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Altered composition of polγunsaturated fattγ acids (PUFA) has been observed in allergic individuals and it has been proposed that this is due to an impairment of δ-6-desaturase activitγ. We have studied the composition of PUFA in serum phospholipids in twentγ-two 12-15 γear old children with asthma and/or allergic dermatitis and 23 non-atopic controls of similar age. The relative levels of docosahexaenoic acid (DHA, C22:6n-3) and total n-3 long-chain polγunsaturated fattγ acids (LCP) were lower (1.46% ± 0.54 vs. 1.90% ± 0.58, P = 0.01 for DHA and 2.34% ± 0.67 vs. 2.80% ± 0.77, P < 0.05 for total n-3 LCP) and the ratio of total n-6 to n-3 LCP was higher (P < 0.01) in the allergic children than in the controls. In addition to these differences, the relative levels of docosapentaenoic acid (DPA, C22:5n-3) and the ratio of arachidonic acid (AA, C20:4n-6) to dihomo-gamma-linolenic acid (DHGLA, C20:3n-6) were also lower in the 12 allergic children with positive skin prick test, as compared with the SPT negative children (both P < 0.05). In non-allergic children, the levels of total n-3 correlated with n-6 LCP (r = 0.76, p < 0.001). Furthermore, the n-3 LCP, i.e. EPA, DPA and DHA, correlated significantlγ with each other (r = 0.52-0.78, all p < 0.01) and correlated with n-6 LCP, i.e. C20:2, DHGLA and AA respectivelγ (r = 0.56-0.83, all P < 0.01). Most of these correlations were absent in allergic children. Higher levels of C20:2n-6 and lower levels of eicosapentaenoic acid (EPA, C20:5n-3) were recorded in 11 allergic children with serum IgE above the median level (56 kU/l), as compared to 11 with lower IgE levels (both P < 0.05). Furthermore, the levels of C20:2n-6 correlated with the IgE levels in the children (r = 0.65, P = 0.001). The findings could not confirm an impaired δ-6-desaturase activitγ in allergic school children and suggest that a disturbance of LCP metabolism is associated with allergic diseases [ABSTRACT FROM AUTHOR]

In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed. We discuss why the traditional drug development and reimbursement pathway is not fit for purpose in this field, and outline the pragmatic, regulatory and ethical challenges this poses for future access to N-of-1 therapies. Finally, we provide a roadmap for N-of-1 individualized therapy development., (© 2024. Springer Nature Limited.)

Background: Coronavirus-2019 (COVID-19) vaccination in Australia commenced in February 2021. The first vaccines recommended for use were AZD1222 and BNT162b2, both delivered as a two-dose primary schedule. In the absence of sustained immunity following immunisation, recommendations for booster vaccination have followed. It is likely that periodic boosting will be necessary for at least some Australians, but it is unknown what the optimal booster vaccines and schedules are or for whom vaccination should be recommended., Methods: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, randomised, Bayesian adaptive platform trial evaluating different booster vaccine interventions in immunocompetent children and adults, stratified by their primary vaccination schedule and age. Participants are randomised to receive one of three licensed COVID-19 booster vaccines available for use in Australia. PICOBOO aims to generate evidence about the immunogenicity, reactogenicity, and cross-protection of different booster vaccine strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants/subvariants. The protocol structure specifying PICOBOO is modular and hierarchical. We have previously published the PICOBOO core (master) protocol. Here, we detail the substudy protocol which outlines the study processes which are specific to PICOBOO participants enrolled in the booster vaccination substudy., Discussion: PICOBOO is an adaptive platform trial evaluating different COVID-19 booster vaccination strategies to generate evidence to inform immunisation practice and policy. The modular and flexible protocol structure is intended to enable investigators to respond with agility to new research questions as they arise, such as immunogenicity targeting emergent virus variants, and the immunogenicity and reactogenicity of new vaccines as they become available for use., Trial Registration: Australian and New Zealand Clinical Trials Register ACTRN12622000238774; registered on 10/02/2022. Protocol V8.0&#95;23112023., (© 2024. Crown.)

Objective: To compare the prevalence of parental diabetes between children with and without type 1 diabetes (T1D), and to compare clinical characteristics at diagnosis of T1D in children with, versus without, a family history of diabetes., Research Design and Methods: Parental diabetes among children with T1D was compared with a general population cohort. Clinical characteristics were compared by family history of diabetes in parents and grandparents of 3,603 children with T1D using relative risk (RR) and ANOVA., Results: Children with T1D more often had parents with type 2 diabetes (T2D) (RR 1.88; P < 0.001) than did children without diabetes. Children with T1D and a family history of T2D were more likely to be overweight or obese (P = 0.002)., Conclusions: A family history of T2D and being overweight may contribute to increased risk of T1D., (© 2024 by the American Diabetes Association.)

