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BackgroundThe aim of this study was to evaluate the clinical prognostic value of the CD4+T-cell percentage (%CD4), the CD4+/CD8+T-cell ratio or the CD8+T-cell count, in addition to the CD4+T-cell count and viral load (VL) in antiretroviral-naive HIV- infected patients with CD4+T-cell counts >200 cells/ mm3.MethodsAntiretroviral-naive patients ( n=9,740) who were AIDS-free and had a CD4+T-cell count >200 cells/ mm3at their first visit after January 1997 were followed-up until treatment initiation or clinical progression (mean follow- up 17 months and 13,660 person-years). Poisson regression was used for statistical analyses.ResultsProgression to AIDS-defining events (ADEs), serious ADEs and death occurred in 228 patients (crude rate 1.69 per 100 person-years), 105 patients (0.77 per 100 person-years) and 67 patients (0.49 per 100 person-years), respectively. Regarding progression to ADE, the data fit was improved when the model also included the %CD4 (Akaike's information criteria [AIC] 2,049) and, to a lesser extent, the CD4+/CD8+T-cell ratio (AIC 2,053), in addition to CD4+T-cell count and VL (AIC 2,056). After adjustment for VL and baseline characteristics, patients with CD4+T-cell counts of 350–500 cells/mm3and %CD4+T-cell counts of 200–350 cells/mm3and %CD4>15%. The %CD4 was also significantly associated with the risk of serious ADE. By contrast, %CD4, CD4+/CD8+T-cell ratio or CD8+T-cell count had no additional prognostic value for the risk of death.ConclusionsIn antiretroviral-naive HIV-infected patients with CD4+T-cell counts >200 cells/mm3, the %CD4 was predictive of the risk of clinical progression independently of CD4+T-cell count and VL.

Background— The pathophysiology of infective endocarditis involves a pathogen/host tissue interaction, leading to formation of infected thrombotic vegetations. Annexin V is a ligand of phosphatidylserines exposed by activated platelets and apoptotic cells. Because vegetations are platelet-fibrin clots in which platelet proaggregant activity is enhanced by bacterial colonization, we investigated the ability of annexin V labeled with technetium Tc 99m ( 99m Tc-ANX) to provide functional imaging of these vegetations in experimental models of infective endocarditis. This ability was assessed in rabbits and rats because of the different interest of these 2 species in preclinical analysis. Methods and Results— Nonbacterial thrombotic endocarditis was induced with the use of a catheter left indwelling through the aortic or tricuspid valve, and animals were injected with either a bacterial inoculum or saline. Scintigraphic investigations were performed 5 days later and showed a higher 99m Tc-ANX uptake by vegetations in infected versus noninfected animals (ratio, 1.3 for in vivo acquisitions and 2 for autoradiography; P 99m Tc-ANX at the interface between circulating blood and vegetation. In parallel, underlying myocardial tissue showed myocyte apoptosis and mucoid degeneration, without extracellular matrix degradation at this stage. Conclusions— 99m Tc-ANX is suitable for functional imaging of platelet-fibrin vegetations in endocarditis, as well as embolic events. 99m Tc-ANX uptake reflects mainly platelet activation in the luminal layer of vegetations. This uptake is enhanced by bacterial colonization.

BackgroundIdentifying subgroups of asymptomatic patients with aortic stenosis (AS) who may benefit from early intervention is a critical challenge due to the risk of sudden death and irreversible myocardial dysfunction without preceding symptoms. In this study, we analyzed the determinants and prognostic value of Galectin-3 in a large cohort of patients with AS.MethodsWe included patients with at least mild degenerative AS enrolled in 2 ongoing prospective clinical studies, COFRASA and GENERAC, aiming at assessing the determinants of AS occurrence and progression.ResultsBetween November 2006 and July 2013, 583 patients were prospectively enrolled. Severe AS was diagnosed in 312 (56%) patients among whom 220 (38%) were symptomatic. Age (p

International audience; AIMS: Indications for surgery in acute infective endocarditis (IE) are detailed in guidelines, but their application is not well known. We analysed the agreement between the patient's attending physicians and European Society of Cardiology guidelines regarding indications for surgery. We also assessed whether surgery was performed in patients who had an indication. METHODS AND RESULTS: From the 2008 prospective population-based French survey on IE, 303 patients with definite left-sided native IE were identified. For each case, we prospectively recorded (i) indication for surgery according to the attending physicians and (ii) indication for surgery according to guidelines. Surgery was indicated in 194 (65%) patients according to attending physicians and in 221 (73%) according to guidelines, while 139 (46%) underwent surgery. Agreement was moderate between attending physicians and guidelines (kappa 0.41-0.59) and between indication according to guidelines and the performance of surgery (kappa 0.38). Of the 90 (30%) patients not operated despite indication, contraindication to surgery was reported by the attending physicians in 42 (47%), and indication was not identified in 48 (53%). One-year survival was 76% in patients with indication and surgery performed (n = 131), 69% in patients without indication and no surgery (n = 74), 56% in patients with identified indication and contraindication to surgery (n = 42), and 60% in patients with no identified indication (n = 48; P = 0.059). CONCLUSION: Cardiac surgery during acute IE was recommended in almost three out of four patients, although fewer than half were actually operated. Indication was not acknowledged by the attending physicians in one out of six patients

International audience; Background: Influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups. Objectives Aim of this study was to identify factors associated with poor outcomes among adults hospitalized in France for laboratory-confirmed seasonal influenza. Study design Patients hospitalized for influenza were identified in a prospective, multicenter study carried out in French hospitals during three consecutive influenza seasons (2012–2015). Influenza virus infection was confirmed by reverse transcription polymerase chain reaction. Sociodemographic and clinical variables were compared according to the virus type and subtype. Risk factors for complications, intensive care unit (ICU) admission and death were analyzed by backward stepwise logistic regression. Results The study population consisted of 566 patients, of whom 56% were older than 65 years and 82% had underlying chronic illnesses. Type A influenza viruses infected 422 patients (75%), including subtype H3N2 in 239 patients (57%). The prior vaccine coverage rate was 38%. Complications occurred in 255 patients (45%), consisting mainly of pneumonia (n = 143, 30%) and respiratory failure (n = 116, 20%). Eighty-three patients (15%) were admitted to an ICU, and the in-hospital mortality rate was 4% (n = 21). Sixty-six patients (12%) received oseltamivir. Age over 65 years was the only identified risk factor for complications. Risk factors for ICU admission were an absence of vaccination, no oseltamivir administration before admission, pre-existing chronic respiratory disease, and current smoking. Age over 65 years and ICU admission were risk factors for death. Conclusions Older individuals and patients with underlying conditions are most at risk of influenza complications. Vaccination and early oseltamivir administration, both of which are recommended for these patients, appear to reduce ICU admissions

Subgroup analyses examine the effect of a treatment regimen on different subgroups in the overall population. If the subgroups are not comparable, differences between them cannot be attributed to the treatment alone, and analyses can only be considered as exploratory. When, however, strata are defined before randomization and subjects are randomly allocated to treatment groups within each stratum, analysis can be conducted within these subgroups and differences between them can be shown to be caused by the treatment. Intermediate analyses, by multiplying the number of statistical tests, increase the risk of rejecting the null hypothesis when it is in fact true. Accordingly, specific statistical methods should be used to compensate for this risk. Composite outcome criteria combine several different elements, all of which must be clinically relevant. Unequal treatments effects on the various criteria may complicate interpretation of the results.

