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ObjectiveTo determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents.DesignNationwide, population-based cohort study. Setting: Norway from 1 March 2020 to 31 April 2021. Participants: All Norwegian residents Main outcome measuresPopulation-based health care and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin, and pre-existing chronic comorbidities. All residents were followed until age 18, emigration, death, or end of follow-up. Hazard ratios (HR) estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated.ResultsOf 1 182 796 residents, 22608 (1.9%) tested positive by polymerase chain reaction or lateral flow tests, of whom 107 (0.5%) were admitted to a hospital. Low family income (aHR 1.40, 95% confidence interval 1.36 to 1.46), crowded housing (1.35, 1.30 to 1.39), household size, age, and area of living were independent risk factors for infection. A non-Nordic country of origin was the strongest risk factor (aHR 2.37, 95% CI 2.30 to 2.49), whereas chronic comorbidity was not associated with the risk of infection. Chronic comorbidity was associated with hospitalisation (aHR 4.15, 2.63 to 6.56), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected.ConclusionsSocioeconomic factors, country of origin, and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with the risk of admission but not with the overall risk of acquiring SARS-CoV-2.What is already known on this topicHospital admissions rates for covid-19 among children and adolescents are low compared to adults. Admission rates to hospitals and intensive care units for covid-19 have been higher in minority groups and in children and adolescents with chronic comorbidity.Whether underlying differences in susceptibility for severe disease or the incidence of infections are driving these associations have not been investigated.What this study addsLow family income, crowded housing and household size, and country of origin outside the Nordic countries were associated with increased risk of infection with SARS-CoV-2.None of these factors, but chronic comorbidities, were associated with the risk of hospital admission among those infected.

A four- and a half-month-old girl with severe dilated cardiomyopathy due to neonatal enterovirus myocarditis, treated with diuretics and milrinone for the past 4 months, was infected with SARS-CoV-2. The disease course was characterised by high fever and gastrointestinal symptoms. Cardiac function, as measured by echocardiography, remained stable. The treatment focused on maintaining a normal heart rate and a stable fluid balance. In children with severe underlying cardiac disease, even a mild SARS-CoV-2 infection can require close monitoring and compound treatment.

Horizontal transfer of antibiotic resistance determinants contributes to dissemination of antibiotic resistance. Such transfer of resistance genes within the human gut has been documented in some in vivo studies. The present study investigated seven blaCTX-M-1-carrying Escherichia coli isolates from three consecutive faecal samples collected from one cystic fibrosis patient in a nine-months period, by analysing whole genome sequencing data. The analyses showed that the seven E. coli isolates represented three genetically diverse strains. All isolates contained blaCTX-M-1-carrying Incl1 plasmids that shared a common 101 kb backbone differing by only four SNPs. The plasmids harboured by the three different E. coli strains varied within limited regions suggestive of recombination events, according to the phylogenetic topology of the genomes of the isolates harbouring them. The findings strongly suggest that horizontal transfer of a blaCTX-M-1-carrying plasmid had occurred within the patient´s gut. The study illustrates the within-host diversity of faecally carried resistant E. coli isolates and highlights the value of collecting multiple bacterial colonies from longitudinally collected samples to assess faecal carriage of resistant enterobacteria. The clustering of the plasmids with the corresponding E. coli strains carrying them indicates that the plasmids appear to have adapted to their respective E. coli hosts.

A novel method to detect resistant faecal Enterobacteriaceae was developed by applying MIC-gradient strips directly onto agar plates inoculated with faeces. The method provided the susceptibility pattern (MICs) of the dominant bacterial population directly on the plates and also detected smaller resistant subpopulations with a sensitivity of 1/10(5).

Source at https://doi.org/10.1371/journal.pone.0187618 We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the observed phenotypic resistance in all 28 multidrug-resistant E. coli isolates examined.

