Publications by authors named "Maria Tsolia"

96 Publications

Infections in Children With Cancer: The Role of the Presence or Absence of Neutropenia.

Pediatr Emerg Care 2021 Mar;37(3):155-160

Department of Paediatric Haematology-Oncology, "Aghia Sophia" Children's Hospital.

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.
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http://dx.doi.org/10.1097/PEC.0000000000002360DOI Listing
March 2021

SARS-CoV-2 molecular testing in Greek hospital pediatric departments: A nationwide study.

Epidemiol Infect 2021 Feb 24:1-12. Epub 2021 Feb 24.

3rd Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Greece.

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http://dx.doi.org/10.1017/S0950268821000455DOI Listing
February 2021

Impact of a clinical decision rule on antibiotic prescription for children with suspected lower respiratory tract infections presenting to European emergency departments: a simulation study based on routine data.

J Antimicrob Chemother 2021 Feb 10. Epub 2021 Feb 10.

Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

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 1 month 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.
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http://dx.doi.org/10.1093/jac/dkab023DOI Listing
February 2021

Variation in hospital admission in febrile children evaluated at the Emergency Department (ED) in Europe: PERFORM, a multicentre prospective observational study.

PLoS One 2021 7;16(1):e0244810. Epub 2021 Jan 7.

Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

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 <1 indicate lower rates than expected based on the ED patient population.

Results: We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1-54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1-5.0), PICU admission rates (0.2-2.2), upper respiratory tract infections (0.4-1.7) and fever without focus (0.5-2.7). Variation was small in sepsis/meningitis (0.9-1.1).

Conclusions: Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790386PMC
January 2021

Persistent Tenosynovitis, Steroid Dependency and a Hyperpigmented Scaly Macular Rash in a Child With Juvenile Idiopathic Arthritis.

Cureus 2020 Oct 27;12(10):e11208. Epub 2020 Oct 27.

Pediatrics, Panagiotis & Aglaia Kyriakou Children's Hospital, Athens, GRC.

Blau syndrome is a rare autoinflammatory disease, characterized by granulomatous symmetric arthritis, skin rash and uveitis. It is caused by mutations in the CARD15/NOD2 gene, which is a significant part of innate immunity. We describe the case of a patient with Blau syndrome, initially misdiagnosed as juvenile idiopathic arthritis. Genetic analysis showed R334Q mutation in the NOD2 gene that is known to be linked to Blau syndrome. Our patient was successfully treated with the IL-1β blocking agent canakinumab, with clinical and laboratory remission without any adverse effects. To our knowledge this is one of the rare cases of Blau syndrome successfully treated with canakinumab. After moving abroad, canakinumab was discontinued and she was treated with adalimumab instead. Change in her treatment resulted in a relapse of her disease. Prompt recognition of Blau syndrome and the optimal treatment, are vital for the prevention of severe sequelae such as vision loss and joint deformities. Canakinumab constitutes a promising therapeutic approach for Blau syndrome and requires further investigation.
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http://dx.doi.org/10.7759/cureus.11208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704009PMC
October 2020

Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments: MOFICHE, a prospective observational study.

Arch Dis Child 2020 Nov 18. Epub 2020 Nov 18.

General Paediatrics, Erasmus MC Sophia Children's Hospital, Rotterdam, Zuid-Holland, The Netherlands

Objectives: To develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers.

Design: Prospective observational study.

Setting: 12 emergency departments (EDs) in 8 European countries.

Patients: Febrile children aged 0-18 years.

Main Outcome Measures: IBI, defined as bacteraemia, meningitis and bone/joint infection. We derived and cross-validated a model for IBI using variables from the Feverkidstool (clinical symptoms, C reactive protein), neurological signs, non-blanching rash and comorbidity. We assessed discrimination (area under the receiver operating curve) and diagnostic performance at different risk thresholds for IBI: sensitivity, specificity, negative and positive likelihood ratios (LRs).

Results: Of 16 268 patients, 135 (0.8%) had an IBI. The discriminative ability of the model was 0.84 (95% CI 0.81 to 0.88) and 0.78 (95% CI 0.74 to 0.82) in pooled cross-validations. The model performed well for the rule-out threshold of 0.1% (sensitivity 0.97 (95% CI 0.93 to 0.99), negative LR 0.1 (95% CI 0.0 to 0.2) and for the rule-in threshold of 2.0% (specificity 0.94 (95% CI 0.94 to 0.95), positive LR 8.4 (95% CI 6.9 to 10.0)). The intermediate thresholds of 0.1%-2.0% performed poorly (ranges: sensitivity 0.59-0.93, negative LR 0.14-0.57, specificity 0.52-0.88, positive LR 1.9-4.8) and comprised 9784 patients (60%).