Myocardial fibrosis has been proposed as an outcome predictor in asymptomatic patients with severe aortic stenosis (AS) that may lead to consider prophylactic surgery. It can be detected using MRI but its widespread use is limited and development of substitute biomarkers is highly desirable. We analysed the determinants and prognostic value of galectin-3, one promising biomarker linked to myocardial fibrosis.Patients with at least mild degenerative AS enrolled between 2006 and 2013 in two ongoing studies, COFRASA/GENERAC (COhorte Française de Rétrécissement Aortique du Sujet Agé/GENEtique du Rétrécissement Aortique), aiming at assessing the determinants of AS occurrence and progression, constituted our population.We prospectively enrolled 583 patients. The mean galectin-3 value was 14.3±5.6 ng/mL. There was no association between galectin-3 and functional status (p=0.55) or AS severity (p=0.58). Independent determinants of galectin-3 were age (p=0.0008), female gender (p=0.04), hypertension (p=0.002), diabetes (p=0.02), reduced left ventricular ejection fraction (p=0.01), diastolic dysfunction (E/e', p=0.02) and creatinine clearance (p0.0001). Among 330 asymptomatic patients at baseline, galectin-3 was neither predictive of outcome in univariate analysis (p=0.73), nor after adjustment for age, gender, rhythm, creatinine clearance and AS severity (p=0.66).In a prospective cohort of patients with a wide range of AS severity, galectin-3 was not associated with AS severity or functional status. Main determinants of galectin-3 were age, hypertension and renal function. Galectin-3 did not provide prognostic information on the occurrence of AS-related events. Our results do not support the use of galectin-3 in the decision-making process of asymptomatic patients with AS.COFRASA NCT00338676 and GENERAC CT00647088.

International audience; Background. During antibiotic treatments, antibiotics reach the colon and alter the microbiome, resulting in emergence and dissemination of resistant bacteria, antibiotic-associated diarrhea (AAD) and occurrence of Clostridium difficile (Cd) infections (CDI). We developed an oral adsorbent-based product, DAV132, to be co-administered with antibiotics in order to prevent these effects. We report here the results of protection of the microbiome in human volunteers treated with oral moxifloxacin (MOX), and protection against CDI in vitro in a human gut model (HGM) and in vivo in experimental hamsters.Methods. Four groups (MOX [400 mg OD for 5 days], MOX + DAV132 [7.5 g TID for 7 days], DAV132, or control) of healthy volunteers (n = 44) were included in a randomized clinical trial. Feces were collected at screening, daily from D1 to D9 and at D12, D16, D23, D30, D37 and plasma PK assayed at D1and5. Metagenomic analyses were done by shotgun sequencing at screening, D3, D6, D9, D16 and D37. The effect of DAV132 on MOX was also assessed in a HGM inoculated with Cd spores (ribotype 027, MOX MIC 32 mg/L); bacterial counts, toxin production and MOX concentrations were measured over time. MOX dosed hamsters were inoculated with 104 spores of a non-epidemic Cd (TcdA + , TcdB + , cdtB−) and treated ±DAV132. Mortality and Cd counts were assessed over time.Results. In humans, DAV132 was well tolerated and decreased free fecal MOX by > 99% compared to MOX alone: ratio of mean LogAUCD1-D16 = 0.0093 (95% CI 0.0061-0.0144), p = 0.03 × 10−16; MOX plasma PK was not changed significantly. Alterations of the fecal microbiome observed with MOX were prevented. In the HGM, DAV protected the microbiota and prevented Cd overgrowth and toxin production. Hamsters were fully protected by DAV against MOX-induced CDI (dose dependent), with decreased free fecal MOX and Cd counts.Conclusion. DAV132 protects humans against fecal microbiome disruption after oral MOX treatment, without altering its plasma PK. In vitro results in HGM and in vivo results in hamsters suggest that DAV132 should be protective against antibiotic-induced CDI. These results warrant further clinical development of DAV132 to protect the intestinal microbiota, and so prevent AAD and CDI, in patients receiving oral or parenteral antibiotics.

Infective endocarditis (IE) due to gram-negative bacilli (GNB) is rare. However, several studies described a change in the epidemiological profile of patients within the past few years.We reviewed all cases diagnosed and followed in the infectious diseases ward of a French teaching hospital in Paris between 2009 and 2014, inclusive.Among the 17 patients with definite GNB-IE (11 male, mean age 54 years), 12 (70%) were due to non-HACEK GNB and 5 (30%) to HACEK group GNB. A prosthetic valve was involved in 10 cases (8 in non-HACEK and 2 in HACEK group). Escherichia coli (4/12 patients) and Pseudomonas aeruginosa (3/12 patients) were the most common pathogens in the first group; all the pathogens in the second group were Haemophilus spp. One-third of the patients with non-HACEK GNB had nosocomial IE, whereas injection drug use-related infections were rare (2/12). All patients with HACEK infection had at least one complication (intracardiac abscess, stroke or other systemic embolization). All patients were treated by antibiotic combination therapy during a median time of 42 days (interquartile range (IQR) = 42-42) and 10 (59%) underwent cardiac surgery. One death at 9 months was observed in the non-HACEK group.Regarding HACEK IE, this report supports the frequent association with vascular complications. Regarding non-HACEK GNB IE, this report supports the increasing proportion of nosocomial infections. We reported a high proportion of surgery in the therapeutic management of both HACEK and non-HACEK groups associated with no in-hospital mortality.