Objective: The objective was to investigate the feasibility of prospectively validating multiple clinical prediction scores (CPSs) for pediatric appendicitis in an Australian pediatric emergency department (ED)., Methods: A literature search was conducted to identify potential CPSs and a single-center prospective observational feasibility study was performed between November 2022 and May 2023 to evaluate the performance of identified CPSs. Children 5-15 years presenting with acute right-sided or generalized abdominal pain and clinician suspicion of appendicitis were included. CPSs were calculated by the study team from prospectively clinician-collected data and/or review of medical records. Accuracy of CPSs were assessed by area under the receiver operating characteristic curve (AUC) and proportions correctly identifiable as either low-risk or high-risk with the best performing CPS compared to clinician gestalt. Final diagnosis of appendicitis was confirmed on histopathology or by telephone/email follow-up for those discharged directly from ED., Results: Thirty CPSs were identified in the literature search and 481 patients were enrolled in the study. A total of 150 (31.2%) patients underwent appendectomy with three (2.0%) having a normal appendix on histopathology. All identified CPSs were calculable for at least 50% of the patient cohort. The pediatric Appendicitis Risk Calculator for pediatric EDs (pARC-ED; n = 317) was the best performing CPS with AUC 0.90 (95% confidence interval [CI] 0.86-0.94) and specificity 99.0% (95% CI 96.4%-99.7%) in diagnosing high-risk cases and a misclassification rate of 4.5% for low-risk cases., Conclusions: The study identified 30 CPSs that could be validated in a majority of patients to compare their ability to assess risk of pediatric appendicitis. The pARC-ED had the highest predictive accuracy and can potentially assist in risk stratification of children with suspected appendicitis in pediatric EDs. A multicenter study is now under way to evaluate the potential of these CPSs in a broader range of EDs to aid clinical decision making in more varied settings., (© 2024 The Author(s). Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Perinatal antibiotic exposure potentially leads to gut microbiota dysbiosis, which is associated with functional gastrointestinal disorders (FGIDs). We aimed to investigate the effects of Limosilactobacillus reuteri DSM 17938 supplementation on the development of FGIDs, crying and sleep duration, and the gut microbial composition in infants exposed to antibiotics during the neonatal period. In this randomised, double-blind, placebo-controlled study, we included 89 term neonates treated with antibiotics. Neonates received the study product for six weeks. FGIDs, assessed by the Infant Gastrointestinal Symptom Questionnaire, crying and sleep duration were assessed at four and eight weeks, and six months after enrolment. Faecal samples were collected six weeks and twelve months after enrolment. The gut microbial community composition was analysed using 16S amplicon sequencing and qPCR. The proportion of infants with FGIDs was greater in the control group, although the difference between the groups was significant only six months after enrolment. At all time points, the probiotic group presented a longer sleep duration and shorter crying time than the control group, but the difference was not statistically significant. Probiotic consumption had no significant effect on the gut microbiota composition except for increased L. reuteri DSM 17938 abundance in the probiotic group at six weeks after enrolment. At specific time points after supplementation with L. reuteri DSM 17938, a reduction in the prevalence of FGIDs was observed in the probiotic group. However, no observable effect on the gut microbiota was detected during the intervention. We believe that probiotic supplementation in neonates during and after antibiotic treatment to minimise the negative effects of antibiotics on gut function during this vulnerable period of human development warrants further investigation. The trial is registered at ClinicalTrials.gov (NCT02865564).