Conclusions: The rule-out threshold of this model has potential to reduce antibiotic treatment while the rule-in threshold could be used to target treatment in febrile children at the ED. In more than half of patients at intermediate risk, sensitive biomarkers could improve identification of IBI and potentially reduce unnecessary antibiotic prescriptions.
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http://dx.doi.org/10.1136/archdischild-2020-319794DOI Listing
November 2020

Diagnosis and Management of a Young Girl With Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) Linked to a Novel Mutation.

Cureus 2020 Oct 2;12(10):e10766. Epub 2020 Oct 2.

Rheumatology, "P. & A. Kyriakou" Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GRC.

A nine-year-old girl with a two-month history of fever and generalized malaise, along with intermittent abdominal pain, immigrant myalgia, throat pain, anorexia, and long-standing failure to thrive, was admitted to our department for further investigation and treatment. Detailed medical history revealed recurrent inflammation attacks from a very young age and a heavily burdened family history. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) was highly suspected. Genetic screening was performed and several members of the family were found to be carriers of C73Y mutation in exon 3, which is a novel tumor necrosis factor superfamily receptor 1A (TNFRSF1A) mutation. The girl was treated with an interleukin-1β inhibitor, canakinumab, which induced immediate and complete remission of disease that interestingly lasted for a long period even after medication discontinuation.
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http://dx.doi.org/10.7759/cureus.10766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606205PMC
October 2020

BCG Vaccine Protection against TB Infection among Children Older than 5 Years in Close Contact with an Infectious Adult TB Case.

J Clin Med 2020 Oct 8;9(10). Epub 2020 Oct 8.

Second Department of Paediatrics, National and Kapodistrian University of Athens, School of Medicine, 'P. and A. Kyriakou' Children's Hospital, 30601 Athens, Greece.

The Bacille Calmette-Guérin (BCG) vaccine has been shown to provide considerable protection against miliary or meningeal tuberculosis (TB), but whether it prevents other forms of disease remains controversial. Recent evidence has shown that the BCG vaccine also provides protection against latent TB infection (LTBI). The aim of the current study was to examine whether BCG has a protective role against LTBI among children in close contact with an adult index case in a low TB endemicity setting with the use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT). A cross-sectional study was conducted over a 10-year period among children referred to our outpatient TB clinic with a history of close contact with an adult with pulmonary TB. All subjects had a QFT-GIT performed. In total, 207 children > 5 to 16 years of age with known recent exposure were enrolled. BCG-vaccinated subjects had a 59% lower risk of presenting with LTBI after close contact with an adult index case compared with unvaccinated subjects (OR = 0.41, 95% CI: 0.23-0.73, = 0.002). After adjustment for possible confounders, the protective effect of prior BCG immunization was estimated at 68% (OR = 0.32, 95% CI: 0.15-0.66, = 0.002). Other risk factors for LTBI included a history of migration (OR = 2.27, 95% CI: 1.13-4.53, = 0.021) and transmission of infection to other exposed child contacts (OR = 4.62, 95% CI: 2.27-9.39, = 0.001). We were able to determine a strong protective role of BCG vaccination among children older than 5 years, immunized at school entry, who had close contact with an adult infectious TB case.
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http://dx.doi.org/10.3390/jcm9103224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601378PMC
October 2020

Children and Adolescents With SARS-CoV-2 Infection: Epidemiology, Clinical Course and Viral Loads.

Pediatr Infect Dis J 2020 12;39(12):e388-e392

Second Department of Pediatrics, National and Kapodistrian University of Athens, Aglaia Kyriakou Children's Hospital, Athens, Greece.

Background: There is limited information on severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in children.

Methods: We retrieved data from the national database on SARS-CoV-2 infections. We studied in-family transmission. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values.

Results: We studied 203 SARS-CoV-2-infected children (median age: 11 years; range: 6 days to 18.4 years); 111 (54.7%) had an asymptomatic infection. Among the 92 children (45.3%) with coronavirus disease 2019 (COVID-19), 24 (26.1%) were hospitalized. Infants <1 year were more likely to develop COVID-19 (19.5% of all COVID-19 cases) (P-value = 0.001). There was no significant difference between viral load and age, sex, underlying condition, fever and hospitalization, as well as between type of SARS-CoV-2 infection and age, sex, underlying condition and viral load. Transmission from a household member accounted for 132 of 178 (74.2%) children for whom the source of infection was identified. An adult member with COVID-19 was the first case in 125 (66.8%) family clusters. Child-to-adult transmission was found in one occasion only.

