Search

BACKGROUND Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear. METHODS We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed. RESULTS The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%]). CONCLUSIONS In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. [ABSTRACT FROM AUTHOR]

Objective: To investigate a dose-response relationship between the magnitude of decrease in pediatric respiratory tract infections (RTI) during the 2020 implementation of non-pharmaceutical interventions (NPI) and the rise thereafter during NPI lifting., Study Design: We conducted an interrupted, time-series analysis, based on a multinational surveillance system. All patients <16 years of age coming to medical attention with various symptoms and signs of RTI at 25 pediatric emergency departments from 13 European countries between January 2018 and June 2022 were included. We used generalized additive models to correlate the magnitude of decrease of each RTI during NPI (such as social distancing) implementation and its subsequent increase during NPI lifting. Urinary tract infections (UTI) served as control outcome., Results: 528,055 patients were included. We observed reductions in cases during the NPI period, from -76% (95%CI -113;-53) in pneumonia) to -65% (95%CI[-100;-39) for tonsillitis/pharyngitis), followed by strong increases during NPI lifting, from +83% (95%CI 29;150) for tonsillitis/pharyngitis) to +329% (95%CI (149;517) bronchiolitis). For each RTI, we found a significant association between the magnitude of decrease during NPI implementation and the increase during NPI lifting. UTI cases remained stable., Conclusions: The magnitude of increase in RTI observed following NPI lifting was directly correlated to the magnitude of cases' reduction during NPI implementation, suggesting a "dose-response" relationship from an "immune debt" phenomenon. The likely rebound in RTIs should be expected when implementing and lifting NPI in the future., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To study the impact of nonpharmaceutical interventions implemented during the COVID-19 pandemic on the monthly incidence of sudden unexpected death in infancy (SUDI) cases overall and those with a viral or bacterial identification., Study Design: We conducted an interrupted time-series analysis using seasonally adjusted Poisson regression models from the French national prospective and multicenter SUDI registry, that included all SUDI cases below the age of 1 year who died from 2016 to 2021 in mainland France., Results: Of 998 SUDI cases analyzed, 750 were recorded during the prepandemic period (January 2016 through March 2020) and 248 during the NPI period (April 2020 through December 2021). We found a significant seasonal pattern of overall monthly SUDI incidence, with a peak observed periodically from November to February. The monthly SUDI incidence decreased significantly from the prepandemic to NPI periods (adjusted incidence rate ratio 0.83 [95% CI 0.72-0.96]). In particular, the monthly incidence of SUDI cases with a viral or bacterial identification decreased significantly, while no significant difference was found for SUDI cases without a viral or bacterial identification., Conclusions: Nonpharmaceutical interventions were associated with a significant change in the incidence of SUDI cases with a viral or bacterial identification. Further investigations are needed to analyze the pathophysiologic role of viruses and bacteria in the SUDI., Competing Interests: Declaration of Competing Interest The French SUDI registry receives main funding from AXA, France; MSDAvenir, France; Sanofi Pasteur-MSD, France; the French national public health agency (Santé Publique France), France; the National Institute of Health and Medical Research (Inserm), France; and 3 French parent associations (SA VIE, Naitre et Vivre, and Les Rires d'Anna); it also received gifts from private organizations and companies. This particular work was supported by the Fondation de France (Alliance “Tous unis contre le virus”, grant n°APHP220322). Funders were not involved in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. No support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work, and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Mental disorders among the pediatric population are a major area of public health concern. Little is known regarding changes in pediatric hospital resource use related to mental health (MH) long after the onset of the COVID-19 pandemic in March 2020., Objective: To assess rates and trends of hospitalizations and emergency department (ED) visits related to MH and self-harm (SH) among children before and during the 3 years following the pandemic onset., Design, Setting, and Participants: This cross-sectional study used national hospital data. The study sample included all MH- and SH-related hospitalizations and ED visits among children aged 6 to 17 years in France between January 1, 2016, to May 31, 2023., Main Outcomes and Measures: Interrupted time-series analysis of monthly rates of MH- and SH-related hospitalizations and ED visits per 100 000 children was conducted to assess changes before and every year after the pandemic onset. Rate ratios (RRs) between estimated and expected rates were calculated., Results: Overall, 583 244 hospitalizations (81.4% for MH and 18.6% for SH) and 432 725 ED visits (79.9% for MH and 20.1% for SH) were analyzed. The mean (SD) age of the children was 13.7 (2.9) and 14.8 (1.7) years for MH-related and SH-related hospitalizations, respectively, and 14.2 (2.6) and 14.6 (2.1) years for MH-related and SH-related ED visits, respectively. For MH-related hospitalizations, 52.6% were female and 47.4% were male; for SH-related hospitalizations, 83.1% were female and 16.9% were male. For MH-related ED visits, 62.8% were female and 37.2% were male; for SH-related ED visits, 77.4% were female and 22.6% were male. Before the pandemic, an increasing trend in all monthly rates, except that of MH-related hospitalizations, was observed. After an immediate decrease in hospitalization and ED visit rates during the initial pandemic period (March 1 to May 31, 2020), trends increased in the first 2 years following the pandemic onset and decreased thereafter. Overall, rates of MH-related hospitalizations and ED visits exceeded expected rates in only the second year after the pandemic onset, with increases of 6.0% (RR, 1.06 [95% CI, 1.05-1.06]) and 5.0% (RR, 1.05 [95% CI, 1.04-1.05]), respectively. However, rates of hospitalizations and ED visits for behavioral syndromes (mainly eating and sleeping disorders) persistently exceeded expected rates, with increases of 29.0% (RR, 1.29 [95% CI, 1.25-1.34]) and 26.0% (RR, 1.26 [95% CI, 1.21-1.31]) in the third year, respectively. Likewise, rates of SH-related hospitalizations and ED visits persistently rose above expected rates, with increases of 29.0% (RR, 1.29 [95% CI, 1.26-1.32]) and 43.0% (RR, 1.43 [95% CI, 1.40-1.47]) in the third year, respectively., Conclusions and Relevance: In this cross-sectional study, persistent increases in the use of hospital resources to treat eating and sleeping disorders and intentional SH among pediatric patients were observed long after the onset of the COVID-19 pandemic. These findings warrant future research to identify persistent stress factors in children.