Background: Rising proportions of antimicrobial resistance (AMR) have been observed in both Staphylococcus aureus and Enterococcus spp. isolates., Methods: The Australian Group on Antimicrobial Resistance (AGAR) surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia. EUCAST 2022 was used for MIC interpretation and the AMR package in R for data analysis., Results: There were 2,091 BSIs with S. aureus and 534 enterococcal BSI episodes over the nine years. Three-quarters of S. aureus BSI episodes were community-onset (78.3%) whilst more than half of enterococcal BSIs were hospital-onset (56.9%). The median age for S. aureus BSIs was 6 years, whilst >50% enterococcal BSIs were in children <12 months old.Fifteen percent of S. aureus isolates were methicillin-resistant (MRSA). Overall, 85.3% of S. aureus were resistant to penicillin, 12.5% resistant to erythromycin, 10.3% to clindamycin, and 4.7% to ciprofloxacin. Resistance to penicillin decreased over time whilst clindamycin resistance increased.Resistance in Enterococcus spp. was almost entirely observed in E. faecium; only one E. faecalis isolate was ampicillin resistant, and no E. faecalis isolates were vancomycin or teicoplanin resistant. Seventy-three percent of E. faecium were resistant to ampicillin, 25.5% to vancomycin (VREfm) and 8.8% to teicoplanin., Conclusion: Significant shifts in the epidemiology and resistance profiles of S. aureus and Enterococcus spp. BSIs in Australian children were observed, making clear the importance of age-stratified reporting in antimicrobial resistance data., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Gram-negative bloodstream infections are associated with significant morbidity and mortality in children. Increasing antimicrobial resistance (AMR) is reported globally, yet efforts to track pediatric AMR at a national level over time are lacking., Methods: The Australian Group on Antimicrobial Resistance (AGAR) surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia. EUCAST 2022 was used for MIC interpretation and the AMR package in R for data analysis., Results: Over a nine-year period, there were 3,145 bloodstream infections with 3,266 gram-negative isolates reported in hospitalized children aged <18 years; 21.0% were from neonates. The median length of stay was 9 days, and 30-day all-cause mortality was 5.2%. A greater odds of death was observed in those with a multi-drug resistant organism (aOR: 2.1, 95%CI: 1.3, 3.3, p: 0.001). Escherichia coli (44.5%) and Klebsiella pneumoniae complex (12.6%) were the two most frequently reported organisms. Overall resistance in Enterobacterales to gentamicin/tobramycin was 11.6%, to ceftazidime/ceftriaxone was 12.9%, and 13.2% to ciprofloxacin. Resistance increased over time.Of 201 Pseudomonas aeruginosa isolates reported, 19.7% were resistant to piperacillin-tazobactam, 13.1% resistant to cefepime/ceftazidime and 9.8% to ciprofloxacin. Of 108 Acinetobacter spp. isolates, one was resistant to meropenem, and two were resistant to ciprofloxacin. Resistance did not increase over time., Conclusion: AMR in gram-negative organisms causing bloodstream infections in Australian children is increasing which should be considered when updating guidelines and empiric treatment regimens. Ongoing pediatric-specific national surveillance with pediatric reporting must remain a priority to strengthen antimicrobial stewardship and infection control programs., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: LS has given consultancy/lectures for Biogen, Novartis, Roche, BioHaven, Scholar Rock, Zentech and Sysnav. He is part of the Data Safety Monitoring Board of NMB biopharma.

