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International audience; Background: Childhood severe traumatic brain injury (TBI) is a leading cause of long-lasting acquired disability, but predicting long-term functional outcome remains difficult.Objectives: This study aimed to 1) describe the functional outcome at 1 and 7 years post-TBI; 2) determine the initial and concurrent factors associated with long-term outcome; and 3) evaluate the predictive value of functional status, overall disability level and intellectual ability measured at 1 year post-injury to determine 7-year clinically meaningful outcomes.Methods: Among the children (

Salam Abbara,1,2 Didier Guillemot,1– 3 Salma El Oualydy,4 Maeva Kos,4 Cécile Poret,5 Stéphane Breant,5 Christian Brun-Buisson,1,2 Laurence Watier1,2 1Anti-Infective Evasion and Pharmacoepidemiology Team, Inserm, UVSQ, University Paris-Saclay, CESP, Montigny-Le-Bretonneux, France; 2Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE), University Paris Cité, Paris, France; 3Public Health, Medical Information, Clinical Research, AP-HP, University Paris Saclay, Le Kremlin-Bicêtre, France; 4Plateforme des données de santé - Health Data Hub, Paris, France; 5AP-HP, Direction des Systèmes d’Information, Pôle Innovation et Données, Paris, FranceCorrespondence: Salam Abbara, Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE) Unit, 25-28 rue du Docteur Roux, Paris, 75015, France, Tel +33 1 45 68 80 00, Email salam.abbara@gmail.comPurpose: Antibiotic-resistant bacteremia is a leading global cause of infectious disease morbidity and mortality. Clinical data warehouses (CDWs) allow for the secure, real-time coupling of diverse data sources from real-world clinical settings, including care-based medical-administrative data and laboratory-based microbiological data. The main purpose of this study was to assess the contribution of CDWs in the epidemiological study of antibiotic resistance by constructing a database of bacteremia patients, BactHub, and describing their main clinico-microbiological features and outcomes.Patients and Methods: Adult patients with bacteremia hospitalized between January 1, 2016 and December 31, 2019 in 14 acute care university hospitals from the Greater Paris area were identified; their first bacteremia episode was included. Data describing patients, episodes of bacteremia, bacterial isolates, and antimicrobial resistance were structured.Results: Among 29,228 patients with bacteremia, 41% of episodes were community-onset (CO) and 59% were hospital-acquired (HA). Thirty-day and ninety-day mortality rates were 15% and 20% in CO episodes, and 18% and 36% in HA episodes. Overall resistance rates were high, including third-generation cephalosporin resistance among Klebsiella pneumoniae (CO 21%, HA 37%) and Escherichia coli (CO 13%, HA 17%), and methicillin resistance among Staphylococcus aureus (CO 11%, HA 14%). Annual incidence rates increased significantly from 2017 to 2019, from 20.0 to 20.9 to 22.1 stays with bacteremia per 1000 stays (p < 0.0001).Conclusion: The Bacthub database provides accurate clinico-microbiological data describing bacteremia across France’s largest hospital group. Data from Bacthub may inform surveillance and the clinical decision-making process for bacteremia patients, including choice of antimicrobial therapy. The database also offers opportunities for research, including analysis of hospital care pathways and significant patient outcomes such as mortality and recurrence of infection.Keywords: data warehousing, bacteremia, drug resistance, microbial, anti-bacterial agents, mortality, incidence

ObjectiveThis study aims to provide a case definition of sepsis of presumed bacterial aetiology based on 10th revision of the International Classification of Diseases (ICD-10) codes, to assess trends in sepsis incidence and mortality between 2015 and 2019 in France, and to describe the characteristics of affected patients and hospital stays.DesignNationwide, population-based, retrospective observational study.SettingMetropolitan France between 2015 and 2019.ParticipantsBetween 2015 and 2019, 1 224 433 patients with sepsis of presumed bacterial aetiology were selected from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d’Information) and were identified from corresponding ICD-10 codes for explicit sepsis or implicit sepsis.Main outcomes measuresAnnual overall and age-specific and gender-specific incidence and 95% CI, as well as trends in sepsis incidence and mortality, were estimated. Comorbidities, length of hospital stay and outcomes were described.ResultsThe sex-standardised and age-standardised incidence per 100 000 (95% CI) increased from 357 (356.0 to 359.0) in 2015 to 403 (401.9 to 405.0) in 2019 and remained higher for males compared with females. Children under 1 year and patients over 75 years consistently had the highest incidence. The most common comorbidities were cancer and chronic heart failure. The median hospital length of stay was 12 days. Most patients came from home, but only half returned home after their hospital stay and approximately 15% were discharged to long-term care. In-hospital mortality was about 25% and declined along the study period.ConclusionsMedico-administrative databases can be used to provide nationwide estimates of the in-hospital burden of bacterial sepsis. The results confirm the high burden of sepsis in France. These data should be complemented by estimating the additional burden associated with fungal and viral infections during the COVID-19 pandemic.