Background: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated., Objective: This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes., Study Design: We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia., Results: After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial., Conclusion: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is the leading cause of lower-respiratory-tract infection in children. Nirsevimab, a monoclonal antibody against RSV, was implemented in a few countries in September 2023. However, its post-license effectiveness in ambulatory care settings is unknown. We aimed to assess the effectiveness of nirsevimab against RSV-bronchiolitis in outpatients aged <12 months., Methods: We conducted a test-negative case-control study based on a national ambulatory surveillance system. We included all infants aged <12 months who had bronchiolitis and results of an RSV rapid antigen test performed, visiting a network of 107 ambulatory paediatricians from September 15, 2023, to February 1, 2024. Case patients were infants with bronchiolitis and a rapid antigen test positive for RSV. Control patients were infants with bronchiolitis and a rapid antigen test negative for RSV. Effectiveness was assessed by a logistic regression model adjusted for potential confounders. A range of sensitivity analyses were conducted to assess the robustness of the findings., Findings: We included 883 outpatients who had bronchiolitis and results of an RSV rapid antigen test (453 were case patients, and 430 were control patients). Overall, 62/453 (13.7%) case patients and 177/430 (41.2%) control patients had been previously immunised for nirsevimab. The adjusted effectiveness of nirsevimab against RSV-bronchiolitis was 79.7% (95% CI 67.7-87.3). Sensitivity analyses gave similar results., Interpretation: This post-license study indicates that nirsevimab was effective in preventing RSV-bronchiolitis in ambulatory care settings., Funding: The study was supported by Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), French Pediatrician Ambulatory Association (AFPA) and unrestricted grants from GSK, MSD, Pfizer and Sanofi., Competing Interests: YL has no conflicts of interest to disclose. RB declares receiving fees from Sanofi and MSD for medical conferences or scientific meetings. CL declares receiving travel grants from MSD, Pfizer and fees from MSD and Pfizer for scientific meetings and expert board participation. AW declares receiving fees from Sanofi, GSK and MSD for medical conferences or scientific meetings. FCS declares receiving fees from Sanofi for expert board participation. CB declares receiving fees from Sanofi, GSK and MSD for medical conferences or scientific meetings. RC reports personal fees and non-financial support from Pfizer and personal fees from GSK, Merck, Pfizer, Sanofi, Viatris outside the submitted work. NO declares receiving travel grants from MSD, Pfizer, Sanofi, and GSK., (© 2024 The Authors.)