Conclusions: SARS-CoV-2 infection is mainly asymptomatic or mild during childhood. Adults appear to play a key role in spread of the virus in families. Most children have moderate or high viral loads regardless of age, symptoms or severity of infection. Further studies are needed to elucidate the role of children in the ongoing pandemic and particularly in light of schools reopening and the need to prioritize groups for vaccination, when COVID-19 vaccines will be available.
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http://dx.doi.org/10.1097/INF.0000000000002899DOI Listing
December 2020

Pseudohypoparathyroidism type 1B (PHP1B), a rare disorder encountered in adolescence.

J Pediatr Endocrinol Metab 2020 Nov;33(11):1475-1479

2nd Department of Paediatrics, University of Athens, "P & A Kyriakou" Children's Hospital, Athens, Greece.

Objectives The objective of this paper is to report a peculiar case of a patient with pseudohypoparathyroidism type 1b (PHP1B). Pseudohypoparathyroidism (PHP) refers to a group of disorders characterized by hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) concentrations as the result of end-organ unresponsiveness to PTH. Case presentation We present a 14-year-old boy, who was admitted with severe symptomatic hypocalcaemia, absence of dysmorphic features and Albright's hereditary osteodystrophy features. Laboratory investigations revealed markedly low serum calcium, high phosphate, markedly elevated PTH levels and vitamin D insufficiency, while magnesium, albumin, ALP and TSH were normal. The clinical and laboratory findings were consistent with PHP1B. Molecular analysis revealed loss of methylation at the AB DMR of the GNAS locus, confirming the diagnosis. Yet no STX16 deletion was detected. Conclusions It is possible that delSTX16- patients carry a defect in an element that controls the methylation both at the GNAS-A/B DMR and at the GNAS-AS2. This rare case emphasizes the need of individualized molecular analysis in PHP1B patients in order to elucidate the possible molecular defect.
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http://dx.doi.org/10.1515/jpem-2020-0192DOI Listing
November 2020

Psychosocial consequences of COVID-19 in children, adolescents and young adults: A systematic review.

Psychiatry Clin Neurosci 2020 11 15;74(11):615-616. Epub 2020 Sep 15.

Second Department of Pediatrics, "P. & A. Kyriakou" Children's Hospital, National and Kapodistrian University of Athens, Attica, Greece.

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http://dx.doi.org/10.1111/pcn.13134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461527PMC
November 2020

Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE): A multicentre observational study.

PLoS Med 2020 08 19;17(8):e1003208. Epub 2020 Aug 19.

Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.

Background: The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe.

Methods And Findings: Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0-18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%-41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%-90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%-29.3%), and inconclusive in 22.5% (range across EDs: 0.4%-60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%-59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%-47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%-100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country.

Conclusions: In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.
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http://dx.doi.org/10.1371/journal.pmed.1003208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444592PMC
August 2020

Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood.

Front Pediatr 2020 22;8:355. Epub 2020 Jul 22.

Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication-the development of coronary artery aneurysms (CAA)-can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases. The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients ( = 48) from patients with infection ( = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients ( = 26) from those with infections ( = 150), with an AUC of 0.78. The second validation cohort of acute KD patients ( = 25) and febrile controls ( = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included. When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection.
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http://dx.doi.org/10.3389/fped.2020.00355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388698PMC
July 2020

Development and validation of a Paediatric Early Warning Score for use in the emergency department: a multicentre study.

Lancet Child Adolesc Health 2020 08 22;4(8):583-591. Epub 2020 Jul 22.

Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Centre Rotterdam, Rotterdam, Netherlands. Electronic address:

Background: Paediatric Early Warning Scores (PEWSs) are being used increasingly in hospital wards to identify children at risk of clinical deterioration, but few scores exist that were designed for use in emergency care settings. To improve the prioritisation of children in the emergency department (ED), we developed and validated an ED-PEWS.

Methods: The TrIAGE project is a prospective European observational study based on electronic health record data collected between Jan 1, 2012, and Nov 1, 2015, from five diverse EDs in four European countries (Netherlands, the UK, Austria, and Portugal). This study included data from all consecutive ED visits of children under age 16 years. The main outcome measure was a three-category reference standard (high, intermediate, low urgency) that was developed as part of the TrIAGE project as a proxy for true patient urgency. The ED-PEWS was developed based on an ordinal logistic regression model, with cross-validation by setting. After completing the study, we fully externally validated the ED-PEWS in an independent cohort of febrile children from a different ED (Greece).