Objectif Mesurer l’efficacite du vaccin grippal saisonnier dans la prevention de la grippe hospitalisee (saisons 2012-2013 et 2013-2014) chez l’adulte presentant une anomalie metabolique (diabete ou obesite). Patients et methodes Etude cas-temoins incidents conduite dans 6 hopitaux francais (Montpellier, Lyon, Cochin, Bichat, Limoges, Rennes) sur 848 adultes hospitalises avec syndrome grippal recent (debut ≤ 7 jours). Le virus grippal etait recherche par RT-PCR sur prelevement naso-pharynge ou LBA au centre national de reference de Lyon. Les cas etaient les patients avec une PCR positive pour le virus A et/ou B, les temoins ceux negatifs pour tout virus grippal. La vaccination contre la grippe saisonniere, la presence d’un diabete, d’une obesite ou d’une autre indication vaccinale etaient enregistrees. L’efficacite vaccinale (EV) a ete calculee selon la formule EV = 1 – OR, et ajustee sur l’âge, le sexe, et le nombre d’enfants au foyer. Resultats Un diabete (D) ou une obesite (O) etaient presents chez 286 sujets (D: 127 ; O: 89 ; D et O: 63), dont 85 (30 %) positifs pour la grippe. La couverture vaccinale etait de: D: 54 % ; D et O: 54 % ; O: 38 % ; autres: 44 % (p = 0,05). L’EV ajustee est de: – D ou O: 55 % (95 % CI 19 % ; 75 %) – D: 47 % (95 % CI – 4 % ; 73 %) – O: 63 % (95 % CI 8 % ; 85 %) L’EV ajustee variait selon le type ou le sous-type de virus grippal. Elle etait de 81 % (95 % IC: 38 ; 94) contre AH1N1 vs, 55 % (95 % IC: -18 ; 83) contre B, et 29 % (95 % IC: – 63 ; 69) contre AH3N2. Discussion Dans cette population, l’efficacite vaccinale sur la prevention des formes hospitalisee de grippe chez les sujets obeses ou diabetiques est similaire a celle retrouvee en population generale. La couverture vaccinale est plus faible chez les obeses, alors que l’efficacite vaccinale chez eux est au moins aussi bonne et que le vaccin n’est pas rembourse chez eux.

Growth chamber and orchard experiments were carried out to clarify the response of the cherry leaf spot pathogen, Blumeriella jaapii, and microorganisms in the leaf litter to two levels of urea (2.5% or 5%) applied post leaf fall to sour cherry leaves. In general, urea application reduced the development of B. jaapii measured as biomass by quantitative PTA-ELISA in the leaf litter and spore counting in the spring and increased the overall microbial biomass (measured with biomarker phospholipid fatty acids (PLFAs)) and fungal activity (assessed as β-N-acetylglucosaminidase activity). The biomass increase of all groups of microorganisms in the litter generally began immediately after application of urea and, with the notable excepts of B. jaapii and Gram-negative bacteria containing the biomarker PLFA cyclo17:0, continued after the ammonia and pH levels had stabilized to levels similar to the control leaves approximately 10 days later. Application of 2.5% urea increased the biomass of most groups of saprotrophic microorganisms and accelerated litter decomposition to a higher extent than application of 5% urea and during the first week after treatment applications the 5% urea level inhibited the total microbial biomass. This may be ascribed to ammonia toxicity as 5% urea resulted in a markedly higher ammonia elevation than 2.5% urea, the first week after application. From then onwards in both the 2.5% and 5% treatments the fungal and Gram-positive communities benefited from a lowered C:N ratio, increasing their activities approximately 2 times compared to a water-treated control. Inhibition of B. jaapii coincided with the period of urea breakdown in which elevated levels of ammonia and leaf pH were measured in the treated leaves. This period lasted for approximately 10 days after which the biomass of B. jaapii in the treated leaves continued to decrease at a slow but faster rate than in the untreated leaves. Our results indicate that the urea application caused an elevation in leaf pH and ammonia levels, which together with an acceleration in litter decomposition, adversely affected the saprotrophic growth of B. jaapii, leading to reduced production of ascospores and winter-conidia the following spring.

Infective endocarditis is a rare but severe disease, the incidence of which seems to have been stable over the past decades. Streptococci are the most frequent causative organisms. In France, infective endocarditis ranges from 25–30 cases/million inhabitants/year (about 1500 cases/year). The profile of patients presenting with infective endocarditis, though, is changing, with an increased proportion of elderly patients and a decrease of endocarditis due to oral streptococci. Valve surgery for endocarditis is performed in about one patient in two with a perioperative mortality that remains high. Since 1992, the date of the French consensus conference on the prophylaxis of infective endocarditis, new data have been published, requiring an update of its conclusions. These new data feature the following points: Consequently the working group suggests: This is the executive summary …

To study the respective roles of indinavir concentrations and treatment adherence as predictors of early virologic response, we analyzed the patients of the APROCO cohort treated by indinavir 800 mg TID during the first 4 months. Minimum (Cmin), maximum (Cmax), and the ratio of the measured to expected concentrations (CR) were estimated for each patient at M4, from a population pharmacokinetic analysis of all data. The relationship among virologic success at M4 [plasma HIV RNA (VL)

Immune reconstitution inflammatory syndrome (IRIS) occurred in 16 of 37 antiretroviral-naive patients who were treated subsequently for tuberculosis and human immunodeficiency virus (HIV) type 1 infection. IRIS was related to increases in the CD4 cell percentage and in the ratio of CD4 cells to CD8 cells after 1 month of antiretroviral therapy and to dissemination of tuberculosis. These results have implications for the diagnosis of IRIS and the understanding of its pathogenesis.

8 Unite ´ de Maladies Infectieuses et Tropicales, Hotel-Dieu, Nantes, France Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval (CI), 6.8-8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline charac- teristics, plasma human immunodeficiency virus RNA levels of 5l og 10 copies/mL (hazard ratio (HR), 1.5; 95% CI, 1.1-2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1- 1.2), creatinine clearance levels of !70 mL/min (HR, 2.1; 95% CI, 1.2-3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8-3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2-2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.

To describe characteristics of infective endocarditis (IE) in pacemaker (PM) recipients, including the annual incidence and exact localization of IE on PM leads, cardiac valves, or both, we prospectively analyzed 45 PM recipients from a group of 559 patients with definite IE who responded to a population-based survey conducted in France in 1999. Thirty-three patients had definite PM-lead IE (group I), and 12 had valvular IE without evidence of PM involvement (group II). The valvular structure was involved in almost two-thirds of IE cases among PM recipients. Of the 28 patients (62%) with valvular IE, 10 group I patients had tricuspid involvement, and 6 group I patients had left heart-valve involvement. The most frequent causative organisms in groups I and II were staphylococci (82%) and streptococci (50%), respectively. The incidence of age- and sex-standardized IE was 550 cases/million PM recipients per year. The incidence of IE with PM involvement is between that of valvular IE in the general population and prosthetic valve IE.

