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Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment. There is practice variation in management due to differences in guidelines and their usage and adherence. We aimed to assess whether management in febrile children below 3 months attending European Emergency Departments (EDs) was according to the guidelines for fever. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0–18 years) attending twelve EDs in eight European countries. In febrile children below 3 months (excluding bronchiolitis), we analyzed actual management compared to the guidelines for fever. Ten EDs applied the (adapted) NICE guideline, and two EDs applied local guidelines. Management included diagnostic tests, antibiotic treatment, and admission. We included 913 children with a median age of 1.7 months (IQR 1.0–2.3). Management per ED varied as follows: use of diagnostic tests 14–83%, antibiotic treatment 23–54%, admission 34–86%. Adherence to the guideline was 43% (374/868) for blood cultures, 29% (144/491) for lumbar punctures, 55% (270/492) for antibiotic prescriptions, and 67% (573/859) for admission. Full adherence to these four management components occurred in 15% (132/868, range 0–38%), partial adherence occurred in 56% (484/868, range 35–77%).Conclusion: There is large practice variation in management. The guideline adherence was limited, but highest for admission which implies a cautious approach. Future studies should focus on guideline revision including new biomarkers in order to optimize management in young febrile children. What is Known:• Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment.• There is practice variation in management of young febrile children due to differences in guidelines and their usage and adherence. What is New:• Full guideline adherence is limited, whereas partial guideline adherence is moderate in febrile children below 3 months across Europe.• Guideline revision including new biomarkers is needed to improve management in young febrile children.

The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods. Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings. Of 4,611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3,477 (75%) had uncertain aetiology. 1,061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N.meningitidis (OR: 3.37, 95% CI: 1.92 – 5.99), S.pneumoniae (OR: 3.89, 95% CI: 2.07 – 7.59), Group A streptococcus (OR 2.73, 95% CI 1.13 – 6.09) and E.coli (OR 2.7, 95% CI 1.02 – 6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11 – 0.46), Influenza B (OR 0.12, 95% CI 0.02 – 0.37) and RSV (OR 0.16, 95% CI: 0.06 – 0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23 – 0.72) and EBV (OR 0.71, 95% CI 0.56 – 0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation. Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.

Fear of COVID-19, especially in vulnerable groups such as pregnant women, created excessive concern leading to unexpected psychoemotional consequences and a need to summarize the most recent knowledge about this topic. Therefore, we conducted a narrative review of the relevant literature, synthesizing data from available databases. According to the findings of this review, pregnant women during COVID-19 pandemic were more anxious and depressed mainly due to the fear of contacting the virus, restricting measures, and concerns about the health of their unborn children. The elevated stress levels in pregnant women due to the pandemic could represent risk factors for physical health complications. Thus, strategies including relaxation, mindfulness, acceptance, and positive attitude to COVID-19 should be promoted for pregnant women. © Authors, 2022

