection step, numerous changes were observed, including decreased representation of Proteobacteria phylotypes. Our results indicate that the use of molecular methods to investigate changes in the abundance of certain bacterial groups following chlorine-based disinfection will aid in further understanding the bacterial ecology of drinking water treatment plants (DWTPs), particularly the disinfection step, as it constitutes the final barrier before drinking water distribution to the consumer's tap.

International audience; BACKGROUND: Early family-level and social-level stressors are both assumed to be the components of two main path models explaining the association between exposure to interparental violence in childhood and its long-term consequences on mental health explored through life-course epidemiological studies. AIMS: To investigate the association between exposure to interparental violence in childhood and mental health outcomes in adulthood when taking into account early family and social stressors. METHODS: A retrospective French cohort study of 3023 adults representative of the general population in the Paris metropolitan area was conducted in 2005 through at-home, face-to-face interviews. The outcomes measures were current depression and lifetime suicide attempt, intimate partner violence, violence against children and alcohol dependence. RESULTS: The adults exposed to interparental violence during childhood had a higher risk of psychosocial maladjustment. After adjusting for family- and social-level stressors in childhood, this risk was, respectively, 1.44 (95% CI 1.03 to 2.00) for depression, 3.17 (1.75 to 5.73) for conjugal violence, 4.75 (1.60 to 14.14) for child maltreatment and 1.75 (1.19 to 2.57) for alcohol dependence. CONCLUSIONS: The adult consequences of parental violence in childhood-and this independently of the other forms of domestic violence and the related psychosocial risks-should lead to intensifying the prevention of and screening for this form of maltreatment of children.

International audience; Letter to the Editor. no abstract

International audience; BACKGROUND: Strategies for ordering bedside chest radiographs (CXRs) have substantial logistic and financial consequences in the ICU. Many of the indications for CXRs in the ICU are controversial, such as the ordering of daily routine CXRs for intubated patients. The opinions of intensivists about ordering CXRs have not been reported. Comparing these opinions to established guidelines and identifying situations where opinions diverge in the absence of guidelines are of considerable interest. METHODS: We asked 190 intensivists from 34 ICUs in the area of Paris, France, to anonymously complete a 29-item questionnaire about their opinions regarding the ordering of CXRs; each item described a clinical scenario. Of the 29 scenarios, 10 dealt with the placement of medical devices, 8 with the presence of medical devices, and 11 with other clinical situations. The study was based on a Delphi process deployed over the Internet through an original software application. Three Delphi rounds were run between January and March 2006, using the same questionnaire. Detailed feedback for the answers given during the previous round was supplied to each intensivist solicited for updating his answers. RESULTS: Eighty-two intensivists from 32 ICUs completed the study. A consensus emerged that routine CXRs were necessary for eight scenarios and unnecessary for two scenarios. The study also shed light on items without a consensus. In particular, 75% of intensivists (58% on the first round) did not support obtaining daily routine CXRs in intubated patients. CONCLUSION: The study underlines situations in which intensivists do not support the guidelines and outlines recommendations likely to be followed in clinical practice.

International audience; OBJECTIVE: To examine perceptions by intensive care unit (ICU) workers of unrestricted visitation, to measure visiting times, and to determine prevalence of symptoms of anxiety and depression in family members. DESIGN: Observational, prospective, single-center cohort. SETTING: Medical-surgical ICU in a 460-bed tertiary-care hospital. PATIENTS: Two hundred nine consecutive patients hospitalized >3 days were studied over the first 5 ICU days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics of patients (n = 209), families (n = 149), and ICU workers (n = 43) were collected. ICU workers reported their perceptions of unrestricted visitation, and family members completed the Hospital Anxiety and Depression Scale. Daily severity scores (Simplified Acute Physiology Score II and Logistic Organ Failure) and a workload score (Nine Equivalents of Nursing Manpower) were computed. Maximum median visit length was 120 mins per patient per day and occurred on days 4 and 5. No correlations were found among severity of illness, workload, and visit length. For 115 patients, both nurse and physician questionnaires were available; although several differences were noted, neither nurses nor physicians perceived open visitation as disrupting patient care. The median rating for delay in organizing care was "never" for physicians and "occasionally" for nurses. Nurses perceived more disorganization of care than physicians (p = .008). Compared with nurses, the physicians reported greater family trust (p = .0023), more family stress (p = .047), and greater unease when examining the patient (p = .02). The Hospital Anxiety and Depression Scale indicated symptoms of anxiety in 73 (49%) family members and depression in 44 (29.5%). CONCLUSIONS: The 24-hr visitation policy was perceived favorably by families. It induced only moderate discomfort among ICU workers, due to the potential for care interruption, in particular for nurses.