Resume Introduction L’incidence des infections du site operatoire (ISO) apres chirurgie rachidienne est estimee entre 1 et 10 %. Ces evenements sont responsables d’une augmentation de la morbidite, de la mortalite et des couts de prise en charge. La decontamination du portage du Staphylococcus aureus (S. aureus) a deja montre son efficacite dans la prevention d’infection du site operatoire dans de nombreuses disciplines chirurgicales. L’objectif de cette etude etait d’evaluer l’interet de strategie de prevention des ISO, et en particulier la decolonisation du portage nasal du SA part un protocole d’application de mupirocine. Materiel et methodes Nous avons conduit une etude operationnelle bicentrique, permettant d’evaluer 5314 patients apres chirurgie rachidienne au cours d’une periode de sept ans. Dans les deux centres nous avons compare des periodes avant et apres implantation de deux mesures : la modification de l’antibioprophylaxie et la decolonisation du portage du SA. L’homogeneite des differents echantillons de patient a ete evaluee par le recueil de caracteristiques chirurgicales et individuelles. L’efficacite a ete evaluee par la mesure mensuelle de l’incidence des ISO, permettant de mesurer son evolution apres l’implantation de mesures. Resultats L’incidence des ISO etait divisee par 2, de 7,3 % a 3 % a l’hopital Beaujon est de 8,3 % a 3,9 % a l’hopital europeen Georges Pompidou (HEGP). Nous n’avons observe aucune diminution significative du taux de SA a dans la par desinfection du site operatoire apres implantation de mesures. Conclusions Les mesures de decolonisation du portage du SA doivent etre recommandees apres chirurgie rachidienne. Elles doivent etre integrees a une reflexion globale d’amelioration de la prise en charge des patients operes pour ameliorer la prevention des infections du site operatoire.

International audience; Objective: To investigate presence of and factors associated with self- and parent-reported fatigue 7 years after severe childhood traumatic brain injury (TBI) in the prospective longitudinal study TGE (Traumatisme Grave de l'Enfant-severe childhood trauma).Methods: Self-reports and/or parent reports on the Multidimensional Fatigue Scale were collected for 38 participants (aged 7-22 years) 7 years after severe childhood TBI, and 33 controls matched for age, gender, and parental educational level. The data collected included sociodemographic characteristics, age at injury and injury severity scores, overall disability (Glasgow Outcome Scale Extended), intellectual outcome (Wechsler scales), and questionnaires assessing executive functions, health-related quality of life, behavior, and participation.Results: Fatigue levels were significantly worse in the TBI than in the control group, especially for cognitive fatigue. Correlations of reported fatigue with age at injury, gender, TBI severity, and intellectual ability were moderate and often not significant. Fatigue was significantly associated with overall level of disability (Glasgow Outcome Scale Extended) and with all questionnaires completed by the same informant.Conclusion: High levels of fatigue were reported by 30% to 50% of patients 7 years after a severe childhood TBI. Reported fatigue explained more than 60% of the variance of reported health-related quality of life by the same informant (patient or parent).

SummaryBackgroundAntibiotic resistance (ABR) is a major concern for global health. However, factors driving its emergence and dissemination are not fully understood. Identification of such factors is crucial to explain heterogeneity in ABR rates observed across space, time and species and antibiotics.MethodsWe analyzed count data of clinical isolates from 51 countries over 2006-2019 for thirteen drug-bug pairs from the ATLAS surveillance system. We characterized ABR spatial and temporal patterns and used a mixed-effect negative binomial model, accounting for country-year dependences with random effects (RE), to investigate associations with potential drivers including antibiotic sales, economic and health indicators, meteorological data, population density and tourism.FindingsABR patterns were strongly country and drug-bug pair dependent. In 2019, median ABR rates ranged from 6×3% (interquartile range (IQR): 19×7%) for carbapenem-resistant (CR)Klebsiella pneumoniaeto 80×7% (IQR: 41×8%) for fluoroquinolone-resistant (FR)Acinetobacter baumannii, with heterogeneity across countries. Over 2006-2019, carbapenem resistance was on the rise in >60% of investigated countries, while no global trend was observed for other resistances. Multivariable analyses identified significant associations of ABR with country-level selecting antibiotic sales, but only in FR-Escherichia coli, FR-Pseudomonas aeruginosaand CR-A. baumannii;with temperature in investigated Enterobacterales but not in other drug-bug pairs; and with the health system quality for all drug-bug pairs exceptEnterococciandStreptococcus pneumoniaepairs. Despite wide consideration of possible explanatory variables, drug-bug pairs ABR rates still showed unexplained spatial RE variance.InterpretationOur findings reflect the diversity of mechanisms driving global antibiotic resistance across pathogens and stress the need for tailored interventions to tackle bacterial resistance.FundingIndependent research Pfizer Global Medical Grant; ANR Labex IBEID (ANR-10-LABX-62)