Aims: Interindividual variations in efavirenz (EFV) plasma concentrations are extensive, but paediatric data on its consequences for viral control are scarce. The aim of this study was to explore the role of genetic variation in achieving therapeutic efavirenz plasma concentrations in a cohort of Ugandan children and the linkage between genetic CYP2B6 variants, EFV plasma variability, viral resistance and viral outcome., Methods: Ninety-nine treatment-naïve children, aged 3-12 years and living with HIV, were followed for 24 weeks after ART initiation assessing mid-dose efavirenz plasma concentrations, HIV RNA, HIV drug resistance and adherence. Polymorphisms in genes coding for drug-metabolizing enzymes were genotyped. Efavirenz concentrations were determined by liquid chromatography coupled with high-resolution tandem mass spectrometry. Metabolizer phenotype was predicted from composite genotypes of CYP2B6 (c.516G>T and c.983 T>C). A mixed effects restricted maximum likelihood regression model was used to identify important factors for efavirenz exposure., Results: Efavirenz plasma concentrations were below the therapeutic interval (1000-4000 mg/mL) in 12-17% and above in 21-24% of measurements. Eight children had persisting subtherapeutic concentrations, five of which failed virologically and three acquired at least one new resistant mutation. Multivariate modelling explained 70% of interindividual variation in plasma concentration, with treatment duration, adherence, CYP2B6c.136A>G, and metabolizer phenotype as independent predictors of EFV concentration. In univariate analysis, metabolizer phenotype explained 50% of interindividual variation., Conclusions: Metabolizer phenotype explained 50% of interindividual variation in efavirenz plasma concentration. Autoinduction was not confirmed and >33% of the concentrations were outside the therapeutic interval. Subtherapeutic concentrations worsened virological resistance and outcomes. Genotype-based dosing may help avert both sub- and supratherapeutic efavirenz plasma concentrations in Ugandan children., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aim: To identify the barriers and facilitators for timely detection and optimal management of otitis media (OM) in Aboriginal children in a primary care setting from the perspective of carers of Aboriginal children., Methods: A qualitative, Aboriginal co-designed, participatory action research study with interviews and focus groups in a large town in the Kimberley, Western Australia. The Consolidated Framework for Implementation Research informed stakeholder group identification and interview framework development. Data underwent thematic analysis using NVivo software., Results: Thirty-two carers of Aboriginal children participated. Key barriers identified for the detection of OM were limited information about OM provided to carers and carers feeling disempowered to express their concerns. Key facilitators identified were the provision of health information through health promotion and the use of culturally secure resources. Having a culturally secure clinical environment was identified as essential, with Aboriginal Health Workers playing a vital role in clinical care. No barriers to management of OM in primary care were reported. Facilitators included health care practitioners (HCPs) emphasising the importance of completing antibiotic course and the clinic providing necessary medications., Conclusions: A culturally secure health promotion strategy with health promotion teams, campaigns and resources is needed to increase community awareness of OM signs and symptoms and facilitate appropriate health seeking. It is essential that the local Aboriginal community co-lead and co-develop these initiatives to ensure the unique wisdom and knowledge of Aboriginal people are captured. HCPs and the clinic effectively facilitate management of OM by providing medications and emphasising completion of antibiotics., (© 2024 The Author(s). Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Purpose: Anterior drooling is a common comorbidity in children and young people (CYP) with neurodevelopmental disabilities. This study aimed to assess the social and emotional impact of drooling in CYP with a developmental age (DA) of 6 years and older, in whom this impact may differ from those with a lower DA due to their developing sense of self and awareness of their position within social groups., Methods: Questionnaire data collected for routine clinical care were used to assess parental perceptions of the impact of drooling on (1) social interaction; (2) satisfaction with social interaction, appearance, family relations and life in general and (3) the way CYP expressed feelings on appearance, acceptance by peers and acceptance by adults. Fisher's exact tests and Mann-Whitney U tests were applied to identify associations between clinical characteristics and the social and emotional impact of drooling., Results: Seventy-nine CYP with an estimated DA ≥ 6 years were included. The majority experienced frequent to constant (83%) and profuse (61%) drooling. Drooling frequently compromised social interaction with peers (49%) and adults (28%), and cognitive abilities were underestimated in 40%. Dissatisfaction with physical appearance (25%) related to drooling was noted. One-fifth of CYP reportedly expressed negative feelings on acceptance by peers related to drooling., Conclusions: These findings underscore the substantial impact of drooling on CYP with a DA of 6 years and older, primarily through avoidance by peers and underestimated cognitive abilities, emphasizing that recognizing and addressing these social-emotional consequences should be integral to clinical care., What Is Known: • Anterior drooling is common among children and youth with neurodevelopmental disabilities., What Is New: • There seems to be a heightened prevalence of impaired social interaction with peers and underestimation of cognitive abilities due to drooling among children with a developmental age of at least 6 years compared to previous studies with more heterogeneous populations. • The impact of drooling can extend to domains that affect self-esteem, although this may not be fully captured with standardized questions, requiring clinicians to address these consequences in a way that is tailored to the child's experiences., (© 2024. The Author(s).)

