Fellowship Programs

Autism spectrum disorder is a neurodevelopmental condition that impacts brain development, diagnosed in more than 1% of the population. A diagnosis is currently based solely on behavioural symptoms emerging in early childhood. However, the underlying biological mechanisms contributing to a diagnosis remain unknown. One such mechanism may be differences in the metabolome, or the collection of small-molecule chemicals called metabolites. To conduct such research, very large and well-characterised sample cohorts are required, particularly in complex and heterogeneous conditions like autism. This project aimed to explore the metabolic differences from urine and blood samples of a large cohort of children with autism, to provide a first step towards establishing a phenomics analysis platform for autism research. To further our understanding of metabolic differences in children on the autism spectrum, this project conducted a large scoping review, implicating several metabolites that differ between children with and without an autism diagnosis. The findings from this research are now being used to inform analytical strategies for investigating urine samples of children on the autism spectrum, their siblings, and unrelated children from the general community. This project is contributing to a broader research program into understanding more effective and personalised therapies for children on the autism spectrum towards better health outcomes.

The Learn, Engage and Play (LEaP) study developed and evaluated the effectiveness of a therapeutic playgroup for children with developmental delays when first referred to an early intervention service. This consumer driven study arose from parents’ desire to have a way of accessing information early to support their child’s development and connect with other families experiencing the same challenges. Embedded into the Child Development Service of Western Australia and supported by Curtin University, Western Australian Health Translation Network (WAHTN), Collaborate for Kids (CoLab) and the Perth Children’s Hospital Foundation; this study collaborated with over 150 consumers, policy‐makers, practitioners and community members during the planning, development, and evaluation of the LEaP playgroup. Study findings indicated the LEaP playgroup was highly valued by families and positively improved child outcomes and levels of family support. In a research environment characterised by inconsistent playgroup definitions and models, this study created new playgroup knowledge, clarifying therapeutic playgroup practice principles and producing the first evidence‐based and empirically tested manualised therapeutic playgroup for young children with significant developmental delays. It also demonstrates how academic institutions and health services can partner to address consumer identified needs and develop evidence‐based interventions that can be translated into practice.

Failure to detect and act on signs of clinical deterioration in a timely manner can result in serious adverse outcomes with devastating results, particularly in children. In WA, there is not a uniform approach to recognising and responding to clinical deterioration for hospitalised children and this may contribute in failure to recognise or respond in a timely manner to critical changes in a child’s condition. The Project aimed to develop an evidence based state-wide system for recognising and responding to clinical deterioration in WA paediatric settings inclusive of family participation and to evaluate the feasibility and factors necessary to ensure successful implementation. The project was successful in developing and trialling a proposed uniform ESCALATION System that was a product of widespread stakeholder and consumer input and review. This system is unique in incorporating a chart – PARROT, a framework for escalation communication and integrated parent concern. At the six pilot sites (PCH, Fiona Stanley Hospital, Joondalup Health Campus, Narrogin Hospital, Albany Hospital and Broome Hospital) the trial system was well received by staff and families, with feedback provided to further fine tune prior to full implementation. Final testing is now underway at two sites (PCH and Broome Hospital) prior to state-wide implementation planned for 2021.

Fever without source is one of the most common reasons young infants less than 3 months old present to hospital. Although most will have a minor viral infection, all infants are currently hospitalised for at least 48 hours to undergo investigations and receive intravenous antibiotics until serious bacterial infection is excluded. Recent international evidence indicates that many infants may be safely be discharged home much earlier. Earlier discharge of low-risk infants may help reduce the risk of iatrogenic complications, promotion of antibiotic resistance, and unnecessary burden for families and the health-care system. The FeBRILe3 project looks at the safety of a new clinical practice guideline allowing earlier discharge home for well-looking, low-risk infants with fever. FeBRILe3 monitors for unplanned hospital presentations and other complications to show the safety and impact of this intervention, utilising a novel prospective real-time Bayesian monitoring approach. By implementing the clinical practice guideline within an active safety monitoring framework, FeBRILe3 will improve clinician confidence in the change, help standardise and optimise local patient care, and provide evidence to translate practice to other paediatric centres across Australia and beyond. The new research collaborations developed through FeBRILe3 will support future local research into optimising the management of childhood infections.

Breast conserving surgery (BCS) is standard treatment for early breast cancer. BCS involves removal of the cancer along with a surrounding area of normal tissue (the “margin”). In 2014, guidelines were published that mandated smaller margins than previously recommended, with the aim of minimising practice variation and reducing reoperations to achieve unnecessarily large margins. This project sought to establish the impact of these guidelines on clinical practice and outcomes for women with early breast cancer. We found that reoperation rates in women having BCS in WA decreased in the five years after the guidelines were published, compared with the previous five years. We also found that this decrease was consistent with estimates from international population-based studies. Internationally, avoidance of reoperation was greater in individual centres that specifically adopted the guidelines as surgical policy, and in centres that accepted wider margins prior to the guidelines. Women avoiding an unnecessary second operation avoid the surgical risks and complications, distress, and inconvenience associated with that operation. We also found that there was a median cost saving to health systems of US$3,450 per woman avoiding reoperation.