To evaluate factors associated with durable viral suppression (DVS), low viral rebound (virus load of 500-5000 copies/mL), and high viral rebound (virus load above 5000 copies/mL), we studied 3736 patients who achieved an undetectable virus load (i.e.

Background In a context of controversy about influenza antiviral treatments, this study assessed primary healthcare physicians’ prescription of neuraminidase inhibitors (NIs) in France during pandemic and seasonal influenza between 2009 and 2013. Methods This observational study, using data recorded in three national databases, estimated the rate of NI prescription among influenza-like illness (ILI) patients seen in GP and paediatrician consultations, and determined factors associated with this prescription according to a multivariate analysis. NI delivery by pharmacists was also evaluated. Results Rates of NI prescription were estimated to be 61.1% among ILI patients with a severe influenza risk factor seen in GP consultation during the A(H1N1)pdm2009 pandemic versus an average rate of 25.9% during the three following seasonal influenza epidemics. Factors associated with NI prescription were a chronic disease in patients under 65 years (OR 14.85; 95% CI 13.00, 16.97) and in those aged 65 and older (OR 7.54; 5.86, 9.70), an age ≥65 years in patients without chronic disease (OR 1.35; 1.04, 1.74), a pregnancy (OR 10.63; 7.67, 15.76), obesity (OR 4.67; 3.50, 6.22) and a consultation during the pandemic A(H1N1)pdm2009 (OR 3.19; 2.93, 3.48). The number of antiviral treatments delivered by pharmacists during the A(H1N1)pdm2009 pandemic was 835 per 100,000 inhabitants, and an average of 275 per 100,000 inhabitants during the three following seasonal influenza epidemics. Conclusions Although physicians seem to follow the recommended indications for NIs in primary health-care practice, this study confirms the low rate of NI prescription to ILI patients with a severe influenza risk factor, especially during seasonal epidemics.

International audience

The efficacy of an amprenavir (APV)-containing therapy without (group A) or with (group B) ritonavir was assessed in patients with failure of previous protease inhibitor therapy for human immunodeficiency virus (HIV) infection. The mean minimal plasma APV concentrations in groups A and B were 58 and 1,320 ng/ml, respectively, corresponding to APV inhibitory quotients of 0.2 (range, 0.03 to 0.70) and 7.0 (range, 1.4 to 145), respectively. At week 24, 2 of 8 and 13 of 14 patients in groups A and B, respectively, had

Objectives We aimed to evaluate and compare non-adherence to oral and inhaled antiviral therapies prescribed of a randomised clinical trial in outpatients with influenza A infection. Design A parallel, three-arm, double-blinded trial randomly allocated antiviral therapies twice daily for 5 days: (1) oral oseltamivir plus inhaled zanamivir (arm OZ); (2) oseltamivir plus inhaled placebo (arm Opz); or (3) oral placebo plus inhaled zanamivir (arm poZ). Analysis of non-adherence was a secondary objective of the trial. Settings Outpatients were enrolled by 145 general practitioners throughout France during the 2008–2009 seasonal influenza epidemics. Participants A total of 541 adults presenting with influenza-like illness for less than 36 hours. Primary outcomes Non-persistence, the time between inclusion and the last dose treated as a failure time, was used as the primary endpoint. Results The proportions of patients who persisted on treatment until the end of prescription were estimated at 85.73% (±3.28%) for the oral route and 82.73% (±3.44%) for the inhaled route. Based on multivariable models, non-persistence was associated with a PCR confirmation of influenza for both the oral (HR=0.54, p=0.010) and inhaled (HR=0.59, p=0.018) drugs and antibiotic coprescriptions (HR=2.07, p=0.007; and HR=1.88, p=0.017, respectively) and active combination treatment (HR=1.71, p=0.035; and HR=1.58, p=0.035, respectively). The hazard of non-persistence of the inhaled therapy was increased compared with that of the oral therapy (HR=1.23, p=0.043). Conclusion In addition to the clinical and virological profiles of influenza infection, non-persistence may have been influenced by an active combination and the route of administration. RCT registration number NCT00799760. This is a post-result analysis.

Background Infective endocarditis after Bentall operation is rare and its diagnosis may be difficult. Purpose We described clinical presentation, management, outcomes and the use of new imaging added in the 2015 European Society of Cardiology guidelines (18F-fluorodeoxyglucose positron emission tomography/computed tomography, radiolabelled white blood cell single-photon emission computed tomography/computed tomography and Cardiac computed tomography) in patient with infective endocarditis after Bentall. Methods We retrospectively identified all patients with definite infective endocarditis after Bentall hospitalized in a tertiary care centre in Paris, France between 2005 and 2016. Results Twenty patients were identified (Median age 61 years, 95% male). Most cases occurred more than twelve months after the Bentall procedure (65%). Ten patients had complications (mainly stroke). The most common pathogen was Staphylococcus aureus (45%). Lesions using echocardiography were observed at the aortic valve and/or tube level in 18 patients. The most frequent lesion was a peri-prosthetic abscess and peritubular thickening/collection. At least one new imaging testing was performed in 12 patients (60%). The diagnosis of definite infective endocarditis relied on the modified Duke criteria in 17 patients and on new imaging in 3 patients. Disagreement between the different new imaging tests was relatively common. Eighteen patients (90%) underwent surgery and 4 died during their hospital stay (20%). Conclusion Infective endocarditis after Bentall mainly occurred late after surgery and was due to S. aureus. New imaging was a useful adjunct in patients with non-definite infective endocarditis and should be integrated into clinical judgment. Mortality was high and surgery was a cornerstone of the management.

Despite effective highly active antiretroviral treatment, anal cancer incidence has recently strongly increased in HIV-infected population. Treatment strategy in HIV-infected patients does not differ from general population. HIV-infected patients treated by chemo-radiotherapy are exposed to high-grade toxicities and should be closely monitored to deliver the optimal treatment. Close collaboration between oncologist and infectiologist is highly recommended to adjust antiretroviral therapy if necessary.

