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摘要： Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes. Determination of the underlying aetiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This can make the diagnostic process time-consuming and difficult. In this overview, we present a diagnostic approach for PMDs, with emphasis on genetic causes. This approach can serve as a framework to lead the clinician through the diagnostic process in eight consecutive steps, including recognition of the different movement disorders, identification of a clinical syndrome, consideration of acquired causes, genetic testing including next-generation sequencing, post-sequencing phenotyping, and interpretation of test results. The aim of this approach is to increase the recognition and diagnostic yield in PMDs.

关键词： doses   paediatrics   physiologically based pharmacokinetics  

摘要： Aims To build and verify a physiologically based pharmacokinetic (PBPK) model for radiprodil in adults and link this to a pharmacodynamic (PD) receptor occupancy (RO) model derived fromin vitrodata. Adapt this model to the paediatric population and predict starting and escalating doses in infants based on RO. Use the model to guide individualized dosing in a clinical trial in 2- to 14-month-old children with infantile spasms. Methods A PBPK model for radiprodil was developed to investigate the systemic exposure of the drug after oral administration in fasted and fed adults;this was then linked to RO via a PD model. The model was then expanded to include developmental physiology and ontogeny to predict escalating doses in infants that would result in a specific RO of 20, 40 and 60% based on average unbound concentration following a twice daily (b.i.d.) dosing regimen. Dose progression in the clinical trial was based on observed concentration-time data against PBPK predictions. Results For paediatric predictions, the elimination of radiprodil, based on experimental evidence, had no ontogeny. Predicted b.i.d. doses ranged from 0.04 mg/kg for 20% RO, 0.1 mg/kg for 40% RO to 0.21 mg/kg for 60% RO. For all infants recruited in the study, observed concentration-time data following the 0.04 mg/kg and subsequent doses were within the PBPK model predicted 5(th)and 95(th)percentiles. Conclusion To our knowledge, this is the first time a PBPK model linked to RO has been used to guide dose selection and escalation in the live phase of a paediatric clinical trial.

关键词： blood‐   to‐   plasma ratio   carvedilol   enalapril   paediatrics   pharmacokinetic  

摘要： Evidence-based pharmacotherapy with carvedilol and enalapril in children suffering from heart failure is insufficient owing to limited pharmacokinetic data. Although a few data sets regarding enalapril, its metabolite enalaprilat and carvedilol in children have been published, pharmacokinetic data on carvedilol metabolites are missing. However, for both drug substances, their active metabolites contribute substantially to drug efficacy. As data can hardly be derived from adults owing to the unknown impacts of enzymatic maturation and ontogeny during childhood, customised assays are important to facilitate paediatric evidence-based pharmacotherapy. Considering ethical paediatric constraints, a low-volume liquid chromatography coupled to mass spectrometry (LC-MS/MS) assay was developed using whole blood or plasma for the quantification of enalapril, enalaprilat, carvedilol, O-desmethyl carvedilol, 4- and 5-hydroxyphenyl carvedilol as well as 3- and 8-hydroxy carvedilol. To facilitate broader applications in adults, the elderly and children, a wide calibration range-between 0.024/0.049 and 50.000 ng/ml-was achieved with good linearity (r >= 0.995 for all analytes). In compliance with international bioanalytical guidelines, accuracy, precision, sensitivity and internal standard normalised matrix effects were further successfully validated with the exception of those for 3-hydroxy carvedilol, which was therefore assessed semi-quantitatively. Distinct haematocrits did not impact matrix effects or recoveries when analysing whole blood. Blood-to-plasma ratios were determined for all analytes to form the basis for pharmacokinetic modelling. Finally, incurred sample reanalysis of paediatric samples confirmed the reproducibility of the developed low-volume LC-MS/MS method during study sample analysis. The assay facilitates the reliable generation of important data and contributes towards a safe drug therapy in children.

关键词： Paediatric intensive care   Critically ill children   Nutrition   Enteral feeding   COVID-19  

摘要： There are reports of children COVID-19 or COVID-19 like symptoms with hyperinflammatory multi system syndrome, ARDS, gastrointestinal and atypical Kawasaki disease presenting to PICU worldwide temporally associated with COVID-19, for which there are important nutrition support considerations. As a result, the European Society of Pediatric and Neonatal Intensive Care Metabolism, Endocrine and Nutrition group (ESPNIC-MEN) and paediatric nutritionists working in PICUs are being consulted regarding nutrition management of critically ill children with COVID-19 or COVID-19 like symptoms. Therefore, the aim of this short report is to provide a summary of nutrition support recommendations for critically ill children with COVID-19. They are based on the ESPNIC-MEN section recommendations published in January 2020 and surviving sepsis recommendations from February 2020. (c) 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://***/licenses/by/4.0/).

