Biomarkers for rapid diagnosis of paediatric sepsis

Sepsis is a time critical medical emergency that arises when the body starts to attack its own tissues and organs in response to an infection. Sepsis can result in organ dysfunction, multi-organ failure and death if not treated promptly, and is a leading cause of death in children worldwide. Sepsis often presents with non-specific signs common to many mild infections, making it difficult to detect early and accurately, leading to delaying appropriate treatments and resulting in severe sepsis. Therefore, it is vital to identify new approaches to rapidly identify the type of infection and predict the severity of the condition in patients presenting with suspected sepsis to enable early initiation of appropriate treatments.

Recent advances in genomic technologies have shown that gene expression based infection testing has the potential to provide much faster and more precise results. This results in more accurate diagnosis of infections and appropriate timely treatments. Our study will utilise an advanced gene expression analysis approach named single-cell RNA sequencing to identify new approaches for sepsis diagnosis. This could lead to development of a rapid testing method which can predict the type of infection (bacterial or viral) and the severity of the condition with a quick turnaround time for results, improving patient outcomes, reducing unnecessary antibiotic use, and shortening hospital length of stay.

Pharmacological Emergency management of Agitation in Children and Young People – randomised controlled trials of Oral and intraMuscular medication: PEAChY-O and PEAChY-M

Acute severe behavioural disturbance (ASBD) is an emergency situation where a patient experiences severe agitation or aggression. These individuals commonly present to the emergency department (ED) for treatment. Medications are often provided to assist the person to feel calmer. In most instances, oral medications are used. When the patient is extremely agitated, an intramuscular (IM) injection will be given.

In individuals less than 18 years, there is minimal available evidence to guide doctors about which medications work best. It is also not known how well these medications are tolerated by these young people. Therefore, the PREDICT (Paediatric Research in Emergency Departments International Collaborative) network is running two trials across a number of Australian EDs to create evidence to be used to guide the treatment for these young people.

The first study (PEAChY-O) compares two oral medications - olanzapine and diazepam - to determine which medication works better. The second study (PEAChY-M) compares two IM medications – olanzapine and droperidol. These medications were chosen because they are used as standard of care in Australian EDs and are recommended on current Clinical Practice Guidelines (CPGs). These are important studies because they will be the first trials to compare any medications head-to-head in a randomised trial across either the oral or IM routes.
Once the results are available, they will be used to guide future clinical practice including influencing the recommendations made in Australian guidelines, ensuring that these young people receive evidence-based treatments.

Composition, Quality and Delivery of Major Haemorrhage Protocols (MHP) and critical bleeding clinical practice guidelines in hospitals across Queensland Health

Major bleeding is a leading cause of death in trauma patients. Blood product replacement is a key component of damage control resuscitation aimed at limiting coagulopathy until definitive control of bleeding is achieved. Although Major Haemorrhage Protocols (MHP) are now widely used in the initial resuscitation of traumatically injured patients (1), protocols can vary based upon individual institutions' capabilities and processes.

Within Australia, the National Blood Authority 2011 Patient Blood Management Guideline Module 1: Critical Care/ Massive Transfusion (2) recommended institutions develop standardized MHP to guide clinicians regarding the dose, timing and ratio of blood component therapy for bleeding trauma patients. However, it is currently unknown if these guidelines are implemented and if so, what institutional variations occur. While the guidelines provide a robust review of the evidence base for MHP, there is little information about the logistics of MHP implementation.

Our project aims are firstly to compare the available trauma bleeding protocols across Queensland for content and quality. Secondly, we wish to understand the institution's capabilities of delivering an MHP in terms of the structure and processes available to them. Thirdly we want to explore the experiences of clinicians involved in delivering an MHP for trauma patients in both tertiary, rural and remote hospitals within Queensland.

Expected benefits are to identify potential disparity of care for trauma patients in terms of MHP content, availability of resources and access to blood products. This information can help guide improvements in education, blood products availability and cost-effective care across Queensland.

PaNURAMA Inter-facility Transfer Tool: a validation study of the Paediatric Non-Urgent, Risk Assessment, Management and nurse escort Assessment Tool for safe children’s inter-facility Transfer

Most paediatric inter-facility transfers within Australia are for children that do not qualify for specialist paediatric retrieval services but still require access to specialised paediatric care not offered at the local healthcare facility.

Evidence-based transfer guidance for children requiring retrieval are well established. However, for children who do not meet retrieval criteria, there is little guidance for referring and accepting clinicians on how to coordinate safe transfer. Nurse escorts are often deployed but may not be trained sufficiently to deal with arising complications during transfer. Additionally, with the availability and scope of paramedics, the deployment of nurse escorts may not be required, and unecessarily deplete valuable resources at referring facilities.

A risk stratification tool has been developed to determine which non-urgent transfers require higher level consultation and management prior to and during transfer, and nursing escort. The validation of this tool may assist to accurately identify higher-risk children, enabling application of appropriate safeguards, an appropriate level of consultation and escort, and supporting clinician decision-making surrounding transport Australia-wide.

SONIC: Study of Neck Injuries in Children. A PREDICT study

Currently in Australia, children with suspected neck injuries undergo neck scans such as x-rays, computed tomography (CT) or magnetic resonance imaging (MRI). However these scans may carry risks from radiation exposure, and are often associated with discomfort and distress for young patients and the need for sedation.

