Self-injurious behaviour (SIB) consists of persistent, repetitive movements that can result in serious injury without suicidal intent. These behaviours are prevalent among children with neurodevelopmental disorders, including profound autism. Although many individuals benefit from currently available therapies, some exhibit treatment-refractory SIB that necessitates ongoing use of personal protective equipment and restraint, presumably due to stronger neurobiological drivers. We recently completed a phase I, open-label clinical trial demonstrating the safety, feasibility and preliminary efficacy of bilateral deep brain stimulation targeting the nucleus accumbens (NAc-DBS) in children with profound autism and severe, refractory SIB. The objective of the proposed study is to characterise the effectiveness of NAc-DBS in treating severe, refractory SIB in this unique and vulnerable population.

A single-centre, randomised double-blinded, crossover trial is proposed. Informed by the results of our pilot study, 25 subjects with autism spectrum disorder and severe, refractory SIB will undergo bilateral NAc-DBS. Following a 4-week recovery period, participants will be randomised to either group A (stimulation ON then OFF) or group B (stimulation OFF then ON). Each block will last 12 weeks, separated by a 2-week washout period. Following completion of the second block, all participants will enter a 6-month open-label phase with stimulation ON. The primary outcome is the difference in the Repetitive Behaviour Scale–Revised total score, between DBS-ON and DBS-OFF conditions. Secondary outcomes include measures of quality of life, caregiver burden, daily logs of SIB events and direct observation of SIB under structured analogues.

The proposed trial has been approved by the institutional Research Ethics Board (1000081171). Trial results will be disseminated through peer-reviewed publications and conference presentations.

NCT06529380

Newborn bloodspot screening (NBS) is freely and universally available to babies born in Australia, with nearly 300 000 newborns screened each year. The NBS programme screens for approximately 30 conditions; however, there are hundreds of childhood conditions that could be treated if identified earlier and asymptomatically. Contemporary screening platforms have relied on mass spectrometry-based technologies, limiting surveillance to conditions with validated biomarkers detectable within the neonatal period. Advancements in metabolic techniques and genomics have expanded the range of conditions that could be detected. The NewbornsInSA research study will develop, validate and evaluate a novel multi-omic model of newborn screening, integrating metabolomic and genomic newborn screening as complementary methodologies.

Parents can opt in to additional NBS through NewbornsInSA during pregnancy or shortly after birth. One thousand prospectively recruited families will be offered genomic NBS by whole-genome sequencing, including analysis of a virtual gene panel of over 600 genes, and concurrent metabolomic screening. Clinically actionable pathogenic or likely pathogenic genetic variants will be reported to parents and whole genome sequencing data will be available on request for diagnostic reanalysis, if required later in life.

Acceptability of the NewbornsInSA programme will be evaluated through stakeholder engagement activities with healthcare professionals, members of the public and patient advocacy groups. Family experiences will be assessed using online surveys. The diagnostic yield, accuracy and the costs and consequences of the multi-omic NBS model will be assessed by comparison to standard-of-care NBS.

NewbornsInSA will investigate the acceptability, feasibility and cost-effectiveness of a multi-omic newborn screening model in a prospectively recruited South Australian population. We hypothesise that this approach will increase the number of conditions identified, reduce the time to diagnosis and facilitate earlier care with better outcomes for newborns with genetic conditions.

This research study has been ethically approved by the Women’s and Children’s Health Network Human Research Ethics Committee (2022/HRE00258 and 2023/HRE00236). Findings will be disseminated through peer-reviewed publication and conferences.

Cardiopulmonary bypass has been used to perform complex cardiac surgery for over 70 years. Advances in bypass techniques and perioperative medicine have increased the safety of cardiac procedures, leading to reduced morbidity and mortality. Nevertheless, cardiopulmonary bypass still carries risks, including systemic inflammation and dysfunction of various organs. To date, optimal blood pressure management during cardiopulmonary bypass remains a subject of ongoing debate. Conflicting evidence exists regarding negative outcomes associated with both low and high mean arterial pressures. Current clinical guidelines recommend a broad target range for mean arterial pressure during cardiopulmonary bypass, which underscores the existing gap in knowledge. In non-cardiac surgery, the time-weighted average of mean arterial pressure has been used to determine minimum safe thresholds, with greater deviation from 65 mm Hg associated with an increased risk of adverse outcomes. However, the definition and reporting of low blood pressure during cardiopulmonary bypass varies between studies, and the use of time-weighted averages below the threshold is still uncommon. Details on pump flow during extracorporeal circulation are seldom reported.

We plan to conduct a retrospective, single-centre data analysis to investigate the effects of both arterial blood pressure and extracorporeal pump flow, including their time-weighted averages and areas under defined thresholds, during cardiopulmonary bypass on neurological outcomes in adult patients undergoing cardiac surgery between 2014 and 2023. The study will include both elective and emergency procedures, with separate analyses conducted based on the urgency and complexity of the operations. Digitally recorded anaesthesia and perfusion records will be imported and validated to extract information on haemodynamic parameters, neurological monitoring and extracorporeal circulation. Ischaemic and haemorrhagic strokes will be identified by screening postoperative brain imaging records for keywords indicating neurological events. Diagnostic data and additional patient and procedural information will be extracted from the local cardiac surgery database and hospital information system. Information about incidence and course of postoperative delirium will be extracted from the patient data management system used in intensive care. We expect to include approximately 500–700 cases per year in the final analysis.

The local ethics committee approved our study (Ethics Committee of the Medical University of Graz, IRB00002556, 36-296 ex 23/24). We aim to publish the results of our study preferably in an open access format.

The study protocol was registered at the Center for Open Science (https://doi.org/10.17605/OSF.IO/FAMV3).