Backround: This systematic review aims to examine the associations between features of gut microbiome and Attention Deficit/Hyperactivity Disorder (ADHD) risk or severity in children, adolescents and young adults. Methods: Eligible studies were identified in PubMed and Google Scholar databases until December 31, 2020. Results: The search identified a total of 1197 items, of which 11 were included in this systematic review. The findings regarding alpha, beta diversity, bacterial phyla, orders and families were inconclusive. At the genus level an increased abundance of Odoribacter (two studies) and Eggerthella (two studies) was found in ADHD; on the contrary, decreased abundance of Faecalibacterium (three studies) was noted, whereas one study suggested its inverse association with ADHD severity and hyperactivity. One study indicated that Bacteroides species also correlated with levels of hyperactivity and impulsivity. At the species level, a lower abundance of Faecalibacterium prausnitzii, but higher of Odoribacter splanchnicus and Bacteroides uniformis was reported. Conclusions: This systematic review highlights associations between gut microbiome features and ADHD. Potential mechanisms differ by microorganism and include effects on neurotransmitter production, dopamine metabolism, modulation of inflammation and neurodevelopment through the release of cytokines. Impact: The existence of correlations between features of gut microbiome and ADHD manifestation or its severity in children, adolescents and young adults.Associations between gut microbiome features and ADHD are highlighted. Potential mechanisms seem to differ by microorganism and include effects on neurotransmitter production, dopamine metabolism, modulation of inflammation and neurodevelopment through the release of cytokines.As correlations between gut microbiome features and ADHD seem to exist, additional studies are needed for further investigation. © 2022, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Objective Most studies on febrile children have focused on infants and young children with serious bacterial infection (SBI). Although population studies have described an increased risk of sepsis in adolescents, little is known about febrile adolescents attending the emergency department (ED). We aimed to describe patient characteristics and management of febrile adolescents attending the ED. Design and setting The MOFICHE/PERFORM study (Management and Outcome of Febrile Children in Europe/Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union), a prospective multicentre study, took place at 12 European EDs. Descriptive and multivariable regression analyses were performed, comparing febrile adolescents (12-18 years) with younger children in terms of patient characteristics, markers of disease severity (vital signs, clinical alarming signs), management (diagnostic tests, therapy, admission) and diagnosis (focus, viral/bacterial infection). Results 37 420 encounters were included, of which 2577 (6.9%) were adolescents. Adolescents were more often triaged as highly urgent (38.9% vs 34.5%) and described as ill appearing (23.1% vs 15.6%) than younger children. Increased work of breathing and a non-blanching rash were present less often in adolescents, while neurological signs were present more often (1% vs 0%). C reactive protein tests were performed more frequently in adolescents and were more often abnormal (adjusted OR (aOR) 1.7, 95% CI 1.5 to 1.9). Adolescents were more often diagnosed with SBI (OR 1.8, 95% CI 1.6 to 2.0) and sepsis/meningitis (OR 2.3, 95% CI 1.1 to 5.0) and were more frequently admitted (aOR 1.3, 95% CI 1.2 to 1.4) and treated with intravenous antibiotics (aOR 1.7, 95% CI 1.5 to 2.0). Conclusions Although younger children presented to the ED more frequently, adolescents were more often diagnosed with SBI and sepsis/meningitis. Our data emphasise the importance of awareness of severe infections in adolescents. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Respiratory syncytial virus (RSV) causes a spectrum of respiratory illnesses in infants and young children that may lead to hospitalizations and a substantial number of outpatient visits, which result in a huge economic and healthcare burden. Most hospitalizations happen in otherwise healthy infants, highlighting the need to protect all infants against RSV. Moreover, there is evidence on the association between early-life RSV respiratory illness and recurrent wheezing/asthma-like symptoms As such, RSV is considered a global health priority. However, despite this, the only prevention strategy currently available is palivizumab, a monoclonal antibody (mAb) indicated in a subset of preterm infants or those with comorbidities, hence leaving the majority of the infant population unprotected against this virus. Therefore, development of prevention strategies against RSV for all infants entering their first RSV season constitutes a large unmet medical need. The aim of this review is to explore different immunization approaches to protect all infants against RSV. Prevention strategies include maternal immunization, immunization of infants with vaccines, immunization of infants with licensed mAbs (palivizumab), and immunization of infants with long-acting mAbs (e.g., nirsevimab, MK-1654). Of these, palivizumab use is restricted to a small population of infants and does not offer a solution for all-infant protection, whereas vaccine development in infants has encountered various challenges, including the immaturity of the infant immune system, highlighting that future pediatric vaccines will most likely be used in older infants (>6 months of age) and children. Consequently, maternal immunization and immunization of infants with long-acting mAbs represent the two feasible strategies for protection of all infants against RSV. Here, we present considerations regarding these two strategies covering key areas which include mechanism of action, "consistency" of protection, RSV variability, duration of protection, flexibility and optimal timing of immunization, benefit for the mother, programmatic implementation, and acceptance of each strategy by key stakeholders. We conclude that, based on current data, immunization of infants with long-acting mAbs might represent the most effective approach for protecting all infants entering their first RSV season. Copyright © 2022 Esposito, Abu Raya, Baraldi, Flanagan, Martinon Torres, Tsolia and Zielen.