Background: Bronchiolitis 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., Methods: We 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., Results: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis., Conclusions: Several 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., Competing Interests: Conflict of interest: N. Ouldali reports travel grants from Pfizer, GSK and Sanofi. No other authors have conflicts of interest to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Testing for SARS-CoV-2 is central to COVID-19 management. Rapid antigen test from self-collected anterior nasal swabs (SCANS-RAT) are often used in children but their performance have not been assessed in real-life. We aimed to compare this testing method to the two methods usually used: reverse transcription polymerase chain reaction from nasopharyngeal swabs collected by healthcare workers (HCW-PCR) and rapid antigen test from nasopharyngeal swabs collected by healthcare workers (HCW-RAT), estimating the accuracy and acceptance, in a pediatric real-life study. From September 2021 to January 2022, we performed a manufacturer-independent cross-sectional, prospective, multicenter study involving 74 pediatric ambulatory centers and 5 emergency units throughout France. Children ≥6 months to 15 years old with suggestive symptoms of COVID-19 or children in contact with a COVID-19-positive patient were prospectively enrolled. We included 836 children (median 4 years), 774 (92.6%) were symptomatic. The comparators were HCW-PCR for 267 children, and HCW-RAT for 593 children. The sensitivity of the SCANS-RAT test compared to HCW-RAT was 91.3% (95%CI 82.8; 96.4). Sensitivity was 70.4% (95%CI 59.2; 80.0) compared to all HCW-PCR and 84.6% (95%CI 71.9; 93.1) when considering cycle threshold <33. The specificity was always >97%. Among children aged ≥6 years, 90.9% of SCANS-RAT were self-collected without adult intervention. On appreciation rating (from 1, very pleasant, to 10, very unpleasant), 77.9% of children chose a score ≤3. SCANS-RAT have good sensitivity and specificity and are well accepted by children. A repeated screening strategy using these tests can play a major role in controlling the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cohen, Aupiais, Filleron, Cahn-Sellem, Romain, Béchet, Auvrignon, Batard, Virey, Jung, Rybak and Levy.)

Background: Infants 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., Methods: 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)., Results: 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 values <0.5 ng/mL and only 1 had C-reactive protein level >20 mg/L., Conclusions: 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 infants <90 days old., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Antenatal 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., Methods: We 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., Findings: Between 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., Interpretation: Because 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., Funding: French Ministry of Health., Competing Interests: Declaration of interests TS reports receiving consulting fees from Dilafor. LS reports receiving consulting fees from Dilafor; lecture fees from Bayer, GlaxoSmithKline, and Sigvaris; and lecture and consulting fees from Ferring Pharmaceuticals. AJV reprts receiving consulting fees from Norgine. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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 < 18 years attending the international travel clinics of three large paediatric centres and requiring a first YF vaccination were included in a prospective study. Adverse events were collected 2 weeks after vaccination. YF vaccine antibody titres were measured ~6 months after vaccination., 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., (© International Society of Travel Medicine 2021. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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-Hôpitaux de Paris; Mairie de Paris, Conseil Départemental de Seine Saint Denis., Translations: For the French translation of the abstract see Supplementary Materials section., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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 <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children ( n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 ( n = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1-10.3), hypoxemia (OR = 8.9 [2.6-29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4-27.5])., Conclusions: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

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 < 6-year-old children, hospitalized at a French tertiary center for acute mono-arthritis, who underwent a joint aspiration. Non-parametric tests were performed to compare children with JIA, SA or UA. Bonferroni correction for multiple comparisons was applied with threshold for significance at 0.025. Among the 196 included patients, 110 (56.1%) had SA, 20 (10.2%) had JIA and 66 (33.7%) had UA. Patients with JIA were older when compared to SA (2.7 years [1.8-3.6] versus 1.4 [1.1-2.1], p < 0.001). Presence of fever was not different between JIA and SA or UA. White blood cells in serum were lower in JIA (11.2 × 10 9 /L [10-13.6]) when compared to SA (13.2 × 10 9 /L [11-16.6]), p = 0.01. In synovial fluid leucocytes were higher in SA 105.5 × 10 3  cells/mm 3 [46-211] compared to JIA and UA (42 × 10 3  cells/mm 3 [6.4-59.2] and 7.29 × 10 3  cells/mm 3 [2.1-72] respectively), p < 0.001. Intravenous antibiotics were administered to 95% of children with JIA, 100% of patients with SA, and 95.4% of UA. Arthrotomy-lavage was performed in 66.7% of patients with JIA, 79.6% of patients with SA, and 71.1% of patients with UA. In children less than 6 years of age with acute mono-arthritis, the clinical and biological parameters currently used do not reliably differentiate between JIA, AS and UA. JIA subgroups that present a diagnostic problem at the onset of monoarthritis before the age of 6 years, are oligoarticular JIA and systemic JIA with hip arthritis. The development of new biomarkers will be required to distinguish JIA and AS caused by Kingella kingae in these patients.