Background & Aims: Previous studies have observed changes in fat and fat-free mass among preterm infants when compared to term-born infants. However, these studies have mainly focused on moderate or very preterm infants, with a scope limited to the first few years of life. We aimed to compare body composition in extremely preterm infants to term-born infants in early childhood. Additionally, we investigated whether early neonatal nutrition was associated with the distribution of fat- and fat-free mass in later life., Methods: The study used dual-energy x-ray absorptiometry to evaluate the body composition of 52 children aged 6-9-years, of whom 35 were born extremely preterm and 17 were born at term and was analyzed using multivariate linear regression. Nutritional intakes of fluids, energy, and macronutrients during the first eight postnatal weeks for 26 extremely preterm infants were investigated in relation to body composition at age 6-9 years using Bayesian regression analysis and Gradient Boosting Machine., Results: Children born extremely preterm had smaller head circumference (confidence interval -8.7 to -1.7), shorter height (confidence interval -2.7 to -0.6), higher waist to height ratio (confidence interval 0.01-0.05) and lower fat-free mass (confidence interval -3.9 to -0.49), compared to children born at full-term. Children born extremely preterm had a differing response to amount of fluid and macronutrient intake for both fat mass index and fat-free mass index. A bimodal response showed high intake of fluid and macronutrients as associated with high fat mass index for some children, whereas others demonstrated an inverse association, suggesting analysis on cohort-level as problematic., Conclusions: Childhood body composition differs between extremely preterm infants and term-born infants. Extremely preterm infants display differing responses in their body composition to varying levels of fluids and macronutrient intake during the neonatal period., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Discomfort can be the cause of noninvasive respiratory support (NRS) failure in up to 50% of treated patients. Several studies have shown how analgosedation during NRS can reduce the rate of delirium, endotracheal intubation, and hospital length of stay in patients with acute respiratory failure. The purpose of this project was to explore consensus on which medications are currently available as analgosedatives during NRS, which types of patients may benefit from analgosedation while on NRS, and which clinical settings might be appropriate for the implementation of analgosedation during NRS., Methods: The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects of the use of analgesics and sedatives during NRS treatment. The methodology applied is in line with the principles of the modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales which were then subjected to blind votes for consensus., Results: The use of an analgosedation strategy in adult patients with acute respiratory failure of different origins may be useful where there is a need to manage discomfort. This strategy should be considered after careful assessment of other potential factors associated with respiratory failure or inappropriate noninvasive respiratory support settings, which may, in turn, be responsible for NRS failure. Several drugs can be used, each of them specifically targeted to the main component of discomfort to treat. In addition, analgosedation during NRS treatment should always be combined with close cardiorespiratory monitoring in an appropriate clinical setting., Conclusions: The use of analgosedation during NRS has been studied in several clinical trials. However, its successful application relies on a thorough understanding of the pharmacological aspects of the sedative drugs used, the clinical conditions for which NRS is applied, and a careful selection of the appropriate clinical setting., (© 2024. The Author(s).)

Profound and transient thrombocytopenia of functional platelets without bleeding was observed in patients envenomed by Vipera a. ammodytes ( Vaa ). This condition was rapidly reversed by administration of F(ab) 2 fragments of immunoglobulin G targeting the whole venom, leaving platelets fully functional. To investigate the potential role of snake venom C-type lectin-like proteins (snaclecs) in this process, Vaa -snaclecs were isolated from the crude venom using different liquid chromatographies. The purity of the isolated proteins was confirmed by Edman sequencing and mass spectrometry. The antithrombotic effect was investigated by platelet agglutination and aggregation assays and blood coagulation tests. Using flow cytometry, the platelet activation and binding of Vaa -snaclecs to various platelet receptors was analyzed. Antithrombotic efficacy was tested in vivo using a mouse model of vascular injury. Two Vaa -snaclecs were purified from the venom. One of them, Vaa -snaclec-3/2, inhibited ristocetin-induced platelet agglutination. It is a covalent heterodimer of Vaa -snaclec-3 (α-subunit) and Vaa -snaclec-2 (β-subunit). Our results suggest that Vaa -snaclec-3/2 induces platelet agglutination and consequently thrombocytopenia by binding to the platelet receptor glycoprotein Ib. Essentially, no platelet activation was observed in this process. In vivo, Vaa -snaclec-3/2 was able to protect the mouse from ferric chloride-induced carotid artery thrombosis, revealing its applicative potential in interventional angiology and cardiology., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aim: We aimed to investigate plasma lamotrigine concentrations and clinical effects in infants exposed to lamotrigine through breastfeeding., Methods: This was a retrospective study of mother-infant dyads in a clinical follow-up programme in Stockholm, Sweden. Data were collected from medical records., Results: We included 47 breastfed infants, born from 2011 to 2021, with a median gestational age of 39 + 6 weeks/days and a median birth weight of 3420 g. The median lamotrigine concentration in the infants' plasma was 2.5 (range 2.5-14.0) μmol/L. These concentrations correlated significantly with both the maternal plasma concentrations and the maternal doses (R = 0.79, p < 0.001 versus R = 0.54, p < 0.001). During the follow up, lamotrigine concentrations within the reference range for epilepsy treatment were detected in six (14%) infants and one had clinical symptoms that were probably related to lamotrigine exposure. Liver transaminases were elevated in three of 21 infants. All infants whose mothers had a dose of 150 mg or less had undetectable plasma concentrations and no symptoms during follow up., Conclusion: Infants exposed to lamotrigine through breastfeeding had a low risk of toxic effects. All infants whose mothers had low lamotrigine doses had unmeasurable plasma concentrations and no symptoms of lamotrigine exposure. These low-risk infants might be offered a simplified follow up., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Patient safety incidents in paediatric radiology have profound impacts not only on the patient and their family, but also on the well-being and professional practice of healthcare professionals. These incidents, which range from procedural and diagnostic incidents to serious adverse events leading to harm or even death of the patient, may evoke feelings of distress, guilt, and anxiety among paediatric radiologists (in-training), ultimately affecting their confidence and ability to deliver high-quality care. Recognizing the importance of addressing these challenges, healthcare organizations should implement strategies to support professionals in coping with and learning from these incidents. By fostering a culture of open communication, providing access to peer support, and offering structured debriefing and educational opportunities, healthcare institutions can help mitigate the psychological toll of patient safety incidents and promote resilience among their staff. This article examines the multifaceted impacts of patient safety incidents on paediatric radiologists (in-training) and their staff and outlines effective approaches for handling these incidents to support professional well-being and enhance patient safety., (© 2024. The Author(s).)

