Variation in antibiotic consumption in very preterm infants-a 10 year population-based study.

OBJECTIVES: Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. PATIENTS AND METHODS: All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009-18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. RESULTS: We included 5296 infants: 3646 (69%) were born at 28-31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum ß-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum ß-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum ß-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. CONCLUSIONS: The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum ß-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development.

Hearing impairment after asphyxia and neonatal encephalopathy: a Norwegian population-based study.

The purpose of this study is to evaluate the association between perinatal asphyxia, neonatal encephalopathy, and childhood hearing impairment. This is a population-based study including all Norwegian infants born ≥ 36 weeks gestation between 1999 and 2014 and alive at 2 years (n = 866,232). Data was linked from five national health registries with follow-up through 2019. Perinatal asphyxia was defined as need for neonatal intensive care unit (NICU) admission and an Apgar 5-min score of 4-6 (moderate) or 0-3 (severe). We coined infants with seizures and an Apgar 5-min score < 7 as neonatal encephalopathy with seizures. Infants who received therapeutic hypothermia were considered to have moderate-severe hypoxic-ischemic encephalopathy (HIE). The reference group for comparisons were non-admitted infants with Apgar 5-min score ≥ 7. We used logistic regression models and present data as adjusted odds ratios (aORs) with 95% confidence intervals (CI). The aOR for hearing impairment was increased in all infants admitted to NICU: moderate asphyxia aOR 2.2 (95% CI 1.7-2.9), severe asphyxia aOR 5.2 (95% CI 3.6-7.5), neonatal encephalopathy with seizures aOR 7.0 (95% CI 2.6-19.0), and moderate-severe HIE aOR 10.7 (95% CI 5.3-22.0). However, non-admitted infants with Apgar 5-min scores < 7 did not have increased OR of hearing impairment. The aOR for hearing impairment for individual Apgar 5-min scores in NICU infants increased with decreasing Apgar scores and was 13.6 (95% CI 5.9-31.3) when the score was 0.          Conclusions: An Apgar 5-min score < 7 in combination with NICU admission is an independent risk factor for hearing impairment. Children with moderate-severe HIE had the highest risk for hearing impairment. What is Known: • Perinatal asphyxia and neonatal encephalopathy are associated with an increased risk of hearing impairment. • The strength of the association, and how other co-morbidities affect the risk of hearing impairment, is poorly defined. What is New: • Among neonates admitted to a neonatal intensive care unit (NICU), decreased Apgar 5-min scores, and increased severity of neonatal encephalopathy, were associated with a gradual rise in risk of hearing impairment. • Neonates with an Apgar 5-min score 7, but without NICU admission, did not have an increased risk of hearing impairment.

Nordic survey showed wide variation in discharge practices for very preterm infants.

AIM: We aimed to describe clinical practices and criteria for discharge of very preterm infants in Nordic neonatal units. METHODS: Medical directors of all 89 level-2 and level-3 units in Denmark, Finland, Iceland, Norway and Sweden were invited by e-mail to complete a web-based multiple-choice survey with the option to make additional free-text comments. RESULTS: We received responses from 83/89 units (93%). In all responding units, discharge readiness was based mainly on clinical assessment with varying criteria. In addition, 36% used formal tests of cardiorespiratory stability and 59% used criteria related to infant weight or growth. For discharge with feeding tube, parental ability to speak the national language or English was mandatory in 45% of units, with large variation among countries. Post-discharge home visits and video-consultations were provided by 59% and 51%, respectively. In 54% of units, parental preparation for discharge were not initiated until the last two weeks of hospital stay. CONCLUSION: Discharge readiness was based mainly on clinical assessment, with criteria varying among units despite similar population characteristics and care structures. This variation indicates a lack of evidence base and may unnecessarily delay discharge; further studies of this matter are needed. Earlier parental preparation and use of interpreters might facilitate earlier discharge.

Early Empirical Antibiotics and Adverse Clinical Outcomes in Infants Born Very Preterm: A Population-Based Cohort.

