Determinants of incomplete vaccination in children at age two in France: results from the nationwide ELFE birth cohort.

Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries, but its determinants are poorly understood. Their identification is necessary to design target actions that can improve vaccination uptake. Our aim was to assess the determinants of incomplete vaccination in two-year-old children in France. Among the 18,329 children included in the 2011 ELFE French nationwide population-based birth cohort, we selected those for whom vaccination status was available at age two years. Incomplete vaccination was defined as ≥ 1 missing dose of recommended vaccines. Potential determinants of incomplete vaccination were identified by using logistic regression, taking into account attrition and missing data. Of the 5,740 (31.3%) children analyzed, 46.5% (95% confidence interval [CI] 44.7-48.0) were incompletely vaccinated. Factors independently associated with incomplete vaccination were having older siblings (adjusted odds ratio 1.18, 95% CI [1.03-1.34] and 1.28 [1.06-1.54] for one and ≥ 2 siblings, respectively, vs. 0), residing in an isolated area (1.92 [1.36-2.75] vs. an urban area), parents not following health recommendations or using alternative medicines (1.81 [1.41-2.34] and 1.23 [1.04-1.46], respectively, vs. parents confident in institutions and following heath recommendations), not being visited by a maternal and child protection service nurse during the child's first two months (1.19 [1.03-1.38] vs. ≥ 1 visit), and being followed by a general practitioner (2.87 [2.52-3.26] vs. a pediatrician). CONCLUSIONS: Incomplete vaccination was highly prevalent in the studied pediatric population and was associated with several socio-demographic, parental, and healthcare service characteristics. These findings may help in designing targeted corrective actions. WHAT IS KNOWN: • Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries. • The partial understanding of the determinants of incomplete vaccination precludes the design of effective targeted corrective actions. WHAT IS NEW: • High prevalence of incomplete vaccination at age two years in France. • Incomplete vaccination was independently associated with several socio-demographic, parental, and healthcare service characteristics.

A simple clinical decision rule may help to rule out severe bacterial infection and spare antibiotics in febrile young children.

AIM: To assess the performance of a new clinical decision rule (CDR) to identify patients at a low risk of invasive bacterial infection (IBI) among febrile children and its theoretical impact on antibiotic use. METHODS: Prospective study including consecutive children <5 years of age who presented in one French paediatric emergency department with fever without source between January and December 2016. With the collected data, we constructed a CDR based on a sequential approach based on age, clinical toxic signs, urinalysis and procalcitonin level. We evaluated its diagnostic performances to identify IBI and its potential impact on antibiotic use. RESULTS: Among the 1061 children (IBI 11/1061, 1.0%), 693 (65.3%) were classified at low or intermediate risk of IBI, with an IBI prevalence of 0%. The sensitivity and specificity of the CDR to predict IBI were 100% and 73.9%. Negative and positive predictive value were 100% and 3.9%, respectively. Using this new CDR, the current antibiotics exposure would theoretically be reduced from 33.6% to 24.1%. CONCLUSION: The promising interest of this clinical decision rule, using simple and accessible biological and clinical tools, needs to be confirm with an external validation study, which will allow its use in clinical practice.

Adverse Drug Reactions in Pediatric Emergency Medicine.

BACKGROUND: The pediatric population displays its own pharmacological characteristics, making children vulnerable to adverse drug reactions (ADRs). OBJECTIVE: To determine the incidence of ADRs among the pediatric emergency department (PED) population. METHODS: This is a descriptive, noncontrolled, prospective, and single-center study, during 4 consecutive months in the PED of Nantes University Hospital. RESULTS: Setting up active gathering of data on ADRs enabled 121 reports of 11 095 consultations at the emergency department, which corresponds to an ADR incidence of 1.09%. Digestive and cutaneous reactions made up the majority of reactions judged as being nonserious (53%) and were mainly found in children between 2 -11 years old. Of the serious ADRs, 25% were found in the 12-15-year-old age range because of the drug overdose. The main medications administered, which were responsible for the majority of the ADRs, were an equimolar mix of oxygen and nitrogen monoxide, amoxicillin, and acetaminophen. Three means of collecting data were possible: collecting files data, oral communication, or filling a form, the last being the most used method. CONCLUSIONS: This active data gathering shows the incidence and nature of the adverse effects as well as the age distribution in the PED population. It highlights the considerable misuse of medications among young teenagers and the high incidence of overmedication in the younger age group. This work also revealed the need for a better reporting system. Future joint studies should be carried out between clinical and pharmacological departments to optimize communication and the correct use of medications in children.

Pharmacokinetics of linezolid treatment using intravenous and oral administrations in extremely premature infants.