SETTING The management of multidrug-resistant tuberculosis (MDR-TB) is strictly regulated in Norway. However, nationwide studies of the epidemic are lacking. OBJECTIVE To describe the MDR-TB epidemic in Norway over two decades. DESIGN Retrospective analysis of data on MDR-TB cases in Norway, 1995-2014, obtained from the national registry, patient records and the reference laboratory, with genotyping and cluster analysis data. Data for non-MDR-TB cases were collected from the national registry. RESULTS Of 4427 TB cases, 89 (2.0%) had MDR-TB, 7% of whom had extensively drug-resistant TB (XDR-TB) and 24% pre-XDR-TB. Of the 89 MDR-TB cases, 96% were immigrants, mainly from the Horn of Africa or the former Soviet Union (FSU); 37% had smear-positive TB; and 4% were human immunodeficiency virus co-infected. Of the 19% infected in Norway, the majority belonged to a Delhi/Central Asian lineage cluster in a local Somali community. Among the MDR-TB cases, smear-positive TB and FSU origin were independent risk factors for XDR/pre-XDR-TB. Treatment was successful in 66%; 17% were lost to follow-up, with illicit drug use and adolescence being independent risk factors. Forty-four per cent of patients treated with linezolid discontinued treatment due to adverse effects. CONCLUSION MDR-TB is rare in Norway and is predominantly seen in immigrants from the Horn of Africa and FSU. Domestic transmission outside immigrant populations is minimal.

Aims: To explore whether gender differences in the Scandinavian Cystic Fibrosis (CF) patients exist in the areas of key clinical parameters, complications, and medication. Methods: Cross-sectional data on 890 (416 female) pancreatic insufficient CF patients were evaluated regarding chronic infection, body mass index, lung function, medication, and diabetes, as well as data of Pseudomonas infection status, antibiotic treatment and hospitalization from 1-year follow-up. Results: We found no differences in lung function, body mass index, or frequency of diabetes. The adult group consisted of more males than females (208:168). We found no significant difference in prevalence of chronic Pseudomonas aeruginosa infection, but during the follow-up the incidence of new chronic infection was higher in adult females (10/33 vs. 4/56). Females had higher prevalence of Burkholderia infection (21/416 vs. 11/474). Adult females had more days on intravenous antibiotics (median 39 vs. 26 days/year), and days in hospital (median 2 vs. 0 days/year). More adult females received inhaled and oral steroids. In the pediatric cohort, females were treated more often with macrolides as an anti-inflammatory agent. Conclusion: We found no gender difference in key clinical parameters in our CF population. However, our study showed a higher risk of Pseudomonas and Burkholderia infection among the female patients. Additionally, we found that female patients require more intensified treatment regarding antibiotics, macrolides, steroids and days of hospitalization, indicating a true female disadvantage even with modern aggressive treatment. The finding of more males than females in the adult population suggesting a male advantage, warrants a mortality study. Pediatr Pulmonol. 2010; 45:959-965. (C) 2010 Wiley-Liss, Inc.

The aim of the study was to evaluate three serological methods for their ability to identify CF patients in different infection status especially those at risk of developing chronic Pseudomonas aeruginosa (Pa) infection. Methods: Two ELISA methods: exotoxin A (ExoA) and CF-IgG-ELISA (CF-IgG) and Crossed Immunoelectrophoresis (CIE) were used for measurement of Pa-antibodies in sera from 791 Scandinavian CF patients. Results: 381 patients were cultured negative for Pa in the year before study start, 129 patients were intermittently colonized and 281 patients were chronically infected. The sensitivity of the investigated assays was 96%, 93% and 97%, specificity 89%, 89% and 83% for CIE, ExoA and CF-IgG respectively. The negative predictive value was for CIE 97%, for ExoA 95% and for CF-IgG 98% and positive predictive values 87%, 86% and 80%. Out of the 381 patients cultured negative for Pa, 11 changed status to chronically infected. Twenty-four out of the 129 patients intermittently colonized became chronically infected. The antibody levels in this latter group of patients were significantly higher already at the study start and increased significantly during the study period (p < 0.05). Elevated levels of specific anti-Pseudomonal antibodies showed to be the risk factor for developing chronic P. aeruginosa infection (OR 4.9 and OR 2.7, p < 0.05 for CF-IgG and ExoA). Conclusion: All three serological assays were equally informative. The very high sensitivity of the assays made it possible to characterize patients with different infection status. Elevated levels of specific anti-Pseudomonas antibodies showed to be the risk factor for developing chronic Pa infection. Due to the specificity of the tests, antibiotic treatment based on serology might be considered in selected cases. There is a window of opportunity for suppression and eradication of initial P aeruginosa infection making measurement of specific anti-Pseudomonas antibodies helpful. (c) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. (Less)