International audience; OBJECTIVES: Lack of information is a frequent complaint with regard to physicians dealing with prenatal diagnosis (PD). The aim of the study was to find out how information on PD was perceived by patients and if they considered that they had been correctly informed by their physicians. METHODS: We conducted a prospective study in Lariboisi? Hospital (Paris) with 86 patients undergoing prenatal diagnosis between 2001 and 2003. A 23-item questionnaire was given to patients after delivery or termination of pregnancy (TP). RESULTS: Fifty patients out of 86 answered the questionnaire. Twelve patients out of 50 underwent a TP. Information on foetal anomaly was insufficient for 11 patients out of 50 (22%). Some patients found the information too technical; others would like to see photos to illustrate the anomalies and the possible surgical repairs to be performed. Information was insufficient for one in four patients concerning maternal serum screening for Down's syndrome. Information before amniocentesis was considered sufficient by 9 out of 10 patients. Information on the risks of TP was not given or not understood by 10 out of 12 patients. CONCLUSION: Information on prenatal diagnosis could be improved by using simple and accessible language, supported by written documents and photos for certain anomalies. More information should be given in cases of abstract anomalies and should be adapted to the social, ethnic and cultural background of the patient.

International audience; OBJECTIVES: Apparent increases in human male reproductive disorders, including low sperm production, may have occurred because of increased chemical exposure. Various glycol ether-based solvents have pronounced adverse effects on sperm production and male fertility in laboratory animals. The authors investigated the effects of past and current exposure to glycol ether-containing products on semen quality and reproductive hormones among men employed by the Paris Municipality. METHODS: Between 2000 and 2001 the authors recruited 109 men who gave semen, blood and urine samples and underwent an andrological examination. Information on lifestyle, occupation, exposure and medical history was obtained by interview. According to their job and chemical products used during the period 1990-2000, men were classified as either occupationally exposed or non-exposed. Current exposure levels to glycol ethers at the time of the study were evaluated by biological monitoring of six urinary metabolites. RESULTS: Previous exposure to glycol ethers was associated with an increased risk for sperm concentration, for rapid progressive motility and for morphologically normal sperm below the World Health Organization semen reference values. No effect of previous glycol ether exposure on hormones levels was observed. By contrast, current glycol ether exposure levels were low and not correlated with either seminal quality or hormone levels. CONCLUSIONS: This study suggests that most glycol ethers currently used do not impact on human semen characteristics. Those that were more prevalent from the 1960s until recently may have long lasting negative effects on human semen quality.

International audience; OBJECTIVE: To identify subjective factors that lead investigators not to invite eligible individuals to participate in pediatric studies. DESIGN: Qualitative study with semistructured interviews. SETTING: Four pediatric teaching hospitals in Paris. PARTICIPANTS: Pediatric investigators (n=24). MAIN OUTCOME MEASURE: Report by investigator that eligible patients were not invited by him or her to participate in a clinical research study. RESULTS: Sixty-three percent of investigators (15 of 24) reported not inviting eligible patients. The noninvitation patterns were global (ie, investigators did not invite anyone) (37.5% [9/24]) or targeted specific patient subgroups (37.5% [9/24]). Noninvitation was often described as driven by ethical concerns related to the study design or patients or by anticipated patient refusal (58.3% [14/24]). None of the investigators kept records of noninvitation rates or refusal rates. Investigators estimated refusal rates of 1% to 10%, and none remembered a study that had failed because of potential subjects' refusals (including healthy participants). CONCLUSIONS: Noninvitation to participate in studies is not an absence of action but rather is an organized practice that reflects investigators' perceptions. Consequences are practical (eg, recruitment bias and study failure) and ethical (eg, unequal access to trials and failure to respect the autonomy of eligible patients). Our data suggest an urgent need for quantitative studies aimed at documenting and understanding noninvitation of eligible patients to participate in research studies in pediatrics and in other medical specialties.

