Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.

The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.

This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.

NCT03559114.

Adolescence is a critical period marked by rapid brain development and the onset of many mental health disorders. Brain MRI studies during adolescence, especially when paired with behavioural phenotypes and information about genetic risk factors, hold promise to advance early identification of mental health risk and spur the creation of targeted treatments to improve patient function, prognosis and quality of life. However, prospective neuroimaging is costly and time-intensive, and individuals who participate may not be reflective of the general population. These challenges are compounded when examining adolescents, as many families lack the time, energy or resources to participate in studies that use research-grade imaging. Repurposing clinical MRIs obviates many of the challenges of neuroimaging research. Here, we describe the brain-behaviour-genetics study protocol. This protocol describes procedures used to recruit participants with recent high-quality clinical brain MRIs and prospectively acquire genetic and sociobehavioural data, resulting in a highly cost-efficient design that harnesses a vast and underused neuroscientific resource.

The brain-behaviour-genetics protocol aims to recruit 1000 adolescents who have clinical brain MRIs contained in Children’s Hospital of Philadelphia’s electronic health record. One or both parents of the adolescent proband will be recruited when possible. Parents and adolescents will complete a series of self-report scales spanning the domains of mental health, trauma, risk and resilience. Saliva samples will be collected from the adolescent and at least one biological parent, using an at-home saliva collection kit. Subsequent analysis will examine associations between brain development, genetics and behavioural measures in adolescence.

Approval for the study had been obtained from the Children’s Hospital of Philadelphia’s institutional review board (IRB #23–0 20 851). Results will be published in peer-reviewed journals.