The beneficial effect of achieving a sustained virological response (SVR) after antiviral treatment against hepatitis C virus is well established. However, it remains unclear whether unsuccessful treatment (non-SVR) also improves patient survival, especially in patients with advanced liver fibrosis. We retrospectively evaluated the incidence of death or liver transplantation in the 427 naive patients with a Child-Pugh score of A and advanced fibrosis newly admitted to the Hospital Beaujon between 2000 and 2010. Patients were followed for a median time of 5.5 years. The baseline characteristics of untreated ( n = 102) and treated ( n = 325) patients were largely similar, and there was no evidence of a bias of indication. Treated patients received a combination of interferon and ribavirin and had an SVR rate of 32%. The incidence of death or liver transplantation per 100 person-years was 1.00, 3.20, and 5.44 in SVR, non-SVR, and untreated patients, respectively. After adjusting for baseline characteristics, the risk of death or liver transplantation was significantly lower in SVR than in non-SVR patients and in non-SVR than in untreated patients (hazard ratios, 0.35 and 0.51, respectively; P = 0.019 and 0.038, respectively). The effect of treatment in non-SVR patients was higher in patients who had a virological or a biochemical response than in those who did not have a virological or a biochemical response. The risk of death or liver transplantation was significantly lower in treated than in untreated patients. Moreover, there was a gradient of mortality between patients with SVRs, virological or biochemical responders, and untreated patients, suggesting that treatment, even in the absence of viral eradication, has a beneficial effect on survival.

Aortic valve stenosis (AS) is a progressive disease, but the impact of baseline AS haemodynamic or anatomic severity on AS progression remains unclear.In 149 patients (104 mild AS, 36 moderate AS and 9 severe AS) enrolled in 2 ongoing prospective cohorts (COFRASA/GENERAC), we evaluated AS haemodynamic severity at baseline and yearly, thereafter, using echocardiography (mean pressure gradient (MPG)) and AS anatomic severity using CT (degree of aortic valve calcification (AVC)).After a mean follow-up of 2.9±1.0 years, mean MGP increased from 22±11 to 30±16 mm Hg (+3±3 mm Hg/year), and mean AVC from 1108±891 to 1640±1251 AU (arbitrary units) (+188±176 AU/year). Progression of AS was strongly related to baseline haemodynamic severity (+2±3 mm Hg/year in mild AS, +4±3 mm Hg/year in moderate AS and +5±5 mm Hg/year in severe AS (p=0.01)), and baseline haemodynamic severity was an independent predictor of haemodynamic progression (p=0.0003). Annualised haemodynamic and anatomic progression rates were significantly correlated (r=0.55, p0.0001), but AVC progression rate was also significantly associated with baseline haemodynamic severity (+141±133 AU/year in mild AS, +279±189 AU/year in moderate AS and +361±293 AU/year in severe AS, p0.0001), and both baseline MPG and baseline AVC were independent determinants of AVC progression (p0.0001).AS progressed faster with increasing haemodynamic or anatomic severity. Our results suggest that a medical strategy aimed at preventing AVC progression may be useful in all subsets of patients with AS including those with severe AS and support the recommended closer follow-up of patients with AS as AS severity increases.COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088).

International audience; Historically, infective endocarditis (IE) affected patients with predisposing cardiac conditions and community-acquired bacteremia. Over the past 30 years, significant changes have occurred, regarding microorganisms, underlying valvular heart diseases, portals of entry, and patients' comorbidities. Given these epidemiological changes and unproven prophylaxis efficacy, experts in most countries currently limit antibiotic indications to patients with high-risk cardiac conditions having oral procedures and, in the UK, recommend discontinuing their use altogether. To date, no epidemiological impact on streptococcal IE incidence has been observed. Policy must now address these epidemiological modifications, focus on community-acquired and health care-associated staphylococcal bacteremia prevention, and prompt the adoption of broader and nonexclusively antibiotic-based strategies.

OBJECTIVE: To report the first 6 months of experience of a nongovernmental-organization-managed obstetric care unit in a war refugee camp with problems encountered and solutions implemented. DESIGN: Prospective observational study of the maternity activity of Gynecologie Sans Frontieres (GSF). SETTING: GSFs maternity unit in Zaatari camp (Jordan). POPULATION: All pregnant women among Syrian refugees who came to the unit for delivery. METHODS: The GSFs maternity unit is a light structure built with three tents permitting low-risk pregnancy care and childbirth. Emergency cesarean deliveries were performed in the Moroccan army field hospital. High-risk pregnancies were transferred to Al Mafraq or Amman Hospital (Jordan) after assessment. MAIN OUTCOME MEASURES: Delivery characteristics indications for referral. RESULTS: From September 2012 to February 2013 371 women attended the unit and 299 delivered in it. Delivery rates increased from 5/month to 112/month over the period. Mean gestational age at birth was 39(+3) gestational weeks (SD = 1.9). Median birthweight was 3100 g (25-75% interquartile range 2840-3430 g). Spontaneous vaginal deliveries were dominant and the major maternal complication was postpartum hemorrhage (n = 13). Eighty-two women were referred to Al Mafraq or Amman hospitals mainly for preterm labor (32%) and congenital malformations (11%). We managed one case of stillbirth. Maternal mortality did not occur. CONCLUSIONS: Despite the difficulties of war high-risk pregnant women were properly identified permitting referrals when required. Cooperation with other nongovernmental organizations including the United Nations High Commissioner for Refugees was essential for the management of situations at risk of complications and to contain perinatal and maternal mortality. (c) 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Anaemia is frequent in critically ill patients. Iron deficiency, secondary to blood losses or prior to admission, is in part responsible for this anaemia. Iron may thus be proposed to critically ill patients (CI). However, iron may promote oxidative stress, which is potentially deleterious. In a mouse model, we previously demonstrated that iron induces less oxidative stress in inflamed mice than in control ones [1], but no data are available in the CI.

Objective Whether sex-related differences in the prognosis of infective endocarditis (IE) are due to differences in disease severity or comorbid patterns, physiological specificities or a treatment indication bias is unclear. We conducted an analysis of the pooled database of two population-based cohorts of IE to reassess the relationships between sex, early valve surgery (EVS) and outcome in patients with IE. Methods Demographic and baseline characteristics, complications and outcome were compared in men and women with Duke-definite left-sided IE. A propensity model for EVS was constructed using multivariate logistic regression. Factors associated with 1-year mortality were identified using multivariate Cox models adjusted for EVS factors. Results The study population included 466 (75%) men and 154 (25%) women. Compared with men, women were older (p=0.005), were more often on haemodialysis (p=0.04), more often had a mitral valve IE (50.0% vs 35.8%, p=0.02), less often developed a septic shock (p=0.05), less often underwent EVS (p=0.001) yet had comparable inhospital mortality rates (20.1% vs 20.0%, p=0.96) and similar 1-year survival probability (logrank p=0.68). Female sex was neither associated with EVS (OR 0.76 (95% CI 0.49 to 1.16)) nor mortality (HR 1.17 (95% CI 0.80 to 1.69)). However EVS was associated with an increased risk of death in women in the early postoperative period (HR 8.72 (95% CI 3.42 to 22.24), p= Conclusions Women underwent EVS less often than men. However female sex was independently associated with neither EVS nor 1-year mortality. The reasons for a higher risk of early postoperative mortality in women must still be elucidated.

