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International audience; BackgroundAntenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome.MethodsWe designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks’ gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076.FindingsBetween Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI –0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI –0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3–4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia.InterpretationBecause non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction.

Infants with COVID-19 can often present with fever without source, which is a challenging situation in infants90 days old. The "step-by-step" algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm.We performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the "step-by-step" algorithm to 4 clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk (ill-appearing, ≤21 days old, with leukocyturia or procalcitonin level ≥0.5 ng/mL).Among the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but 1 infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill-appearance (72%), an age ≤21 days (27%), or leukocyturia (19%). All these infants had procalcitonin values0.5 ng/mL and only 1 had C-reactive protein level20 mg/L.The "step-by-step" algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants90 days old.

BackgroundInfants with COVID-19 can often present with fever without source which is a challenging situation in infants < 90 days old. The “step-by-step” algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm.MethodsWe performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the “step-by-step” algorithm to four clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk.ResultsAmong the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but one infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill appearance (72%), an age ≤ 21 days (27%) and/or leukocyturia (19%). All these infants had procalcitonin values < 0.5 ng/mL and only one had C-reactive protein level > 20 mg/L.ConclusionsThe “step-by-step” algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants < 90 days old.

Infliximab (IFX) is a frequent therapeutic option for Crohn disease (CD) patients. Early detection of responders to IFX is critical for the management of CD in order to avoid long-term exposure to the drug without benefit. This retrospective study aimed at analysing which early parameters recorded during the induction period are able to predict response to IFX during the maintenance period in pediatric CD.Medical records of all CD patients ages from 2 to 18 years who received IFX at a tertiary IBD center were retrospectively analyzed. Children were classified in 3 groups according to their response at week 14 (W14) remission, clinical response or , no response. The factors recorded at W0, W2, and W6, which were associated with remission at W14 were analyzed using a logistic regression.Among the 111 patients included, 74.8% patients were responders to IFX at W14, including 38.7% in clinical remission and 36% with partial clinical response. Clinical remission at W14 was associated with normal growth (P 0.01), and normal albuminemia (P = 0.01) at baseline, It was also associated with trough levels to IFX8.3 μg/ml at week 6 (P 0.01).Trough levels to IFX8.3 μg/ml at week 6 are predictive of remission at W14 for luminal disease.

Objectives In adult inflammatory bowel disease (IBD) treated by anti-TNF antibodies, paradoxical psoriasis has an estimated prevalence of 1.6 to 22%, especially in infliximab (IFX)-treated patients. Little is known in the pediatric IBD (PIBD) populations. Methods All patients ages from 2 to 18 years with Crohn disease (CD) or ulcerative colitis (UC) and treated for the first time by IFX between January 2002 and March 2014, were considered for inclusion in this retrospective study performed in a tertiary PIBD centre. Paradoxical psoriasis events together with clinical and biological data were collected in all patients. Comparisons between psoriasis and control groups were performed using univariate statistical analyses. Results One hundred and twenty-three CD patients and 24 UC patients were treated with IFX. Twenty patients (13.6%) experienced a paradoxical psoriasis. All of them were affected by CD. Perianal CD was more frequent in the psoriasis group (P = 0.033). Fourteen patients (70%) were in remission when skin lesions occurred. Paradoxical psoriasis was diagnosed 355 days (median, interquartile range [IQR] 239; 532) after the initiation of IFX corresponding to the eighth injection (median, IQR: 6; 15). Psoriasis lesions were controlled by local steroids in all cases and no patients discontinued IFX therapy. Conclusions 13.6% of our IBD patients treated with IFX developed psoriasis during a median follow-up of 23.9 months (IQR: 11.6; 36.5). Crohn disease patients with perianal disease were at a higher risk to develop this common side effect.

This cohort study uses COVID-19 Pediatric Observatory study data to analyze the vaccination status of parents with young children hospitalized for SARS-CoV-2 variants Delta and Omicron.

BackgroundBronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries.MethodsWe conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling.ResultsIn total, 42 916 children were included. We observed an overall cumulative 78% (95% CI −100– −54%; pConclusionsSeveral NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