Members of the BIRDY study group : Bodonirina Tanjona Raheliarivao, Frédérique Randrianirina, Perlinot Herindrainy, Zafitsara Zo Andrianirina, Feno Manitra Jacob Rakotoarimanana, Benoit Garin, Jean-Marc Collard, Agathe de Lauzanne, Laurence Borand, Patrice Piola, Alexandra Kerléguer, Thida Chon, Sok Touch, Arnaud Tarantola, Sophie Goyet, Siyin Lach, Veronique Ngo, Muriel Vray, Marguerite Diatta, Joseph Faye, Abibatou Ndiaye, Vincent Richard, Abdoulaye Seck, Raymond Bercion, Amy Gassama Sow, Jean Baptiste Diouf, Pape Samba Dieye, Balla Sy, Bouya Ndao, Didier Guillemot, Bich-tram Huynh, Maud Seguy, Laurence Watier, Abdou Armya Youssouf and Michael Padget.; International audience; BACKGROUND:Salmonella enterica is a leading cause of human gastroenteritis. S. enterica strains that produce ESBLs (ESBL-Salm) remain rare in Europe and North America, but less is known about their prevalence among animal-derived foods in countries with weaker food safety practices and unregulated veterinary antibiotic use.OBJECTIVES:To examine the prevalence and characteristics of ESBL-Salm from retail meats in Phnom Penh, Cambodia.METHODS:We tested fish, pork and chicken from two markets for ESBL- and carbapenemase-producing Salmonella from September-December 2016, using cefotaxime- and ertapenem-supplemented media, respectively. ESBL-Salm were sequenced and their genomes characterized. We performed plasmid conjugation experiments to assess the co-transferability of ESBL-encoding genes and MDR phenotypes.RESULTS:Twenty-six of 150 fish and meat samples (17%) were positive for ESBL-Salm, including 10/60 fish (17%), 15/60 pork (25%) and 1/30 chicken (3%). Carbapenemase-producing Salmonella strains were not detected. Pork-origin ESBL-Salm were primarily serotypes Rissen (10/15) or a monophasic variant of Typhimurium 4,5,12:i:- (3/15), whereas Saintpaul (3/10) and Newport (4/10) were more common among fish. Most ESBL enzymes were encoded by blaCTX-M-55 genes (24/26) harboured on conjugative IncA/C2 (n = 14) or IncHI2 (n = 10) plasmids. Resistance to up to six additional drug classes was co-transferred by each plasmid type. ESBL-Salm were resistant to almost every antibiotic recommended for severe salmonellosis treatment.CONCLUSIONS:CTX-M-55-type S. enterica are highly prevalent among pork and fish from Phnom Penh markets and their spread appears to be mediated by MDR IncA/C2 and IncHI2 plasmids. Food safety must be improved and veterinary antibiotic use should be regulated to protect public health.

International audience; Objective: To explore memory functioning 7 years after severe paediatric traumatic brain injury (TBI), associated factors, and relationships with other outcomes.Method: Children aged 0-15 years (n = 65), consecutively admitted over a 3-year period in a single trauma centre, who survived after severe non-inflicted TBI, were included in a prospective longitudinal study. Memory assessments were performed 7 years post-injury using the Children's Memory Scale or the Wechsler Memory Scale (WMS IV), according to age. The General Memory Score (GMS-7) was the primary outcome.Results: Thirty-seven patients were available for assessment at 7 years post-injury. Mean GMS-7 was in the low average range (M = 84.9, SD = 12.1). Lower GMS-7 was significantly associated with markers of higher injury severity, such as length of coma. One year post-injury functional and disability outcomes explained 74% of the variance of GMS-7. Concurrent intellectual ability and type of ongoing education correlated strongly with GMS-7. Age at injury and parental education were not associated with memory outcome.Conclusions: Memory functioning is variable but often strongly impaired several years after severe paediatric TBI, and is mostly related to injury severity, functional outcomes measured 1 year post-injury, and concomitant cognitive and educational outcomes. GMS-7 was lower at 7 years than one year post-injury, supporting the importance of long term follow-up.

Antibiotic stewardship requires clear insight into antibiotic overuse and the syndromes that lead to prescription. The aim of this study was to estimate the proportion of antibiotic prescriptions attributable to acute lower respiratory tract infections (LRTIs) during the cold season. Using individual data from the French National Health Insurance (NHI) database, weekly time series were constructed of outpatient antibiotic (beta-lactams and macrolides) prescriptions between January 2010 and December 2017. Time series were also constructed of tenth edition of the International Classification of Diseases (ICD-10) discharge diagnoses from a national network of emergency departments (EDs), stratified by specific syndromes (pneumonia, bronchitis, bronchiolitis and influenza-like illness). The number of outpatient antibiotic prescriptions attributable to these syndromes during the cold season in France was modeled and estimated for the entire population, young children (≤5 years) and the elderly (≥75 years). LRTIs accounted for 40% (95% confidence interval [95% CI]: 29, 52) of outpatient antibiotic use during the cold season for the entire population, including 23% (95% CI: 13, 33) and 17% (95% CI: 13, 22) for bacterial and viral infections, respectively. In children and the elderly, viral LRTIs were the reason for 38% (95% CI: 31, 46) and 20% (95% CI: 16, 25) of outpatient antibiotic use, respectively (with bronchiolitis accountable for half of use in young children). In the entire population and in children, respectively, outpatient antibiotic overuse attributable to viral LRTIs was estimated to be 289 (95% CI: 221, 374) and 1588 (95% CI: 1295, 1922) prescriptions per 100 000 inhabitants per week. These results highlight the major role of viral infections in driving antibiotic prescriptions, particularly in young children.

International audience; Background: The impact of antibiotic resistance (AMR) on initial hospital management has been extensively studied but its consequences after hospital discharge remain largely unknown. We aimed to analyze hospital care trajectories, cumulative length of hospital stays (c-LOS) and associated costs of care over a 1-year period after hospitalization with incident AMR infection.Method: All incident bacterial infection-related hospitalizations occurring from January 1, 2015, to December 31, 2015 and recorded in the French national health data information system were extracted. Bacterial resistance ICD-10 codes determined six infection status. Inpatient and outpatient care consumption and associated costs were studied. The impact of resistance on c-LOS was estimated using a Poisson regression. A sequence analysis through optimal matching method was conducted to identify hospital trajectories along with an extrapolation.Finding: Of the 73,244 patients selected, 15.9% had AMR infection, thus providing 58,286 incident AMR infections after extrapolation. c-LOS was significantly longer for infections with resistant bacteria, reaching 20.4 days and 2.9 additional days IC95%[2.6; 3.2] for skin and soft tissue infections. An estimated 29,793 (51.1%) patients had hospital readmission within the following year, for a total cost of €675 million. Five post-discharge trajectories were identified: Post-hospitalization mainly at home (68.4% of patients); Transition to home from rehabilitation care (12.3%); Early death (