OBJECTIVE: The objective of this study was to evaluate the association between empirical antibiotic therapy in the first postnatal week in uninfected infants born very preterm and the risk of adverse outcomes until discharge. STUDY DESIGN: Population-based, nationwide registry study in Norway including all live-born infants with a gestational age <32 weeks surviving first postnatal week without sepsis, intestinal perforation, or necrotizing enterocolitis (NEC) between 2009 and 2018. Primary outcomes were severe NEC, death after the first postnatal week, and/or a composite outcome of severe morbidity (severe NEC, severe bronchopulmonary dysplasia [BPD], severe retinopathy of prematurity, late-onset sepsis, or cystic periventricular leukomalacia). The association between empirical antibiotics and adverse outcomes was assessed using multivariable logistic regression models, adjusting for known confounders. RESULTS: Of 5296 live-born infants born very preterm, 4932 (93%) were included. Antibiotics were started in first postnatal week in 3790 of 4932 (77%) infants and were associated with higher aOR of death (aOR 9.33; 95% CI: 1.10-79.5, P = .041), severe morbidity (aOR 1.88; 95% CI: 1.16-3.05, P = .01), and severe BPD (aOR 2.17; 95% CI: 1.18-3.98; P = .012), compared with those not exposed. Antibiotics ≥ 5 days were associated with higher odds of severe NEC (aOR 2.27; 95% CI: 1.02-5.06; P = .045). Each additional day of antibiotics was associated with 14% higher aOR of death or severe morbidity and severe BPD. CONCLUSIONS: Early and prolonged antibiotic exposure within the first postnatal week was associated with severe NEC, severe BPD, and death after the first postnatal week.

Dual inhibition of complement C5 and CD14 attenuates inflammation in a cord blood model.

BACKGROUND: Escherichia coli and Group B streptococci (GBS) are the main causes of neonatal early-onset sepsis (EOS). Despite antibiotic therapy, EOS is associated with high morbidity and mortality. Dual inhibition of complement C5 and the Toll-like receptor co-factor CD14 has in animal studies been a promising novel therapy for sepsis. METHODS: Whole blood was collected from the umbilical cord after caesarean section (n = 30). Blood was anti-coagulated with lepirudin. C5 inhibitor (eculizumab) and anti-CD14 was added 8 min prior to, or 15 and 30 min after adding E. coli or GBS. Total bacterial incubation time was 120 min (n = 16) and 240 min (n = 14). Cytokines and the terminal complement complex (TCC) were measured using multiplex technology and ELISA. RESULTS: Dual inhibition significantly attenuated TCC formation by 25-79% when adding inhibitors with up to 30 min delay in both E. coli- and GBS-induced inflammation. TNF, IL-6 and IL-8 plasma concentration were significantly reduced by 28-87% in E. coli-induced inflammation when adding inhibitors with up to 30 min delay. The dual inhibition did not significantly reduce TNF, IL-6 and IL-8 plasma concentration in GBS-induced inflammation. CONCLUSION: Dual inhibition of C5 and CD14 holds promise as a potential future treatment for severe neonatal EOS. IMPACT: Neonatal sepsis can cause severe host inflammation with high morbidity and mortality, but there are still no effective adjunctive immunologic interventions available. Adding CD14 and complement C5 inhibitors up to 30 min after incubation of E. coli or Group B streptococci in a human umbilical cord blood model significantly reduced complement activation and cytokine release. Dual inhibition of C5 and CD14 is a potential future therapy to modulate systemic inflammation in severe cases of neonatal sepsis.

Kidney biopsy diagnosis in childhood in the Norwegian Kidney Biopsy Registry and the long-term risk of kidney replacement therapy: a 25-year follow-up.