Enterovirus D68 (EV-D68), phylogenetic clade B was identified in nasopharyngeal specimens of two cases of severe acute flaccid myelitis. The cases were six and five years-old and occurred in September and November 2014. EV-D68 is increasingly associated with acute flaccid myelitis in children, most cases being reported in the United States. Awareness of this possible neurological complication of enterovirus D68 infection is needed.

Abdominal pain combined with fever is common during childhood. We present a 12-year-old girl who was admitted to hospital with abdominal pain, fever and nausea, but she also complained of cough, weight loss and night sweat. Investigations revealed multiple and randomly distributed lung nodules, impaired lung function, meningitis and multiple small brain lesions, consistent with tuberculomas. The polymerase chain reaction was positive for Mycobacterium tuberculosis in sputum. Cultures of sputum and cerebrospinal fluid were also positive and confirmed miliary tuberculosis with concomitant meningitis. The result of the Mantoux test was 13 mm and that of the Quantiferon-TB Gold was 5.17 IU/ml. She was given four antituberculous drugs (isoniazide, rifampicin, pyrazinamide and ethambutol) for two months and two drugs (isoniazide and rifampicin) for an additional ten months. The intracranial tuberculomas increased in size during the first two months of treatment, but demonstrated regression after seven months. The girl was HIV-negative and had no sign of immunodeficiency, but had recently been ill with mononucleosis and varicella infections. She recovered completely. The combination of miliary tuberculosis and meningitis is uncommon, particularly among previously healthy children of this age. Temporary immune suppression, caused by viral infections, could possibly explain the unusual clinical course. Pediatricians should be aware of miliary tuberculosis as a possible diagnosis in children presenting with common symptoms.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, characterized by non-infectious, recurrent osteomyelitis, which typically affects the metaphyseal regions of lo...

Abdominal pain combined with fever is common during childhood. We present a 12-year-old girl who was admitted to hospital with abdominal pain, fever and nausea, but she also complained of cough, weight loss and night sweat. Investigations revealed multiple and randomly distributed lung nodules, impaired lung function, meningitis and multiple small brain lesions, consistent with tuberculomas. The polymerase chain reaction was positive for Mycobacterium tuberculosis in sputum. Cultures of sputum and cerebrospinal fluid were also positive and confirmed miliary tuberculosis with concomitant meningitis. The result of the Mantoux test was 13 mm and that of the Quantiferon-TB Gold was 5.17 IU/ml. She was given four antituberculous drugs (isoniazide, rifampicin, pyrazinamide and ethambutol) for two months and two drugs (isoniazide and rifampicin) for an additional ten months. The intracranial tuberculomas increased in size during the first two months of treatment, but demonstrated regression after seven months. The girl was HIV-negative and had no sign of immunodeficiency, but had recently been ill with mononucleosis and varicella infections. She recovered completely. The combination of miliary tuberculosis and meningitis is uncommon, particularly among previously healthy children of this age. Temporary immune suppression, caused by viral infections, could possibly explain the unusual clinical course. Pediatricians should be aware of miliary tuberculosis as a possible diagnosis in children presenting with common symptoms.

Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis-related glucose intolerance.We enrolled 898 cystic fibrosis patients from Sweden, Norway and Denmark. Vitamin D intake was assessed using a seven-day food record. Serum 25-hydroxyvitamin D (s25OHD) and HbA(1c) were measured, and an OGTT was carried out. Multiple linear and logistic regressions were used for HbA(1c) and cystic fibrosis-related diabetes/OGTT result as outcome variables, respectively. Each model was controlled for country, and for known cystic fibrosis-related diabetes risk factors: age, sex, genotype, liver dysfunction, long-term corticosteroid treatment, and lung and pancreatic function.Degree of vitamin D insufficiency (OR 1.36; p = 0.032) and s25OHD 30 nmol/l (OR 1.79; p = 0.042) were significant risk factors for cystic fibrosis-related diabetes. Accordingly, HbA(1c) value was positively associated with s25OHD 30 nmol/l and 50 nmol/l, as well as with degree of vitamin D insufficiency (adjusted R (2) = 20.5% and p 0.05 in all). In subgroup analyses, s25OHD 30 nmol/l determined the HbA(1c) value in paediatric patients (adjusted R (2) = 20.2%; p = 0.017), but not in adults.Vitamin D status is associated with HbA(1c) and diabetes in cystic fibrosis, particularly in children. The study justifies prospective studies on the proposed role of vitamin D deficiency in the pathophysiology of diabetes mellitus.

To explore whether gender differences in the Scandinavian Cystic Fibrosis (CF) patients exist in the areas of key clinical parameters, complications, and medication.Cross-sectional data on 890 (416 female) pancreatic insufficient CF patients were evaluated regarding chronic infection, body mass index, lung function, medication, and diabetes, as well as data of Pseudomonas infection status, antibiotic treatment and hospitalization from 1-year follow-up.We found no differences in lung function, body mass index, or frequency of diabetes. The adult group consisted of more males than females (208:168). We found no significant difference in prevalence of chronic Pseudomonas aeruginosa infection, but during the follow-up the incidence of new chronic infection was higher in adult females (10/33 vs. 4/56). Females had higher prevalence of Burkholderia infection (21/416 vs. 11/474). Adult females had more days on intravenous antibiotics (median 39 vs. 26 days/year), and days in hospital (median 2 vs. 0 days/year). More adult females received inhaled and oral steroids. In the pediatric cohort, females were treated more often with macrolides as an anti-inflammatory agent.We found no gender difference in key clinical parameters in our CF population. However, our study showed a higher risk of Pseudomonas and Burkholderia infection among the female patients. Additionally, we found that female patients require more intensified treatment regarding antibiotics, macrolides, steroids and days of hospitalization, indicating a true female disadvantage even with modern aggressive treatment. The finding of more males than females in the adult population suggesting a male advantage, warrants a mortality study.

Background: Chronic Pseudomonas aeruginosa (PA) infection causes increased morbidity and mortality in cystic fibrosis (CF). This study aimed to answer the following questions: Does the prevalence of chronic infection with PA differ between the CF centres in Scandinavia? Which differences exist concerning segregation and treatment of PA? Methods: 989 patients (86%) from all eight CF-centres in Scandinavia were included. Demographic and clinical data, including PA colonisation status based oil cultures and serology, were recorded at inclusion. The patients were followed prospectively for 1 year, recording number of days with anti-PA antibiotic treatment. Results: In all pancreatic insufficient (PI) patients (n=890) the prevalence of chronic PA infection at each centre ranged from 25.8% to 48.9%, but were not significantly different. In PI patients

