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关键词： SCID surveillance newborn screening paediatric incidence  

摘要： Purpose Severe combined immunodeficiencies (SCID) are a heterogeneous group of fatal genetic disorders, in which the immune response is severely impaired. SCID can be cured if diagnosed early. We aim to determine the incidence of clinically defined SCID cases, acquire data of reported cases and evaluate their possible prediction by newborn screening, before introduction of a general screening program in Germany. Methods The German Surveillance Unit for rare Paediatric Diseases (ESPED) prospectively queried the number of incident SCID cases in all German paediatric hospitals in 2014 and 2015. Inclusion criteria were (1) opportunistic or severe infections or clinical features associated with SCID (failure to thrive, lacking thymus or lymphatic tissue, dysregulation of the immune system, graft versus host reaction caused by maternal T cells), (2) dysfunctional T cell immunity or proof of maternal T cells and (3) exclusion of a secondary immunodeficiency such as human immunodeficiency virus (HIV) infection. In a capture-recapture analysis, cases were matched with cases reported to the European Society for Immunodeficiencies (ESID). Results Fifty-eight patients were initially reported to ESPED, 24 reports could be confirmed as SCID, 21 patients were less than 1 year old at time of diagnosis. One SCID case was reported to ESID only. The estimated incidence of SCID in Germany is 1.6/100,000 (1:62,500) per year in children less than 1 year of age. Most patients reported were symptomatic and mortality in regard to reported outcome was high (29% (6/22)). The majority of incident SCID cases were considered to be probably detectable by newborn screening. Conclusions SCID is a rare disease with significant mortality. Newborn screening may give the opportunity to improve the prognosis in a significant number of children with SCID.

关键词： Therapeutic plasma exchange (TPE)   Paediatric neuro-immunological disorders (PNID)  

摘要： Background: There is limited data available on the safety of therapeutic plasma exchange (TPE) for paediatric neuro-immunological disorders (PNID). In this study, we report our data on safety and feasibility of TPE for these disorders. Methods: Retrospective chart review was performed to include all patient who received TPE for four major PNID conditions: autoimmune encephalitis (AIE), acute disseminated encephalomyelitis (ADEM), Neuromyelitis optic spectrum disorder (NMOSD) and transverse myelitis (TM). We recorded minor and major adverse effects (AEs) associated with each TPE procedure. Secondary analysis also looked at the efficacy data of TPE on these patients. Results: Thirty-two patients with PNID received a total of 186 TPE cycles. Out of these, only 1 cycle (0.89%) in AIE subgroup, 1 (4.3%) in NMOSD and 1 (4.5%) in TM had adverse effects. No patients had major side effects. Conclusion: TPE was safe and well tolerated in our PNID patients. (C) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

关键词： drug manipulation   food   drinks   solubility   physicochemical properties   multivariate analysis   paediatrics  

摘要： Food and drinks are commonly used to facilitate administration of paediatric medicines to improve palatability and enhance patient compliance. However, the impact of this practice on drug solubility and on oral drug bioavailability is not usually studied. Based on recommended strategies for oral administration of paediatric medicines with food and drink vehicles, the aims of this study were (i) to measure the physicochemical properties of (soft) food and drink vehicles, commonly mixed with paediatric medicines prior to administration, and (ii) to assess the impact of the co-administered vehicles on the solubility of two poorly soluble paediatric drugs. Montelukast (sodium) and mesalazine were selected as the model compounds. Distinct differences were observed between the physicochemical properties (***, surface tension, osmolality, viscosity and buffer capacity) and macronutrient composition (***, sugar and protein content) of the different soft foods and drinks, not only among vehicle type but also within vehicles of the same subtype. Solubility studies of the two model compounds in selected drinks and soft foods resulted in considerably different drug solubility values in each vehicle. The solubility of the drugs was significantly affected by the vehicle physicochemical properties and macronutrient composition, with the solubility of montelukast being driven by the pH, fat and protein content of the vehicles and the solubility of mesalazine by vehicle osmolality, viscosity and sugar content. This vehicle-dependent impact on drug solubility could compromise its bioavailability, and ultimately affect the safety and/or efficacy of the drug and should be taken into consideration during paediatric product development.