Objective: 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., Patients and Methods: 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., Results: 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 IFX >8.3 μg/ml at week 6 (P < 0.01)., Conclusion: Trough levels to IFX >8.3 μg/ml at week 6 are predictive of remission at W14 for luminal disease.

Background: When 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., Methods: A 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., Results: The 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., Conclusions: In 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.

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.

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., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Although antenatal betamethasone is recommended worldwide for women at risk of preterm delivery, concerns persist regarding the long-term effects associated with this treatment. Indeed, adverse events, mainly dose-related, have been reported. The current recommended dose of antenatal betamethasone directly derives from sheep experiments performed in the late 60's and has not been challenged in 45 years. Therefore, randomized trials evaluating novel dose regimens are urgently needed., Methods: A randomised, double blind, placebo-controlled, non-inferiority trial will be performed in 37 French level 3 maternity units. Women with a singleton pregnancy at risk of preterm delivery before 32 weeks of gestation having already received a first 11.4 mg injection of betamethasone will be randomised to receive either a second injection of 11.4 mg betamethasone (full dose arm) or placebo (half dose arm) administered intramuscularly 24 h after the first injection. The primary binary outcome will be the occurrence of severe respiratory distress syndrome (RDS), defined as the need for exogenous intra-tracheal surfactant in the first 48 h of life. Considering that 20% of the pregnant women receiving the full dose regimen would have a neonate with severe RDS, 1571 patients in each treatment group are required to show that the half dose regimen is not inferior to the full dose, that is the difference in severe RDS rate do not exceed 4% (corresponding to a Relative Risk of 20%), with a 1-sided 2.5% type-1 error and a 80% power. Interim analyses will be done after every 300 neonates who reach the primary outcome on the basis of intention-to-treat, using a group-sequential non-inferiority design., Discussion: If the 50% reduced antenatal betamethasone dose is shown to be non-inferior to the full dose to prevent severe RDS associated with preterm birth, then it should be used consistently in women at risk of preterm delivery and would be of great importance to their children., Trial Registration: ClinicalTrials.gov identifier: NCT 02897076 (registration date 09/13/2016).

Introduction: Emergency services are faced with people over the age of 75 whose frailty leads to states of agitation., Objective: To improve the quality of the care of this situation through the invention of an advanced practice nurse., Method: A phenomenological and monocentric study from interviews with professionals intervening in emergencies about the difficulties they encountered. A thematic tree was constructed once the interviews were transcribed and coded., Results: Five themes emerged from nine interviews, including: definition of agitation, its causes, and contributing factors. The consequences, the risks for the elderly, and the impact on care. The significance of this phenomenon. The link between agitation and frailty. Difficulties and possible measures to improve care., Discussion: The data collected correspond to the data featuring in the literature and allow advanced practice nurses to pinpoint their actions., Conclusion: Advanced practice nurses can contribute to improving the care of the agitated elderly through primary and secondary prevention.

Objective: To review characteristics, methodology and reporting of non-inferiority and equivalence trials in the specific context of paediatrics., Design: 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 ( > 5.0 for general/specialist medical journals; >2.2 for paediatric journals)., Results: 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/p<0.01 for binary/continuous outcomes, respectively). We did not agree with the authors' conclusions in 11% (11/103) of the reports that provided sufficient information., Conclusions: 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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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 PaO 2 , PaCO 2, or PaO 2- PaCO 2 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 (PaO 2 median [IQR] PCD -1.80 [-3.40; -0.40]; CF -1.80 [-4.20; 0.60] z-scores; P = 0.72). PaO 2 and PaO 2 -PaCO 2 ratio similarly and significantly decreased with age in both groups (P < 0.01) whereas PaCO 2 increased more in CF (P = 0.02) remaining within the range of normal (except for one child). To conclude, gas exchange characteristics, similarly initially impaired in PCD and CF children, tended to less deteriorate with time in PCD children who could benefit from an early diagnosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (© International Society of Travel Medicine, 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2017 Endocrine Society)