INTRODUCTION: Vancomycin is the usual antibiotic treatment in coagulase-negative staphylococcus sepsis in premature infants but causes renal toxicity. As linezolid is effective in Gram-positive cocci infection, and devoid of renal side-effects, it has been used in Nantes neonatal intensive care units and linezolid plasma concentrations were monitored. AIM: The aims of this study are to report data on linezolid concentrations in premature infants, describe clinical and bacteriological evolution during treatment, and determine potential side effects. METHODS: A retrospective observational study of premature infants treated with linezolid in Nantes Hospital from January 2008 through November 2011 was conducted. Linezolid plasma concentrations, possible side effects due to linezolid, and clinical response to linezolid treatment were collected from folder review. RESULTS: Twenty-four linezolid plasma concentrations were monitored in 16 premature patients, at steady state for continuous intravenous administration or 7 ± 1.5 h after last oral administration. Except for one case, linezolid plasma concentrations were ≥minimal inhibition concentration (MIC) for linezolid for both parenteral and oral administrations. We observed three cases of thrombocytopenia, two of leukopenia, three of neutropenia, and one of severe hyperlactacidemia, resolving after discontinuation of treatment. Clinical signs of infection resolved in 13/16 cases. Bacteria were coagulase-negative Staphylococci in 12/16 cases and were eradicated in 9/12 evaluable cases. CONCLUSIONS: This study reports an adequate linezolid plasma concentration with regard to the linezolid MIC in extremely premature infants. However, considering adverse events reported, its use should be cautious and may concern only oral administration during the late phase of infection, to limit paradoxical catheter use to treat nosocomial infections. Moreover, safe and efficient anti-Staphylococcus therapies should be identified to treat this vulnerable population.

Low SARS-CoV-2 prevalence in asymptomatic children during the first year of the pandemic: A French retrospective study.

BACKGROUND: Since the beginning of the pandemic, children's role in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been debated. We aimed to describe the prevalence of SARS-CoV-2 in asymptomatic children undergoing institutional systematic screening. METHODS: From 2020 to 2021, this retrospective study in a French university hospital included consecutive asymptomatic children routinely screened for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay before surgery. RESULTS: Among the 816 test samples, the prevalence of positive PCR results was 0.49 % (95 % CI: 0.01-0.97, n = 4); half of the cases involved close contacts with an adult case. CONCLUSION: These results support the low prevalence of SARS-CoV-2 in asymptomatic children during the first pandemic periods in France.

Humoral immunity to SARS-CoV-2 and seasonal coronaviruses in children and adults in north-eastern France.

BACKGROUND: Children are underrepresented in the COVID-19 pandemic and often experience milder disease than adolescents and adults. Reduced severity is possibly due to recent and more frequent seasonal human coronaviruses (HCoV) infections. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France. METHODS: In this cross-sectional seroprevalence study, serum samples were collected from children and adults requiring hospital admission for non-COVID-19 between February and August 2020. Antibody responses to SARS-CoV-2 and seasonal HCoV (229E, HKU1, NL63, OC43) were assessed using a bead-based multiplex assay, Luciferase-Linked ImmunoSorbent Assay, and a pseudotype neutralisation assay. FINDINGS: In 2,408 individuals, seroprevalence of SARS-CoV-2-specific antibodies was 7-8% with three different immunoassays. Antibody levels to seasonal HCoV increased substantially up to the age of 10. Antibody responses in SARS-CoV-2 seropositive individuals were lowest in adults 18-30 years. In SARS-CoV-2 seronegative individuals, we observed cross-reactivity between antibodies to the four HCoV and SARS-CoV-2 Spike. In contrast to other antibodies to SARS-CoV-2, specific antibodies to sub-unit 2 of Spike (S2) in seronegative samples were highest in children. Upon infection with SARS-CoV-2, antibody levels to Spike of betacoronavirus OC43 increased across the whole age spectrum. No SARS-CoV-2 seropositive individuals with low levels of antibodies to seasonal HCoV were observed. INTERPRETATION: Our findings underline significant cross-reactivity between antibodies to SARS-CoV-2 and seasonal HCoV, but provide no significant evidence for cross-protective immunity to SARS-CoV-2 infection due to a recent seasonal HCoV infection. In particular, across all age groups we did not observe SARS-CoV-2 infected individuals with low levels of antibodies to seasonal HCoV. FUNDING: This work was supported by the « URGENCE COVID-19 ¼ fundraising campaign of Institut Pasteur, by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), and by the REACTing (Research & Action Emerging Infectious Diseases), and by the RECOVER project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 101003589, and by a grant from LabEx IBEID (ANR-10-LABX-62-IBEID).

Earlier diagnosis in anorexia nervosa: better watch growth charts!