Findings: Of 119 209 children, 2007 (1·7%) were of high urgency and 29 127 (24·4%) of intermediate urgency, according to our reference standard. We developed an ED-PEWS consisting of age and the predictors heart rate, respiratory rate, oxygen saturation, consciousness, capillary refill time, and work of breathing. The ED-PEWS showed a cross-validated c-statistic of 0·86 (95% prediction interval 0·82-0·90) for high-urgency patients and 0·67 (0·61-0·73) for high-urgency or intermediate-urgency patients. A cutoff of score of at least 15 was useful for identifying high-urgency patients with a specificity of 0·90 (95% CI 0·87-0·92) while a cutoff score of less than 6 was useful for identifying low-urgency patients with a sensitivity of 0·83 (0·81-0·85).

Interpretation: The proposed ED-PEWS can assist in identifying high-urgency and low-urgency patients in the ED, and improves prioritisation compared with existing PEWSs.

Funding: Stichting de Drie Lichten, Stichting Sophia Kinderziekenhuis Fonds, and the European Union's Horizon 2020 research and innovation programme.
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http://dx.doi.org/10.1016/S2352-4642(20)30139-5DOI Listing
August 2020

Autism Spectrum Disorders in Greece: Nationwide Prevalence in 10-11 Year-Old Children and Regional Disparities.

J Clin Med 2020 Jul 8;9(7). Epub 2020 Jul 8.

Developmental Assessment Unit, Second Department of Pediatrics "P. & A. Kyriakou" Children's Hospital, National and Kapodistrian University of Athens School of Medicine, 11527 Athens, Greece.

Autism spectrum disorders (ASD) constitute a public health concern with increasing prevalence worldwide. We aimed to estimate prevalence and age at diagnosis in Greece, where no large-scale prevalence study has ever been conducted. Aggregate data were collected on ASD diagnoses by gender and calendar year of diagnosis up to 2019, for children born in 2008 and 2009, from the Centers for Educational and Counseling Support, which evaluate children to receive special educational support in school. Coverage was 87.1% of centers and 88.1% of schoolchildren born in 2008-9. ASD prevalence overall was 1.15% (1.83% males, 0.44% females; ratio 4.14:1), ranging from 0.59% to 1.50% in Greece's 13 regions. In five regions, prevalence differed significantly between centers. Overall, only 3.8% of diagnoses were made before the fourth year after birth and 42.7% before the sixth year, with considerable variation between regions. Approximate mean age at diagnosis was six years and one month, and about three months earlier for girls than for boys. Our results provide evidence-based information to guide service planning and development at national and regional levels. Particular attention should be paid to smoothing out inequalities regarding service accessibility and provision. Emphasis should be given to earlier identification and diagnosis of ASD.
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http://dx.doi.org/10.3390/jcm9072163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408756PMC
July 2020

Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study.

Eur Respir J 2020 07 2;56(1). Epub 2020 Jul 2.

Dept of Paediatric Infectious Diseases and Immunology, Evelina London Children's Hospital, Guy's and St. Thomas' NHS Foundation Trust, London, UK

Introduction: Tuberculous meningitis (TBM) is often diagnostically challenging. Only limited data exist on the performance of interferon-γ release assays (IGRA) and molecular assays in children with TBM in routine clinical practice, particularly in the European setting.

Methods: Multicentre, retrospective study involving 27 healthcare institutions providing care for children with tuberculosis (TB) in nine European countries.

Results: Of 118 children included, 54 (45.8%) had definite, 38 (32.2%) probable and 26 (22.0%) possible TBM; 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Of 108 patients who underwent cranial imaging 90 (83.3%) had at least one abnormal finding consistent with TBM. At the 5-mm cut-off the tuberculin skin test had a sensitivity of 61.9% (95% CI 51.2-71.6%) and at the 10-mm cut-off 50.0% (95% CI 40.0-60.0%). The test sensitivities of QuantiFERON-TB and T-SPOT.TB assays were 71.7% (95% CI 58.4-82.1%) and 82.5% (95% CI 58.2-94.6%), respectively (p=0.53). Indeterminate results were common, occurring in 17.0% of QuantiFERON-TB assays performed. Cerebrospinal fluid (CSF) cultures were positive in 50.0% (95% CI 40.1-59.9%) of cases, and CSF PCR in 34.8% (95% CI 22.9-43.7%). In the subgroup of children who underwent tuberculin skin test, IGRA, CSF culture and CSF PCR simultaneously, 84.4% had at least one positive test result (95% CI 67.8%-93.6%).

Conclusions: Existing immunological and microbiological TB tests have suboptimal sensitivity in children with TBM, with each test producing false-negative results in a substantial proportion of patients. Combining immune-based tests with CSF culture and CSF PCR results in considerably higher positive diagnostic yields, and should therefore be standard clinical practice in high-resource settings.
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http://dx.doi.org/10.1183/13993003.02004-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330130PMC
July 2020

A national educational campaign to raise awareness of child physical abuse among health care professionals.

Eur J Pediatr 2020 Sep 9;179(9):1395-1402. Epub 2020 Mar 9.