Objectives: Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post-HCT in a cohort of Australian children and identify risk factors for the development of these complications., Methods: Patients were identified from the HCT databases at two paediatric transplant centres in Australia. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio., Results: In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non-infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, P  = 0.02), matched unrelated donor (RR1.34, P  = 0.03), peripheral blood (RR 1.36, P  = 0.028) or cord blood (RR 1.73, P  = 0.012) as the stem cell source and pre-existing lung disease (RR1.72, P  < 0.0001). Children with a post-HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, P  < 0.0001)., Conclusion: This study demonstrates pulmonary complications continue to occur frequently in children post-HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre-transplant and enhanced treatments for those who develop lung disease., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Objective: To determine the efficacy of advanced hybrid closed loop (AHCL) therapy in a high-risk cohort of youth on continuous subcutaneous insulin infusion (CSII) ± continuous glucose monitoring (CGM) with suboptimal glycemia., Research Design and Methods: In a 6-month multicenter clinical trial, youth with type 1 diabetes with mean and most recent HbA1c > 8.5% (65 mmol/mol) were randomly assigned 1:1 to AHCL or treatment as usual (CSII ± CGM). The primary outcome was the 24-week between-group difference in HbA1c. Secondary outcomes included CGM metrics from masked CGM and psychological measures (youth-reported problem areas in diabetes [PAID], quality of life, anxiety, depression, and hypoglycemia fear) assessed using validated questionnaires., Results: A total of 42 participants were randomized (mean [SD] age 16.2 [2.5] years, HbA1c 9.8 [1.1]% or 84 [12] mmol/mol, PAID score 50.3 [19.8]). At study end, the mean (SD) HbA1c was 8.8 (1.1)% or 73 (12) mmol/mol with AHCL and 9.9 (1.2)% or 85 (13.1) mmol/mol with CSII ± CGM, with mean adjusted group difference of -0.77% (95% CI -1.45 to -0.09) or -8.4 mmol/mol (-15.8 to -1.0); P = 0.027. AHCL increased time in range 70-180 mg/dL (difference 19.1%; 95% CI 11.1 to 27.1), reduced time >180 mg/dL (difference -17.7%; 95% CI -26.6 to -8.8), with no increase in time spent <70 mg/dL (difference -0.8%; 95% CI -2.7 to 0.6). There was no evidence for difference in psychosocial outcomes between the two groups at study end., Conclusions: AHCL should be encouraged in youth with suboptimal glycemia, as AHCL improves glycemia. However, psychological support remains vital, as technology alone may not be able to reduce the burden of diabetes care in this subgroup., (© 2024 by the American Diabetes Association.)