Summary Background The extent to which very young children contribute to the transmission of SARS-CoV-2 is unclear. We aimed to estimate the seroprevalence of antibodies against SARS-CoV-2 in daycare centres that remained open for key workers' children during a nationwide lockdown in France. Methods Children and staff who attended one of 22 daycare centres during a nationwide lockdown in France (between March 15 and May 9, 2020) were included in this cross-sectional, multicentre, seroprevalence study. Hospital staff not occupationally exposed to patients with COVID-19, or to children, were enrolled in a comparator group. The primary outcome was SARS-CoV-2 seroprevalence in children, daycare centre staff, and the comparator group. The presence of antibodies against SARS-CoV-2 in capillary whole blood was measured with a rapid chromatographic immunoassay. We computed raw prevalence as the percentage of individuals with a positive IgG or IgM test, and used Bayesian smoothing to account for imperfect sensitivity and specificity of the assay. This study is registered with ClinicalTrials.gov, NCT04413968. Findings Between June 4 and July 3, 2020, we enrolled 327 children (mean age 1·9 [SD 0·9] years; range 5 months to 4·4 years), 197 daycare centre staff (mean age 40 [12] years), and 164 adults in the comparator group (42 [12] years). Positive serological tests were observed for 14 children (raw seroprevalence 4·3%; 95% CI 2·6–7·1) and 14 daycare centre staff (7·7%; 4·2–11·6). After accounting for imperfect sensitivity and specificity of the assay, we estimated that 3·7% (95% credible interval [95% CrI] 1·3–6·8) of the children and 6·8% (3·2–11·5) of daycare centre staff had SARS-CoV-2 infection. The comparator group fared similarly to the daycare centre staff; nine participants had a positive serological test (raw seroprevalence 5·5%; 95% CI 2·9–10·1), leading to a seroprevalence of 5·0% (95% CrI 1·6–9·8) after accounting for assay characteristics. An exploratory analysis suggested that seropositive children were more likely than seronegative children to have been exposed to an adult household member with laboratory-confirmed COVID-19 (six [43%] of 14 vs 19 [6%] of 307; relative risk 7·1 [95% CI 2·2–22·4]). Interpretation According to serological test results, the proportion of young children in our sample with SARS-CoV-2 infection was low. Intrafamily transmission seemed more plausible than transmission within daycare centres. Further epidemiological studies are needed to confirm this exploratory hypothesis. Funding Assistance Publique—Hopitaux de Paris; Mairie de Paris, Conseil Departemental de Seine Saint Denis. Translations For the French translation of the abstract see Supplementary Materials section.

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution. METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement. RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children

Acute arthritis is a common cause of consultation in pediatric emergency wards. Arthritis can be caused by juvenile idiopathic arthritis (JIA), septic (SA) or remain undetermined (UA). In young children, SA is mainly caused by Kingella kingae (KK), a hard to grow bacteria leading generally to a mild clinical and biological form of SA. An early accurate diagnosis between KK-SA and early-onset JIA is essential to provide appropriate treatment and follow-up. The aim of this work was to compare clinical and biological characteristics, length of hospital stays, duration of intravenous (IV) antibiotics exposure and use of invasive surgical management of patients under 6 years of age hospitalized for acute monoarthritis with a final diagnosis of JIA, SA or UA. We retrospectively analyzed data from 9/L [10–13.6]) when compared to SA (13.2 × 109/L [11–16.6]), p = 0.01. In synovial fluid leucocytes were higher in SA 105.5 × 103 cells/mm3 [46–211] compared to JIA and UA (42 × 103 cells/mm3 [6.4–59.2] and 7.29 × 103 cells/mm3 [2.1–72] respectively), p Kingellakingae in these patients.

Background Sickle cell disease (SCD) children are frequent travellers to countries where yellow fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU. Method SCD children Results Among the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57 and 35%, respectively, P = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0 months (3.5–8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group vs 100% in the non-HU group (P = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines. Conclusion YF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU.

Introduction : les personnes âgees fragiles de plus de 75 ans ont de plus en plus recours aux services d’urgence ; leur etat de fragilite conduit souvent a des situations d’agitation qui soulevent des questions de prise en soins particulierement complexes.Objectif : comprendre la situation des personnes âgees, fragiles et agitees dans les services d’urgence et examiner la possibilite d’ameliorer la qualite des soins avec l’intervention d’une infirmiere de pratique avancee. Methode : etude exploratoire, descriptive qualitative, s’appuyant sur la realisation de neuf entretiens semi-directifs aupres de professionnels intervenant aux urgences et sur l’observation de situations de soins dans ces services. L’analyse est fondee sur l’elaboration d’un arbre thematique et l’examen de la signification des phenomenes observes.Resultats : cinq themes emergent des entretiens : definition de l’agitation, causes et facteurs favorisants, consequences, risques pour la personne âgee et impact sur les soins. Les contenus des entretiens permettent d’identifier la signification du phenomene, le lien entre agitation et fragilite, les difficultes et les mesures possibles permettant d’ameliorer la prise en charge.Discussion : les resultats rejoignent ceux de la litterature et permettent a l’infirmiere de pratique avancee d’identifier sa contribution a la gestion de ces situations complexes.Conclusion : la fragilite etant un processus reversible, la pratique infirmiere avancee pourra ameliorer la qualite des soins dispenses aux personnes âgees fragiles et agitees aux urgences.

