European intensive care physicians’ experience of infections due to antibiotic-resistant bacteria

Background Antimicrobial resistance (AMR) compromises the treatment of patients with serious infections in intensive care units (ICUs), and intensive care physicians are increasingly facing patients with bacterial infections with limited or no adequate therapeutic options. A survey was conducted to assess the intensive care physicians' perception of the AMR situation in the European Union/European Economic Area (EU/EEA). Methods Between May and July 2017, physicians working in European ICUs were invited to complete an online questionnaire hosted by the European Society of Intensive Care Medicine. The survey included 20 questions on hospital and ICU characteristics, frequency of infections with multidrug-resistant (MDR) bacteria and relevance of AMR in the respondent's ICU, management of antimicrobial treatment as well as the use of last-line antibiotics in the six months preceding the survey. For the analysis of regional differences, EU/EEA countries were grouped into the four sub-regions of Eastern, Northern, Southern and Western Europe. Results Overall, 1062 responses from four European sub-regions were analysed. Infections with MDR bacteria in their ICU were rated as a major problem by 257 (24.2%), moderate problem by 360 (33.9%) and minor problem by 391 (36.8%) respondents. Third-generation cephalosporin-resistant Enterobacteriaceae were the most frequently encountered MDR bacteria followed by, in order of decreasing frequency, meticillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and vancomycin-resistant enterococci. Perception of the relevance of the AMR problem and the frequency of specific MDR bacteria varied by European sub-region. Bacteria resistant to all or almost all available antibiotics were encountered by 132 (12.4%) respondents. Many physicians reported not having access to specific last-line antibiotics. Conclusions The percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies. The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern

The microRNA Signature in Response to Insulin Reveals Its Implication in the Transcriptional Action of Insulin in Human Skeletal Muscle and the Role of a Sterol Regulatory Element–Binding Protein-1c/Myocyte Enhancer Factor 2C Pathway

International audienceOBJECTIVE: Factors governing microRNA expressions in response to changes of cellular environment are still largely unknown. Our aim was to determine whether insulin, the major hormone controlling whole-body energy homeostasis, is involved in the regulation of microRNA expressions in human skeletal muscle. RESEARCH DESIGN AND METHODS: We carried out comparative microRNA (miRNA) expression profiles in human skeletal muscle biopsies before and after a 3-h euglycemic-hyperinsulinemic clamp, with TaqMan low-density arrays. Then, using DNA microarrays, we determined the response to insulin of the miRNA putative target genes in order to determine their role in the transcriptional action of insulin. We further characterized the mechanism of action of insulin on two representative miRNAs, miR-1 and miR-133a, in human muscle cells. RESULTS: Insulin downregulated the expressions of 39 distinct miRNAs in human skeletal muscle. Their potential target mRNAs coded for proteins that were mainly involved in insulin signaling and ubiquitination-mediated proteolysis. Bioinformatic analysis suggested that combinations of different downregulated miRNAs worked in concert to regulate gene expressions in response to insulin. We further demonstrated that sterol regulatory element-binding protein (SREBP)-1c and myocyte enhancer factor 2C were involved in the effect of insulin on miR-1 and miR-133a expression. Interestingly, we found an impaired regulation of miRNAs by insulin in the skeletal muscle of type 2 diabetic patients, likely as consequences of altered SREBP-1c activation. CONCLUSIONS: This work demonstrates a new role of insulin in the regulation of miRNAs in human skeletal muscle and suggests a possible implication of these new modulators in insulin resistance

Influenza transmissibility among patients and health-care professionals in a geriatric short-stay unit using individual contact data