Introduction: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. RSV-induced bronchiolitis has been associated with preschool wheeze and asthma in cohort studies where the comparison groups consist of healthy infants. However, recent studies identify rhinovirus (RV)–induced bronchiolitis as a potentially stronger risk factor for recurrent wheeze and asthma. Aim: This systematic review and meta-analysis aimed to compare the associations of RSV- and RV-induced bronchiolitis with the development of preschool wheeze and childhood asthma. Methods: We performed a systematic search of the published literature in five databases by using a MeSH term-based algorithm. Cohort studies that enrolled infants with bronchiolitis were included. The primary outcomes were recurrent wheeze and asthma diagnosis. Wald risk ratios and odds ratios (ORs) were estimated, along with their 95% confidence intervals (CIs). Individual and summary ORs were visualized with forest plots. Results: There were 38 studies included in the meta-analysis. Meta-analysis of eight studies that had data on the association between infant bronchiolitis and recurrent wheeze showed that the RV-bronchiolitis group were more likely to develop recurrent wheeze than the RSV-bronchiolitis group (OR 4.11; 95% CI 2.24–7.56). Similarly, meta-analysis of the nine studies that had data on asthma development showed that the RV-bronchiolitis group were more likely to develop asthma (OR 2.72; 95% CI 1.48–4.99). Conclusion: This is the first meta-analysis that directly compares between-virus differences in the magnitude of virus-recurrent wheeze and virus-childhood asthma outcomes. RV-induced bronchiolitis was more strongly associated with the risk of developing wheeze and childhood asthma. © 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

BackgroundEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.MethodsWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.ResultsData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.ConclusionsWe found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Rapid antigen detection (RAD) tests for the detection of SARS-CoV-2 are simpler, faster, and less expensive than the reverse-transcription polymerase chain reaction (RT-PCR) that is currently considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19). The objective of this study was to determine the performance of the PANBIO COVID-19 Ag RAD (Abbott) test, a lateral flow immunoassay that detects the nucleocapsid protein, using as a reference RT-PCR method the Cobas®8800 System (Roche Diagnostics). This prospective study was conducted in a tertiary Children's Hospital and included individuals aged ≤16 years with COVID-19-related symptoms or epidemiological criteria for COVID-19. Two nasopharyngeal samples were collected to perform the PANBIO RAD test and RT-PCR. Of 744 children included, 51 (6.86%) had a positive RT-PCR result. The RAD test detected 42 of 51 PCR-positive children while there were no false-positive results. The overall sensitivity and specificity were 82.35% (95% CI, 71.9%–92.8%) and 100%, respectively. Sensitivity was >95% in symptomatic children. The assay performed poorly in asymptomatically infected children. In agreement with previous studies in adults, the PANBIO RAD test can be useful in screening for COVID-19 in children admitted with symptoms suggestive of the disease, especially in the first days of the illness. © 2021 Wiley Periodicals LLC

BACKGROUND Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. Copyright © 2021 Massachusetts Medical Society.