BACKGROUND: There is scarce information on biopsy-verified kidney disease in childhood and its progression to chronic kidney disease stage 5 (CKD 5). This study aims to review biopsy findings in children, and to investigate risk of kidney replacement therapy (KRT). METHODS: We conducted a retrospective long-term follow-up study of children included in the Norwegian Kidney Biopsy Registry (NKBR) and in the Norwegian Renal Registry (NRR) from 1988 to 2021. RESULTS: In total, 575 children with a median (interquartile range, IQR) age of 10.7 (6.1 to 14.1) years were included, and median follow-up time (IQR) after kidney biopsy was 14.3 (range 8.9 to 21.6) years. The most common biopsy diagnoses were minimal change disease (MCD; n = 92), IgA vasculitis nephritis (IgAVN; n = 76), IgA nephropathy (n = 63), and focal and segmental glomerulosclerosis (FSGS; n = 47). In total, 118 (20.5%) of the biopsied children reached CKD 5, median (IQR) time to KRT 2.3 years (7 months to 8.4 years). Most frequently, nephronophthisis (NPHP; n = 16), FSGS (n = 30), IgA nephropathy (n = 9), and membranoproliferative glomerulonephritis (MPGN; n = 9) led to KRT. CONCLUSIONS: The risk of KRT after a kidney biopsy diagnosis is highly dependent on the diagnosis. None of the children with MCD commenced KRT, while 63.8% with FSGS and 100% with NPHP reached KRT. Combining data from kidney biopsy registries with registries on KRT allows for detailed information concerning the risk for later CKD 5 after biopsy-verified kidney disease in childhood. A higher resolution version of the Graphical abstract is available as Supplementary information.

Preterm birth in the Nordic countries-Capacity, management and outcome in neonatal care.

AIM: Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. METHODS: Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared. RESULTS: Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities. CONCLUSION: Management of very preterm infants exhibited significant regional variations in the Nordic countries.

[Hip dysplasia in infants ­ screening, treatment and follow-up]. / Hofteleddsdysplasi hos spedbarn ­ screening, behandling og oppfølging.

BACKGROUND: Hip dysplasia occurs in up to 3 % of neonates and if untreated can lead to dislocated hip, osteoarthritis and the need for a hip prosthesis. The study aimed to identify routines for ultrasound screening, treatment and follow-up of hip dysplasia in Norwegian hospitals. MATERIAL AND METHOD: An online questionnaire was sent to radiologists responsible for paediatric examinations at all hospitals with paediatric departments. INTERPRETATION: Routines for screening, treatment and follow-up of hip dysplasia varied to a considerable degree between the hospitals.

Gentamicin serum concentration measurement in children. / Serumkonsentrasjonsmåling av gentamicin hos barn.

BACKGROUND: Gentamicin is often used to treat serious paediatric infections. It has been standard practice in Norway to measure the serum concentration of gentamicin immediately prior to the second or third dose (pre-dose [trough] concentration) to assess the risk of toxicity. The clinical significance of such measurements in children has not previously been evaluated in Norway. MATERIAL AND METHOD: This is a retrospective study of routine pre-dose samples obtained for the measurement of serum gentamicin in paediatric patients aged 1 month to 17 years at four hospitals in Norway. Clinical data were extracted from electronic medical records from two of the hospitals. All children received treatment with intravenous gentamicin at a dose of 7 mg/kg once daily in accordance with Norwegian guidelines. RESULTS: The most common indications for treatment were febrile urinary tract infection, febrile neutropenia, and suspected or confirmed sepsis. The median (interquartile range) duration of treatment in 353 episodes at two of the hospitals was 4 (3-5) days. Serum gentamicin pre-dose samples were analysed for 1,288 treatment episodes across four hospitals. In 1,223 episodes (95 %), the pre-dose sample showed a serum gentamicin concentration of less than 0.6 mg/L. In 7 episodes (0.5 %), the pre-dose sample showed an elevated gentamicin concentration, defined as greater than 1.0 mg/L. INTERPRETATION: An in most cases mildly elevated serum gentamicin concentration was found in the pre-dose sample in 7 of 1,288 treatment episodes. Routine measurement of serum gentamicin via a pre-dose sample should in future be reserved for children receiving long-term gentamicin treatment, those with impaired kidney function, or those who are also receiving nephro- or ototoxic drugs.

Neonates and COVID-19: state of the art : Neonatal Sepsis series.

