Publications by authors named "Mark G Coulthard"

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.

View Article and Find Full Text PDF

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).

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Aim: This study evaluates the implementation rate and strength of the recommendations developed in all root cause analyses (RCAs) performed following serious clinical incidents involving children that have resulted in permanent harm or death in Queensland public hospitals over a 3-year period.

Methods: Severity assessment classification 1 events were identified from a Queensland Paediatric Quality Council database of paediatric clinical incidents that occurred in Queensland between 1 January 2012 and 31 December 2014. There were 150 recommendations extracted from RCAs pertaining to the 42 serious adverse events involving paediatric patients.

View Article and Find Full Text PDF

Severe respiratory infections make up a large proportion of Australian paediatric intensive care unit (ICU) admissions each year. Identification of the causative pathogen is important and informs clinical management. We investigated the use of polymerase chain reaction (PCR) in the ICU-setting using data collated by the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry from five ICUs in Queensland, Australia.

View Article and Find Full Text PDF

The paediatric intensive care unit (PICU) provides care to critically ill neonates, infants and children. These patients are vulnerable and susceptible to the environment surrounding them, yet there is little information available on indoor air quality and factors affecting it within a PICU. To address this gap in knowledge we conducted continuous indoor and outdoor airborne particle concentration measurements over a two-week period at the Royal Children's Hospital PICU in Brisbane, Australia, and we also collected 82 bioaerosol samples to test for the presence of bacterial and viral pathogens.

View Article and Find Full Text PDF

Objective: To review the epidemiology of pertussis-related intensive care unit (ICU) admissions across Australia, over a 17-year period.

Design: Retrospective descriptive study.

Setting: Australian ICUs contributing data to the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry.

View Article and Find Full Text PDF

Background: The University of Queensland (UQ), Ochsner Clinical School (OCS) is a partnership between Ochsner Health System in New Orleans, LA, and UQ in Brisbane, Australia. OCS medical students are trained on both continents, receiving their didactic education in Australia and their clinical education in the United States.

Methods: We review the OCS experience and compare the pediatric rotations at OCS and UQ.

View Article and Find Full Text PDF

Background: Influenza virus predictably causes an annual epidemic resulting in a considerable burden of illness in Australia. Children are disproportionately affected and can experience severe illness and complications, which occasionally result in death.

Methods: We conducted a retrospective descriptive study using data collated in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry of influenza-related intensive care unit (ICU) admissions over a 17-year period (1997-2013, inclusive) in children <16 years old.

View Article and Find Full Text PDF

The inflammatory response is characterized by increased endothelial permeability, which permits the passage of fluid and inflammatory cells into interstitial spaces. The Eph/ephrin receptor ligand system plays a role in inflammation through a signaling cascade, which modifies Rho-GTPase activity. We hypothesized that blocking Eph/ephrin signaling using an EphA4-Fc would result in decreased inflammation and tissue injury in a model of ischemia/reperfusion (I/R) injury.

View Article and Find Full Text PDF

Background: Maintenance intravenous fluids are frequently used in hospitalised children who cannot maintain adequate hydration through enteral intake. Traditionally used hypotonic fluids have been associated with hyponatraemia and subsequent morbidity and mortality. Use of isotonic fluid has been proposed to reduce complications.

View Article and Find Full Text PDF

Background: In many health systems, specialist services for critically ill children are typically regionalised or centralised. Studies have shown that high-risk paediatric patients have improved survival when managed in specialist centres and that volume of cases is a predictor of care quality. In acute cases where distance and time impede access to specialist care, clinical advice may be provided remotely by telephone.

View Article and Find Full Text PDF

Ephrin (Eph) signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT) and EphA2-deficient (EphA2(-/-)) mice by middle cerebral artery occlusion (MCAO; 60 min), followed by reperfusion (24 or 72 h).

View Article and Find Full Text PDF

Background: Checklists have been recognized by multiple industries as a valuable tool to reduce errors of omission. In the busy environment of a pediatric intensive care unit, adverse events are common and can have severe consequences. Researchers have focused on developing evidence-based practice guidelines; however, the nature of human error means that consistent application of this evidence in practice is challenging.

View Article and Find Full Text PDF

The Eph/ephrin receptor-ligand system plays an important role in embryogenesis and adult life, principally by influencing cell behavior through signaling pathways, resulting in modification of the cell cytoskeleton and cell adhesion. There are 10 EphA receptors, and six EphB receptors, distinguished on sequence difference and binding preferences, that interact with the six glycosylphosphatidylinositol-linked ephrin-A ligands and the three transmembrane ephrin-B ligands, respectively. The Eph/ephrin proteins, originally described as developmental regulators that are expressed at low levels postembryonically, are re-expressed after injury to the optic nerve, spinal cord, and brain in fish, amphibians, rodents, and humans.

View Article and Find Full Text PDF

Background: About two-thirds of medical students are distributed among the major metropolitan tertiary teaching hospitals in Queensland, while the remainder are sent to regional hospitals up to 500 km away. The aim of this study was to investigate the feasibility and effectiveness of conducting surgical tutorials via videoconferencing (VC) for medical students undertaking at remote hospitals.

Methods: Surgical tutorials were offered to final-year medical students at the Royal Children's Hospital (RCH) in Brisbane and shared by VC to students undertaking clinical placement at nine remotely located hospitals in Queensland.

View Article and Find Full Text PDF

Objective: To compare the difference in plasma sodium at 16-18 h following major surgery in children who were prescribed either Hartmann's and 5% dextrose or 0.45% saline and 5% dextrose.

Design: A prospective, randomised, open label study.

View Article and Find Full Text PDF

In Queensland, the majority of rural hospitals and some regional hospitals lack paediatricians or paediatric sub-specialists. Many specialist referrals result in a transfer to a tertiary paediatric hospital in Brisbane--up to 3000 km away. Travel is difficult, time-consuming and expensive, especially from rural and remote areas in Queensland.

View Article and Find Full Text PDF