BACKGROUND: Infections in patients with cancer are a major cause of morbidity and mortality. In most cases, the presence of neutropenia renders them prone to infections to either common or opportunistic pathogens. A wide spectrum of bacterial, viral, or fungal agents is encountered in these patients. AIM: The aim of this study was to evaluate infection types and pathogens in pediatric patients with cancer with and without neutropenia. METHODS: A total of 37 pediatric patients with cancer (median age ± 25% quartile, 6.0 ± 2.0% years) with 70 febrile episodes were evaluated at fever's onset and 48 hours later with complete blood count, C-reactive protein, cultures of biological fluids, polymerase chain reaction, and antibody titers. RESULTS: Of 70 infections, 30 (42.85%) were bacterial, 13 (18.57%) were viral, 3 (4.28%) were fungal, 16 (22.85%) were fever of unknown origin, 18 (25.71%) were opportunistic, and 12 (17.14%) were mixed infections. Neutropenia was detected in 42 (60.0%) of 70 febrile episodes, mainly in patients with hematological malignancies [odds ratio, 2.81 (0.96-8.22); P = 0.059]. Neutropenic patients had higher prevalence of mucocutaneous infections (47.6% vs 7.14%; P = 0.004). Herpes simplex virus 1 infections occurred only in the neutropenic group (14.3%). CONCLUSIONS: Patients with cancer exhibited a high prevalence of bacterial (42.85%), opportunistic (25.7%), and mixed infections (17.14%). Patients with hematological malignancies and neutropenia presented higher frequency of mucocutaneous and herpes simplex virus 1 infections than the nonneutropenic ones. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Children and adolescents with severe acute respiratory syndrome coronavirus 2 infection usually have a milder illness, lower mortality rates and may manifest different clinical entities compared with adults. Acute effusive pericarditis is a rare clinical manifestation in patients with COVID-19, especially among those without concurrent pulmonary disease or myocardial injury. We present 2 cases of acute pericarditis, in the absence of initial respiratory or other symptoms, in adolescents with COVID-19. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Background Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation. Methods 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets. Results RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses. Conclusion RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent. © 2016 Georg Thieme Verlag. All rights reserved.

Background: COVID-19 outbreak and the followed confinement measures have raised concerns to specialists worldwide regarding the imminent increase in domestic violence cases. The present systematic review aims to identify the international trends in domestic violence during the COVID-19 epidemic and to examine the possible differences among all population groups and different geographic areas worldwide. Method: The following databases were accessed: DOAJ, ERIC, Google Scholar, ProQuest, Pubmed, PsycNet, and SCOPUS, up to July 22, 2020. Results: A total of 32 studies were considered eligible. Data from North America, Europe, Asia-Pacific Area, Africa, and worldwide researches were retrieved. COVID-19 has caused an increase in domestic violence cases, especially during the first week of the COVID-19 lockdown in each country. In children, however, although the specialists’ estimations suggested an increase in child maltreatment and abuse cases, the rate of police and social services’ reports has declined during the COVID-19 pandemic. School closures that isolated students at home seemed to have contributed to this decrease. Conclusions: Domestic violence has been a considerable issue imposed by the COVID-19 epidemic to a worldwide context. The home confinement led to constant contact between perpetrators and victims, resulting in increased violence and decreased reports. In order to minimize such issues, prevention measures and supporting programs are necessary. © The Author(s) 2021.

Since the beginning of the COVID-19 pandemic, there have been numerous reports and reviews on the complications caused by the disease, analyzing the acute and chronic consequences. The main symptoms of SARS-CoV-2 are dry cough, fever, and fatigue. COVID-19 appears to affect all systems, including renal, cardiovascular, circulatory, and respiratory systems, causing chronic obstructive pulmonary disease. We report on a 14-year-old male adolescent, who presented with thrombocytopenia (platelet count 92 × 109 /L) and leukopenia (white blood count 4.2 × 103 /µL) that was observed two months ago. Ten days before the first blood test, a viral infection with nasal congestion and runny nose was reported, without other accompanying symptoms. Viral antibodies screening revealed positivity for all the three specific COVID-19 antibodies. Further haematological evaluation with bone marrow aspiration revealed non-specific dysplastic features of the red cell and megakaryocyte progenitors. Although haematological alterations due to COVID-19 infection are available from adult patients’ reports, the effect of COVID-19 infection in the pediatric population is underestimated and this is the first case with such haematological involvement. Noteworthy, in the current case, the impact of the COVID-19 infection was not related to the severity of the disease, as the symptoms were mild. In similar cases, bone marrow aspiration would not be performed as a part of routine work-up. Thus, it is important when evaluating pediatric patients with COVID-19 infection to search and report those alterations in order to better understand the impact and the spectrum of clinical manifestations of the specific viral infection in children and adolescents. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