BACKGROUND: Friedreich ataxia (FA) is the most frequent autosomal recessive cerebellar ataxia. Although the phenotype is well known, disease progression has not been evaluated in a prospective manner. OBJECTIVE: To perform a long-term prospective follow-up of neurological, cardiological, and oculomotor function in patients with FA (FA patients). DESIGN: In this open-labeled prospective survey, we examined 104 FA patients every 6 months during a median period of 5 years (range, 6 months to 7 years), with a systematic standardized protocol. Data are reported as mean +/- SD. SETTING: Neurological examinations were performed at the Federation of Neurology and the Department of Genetics of the Salp?i? Hospital, Paris, France. Cardiological follow-up was performed at the Department of Cardiology; oculomotor examinations were performed at the Institut National de la Sant?t de la R?erche M?cale Unit 679, at the same hospital. Patients We studied 104 FA patients with a confirmed molecular diagnosis. None were receiving antioxidant therapy at baseline; 88 accepted treatment with the coenzyme Q(10) analogue idebenone (5 mg/kg per day). Sixteen preferred not to be treated. INTERVENTIONS: Neurological status was evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and a quantitative writing test. Cardiological evaluations included echocardiography, electrocardiography, and Holter monitoring. Oculomotor function was evaluated by electro-oculography to determine the frequency of square wave jerks. RESULTS: The total ICARS score worsened during follow-up, whether or not the patients were treated with idebenone (1.93 +/- 0.25 and 4.43 +/- 1.56 points per year, respectively). The total ICARS score increased faster in patients with onset before age 15 years compared with the others (2.6 +/- 0.4 [n = 51] vs 1.1 +/- 0.3 [n = 37]; P = .05). The posture subscore increased faster in patients able to stand at baseline, who also had shorter disease durations than patients unable to stand (1.25 +/- 0.12 vs 0.47 +/- 0.22 point per year; P

One hundred twenty CTX-M-15-producing Escherichia coli strains isolated in 10 different hospitals from Paris (France), in the Hospital Charles Nicolle in Tunis (Tunisia), and in the Pasteur Institute in Bangui, Central African Republic (CAR), between 2000 and 2004 were studied. Eighty isolates, recovered from the three countries, were clonally related by repetitive extragenic palindromic PCR and pulsed-field gel electrophoresis. Various resistance profiles were identified among these clonal strains. After conjugation or electroporation of plasmids from E. coli strains representative of each profile and each geographic region, we observed seven resistance profiles in the recipient strains. Incompatibility typing showed that all the plasmids transferred from the clonal strains studied, except one, belonged to the incompatibility group FII. They all shared a multidrug resistance region (MDR) resembling the MDR region located in pC15-1a, a plasmid associated with an outbreak of a CTX-M-15-producing E. coli strain in Canada. They also shared the common backbone of an apparent mosaic plasmid, including several features present in pC15-1a and in pRSB107, a plasmid isolated from a sewage treatment plant. This study suggests that although the plasmid-borne bla CTX-M-15 gene could be transferred horizontally, its dissemination between France, Tunisia, and CAR was due primarily to its residence in an E. coli clone with a strong propensity for dissemination.