Background There are very few studies on the incidence and risk factors of hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) in the absence of advanced fibrosis. Our objective was to identify the clinical–pathological features of these patients. Methods We retrospectively reviewed 162 patients admitted to our hospital for HCV-related HCC between 2000 and 2010. Patients with hepatitis of other aetiologies, human immunodeficiency virus co-infection, or treated with interferon were excluded. We compared demographic, laboratory, clinical and outcome parameters of patients with and without advanced fibrosis. Results 137 patients had advanced fibrosis (85%). Median age was higher in the advanced fibrosis vs. the non-advanced fibrosis group (62 vs. 65 years, respectively; p = 0.025). Steatosis was significantly more frequent in patients with advanced fibrosis compared to those without advanced fibrosis (43% vs. 20%, respectively; p = 0.032). Independent predictors associated to the occurrence of HCC in patients without advanced fibrosis were hepatitis B core antigen (odds ratio: 3.86; p = 0.044) and duration of hepatitis C infection (odds ratio: 1.21; p = 0.003). Conclusions Risk factors such as steatosis or diabetes were not frequent in patients without advanced fibrosis. Further studies are needed to evaluate the role of occult hepatitis B and the duration of hepatitis infection in patients with HCC and chronic hepatitis C without advanced fibrosis.

Background Legionellosis is a life-threatening disease. The clinical superiority of quinolones or macrolides for treating patients with legionellosis has not been established. Methods We performed a systematic review and meta-analysis of studies reporting data that allowed the comparison of quinolones versus macrolides in the treatment of proven legionellosis published from 1 January 1985 to 31 January 2013. We collected baseline aggregate patient characteristics. Studied outcomes included mortality, clinical cure, time to apyrexia, length of hospital stay and occurrence of complications in each treatment group. Treatment effect was assessed using a Mantel-Haenszel random effects model. Results Among 1005 abstracts reviewed, 12 studies were selected (n=879 patients). No randomized controlled trial was performed directly comparing quinolone and macrolide efficacy in legionellosis. Mean age was 58.3 years, 27.7% were women and Fine score was ≥ 4 in 35.8%. Among 253 patients who received quinolone monotherapy, 10 died (4.0%). Among 211 patients who received macrolide monotherapy, 23 died (10.9%). The pooled OR of death for treatment with a quinolone versus a macrolide was 0.5 (95% CI 0.2-1.3, n=8 studies, 464 patients). Length of stay was significantly shorter in the quinolone monotherapy group. The difference was 3.0 days (95% CI 0.7-5.3, P=0.001, n=3 studies, 263 patients). Neither of two tests for heterogeneity was significant (I (2)=0% for both, P=1). Other studied outcomes were not significantly different among treatment groups. Conclusions Few clinical data on legionellosis treatment are available. This first meta-analysis showed a trend toward a lower mortality rate and a significant decrease in length of hospital stay among patients receiving quinolones. These results must be confirmed by a randomized controlled trial.

Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. We assessed the impact of linezolid on the microbiota and the emergence of resistance and investigated its relationship with plasma pharmacokinetics of the antibiotic. Twenty-eight patients were treated for the first time with linezolid administered orally ( n = 17) or parenterally ( n = 11) at 600 mg twice a day. Linezolid plasma pharmacokinetic analysis was performed on day 7. Colonization by fecal enterococci, pharyngeal streptococci, and nasal staphylococci were assessed using selective media with or without supplemental linezolid. The resistance to linezolid was characterized. The treatment led to a decrease of enterococci, staphylococci, and streptococci in the fecal ( P = 0.03), nasal, and pharyngeal ( P < 0.01) microbiotas. The appearance of resistant strains was observed only in enterococci from the fecal microbiota between the 7th and 21st days of treatment in four patients (14.3%). The resistance was mainly due for the first time to the mutation G2447T in the 23S rRNA gene. No pharmacokinetic parameters were significantly different between the patients, regardless of the appearance of resistance. The emergence of linezolid resistance during treatment was observed only in the intestinal microbiota and unrelated to pharmacokinetic parameters. However, colonization by Gram-positive bacteria was reduced as a result of treatment in all microbiotas.

Objectif Evaluer le lien entre survenue de complications et pathologies metaboliques (diabete ou obesite) chez les patients hospitalises avec syndrome grippal recent (saisons 2012-2013 et 2013-2014). Patients et methodes Etude conduite dans 6 hopitaux francais (Montpellier, Lyon, Cochin, Bichat, Limoges, Rennes) sur 848 adultes hospitalises avec syndrome grippal recent (debut ≤ 7 jours), defini par l’association d’un signe respiratoire (toux, dyspnee) et d’un signe systemique (fievre, cephalees, malaise, myalgies). Le virus grippal etait recherche par RT-PCR sur prelevement nasopharynge ou LBA au centre national de reference de Lyon. La vaccination contre la grippe saisonniere, la presence d’un diabete ou d’une obesite, les complications survenues au cours de l’hospitalisation (insuffisance renale, cardiaque, respiratoire, pneumonie, deces) et la duree moyenne de sejour (DMS) etaient enregistrees. Le risque de complications a ete etudie par regression logistique multivariee ajustee sur âge, sexe, infection grippale, vaccination, dia-bete et obesite. Resultats Un diabete (D) ou une obesite (O) etaient presents chez 286 sujets (D: 127 ; O: 89 ; D et O: 63). Les diabetiques etaient plus âges (D: 71 ± 17 ; O: 61 ± 18 ; D et O: 69 ± 12 ; autres: 65 ± 20 ans, p = 0,001) et presentaient plus souvent une insuffisance renale (D: 17 % ; O: 9 % ; D et O: 24 % ; autres: 7 %,p < 0,0001) ou cardiaque (D: 16 % ; O: 10 % ; D et O: 27 % ; autres: 10 %, p = 0,001). En analyse multivariee, le risque d’insuffisance renale etait lie au diabete (OR 2,57 ; 95 % CI: 1,55-2,48, p < 0,001) avec une tendance pour l’obesite (OR 1,73 ; 95 % CI: 0,99-3,03, p = 0,056). Le risque d’insuffisance cardiaque etait lie a l’obesite (OR 1,76 ; 95 % CI: 1,04-3,00, p = 0,03) avec une tendance pour le diabete (OR 1,55 ; 95 % CI: 0,99-2,51, p = 0,07). Le risque d’insuffisance respiratoire, le deces et la DMS n’etaient pas influences par les pathologies metaboliques. Conclusion Le diabete et l’obesite semblent etre des facteurs de complications renales et cardiaques, mais pas respiratoires, chez les patients hospitalises avec syndrome grippal.