关键词： follow-up   paediatric intensive care   post-intensive care syndrome paediatrics   survey  

摘要： The objective of this study was to examine the characteristic, content, and role of Paediatric Intensive Care Units (PICUs) in the provision of follow-up for children and their families' post-intensive care discharge in the United Kingdom (UK) and Republic of Ireland (RoI). The study followed a descriptive self-reported, web-based survey design. "In-hospital PICU follow-up" was defined as follow-up delivered by the PICU team following PICU discharge but before hospital discharge and "post-discharge PICU follow-up" was defined as follow-up delivered by the PICU team following hospital discharge. The survey was administered to all 28 PICUs in the UK and RoI. Paediatric intensive care medical directors or delegated individuals participated. Data were collected between September 2017 and January 2018 with a response rate of 79% (n = 22/28). Twelve units provided either in-hospital and/or post-discharge PICU follow-up. Ten (45%) PICUs reported providing in-hospital follow-up, with half (n = 5) using an eligibility criteria for in-hospital follow-up, which related to disease groups. The most frequently reported form of in-hospital PICU follow-up consisted of face-to-face patient consultation (n = 8) by a PICU doctor (n = 5) and/or nurse (n = 4). The time at which initial contact was made was usually not predetermined (n = 4) and the assessment of care needs included are tracheostomy care (n = 4), respiratory care (n = 4), and sedative medication weaning plan (n = 5). Four PICUs reported to provide post-discharge follow-up. This involved telephone (n = 2), follow-up clinic consultations (n = 1) or home visits (n = 1), provided predominantly by PICU doctors (n = 2), with their activity directed by patient needs (n = 3). Despite increasing evidence to suggest PICU survivors and their families experience negative sequalae post-PICU discharge, less than half of PICUs surveyed provide in-hospital follow-up and only a minority provide post-discharge follow-up. There is variation

关键词： Liver transplantation   Portosystemic shunts   Portal hypertension   Pulmonary arterial hypertension   Medical treatment   Paediatrics  

摘要： Portopulmonary hypertension is a rare but serious complication of portal hypertension or portosystemic shunting. Portopulmonary hypertension is an indication for liver transplantation or shunt closure. However, liver transplantation is contraindicated in patients with severe pulmonary arterial hypertension. Reported mortality rates are high in children with portopulmonary hypertension and there are scarce recommendations on its management. Our aim was to report on our real-world experience of managing portopulmonary hypertension in a specialised centre. We describe a series of 6 children with portopulmonary hypertension. Their median age at diagnosis was 13 years (range 10-15). The underlying liver conditions were cirrhosis of unknown origin (1), congenital portocaval shunts (3), biliary atresia (1), and portal vein cavernoma with surgical mesenterico-caval shunt (1). Median mean pulmonary arterial pressure was 47 mmHg (range 32-70), and median pulmonary vascular resistance was 6.6 Wood units (range 4.3-15.4). All patients except one were treated with a combination of pulmonary arterial hypertension-specific therapy (phosphodiesterase type 5 inhibitors and/or endothelin receptor antagonists and/or prostacyclin analogues). Three patients then benefited from shunt closure and the others underwent liver transplantation. Five patients showed improvement or stabilisation of pulmonary arterial hypertension with no deaths after a mean follow-up of 39 months. Based on our limited experience, early and aggressive treatment with a combination of pulmonary arterial hypertension-specific therapy significantly improves patients' haemodynamic profile and enables the performance of liver transplantation and shunt closure with satisfactory outcomes. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.

关键词： Health-related quality of life   paediatric quality of life family impact module   paediatric heart transplantation   family functioning  

摘要： In a cross-sectional study, we assessed family functioning prior to outpatient visits and routine heart catheterisations in the families of paediatric heart transplant recipients. Caregivers rated higher short-term family functioning prior to outpatient visits, but not prior to catheterisations. This finding may indicate that family functioning benefits from the support provided during outpatient visits.