关键词： Malawi   Emergency care   Paediatrics   Health systems  

摘要： Background Emergency care is among the weakest parts of health systems in low-income countries with both quality and accessibility constraints. Previous studies estimated accessibility to surgical or emergency care based on population travel times to nearest hospital with no assessment of hospital readiness to provide such care. We analysed a Malawi national facility census with comprehensive inventory audits and geocoded facility locations to identify hospitals equipped to provide basic paediatric emergency care with estimated travel times to these hospitals from non-equipped facilities and in relation to Malawi's population distribution. Methods We analysed a Malawi national facility census in 2013-2014 to identify hospitals equipped to manage critically ill children according to an extended version of WHO Emergency Triage, Assessment and Treatment (ETAT) guidelines. These guidelines include 25 components including staff, transport, equipment, diagnostics, medications, fluids, feeds and consumables that defined an emergency-equipped hospital in our study. We estimated travel times to emergency-equipped hospitals from non-equipped facilities and relative to population distributions using geocoded facility locations and an established accessibility mapping approach using global road network datasets from OpenStreetMap and Google. Results Four (3.5, 95% CI: 1.3-8.9) of 116 Malawi hospitals were emergency-equipped. Least available items were nasogastric tubes in 34.5% of hospitals (95% CI: 26.4-43.6), blood typing services (40.4, 95% CI: 31.9-49.6), micro nebulizers (50.9, 95% CI: 41.9-60.0), and radiology (54.2, 95% CI: 45.1-63.0). Nationally, the median travel time from non-equipped facilities to the nearest emergency-equipped hospital was 73 min (95% CI: 67-77) ranging 1-507 min. Approximately one-quarter (27%) of Malawians lived over 120 min from an emergency-equipped hospital with significantly better accessibility in Central than North and South regions (16% vs.

关键词： Paediatric intensive care   Paediatric transport   Critical care transport  

摘要： Background Reaching the bedside of a critically ill child within three hours of agreeing the child requires intensive care is a key target for Paediatric Critical Care Transport teams (PCCTs) to achieve in the United Kingdom. Whilst timely access to specialist care is necessary for these children, it is unknown to what extent time taken for the PCCT to arrive at the bedside affects clinical outcome. Methods Data from transports of critically ill children who were admitted to Paediatric Intensive Care Units (PICUs) in England and Wales from 1 January 2014 to 31 December 2016 were extracted from the Paediatric Intensive Care Audit Network (PICANet) and linked with adult critical care data and Office for National Statistics mortality data. Logistic regression models, adjusted for pre-specified confounders, were fitted to investigate the impact of time-to-bedside on mortality within 30 days of admission and other key time points. Negative binomial models were used to investigate the impact of time-to-bedside on PICU length of stay and duration of invasive ventilation. Results There were 9116 children transported during the study period, and 645 (7.1%) died within 30 days of PICU admission. There was no evidence that 30-day mortality changed as time-to-bedside increased. A similar relationship was seen for mortality at other pre-selected time points. In children who waited longer for a team to arrive, there was limited evidence of a small increase in PICU length of stay (expected number of days increased from: 7.17 to 7.58). Conclusion There is no evidence that reducing the time-to-bedside target for PCCTs will improve the survival of critically ill children. A shorter time to bedside may be associated with a small reduction in PICU length of stay.

关键词： Acute appendicitis   Magnetic resonance imaging   Ultrasound   Paediatric  

摘要： Objectives To assess the diagnostic accuracy of fast acquisition MRI in suspected cases of paediatric appendicitis presenting to a tertiary referral hospital. Materials and methods A prospective study was undertaken between May and October 2017 of 52 children who presented with suspected appendicitis and were referred for an abdominal ultrasound. All patients included in this study received both an abdominal ultrasound and five-sequence MRI consisting of axial and coronal gradient echo T2 scans, fat-saturated SSFSE and a diffusion-weighted scan. Participants were randomised into groups of MRI with breath-holds or MRI with free breathing. A patient satisfaction survey was also carried out. Histopathology findings, where available, were used as a gold standard for the purposes of data analysis. Statistical analysis was performed, andpvalues < 0.05 were considered statistically significant. Results Ultrasound had a sensitivity and specificity of 25% and 92.9%, respectively. MRI with breath-hold had a sensitivity and specificity of 81.8% and 66.7%, respectively, whilst MRI with free breathing was superior with sensitivity and specificity of 92.3% and 84.2%, respectively. MRI with free breathing was also more time efficient (p< 0.0001). Group statistics were comparable (p< 0.05). Conclusions The use of fast acquisition MRI protocols, particularly free breathing sequences, for patients admitted with suspected appendicitis can result in faster diagnosis, treatment and discharge. It also has a statistically significant diagnostic advantage over ultrasound. Additionally, the higher specificity of MR can reduce the number of negative appendectomies performed in tertiary centres.