Context: Very few studies have evaluated the role of procalcitonin (PCT) in infants with bronchiolitis., Aims: To describe infants who had both a diagnosis of bronchiolitis at the emergency department and a blood test including PCT, and to compare the characteristics of children according to the PCT value., Methods: Infants admitted to the Pediatric Emergency Department between 1 January 2014 and 31 December 2014 who had a diagnosis of bronchiolitis and a blood test including PCT were included. The clinical, biological, and radiological characteristics of the infants with PCT <1 or ≥1g/L were compared., Results: One hundred thirty six infants were included. Patients with high PCT (n=20) had a higher temperature (38.5°C, IQR=37.8-38.6 vs. 37.5°C, IQR=37.1-38.2; P<0.01), C-reactive protein (50mg/L, IQR=25-83 vs. 5mg/L, IQR=0-19; P<0.01), and neutrophils (7.8×10 9 /L, IQR=6.0-8.5 vs 4.5×10 9 /L, IQR=2.9-6.6; P<0.01) higher than patients with low PCT (n=116). Presence on the chest x-ray of alveolar condensation did not differ between the two PCT groups. Infants coming from the low-PCT group received fewer antibiotics (14.7% vs 65%; P<0.01)., Conclusion: In a Pediatric Emergency Department, PCT with a value of 1 or more cannot predict the presence of alveolar condensation on the chest x-ray. It seems to be associated with the antibiotics prescription, even if this could not be proved because of the design of the study., (Copyright © 2017. Published by Elsevier SAS.)

Aim: Childhood 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., Methods: Children <16 years of age hospitalised in a French tertiary care centre for a first episode of arthritis lasting for less than 6 weeks who underwent joint aspiration were retrospectively included. We performed non-parametrical tests to compare groups (septic arthritis (SA), juvenile idiopathic arthritis (JIA) and arthritis with no definitive diagnosis). The time before apyrexia or C reactive protein (CRP) <10 mg/L was analysed using the Kaplan-Meier method., Results: We 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 ×10 3 /mm 3 , IQR 71-227, vs 51 cells ×10 3 /mm 3 , 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 CRP<10 mg/L (18% at 7 days, 95% CI 6.3% to 29.6% vs 82.1%, 95% CI 76.1% to 89.7%, p=0.01)., Conclusions: There 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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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 < .01)., Conclusion: Persistent childhood asthma was associated with increased risk of migraine and higher frequency of migraine attacks. History of anti-asthmatic or anti-allergic therapies was associated with decreased risk of migraine in children and adolescents. The role of these therapies on the pathogenesis and occurrence of migraine needs to be further elucidated because of the huge potential impact in terms of public health., (© 2017 American Headache Society.)

Background: Increasing numbers of young people with perinatally acquired HIV are surviving to adulthood. When they come of age, they leave pediatric services in which they were followed and have to be transferred to the adult health care system. Difficulties in adaptation to adult care and the numbers of young people lost to follow up after transfer to adult care have been reported. This transition phase and their retention in adult care are crucial in maintaining the clinical status of these young with HIV in adulthood. Our study aimed to explore how HIV professionals working in adult care perceive and adapt their practices to young people in transition., Methods: Qualitative interviews were conducted with 18 health and social services professionals in hospitals or patient associations in France. A thematic analysis was conducted., Results: Adult care professionals were found to be making a distinction between these young people and their patients who were infected during adulthood. On the basis of the healthcare teams' experience, a simplified categorization of these young people into four levels can be used: those "who have everything good"; those who have some deficiencies that must be addressed; those "who have everything bad"; and those lost to follow up. Professionals interviewed highlighted the difficulties they encountered with young people in transition. Three types of problematic situations were identified: problems of acceptance of the disease; communication problems; and problems of disorientation in the new care environment., Conclusions: Despite the lack of specific training or national policy recommendations for the integration of young people with perinatally acquired HIV into adult services, all the adult healthcare teams interviewed tried to adapt their practice to this population. The results suggested that professional involvement during transition should depend on the characteristics of the patient, not be limited to a single transition model and that a dedicated structure for transition care is not appropriate for all young people., Competing Interests: The authors have declared that no competing interests exist.