International audience; Objectives: Severe childhood traumatic brain injury (TBI) leads to long-standing executive function and attention deficits, with negative consequences for participation, academic outcome and independence. This study aimed to assess executive function and attention 7 years after severe childhood TBI in comparison with a matched control group and to investigate associated factors. Methods: Children (< 15 years) with severe accidental TBI consecutively admitted in a single trauma center over 3 years were included in the Traumatisme Grave de l'Enfant (TGE) prospective longitudinal study. Of the 81 children initially included, 65 survived. At 7 years post-TBI, executive functions and attention were assessed in 27 participants (42 % of the 65 survivors) by using a combination of computerized tasks from the Test of Attentional Performance (TAP) and the Behavioral Rating of Executive Functions (BRIEF) questionnaire. Patients were compared to a group of 27 typically developing controls who were matched for sex, age and parental education level. Results: Among the 27 participants, mean (SD) age at injury was 7.7 (4.6) years, and mean length of coma 5.6 (4.6) days. Regarding the TAP, the number of errors was significantly higher (P = 0.003) and reaction time marginally slower (P = 0.08) in the TBI than control group. The BRIEF questionnaire completed by parents indicated significantly more executive difficulties in the TBI than control group (Behavior Regulation Index, P = 0.005; Metacognitive index, P = 0.02; Global Executive Composite, P = 0.012). Correlations between BRIEF and TAP scores did not reach statistical significance. BRIEF total score was correlated moderately with length of coma (r = 0.40, P = 0.037), and TAP scores were correlated with the Full-Scale Intellectual Quotient (total number of errors: r = -0.48; P = 0.01; mean reaction time: r = −0.51; P = 0.009). Conclusions: Executive and attention deficits were evident 7 years after severe childhood TBI. Computerized tasks and questionnaires provide complementary and non-redundant information. Systematic long-term follow-up should be provided until the transition to adulthood, to assess ongoing development and to implement timely tailored interventions.

International audience; Purpose: To investigate self- and parent-reported Health-Related Quality-of-Life (HRQoL) and their associations after severe childhood traumatic brain injury (TBI) in the Traumatisme Grave de l'Enfant (TGE) cohort.Methods: Self- (n = 34) and/or parent-reports (n = 25) of HRQoL were collected for 38 participants (age 7-22 years) 7 years after severe childhood TBI. The collected data included sociodemographic characteristics, injury severity indices, and overall disability and functional outcome at 3-months, 1- and 2-years post-injury. At 7-years post-injury, data were collected in the TBI group and in a control group (n = 33): overall disability (Glasgow Outcome Scale Extended), intellectual ability (IQ), and questionnaires assessing HRQoL (Pediatric Quality of Life Inventory), executive functions (Behavior Rating Inventory of Executive Functions), behavior (Child Behavior Checklist), fatigue (Multidimensional Fatigue Scale) and participation (Child and Adolescent Scale of Participation).Results: Parent- and self-reports of HRQoL were significantly lower in the TBI group than in the control group. Parent-rated HRQoL was not associated with objectively assessed factors, whereas self-reported HRQoL was associated with gender (worse in females) and initial functional outcome. All questionnaire scores completed by the same informant (self or parent) were strongly inter-correlated.Conclusions: Reported HRQoL 7-years after severe childhood TBI is low compared to controls, weakly or not-related to objective factors, such as injury severity indices, clinically assessed functional outcomes, or IQ, but strongly related to reports by the same informant of executive deficits, behavior problems, fatigue, and participation.

International audience; Introduction: L'incidence des infections du site opératoire (ISO) après chirurgie rachidienne est estimée entre 1 et 10 %. Ces évènements sont responsables d'une augmentation de la morbidité, de la mortalité et des coûts de prise en charge. La décontamination du portage du Staphylococcus aureus (S. aureus) a déjà montré son efficacité dans la prévention d'infection du site opératoire dans de nombreuses disciplines chirurgicales. L'objectif de cette étude était d’évaluer l'intérêt de stratégie de prévention des ISO, et en particulier la décolonisation du portage nasal du SA part un protocole d'application de mupirocine. Matériel et méthodes: Nous avons conduit une étude opérationnelle bicentrique, permettant d’évaluer 5314 patients après chirurgie rachidienne au cours d'une période de sept ans. Dans les deux centres nous avons comparé des périodes avant et après implantation de deux mesures: la modification de l'antibioprophylaxie et la décolonisation du portage du SA. L'homogénéité des différents échantillons de patient a été évaluée par le recueil de caractéristiques chirurgicales et individuelles. L'efficacité a été évaluée par la mesure mensuelle de l'incidence des ISO, permettant de mesurer son évolution après l'implantation de mesures. Résultats: L'incidence des ISO était divisée par 2, de 7,3 % à 3 % à l'hôpital Beaujon est de 8,3 % à 3,9 % à l'hôpital européen Georges Pompidou (HEGP). Nous n'avons observé aucune diminution significative du taux de SA à dans la par désinfection du site opératoire après implantation de mesures. Conclusions: Les mesures de décolonisation du portage du SA doivent être recommandées après chirurgie rachidienne. Elles doivent être intégrées à une réflexion globale d'amélioration de la prise en charge des patients opérés pour améliorer la prévention des infections du site opératoire.