OBJECTIVES: The authors had for aim to assess incident HIV+ patients in Saint-Antoine hospital, Paris in 2002-2003 (transfers excluded). METHODS: Sociodemographic, clinical, and virological data were collected to compare French and sub-Saharan patients. RESULTS: Three hundred new HIV+ patients were identified: mean age 36.2 year; ratio M/W 65/35; origin: Caucasian 43%, African 44%, Maghrebian 8%, Asian 3%; nationality: French 45%, sub-Saharan African 44%; illegal aliens 65%; employed 51%; transmission: heterosexual 54%, homosexual 39%, intravenous drug user (IVDU) 2%; circumstances for diagnosis: HIV exposure 34%, primary infection 9%, symptoms/AIDS 23%, pregnancy 6%, other 28%; CDC stage: A 77%, B 9%, C 14%; mean T-CD4+ 374/mm3, median HIV-RNA 30780 cp/mL; co-infection HBV 7.3% HCV 5%. Outcome: 88% still followed up in Saint-Antoine, 2% transferred, 9% lost to follow-up, 1% dead. A significant difference was shown: 1) between French (N = 123) and African (N = 46) men for heterosexual transmission (10 vs 91%), working status (85 vs 28%), T-CD4+ (354 vs 251/mm3), outcome (lost to follow-up 5 vs 24%) [P < 0.01]; 2) between French (N=13) and African (N = 85) women for age (41 vs 32 years), working status (38 vs 10%), stage A (54 vs 81%) [P < 0.05]; 3) between African patients according to sex (46M/85W) for age (39 vs 32 years), working status (28 vs 10%; P = 0.01), outcome (lost to follow-up 24 vs 6%) [P < 0.01]. CONCLUSION: This study highlights the persistence of HIV in native homosexual French men and the increasing prevalence in African migrant with precarious social status.

BACKGROUND: Over the last decade, the increasing number of people experiencing difficult social conditions--especially in urban areas--has led to the implementation of free (health and social care) clinics for uninsured and/or poor people. METHODS: In this paper, we give some results of multidisciplinary (sociological and epidemiological) research conducted among patients attending five of these free clinics in the Paris area. RESULTS: The statistical and qualitative analyses revealed the diversity of the studied population, as well as the conditions in which these consultants attended such clinics, what kind of services and help they used and, furthermore, what kind of social ties were strengthened. CONCLUSION: These results lead us to discuss our present knowledge of the determinants of the utilization of the healthcare system, not only among vulnerable people, but perhaps also amongst the general population.

OBJECTIVE: To evaluate the impact of policy and practice changes in prenatal screening for Down's syndrome on prenatal diagnosis and live birth prevalence of Down's syndrome. DESIGN: Population-based observational study. SETTING: Greater Paris. POPULATION: Residents of Greater Paris who gave birth or had a termination of pregnancy in Paris during 1981-2000 (approximately 38,000 births per year). METHODS: Data on 1916 cases of Down's syndrome were obtained from the Paris Registry of Congenital Anomalies. Analyses included binomial and Poisson models of trends in three periods: prior to 1989 (reference period), 1989-1995 (reimbursement of amniocentesis in case of ultrasonographic anomalies) and 1996-2000(widespread use of reimbursed serum screening and measurement of nuchal translucency). MAIN OUTCOME MEASURES: Trends in proportion of Down's syndrome cases diagnosed prior to birth; live birth prevalence of Down's syndrome. RESULTS: The proportion of Down's syndrome detected prenatally for women 38 years of age, the increase was 1.5-fold. The live birth prevalence of Down's syndrome decreased by 3% per year (prevalence ratio [PR] 0.97, 95% CI 0.96-0.99); the age-adjusted decrease was 13%. The analysis by period showed that the decrease in live birth prevalence of Down's syndrome was greater after 1988. CONCLUSIONS: By far, most cases of Down's syndrome are currently detected prenatally in the Parisian population. Consequently, the live birth prevalence of Down's syndrome has decreased despite consistent trends towards delayed childbearing. These positive public health effects have to be balanced against a relatively high rate of amniocentesis and the potentially negative consequences of widespread prenatal testing for individuals born with Down's syndrome.