OBJECTIVE: This paper aims to study the views, perceptions and representations of online hate speech among adolescents in the Greek cohort of the SELMA Project. METHODS: Qualitative research was conducted in focus groups of 36 Greek adolescents and the data were processed through thematic analysis method. RESULTS: The majority was unfamiliar with the term "hate speech" and confused it with cyberbullying. The target characteristics of hate, ethnicity, race, gender, religion, physical weakness, disability, sexual orientation, and appearance emerged. Regarding people involved in hate speech, perpetrators in both hate speech and bullying were described to share common characteristics. The emphasis was placed on the victims' resilience, as well as their socialization, as protective behaviors. Participants stressed the value of the right to freedom of speech, although there was no agreement on its limits. Additionally, it was highlighted that awareness of what is right and wrong is mostly taught by parents, while the role of education was also important. An important finding was that the majority of teenagers were optimistic, supporting the belief that it is possible to find a realistic solution. CONCLUSION: The findings support the need for prevention strategies in the school environment, so that adolescents will be able to recognize and potentially combat hate speech in the online and offline worlds. Copyright © 2021 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Background: Discriminating viral from bacterial lower respiratory tract infections (LRTIs) in children is challenging thus commonly resulting in antibiotic overuse. The Feverkidstool, a validated clinical decision rule including clinical symptoms and C-reactive protein, safely reduced antibiotic use in children at low/intermediate risk for bacterial LRTIs in a multicentre trial at emergency departments (EDs) in the Netherlands. Objectives: Using routine data from an observational study, we simulated the impact of the Feverkidstool on antibiotic prescriptions compared with observed antibiotic prescriptions in children with suspected LRTIs at 12 EDs in eight European countries. Methods: We selected febrile children aged 1month to 5 years with respiratory symptoms and excluded upper respiratory tract infections. Using the Feverkidstool, we calculated individual risks for bacterial LRTI retrospectively. We simulated antibiotic prescription rates under different scenarios: (1) applying effect estimates on antibiotic prescription from the trial; and (2) varying both usage (50%-100%) and compliance (70%-100%) with the Feverkidstool s advice to withhold antibiotics in children at low/intermediate risk for bacterial LRTI (10%). Results: Of 4938 children, 4209 (85.2%) were at low/intermediate risk for bacterial LRTI. Applying effect estimates from the trial, the Feverkidstool reduced antibiotic prescription from 33.5% to 24.1% [pooled risk difference: 9.4% (95% CI: 5.7%-13.1%)]. Simulating 50%-100% usage with 90% compliance resulted in risk differences ranging from 8.3% to 15.8%. Our simulations suggest that antibiotic prescriptions would be reduced in EDs with high baseline antibiotic prescription rates or predominantly (85%) low/intermediate-risk children. Conclusions: Implementation of the Feverkidstool could reduce antibiotic prescriptions in children with suspected LRTIs in European EDs. © 2021 Oxford University Press. All rights reserved.

Background: Anorexia nervosa (AN) is a serious, multifactorial mental disorder affecting predominantly young females. This systematic review examines neuroimaging findings in adolescents and young adults up to 24 years old, in order to explore alterations associated with disease pathophysiology. Methods: Eligible studies on structural and functional brain neuroimaging were sought systematically in PubMed, CENTRAL and EMBASE databases up to 5 October 2020. Results: Thirty-three studies were included, investigating a total of 587 patients with a current diagnosis of AN and 663 healthy controls (HC). Global and regional grey matter (GM) volume reduction as well as white matter (WM) microstructure alterations were detected. The mainly affected regions were the prefrontal, parietal and temporal cortex, hippocampus, amygdala, insula, thalamus and cerebellum as well as various WM tracts such as corona radiata and superior longitudinal fasciculus (SLF). Regarding functional imaging, alterations were pointed out in large-scale brain networks, such as default mode network (DMN), executive control network (ECN) and salience network (SN). Most findings appear to reverse after weight restoration. Specific limitations of neuroimaging studies in still developing individuals are also discussed. Conclusions: Structural and functional alterations are present in the early course of the disease, most of them being partially or totally reversible. Nonetheless, neuroimaging findings have been open to many biological interpretations. Thus, more studies are needed to clarify their clinical significance. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Objectives Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation. Design MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission. Setting and participants Data were collected on febrile children aged 0–18 years presenting to 12 European EDs (2017–2018). Main outcome measures We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates

Background: The maturation of innate immune responses in health and atopy is still incompletely understood. Methods: We aimed to evaluate age-related trajectories of the TLR3 and TLR7/8 pathways from birth to adulthood and whether these differ between healthy and atopic individuals. Peripheral blood mononuclear cells (PBMCs) were isolated from 39 otherwise healthy, atopic and 39 non-atopic subjects, aged 0–45 years. Selected cytokines involved in antiviral responses were measured by Luminex in culture supernatants of poly(I:C)- and R848-stimulated PBMCs. The non-parametric correlation between age and cytokine expression and differences in developmental trajectories between healthy and atopic subjects were estimated. Patterns of cytokine development were identified with principal component analysis. Results: Normal innate immune maturation entails significant and progressive age-related changes in the production of IL-1β, TNF-α, MIP-1β, MCP-3, IP-10, IL-10, IL-12p70, and IFN-γ upon TLR3 and/or TLR7/8 stimulation. Individual cytokines made small contributions to the observed variability; chemokines MCP-3 and IP-10 were key contributors. The development of these pathways deviated in atopic subjects with significant differences observed in the trajectories of IL-1β, MIP-1β, and IL-10 syntheses. Conclusion: TLR3 and TLR7/8 pathways mature during childhood, while atopy is associated with an abnormal maturation pattern. Suboptimal responses in Th1, inflammatory cytokine, and chemokine production may be implicated in poor antiviral immunity in atopics. Moreover, the deficient maturation of IL-10 synthesis may be implicated in the breaking of tolerance, characterizing the onset of atopic disease. © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Background: The COVID-19 pandemic has led to special circumstances and changes to everyday life due to the worldwide measures that were imposed such as lockdowns. This review aims to evaluate obesity in children, adolescents and young adults during the COVID-19 pandemic. Methods: A literature search was conducted to evaluate pertinent studies up to 10 November 2020. Results: A total of 15 articles were eligible; 9 identified 17,028,111 children, adolescents and young adults from 5–25 years old, 5 pertained to studies with an age admixture (n = 20,521) and one study included parents with children 5–18 years old (n = 584). During the COVID-19 era, children, adolescents and young adults gained weight. Changes in dietary behaviors, increased food intake and unhealthy food choices including potatoes, meat and sugary drinks were noted during the ongoing COVID-19 pandemic. Food insecurity associated with financial reasons represents another concern. Moreover, as the restrictions imposed reduced movements out of the house, physical activity was limited, representing another risk factor for weight gain. Conclusions: COVID-19 restrictions disrupted the everyday routine of children, adolescents and young adults and elicited changes in their eating behaviors and physical activity. To protect them, health care providers should highlight the risk of obesity and provide prevention strategies, ensuring also parental participation. Worldwide policies, guidelines and precautionary measures should ideally be established. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

As most children infected with SARS-CoV-2 present with mild symptoms or they are asymptomatic, the optimal strategy for molecular testing it is not well defined. The aim of the study was to determine the extent and etiology of molecular testing for SARS-CoV-2 in Greek pediatric departments during the first phase of the pandemic and identify possible differences in incidence, depending on the age group and geographical area. We conducted a nationwide study of molecular testing for SARS-CoV-2 of children in pediatric departments between March and June 2020. A total of 65 pediatric departments participated to the study, representing 4901 children who were tested for SARS-CoV-2 and 90 (1.8%) were positive. Most pediatric cases were associated with topical outbreaks. Adolescents 11-16 years had the highest positivity rate (3.6%) followed by children 6-10 years (1.9%). However, since testing rate significantly differed between age groups, the modified incidence of SARS-CoV-2 infection per age group was highest in infants 1 year (19.25/105 population). Most children tested presented with fever (70.9%), respiratory (50.1%) or gastrointestinal symptoms (28.1%). Significant differences were detected between public and private hospitals regarding positivity rate (2.34% vs 0.39%, P-value: 0.001). Significant variation in SARS-CoV-2 molecular testing positivity rate and incidence between age groups indicate discrepancies in risk factors among different age groups that shall be considered when ordering molecular testing. © 2021 Cambridge University Press. All rights reserved.