International audience; Purpose: Participation in home, school and community activities is considered as the ultimate aim of rehabilitation. The aims of this study were to examine participation seven years post-severe childhood traumatic brain injury and factors associated with participation. Materials and methods: Participants were enrolled in the Traumatisme Grave de l’Enfant (Severe Childhood Injury) cohort study following severe accidental childhood traumatic brain injury. Participation seven years post-injury, was examined using parent- and self-report forms of the Child and Adolescent Scale of Participation among 37 patients [62% males, mean age 15.4 years (SD = 4.4), mean length of coma 6.68 days (SD = 4.96)] and 33 matched controls. Results: Parent reports indicated significantly lower participation among patients compared to controls, but the self-reports did not. In the traumatic brain injury group, parent-reported participation was variable, with 22% of the patients clearly showing greater restrictions than controls. Participation restrictions were significantly associated with injury severity, poor functional outcome one-year post-injury, executive and behavioral difficulties and higher fatigue levels seven years post-injury, but not with pre-injury nor family factors. Conclusions: Several years after severe childhood traumatic brain injury, participation appears to depend more on injury-related factors than on environmental factors. In self-reports assessments of participation, it could be difficult for children and adolescents to distinguish capacity from performance.

Background and Objective Antimicrobial resistance (AMR) has become one of the biggest threats to global public health given its association with mortality, morbidity and cost of health care. However, little is known on the economic burden of hospitalization attributable to AMR from a public health insurance perspective. We assessed the excess costs to the French public health insurance system attributable to AMR infections in hospitals. Methods Bacterial infectious disease-related hospitalizations were extracted from the National health data information system for all stays occurring in 2015. Bacterial infections, strains, and microbial resistance were identified by specific French ICD-10 codes. Information about health care expenditure, co-morbidities and demographic characteristics (i.e. gender, age) are provided. We used a matched case–control approach to determine the excess of reimbursements paid to stays with AMR compared to stays with an infection without resistance. Cases and controls were matched on gender, age, Charlson comorbidity index, category of infection, infection as principal diagnosis (two classes), microorganism and hospital status. The overall AMR cost was extrapolated to stays with AMR and excluded from the sample (multiple infections), and a second extrapolation was performed to consider stays with unknown resistance status. Results The final sample included 52,921 matched-pairs (98.2% cases). Our results suggest that AMR overall cost reached EUR109.3 million in France with a mean of EUR1103 per stay; extrapolation to the entire database shows that the overall cost could potentially reach EUR287.1 million if all cases would be identified. The mean excess length of hospital stay attributable to AMR was estimated at 1.6 days. Conclusion AMR causes substantial cost burden in France for the public health insurance. Our study confirms the need to reinforce programs to prevent AMR infection and thereby reduce their economic burden. Electronic supplementary material The online version of this article (10.1007/s40258-018-0451-1) contains supplementary material, which is available to authorized users.

A prospective audit and feedback antimicrobial stewardship intervention conducted in the Orthopaedics Department of a university hospital in Portugal was evaluated by comparing an interrupted time series in the intervention group with a non-intervention (control) group. Monthly antibiotic use (except cefazolin) was measured as the World Health Organization's Anatomical Therapeutic Chemical defined daily doses (ATC-DDD) from January 2012 to September 2016, excluding the 6-month phase of intervention implementation starting on 1 January 2015. Compared with the control group, the intervention group had a monthly decrease in the use of fluoroquinolones by 2.3 DDD/1000 patient-days [95% confidence interval (CI) −3.97 to −0.63]. An increase in the use of penicillins by 103.3 DDD/1000 patient-days (95% CI 47.42 to 159.10) was associated with intervention implementation, followed by a decrease during the intervention period (slope = −5.2, 95% CI −8.56 to −1.82). In the challenging scenario of treatment of osteoarticular and prosthetic joint infections, an audit and feedback intervention reduced antibiotic exposure and spectrum.

Introduction L’antibioresistance (AR) va croissante parmi les microorganismes cause d’infections des voies urinaires (IVU), pouvant mener jusqu’a des impasses therapeutiques. Plusieurs facteurs de risque d’IVU a bacteries AR ont ete reveles dans la litterature, mais peu font consensus. Nous avons etudie les facteurs associes a l’AR chez les patients hospitalises pour IVU, a partir du Systeme national des donnees de sante (SNDS). Methodes Les hospitalisations incidentes (2015 − 2017) pour IVU en DP dues a des Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa ou enterocoques ont ete identifiees en medecine, chirurgie, orthopedie. Seuls les sejours pour lesquels la bacterie a ete identifiee sont concernes. Les cas (avec AR) ont ete apparies (1 :1) aux controles (sans AR) sur l’âge, le sexe, l’infection, l’annee d’admission et l’espece bacterienne. Les infections associees aux soins (IAS) et communautaires (IC) ont ete distinguees et les regressions logistiques conditionnelles stratifiees sur le sexe. Resultats Au total, 98,4 % des cas (6606 IC et 3001 IAS) ont ete apparies. Pour l’ensemble des facteurs, sur fenetre de 12 mois, le risque etait augmente uniquement lorsque l’exposition etait dans les trois mois precedant l’infection. Pour toutes les infections, la consommation d’antibiotiques augmentait le risque d’AR, avec un OR atteignant 3,84 [3,04 − 4,85] pour ≥ 3 delivrances chez les hommes avec IAS. Les antibiotiques a large spectre, qu’ils soient ou non rattaches a un antecedent d’IVU, etaient particulierement associes a l‘AR (OR : 2,59 [2,15 − 3,11] et 1,35 [1,18 − 1,53]). Une procedure chirurgicale sur les voies urinaires etait facteur de risque pour les hommes avec IC (1,39 [1,14 − 1,69]) et les femmes avec IAS (1,72 [1,37 − 2,17]). Avoir sejourne > 7 jours en unite de soins intensifs (USI) augmentait faiblement le risque pour les hommes avec IAS (1,44 [1,03 − 2,02]). Le diabete, l’immunosuppression, les maladies neurologiques, les pathologies des voies urinaires et la grossesse n’etaient pas associees a la resistance. Discussion/Conclusion Cette etude confirme l’importance des antibiotiques a large spectre sur le risque d’IVU a bacterie AR, et suggere d’ameliorer la prevention lors des procedures chirurgicales et sejours prolonges en USI.

