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关键词： Antibiotic resistance   Antimicrobial stewardship   Urinary tract infections  

摘要： Background: The incidence of antibiotic-resistant urinary tract infections (UTIs) in children is increasing. The purpose of this study was to describe the incidence, clinical characteristics, and risk factors for third-generation cephalosporin-resistant UTIs presenting to the paediatric emergency department (ED). Methods: This was a retrospective cohort study conducted at British Columbia Children's Hospital. Children aged 0 to 18 years old presenting to the ED between July 1, 2013 and June 30, 2014 and were found to have UTI due to Enterobacteriaceae and Pseudomonas species were included. Patient demographics, clinical features, laboratory findings, and outcomes were compared using standard statistical analyses. Risk factors for resistant UTIs were analyzed using multiple logistic regression analysis. Results: There were 294 eligible patients. The median age was 27.4 months. A third-generation cephalosporin-resistant organism was identified in 36 patients (12%). Patients with resistant UTI had lower rates of appropriate empiric antibiotic therapy (25% versus 95.3%, P<0.05), higher rates of hospitalization (38.9% versus 21.3%, P<0.05), higher rates of undergoing a voiding cystourethrogram (19.4% versus 5.0%, P<0.05), and higher rates of UTI recurrence within 30 days (13.9% versus 4.7%, P<0.05). In multivariate analysis, recent hospitalization (odds ratio [OR] 4.3, confidence interval [CI] 1.2 to 16) and antibiotic therapy (OR 3.5, CI 1.5 to 8.5) within the previous 30 days were risk factors for resistant UTI. Conclusions: Third-generation cephalosporin-resistant organisms account for a significant proportion of community-acquired paediatric UTIs. Recent hospitalization and antibiotic use are associated with increased risk of resistant UTI.

关键词： Candida krusei   Candidemia   Outbreak   Paediatrics   Molecular typing  

摘要： Background A sudden rise of Candida krusei candidemia cases was noticed in our hospital within 1 year with maximum cases from paediatric unit. The present study reports the results of epidemiological investigation of possible outbreak of candidemia by C. krusei in paediatric unit at our tertiary care centre. Methods Clinical characteristics and risk factors associated with C. krusei candidemia were evaluated. Yeast identification and antifungal susceptibility testing was performed according to standard protocol. To find the potential source of C. krusei in hospital environment and hand colonization, swabs were collected from different fomites (n = 40) and hand washings from 24 health care workers (HCW), respectively. Infection control and prevention practices were intensified following the recognition of outbreak. Genetic typing was done by fluorescent amplified fragment length polymorphism (FAFLP) technique. Case-control comparison was performed with C. tropicalis and C. pelliculosa cases. Results Candida krusei fungaemia significantly affected paediatric group (82/186, 44%) as compared to adults (14/130, 10.8%;p < 0.001). Among paediatric group, maximum isolation was reported from neonatal unit of paediatric emergency (NUPE). C. krusei was isolated from hands of one HCW and washbasin in NUPE. FAFLP revealed clonality between blood and environmental isolates indicating cross-transmission of C. krusei. Gastrointestinal disease (p = 0.018), previous antibiotics (p = 0.021) especially to carbapenems (p = 0.039), was significant among C. krusei candidemia cases compared to C. pelliculosa cases. Conclusion We report the largest outbreak of C. krusei candidemia in paediatric unit within 1 year with isolation of related strains from environment and hands of HCW. Routine screening of hand hygiene practices revealed non-compliance to standard practices leading to the increase in C. krusei candidemia cases.

关键词： Crohn's disease   remission   children   paediatric   nutrition   diet  

摘要： Background Exclusive enteral nutrition (EEN) is known to be a safe and effective treatment option for managing active Crohn's disease (CD) in children, although no uniform protocol exists. The aim of this systematic review was to evaluate and compare the clinical effectiveness of aspects of EEN protocols to ascertain whether an optimum regimen can be identified. Methods A systematic search of the Cochrane Library, PubMed, MEDLINE, EMBASE, CINAHL and AMED was conducted for studies published between 1998 and 2018 that examined paediatric patients being treated with an enteral nutrition protocol to induce remission. Studies that included patients receiving concurrent medication for active disease were excluded. Quality assessment was performed using separate tools for randomised controlled trials, cohort studies and for studies without a control group. Results Sixteen studies met the inclusion criteria. Of these, six found insufficient evidence to support use of a specific formula. One study examined the route of EEN, finding no difference between oral or nasogastric tube administration with respect to inducing remission. Three examined the use of partial enteral nutrition to induce remission, although conflicting results were seen. No studies explored the effect of length of treatment or energy prescription on remission rates Conclusions An optimum enteral nutrition protocol for inducing remission cannot be identified. Further focused research is required by well designed, adequately powered prospective clinical trials to examine aspects of enteral feeding protocols that remain uncertain, including the use of partial enteral nutrition as a potential alternative to EEN.