Resume Contexte L’apport du dosage de la procalcitonine (PCT) chez les nourrissons atteints de bronchiolite reste incertain. Objectifs Les objectifs de cette etude etaient de decrire en pratique les resultats du dosage de PCT chez les nourrissons consultant pour une bronchiolite et de comparer les caracteristiques des nourrissons selon le resultat du dosage. Methodes Cohorte historique de nourrissons admis en urgence pour une bronchiolite entre le 1er janvier 2014 et le 31 decembre 2014 et ayant eu un dosage de PCT. Les caracteristiques cliniques biologiques et radiologiques des nourrissons avec PCT Resultats Cent trente six nourrissons ont ete inclus. Les patients avec PCT elevee (n = 20) avaient une temperature plus elevee (38,5 °C, intervalle interquartile [IIQ] = 37,8 − 38,6 vs 37,5°C, IIQ = 37,1 − 38,2 ; p Conclusion Au service d’accueil des urgences pediatriques, devant une bronchiolite febrile, le taux de PCT au seuil de 1 μg/L ne permet pas de predire l’existence ou non d’un foyer alveolaire mais il semble fortement associe a une prescription d’antibiotique, ce qui suggere qu’il pourrait influencer fortement cette prescription. L’association entre les taux de PCT, les resultats des radiographies de thorax et les prescriptions d’antibiotiques devraient etre evaluees de maniere prospective, afin de proposer une strategie diagnostique et therapeutique.

BackgroundWhen conducing Phase-III trial, regulatory agencies and investigators might want to get reliable information about rare but serious safety outcomes during the trial. Bayesian non-inferiority approaches have been developed, but commonly utilize historical placebo-controlled data to define the margin, depend on a single final analysis, and no recommendation is provided to define the prespecified decision threshold. In this study, we propose a non-inferiority Bayesian approach for sequential monitoring of rare dichotomous safety events incorporating experts’ opinions on margins.MethodsA Bayesian decision criterion was constructed to monitor four safety events during a non-inferiority trial conducted on pregnant women at risk for premature delivery. Based on experts’ elicitation, margins were built using mixtures of beta distributions that preserve experts’ variability. Non-informative and informative prior distributions and several decision thresholds were evaluated through an extensive sensitivity analysis. The parameters were selected in order to maintain two rates of misclassifications under prespecified rates, that is, trials that wrongly concluded an unacceptable excess in the experimental arm, or otherwise.ResultsThe opinions of 44 experts were elicited about each event non-inferiority margins and its relative severity. In the illustrative trial, the maximal misclassification rates were adapted to events’ severity. Using those maximal rates, several priors gave good results and one of them was retained for all events. Each event was associated with a specific decision threshold choice, allowing for the consideration of some differences in their prevalence, margins and severity. Our decision rule has been applied to a simulated dataset.ConclusionsIn settings where evidence is lacking and where some rare but serious safety events have to be monitored during non-inferiority trials, we propose a methodology that avoids an arbitrary margin choice and helps in the decision making at each interim analysis. This decision rule is parametrized to consider the rarity and the relative severity of the events and requires a strong collaboration between physicians and the trial statisticians for the benefit of all. This Bayesian approach could be applied as a complement to the frequentist analysis, so both Data Safety Monitoring Boards and investigators can benefit from such an approach.

Background Migraine is a common cause of headache in childhood. Several studies have investigated the association between migraine and atopic diseases, mostly in the adult population. Objective This study aimed to investigate this association in children. Methods A case-control study was conducted across 3 European tertiary care hospitals between June 2014 and August 2014. Cases (n = 229) were children aged 6-18 years consulting for a migraine episode. Controls in the same age range (n = 406) were consulting for a minor injury and did not have a history of recurrent headache. Logistic regression analyses tested the effect of atopic diseases and anti-allergic therapies on occurrence of migraine. Results Children with migraine were more likely to have persistent asthma compared to absence of asthma (odds ratio [OR]: 4.57, 95% confidence interval [CI]: 2.04-10.24) and less likely to have been treated by inhaled or nasal corticosteroid (OR: 0.34, 95% CI: 0.15-0.76) or antihistamine therapy (OR: 0.33, 95% CI: 0.18-0.60). The median number of monthly migraine episodes was higher in children with persistent asthma (3; interquartile [IQR]: 1-4; range: 0.5-10) compared to children with intermittent asthma (2; IQR: 1-3; range: 0.1-4) or non-asthmatic children (2; IQR: 1-3; range: 0.1-12) (P

Spirometry is the most common pulmonary function test (PFT) used to follow asthmatic patients. It is recommended to withhold Short-Acting Beta 2-Agonists (SABA) a few hours before PFTing, and to withhold Long-Acting Beta 2-Agonists (LABA) for diagnosis purpose but not for the assessment of response to a current treatment [1>]. In asthmatic children, the addition of LABA to inhaled corticosteroids (ICS) has no clear clinical benefit but it has proved to improve baseline Forced Expiratory Volume in 1 s (FEV1) [2]. The maximal increase in FEV1 after a single dose of formoterol was measured 3 h after administration but the remaining effect after 12 h would depend on the inhaled dose [3]. Finally, 25 µg or 50 µg of Salmeterol inhaled at 10 p.m. resulted in higher baseline pulmonary function and decrease in exercise induced bronchoconstriction 10 and 12 h later [4]. In routine practice, children are tested with various delays since last LABA inhalation, but LABA is usually inhaled on the morning of the test ( 12 h) or on the morning the previous day or before (>24 h). It is thought that children with the most recent inhalation should have the best pulmonary function and the lowest reversibility, but the latter has not been studied. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Taytard has nothing to disclose. Conflict of interest: Dr. Aupiais has nothing to disclose. Conflict of interest: Dr. Jovien has nothing to disclose. Conflict of interest: Dr. Assouline Kabla has nothing to disclose. Conflict of interest: Dr. Haziot has nothing to disclose. Conflict of interest: Dr. Fuger has nothing to disclose. Conflict of interest: Dr. Alberti has nothing to disclose. Conflict of interest: Dr. Beydon has nothing to disclose.