The SARS-CoV-2 pandemic has had a significant impact worldwide, particularly in middle- and low-income countries. While this impact has been well-recognized in certain age groups, the effects, both direct and indirect, on the neonatal population remain largely unknown. There are placental changes associated, though the contributions to maternal and fetal illness have not been fully determined. The rate of premature delivery has increased and SARS-CoV-2 infection is proportionately higher in premature neonates, which appears to be related to premature delivery for maternal reasons rather than an increase in spontaneous preterm labor. There is much room for expansion, including long-term data on outcomes for affected babies. Though uncommon, there has been evidence of adverse events in neonates, including Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C). There are recommendations for reduction of viral transmission to neonates, though more research is required to determine the role of passive immunization of the fetus via maternal vaccination. There is now considerable evidence suggesting that the severe visitation restrictions implemented early in the pandemic have negatively impacted the care of the neonate and the experiences of both parents and healthcare professionals alike. Ongoing collaboration is required to determine the full impact, and guidelines for future management. IMPACT: Comprehensive review of current available evidence related to impact of the COVID-19 pandemic on neonates, effects on their health, impact on their quality of care and indirect influences on their clinical course, including comparisons with other age groups. Reference to current evidence for maternal experience of infection and how it impacts the fetus and then neonate. Outline of the need for ongoing research, including specific areas in which there are significant gaps in knowledge.

Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials.

BACKGROUND: The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered. RESULTS: Among 884 abstracts identified, 90 randomised controlled trials (RCTs) were included in this review. Only 30 manuscripts explicitly stated the primary and/or secondary outcomes. A total of 88 distinct outcomes were recorded across all 90 studies included. These were then assigned to seven different domains in line with the taxonomy for classification proposed by the COMET initiative. The most frequently reported outcome was survival with 74% (n = 67) of the studies reporting an outcome within this domain. CONCLUSIONS: This systematic review constitutes one of the initial phases in the protocol for developing a COS in neonatal sepsis. The paucity of standardised outcome reporting in neonatal sepsis hinders comparison and synthesis of data. The final phase will involve a Delphi Survey to generate a COS in neonatal sepsis by consensus recommendation. IMPACT: This systematic review identified a wide variation of outcomes reported among published RCTs on the management of neonatal sepsis. The paucity of standardised outcome reporting hinders comparison and synthesis of data and future meta-analyses with conclusive recommendations on the management of neonatal sepsis are unlikely. The final phase will involve a Delphi Survey to determine a COS by consensus recommendation with input from all relevant stakeholders.

[Methicillin-resistant Staphylococcus aureus in wound drainage in children] / Meticillinresistente gule stafylokokker i sårsekret hos barn.

BACKGROUND: Skin and soft tissue infections are common in children. We wished to investigate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in wound drainage from children in Norway. MATERIAL AND METHOD: We conducted an observational study based on data from the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM) for the period 2013-21. Resistance data from wound drainage with growth of Staphylococcus aureus from children (0-17 years) and adults were included in the study. RESULTS: A total of 1 416 isolates from wound drainage from children and 7 623 isolates from adults with growth of Staphylococcus aureus were included. MRSA was detected in 33 (2.3 %) of the isolates from children and 95 (1.2 %) of the isolates from adults (p = 0.002). In children, the highest prevalence of MRSA was in those of kindergarten age (1-5 years, 4.4 %), compared to infants (< 1 year, 1.0 %) and children of school age (6-17 years, 1.7 %) (p = 0.011). Kindergarten children had the highest prevalence of erythromycin resistance (9.0 %). INTERPRETATION: The prevalence of methicillin-resistant Staphylococcus aureus in wound drainage from children in Norway was generally low, but somewhat higher in drainage from kindergarten children compared to other age groups. It is not generally necessary to take account of methicillin resistance in the empirical treatment of skin and soft tissue infections in children in Norway.

Stratification of Culture-Proven Early-Onset Sepsis Cases by the Neonatal Early-Onset Sepsis Calculator: An Individual Patient Data Meta-Analysis.