Background: Epidemiological studies have shown an association between gastro-oesophageal reflux disease (GORD) and asthma, and oesophageal acid perfusion may cause bronchial constriction. However, no causative relation has been proven. Aim: To assess whether acid suppression would lead to reduced asthma symptoms in children with concomitant asthma and GORD. Methods: Thirty eight children (mean age 10.8 years, range 7.2–16.8; 29 males) with asthma and a reflux index ⩾5.0 assessed by 24 hour oesophageal pH monitoring were randomised to 12 weeks of treatment with omeprazole 20 mg daily or placebo. The groups were similar in age, gender, mean reflux index, and asthma severity. Primary endpoints were asthma symptoms (daytime wheeze, symptoms at night, in the morning, and during exercise) and quality of life (PAQLQ). Secondary endpoints were changes in lung function and the use of short acting bronchodilators. At the end of the study a repeated pH study was performed to confirm the efficacy of acid suppression. Results: The change in total symptom score did not differ significantly between the omeprazole and the placebo group, and decreased by 1.28 (95% CI −0.1 to 2.65) and 1.28 (95% CI −0.72 to 3.27) respectively. The PAQLQ score increased by 0.62 (95% CI 0.29 to 0.95) in the omeprazole group compared to 0.50 (95% CI 0.29 to 0.70) in the placebo group. Change in lung function and use of short acting bronchodilators were similar in the groups. The acid suppression was adequate (reflux index Conclusion: Omeprazole treatment did not improve asthma symptoms or lung function in children with asthma and GORD.

Background Chronic multifocal recurrent osteomyelitis (CRMO) is a rare autoimmune, inflammatory disorder that primarily affects children. The disease is characterised by non-infectious, recurrent osteomyelitis, which can be severe and disabling if left untreated. The diagnosis is often made delayed, patients are treated unnecessarily with antibiotics and there is a paucity of information on outcome and disease course. Objectives The aim of this study was to assess clinical presentation and outcome in a Norwegian Cohort of patients with CRMO. Methods Retrospective chart review was performed in the 26 patients with CRMO registered at the hospital between 2002 and 2013. Data collected were: age, symptoms at presentation, diagnostics and imaging, delay of diagnosis, number of affected skeletal sites, history and effect of medication, state of disease at latest visit: active disease, clinical partial or full remission (defined as minimum 6 months of continious inactive disease). Patients with minor symptoms, but otherwise inactive disease were categorised as having partial remission. Results Mean age at disease-onset was 10.5 years (range 5.4-14.0 years), 77% were female, and all patients were Caucasians (26 patients). The mean delay in diagnosis was 1.5 year (range 0.08 - 4.3) and 39% were initially treated with antibiotics. Disease onset was multifocal in 73% and symmetrical manifestations were seen in 25%. Mean disease duration was 4.0 years (range 0.3 -11.3 years). During disease course 85% developed multifocal disease. The most commonly affected skeletal regions were the fibula (65%), followed by the tibia (50%), the femur (42%), the pelvis (35%) and the clavicula (26%). A biopsy was taken in 70%. NSAIDs were given in most patients (89%), resulting in partial (54%) or total (23%) remission in those treated. Methotrexate and corticosteroids were infrequently used (respectively in 8% and 10%). None of the patients were treated with biologics or bisphosphonates. At the latest follow-up 20% still had active disease, 50% were in partial remission and 30% were in total remission, but only 22% were off all medication. Conclusions We conclude that after a mean disease duration of 4.0 years the majority of patients (80%) obtained a state of remission (partial or total remission), but only a minority (22%) of off all medication. Persistently active disease was seen in 20% of the patients. Methotrexate and corticosteroids were infrequently used and none of our patients were treated with biologics or bisphosphonates. The results may suggest a relative benign disease course in this Norwegian cohort, although few patients reached remission off medication. References Ferguson PJ and Sandu M. Current understanding of the pathogenesis and management of chronic recurrent multifocal osteomyelitis. Curr Rheumatol Rep 2012: 130 -141 Hedrich et al. Autoinflammtory bone disorders with special focus on chronic recurrent multifocal osteomyelitis. Pediatric Rheumatology 2013, 11:47 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3215