Context Growth hormone (GH) therapy may improve statural growth outcomes in patients with severe juvenile idiopathic arthritis (JIA). Objectives To evaluate the effect of GH treatment on adult height and to identify determinants of growth outcomes in JIA. Design and Patients Data from 58 patients with JIA, including 53 receiving GH, enrolled in three prospective clinical trials between 1997 and 2002 were analyzed. Intervention GH (0.056 mg/kg/d [interquartile range (IQR), 0.050 to 0.062]) for a median duration of 6.5 years (IQR, 4.7 to 7.9 years). Main Outcome Measures Factors associated with a favorable growth outcome (adult height - target height ≤ -1.5 standard deviations) were identified by multivariate logistic regression. Results Adult height was available for 48 patients 8.6 years after GH initiation (IQR, 6.0 to 10.2 years). Height standard deviation score (SDS) increased from -2.9 (IQR, -4.4 to -1.6) at baseline to -1.7 (IQR, -3.9 to -0.1) in adulthood (P < 0.001). Median adult height was below target height [SDS, -0.2 (IQR, -1.4 to 0.4); P < 0.001]. Corrected adult height SDS was -1.3 (IQR, -3.0 to -0.2). Growth outcome was favorable in 24 (52.2%) patients. Significant independent determinants of growth outcome were age at GH initiation [adjusted odds ratio (aOR), 0.68 per additional year; 95% confidence interval (CI), 0.47 to 0.99], height at GH initiation (aOR, 2.6 per additional SDS; 95% CI, 1.15 to 5.9), and mean C-reactive protein levels during follow up (aOR, 0.51 per additional 10 mg/L; 95% CI, 0.28 to 0.92). Conclusion Long-term GH treatment significantly increased growth in patients with JIA but did not fully restore the genetic growth potential. The response showed marked interindividual variability and was weaker in patients with severe inflammation.

Aim Studies on bone and joint infections (BJI) in infants under three months are rare. We described the clinical and paraclinical features and outcomes of infants hospitalised with BJI under three months of age. Methods The French National Hospital Discharge Database provided data on BJIs in infants under three months of age from January 2004 to 2015 in three Parisian Paediatric teaching hospitals. Results We included 71 infants under three months of age with BJI, the median age was 25 days, and the interquartile range (IQR) was 17-43 days. The most common infection sites were the hip (32%) and knee (32%). Symptoms included pain (94%), limited mobility (87%) and/or fever (52%). There were 11 (15.5%) cases of nosocomial BJI. A pathogen was identified in 51 infants (71.8%), including Streptococcus agalactiae (45%), Staphylococcus aureus (22%) and Escherichia coli (18%). The initial median C-reactive protein test rate was 31 mg/L (IQR 17-68). Of the 34 infants followed for more than one year, four developed severe orthopaedic conditions such as epiphysiodesis, limb length discrepancy, bone necrosis and/or impaired limb function. Conclusion Streptococcus agalactiae was the most common cause of BJI in infants under three months. Orthopaedic sequelae were rare, but severe, and required long-term follow-up.

To review characteristics, methodology and reporting of non-inferiority and equivalence trials in the specific context of paediatrics.PubMed and Cochrane databases were searched (up to September 2016) for non-inferiority/equivalence randomised controlled trials conducted in children published in high-impact-factor journals (We found that the statistical hypothesis was inconsistent with the objective in 12 (10%) of the 125 reports included. Non-inferiority (n=98) and equivalence trials (n=27) were mostly used to evaluate interventions with easier administration (45%, n=54/120) and/or better safety profile (34%, n=41/120). All the data needed for targeted sample size recalculation were available for 39 reports (31%). The margin-representing the largest difference between arms that would be clinically acceptable-was reported in 119 (95%), and 44/119 (37%) reported the method used for margin determination. The median sample size was 268 (IQR 125-531). Margins were wider in smaller trials (125 randomised patients) than in larger trials (p=0.04/p0.01 for binary/continuous outcomes, respectively). We did not agree with the authors' conclusions in 11% (11/103) of the reports that provided sufficient information.There is still a need to improve the quality of methodology, reporting and interpretation of non-inferiority/equivalence trials in paediatrics. In particular, the margins were often not justified and the conclusion was often not supported by the design and/or the results. As researchers have to cope with small sample size and with lack of evidence, methods for non-inferiority/equivalence trials need to be used and/or developed in this vulnerable population.