International audienceDetailed information are lacking on influenza transmissibility in hospital although clusters are regularly reported. In this pilot study, our goal was to estimate the transmission rate of H3N2 2012-influenza, among patients and health care professionals in a short-term Acute Care for the Elderly Unit by using a stochastic approach and a simple susceptible-exposed-infectious-removed model. Transmission parameters were derived from documented individual contact data collected by Radio Frequency IDentification technology at the epidemic peak. From our model, nurses appeared to transmit infection to a patient more frequently with a transmission rate of 1.04 per day on average compared to 0.38 from medical doctors. This transmission rate was 0.34 between nurses. These results, even obtained in this specific context, might give a relevant insight of the influenza dynamics in hospitals and will help to improve and to target control measures for preventing nosocomial transmission of influenza. The investigation of nosocomial transmission of SARS-COV-2 might gain from similar approaches

ITPA Activity in Adults and Children Treated With or Without Azathioprine: Relationship Between TPMT Activity, Thiopurine Metabolites, and Co-medications

International audienceBACKGROUND: The implication of inosine triphosphate pyrophosphatase (ITPA) on thiopurine drug response variability has been investigated but little data are available on its role on thiopurine metabolites. The ability of ITPA to modify the thiopurine metabolite levels is currently used to optimize azathioprine (AZA) therapy in relation to thiopurine S-methyltransferase (TPMT) activity, the aim of this study is to investigate ITPA phenotype in a large population and to evaluate the relation between ITPA and TPMT activities and thiopurine metabolites. METHODS: ITPA activity was determined in 183 adults and 138 children with or without AZA therapy. 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine nucleotides (6-MeMPN) levels, and ITPA as well as TPMT activities were measured in red blood cells. Using the Gaussian mixture model, distribution of ITPA activity was evaluated. Intraindividual variability and influence of age, sex, AZA treatment and associated co-medications on ITPA activity were also assessed. RESULTS: This retrospective study shows a quadrimodal distribution in ITPA activity. No influence of age, sex, AZA therapy, and co-medications was found. In adults, ITPA activity was not significantly associated with 6-TGN or 6-MeMPN concentrations, whereas a weak negative correlation was observed with 6-MeMPN levels in pediatric populations (rs = -0.261; P = 0.024). A weak positive correlation was observed between ITPA and TPMT activities in children (rs = 0.289; P = 0.001). CONCLUSIONS: ITPA activity was poorly influenced by nongenetic parameters and has no influence on 6-TGN and 6-MeMPN concentrations in adults and only a weak correlation with 6-MeMPN and TPMT activity in children. These results demonstrate that ITPA is not a rate-limiting enzyme in the formation of 6-TGN but suggest that a decrease in ITPA activity in children may be a risk factor for accumulation of 6-MeMPN in cells

Tensile Bond Strengths of Two Adhesives on Irradiated and Nonirradiated Human Dentin

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Treatment for behavioral insomnia in young children with neurotypical development under 6 years of age: A systematic review

International audienceThis literature review examines all treatments for behavioral insomnia in children under 6 years of age todetermine which treatments have empirically demonstrated efficacy. Following PRISMA guidelines, three databases were investigated (Pubmed, Cochrane and Psychinfo) to select randomized controlled trials (RCTs) whichassess treatments for behavioral insomnia in children under 6 years of age, all with neurotypical development. Atotal of 908 articles met the search criteria. 21 articles were selected and analyzed in their entirety for a total of2363 children (ranging from 2 months to 6 years of age). Based on these studies, treatment of behavioralinsomnia in young children under 6 years of age is primarily based on behavioral therapy. There is no evidencethat pharmacological treatments are effective in the long term for neurotypical children. This review highlightsthe lack of RCTs in this field: new RCTs should be carried out among young children to refine and optimize thetherapeutic approach and to address the risk of therapeutic abuse through the use of non-scientifically validatedmethods

Approches d’apprentissage et réussite en première année commune des études de santé (PACES) en France