Adsorbing increasing amounts of methane (CH 4 ) at 80 K on graphite preplated with one monolayer of dichloromethane (CH 2 Cl 2 ) results in a succession of transitions: partial displacement of the preadsorbed film and replacement by a CH 4 monolayer; incorporation of CH 4 in the remaining CH 2 Cl 2 patches so as to form a 2D solution: alternate layer-by-layer condensation on the resulting dual surface. When CH 2 Cl 2 preplating is in the submonolayer range, CH 4 monolayer condensation occurs first on the bare part of the surface. When the graphite surface is saturated with CH 2 Cl 2 the displacement is suppressed.

OBJECTIVES Quinolone-resistant Escherichia coli (QREC) primarily emerge in commensal bacteria under selective pressure. The aim of this work was to investigate the characteristics of QREC from the faecal microbiota after quinolone exposure, as they remain largely unknown. METHODS Forty-eight healthy volunteers received ciprofloxacin from day 1 to day 14. QREC were detected in stools from 14 subjects at day 42. QREC were compared in terms of genetic background, metabolic properties, stress resistance and intestinal colonization abilities with quinolone-susceptible E. coli (QSEC) from the same 14 individuals and from 29 volunteers who remained QREC-free. RESULTS QREC always belonged to a single clone for a given volunteer and to restricted phylogenetic groups. QREC carried significantly more iron capture systems than QSEC. Maximum growth rates in minimal medium with gluconate, general stress regulator RpoS activity assessed by iodine staining and resistance to oxidative and acid stresses were significantly higher for QREC than for QSEC. In a mouse colonization model, QREC efficiently colonized the intestine microbiota despite the presence of QSEC competitors. At day 42, QREC and QSEC faecal counts from the 14 volunteers were comparable except in three subjects where only QREC could be detected. CONCLUSIONS These results suggest that QREC do not have a fitness cost, probably as a result of genetic co-selection, but are highly adapted to a commensal lifestyle. They may not be eliminated easily from the faecal microbiota from healthy subjects once selected.

Pandemic influenza vaccine manufacturing capacity and distribution agility is enhanced through the availability of equivalent antigen-sparing vaccines. We evaluated equivalence in terms of immunogenicity between GlaxoSmithKline Vaccines’ A/California/7/2009 (H1N1)v-like-AS03 vaccines manufactured in Dresden (D-Pan), and Quebec (Q-Pan). In two studies, 334 adults 18-60 years of age received 2 doses of D-Pan or Q-Pan containing 3.75 μg haemagglutinin antigen (HA) adjuvanted with AS03A administered 21 days apart, and 209 children 3-9 years of age received 1 reduced dose of D-Panor Q-Pan (0.9 μg HA) or Q-Pan (1.9 μg HA) with AS03B. Haemagglutination inhibition (HI) titres were assessed before and 21 days post-vaccination. HI persistence was assessed after 12 months in adults and 6 months in children. Pre-defined criteria for immunological equivalence of Q-Pan versus D-Pan were achieved in both populations. After one vaccine dose, ≥97.6% of adults and children had HI titres ≥1:40, with increases in titre ≥25.7-fold. CHMP and CBER regulatory acceptance criteria for influenza vaccines were exceeded by all groups in both studies at Day 21. In adults,the percentage with HI titres ≥1:40 at Month 12 was 82.9% (Q-Pan) and 84.0% (D-Pan). In children, the percentages at Month 6 were 75.3.3% (Q-Pan0.9), 85.1% (D-Pan0.9) and 79.3% (Q-Pan1.9). Safety profile of the study vaccines was consistent with previously published data. Two studies indicate that A/California/7/2009 (H1N1)v-like HA manufactured at two sites and combined with AS03 are equivalent in terms of immunogenicity in adults and children and highly immunogenic. Different HA doses elicited an adequate immune response through 180 days post-vaccination in children 3-9 years of age. ClinicalTrials.gov: NCT00979407 and NCT01161160 .

International audience; The proportion of group D streptococcal infective endocarditis (IE) (predominantly due to Streptococcus gallolyticus) and the incidence of colorectal cancer are higher in France than in most European countries. We assumed that this could be explained by a high group D streptococci (GDS) fecal carriage rate. The aims of this study were to re-assess the GDS fecal carriage rate in France and its relationship with colorectal cancer. Consecutive adult subjects who were to undergo a complete colonoscopy were invited to participate. GDS were searched in subjects' stools before their colonoscopy using biomolecular techniques. Colonoscopic findings were sorted into four subgroups: normal colonoscopy, non-tumoral lesions, benign tumors, and premalignant/malignant tumors. GDS fecal carriages were calculated overall and in each subgroup and compared. The data from 259 subjects were analyzed. GDS were identified in the feces of 12 subjects, with the following distribution: S. lutetiensis (n = 9), S. pasteurianus (n = 2), and S. gallolyticus (n = 1). This accounted for an overall GDS fecal carriage rate of 4.6 %. The GDS fecal carriage rate was 6 % in case of normal colonoscopy, 1.3 % in case of non-tumoral lesions, 3.2 % in case of benign tumors, and 11 % in case of premalignant/malignant tumors. These four percentages were not statistically different. The GDS fecal carriage rate was lower than expected, which did not confirm our working hypothesis. Most strains belonged to S. bovis biotype II, while S. gallolyticus was found only once. These findings suggest that different GDS play different roles in the etiopathogenesis of IE and colorectal cancer.

BACKGROUND AND PURPOSE: Neurologic complications in infective endocarditis are frequent and affect patient prognosis negatively. Additionally, detection of asymptomatic lesions by MR imaging could help early management of this condition. The objective of our study was to describe MR imaging characteristics of cerebral lesions in a neurologically asymptomatic population with infective endocarditis. MATERIALS AND METHODS: One hundred nine patients at the acute phase of a definite or possible infective endocarditis according to the Duke modified criteria and without neurologic manifestations according to the NIHSS were prospectively included. Each patient underwent cerebral MR imaging and MRA within 7 days of admission. RESULTS: MR imaging showed abnormalities in 78 patients (71.5%). Acute ischemic lesions (40 patients, 37%) and cerebral microbleeds (62 patients, 57%) were the most frequent lesions. Eight patients had an acute SAH, 3 patients had brain microabscesses, 3 had a small cortical hemorrhage, and 3 had a mycotic aneurysm. Acute ischemic lesions mostly appeared as multiple small infarcts disseminated in watershed territories (25/40, 62.5%) and as lesions of different ages (21/40, 52.5%). Cerebral microbleeds were preferentially distributed in cortical areas (362/539 cerebral microbleeds, 67%). No significant correlation was found among lesions, in particular between acute ischemia and cerebral microbleeds. CONCLUSIONS: Occult cerebral lesions, in particular cerebral microbleeds and acute ischemic lesions, are frequent in infective endocarditis. The MR imaging pattern of acute small infarcts of different ages predominating in watershed territories and cortical cerebral microbleeds may represent a surrogate imaging marker of infective endocarditis.