International audience; Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) both entail bronchiectasis and pulmonary impairment as measured using spirometry, during childhood. We aimed at looking whether blood gas exchanges progressed differently between CF and PCD children in a retrospective study of repeated measurements. Comparisons between groups (Wilcoxon-Mann-Whitney and Chi-squared tests) and a mixed linear model, adjusted for age, evaluated associations between diseases and PaO2, PaCO2, or PaO2-PaCO2 ratio.Among 42 PCD and 73 CF children, 62% and 59% had respectively bronchiectasis (P = 0.75). Spirometry and blood gases were similar at inclusion (PaO2 median [IQR] PCD −1.80 [−3.40; −0.40]; CF −1.80 [−4.20; 0.60] z-scores; P = 0.72). PaO2 and PaO2-PaCO2 ratio similarly and significantly decreased with age in both groups (P

Background and objectiveArthritis in children has many causes and includes septic and viral arthritis, reactive arthritis and juvenile idiopathic arthritis (JIA). We aimed to describe the different types of arthritis among children hospitalised for a first episode of arthritis.DesignRetrospective, descriptive case series study.SettingA French tertiary care centre.PatientsChildren under 16 years of age hospitalised for an arthritis episode between 1 January 2008 and 31 December 2009.Main outcome measuresDemographic and clinical features were compared with χ2or Fisher's exact tests and non-parametric tests.Results173 children were hospitalised for a first episode of arthritis during the study period, with a male/female ratio of 1.14. The most frequent cause of hospitalisation was septic arthritis (43.4% of cases, 69.3% of which were due toKingella kingaeand 10.7% toStaphylococcus aureus). JIA was responsible for 8.1% of cases and arthritis without any definitive diagnosis for 40.4%. Median age at diagnosis was 2.7 years (IQR 0.3–14.6) and was lower in the septic arthritis group (1.5 years; 1.1–3.4) than in the JIA group (4.7 years; 2.5–10.9) (pConclusionsSeptic arthritis was the most frequent cause of arthritis in hospitalised children. Despite the increasing application of microbiological molecular methods to synovial fluid analysis, further measures are required to improve the diagnosis of arthritis of unknown cause.

Introduction: Studies on first-degree relatives of non-obese patients suggest that genetics play a role in Obstructice Sleep Apnea Syndrome (OSAS). Aim: To study familial aggregation of OSAS and tonsillar hypertrophy. Methods: Prospective monocentre cohort study in non-obese children referred for suspected OSAS, classified as presenting or not a clinical OSAS according to national recommendations criteria. At inclusion, parents completed the Berlin questionnaire, and familial history of tonsillectomy was recorded. Polysomnography (PSG) were performed as recommended. The clinical persistence of OSAS was assessed 1 year later. Results: Seventy three non-obese children (25 girls) median [Q1;Q3] 5.1 [3.3;7.0] years old, were included. Clinical OSAS was present in 62 (85%) of them, 27 (38%) had a familial history of tonsillectomy, and 21 (29%) had at least one parent with a positive Berlin questionnaire. Fifty six children underwent PSG recording, with an Apnea Hypopnea Index, available in 52 children, of 2.9 [1.3;7.5]/h. Children were divided into two groups: no or mild OSAS (n=34 (65%)), and moderate to severe OSAS (n=18 (35%)). There was no difference between groups for the familial history of tonsillectomy (p=0.14) or the frequency of positive Berlin questionnaire (p=0.51). The size of the children’s tonsils was not related to Berlin questionnaire result (p=1). Residual clinical OSAS was detected in 17/37 (46%) children followed-up. It was more frequent in children without tonsillectomy after inclusion compared to these with tonsillectomy (p=0.001) but was not influenced by the Berlin questionnaire (p=0.72). Conclusion: This sudy did not evidence familial aggregation of OSAS and tonsil hypertrophy.

We investigated the knowledge of female genital mutilation (FGM) among 60 general and 52 specialized travel medicine practitioners. Less than 50% of these practitioners had adequate knowledge of FGM. Only 42.9% declared having encountered FGM. FGM is likely underestimated in health facilities. Medical education and supporting information should be developed to better address and prevent FGM.

Septic arthritis has to be suspected in children with joint effusion and fever so as to perform joint aspiration, which will confirm the diagnosis by bacteriological methods, and to perform surgical treatment by joint lavage. Since development of current molecular methods, such as real-time PCR, Kingella kingae has become the first microbial agent of osteoarticular infections in young children, whereas Staphylococcus aureus is second. C-reactive protein (CRP) is an aid used to diagnose septic arthritis, but its elevation could be moderate. In a previous study, conducted at our hospital, 10% of children hospitalized for S. aureus or K. kingae septic arthritis had a CRP level 10 mg/L during septic arthritis in children, it could be negative in up to 20% of patients in different studies. However, a mild inflammatory syndrome or even a CRP