OBJECTIVES: To provide a comprehensive assessment of case stratification by the Neonatal Early-Onset Sepsis (EOS) Calculator, a novel tool for reducing unnecessary antibiotic treatment. STUDY DESIGN: A systematic review with individual patient data meta-analysis was conducted, extending PROSPERO record CRD42018116188. Cochrane, PubMed/MEDLINE, EMBASE, Web of Science, Google Scholar, and major conference proceedings were searched from 2011 through May 1, 2020. Original data studies including culture-proven EOS case(s) with EOS Calculator application, independent from EOS Calculator development, and including representative birth cohorts were included. Relevant (individual patient) data were extracted from full-text and data queries. The main outcomes were the proportions of EOS cases assigned to risk categories by the EOS Calculator at initial assessment and within 12 hours. Evidence quality was assessed using Newcastle-Ottawa scale, Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies, and GRADE tools. RESULTS: Among 543 unique search results, 18 were included, totaling more than 459 000 newborns. Among 234 EOS cases, EOS Calculator application resulted in initial assignments to (strong consideration of) empiric antibiotic administration for 95 (40.6%; 95% CI, 34.2%-47.2%), more frequent vital signs for 36 (15.4%; 95% CI, 11.0%-20.7%), and routine care for 103 (44.0%; 95% CI, 37.6%-50.6%). By 12 hours of age, these proportions changed to 143 (61.1%; 95% CI, 54.5%-67.4%), 26 (11.1%; 95% CI, 7.4%-15.9%), and 65 (27.8%; 95% CI, 22.1%-34.0%) of 234 EOS cases, respectively. CONCLUSIONS: EOS Calculator application assigns frequent vital signs or routine care to a substantial proportion of EOS cases. Clinical vigilance remains essential for all newborns.

International comparison of guidelines for managing neonates at the early phase of the SARS-CoV-2 pandemic.

BACKGROUND: The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers. METHODS: Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies. RESULTS: Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance. CONCLUSIONS: At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus. IMPACT: At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.

Metabolic responses in neonatal sepsis-A systematic review of human metabolomic studies.

AIM: To systematically review human metabolomic studies investigating metabolic responses in septic neonates. METHODS: A systematic literature search was performed in the databases MEDLINE, EMBASE and Cochrane library up to the 1st of January 2021. We included studies that assessed neonatal sepsis and the following outcomes; (1) change in the metabolism compared to healthy neonates and/or (2) metabolomics compared to traditional diagnostic tools of neonatal sepsis. The screened abstracts were independently considered for eligibility by two researchers. PROSPERO ID: CRD42020164454. RESULTS: The search identified in total 762 articles. Fifteen articles were assessed for eligibility. Four studies were included, with totally 78 neonates. The studies used different diagnostic criteria and had between 1 and 16 sepsis cases. All studies with bacterial sepsis found alterations in the glucose and lactate metabolism, reflecting possible redistribution of glucose consumption from mitochondrial oxidative phosphorylation to the lactate and pentose phosphate pathway. We also found signs of increased oxidative stress and fatty acid oxidation in sepsis cases. CONCLUSION: We found signs of metabolomic signatures in neonatal sepsis. This may lead to better understanding of sepsis pathophysiology and detection of new candidate biomarkers. Results should be validated in large-scale multicentre studies.

Antibiotic resistance in paediatric UTIs in Norway. / Antibiotikaresistens ved urinveisinfeksjoner hos barn i Norge.

BACKGROUND: Urinary tract infections are common in children. The purpose of this study was to describe national resistance data from urinary isolates from children with a view to informing antibiotic use. METHOD: We conducted an observational study based on culture responses with resistance determination in urine from the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM). All urinary isolates from children (0-17 years) in the period 2013-17 were included and compared with urinary isolates from adults. For cephalexin resistance, we used data from two Norwegian hospitals covering the period 2015-19. RESULTS: Of 13 211 urinary isolates included in the NORM register, 589 (4.5 %) were from children. Weighted by the number of data collection days, Escherichia coli accounted for 85.2 % of the isolates from children. For E. coli, there was a higher proportion of trimethoprim resistance in urine samples from children (27.0 %) compared to adults (22.9 %), p = 0.02. For ciprofloxacin, we found a lower resistance rate in E. coli in urine samples from children (5.7 %) compared to adults (8.7 %), p = 0.03. For other selected antibiotics, we found the following resistance rates in E. coli in children: nitrofurantoin (0.5 %), mecillinam (4.0 %), cephalexin (4.3 %), amoxicillin-clavulanic acid (7.2 %) and trimethoprim-sulfamethoxazole (24.1 %). INTERPRETATION: Pivmecillinam, cephalexin and amoxicillin-clavulanic acid are relevant choices in the empirical treatment of upper urinary tract infections. Nitrofurantoin and pivmecillinam are relevant for lower urinary tract infections. Trimethoprim and trimethoprim-sulfamethoxazole should only be used after resistance determination.