Infective endocarditis (IE) mimics primary systemic vasculitis, and there are sporadic reports of positivity for antineutrophil cytoplasmic antibodies (ANCAs) among patients with IE. Because the frequency of ANCAs in IE is unknown, this study was undertaken to assess the seroprevalence of ANCAs in a large number of patients with IE.The study was conducted in the framework of a single-center prospective cohort study of incident IE cases. Demographic, clinical, laboratory, and microbiologic data were collected, and magnetic resonance imaging of the brain was performed at diagnosis. For those patients whose serum had been stored at diagnosis, ANCAs were assessed by indirect immunofluorescence assay in ethanol-, formalin-, and methanol-fixed neutrophils. In addition, ANCA specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) was assessed by enzyme-linked immunosorbent assay. Rheumatoid factor (RF), antinuclear antibodies (ANAs), anticardiolipin antibodies (aCL), and serum Ig levels were also measured. Comparisons between groups were made using Wilcoxon's rank sum and chi-square or Fisher's exact tests.Among 109 patients with IE, 18% had cytoplasmic ANCAs (cANCA) and/or perinuclear ANCAs (pANCA) and 8% had PR3-ANCAs or MPO-ANCAs, some with very high titers. Positivity for both cANCA or pANCA and PR3-ANCAs or MPO-ANCAs was found in 6% of patients, and RF, ANAs, and aCL were detected in 35%, 16%, and 23% of samples, respectively. No consistent clinical pattern of IE was observed in the anti-PR3/anti-MPO-positive IE patients, whereas positivity for cANCA/pANCA was associated with younger age (P = 0.022), more frequent occurrence of echocardiographic vegetations (P = 0.043), and above-normal serum IgG levels (P = 0.017).ANCAs, including PR3- and MPO-ANCAs, occur in a substantial proportion of patients with IE. The link between cANCA/pANCA and specific features of IE requires further study.

Objective To analyze the level of agreement between recommendations on preventive services developed by Canada, France and the USA. Methods We gathered recommendations on primary and secondary preventive services to adults up to November 3rd, 2011 from Canadian and US Task Forces, and equivalent French agencies. We excluded recommendations on immunization, long-term diseases or pregnancy. Results Among 250 recommendations, 84 (34%) issued by a single country could not be compared; 43 (26%) of the remaining 166 were in strong agreement (strictly identical grades between advising countries); 25 of 43 resulted in a proposal to be implemented in clinical practice, two others not to be implemented in clinical practice and 16 were indeterminate about implementation. Strong agreement was more frequent for recommendations concerning history-taking and physical examination than for those concerning interventions (odds ratio (OR) = 11.3, 95%CI: 1.6–241.2; p = 0.04), and for recommendations concerning a high-risk population than for those concerning the general population (OR = 3.1, 95%CI: 1.4–7.0; p = 0.006). Agreement did not differ either according to maximum time range between recommendations' publication or according to the advising country. Conclusion Agreement between recommendations is low particularly on those concerning non-clinical preventive services or non-high-risk individuals.

The adherence profile of HIV-infected patients predicts the therapeutic outcome, in particular during the early phase of antiretroviral therapy (ART). We conducted a prospective observational multicenter trial monitoring adherence and virological and immunological parameters over the initial 6 months of treatment. Thirty-five subjects were starting a treatment regimen including atazanavir, ritonavir, and emtricitabine-tenofovir. Adherence was assessed using self-completed questionnaires, announced pill counts, and the medication event monitoring system (MEMS) for each drug. Three MEMS measures were defined: the percentages of doses taken, days with the correct dosing, and doses taken on time (±3 h). Dynamic virological suppression (DVS) was defined as a reduction in the plasma HIV-RNA level of >1 log 10 per month or P < 0.03) and timing compliance (−1.60% per 4-week period, P < 0.003) decreased significantly over time. The MEMS-defined adherence data were concordant with the pill counts during the trial but not with the data from the questionnaires. The median [range] percentages of doses taken (100% [50 to 102]), days with the correct dosing (95% [41 to 100]), and doses taken on time (86% [32 to 100]) were significantly associated with DVS in separate models. Among these three measures, the percentage of doses taken on time had the greatest ability to predict DVS. Timing compliance should be supported to optimize DVS during the early phase of treatment by once-daily boosted protease inhibitor-based ART. (This study has been registered at ClinicalTrials.gov under registration no. NCT00528060.)

BackgroundInfluenza vaccination strategies aim at protecting high-risk population from severe outcomes. Estimating the effectiveness of seasonal vaccines against influenza related hospitalisation is important to guide these strategies. Large sample size is needed to have precise estimate of influenza vaccine effectiveness (IVE) against severe outcomes. We assessed the feasibility of measuring seasonal IVE against hospitalisation with laboratory confirmed influenza through a network of 21 hospitals in the European Union.MethodsWe conducted a multicentre study in France (seven hospitals), Italy (one hospital), and Navarra (four hospitals) and Valencia (nine hospitals) regions in Spain. All ≥18 years hospitalised patients presenting an influenza-like illness within seven days were swabbed. Cases were patients RT-PCR positive for influenza A (H3N2); controls were patients negative for any influenza virus. Using logistic regression with study site as a fixed effect we calculated IVE adjusted for potential confounders. We restricted the analyses to those swabbed within four days.ResultsWe included, 375 A(H3N2) cases and 770 controls. The overall adjusted IVE was 24.9% (95%CI-1.8;44.6). Among the target group for vaccination (N = 1058) the adjusted IVE was 28.8% (95%CI:2.8;47.9); it was respectively 36.8% (95%CI:-48.8; 73.1), 42.6% (95%CI:-16.5;71.7), 17.8%(95%CI:-40.8; 52.1) and 37.5% (95%CI:-22.8;68.2) in the age groups 18-64, 65-74, 75-84 and more than 84 years.DiscussionEstimation of IVE based on the pooling of data obtained through a European network of hospitals was feasible. Our results suggest a low IVE against hospitalised confirmed influenza in 2011-12. The low IVE may be explained by a poor immune response in the high-risk population, imperfect match between vaccine and circulating strain or waning immunity due to a late season. Increased sample size within this network would allow more precise estimates and stratification of the IVE by time since vaccination and vaccine types or brands.