Background Childhood severe traumatic brain injury (TBI) is a leading cause of long-lasting acquired disability, but little is known about functional outcome. Objective We aimed to 1) study clinical recovery and functional outcome over 24 months after severe childhood TBI, 2) identify early sociodemographic and severity factors influencing outcome, and 3) examine the clinical utility of the Pediatric Injury Functional Outcome Scale (PIFOS) to assess functional outcome. Methods Children (0-15 years) consecutively admitted in a trauma centre after accidental severe TBI over 3 years were included in a prospective longitudinal study (Traumatisme Grave de l’Enfant cohort). We measured clinical/neurological recovery, functional status (Pediatric Injury Functional Outcome Scale, [PIFOS]), overall disability (pediatric Glasgow Outcome Scale [GOS-Peds]) as well as intellectual ability (Wechsler scales) and educational outcome (mainstream school vs special education) of survivors at 1, 3, 12 and 24 months post-injury. Results For 45 children (aged 3 to 15 years at injury), functional impairments were severe within the first 3 months. Despite the initial rapid clinical recovery and significant improvement over the first year, substantial alterations persisted for most children at 12 months post-TBI, with no significant improvement up to 2 years. Up to 80% of children still had moderate or severe overall disability (GOS-Peds) at 24 months. The severity of functional impairments (PIFOS) at 12 and 24 months was mostly related to socio-emotional, cognitive and physical impairments, and was significantly correlated with clinical/neurological deficits and cognitive (intellectual, executive) and behavioural disorders. Initial TBI severity was the main prognostic factor associated with functional status over the first 2 years post-injury. Conclusions Our results confirm the significant impact of severe childhood TBI on short- and medium-term functional outcomes and overall disability. All patients should benefit from systematic follow-up. The PIFOS appeared to be an accurate and reliable tool to assess functional impairment evolution and clinically meaningful outcomes over the first 2 years post-injury.

Infections caused by Streptococcus pneumoniae —including invasive pneumococcal diseases (IPDs)—remain a significant public health concern worldwide. The marked winter seasonality of IPDs is a striking, but still enigmatic aspect of pneumococcal epidemiology in nontropical climates. Here we confronted age-structured dynamic models of carriage transmission and disease with detailed IPD incidence data to test a range of hypotheses about the components and the mechanisms of pneumococcal seasonality. We find that seasonal variations in climate, influenza-like illnesses, and interindividual contacts jointly explain IPD seasonality. We show that both the carriage acquisition rate and the invasion rate vary seasonally, acting in concert to generate the marked seasonality typical of IPDs. We also find evidence that influenza-like illnesses increase the invasion rate in an age-specific manner, with a more pronounced effect in the elderly than in other demographics. Finally, we quantify the potential impact of seasonally timed interventions, a type of control measures that exploit pneumococcal seasonality to help reduce IPDs. Our findings shed light on the epidemiology of pneumococcus and may have notable implications for the control of pneumococcal infections.

Massive use of antibiotics has led to increased bacterial resistance to these drugs, making infections more difficult to treat. Few studies have assessed the overall antimicrobial resistance (AMR) burden, and there is a paucity of comprehensive data to inform health policies. This study aims to assess the overall annual incident number of hospitalised patients with AMR infection in France, using the National Hospital Discharge database. All incident hospitalisations with acute infections in 2016 were extracted. Infections which could be linked with an infecting microorganism were first analysed. Then, an extrapolation of bacterial species and resistance status was performed, according to age class, gender and infection site to estimate the total number of AMR cases. Resistant bacteria caused 139 105 (95% CI 127 920–150 289) infections, resulting in a 12.3% (95% CI 11.3–13.2) resistance rate. ESBL-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the most common resistant bacteria (>50%), causing respectively 49 692 (95% CI 47 223–52 142) and 19 493 (95% CI 15 237–23 747) infections. Although assumptions are needed to provide national estimates, information from PMSI is comprehensive, covering all acute bacterial infections and a wide variety of microorganisms.

Geographic variations of invasive pneumococcal disease incidence and serotype distributions were observed after pneumococcal conjugate vaccine introduction at regional levels and among French administrative areas. The variations could be related to regional vaccine coverage (VC) variations that might have direct consequences for vaccination-policy impact on invasive pneumococcal disease, particularly pneumococcal meningitis (PM) incidence. We assessed vaccine impact from 2001 to 2016 in France by estimating the contribution of regional VC differences to variations of annual local PM incidence. Using a mixed-effect Poisson model, we showed that, despite some variations of VC among administrative areas, vaccine impact on vaccine-serotype PM was homogeneously confirmed among administrative areas. Compared with the prevaccine era, the cumulative VC impact on vaccine serotypes led, in 2016, to PM reductions ranging among regions from 87% (25th percentile) to 91% (75th percentile) for 7-valent pneumococcal conjugate vaccine serotypes and from 58% to 63% for the 6 additional 13-valent pneumococcal conjugate vaccine serotypes. Nonvaccine-serotype PM increases from the prevaccine era ranged among areas from 98% to 127%. By taking into account the cumulative impact of growing VC and VC differences, our analyses confirmed high vaccine impact on vaccine-serotype PM case rates and suggest that VC variations cannot explain PM administrative area differences.

