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关键词： Heart transplantation   eculizumab   medical therapy   antiboby-mediated rejection   children   paediatrics  

摘要： Antibody-mediated rejection is a major clinical challenge that limits graft survival. Various modalities of treatment have been reported in small studies in paediatric heart recipients. A novel approach is to use complement-inhibiting agents, such as eculizumab, which inhibits cleavage of C5 to C5a thereby limiting the formation of membrane attack complex and terminal complement-mediated injury of tissue-bound antibodies. This medical modality of treatment has theoretical advantages but the collective experience in its use in the solid organ transplant community remains small. We add to this experience by combining 14 cases from 6 paediatric heart centres in this descriptive study.

摘要： Recent evidence suggest that long inter-pregnancy interval (IPI; defined as a time interval between a live birth and estimated time of conception of a subsequent pregnancy of over 60 months) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (

摘要： Introduction The bioequivalence of two formulations of desmopressin (dDAVP), a vasopressin analogue prescribed for nocturnal enuresis treatment in children, has been previously confirmed in adults but not in children. In this study, we aimed to study the pharmacokinetics (PK) and pharmacodynamics (PD) of these two formulations, in both fasted and fed children, including patients younger than 6 years of age. Methods Previously published data from one PK study and one PK/PD study in children aged between 6 and 16 years were combined with a new PK/PD study in children aged between 6 months and 8 years, and analysed using population PK/PD modelling. Simulations were performed to further explore the relative bioavailability of both formulations and evaluate current dosing strategies. Results The complex absorption behaviour of the lyophilizate was modelled using a double input, linked to a one-compartmental model with linear elimination and an indirect response model linking dDAVP concentration to produced urine volume and osmolality. The final model described the observed data well and elucidated the complexity of bioequivalence and therapeutic equivalence of the two formulations. Simulations showed that current dosing regimens using a fixed dose of lyophilizate 120 mu g is not adequate for children, assuming children to be in the fed state when taking dDAVP. A new age- and weight-based dosing regimen was suggested and was shown to lead to improved, better tailored effects. Conclusions Bioequivalence and therapeutic equivalence data of two formulations of the same drug in adults cannot be readily extrapolated to children. This study shows the importance of well-designed paediatric clinical trials and how they can be analysed using mixed-effects modelling to make clinically relevant inferences. A follow-up clinical trial testing the proposed dDAVP dosing regimen should be performed.

关键词： CHD   preoperative ventilation   paediatric cardiac surgery   respiratory support   noninvasive ventilation   postoperative length of stay  

摘要： Background: Preoperative mechanical ventilation is associated with morbidity and mortality following CHD surgery, but prior studies lack a comprehensive analysis of how preoperative respiratory support mode and timing affects outcomes. Methods: We retrospectively collected data on children <18 years of age undergoing cardiac surgery at an academic tertiary care medical centre. Using multivariable regression, we examined the association between modes of preoperative respiratory support (nasal cannula, high-flow nasal cannula/noninvasive ventilation, or invasive mechanical ventilation), escalation of preoperative respiratory support, and invasive mechanical ventilation on the day of surgery for three outcomes: operative mortality, postoperative length of stay, and postoperative complications. We repeated our analysis in a subcohort of neonates. Results: A total of 701 children underwent 800 surgical procedures, and 40% received preoperative respiratory support. Among neonates, 243 patients underwent 253 surgical procedures, and 79% received preoperative respiratory support. In multivariable analysis, all modes of preoperative respiratory support, escalation in preoperative respiratory support, and invasive mechanical ventilation on the day of surgery were associated with increased odds of prolonged length of stay in children and neonates. Children (odds ratio = 3.69, 95% CI 1.2-11.4) and neonates (odds ratio = 8.97, 95% CI 1.31-61.14) on high-flow nasal cannula/noninvasive ventilation had increased odds of operative mortality compared to those on room air. Conclusion: Preoperative respiratory support is associated with prolonged length of stay and mortality following CHD surgery. Knowing how preoperative respiratory support affects outcomes may help guide surgical timing, inform prognostic conversations, and improve risk stratification models.

关键词： children and adolescents   coeliac disease   diagnostic tests   meta-analysis  

摘要： Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented. Methods: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, human leukocyte antigen genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. Results: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG-based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA-IgA is >= 10 times the upper limit of normal (10x ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. Human leukocyte antigen DQ2-/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA-IgA <10x ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA-IgA and histopathology may require re-evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA-IgA/EMA-IgA+) should be followed closely. Conclusions: CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.

关键词： asthma   paediatric asthma   asthma management guidelines   paediatrics  

摘要： Background and objective We conducted a comprehensive assessment of guideline adherence in paediatric asthma care, including inpatient and ambulatory services, in Australia. Methods National and international clinical practice guidelines (CPG) relating to asthma in children were searched and 39 medical record audit indicator questions were developed. Retrospective medical record review was conducted across hospital inpatient admissions, emergency department (ED) presentations, general practice (GP) and paediatrician consultations in three Australian states for children aged <= 15 years receiving care in 2012 and 2013. Eligibility of, and adherence to, indicators was assessed from medical records by nine experienced and purpose-trained paediatric nurses (surveyors). Results Surveyors conducted 18 453 asthma indicator assessments across 1600 visits for 881 children in 129 locations. Overall, the adherence for asthma care across the 39 indicators was 58.1%, with 54.4% adherence at GP (95% CI: 46.0-62.5), 77.7% by paediatricians (95% CI: 40.5-97.0), 79.9% in ED (95% CI: 70.6-87.3) and 85.1% for inpatient care (95% CI: 76.7-91.5). For 14 acute asthma indicators, overall adherence was 56.3% (95% CI: 47.6-64.7). Lowest adherences were for recording all four types of vital signs in children aged >2 years presenting with asthma attack (15.1%, 95% CI: 8.7-23.7), and reviewing patients' compliance, inhaler technique and triggers prior to commencing a new drug therapy (20.5%, 95% CI: 10.1-34.8). Conclusion The study demonstrated differences between existing care and CPG recommendations for paediatric asthma care in Australia. Evidence-based interventions to improve adherence to CPG may help to standardize quality of paediatric asthma care and reduce variation of care.