The highly aggressive nature of metastatic melanoma demands that we maximise opportunities to intervene with optimal treatment at the earliest time. Currently radiological imaging remains the gold standard for determining treatment response or disease progression, however are typically performed 3-12 monthly. Apart from the high costs and radiation exposure, the time differences may allow the disease to manifest and remain undetected. Circulating tumour DNA {ctDNA) (released from tumour cells into blood), is a valuable tool for measuring disease change in melanoma and we have previously shown a strong correlation between ctDNA and PET-derived metabolic tumour burden (MTB) in a cohort of treatment na’ive metastatic melanoma patients. The utility of serial ctDNA monitoring has not been well documented and as such, we sought to evaluate if ctDNA can predict treatment response or progressive disease in metastatic melanoma patients undergoing active treatment or surveillance. Our study provides some key insights into ctDNA assessment suggesting that with current testing procedures, clinical value is only realised in a subset of patients. Consequently, further improvements in the detection and quantification of ctDNA would be required before it can be effectively translated into the clinic.

Cerebral palsy (CP) is the leading cause of childhood motor impairment and is caused by an injury to the developing brain before or shortly after birth. It is a lifelong condition that is frequently accompanied by additional impairments in sensation, cognition and communication. Four in five children with CP have a reduced sense of touch that further affects their ability to use their hands to complete everyday activities independently. This project worked with clinicians in a state-wide service and in the community to raise awareness of the frequency of sensory impairment and the impact of these on function for children with CP. Therapists received training on how to assess children for sensory impairment and to provide intervention to improve children’s sensation and upper limb use. (An intervention manual and working examples have been compiled and will support the standardised and effective implementation of training.) As a part of this program all children with significant upper limb goals attending the service will be assessed for sensory impairment and offered intervention if it is indicated and a new treatment stream is being examined for children with neurological conditions. Sensory outcomes have been incorporated in the health services clinical database so all team members can see if assessments have been undertaken and what the child is able to do.

"Familial" means it runs in families and "hypercholesterolaemia" means high blood cholesterol. Familial Hypercholesterolaemia (FH) is the most common and serious form of inherited high cholesterol. People with FH are at an increased risk of developing cardiovascular disease. Practical research on prevention strategies can improve cardiovascular health outcomes and lower the burden of health costs. Using data from a national registry, the current project has identified healthcare gaps in the detection and management of FH in Australia. FH patients are diagnosed later in life and often do not achieve adequate cholesterol lowering despite a high frequency of cardiovascular disease and risk factors. The project highlighted the need for earlier diagnosis of FH and earlier initiation of cholesterol-lowering therapy, as well as more comprehensive management of cardiovascular risk factors.

Group A Streptococcus bacteria (Streptococcus pyogenes, Strep A) cause superficial and invasive infections (e.g. sore throat, skin infection, blood infection), the complications of which include acute rheumatic fever and rheumatic heart disease. These diseases of poverty are responsible for significant morbidity and mortality, manifesting in the marginalised populations of the world including Aboriginal and Torres Strait Islander children. Effective prevention strategies (including vaccines) are urgently needed to alleviate the burden from this priority population in Australia. As vaccine candidates progress through the development pipeline, epidemiological surveillance data will facilitate decision-making for the Strep A vaccine targets, vaccine efficacy and implementation strategies. Strep A surveillance is a developing but necessary tool for reducing the burden of Strep A disease. To improve Strep A surveillance, this project has determined the optimal way to store and handle throat swabs collected from children. Our new methods can be applied in low- and high- resource settings to measure the rates of Strep A infection and the impact of preventative measures including health policies and vaccinations. Novel application of a phage-lysin to disrupt Strep A cell walls has also led to optimised DNA extraction protocols which are now being utilised in surveillance studies in Australia.

It is reported 60-85% of children with Cerebral Palsy (CP), have communication problems, with 1 in 4 children unable to talk. Early diagnosis is therefore critical to minimising the cascading consequences of communication impairment. The “B2: I Can Communicate” project evaluated the developmental profile of early vocalisations/speech/language development of infants with/at risk of CP representing the first longitudinal study. Eighteen children with CP and 18 typically developing (TD) children were followed at 3 monthly intervals from 6 months to 18 months of age. Researchers, clinicians and stakeholders were involved throughout the project; with recommended changes in clinician practice and clinical pathways evaluated. Data analyses show significant group differences in both the type of infant vocalisations and developmental trajectory of early speech/language development. TD children displayed an increasing developmental trajectory over time, whilst the trajectory of development for CP was decreasing, indicating increasing communication impairment compared to TD children. A clinical audit, undertaken to assess implementation and translation into clinical practice, shows a significant decrease in the age at which children were assessed, and change in assessment practices. This project contributes to a data-driven knowledge base for clinicians in the early diagnosis and management of communication disorders associated with CP and focuses on building clinical care pathways.

Causal processes underlie all diseases and their clinical management; however, they are rarely recognised and described. Clinicians must make accurate and timely decisions about these processes based on many observations. This is particularly difficult in the case of urinary tract infection (UTI) in children because they often have signs and symptoms that are non-specific to UTI. In addition, urine culture results can be made less useful due to bacterial contamination. By working closely with many experts in the field of medicine, laboratory science, and microbiology, we have created causal models that can help inform clinicians whether a child has UTI caused by bacteria. If so, the models also suggest which antibiotic would be most effective to treat the bacterial infection. We have collected information from children who recently presented to the Emergency Department at Perth Children’s Hospital to test the accuracy and robustness of the model predictions. This project has allowed us to demonstrate how these models are built and can be adapted to other clinical problems. This can help doctors make decisions about other (non-UTI) infections in the future.