摘要： The increasing number of COVID-19 intensive care unit (ICU) admissions in our hospital necessitated increasing the number of physical ICU beds and staffing. PICU physicians and nurses advocated to remain in their environment and use the well-established working relationships within the PICU bedside team when caring for the adult COVID-19 patients because the general principles of intensive care medicine would not be different between children and adults [3]. To increase availability of PICU nurses, we upgraded their employment contract to 1 full-time equivalence, and all granted leaves of absence were revoked until further notice after consulting Human Resources and approval of the Board of Directors.

关键词： Acute lymphocytic leukaemia   Gene expression   High-throughput screening   Oncogenes   Paediatric cancer  

摘要： Background Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Glucocorticoids form a critical component of chemotherapy regimens and resistance to glucocorticoid therapy is predictive of poor outcome. We have previously shown that glucocorticoid resistance is associated with upregulation of the oncogene C-MYC and failure to induce the proapoptotic gene BIM. Methods A high-throughput screening (HTS) campaign was carried out to identify glucocorticoid sensitisers against an ALL xenograft derived from a glucocorticoid-resistant paediatric patient. Gene expression analysis was carried out using Illumina microarrays. Efficacy, messenger RNA and protein analysis were carried out by Resazurin assay, reverse transcription-PCR and immunoblotting, respectively. Results A novel glucocorticoid sensitiser, 2-((4,5-dihydro-1H-imidazol-2-yl)thio)-N-isopropyl-N-phenylacetamide (GCS-3), was identified from the HTS campaign. The sensitising effect was specific to glucocorticoids and synergy was observed in a range of dexamethasone-resistant and dexamethasone-sensitive xenografts representative of B-ALL, T-ALL and Philadelphia chromosome-positive ALL. GCS-3 in combination with dexamethasone downregulated C-MYC and significantly upregulated BIM expression in a glucocorticoid-resistant ALL xenograft. The GCS-3/dexamethasone combination significantly increased binding of the glucocorticoid receptor to a novel BIM enhancer, which is associated with glucocorticoid sensitivity. Conclusions This study describes the potential of the novel glucocorticoid sensitiser, GCS-3, as a biological tool to interrogate glucocorticoid action and resistance.

关键词： Awareness   stigma   Disclosure   Caregiver   Nuclear family   Discrimination  

摘要： BackgroundPoor compliance to highly active antiretroviral therapy (HAART) can result in the poor quality of life in children living with Human immunodeficiency virus/Acquired immunodeficiency syndrome (HIV/AIDS) because of low plasma drug concentration and the possibility of drug resistance. This study evaluates the response of caregivers for determination of adherence and the four quality of life domains in children (aged 14years and under) on *** conducted a cross-sectional study of 188 children, each accompanied by their caregivers at Ola During Children's Hospital and Makeni Government Hospital between September and November 2016. Adherence to HAART and Quality of life was assessed using the WHO Quality of life summary questionnaire (WHOQOL-BREF). We obtained ethical approval from the Sierra Leone Ethics and Scientific Review *** study revealed 5.9% adherence amongst paediatric patients, and a strong association of adherent patients(p=0.019*) to the physical health domain (mean=64.61 SD=8.1). Caregiver HIV status showed a strong association with the physical (mean=58.3, SD=11.7 and p=0.024*), and psychological health domains (mean=68.2, SD=14.7 and p=0.001). Caregiver type (mother/father/sibling) accompanying child to hospital also showed strong associated with the physical (mean=58.0, SD=10.6, p< 0.001), psychological (mean 68.2 SD=14.81 p< 0.001) and environmental health domains (mean=59.7, SD=13.47, p< 0.001). Further regression analysis showed a strong association with physical health domain for HIV positive caregivers (p=0.014) and adherent paediatric patients (p=0.005). Nuclear family also showed a strong association with psychological (p< 0.001) and environmental (p=0.001) health *** study showed a strong association between the quality of life domains and the involvement of nuclear family caregiver, HIV-positive caregiver and adherence to HAART. Our study suggests that the involvement of any member of the n

摘要： An amendment to this paper has been published and can be accessed via the original article.