Nirsevimab and Hospitalization for RSV Bronchiolitis.

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. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.).

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

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.

Ovarian torsion: diagnosis, surgery, and fertility preservation in the pediatric population.

Ovarian torsion is rare in the pediatric population. Delayed diagnosis can significantly impact fertility. The aim of this review is to highlight current knowledge regarding clinical presentation, diagnosis, surgical management, and follow-up in the pediatric population. Whilst the presentation is often very unspecific, most children will present with sudden severe unilateral pelvic pain associated with vomiting. A key diagnostic test is pelvic ultrasonography, which may help demonstrate an asymmetric enlarged ovary with peripherally displaced follicles. In the pediatric population, ovarian torsion may occur in a normal ovary. However, underlying lesions can be found in half of cases. Benign neoplasms (teratomas or cystic lesions) represent the commonest etiology, with the risk of malignancy being less than 2%. Surgical management should be focused on fertility preservation. This is achievable through ovarian detorsion ± ovarian cystectomy ± oophoropexy to avoid recurrence. Follow-up studies demonstrate excellent recovery rates of detorsed ovaries including those with ischemic appearances. What is Known: • Ovarian torsion is a rare diagnosis in the pediatric population. • Aspecific symptoms and differential diagnoses lead to missed or delayed diagnosis increasing the risk of oophoprectomy and further infertility. What is New: • Reviewing the latest knowledge about clinical presentation, diagnostic, surgical management, and follow-up of ovarian torsion in the pediatric population. • Adiponectin was negatively associated with diastolic blood pressure and HOMA-IR, and chemerin was negatively associated with glucose.

The association between gastro-oesophageal reflux and migraine in the paediatric population: a multicentre case-control study.

Infantile regurgitation is one of the most common discomforts in the first months of life. Infantile colic and, in older children, functional dyspepsia have been linked to migraine. To date, this is the first study to investigate a possible association between infantile regurgitation and primary headaches in children. This is a case-control study of 195 children aged 6-17 years, with primary headache (migraine, or tension type headache) in 5 European paediatric hospitals. The control group is composed of 240 same-aged children attending with minor injuries during the same period - February 1st 2020 to December 1st 2020. A structured questionnaire identified a history of infantile regurgitation and other functional gastrointestinal disorders for case and control participants. The outcome was the difference in the prevalence of infantile regurgitation among children with or without a diagnosis of primary headache. The analysis showed a significant association between infantile regurgitation and migraine (OR = 1.88, CI 95 = 1.01-3.4, p = 0.04). No association was found between infantile regurgitation and tension type headache (p = 0.33). Subgroup analysis confirmed that the association was only significant for migraine without aura (OR = 2.3, CI 95 = 1.2-4.4, p = 0.01). In a further subgroup analysis, the presence of functional dyspepsia, irritable bowel syndrome and abdominal migraine was associated with migraine without aura. CONCLUSION: The presence of migraine among children aged 6-17 was associated with a history of infantile regurgitation. Additional longitudinal studies are required to confirm whether infantile regurgitation could be considered as a precursor of migraine. WHAT IS KNOWN: • Children suffering from functional gastrointestinal disorders are more likely to be suffering from migraine and tension-type headache as well. • Children suffering from primary headache are more likely to have had infantile colic in their first six month of life. WHAT IS NEW: • It is the first study to find an association between migraine and infantile regurgitation in children. • These findings could have an impact on the diagnosis and therapeutics of both migraine and infantile regurgitation.

Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens: A Time Series Analysis.

BACKGROUND: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs). RESEARCH QUESTION: What is the respective role of respiratory pathogens in ACS epidemiology? STUDY DESIGN AND METHODS: This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All children aged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen. RESULTS: Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8 to -12.2; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2 to 41.6; P = .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9 to 56.9; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3 to 11.3; P = .004); other respiratory pathogens had only a minor role. INTERPRETATION: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population.

Effectiveness of nirsevimab against RSV-bronchiolitis in paediatric ambulatory care: a test-negative case-control study.

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.

Neurological consequences of SARS-CoV-2 infections in the pediatric population.

COVID-19 in the pediatric population is mostly asymptomatic. However, 1 out of 5 children presents non-specific neurologic symptoms such as headache, weakness, or myalgia. Furthermore, rarer forms of neurological diseases are increasingly being described in association to a SARS-CoV-2 infection. Encephalitis, stroke, cranial nerves impairment, Guillain-Barré syndrome or acute transverse myelitis have been reported and account for around 1% of pediatric COVID-19 cases. Some of these pathologies may occur during or after the SARS-CoV-2 infection. The pathophysiological mechanisms range from direct invasion of the central nervous system (CNS) by SARS-CoV-2 itself to postinfectious immune-mediated CNS inflammation. In most cases, patients presenting neurological pathologies related to SARS-CoV-2 infection are at greater risk of life-threatening complications and should be closely monitored. Further studies are needed to acknowledge the potential long-term neurodevelopmental consequences of the infection.

Sudden onset headaches in paediatric emergency departments: diagnosis and management.

Headache is one of the most common pain syndromes in the paediatric population. Headaches are classified as primary (migraine, tension-type headaches, trigeminal autonomic cephalalgia and other primary headaches) or secondary (e.g. post-traumatic). Non-febrile, non-traumatic headaches represent 1% of all paediatric emergency departments (PED) visits. Many patients present with an acute, moderate to severe pain, sometimes with a sudden onset. Sudden onset headache can be the main symptom of life-threatening neurological conditions as well as a sign of primary headaches such as thunderclap or stabbing headaches. This review aims to describe the presentation of sudden primary headaches in children, in order to help the physician to provide effective management in the emergency setting.

Acute Facial Nerve Palsy in Children: Gold Standard Management.

Facial nerve palsy (FNP) is a common illness in the paediatric emergency department. Missed or delayed diagnosis can have a serious impact on a patient's quality of life. The aim of this article is to give a recent overview of this pathology in terms of the causes, diagnosis, red flag symptoms, complementary examinations, treatments and follow-up in the child population. In cases of acquired, acute onset and isolated FNP, Bell's palsy can be assumed, and no further investigation is required. In any other scenario, complementary examinations are required. Treatment depends on the aetiology. Corticosteroids, in addition to antiviral medication, are recommended to treat Bell's palsy whenever a viral infection is suspected. However, the lack of randomised control trials in the paediatric population does not allow us to comment on the effectiveness of these treatments. In all cases, treated or not, children have a very good recovery rate. This review emphasises the necessity of randomised control trials concerning this frequent neurological pathology in order to better treat these children.

Brain to Belly: Abdominal Variants of Migraine and Functional Abdominal Pain Disorders Associated With Migraine.

Migraine is one of the most frequent causes of primary headache and 9% of children suffer from migraines. Most children will continue to experience migraine attacks as adults, therefore it is imperative that we have a thorough understanding of this major health issue. This article considers the so-called abdominal variants of migraine, which are more commonly seen in children rather than adults: abdominal migraine, cyclic vomiting syndrome, and infantile colic. Other functional abdominal pain disorders such as irritable bowel syndrome and functional dyspepsia have also been linked to migraine in clinical studies. The common pathophysiological root of these diseases seems to be the gut-brain axis mechanism. Abdominal variants of migraine are considered pediatric precursors of migraine whereas the functional abdominal pain disorders related to migraine seem to share a pathophysiological root with no temporarily link as for today. In this review we aim to describe the epidemiological background, the current pathophysiological theories and the relationship of each disease to migraine. This review is the first to compile abdominal variants of migraine and functional abdominal pain disorders associated with migraine and we endeavor to elucidate the broad spectrum of migraine-related episodes in children.