Department of Pediatrics, Yale School of Medicine, 333 Cedar St, New Haven, CT, 06510, USA.

Education is necessary to improve child physical abuse detection and management. A few studies have described national child abuse training programs, but none has measured changes in knowledge among participants. A collaboration of child abuse experts from the USA, an academic pediatric department, and a non-governmental organization in child protection aimed at (a) training hospital physicians in a train-the-trainer course for the detection and management of child physical abuse and (b) conducting workshops and measuring attendance and gain of knowledge of participants. A train-the-trainer and a national curriculum were created. A 78-item and a 20-item knowledge questionnaire were used pre and post the train-the-trainer course and all workshops, respectively. Nineteen physicians from all pediatric departments of the seven medical schools in Greece attended the course. Eight workshops in seven cities took place with a total attendance of 1220 health care professionals. Gain of knowledge was demonstrated for participants in the train-the-trainer course (p = 0.0015) and local workshops (p < 0.001).Conclusion: We successfully engaged physicians from all medical schools in Greece and conducted a train-the-trainer module and eight workshops in major cities that improved the participants' knowledge in child physical abuse. This approach may help address physician deficiencies in emerging areas of child abuse clinical practice. What is Known: • Education is necessary to improve child physical abuse detection and management. • Although national training programs have been described, none has measured participants' changes in knowledge. What is New: • A collaboration of child abuse experts, all medical schools in Greece, and a non-governmental organization resulted in a national educational campaign in child physical abuse and gains in knowledge for participants. • This approach may help address deficiencies in emerging areas of clinical practice.
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http://dx.doi.org/10.1007/s00431-020-03625-4DOI Listing
September 2020

A National Survey Across Primary Care Pediatricians Regarding Immunization Views and Practices in Children With Rheumatic Diseases.

J Clin Rheumatol 2020 Jan 15. Epub 2020 Jan 15.

From the Unit of Rheumatology, Immunology, and Infectious Diseases, Second Department of Pediatrics, "P. & A. Kyriakou" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.

The aims of this study were to describe the knowledge, attitude, and current practice of general pediatricians working in primary care regarding vaccination in children with rheumatic diseases (RDs) and to identify barriers and facilitators that could be used to promote uptake.

Methods: Cross-sectional survey conducted with an anonymous questionnaire of 34 items distributed to pediatricians via an online platform. Four hundred questionnaires were sent, and 256 were returned and analyzed using STATA 13. Data collection included demographics, questions on knowledge, perceptions, and opinions, as well as advice given to families.

Results: The majority of doctors felt that vaccination in children with RDs is essential. Responders were using a variety of guidelines to reach a clinical decision. Fifty percent were hesitant to adhere to the national vaccination scheme without expert input. Reasons were as follows: not convinced from current literature that the vaccine is safe (32%), afraid to cause disease flare (43%), and unable to deal with parental concerns/refusal (54%). Twelve percent of responders felt that the RD may have been triggered by a vaccine. The majority (82%) of doctors were pro annual influenza vaccination. Seventy percent of doctors were keener to administer booster doses rather than primary ones.

Conclusions: Variation in opinion and clinical practice exists. Overall, although general pediatricians are informed regarding efficacy and adverse effects of immunizations in patients with RDs, there are steps to be made from principle to practice. Vaccinating these children is of vital importance, and primary care pediatricians should be updated regarding existing guidelines referring to this field.
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http://dx.doi.org/10.1097/RHU.0000000000001251DOI Listing
January 2020

Human Herpesvirus 7-Related Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion.

Pediatr Infect Dis J 2020 02;39(2):170-172

Second Pediatric Department, School of Medicine, University of Athens.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a recently described entity so far exclusively in East Asian children. AESD diagnosis is based on clinicoradiologic criteria, often without pleocytic CSF and characterized by hyperglycemia and transaminasemia. Here, we present the first case of human herpesvirus 7-related AESD in an immunocompetent child >2 years old and of Caucasian origin.
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http://dx.doi.org/10.1097/INF.0000000000002557DOI Listing
February 2020

Massive Splenic Infarction and Autosplencetomy: First Presentation of Homozygous Sickle Cell Disease in a Toddler.

J Pediatr Hematol Oncol 2020 07;42(5):371-372

Second Department of Paediatrics, School of Medicine, "P. & A. Kyriakou" Children's Hospital, National and Kapodistrian University of Athens (NKUA).

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http://dx.doi.org/10.1097/MPH.0000000000001698DOI Listing
July 2020

Diversity in the emergency care for febrile children in Europe: a questionnaire study.

BMJ Paediatr Open 2019 27;3(1):e000456. Epub 2019 Jun 27.

Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Objective: To provide an overview of care in emergency departments (EDs) across Europe in order to interpret observational data and implement interventions regarding the management of febrile children.

Design And Setting: An electronic questionnaire was sent to the principal investigators of an ongoing study (PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management), www.perform2020.eu) in 11 European hospitals in eight countries: Austria, Germany, Greece, Latvia, the Netherlands, Slovenia, Spain and the UK.

Outcome Measures: The questionnaire covered indicators in three domains: local ED quality (supervision, guideline availability, paper vs electronic health records), organisation of healthcare (primary care, immunisation), and local factors influencing or reflecting resource use (availability of point-of-care tests, admission rates).

Results: Reported admission rates ranged from 4% to 51%. In six settings (Athens, Graz, Ljubljana, Riga, Rotterdam, Santiago de Compostela), the supervising ED physicians were general paediatricians, in two (Liverpool, London) these were paediatric emergency physicians, in two (Nijmegen, Newcastle) supervision could take place by either a general paediatrician or a general emergency physician, and in one (München) this could be either a general paediatrician or a paediatric emergency physician. The supervising physician was present on site in all settings during office hours and in five out of eleven settings during out-of-office hours. Guidelines for fever and sepsis were available in all settings; however, the type of guideline that was used differed. Primary care was available in all settings during office hours and in eight during out-of-office hours. There were differences in routine immunisations as well as in additional immunisations that were offered; immunisation rates varied between and within countries.

Conclusion: Differences in local, regional and national aspects of care exist in the management of febrile children across Europe. This variability has to be considered when trying to interpret differences in the use of diagnostic tools, antibiotics and admission rates. Any future implementation of interventions or diagnostic tests will need to be aware of this European diversity.
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http://dx.doi.org/10.1136/bmjpo-2019-000456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613846PMC
June 2019

Long-term preservation of measles and rubella specific-IgG antibodies in children with enthesitis related arthritis on anti-TNFα treatment: a prospective controlled study.

Rheumatology (Oxford) 2019 09;58(9):1686-1688

Infectious Diseases Unit, Second Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, P. & A. Kyriakou Children's Hospital, Athens, Greece.

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http://dx.doi.org/10.1093/rheumatology/kez096DOI Listing
September 2019

Gambling involvement and problem gambling correlates among European adolescents: results from the European Network for Addictive Behavior study.

Soc Psychiatry Psychiatr Epidemiol 2019 Nov 6;54(11):1429-1441. Epub 2019 May 6.

Adolescent Health Unit, Second Department of Pediatrics, P. and A. Kyriakou Children's Hospital, National and Kapodistrian University of Athens, Leoforos Mesogeion 24, 11527, Athens, Greece.

Purpose: Worldwide, concern has grown over the expansion of gambling among adolescents, who have an increased likelihood of developing risk-taking behaviors. This study aimed to increase knowledge of problem gambling among adolescents in seven European countries and to assess the effect of demographic and lifestyle factors recorded in the European Network for Addictive Behavior survey (https://www.eunetadb.eu).

Methods: A cross-sectional school-based study (n = 13,284) was conducted in Germany, Greece, Iceland, The Netherlands, Poland, Romania and Spain. Anonymous self-completed questionnaires included socio-demographic data, internet usage characteristics, school achievement, parental control, the Internet Addiction Test, the South Oaks Gambling Screen-Revised for Adolescents Test and Achenbach's Youth Self-Report.

Results: 12.5% of the participants reported last year gambling activities either online or offline. 3.6% of the study participants and 28.1% of gamblers (either online or offline) were at risk or had a gambling problem. The study results showed that a higher proportion of adolescents was either at risk or had a gambling problem among males, in the older age group, when the parental educational level was lower/middle, and in the absence of siblings. Furthermore, being at risk or having a gambling problem was associated with lower age at first use of the internet, lower school grades, using the internet 6-7 days per week, and problematic internet use. At risk or problem gamblers had higher scores on all scales of problem behavior and lower scores (lower competence) on activities and academic performance.

Conclusions: Our findings underline the need for better gambling legislation and suggest the importance of developing social responsibility tools that may help diminish adolescent gambling involvement, with special attention to males.
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http://dx.doi.org/10.1007/s00127-019-01706-wDOI Listing
November 2019

Immunogenicity and side-effects of the inactivated hepatitis A vaccine in periodic fever, aphthous stomatitis, pharyngitis, and adenitis patients.

Pediatr Int 2019 Jan;61(1):104-106

Second Department of Paediatrics, "P. & A. Kyriakou" Children's Hospital, University of Athens, Athens, Greece.