In order to design effective public health strategies, and, in particular, effective food safety interventions to reduce the burden of foodborne disease, the most important sources of enteric illnesses should be identified. Both case-control and cohort observational studies have for long been powerful approaches among epidemiologists to investigate the association of exposure and illness. In the literature, there are numerous case-control and cohort studies reporting results on risk factors and routes of transmission of sporadic foodborne infections. The objective of this article is to describe, in depth, the strategies implemented for systematic review and meta-analysis of the associations between multiple risk factors and eleven food and waterborne diseases, namely, non-typhoidal salmonellosis, campylobacteriosis, Shiga-toxin E. coli infection, listeriosis, yersiniosis, toxoplasmosis, norovirus infection, hepatitis A, hepatitis E, cryptosporidiosis and giardiasis. First, this article describes the procedures of systematic searches in five bibliographic engines, screening of relevance and assessment of methodological quality according to pre-set criteria. It proceeds with the explanation of a broad data categorisation scheme established to hierarchically group the risk factors into travel, host-specific factors and pathways of exposure (i.e., person-to-person, animal, environment and food routes), with views to harmonising and supporting the integration of outcomes from studies investigating a variety of potential determinants of disease. Next, the article describes the four meta-analysis models that were devised in order to calculate: (i) overall oddsratios of acquiring the disease due to a specific risk factor by geographical region; (ii) overall odds-ratios of acquiring the disease from the different risk factors; (iii) overall risks of disease from consumption of ready-toeat and barbecued foods; and (iv) overall effects of food handling (i.e., consuming food in raw, undercooked or unwashed state) and food preparation setting (i.e., eating food prepared outside the home) on risk of disease. The procedures for sensitivity analysis and removal of any influential and potentially-biased odds-ratio; and two methods for publication bias assessment are outlined. Finally, details are given on deviations from the standard risk categorisation scheme for specific foodborne hazards. info:eu-repo/semantics/publishedVersion

The first aim of this study was to estimate the prevalence of TBI and epilepsy in a French prison population and to study variables known to be associated with TBI. The second aim was to compare prisoners with and without a history of TBI.All offenders (females, males and juveniles) admitted consecutively to Fleury-Mérogis prison over a period of 3 months were included in the study.During the admission procedure, offenders were interviewed by healthcare staff using a self-reported questionnaire.In all, 1221 prisoners were included. The rates of TBI and epilepsy were high, with a prevalence of 30.6% and 5.9%, respectively. Psychiatric care, anxiolytic and antidepressant treatment, use of alcohol and cannabis were all significantly higher among offenders with a history of TBI. Moreover, the number of times in custody and the total time spent in jail over the preceding 5 years were significantly higher among offenders with a history of TBI.These results provide further evidence that specific measures need to be developed such as, first of all, screening for TBI upon arrival in prison.

Introduction Chaque annee en France, 30 % des enfants âges de moins de deux ans sont infectes par le virus respiratoire syncitial (VRS) a l’origine d’infections respiratoires severes. Ce virus est responsable de nombreuses hospitalisations chez le nourrisson et le jeune enfant. Cette etude vise a estimer le fardeau hospitalier associe au VRS chez l’enfant âge de moins de 5 ans en France. Methodes A partir du PMSI, les enfants âges de moins de 5 ans ayant un sejour hospitalier avec un diagnostic principal ou relie en lien avec le VRS (CIM-10 : J210/J219/J121/J205/J45/R062) ont ete analyses sur huit saisons hivernales (octobre a mars) de 2010/11 et 2017/18. Resultats Entre 2010/11 et 2017/18, l’incidence des hospitalisations pour VRS a augmente de 183 a 240 pour 100 000 personne-mois Discussion/Conclusion Les hospitalisations pour VRS ont augmente sur la periode d’etude et concernent principalement les enfants âges de moins de 2 ans. Un âge

Introduction L’impact de l’antibioresistance sur la prise en charge hospitaliere initiale a ete abondamment etudiee mais ses consequences apres la sortie d’hospitalisation demeurent largement inconnues. L’objectif de cette etude est d’etudier l’impact de la resistance bacterienne sur la duree cumulee des rehospitalisations sur une periode de 12 mois apres un sejour infectieux. Methodes Une liste de codes CIM-10 regroupant les infections bacteriennes de six sites infectieux a permis d’identifier les patients hospitalises pour ces infections en 2015. Seules les hospitalisations en MCO pour infections incidentes ont ete retenues. L’incidence a ete definie par l’absence d’hospitalisation avec la meme infection au cours de l’annee precedente. Le statut de l’infection a ete determine par la presence ou l’absence d’un code de resistance : resistant versus sensible respectivement. Sur une periode de 12 mois, la duree d’hospitalisation cumulee (MCO, SSR, HAD) a ete calculee pour l’ensemble des patients. L’impact de la resistance a ete estime par une regression de Poisson ajuste par : statut de l’infection, sexe, âge, score de Charlson, categories d’infections, germes, antecedent d’hospitalisation et statut hospitalier (public/prive). Resultats Un total de 73 244 patients ont ete selectionnes, dont 11 680 (15,9 %) avec resistance et 61 564 (84,1 %) avec infection sensible. Dans l’analyse multivariee, la duree d’hospitalisation est plus importante toutes activites confondues pour les infections a germes resistants (infections genito-urinaires : 1,3 jours en plus IC95 % [1,2 ; 1,4] atteignant 15,6 jours ; infections de la peau et des parties molles : 2,9 jours en plus [2,6 ; 3,2] atteignant 20,4 jours) a l’exception des infections du cœur et du mediastin (−2,5 jours [−2,9 ; −2,1], soit 27,5 jours d’hospitalisation cumules). Les secteurs d’activite contribuant le plus a cette augmentation sont les hospitalisations en MCO pour une infection et en HAD. Discussion/Conclusion La resistance aux antibiotiques a un impact sur la duree cumulee d’hospitalisations des patients au-dela de l’hospitalisation initiale a travers les sejours en MCO pour infection et en HAD.