Parents of children with Down syndrome and their experiences with the healthcare services. / Erfaringer med helsevesenet blant foreldre til barn med Downs syndrom.

BACKGROUND: Children and adolescents with Down syndrome have a comprehensive need for follow-up in the primary and specialist healthcare services. MATERIAL AND METHOD: In June 2019, we published a questionnaire on the Facebook group of the Norwegian Network for Down syndrome. The purpose was to investigate user experiences among parents of children and adolescents with Down syndrome in the age group 0-20 years, in their encounter with the healthcare services. RESULTS: We received 174 responses. Those most satisfied were parents of children who received follow-up for secondary diagnoses such as vision problems, heart defects and endocrine disorders. Those least satisfied were parents of children with problems associated with behaviour, sleep and puberty. Approximately 6 out of 10 parents reported no negative experiences in their encounter with the healthcare services, but 29/161 (18 %) reported that the diagnosis of Down syndrome had contributed to treatment failure by the paediatrician or in the child rehabilitation service. INTERPRETATION: The study indicates a need for improved follow-up of children and adolescents with Down syndrome, both in the primary and specialist healthcare services.

Staphylococcus borealis sp. nov., isolated from human skin and blood.

When analysing a large cohort of Staphylococcus haemolyticus, using whole-genome sequencing, five human isolates (four from the skin and one from a blood culture) with aberrant phenotypic and genotypic traits were identified. They were phenotypically similar with yellow colonies, nearly identical 16S rRNA gene sequences and initially speciated as S. haemolyticus based on 16S rRNA gene sequence and MALDI-TOF MS. However, compared to S. haemolyticus, these five strains demonstrate: (i) considerable phylogenetic distance with an average nucleotide identity <95 % and inferred DNA-DNA hybridization <70  %; (ii) a pigmented phenotype; (iii) urease production; and (iv) different fatty acid composition. Based on the phenotypic and genotypic results, we conclude that these strains represent a novel species, for which the name Staphylococcus borealis sp. nov. is proposed. The novel species belong to the genus Staphylococcus and is coagulase- and oxidase-negative and catalase-positive. The type strain, 51-48T, is deposited in the Culture Collection University of Gothenburg (CCUG 73747T) and in the Spanish Type Culture Collection (CECT 30011T).

Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases.

BACKGROUND: Variants in POLG are one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. METHODS: A multinational, retrospective study using data from 155 patients with POLG variants recruited from seven European countries. RESULTS: We describe the spectrum of clinical features associated with POLG variants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset-onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. CONCLUSION: Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course.

Active antibiotic discontinuation in suspected but not confirmed early-onset neonatal sepsis-A quality improvement initiative.

AIM: To study whether a simple targeted intervention could reduce unwarranted antibiotic treatment in near-term and term neonates with suspected, but not confirmed early-onset sepsis. METHODS: A quality improvement initiative in three Norwegian neonatal intensive care units. The intervention included an inter-hospital clinical practice guideline for discontinuing antibiotics after 36-48 hours if sepsis was no longer suspected and blood cultures were negative in neonates ≥ 34+0 weeks of gestation. Two units used procalcitonin in decision-making. We compared data 12-14 months before and after guideline implementation. The results are presented as median with interquartile ranges. RESULTS: A total of 284 infants (2.5% of all births ≥ 34+0 weeks of gestation) received antibiotics before and 195 (1.8%) after guideline implementation (P = .0018). The two units that used procalcitonin discontinued antibiotics earlier after guideline implementation than the unit without procalcitonin. Neonates not diagnosed with sepsis were treated 49 (31-84) hours before and 48 (36-72) hours after guideline implementation (P = .68). In all infants, including those diagnosed with sepsis, antibiotic treatment duration was reduced from 108 (60-144) to 96 (48-120) hours (P = .013). CONCLUSION: Antibiotic treatment duration for suspected, but not confirmed early-onset sepsis did not change. However, treatment duration for all infants and the proportion of infants commenced on antibiotics were reduced.