Considerable emergency department time and costs are also associated with these scans and it is unclear when it can be safely avoided. Rules and tools can help doctors decide when scans are necessary. The SONIC study aims to look at whether existing rules for adults are also appropriate for use in children, and to develop and test a specific tool to help doctors decide which children need a neck x-ray or scan. The study will involve a large number of children across multiple hospitals in Australia and New Zealand. The research is expected to help researchers learn more about looking after children with neck injuries and hopefully allow us to safely limit the number of scans that need to be done.

The SONIC study is also supported by the Commonwealth of Australia through a MRFF Grant ID1199748 administered by the Murdoch Children’s Research Institute.

Using bedside ultrasound to diagnose forearm fractures in children

This is a multicentre, open-labelled diagnostic randomised controlled trial to comparing the use of portable ultrasound and x-ray imaging to diagnose a buckle fracture in children. The trial will determine if there are differences in functional outcomes, patient and care-giver preferences, and health system benefits.

Children frequently present to the emergency department with forearm injuries and often have an x-ray to assess if there is a fracture. Due to the soft and plastic nature of the bones in young children, injuries can cause their bones to bend, known as a buckle fracture. Bedside ultrasound is a test that emergency practitioners can use to rapidly diagnose a fracture at the time of examination, without exposing children to ionising radiation. Ultrasound in this setting is well tolerated, only requiring light touch and gentle manipulation of the forearm and has similar accuracy when compared with x-rays for diagnosing children’s forearm fractures.

This is the first trial of its kind to assess whether an x-ray is unnecessary when there is either a buckle fracture or no fracture seen on a portable ultrasound machine. This is important as they can be treated at the time of review without any further delay, which will avoid these children being exposed to ionising radiation. Children will be randomised to receive either an ultrasound or x-ray for their forearm injury. Both groups will be followed up to see whether there are any differences in their recovery and to determine any complications. We will also determine the time and cost implications of this new approach, which could enable families to go home earlier and could be more cost-effective, with less x-rays being ordered.

Early resuscitation in paediatric sepsis

Sepsis is a leading cause of death and disability in children, globally accounting for more than one million childhood deaths per year. Recommended sepsis treatment currently consists of intravenous antibiotics and aggressive fluid boluses followed by inotropes and consideration for intravenous steroids. However, the evidence for interventions other than antibiotics is limited and aggressive fluid administration may be associated with harm. Therefore, fluid-sparing algorithms using early inotropes to treat shock have been proposed. Another strategy to hasten shock resolution consists in intravenous steroids, alone or in combination with thiamine and vitamin C, postulated to support metabolic dysfunction in recent studies.

In this project, the research team is conducting a randomised controlled pilot trial in children presenting with septic shock. They are assessing the feasibility of a fluid-sparing algorithm using early inotropes and early intravenous administration of Vitamin C, Thiamine and Hydrocortisone and the impact on survival free of organ dysfunction.

How are we treating severe childhood asthma in Australasia?

Most children with asthma presenting to an emergency department (ED) are managed with inhaled medications and oral steroids. Infrequently, those children that are very unwell may require assistance with their breathing, or intravenous medication. Currently, there is minimal information to guide clinicians on which treatment to choose for severe acute asthma. It is not known which is most effective and all have side-effects. Studies demonstrate significant variation in practice, while existing Australasian data is approximately 10 years old.

This project aims to determine current management practices for children with severe acute asthma and/or wheeze; how common the condition is, how frequently complications occur; and to understand differences in therapy between states and regions across Australia and New Zealand. When comparing treatments, it is important to determine the ability to reduce the risk of severe complications, or the difference in treatment outcomes. Once complete, this project will inform future research that will help to establish the best treatments for severe asthma.

This study is being run by the PREDICT network and its Chief Investigator is A/Prof Simon Craig. The EMF is funding Queensland sites taking part. The overall study will include 18,000 children aged between 1 and 18 years being treated for asthma in the ED.

Is prednisolone an effective treatment for Bell’s Palsy in children?

Bell’s palsy or acute idiopathic lower motor neurone facial paralysis is characterised by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. It is the third most common neurological reason for children to present acutely to hospital.

In adults, there is conclusive evidence from two major recent trials that a short course of prednisolone, a cheap, widely available and safe steroid, can significantly increase the number of Bell’s palsy patients who completely recover. While the medical problems associated with Bell’s palsy are similar, in children there is no good evidence that prednisolone is an effective treatment.

Many neurological conditions progress differently in children and treatment methods sometimes vary. Children may react differently to prednisolone and without paediatric evidence; treatment guidelines for children with Bell’s palsy remain absent or vague, with variable and overall low rates of steroid use in children by physicians.

The lack of evidence and clinical uncertainty in the treatment of Bell’s palsy in children warrants a definitive trial to determine the efficacy of prednisolone as a treatment for this condition in children. The aim of this study is to assess the utility of steroids in Bell’s palsy in children in a large multicentre randomised, placebo-controlled, trial. The trial will take place in at least 10 hospitals within Australia and New Zealand, involving more than 500 children.

A Prospective Observational Cohort Study of Paediatric Status Epilepticus in Emergency Departments of Australia and New Zealand. The Status Epilepticus Australasian Registry for Children (SEARCh)

Convulsive status epilepticus (CSE) occurs when seizures do not stop spontaneously. It is the most severe form of epilepsy, and can result in long-term disabilities and rarely death. It can affect both adults and children, although the causes and outcomes are different in these groups of patients. Treatments of patients with CSE are largely based on expert opinion rather than strong evidence, due to the difficult nature of conducting quality trials in patients with this relatively infrequent condition in the emergency setting. We will determine the incidence and causes of CSE in children in Australia and New Zealand and collect information on the type of seizure, duration, treatment and outcome to determine ways to improve the management of children with CSE.