关键词： afibrinogenaemia   fibrinogen   haemorrhage   haemostatics   paediatrics  

摘要： Background Congenital fibrinogen deficiency (CFD) is a rare, inherited disorder affecting normal blood clotting function, where patients can experience severe and/or frequent bleeding episodes (BEs). Treatment with human fibrinogen concentrate (HFC) can prevent/arrest bleeding. There is a need for more data on the efficacy, pharmacokinetics (PK) and safety of HFC treatment in paediatric patients with CFD. Methods Haemostatic efficacy of HFC (Fibryga(R), Octapharma AG) for on-demand treatment of bleeding and surgical prophylaxis in patients <12 years old was assessed by investigators and an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) based on an objective 4-point efficacy scale. Maximum clot firmness (MCF;surrogate marker of haemostatic efficacy), single-dose PK and safety were also assessed. Results Of 14 patients receiving HFC (median [range] age 6.0 years [1.0-10.0]), eight received HFC for 10 BEs, three for surgical prophylaxis and 13 for PK. The IDMEAC rated haemostatic efficacy as 100% successful for on-demand BE treatment (95% CI 69.15-100.00) and surgical prophylaxis (95% CI 29.24-100.00). After a mean first dose of 70.78 mg/kg for BEs, mean (+/- SD) MCF significantly increased from pre-treatment to 1-hour post-infusion (3.3 mm [+/- 1.77];P = 0.0002), coinciding with haemostatic efficacy. PK parameters were favourable. Two possibly related adverse events occurred, including one serious (portal vein thrombosis). No allergic/hypersensitivity reactions or deaths were observed. Conclusion HFC treatment for on-demand treatment of BEs and surgical prophylaxis was efficacious for this ultra-rare paediatric population with congenital afibrinogenaemia and showed a favourable PK and safety profile.

摘要： We read the article by Tester et al, which assessed the impact of supraventricular tachycardias (SVTs) on socio-emotional, behavioural and executive function in paediatric patients, with great interest.1 The paper focused on an underrepresented area within the literature, highlighting the increased risk to children and adolescents with SVTs of developing adverse psychological outcomes. Additionally, with patients having had to answer fewer questionnaires than their parents/guardians, it is questionable whether the patient voice was adequately represented in this article. [Extracted from the article]

关键词： Abdominal tumours   bowel gas   children   neuroblastoma   patient selection   proton therapy  

摘要： Aims: Pencil beam scanning (PBS) proton therapy is an increasingly used radiation modality for childhood malignancies due to its ability to minimise dose to surrounding organs. However, the dosimetry is extremely sensitive to anatomical and density changes. The aims of this study were to investigate if there is a dosimetric benefit or detriment with PBS for paediatric abdominal neuroblastoma, assess gastrointestinal air variability and its dosimetric consequences, plus identify if there are factors that could assist case selection for PBS referral. Materials and methods: Twenty neuroblastoma cases were double-planned with PBS and intensity-modulated arc therapy (IMAT). Cases were divided into unilateral, midline unilateral and midline bilateral locations in relation to the kidneys. Plans were recalculated after the gastrointestinal volume was simulated as air (Hounsfield Units -700) and water (Hounsfield Units 0), then compared with nominal plans (recalculated - nominal, Delta D). Forty-three weekly cone beam computed tomography scans were analysed to quantify gastrointestinal air variability during treatment. Results: PBS reduced the mean dose to normal tissues at all tumour locations, particularly unilateral tumours. However, 15% had better dosimetry with IMAT, all of which were midline tumours. Increased gastrointestinal air caused significant compromises to PBS versus IMAT plans for midline tumours [median/maximum Delta D95% clinical target volume (CTV) -2.4%/-15.7% PBS versus 1.4%/0% IMAT, P = 0.003], whereas minimal impact was observed for unilateral tumours (Delta D95% CTV -0.5%/-1.9% PBS versus 0.5%/-0.5% IMAT, P = 0.008). D95% CTV was significantly decreased in PBS plans if planning target volume (PTV) >= 400 cm(3) (median -4.1%, P = 0.001) or PTV extension >= 60% anterior to vertebral body (-2.1%, P = 0.002). A larger variation in gastrointestinal air was observed in patients treated under general anaesthesia (median 38.4%) versus awake (11.5%);P = 0.004.