Introduction Le vaccin de la fievre jaune (FJ) est contre-indique chez les patients ayant une immunosuppression. Malgre l’absence de donnees, les recommandations sanitaires pour le voyageur autorisent cette vaccination chez les patients drepanocytaires traites par hydroxycarbamide (HC). L’objectif de cette etude etait d’evaluer la tolerance et l’efficacite du vaccin FJ chez des enfants drepanocytaires traites ou non par HC. Materiels et methodes Il s’agit d’une etude prospective realisee entre mars 2016 et juillet 2017. Tous les enfants drepanocytaires de mois de 18 ans, traites ou non par HC et recevant un vaccin FJ dans un des 3 centres de vaccination du voyage de l’etude ont ete inclus. La tolerance a ete evaluee par un entretien telephonique a 15 jours de l’injection. L’efficacite a ete evaluee a environ 6 mois par une serologie FJ > 5 en methode PRNT80. Le test Mann–Whitney a ete utilise pour les comparaisons. Resultats Au total, 54 enfants, âge median de 7.6 ans [2,9 ; 12,4], sex-ratio M/F 0,61, ont ete inclus. Tous recevaient une primo-vaccination. Dix-sept sur 54 etaient traites par HC. Les enfants HC + etaient plus âges que les enfants HC − (6,8 vs 9,5 ans, p = 0,0015), plus souvent sous programme d’echange transfusionnel (17 vs 3 %, p = 0,006) et avaient des lymphocytes totaux plus bas (3,3 vs 4,9 G/L, p = 0,014) que les enfants HC −. Quarante-trois pourcent des enfants ont eu des effets indesirables post-vaccination, tous de grade I/II. Les plus frequents etaient une douleur au point d’injection (24 % des patients) ou une fievre (17 % des patients). Globalement, la frequence des effets indesirables etait identique dans les 2 groupes (37 % dans le groupe HC − vs 57 % dans le groupe HC + , p = 0,15). La proportion de seroconversion FJ etait plus faible dans le groupe HC + (85 %) par rapport au groupe HC − (100 %). Le titre d’anticorps median etait comparable dans les deux groupes (40 UI/mL). Conclusion La tolerance de la vaccination FJ semble satisfaisante chez les enfants traites par HC bien que la taille de notre effectif ne permette pas de conclure definitivement. Les enfants drepanocytaires sous HC ont toutefois une moins bonne reponse vaccinale. Un controle serologique est necessaire chez ces enfants afin de discuter la realisation d’une 2e dose de vaccin fievre jaune avant un nouveau depart en zone d’endemie.

Introduction Les essais de non-inferiorite (NI) sont de plus en plus utilises lorsque l’on souhaite demontrer qu’un nouveau traitement - dont le benefice potentiel reside dans son cout, sa facilite d’utilisation et/ou sa tolerance - est aussi efficace qu’un traitement standard. Un des enjeux methodologiques est la determination de la marge de NI, qui doit idealement faire intervenir les donnees historiques comparant le traitement standard au placebo. Le manque de donnees historiques implique parfois de definir ces marges en ne se basant que sur des considerations cliniques. Les essais cliniques de NI comme de superiorite se heurtent parfois au manque de puissance necessaire pour obtenir des conclusions valides quant aux criteres secondaires. Neanmoins, il serait souhaitable pour les decideurs et investigateurs de ne pas avoir a attendre les meta-analyses d’essais cliniques pour avoir des informations sur la securite d’une nouvelle intervention. De telles informations de securite peuvent etre egalement requises lors des analyses intermediaires d’un essai. L’objectif de ce travail est de developper une methodologie sequentielle bayesienne de NI, incorporant des marges basees sur une elicitation d’experts, afin de monitorer des evenements binaires rares. Methodes Notre methode a ete developpee en prenant comme illustration un essai de NI realise chez des femmes enceintes a risque d’accouchement premature (essai BETADOSE, NCT02897076 ). Les objectifs secondaires de cet essai incluent de monitorer, a chaque analyse intermediaire, la survenue de quatre evenements graves chez les nouveau-nes prematures. La methodologie repose sur la construction d’un critere Bayesien de NI pour ces evenements, critere definissant a chaque analyse intermediaire des seuils d’arret pour exces inacceptable d’evenement dans le bras experimental. Ce critere Bayesien integre des marges de NI construites a partir des Resultats d’une elicitation d’expert, sous forme de mixtures de lois Beta, afin de prendre en compte la variabilite intra-experts. Une analyse de sensibilite a evalue plusieurs lois a priori - non-informatives et informatives - et plusieurs seuils d’arret. Les parametres selectionnes doivent permettre de maintenir a des niveaux acceptables les taux de mauvaises conclusions, i.e. les essais qui concluent faussement a une difference inacceptable et vice-versa. Resultats L’opinion de 44 experts a pu etre elicitee. Les taux acceptables de mauvaises conclusions ont ete fixes selon la severite relative de chacun des evenements. Des seuils propres de decision ont ete applique a chaque evenement, permettant de prendre en compte leurs differences de prevalence, de marges de NI et de severite. Les parametres finaux de notre regle de decision donnaient des taux acceptables de mauvaise conclusion. L’application de la regle de decision a un set de donnees simulant l’essai clinique illustre une situation ou le critere bayesien de decision suggere d’arreter l’essai a la sixieme analyse intermediaire pour surcroit inacceptable d’un evenement. Conclusion Motives par le desir de conduire des essais cliniques de non-inferiorite dans des situations ou les donnees historiques manquent et dans le cas ou certains evenements secondaires rares mais graves doivent etre surveilles, nous proposons une methodologie bayesienne de NI permettant de ne pas utiliser des marges de NI arbitraires et d’aider a prendre la decision a chaque analyse intermediaire.