关键词： drug development   model   paediatric   simulation  

摘要： Aims Methoxy polyethylene glycol-epoetin beta (continuous erythropoietin receptor activator, C.E.R.A.) is used for the treatment of anaemia in adults with chronic kidney disease (CKD). Patients treated with shorter-acting erythropoiesis-stimulating agents up to three times weekly can be switched to once-monthly C.E.R.A.. Doses can be adjusted on a monthly basis based on haemoglobin (Hb) levels during the preceding period. A model-based approach was applied to optimise C.E.R.A. development, more specifically the confirmatory trial of the paediatric plan. Methods Pharmacokinetic and pharmacodynamic data from a phase II paediatric study and phase II and III adult studies were analysed together using modelling and simulation to determine the pharmacokinetic/pharmacodynamic characteristics of C.E.R.A. in a broad population. Model-based simulations of C.E.R.A. treatment outcomes in paediatric patients were performed, notably when administered subcutaneously and compared to clinical and real-world data. Results Age and body weight explained differences in pharmacokinetics, while the pharmacodynamic characteristics of C.E.R.A. were similar between adult and paediatric populations. Simulated Hb levels (mean and 95% prediction interval 10.9 [10.6, 11.2] g dL(-1)) and C.E.R.A. doses (median and 95% prediction interval 105 [72, 159] mu g) 20 weeks after switching to subcutaneous C.E.R.A. were confirmed by observed real-world data from International Pediatric Dialysis Network registries (mean Hb was 10.8 g dL(-1) and median C.E.R.A. dose was 100 mu g). Conclusions These analyses have facilitated optimisation of the C.E.R.A. development programme in paediatric patients with anaemia of CKD to provide this patient population with faster access to the drug while avoiding unnecessary clinical trial exposure and related monitoring burden in children.

关键词： Simulation-based medical education   Surgical simulation   Technical skills training   Surgical training  

摘要： In recent years, there has been an increasing interest in employing simulation methodology for teaching surgical skills. Supposedly, skills achieved in the simulation arena, should lead to an improvement of surgical performance in the operating room. In this article we aim to summarise those areas of simulation-based research that relate to paediatric surgery;we present the current evidence behind low-fidelity simulation and computer-based simulation in improving the acquisition of surgical skills. (C) 2020 Published by Elsevier Inc.

关键词： Crohn's disease   Inflammatory bowel disease   Nutrition   Sarcopenia  

摘要： Background & aims: An inability to respond to nutrition could be implicated in low muscle mass in Crohn's disease. We aim to determine skeletal muscle metabolic response to feeding in Crohn's disease and healthy volunteers. Methods: Twenty asymptomatic Crohn's disease participants (15.6 +/- 0.5 yrs;BMI 20.6 +/- 0.9 kg/m(2));9 with active disease (faecal calprotectin, 808 +/- 225 ug/g and C-reactive protein, 2.2 +/- 1.2 mg/dl), 11 in deep remission (faecal calprotectin, 61 +/- 12 ug/g and C-reactive protein, 0.3 +/- 0.2 mg/dl) and 9 matched healthy volunteers (16.0 +/- 0.6 yrs;BMI 20.7 +/- 0.6 kg/m(2)) were recruited. Participants had a dual energy X-ray absorptiometry scan, handgrip dynamometer test, wore a pedometer and completed a food diary. Arterialised hand and venous forearm blood samples were collected concurrently and brachial artery blood flow measured at baseline and every 20 min for 2 hrs after the ingestion of a standardised liquid meal. Net balance of branched chain amino acids (BCAA) and glucose were derived. Results: Controls had a positive mean BCAA balance. CD participants had an initial anabolic response to the meal, with increasing BCAA balance between t = 0 & t = 20, but returned to negative by t = 60. This was associated with reduced FFM z-scores in CD but not with insulin resistance or disease activity. Exploratory analyses suggest that negative postprandial BCAA response seen in CD is predominant in males (p = 0.049), with associated lower appendicular muscle mass (p = 0.034), higher muscle fatigue (p = 0.014) and reduced protein intake (p = 0.026). Conclusions: The inability to sustain a positive protein balance postprandially could provide an explanation for the reduced muscle mass seen in CD. Further mechanistic studies will be needed to confirm these findings. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