The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18 months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1 month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1 month after the second dose. Seroprotection rates remained adequate 1 year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.
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http://dx.doi.org/10.1111/ped.13719DOI Listing
January 2019

Risk Factors Associated With Accelerated Rubella IgG Antibody Loss in Previously Vaccinated, Treatment-Naive Patients With Juvenile Systemic Lupus Erythematosus: A Prospective Study.

Arthritis Rheumatol 2019 06 8;71(6):1022-1023. Epub 2019 Apr 8.

P & A Kyriakou Children's Hospital and National and Kapodistrian University of Athens, Athens, Greece.

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http://dx.doi.org/10.1002/art.40831DOI Listing
June 2019

Emergence of staphylococcal scalded skin syndrome associated with a new toxinogenic, methicillin-susceptible Staphylococcus aureus clone.

J Med Microbiol 2019 Jan 12;68(1):48-51. Epub 2018 Nov 12.

4​2nd Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens, Greece.

A sharp increase in staphylococcal scalded skin syndrome (SSSS) cases has been recorded in our settings since 2015, with 31 cases having been documented during the period 2014-2017. The molecular investigation of strains from the above period showed the emergence of a methicillin-susceptible, mupirocin- and fusidic acid-resistant Staphyloccocus aureus clone that belongs to the ST121 complex and carries both epidermolysin (eta/etb) genes. We concluded that the SSSS caused by the newly emerged, highly virulent community-associated-methicillin sensitive S. aureus strains that have been encountered lately is more severe than impetigo. Physicians should be aware of the probability of SSSS epidemics from strains that are resistant to mupirocin and fusidic acid, which have been used irrationally and excessively.
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http://dx.doi.org/10.1099/jmm.0.000871DOI Listing
January 2019

Staphylococcus aureus osteoarticular infections in children: an 8-year review of molecular microbiology, antibiotic resistance and clinical characteristics.

J Med Microbiol 2018 Dec 23;67(12):1753-1760. Epub 2018 Oct 23.

4​First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Purpose: To investigate the clinical, phenotypic and genotypic characteristics of Staphylococcus aureus strains causing osteoarticular infections in a large paediatric series.

Methodology: Medical records of children who were hospitalized with the diagnosis of community-associated S. aureus (CA-SA) osteomyelitis and/or septic arthritis in the two major tertiary paediatric hospitals of Athens during an 8-year period (2007-2015) were reviewed, and S. aureus isolates were analysed regarding antimicrobial resistance, detection of pathogenicity genes and genotyping using SCCmec, agr typing, PFGE and MLST.

Results: During the study period, 123 children with CA-SA osteoarticular infections were identified, and methicillin-resistant S. aureus (MRSA) accounted for 44 of these (35.8 %). Children with MRSA infection had a significantly higher admission rate to the ICU (5.7  vs 0 %, P=0.04) and longer duration of hospitalization (21.6 vs 16.7 days, P=0.04). Sixty-eight isolates [42 (methicillin-sensitive S. aureus) MSSA and 26 MRSA] were available for molecular analysis. All MRSA strains were mecA-positive and most carried the SCCmec IV cassette (23/26, 88 %) and belonged to the PFGE type C (24/26, 92.3 %), agr type 3 (24/26, 92.3 %) and the MLST ST80 clone (24/26, 92.3 %). In contrast, MSSA strains showed polyclonality by PFGE and agr typing. Regarding pathogenicity genes, MRSA vs MSSA isolates showed higher detection rates of PVL (96.2 vs 4.8 %, P<0.0001) and fib (80.8 vs 50 %, P=0.02).

Conclusions: In our study a considerable number of S. aureus osteoarticular infections were due to CA-MRSA isolates, most of which belonged to the ST80 clone and had a higher incidence of specific virulence factors, entailing higher ICU admission rates and a longer duration of hospitalization.
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http://dx.doi.org/10.1099/jmm.0.000859DOI Listing
December 2018

A Variety of Alu-Mediated Copy Number Variations Can Underlie IL-12Rβ1 Deficiency.

J Clin Immunol 2018 07 11;38(5):617-627. Epub 2018 Jul 11.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Hospital for Sick Children, Paris, France.

Purpose: Inborn errors of IFN-γ immunity underlie Mendelian susceptibility to mycobacterial disease (MSMD). Autosomal recessive complete IL-12Rβ1 deficiency is the most frequent genetic etiology of MSMD. Only two of the 84 known mutations are copy number variations (CNVs), identified in two of the 213 IL-12Rβ1-deficient patients and two of the 164 kindreds reported. These two CNVs are large deletions found in the heterozygous or homozygous state. We searched for novel families with IL-12Rβ1 deficiency due to CNVs.