Contexte : Mise en place en France en septembre 2010, la Première Année Commune des Etudes de Santé (PACES) est caractérisée par un enseignement de masse, un concours très sélectif et une grande quantité d’information à mémoriser. Dans ce contexte très particulier, nous avons, pour la première fois, déterminé les approches d’apprentissage spécifiquement adoptées par les étudiants et étudié leur impact sur la réussite au concours. Matériel et méthodes : Une version française du questionnaire R-SPQ-2F de Biggs a été administrée aux étudiants de PACES 2011-2012 avant les partiels en décembre. Les approches d’apprentissage spécifiques ont été déterminées après analyse factorielle exploratoire du R-SPQ-2F et sélection des items pertinents dans ce contexte. L’association entre les approches et la bonne réussite aux partiels a été étudiée par un modèle de régression binomiale. Résultats : Au total, 1977 étudiants sont inclus dans l’analyse. Les étudiants qui ont le plus de chance de réussir sont i) ceux qui s’intéressent à leurs études (risque relatif (RR) de réussite de 1,5) et ii) ceux qui se limitent au contenu du cours (approche de surface, RR = 1,4). Les étudiants qui apprennent par cœur (approche de surface) ont 1,6 plus de risque d’échouer que les autres. Conclusion : Ce concours de PACES très sélectif et très stressant a pour effet d’encourager une certaine approche de surface très forte en vue de la réussite au concours au détriment d’une approche plus en profondeur indispensable à une formation solide

ITPA Activity in Children Treated by Azathioprine: Relationship to the Occurrence of Adverse Drug Reactions and Inflammatory Response

International audienceAzathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological diseases such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reactions (ADRs) and drug response is observed. This study investigated (i) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, and (ii) the relationship between ITPA activity and the inflammatory activity observed in children with IBD. ITPA and TPMT activities were determined in 106 children with immunological disease on AZA therapy. Markers of hepatotoxicity, myelotoxicity, pancreatitis and inflammation as well as clinical information were retrospectively collected during regular medical visits. No significant association was found between ITPA activity and hepatotoxicity or clinical ADRs such as cutaneous reactions, arthralgia, flulike symptoms and gastrointestinal disorders. Concerning myelotoxicity, a significant relation was observed between ITPA activity and RBC mean corpuscular volume (MCV; p=0.003). This observation may be related to the significant relationship found between high ITPA activity and the increase in -globulin level reflecting inflammation (p=0.005). In our study, ITPA activity was not associated with occurrence of ADRs, but a relationship between high ITPA activity and -globulin, a marker of inflammation, was found in children with IBD. Therefore, measurement of ITPA activity may help to identify children with IBD predisposed to residual inflammation on AZA therapy. Further prospective studies are needed to confirm this result

Development and Cross-National Validation of a French Version of the Jefferson Scale of Empathy for Students

Empathy is a multifaceted personal ability combining emotional and cognitive features modulated by cultural specificities. It is widely recognized as a key clinical competence that should be valued during professional training. The Jefferson Scale of Empathy for medical students (JSE-S) has been developed for this purpose and validated in several languages, but not in French. The aims of this study were to gather validity evidence for a newly developed version of the JSE-S and compare it between two French-speaking contexts. In total, 1,433 undergraduate medical students from the universities of Lyon (UL), France and Geneva (UG), Switzerland participated in the study completing the JSE-S in French. Total and partial scores of the three subscales (“perspective taking,” “compassionate care” and “walking in patient's shoes”) were calculated for each site. Construct validity of the JSE-S was analyzed considering three sources of evidence: content, internal structure and relations to other variables. A first-order Confirmatory Factor Analysis using structural equation modeling examined the three latent variables of the JSE-S subscales. Cronbach's α coefficients were 0.75 (UG) and 0.81 (UL). The items' discrimination power ranged between 0.29 and 1.60 (median effect size of 1.24). The overall correlations between items and total or partial scores derived from the latent JSE-S subscales were consistently similar in both study sites. Findings of this study confirm the latent structure of the JSE-S in French and its cross-national reproducibility. The comparable underlying structure of the questionnaire tested in two distinct French-speaking contexts endorses the generalizability of its measure

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Statistical aggregation of gene expression levels to identif