EphA2 regulates vascular permeability and prostate cancer metastasis via modulation of cell junction protein phosphorylation.

Prostate cancer morbidity and mortality demonstrate a need for more effective targeted therapies. One potential target is EphA2, although paradoxically, pro- and anti-oncogenic effects have been shown to be mediated by EphA2. We demonstrate that unique activating and blocking EphA2-targeting monoclonal antibodies display opposing tumor-suppressive and oncogenic properties in vivo.

Can capillary microsampling facilitate a clinical pharmacokinetics study of cefazolin in critically ill children?

Pharmacokinetic studies in children are limited, in part due to challenges in blood sampling. We compare the use of capillary microsampling and conventional sampling techniques in pediatric patients to show results that can be used in the pharmacokinetic analysis of Cefazolin. Paired blood samples (n = 48) were collected from 12 patients (median age/weight 49 months/18 kg).

Inhibiting Eph/ephrin signaling reduces vascular leak and endothelial cell dysfunction in mice with sepsis.

Sepsis is a life-threatening disease caused by a dysregulated host response to infection, resulting in 11 million deaths globally each year. Vascular endothelial cell dysfunction results in the loss of endothelial barrier integrity, which contributes to sepsis-induced multiple organ failure and mortality. Erythropoietin-producing hepatocellular carcinoma (Eph) receptors and their ephrin ligands play a key role in vascular endothelial barrier disruption but are currently not a therapeutic target in sepsis.

The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

Objectives: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH).

Design: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence.

Managing severe hypertension in children.

Severe childhood hypertension is uncommon and frequently not recognised and is best defined as a systolic blood pressure (SBP) above the stage 2 threshold of the 95th centile + 12 mmHg. If no signs of end-organ damage are present, this is urgent hypertension which can be managed by the slow introduction of oral or sublingual medication, but if signs are present, the child has emergency hypertension (or hypertensive encephalopathy if they include irritability, visual impairment, fits, coma, or facial palsy), and treatment must be started promptly to prevent progression to permanent neurological damage or death. However, detailed evidence from case series shows that the SBP must be lowered in a controlled manner over about 2 days by infusing short-acting intravenous hypotensive agents, with saline boluses ready in case of overshoot, unless the child had documented normotension within the last day.

Optimal dosing of cefotaxime and desacetylcefotaxime for critically ill paediatric patients. Can we use microsampling?

Objectives: To describe the population pharmacokinetics of cefotaxime and desacetylcefotaxime in critically ill paediatric patients and provide dosing recommendations. We also sought to evaluate the use of capillary microsampling to facilitate data-rich blood sampling.

Methods: Patients were recruited into a pharmacokinetic study, with cefotaxime and desacetylcefotaxime concentrations from plasma samples collected at 0, 0.

In vitro measurements of ultrafiltration precision in hemofiltration and hemodialysis devices used in infants.

Background: To determine in vitro whether infant hemofiltration and hemodialysis devices can reliably deliver precise ultrafiltration (UF) control.

Methods: We tested the Prismaflex, Aquarius and NIDUS devices which have different circuit types, by in vitro testing with a bag of saline set up as a dummy patient, and monitoring fluid shifts by precise weighing. We looked for differences between the UF rates set and achieved and between the UF result the device displays to the clinician and the true volumes removed, which may lead to clinical errors.

Queensland Telepaediatric Service: A Review of the First 15 Years of Service.

In November 2000, the Queensland Telepaediatric Service (QTS) was established in Brisbane, Australia, to support the delivery of telehealth services to patients and clinicians in regional and remote locations. The QTS was built on a centralized coordination model, where telehealth services could be effectively managed by a dedicated telehealth coordinator. In doing so, telehealth referral and consultation processes were efficient and clinicians felt better supported as they adjusted to new processes for engaging with patients.

Multi-incident analysis of reviews of serious adverse clinical events in children with serious bacterial infection and/or sepsis in Queensland, Australia between 2012 and 2017.

Aim: To report on findings from a multi-incident analysis of reviews of serious paediatric adverse clinical events related to serious bacterial infection and/or sepsis (hereafter referred to as sepsis for brevity) in Queensland, Australia, between 2012 and 2017.

Methods: The Queensland Paediatric Quality Council reviewed documentation from reviews of serious adverse events occurring in children (<18 years) with a diagnosis of sepsis at Queensland public hospitals between 2012 and 2017, including clinical details, coronial reports, autopsy reports and root cause analysis documents. A multi-incident tool was designed and used by an expert panel to identify patient and facility demographics, contributing factors, and human and system factors associated with paediatric serious adverse events.

Development and validation of a UHPLC-MS/MS method to measure cefotaxime and metabolite desacetylcefotaxime in blood plasma: a pilot study suitable for capillary microsampling in critically ill children.

Critical illness has been shown to affect the pharmacokinetics of antibiotics, which can lead to ineffective antibiotic exposure and the potential emergence of resistant bacteria. The lack of studies describing antibiotic pharmacokinetics in critically ill children has led to significant off-label dosing. This is, in part, due to the ethical and physiological challenges of removing frequent, large-volume samples from children.

Microsampling to support pharmacokinetic clinical studies in pediatrics.

Background: Conventional sampling for pharmacokinetic clinical studies requires removal of large blood volumes from patients. This can result in a physiological/emotional burden for children. Microsampling to support pharmacokinetic clinical studies in pediatrics may reduce this burden.

Medical students' perceptions and expectations regarding digital health education and training: A qualitative study.

Introduction: Digital health - the convergence of digital technologies within health and health care to enhance the efficiency of health-care delivery - is fast becoming an integral part of routine medical practice. The integration of digital health into traditional practice brings significant changes. Logic dictates that for medical practitioners to operate in this new digitally enabled environment, they require specific knowledge, skills and competencies relating to digital health.

Single blood pressure chart for children up to 13 years to improve the recognition of hypertension based on existing normative data.

Objective: To produce a single 'growth-chart-style' blood pressure (BP) chart with clear diagnostic thresholds to assist paediatricians to make prompt and accurate diagnoses of hypertension.

Design: The well-established but complex published data on normal BP ranges in prepubertal children were identified and analysed to determine if it was possible to produce a single, user-friendly, colour-coded chart, showing diagnostic hypertension thresholds for systolic and diastolic BP without losing clinically important information.

Results: There were sufficient published normative childhood BP data available to define systolic and diastolic BP centiles from term onwards but only sufficient to determine systolic BP centiles from 28 weeks of gestation to term.

Using urine nitrite sticks to test for urinary tract infection in children aged < 2 years: a meta-analysis.

Background: This study aimed to determine whether nitrite sticks are as sensitive at detecting urinary tract infection (UTI) in children <2 years as they are in older children.

Methods: I reanalysed data on using nitrite sticks to detect UTIs for children aged either < 2 or 2-18 years. For sensitivity, evidence of a UTI was defined as level 1 when a single uropathogen grew ≥ 10 colony forming units/ml (cfu/ml) in two urine samples, level 2 when just one sample was cultured or a threshold of < 10 cfu/ml was used, and level 3 if mixed growths or Staphylococcus albus was considered to be positive.

A review of children with severe trauma admitted to pediatric intensive care in Queensland, Australia.

Background: The aim of this study is to review patient characteristics, injury patterns, and outcomes of trauma cases admitted to pediatric intensive care in Children's Health Queensland, Brisbane, Queensland, Australia.

Methods: Routinely recorded data collected prospectively from the Children's Health Queensland Trauma Service registry from November 2008 to October 2015 were reviewed. Demographic and clinical characteristics of trauma cases in children under 16 years of age are described, and their association with age and mortality analyzed.