AimChildhood arthritis arises from several causes. The aim of this observational study is to compare the clinical and biological features and short-term outcome of different types of arthritis because they have different treatment and prognoses.MethodsChildren ResultsWe studied 125 children with a sex ratio (M/F) of 1.1 and a median age of 2.2 years (range 0.3 to 14.6). SA was associated with a lower age at onset (1.5 years, IQR 1.2–3.0 vs 3.6 years, IQR 2.2–5.6), shorter duration of symptoms before diagnosis (2 days, IQR 1–4 vs 7 days, IQR 1–19) and higher synovial white blood cell count (147 cells ×103/mm3, IQR 71–227, vs 51 cells ×103/mm3, IQR 12–113), than JIA. Apyrexia occurred later in children with JIA (40% after 2 days, 95% CI 17% to 75%) than children with SA (82%, 95% CI 68% to 92%), as did CRPConclusionsThere were no sufficiently reliable predictors for differentiating between SA and JIA at onset. The outcomes were different; JIA should be considered in cases of poor disease evolution after antibiotic treatment and joint aspiration.

Introduction Les essais de non-inferiorite (NI) et d’equivalence (EQ) sont de plus en plus utilises en recherche clinique lorsque l’on souhaite demontrer qu’un nouveau traitement–dont le benefice potentiel reside dans son cout, sa facilite d’utilisation et/ou sa tolerance–est aussi efficace qu’un traitement standard. Une revue systematique a ete menee pour decrire les essais de NI/EQ en pediatrie, leurs aspects methodologiques et statistiques. Une attention particuliere est portee au calcul de la taille de l’echantillon. Methodes Une recherche electronique sur Medline® et Cochrane Library a identifie les ECR de NI/EQ en pediatrie, publies avant septembre 2016 dans des revues a haut « impact factor ». Les principaux items recueillis etaient : la methodologie de l’essai, les methodes d’analyses et les hypotheses retenues pour le calcul de la taille de l’echantillon. Les marges de NI/EQ sont presentees en difference de risque pour les criteres de jugement (CJ) binaires et en coefficient d de Cohen pour les CJ continus. Les essais dont la taille d’echantillon etait dans le quartile inferieur ont ete compares aux essais plus larges. Resultats Parmi les 125 essais de NI/EQ en pediatrie inclus, 67 % ont ete publies depuis 2010 et 78 % testaient une hypothese alternative de NI. Les benefices des interventions testees etaient : la facilite d’administration (45 %), un meilleur profil de securite (34 %) et/ou un moindre cout (26 %). Tous les essais ont utilise des statistiques frequentistes. La moitie des essais ont effectue les analyses a la fois en intention de traiter (ITT) et en per-protocole (PP), tandis que 38 % et 12 % ont uniquement effectue les analyses ITT ou PP, respectivement. Toutes les donnees necessaires au calcul de la taille de l’echantillon etaient renseignees pour 75 % des publications. La marge de NI/EQ etait rapportee dans 91 % des essais, mais 64 % de ces etudes ne decrivaient pas la methode utilisee pour la determiner. Parmi les essais utilisant un CJ binaire, 74 % utilisaient des marges 15 %. Parmi les essais utilisant un CJ continu, la marge correspondait a un coefficient d de Cohen de −0,5 (IQR : −0,7 ; −0,4). Le nombre median de patients randomises etait de 268 (125 ; 531). Les essais ayant une taille d’echantillon Conclusion Les essais de NI/EQ sont notamment utilises en pediatrie pour l’evaluation de traitements plus faciles d’utilisation. Les essais sur petits echantillons sont frequents dans ce contexte. Le prix a payer semble inclure l’utilisation de marges plus larges de NI/EQ. De nouvelles methodes doivent etre developpees pour analyser ces essais sur petits echantillons sans augmenter les marges.

Antiretroviral treatment interruption (TI) is not recommended in HIV-infected children. We aimed to evaluate the context and consequences of TI in clinical practice.We investigated the probability and risk factors of a first TI in the 483 children treated with combined ART (cART) in the ANRS French national pediatric cohort. Immunologic and virologic outcomes were compared between patients with TI (TI group) and those on continuous treatment (matched control group), from a baseline defined as the age at first interruption for the TI child and the corresponding age for the control child.At least one TI ≥ 3 months occurred in 42.4% of patients, at a median age of 8.0 years, for a median duration of 12.1 months. After cART initiation, the risk of TI was 7.0% (5.0-9.6) at 1 year and 30.3% (26.1-35.0) at 5 years and was higher for children starting treatment before 2000 and for children starting cART before 6 months of age. AIDS-free survival was similar, but severe immunosuppression occurred earlier in the TI group than in the control group (adjusted HR = 3.1; 1.0-9.1; P = 0.04). Four years after baseline, the proportion of patients with CD4% ≥ 25% was lower in the TI group than in the control group (52.0% vs. 72.0%; P0.01), even among children restarting cART at least 6 months earlier (aRR = 0.5; 0.3-0.9; P = 0.03).The risk of TI in clinical practice has decreased but remains high. In intent-to-treat analysis, TI was associated with a greater risk of subsequent immunosuppression, even after cART resumption.