Objective: The aim of our study was to compare the total 25(OH)D fraction, the bioavailable vitamin fraction, and the free vitamin D fraction in spring and fall in a group of healthy individuals. Methods: In our study, we collected blood samples from healthy participants at the end of both summer and winter, and measured serum levels of albumin, DBP, and 25(OH)D. Utilizing these data, we calculated the percentage of free and bioavailable vitamin D. Our cohort comprised 87 participants, with a male-to-female ratio of 14:73, aged 35.95 ± 12.55 years, ranging from 19 to 70 years. We employed the chemiluminescence method to determine the vitamin 25(OH)D levels, the ELISA method was utilized to determine DBP levels, the albumin BCP Assay was performed using the ADVIA biochemical analyzer (Siemens) and an online calculator was used to determine the free and bioavailable 25(OH)D levels. Results: Our findings indicate significantly lower 25(OH)D levels in winter (44.13 ± 17.82 nmol/L) compared to summer (74.97 ± 22.75 nmol/L; p < 0.001). For vitamin D binding protein there was no significant difference from summer (236.2 ± 164.39 mg/L) to winter (239.86 ± 141.9 mg/L; p = 0.77), albumin levels were significantly higher in summer (49.37 ± 4.15 g/L vs. 47.97 ± 3.91 g/L, p = 0.01), but the magnitude of the change may not be large enough to be solely responsible for the stability of vitamin D levels throughout the year. In the winter season a significantly lower calculated bioavailable 25(OH)D vitamin (7.45 ± 5.66 nmol/L against 13.11 ± 8.27 nmol/L; p < 0.001) was observed, and the free fraction also showed a significant decrease (17.3 ± 12.9 pmol/L versus 29.7 ± 19.1 pmol/L; p < 0.0001). We observed a moderately positive correlation between 25(OH)D and bioavailable percentage in winter (r = 0.680; p < 0.001), in contrast with a lower positive association in summer (r = 0.343; p < 0.001). Conclusion: Our data suggest a positive correlation between total and bioavailable 25(OH)D levels. In addition to the statistically significant variation in 25(OH)D between the two observation periods, there was an additional variation in the free vitamin D percentage. The summertime synthesis of vitamin D in the skin could contribute directly to the free fraction of vitamin D. Standardizing the measurement of free 25(OH)D and clinical studies is necessary to establish reference values before these methods can be implemented in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Osredkar, Vičič, Hribar, Benedik, Siuka, Jerin, Čegovnik Primožič, Fabjan, Kumer, Pravst and Žmitek.)

Congenital heart disease (CHD) is the most commonly detected congenital anomaly and affects up to 1% of all live-born neonates. Current guidelines support the use of chromosomal microarray analysis (CMA) and next-generation sequencing (NGS) as diagnostic approaches to identify genetic causes. The aim of our study was to evaluate the diagnostic yield of CMA and NGS in a cohort of neonates with both isolated and syndromic CHD. The present study included 188 infants under 28 days of age with abnormal echocardiography findings hospitalized at the Department of Neonatology, UMC Ljubljana, between January 2014 and December 2023. Phenotypic data were obtained for each infant via retrospective medical chart review. We established the genetic diagnosis of 22 distinct syndromes in 17% (32/188) of neonates. The most frequent genetic diagnoses in diagnosed cases were 22q11.2 microdeletion and CHARGE syndromes, followed by Noonan syndrome and Williams syndrome. In addition, we detected variants of uncertain significance in 4.8% (9/188) of neonates. Timely genetic diagnosis is important for the detection of syndrome-related comorbidities, prognosis, reproductive genetic risks and, when appropriate, genetic testing of other family members.

Background/Objectives : Rubinstein-Taybi Syndrome (RSTS-OMIM, #180849) is a rare genetic disorder associated with distinctive clinical features, including a typical craniofacial appearance, global developmental delay, intellectual disability and broad, angular thumbs and fingers. The main aim of the study was to evaluate the health problems of children with RTST, their quality of life and the impact of the disease on family functioning. In addition, we investigate whether comorbidities, autistic behavior and eating problems affect the children's overall QOL. Methods : A cross-sectional study was performed, including a total of 13 caregivers of children diagnosed with RSTS. A self-reported questionnaire [SRQ], medical records and the Pediatric Impact Module PedsQL TM 2.0, the Pediatric Quality of Life PedsQL TM 4.0 were used to obtain data on QOL and the impact of the disease on family functioning. Results : The overall QOL score for children with RSTS was x = 52.40; SD 13.01. The highest QOL was in emotional functioning (EF; x = 59.23; SD 18.69), while the lowest QOL was in physical functioning (PF; x = 48.56; SD 16.32) and social functioning (SF; x = 48.85; SD 18.84). There was a statistically significant negative correlation ( p < 0.03; r = -2.01) between the age of the child and their QOL, indicating that older children had lower QOL scores. The mean overall rating for the impact of RSTS on family functioning was x = 50.00; SD 10.91. Caregivers reported the highest scores for cognitive functioning (CF; x = 64.23; SD 23.70) and family relationships (FR; x = 60.00; SD 17.17). The lowest scores were for daily activities (DA; x = 41.03; SD 17.17) and worry (W; x = 37.69; SD 18.55). Conclusions : This study provides the first comprehensive exploration of the QOL of children with RSTS) and its impact on family functioning.