Methods: We studied six MSMD patients from five unrelated kindreds displaying adverse reactions to BCG vaccination. Three of the patients also presented systemic salmonellosis, two had mucocutaneous candidiasis, and one had disseminated histoplasmosis. We searched for CNVs and other variations by IL12RB1-targeted next-generation sequencing (NGS).

Results: We identified six new IL-12Rβ1-deficient patients with a complete loss of IL-12Rβ1 expression on phytohemagglutinin-activated T cells and/or EBV-transformed B cells. The cells of these patients did not respond to IL-12 and IL-23. Five different CNVs encompassing IL12RB1 (four deletions and one duplication) were identified in these patients by NGS coverage analysis, either in the homozygous state (n = 1) or in trans (n = 4) with a single-nucleotide variation (n = 3) or a small indel (n = 1). Seven of the nine mutations are novel. Interestingly, four of the five CNVs were predicted to be driven by nearby Alu elements, as well as the two previously reported large deletions. The IL12RB1 locus is actually enriched in Alu elements (44.7%), when compared with the rest of the genome (10.5%).

Conclusion: The IL12RB1 locus is Alu-enriched and therefore prone to rearrangements at various positions. CNVs should be considered in the genetic diagnosis of IL-12Rβ1 deficiency.
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http://dx.doi.org/10.1007/s10875-018-0527-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329663PMC
July 2018

Cross-national aspects of cyberbullying victimization among 14-17-year-old adolescents across seven European countries.

BMC Public Health 2018 07 10;18(1):800. Epub 2018 Jul 10.

Adolescent Health Unit, Second Department of Pediatrics, P. and A. Kyriakou Children's Hospital, University of Athens, Leoforos Mesogeion 24, 11527, Athens, Greece.

Background: The increasing use of the Internet and social network sites (SNS) has created a new domain of socio-emotional development for adolescents. The aim of this cross-sectional study was to explore cybervictimization across seven European countries, in relation to socio-demographic, Internet use and psychosocial variables.

Methods: A cross-sectional school-based study was conducted in the participating countries: Germany, Greece, Iceland the Netherlands, Poland, Romania and Spain. Anonymous self-completed questionnaires included sociodemographic data, internet usage characteristics, school achievement, parental control, the Internet Addiction Test and Achenbach's Youth Self-Report.

Results: The highest rate of cyber victimization was found in Romania (37.3%) and the lowest in Spain (13.3%). Multiple logistic regression analyses gave differing results between countries. In Romania, Poland and Germany cyberbullying victimization was associated with SNS use, whereas Internet use was associated with increased odds of cybervictimization only in Romania. Cybervictimization was associated with greater internalizing behavior problems in all countries analysed, and with externalizing problems in all except Romania.

Conclusions: Cyberbullying victimization is an on-going problem, which is subject to country-specific socio-demographic factors and diverse patterns of current Internet use and its development. Preventive measures should emphasize the integration of Internet communication technology education in educational contexts, and focus on the consistent association between cybervictimization and internalizing and externalizing difficulties.
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http://dx.doi.org/10.1186/s12889-018-5682-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038297PMC
July 2018

Epidemiology of infections and antimicrobial use in Greek Neonatal Units.

Arch Dis Child Fetal Neonatal Ed 2019 May 28;104(3):F293-F297. Epub 2018 Jun 28.

Department of Paediatrics, Patras Medical School, University Hospital of Patras, Patras, Greece.

Objective: To describe the epidemiology of neonatal infections and of antimicrobial use in Greek Neonatal Units (NNUs) in order to develop national, evidence-based guidelines on empiric antimicrobial use for neonatal sepsis in Greece.

Design: Retrospective analysis of prospectively collected infection surveillance data from 2012 to 2015, together with a Point Prevalence Survey (PPS) on antimicrobial use and the collection of data on local empiric antimicrobial policies.

Setting: 16 NNUs in Greece participating in the neonIN infection surveillance network PATIENTS: Newborns in participating NNUs who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of antibiotics.

Results: 459 episodes were recorded in 418 infants. The overall incidence of infection was 50/1000 NNU-admissions. The majority of episodes were late-onset sepsis (LOS) (413, 90%). (80%) were the most common Gram-positive organisms causing LOS and spp (39%) the most common Gram-negative. Nearly half (45%) of the spp were resistant to at least one aminoglycoside. The PPS revealed that 196 of 484 (40%) neonates were on antimicrobials. The survey revealed wide variation in empiric antimicrobial policies for LOS.

Conclusions: This is the largest collection of data on the epidemiology of neonatal infections in Greece and on neonatal antimicrobial use. It provides the background for the development of national evidence-based guidelines. Continuous surveillance, the introduction of antimicrobial stewardship interventions and evidence-based guidelines are urgently required.
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http://dx.doi.org/10.1136/archdischild-2018-315024DOI Listing
May 2019