Introduction L’antibioresistance est une menace majeure pour la sante publique. Peu d’etudes decrivent la prise en charge hospitaliere apres infection a germe antibioresistant. L’objectif de cette etude est de decrire et d’identifier les trajectoires de soins hospitalieres et le cout de prise en charge a 12 mois d’une hospitalisation pour infection a germe resistant. Methodes Une liste de codes CIM-10 regroupant les infections bacteriennes de six sites infectieux a permis d’identifier les patients hospitalises pour ces infections en 2015. Seules les infections incidentes (sans hospitalisation en MCO avec infection l’annee precedente) presentant un code de resistance ont ete retenues. Toute la consommation de soins hospitaliers (MCO, SSR, HAD) a ete etudiee sur une periode de 12 mois suivant la sortie de l’hopital. Pour les patients rehospitalises au moins une journee, une analyse de sequence a ete effectuee pour identifier des trajectoires hospitalieres types. Pour chaque trajectoire, une description des patients et les couts (hospitaliers et ambulatoires) associes sont presentes. Resultats Au total, 58 286 patients ont ete hospitalises en 2015 pour une infection incidente a bacterie resistante et 29 793 (51,1 %) ont ete rehospitalises au moins une journee au cours du suivi. Cinq trajectoires hospitalieres ont ete identifiees: post-hospitalisation principalement a domicile (68,4 % des patients) ; transition en SSR vers le domicile (12,3 %) ; deces precoce (9,7 %) ; deces tardif (7,4 %) ; sejour prolonge en SSR (2,2 %). Les durees cumulees hospitalieres les plus longues (> 250 j) etaient observees suite a une infection osteoarticulaire, et une mortalite elevee concernait les infections du cœur et du mediastin ou des voies respiratoires basses. Ces trajectoires de soins ont un cout total estime a 700 millions d’euros avec un cout par patient observe allant jusqu’a 68 922 euros pour la trajectoire « Sejour prolonge en SSR ». Discussion/Conclusion La moitie des patients hospitalises pour infection resistante est rehospitalisee dans l’annee qui suit. Nous observons des disparites importantes dans les trajectoires et leurs couts selon les categories d’infections.

International audience; The seasonalities of influenza-like illnesses (ILIs) and invasive pneumococcal diseases (IPDs) remain incompletely understood. Experimental evidence indicates that influenza-virus infection predisposes to pneumococcal disease, so that a correspondence in the seasonal patterns of ILIs and IPDs might exist at the population level. We developed a method to characterize seasonality by means of easily interpretable summary statistics of seasonal shape-or seasonal waveforms. Nonlinear mixed-effects models were used to estimate those waveforms based on weekly case reports of ILIs and IPDs in 5 regions spanning continental France from July 2000 to June 2014. We found high variability of ILI seasonality, with marked fluctuations of peak amplitudes and peak times, but a more conserved epidemic duration. In contrast, IPD seasonality was best modeled by a markedly regular seasonal baseline, punctuated by 2 winter peaks in late December to early January and January to February. Comparing ILI and IPD seasonal waveforms, we found indication of a small, positive correlation. Direct models regressing IPDs on ILIs provided comparable results, even though they estimated moderately larger associations. The method proposed is broadly applicable to diseases with unambiguous seasonality and is well-suited to analyze spatially or temporally grouped data, which are common in epidemiology.

International audience; BACKGROUND: Transparency when documenting and assessing weight of evidence (WOE) has been an area of increasing focus for national and international health agencies. OBJECTIVE: The objective of this work was to conduct a critical review of WOE analysis methods as a basis for developing a practical framework for considering and assessing WOE in hazard identification in areas of application at the French Agency for Food, Environmental and Occupational Health and Safety (ANSES). METHODS: Based on a review of the literature and directed requests to 63 international and national agencies, 116 relevant articles and guidance documents were selected. The WOE approaches were assessed based on three aspects: the extent of their prescriptive nature, their purpose-specific relevance, and their ease of implementation. RESULTS: Twenty-four approaches meeting the specified criteria were identified from selected reviewed documents. :Most approaches satisfied one or two of the assessed considerations, but not all three. The approaches were grouped within a practical framework comprising the following four stages: (1) planning the assessment, including scoping, formulating the question, and developing the assessment method; (2) establishing lines of evidence (EOEs), including identifying and selecting studies, assessing their quality, and integrating with studies of similar type; (3) integrating the LOEs to evaluate WOE; and (4) presenting conclusions. DISCUSSION: Based on the review, considerations for selecting methods for a wide range of applications are proposed. Priority areas for further development are identified. https:/doi.org/10.1289/EHP3067