关键词： adolescent   chronic fatigue syndrome   feedback   management strategies   myalgic encephalomyelitis  

摘要： Aim The aim of this study was to document qualitative questionnaire feedback regarding management from a cohort observational study of young people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Methods Between 1991 and 2009, 784 paediatric patients, age 6-18 years, were diagnosed with ME/CFS following referral to a specialised clinic at the Royal Children's Hospital, Melbourne. Over a 14-year period, feedback was requested on up to seven occasions. Management included the following: symptom management and a self-management lifestyle plan that included social, educational, physical and a pleasurable activity outside of home. They adjusted it by severity of illness, stage of education, family circumstances and life interests. Results Questionnaires were returned from 626 (80%) with 44% providing feedback more than once. They reported that their management plan allowed them to regain control over their lives. They cited early diagnosis, empathetic, informed physicians, self-management strategies and educational liaison as helping them to function and remain socially engaged. Ongoing support, particularly assistance to navigate the education system, was essential for general well-being and ability to cope. Conclusion Young people valued regaining the control over their lives that was lost through illness, support to maintain social contacts and assistance to achieve educational and/or life goals.

关键词： ponatinib   paediatrics   chronic myeloid leukaemia   acute lymphoblastic leukaemia   Philadelphia chromosome  

摘要： Ponatinib has proven to be effective in adults with Philadelphia chromosome-positive leukaemias, but data in paediatrics are scarce. Among paediatric patients with chronic myeloid leukaemia (n = 9) or acute lymphoblastic leukaemia (n = 12) treated with varying doses of ponatinib in 13 centres, 71% showed a decrease in disease burden after a median of three months. Ponatinib was well tolerated, with grade 3 toxicities occurring in 29% of patients. Toxicities were similar to those reported in adults, with the exception of arterial thrombotic events, which were not observed. Ponatinib has a favourable safety profile in this paediatric cohort, but dose-finding studies are needed.

摘要： A correction to the article 'European Consensus-Based Recommendations for the Diagnosis and Treatment of Rare Paediatric Vasculitides--the SHARE Initiative,' by Nienke de Graeff and colleagues, published in a previous issue is presented.

关键词： breast milk   breastfeeding   feeding frequency   pharmacokinetics   preterm infants   risk assessment   volume of intake  

摘要： Despite the many benefits of breast milk, mothers taking medication are often uncertain about the risks of drug exposure to their infants and decide not to breastfeed. Physiologically based pharmacokinetic models can contribute to drug-in-milk safety assessments by predicting the infant exposure and subsequently, risk for toxic effects that would result from continuous breastfeeding. This review aimed to quantify breast milk intake feeding parameters in term and preterm infants using literature data for input into paediatric physiologically based pharmacokinetic models designed for drug-in-milk risk assessment. Ovid MEDLINE and Embase were searched up to July 2, 2019. Key study reference lists and grey literature were reviewed. Title, abstract and full text were screened in nonduplicate. Daily weight-normalized human milk intake (WHMI) and feeding frequency by age were extracted. The review process retrieved 52 studies. A nonlinear regression equation was constructed to describe the WHMI of exclusively breastfed term infants from birth to 1 year of age. In all cases, preterm infants fed with similar feeding parameters to term infants on a weight-normalized basis. Maximum WHMI was 152.6 ml/kg/day at 19.7 days, and weighted mean feeding frequency was 7.7 feeds/day. Existing methods for approximating breast milk intake were refined by using a comprehensive set of literature data to describe WHMI and feeding frequency. Milk feeding parameters were quantified for preterm infants, a vulnerable population at risk for high drug exposure and toxic effects. A high-risk period of exposure at 2-4 weeks of age was identified and can inform future drug-in-milk risk assessments.