Objectifs Decrire les infections osteoarticulaires (IOA) des nourrissons de moins de 3 mois. Materiels et methodes Les donnees ont ete collectees retrospectivement chez tous les enfants âges de moins de 3 mois hospitalises pour une IOA sur une periode de 11 ans (2004–2015) dans les CHU Debre, Trousseau et Necker (Paris). Resultats Au total, 71 enfants ont ete inclus avec un sexe ratio (M/F) de 1,4 et un âge median de 25 jours [0–90] ; 11 enfants (15,4 %) etaient prematures, 11 avaient une IOA nosocomiale. Les atteintes les plus frequentes etaient la hanche (32 % des enfants) et le genou (32 %). Les symptomes etaient la douleur (94 %), l’impotence fonctionnelle (87 %), la fievre (52 %). Le delai diagnostique median etait de 2 jours [0–15]. Un germe a ete identifie chez 51 enfants (72 %) : Streptocoque du groupe B (45 % des germes), S. aureus (23,5 %), E. coli (17,6 %). La CRP mediane initiale etait de 31 mg/L [1–226]. Cinq patients (sur 34 avec suivi > a 1 an) ont presente des sequelles orthopediques, dont : inegalite de longueur de membre (n = 3), epiphysiodese (n = 2), osteonecrose (n = 1). Conclusion Le streptocoque du groupe B est le germe le plus frequent dans les IOA communautaires du moins de 3 mois. Les sequelles orthopediques peuvent etre severes justifiant un suivi orthopedique prolonge.

Objectif Decrire les infections osteo-articulaires (IOA) des nourrissons de moins de 3 mois. Patients et methodes Les donnees ont ete collectees retrospectivement chez tous les enfants âges de moins de 3 mois hospitalises pour une IOA sur une periode de 11 ans (2004–2015) dans les CHU Debre, Trousseau et Necker (Paris). Resultats Au total, 71 enfants ont ete inclus avec un sex-ratio (M/F) de 1,4 et un âge median de 25 jours [0–90] ; 11 enfants (15,4 %) etaient prematures, 11 avaient une IOA nosocomiale. Les atteintes les plus frequentes etaient la hanche (32 % des enfants) et le genou (32 %). Les symptomes etaient la douleur (94 %), l’impotence fonctionnelle (87 %), la fievre (52 %). Le delai diagnostique median etait de 2 jours [0–15]. Un germe a ete identifie chez 51 enfants (72 %) : Streptocoque du groupe B (45 % des germes), S. aureus (23,5 %), E. coli (17,6 %). La CRP mediane initiale etait de 31 mg/L [1–226]. Cinq patients (sur 34 avec suivi > 1 an) ont presente des sequelles orthopediques, dont : inegalite de longueur de membre ( n = 3), epiphysiodese ( n = 2), osteonecrose ( n = 1). Conclusion Le streptocoque du groupe B est le germe le plus frequent dans les IOA communautaires du moins de 3 mois. Les sequelles orthopediques peuvent etre severes justifiant un suivi orthopedique prolonge.

International audience; BACKGROUND: Group A rotaviruses are the main viral causative agent of acute diarrhea, and cause considerable morbidity in children. G9 rotaviruses have recently emerged all over the world and are thought to give more severe symptoms because of a lack of previous exposure and the absence of maternal antibodies in patients. OBJECTIVES: To determine the clinical severity of G9 infections compared to G1 infections in hospitalized children. STUDY DESIGN: The prospective study was conducted from 2004 to 2007 in French children under 5 years old hospitalized for acute gastroenteritis. The rotaviruses were detected in stools by ELISA tests and genotyped by RT-PCR on the basis of their outer capsid proteins. The duration of hospitalization, the Vesikari clinical score, and the requirement for intravenous rehydration were compared. RESULTS: The stools from 370 children were analyzed and 162 stools infected by G1 (n=76) or G9 (n=86) rotaviruses were analyzed. Age and gender distribution were similar in the two groups as was the mean duration of hospitalization (2.7 days). The Vesikari scores were 12.96 and 12.83 in G1P[8] and G9P[8] groups (p=0.417), respectively, in which 55.3 and 53.5% of the children, respectively, were rehydrated with an intravenous line. CONCLUSIONS: No difference in severity was found between G1 and G9 rotavirus infections. Rigorous surveillance to monitor changes in the ecology of rotavirus infections is necessary, as emerging strains are more likely to cause severe gastroenteritis and not respond to current rotavirus vaccines.