BACKGROUND: A better understanding of the healthcare pathway of children and adolescents with anorexia nervosa (AN) may contribute to earlier detection and better disease management. Here we measured and compared the symptomatic time to diagnosis (TTD) (time between the first symptoms, as reported by parents, and the diagnosis) and the auxological TTD (time between the deviation in the weight growth curve and the diagnosis). METHODS: We performed a monocentric retrospective study including all patients age 9 years to 16 years who were hospitalized in Nantes University Hospital for AN between 2013 and 2016. We analysed the two TTDs by medical record review and growth curve investigation. TTDs were described by medians and Kaplan-Meier curves. Two profiles of patients were compared according to the kinetics of growth deviation and the occurrence of symptoms. RESULTS: Among the 137 patients included, the median symptomatic and auxological TTDs was 7.0 months (IQR: 4.0-12.0) and 7.2 months (IQR: 2.0-18.0). TTDs were significantly different but clinically similar. For 48% of the patients, a deviation in the growth curve could have been noted at a median of 9.7 months (IQR: 3.0-18.0) before the first symptoms were reported by parents. Those patients showed significantly slower weight loss than did patients with first symptoms reported before growth deviation (weight loss rate 0.41% vs 1.90% per month, p < 0.0001). CONCLUSIONS: Careful study of growth curves remains an essential step in detecting eating disorders, possibly allowing for earlier detection of the disease in nearly half of these patients.

Do abused young children feel less pain?

The objective of this study was to investigate whether acute pain in abused children was under recognized by doctors and nurses compared to children evaluated for accidental injuries. We hypothesize that an abused child's reaction to physical pain could be an additional symptom of this challenging diagnosis. For the observational prospective case control study in an emergency department, children were eligible when: younger than six years old, the reported trauma occurred within the previous seven days, the trauma comprised a bone injury or burn, and the child was able to express his or her pain. The case group comprised children for whom the medical team reported their abuse suspicions and supporting information to a court, and whose cases of abuse were subsequently confirmed. The control group consisted of children with a plausible cause for their injury and no obvious signs of abuse. The children were matched according to their age and type of trauma. The pain was assessed by doctors and nurses before analgesic administration using a certified pain scale. Among the 78 included children, pain was significantly less recognized in the abused children vs. the controls (relative risk=0.63; 95% CI: 0.402-0.986; p=0.04). We observed a discrepancy between the nurses' and doctors' scores for the pain assessments (Kappa coefficient=0.59, 95% CI: 0.40-0.77). Our results demonstrate that pain expression in abused children is under recognized by medical staff. They also suggest that abused children may have reduced pain expression after a traumatic event. Paying particular attention to the pain of abused children may also optimize the analgesic treatment.

Inappropriate prescription of antibiotics in pediatric practice: Analysis of the prescriptions in primary care.

Misuse of antibiotics is largely responsible for the emergence of bacterial resistance. Children represent a subset of the population who frequently receive antibiotics. The objectives were to calculate the frequency of antibiotic prescriptions that do not comply with best practice recommendations in paediatrics primary care and to examine the thoughts and feelings of physicians and parents about antibiotic prescription and recommendations from the national health authorities. We included children admitted at the paediatric emergency room (PER) of the NANTES university hospital between June 2011 and October 2012 and who were under antibiotic drugs. Two independent experts evaluated the compliance with the national recommendations. Parents and general practitioner (GP) who prescribed the antibiotic before admission to PER were called to collect their thoughts and feeling about antibiotic prescription. The median age of the 88 included children was 2.8 years. The upper respiratory tract infection motivated the prescription of antibiotic in 59%. Seventy-six per cent of the prescriptions analysed were inappropriate, 72% of the antibiotics had a too broad spectrum, and one-third was not indicated. Ninety-one per cent of the interviewed parents thought that the antibiotic prescribed to their child was adequate. Among the 77 prescribing GP who were called, 33% agreed that they lacked time during consultation to explain to parents that no antibiotics were required. Antibiotic prescriptions were too often inadequate in this sample of children admitted in a French PER. Efforts have to be made with physicians and general public to optimize the antibiotic drug use.

Role of biomarkers in the management of antibiotic therapy: an expert panel review: I - currently available biomarkers for clinical use in acute infections.

In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics.

Contribution of procalcitonin to occult bacteraemia detection in children.

We conducted a prospective study in 215 children, 3 to 36 months of age, presenting with fever > or = 39 degrees C without obvious origin, in order to evaluate the diagnostic value of procalcitonin (PCT) in detection of occult bacteraemia. PCT associated with white blood cell count constitutes an efficient screening method with sensitivity 100%, specificity 61.9% and positive and negative likelihoods ratios of 2.62 and 0, respectively.