International audience; BACKGROUND: Lead exposure and total immunoglobulin E (IgE) have been shown to be positively related in animals and humans even at lead levels below those recognized as toxic. In the last decades, exposure to lead has become more frequent in urban areas of industrialized as well as of developing countries where IgE-mediated allergy prevalence has also increased. METHODS: We examined for the first time the relationship between in utero exposure to lead and cord blood total IgE in two samples of 137 and 237 mother-newborn pairs, respectively, recruited in Paris. RESULTS: Cord blood IgE was positively related to hair lead level at birth, providing an integrated measure of long-term exposure in utero, in each cohort (Spearman's coefficient r = 0.32, P < 0.001 and r = 0.19, P < 0.01, respectively) and in the combined cohort (r = 0.21; P < 0.01). The relationship appeared to be more pronounced in newborns of nonallergic mothers (r = 0.24; P < 0.01) than in those of allergic mothers (r = 0.12). This could be due to the fact that familial history of allergy, the strongest determinant of IgE development, may overshadow the influence of lead on IgE in the offspring. CONCLUSIONS: Our findings suggest a possible intervention of environmental exposure besides genetic factors in early life development of IgE production. Further studies are needed to confirm the finding.

AIMS/HYPOTHESIS: We examined whether the 2-h plasma glucose (2 hPG) concentration after a 75 g OGTT is predictive of death in men with a diabetic, an impaired or a normal fasting plasma glucose concentration (DM-FPG: > or =7.0 mmol/l; IFG: 6.1-6.9 mmol/l; normal-FPG

International audience; The validity of scales used for subjective assessment of health, particularly transitional indices, is under discussion. The aim of the present study was to assess the concurrent and predictive validity of a simple estimate of long-term subjective assessment of respiratory health changes. A longitudinal study of 915 workers was conducted over 30 yrs, with both retrospective self-assessment of respiratory health changes and objective measurements of spirometric values 12 yrs apart. An assessment of the reason for death during the subsequent 20 yrs was performed. Subjective assessment of respiratory deterioration over 12 yrs was significantly related to both cross-sectional lung function values and longitudinal lung function changes (forced expiratory volume in one second (FEV1) decline), an association which remained after adjustment for FEV1 level. It was also related to the same risk factors as decline in FEV1 (smoking, occupational exposure). Self-evaluation of respiratory deterioration was significantly predictive of death from all causes, with the highest (but nonsignificant) rate ratio for respiratory causes. Asthmatics exhibited greater long-term variability (objective and subjective) than nonasthmatics. Independent of dyspnoea, self-assessment of respiratory health deterioration was significantly related to FEV1. Subjective assessment of long-term changes in respiratory health provides valid information.

International audience; Data derived from a cohort study of 191 men, seen 5 years apart, were used to investigate the involvement in allergic as well as in nonallergic upper airway disease (UAD) of two risk factors, immediate hypersensitivity and tobacco smoking, the roles of which have been well established in lower airway disease. At both surveys, UAD and smoking habits were assessed by an extended version of the BMRC/ECSC questionnaire. UAD consisted of usual or chronic rhinitis, seasonal allergic rhinitis and perceived nasal hyperresponsiveness (PNHR) to tobacco smoke, cold air or exercise. Immediate hypersensitivity was determined either in vivo (skin prick test, SPT, positivity) or in vitro (total IgE). UAD prevalence and smoking habits did not vary significantly over 5 years. On the contrary, SPT positivity increased significantly between the two surveys. At both surveys, SPT positivity for common aeroallergens (grass pollens overall) was significantly related to seasonal allergic rhinitis but not to usual or chronic rhinitis and to PNHR. Similarly, the total IgE level was increased in seasonal allergic rhinitis, but never significantly. Current smoking was always a habit significantly more frequent in men reporting chronic rhinitis (odds ratios of 5.3 and 4.9 in 1985 and 1990, respectively). The relationship was of the dose-response type: the more the subjects smoked, the more they reported chronic rhinitis. In contrast, seasonal allergic rhinitis was more associated with exsmoking, either in 1985 or in 1990. These results were confirmed longitudinally and after exclusion of asthmatics. Further investigations are needed to support the hypothesis raised by our data according to which immediate hypersensitivity, as assessed by SPT positivity for common aeroallergens, and tobacco smoking might intervene alternatively in UAD, probably because of the 'healthy smoker effect'.