Introduction: The continuously increasing prevalence of childhood obesity is reaching epidemic proportions. Greece is among the countries with the highest childhood obesity prevalence rates. The present study aims to identify psychosocial factors associated with excess body weight of adolescents. Methods: This case-control study was conducted in Athens, Greece, and included 414 adolescents aged 11–18 years. Anthropometric measurements were recorded, and an anonymous self-completed questionnaire captured the psychosocial background, family environment, peer relations, and school environment. Results: Of the total sample of adolescents, 54.6% had normal body weight and 45.4% were overweight or obese. A multivariate logistic regression analysis showed that the factors related to the presence of overweight/obesity were adolescents’ age (OR = 0.416, p < 0.001), area of residence, presence of anxiety (OR = 4.661, p = 0.001), presence of melancholia (OR = 2.723, p = 0.016), participation in sports (OR = 0.088, p

Background: overweight and obese individuals may often face aggressive messages or comments on the internet. This study attempts to evaluate the association between cyberbullying victimization and overweight/obesity in adolescents participating in the European Network for Addictive Behavior (EU NET ADB) survey. Methods: a school-based cross-sectional study of adolescents aged 14–17.9 years was conducted (n = 8785) within the EU NET ADB survey, including data from seven European countries (Germany, Greece, Iceland, the Netherlands, Romania, Poland, Spain). Complex samples and univariate and multivariate logistic regression analyses were performed. Results: overall, overweight adolescents were more likely to have been cyberbullied compared to their normal weight peers (adjusted OR (Odds ratio) = 1.20, CI (confidence intervals): 1.01–1.42); this association was pronounced in Germany (adjusted OR = 1.58, CI: 1.11–2.25). In Iceland, obese adolescents reported cyberbullying victimization more frequently compared to their normal weight peers (adjusted OR = 2.87, 95% CI: 1.00–8.19). No significant associations with cyberbullying victimization were identified either for obese or overweight adolescents in Greece, Spain, Romania, Poland, and the Netherlands. Conclusions: this study reveals an overall association between cyberbullying victimization and overweight on the basis of a sizable, representative sample of adolescent population from seven European countries. Country-specific differences might reflect differential behavioral perceptions, but also normalization aspects. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Invasive meningococcal disease (IMD) is associated with high case fatality rates and long-term sequelae among survivors. Meningococci belonging to six serogroups (A, B, C, W, X, and Y) cause nearly all IMD worldwide, with serogroup B meningococci (MenB) the predominant cause in many European countries, including Greece (~80% of all IMD). In the absence of protein-conjugate polysaccharide MenB vaccines, two protein-based vaccines are available to prevent MenB IMD in Greece: 4CMenB (Bexsero™, GlaxoSmithKline), available since 2014; and MenB-FHbp, (Trumenba™, Pfizer), since 2018. This study investigated the potential coverage of MenB vaccines in Greece using 107 MenB specimens, collected from 2010 to 2017 (66 IMD isolates and 41 clinical samples identified solely by non-culture PCR), alongside 6 MenB isolates from a carriage study conducted during 2017–2018. All isolates were characterized by multilocus sequence typing (MLST), PorA, and FetA antigen typing. Whole Genome Sequencing (WGS) was performed on 66 isolates to define the sequences of vaccine components factor H-binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA), and Neisseria adhesin A (NadA). The expression of fHbp was investigated with flow cytometric meningococcal antigen surface expression (MEASURE) assay. The fHbp gene was present in-frame in all isolates tested by WGS and in 41 MenB clinical samples. All three variant families of fHbp peptides were present, with subfamily B peptides (variant 1) occurring in 69.2% and subfamily A in 30.8% of the samples respectively. Sixty three of 66 (95.5%) MenB isolates expressed sufficient fHbp to be susceptible to bactericidal killing by MenB-fHbp induced antibodies, highlighting its potential to protect against most IMD in Greece. © 2021 Elsevier Ltd