Objective: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors (TNFi) in JIA patients., Methods: This was a retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalization) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal)., Results: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9165/patient on active treatment (pre-withdrawal) and decreased significantly to €5063/patient (-44.8%) and €6569/patient (-28.3%) in the first and second year post-withdrawal, respectively (P < 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1180/patient, and €1320/patient in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first and second year post-withdrawal period, respectively., Conclusion: In the first two years after initiating withdrawal, the total annual costs were decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdrawal decisions, future research should assess the full long-term societal cost impacts, and include all biologics., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Anterior and posterior drooling are prevalent comorbidities in children with neurodevelopmental disabilities. Considering the heterogeneity of the patient population and the multifactorial aetiology of drooling, an interdisciplinary and individualised treatment approach is indispensable. However, no tool for stepwise decision-making in the treatment of paediatric drooling has been developed previously. Within the Radboudumc Amalia Children's Hospital, care for children with anterior and/or posterior drooling secondary to neurodevelopmental disabilities is coordinated by a saliva control team with healthcare professionals from six disciplines. In alignment with international literature, published guidelines, and evidence gained from two decades of experience and research by our team, this paper proposes an algorithm reflecting the assessment and treatment approach applied in our clinic. First, directions are provided to decide on the necessity of saliva control treatment, taking type of drooling, the child's age, and the severity and impact of drooling into account. Second, the algorithm offers guidance on the choice between available treatment options, highlighting the importance of accounting for child characteristics and child and caregiver preferences in clinical (shared) decision-making., Conclusions: With this algorithm, we aim to emphasise the importance of repeated stepwise decision-making in the assessment and treatment of drooling in children during their childhood, encouraging healthcare professionals to apply a holistic approach., What Is Known: • Children with anterior or posterior drooling secondary to neurodevelopmental disabilities comprise a heterogeneous group, necessitating an individualised treatment approach. • No stepwise decision-making tool is available for the treatment of paediatric drooling., What Is New: • Deciding on the necessity of saliva control treatment should be a conscious process, based on type of drooling, age, and drooling severity and impact. • Type of drooling, age, cognition, oral motor skills, self-awareness, posture, diagnosis, and child/caregiver preferences need to be considered to decide on the optimal treatment., (© 2024. The Author(s).)

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb + ) children and adults who are at risk of (confirmed single IAb + ) or living with (multiple IAb + ) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb + ; (2) when people who are IAb + are initially identified there is a need for confirmation using a second sample; (3) single IAb + individuals are at lower risk of progression than multiple IAb + individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care., (© 2024. American Diabetes Association and European Association for the Study of Diabetes.)

Objective: To analyze the clinical and physiological outcomes of NIV-NAVA in preterm infants compared with other non-invasive respiratory support., Study Design: We conducted a meta-analysis of RCTs and randomized crossover studies comparing NIV-NAVA to other non-invasive strategies in preterm neonates., Results: NIV-NAVA was superior to other non-invasive support in maximum EAdi (MD - 0.66 µV; 95% CI - 1.17 to -0.15; p = 0.01), asynchrony index (MD - 49.8%; 95% CI - 63.1 to -36.5; p < 0.01), and peak inspiratory pressure (MD - 2.2 cmH2O; 95% CI - 2.7 to -1.7; p < 0.01). However, there were no significant differences in the incidences of intubation (RR 0.91; 95% CI 0.56-1.48; p = 0.71), reintubation (RR 0.72; 95% CI 0.45-1.16; p = 0.18), or bronchopulmonary dysplasia (RR 0.77; 95% CI 0.37-1.60; p = 0.48)., Conclusion: NIV-NAVA was associated with improvements in maximum Edi, asynchrony index, and peak inspiratory pressure relative to other non-invasive respiratory strategies, without significant differences in clinical outcomes between groups., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

A type 1 diabetes (T1D) transition clinic in Sydney, Australia, provides age specific care for young adults (aged 16-25 years) and for adults (aged 21 years and above), and has reported improved clinical outcomes post transition to adult care over a 21-year period. This study investigated the contribution of digital technology to long-term resilient capacity of the clinic. Clinic observations and interviews with eight providers and 17 young adults were conducted. Using a framework to analyze resilient capacity in healthcare, seven strong themes emerged from the data: Leadership, Involvement, Communication, Coordination, Risk Awareness, Competence and Alignment with three themes, Structure, Learning and Facilitators also supported. Patient service adaptations included offering out of hours appointment times and telehealth to accommodate young adults' availability. This study provides evidence for the important role that digital technologies contribute to a system of care with capacity for resilience. Our findings contribute to the understanding of the factors needed to support young adults with T1D and may be valuable to inform models of care for young adults living with other chronic health conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)