International audience; Despite a consensus on the need for Pneumocystis carinii pneumonia (PCP) prophylaxis for HIV-infected patients with fewer than 200 CD4+ lymphocytes/mm3, the number of cases of PCP has remained stable, and about 70% involve patients who are not receiving prophylaxis. The aim of this study was to determine why these patients are not covered by prophylaxis. It was based on a retrospective analysis of semidirective interviews with 32 patients who developed PCP while not receiving prophylaxis. The reasons given were a lack of knowledge of risk factors for HIV infection, the fear of HIV testing, unawareness of the existence of PCP prophylaxis, a refusal to see a doctor in the absence of symptoms, unwillingness to be monitored and in four cases a failure of the doctor to prescribe prophylaxis.

International audience; We assessed (1) the sensitivity and specificity of exercise oxygen saturation measurement (EOS) for the diagnosis of Pneumocystis carinii pneumonia (PCP); and (2) the cost of introducing this indirect diagnostic test compared with that of standard diagnostic strategies for PCP. In a prospective study, 85 HIV-infected patients with suspected PCP underwent EOS, followed by induced sputum (IS) and bronchoalveolar lavage (BAL) if IS was negative for P. carinii. The prevalence of PCP was 0.22, the sensitivity of IS was 0.6, and its specificity was perfect. The cost ratios of IS to BAL and EOS to BAL were 0.1 and 0.2, respectively. A desaturation of three points was the best cutoff point, giving perfect sensitivity and a specificity of 0.77. The cost analysis showed that the introduction of EOS into diagnostic strategies for PCP is highly justified when the local prevalence is low. Exercise oxygen saturation measurement is simple and safe, and the results are available rapidly; its sensitivity is perfect and its specificity good. Its economic utility depends on its cost and the local prevalence of PCP in the test population.

International audience; The relationship between smoking and percentages and counts of T-cell subsets, in particular CD45R0+ (memory) and CD45RA+ (naive) CD4+ lymphocytes, have been assessed in a sample of 311 middle-aged men working in the Paris area. Percentages of lymphocytes with the phenotypes CD4+, CD8+, CD4+CD45R0+, and CD4+CD45RA+ were determined using double immunofluorescence labeling. All cell counts, including CD4+CD45R0+, and CD4+CD45RA+ lymphocytes increased significantly with tobacco consumption, as did the percentages of lymphocytes with the CD4+CD45R0+ and CD4+ phenotypes. The increase in the percentage of lymphocytes with the CD4+CD45RA+ phenotype, although not significant, was similar to that observed in the percentage of CD4+CD45R0+ lymphocytes. When the proportions of CD4+ cells with the CD45R0+ or the CD45RA+ phenotype were considered, no specific modification of any of these two sub-populations was observed: the effect of smoking on memory and naive Cd4+ lymphocytes seemed to be equivalent.

International audience; A previous cross-sectional analysis of 1980 data from a population of working men in the Paris area has shown a significant relationship of blood eosinophilia to a reduced FEV1 among nonsmokers, remaining after excluding men with a history of asthma. In the present report, we reexamine this relationship, after taking into account asthma, bronchial hyperresponsiveness, and positive skin prick tests, using data collected in 1985 in a subsample of 363 men from the initial population. Blood eosinophilia, defined by 5% or more eosinophils or by 250 or more eosinophils per cubic millimeter appeared to be associated with a lower FEV1, primarily in nonsmokers. A difference of approximately 0.40 L was observed in never-smokers with eosinophilia (greater than or equal to 5% of eosinophils) compared with those without. This association persisted after exclusion of subjects with atopy, asthma, and bronchial hyperresponsiveness. Longitudinally, no significant association was observed between 1980 eosinophilia and the annual FEV1 decline between 1980 and 1985, even in nonsmokers. The results of our cross-sectional analyses suggest that asthma or asthma-like disorder does not explain the association between eosinophilia and FEV1. The role of eosinophil in respiratory disorders may go beyond its intervention in allergy. Further longitudinal studies are needed to better understand discrepancies between cross-sectional and longitudinal data and whether eosinophilia is a risk factor for chronic air-flow limitation.

In November 2014, French public health authorities renewed the recommendation to target for vaccination against invasive meningococcal disease men who have sex with men (MSM) and all individuals ≥25 years attending social venues associated with the gay community. This policy was extended beyond the Paris region as a reaction to the continuing spread of serogroup C isolates belonging to a new lineage within clonal complex cc11 since the recommendation was first issued in July 2013.