Education-only versus a multifaceted intervention for improving assessment of rehabilitation needs after stroke: a cluster randomised trial

In 2011, more than half of the patients with stroke in Australian hospitals were not assessed for the need for rehabilitation. Further, there were no recommended criteria to guide rehabilitation assessment decisions. Subsequently, a decision-making tool called the Assessment for Rehabilitation Tool (ART) was developed. The ART was designed to assist Australian hospital clinicians to identify the rehabilitation needs of patients with stroke using evidence-based criteria. The ART was released and made freely available for use in 2012. This study evaluated the effectiveness of an education-only intervention (1 onsite education session and distribution of the ART) and a multifaceted intervention (2 or more onsite education sessions, distribution of the ART, audit and feedback, barrier identification, site-specific strategy development, promotion of interdisciplinary teamwork, opinion leaders and reminders) for improving assessments of rehabilitation needs after stroke. Ten hospitals in 2 states of Australia were randomly assigned to an education-only or a multifaceted intervention. Medical records were audited by assessors blinded to group allocation before and after the implementation period. Difference in the proportion of patients assessed for rehabilitation before and after the intervention was analysed using mixed-effects logistic regression analysis, with time period as the dependent variable, an interaction between intervention type and time included to test for differences between the interventions, and hospital included as the random effect to account for patient clustering. Data from 586 patients (284 pre-intervention; 302 post-intervention; age 76 years, 59 % male) showed that the multifaceted intervention was not more effective than education-only in improving the proportion of patients whose rehabilitation needs were assessed (reference category education-only; odds ratio 1.29, 95 % confidence interval 0.63-2.67, p = 0.483). Post-intervention, the odds of a patient's rehabilitation needs being assessed was 3.69 times greater than pre-intervention (95 % confidence interval 2.57-5.30, p < 0.001). Evidence-based criteria were not consistently used when patients were deemed to have no rehabilitation needs. A multifaceted intervention was not more effective than education-only in improving the assessment of rehabilitation needs of patients with stroke. Further interventions are required to ensure that all patients are assessed for the need for rehabilitation using evidence-based criteria. ANZCTR (Australian New Zealand Clinical Trials Registry), ACTRN12616000340437.Elizabeth A. Lynch, Dominique A. Cadilhac, Julie A. Luker and Susan L. Hillie

A fluorescent perilipin 2 knock-in mouse model visualizes lipid droplets in the developing and adult brain

Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in health and disease. Most LD studies in vivo rely on staining methods, providing only a snapshot. We therefore developed a LD-reporter mouse by endogenously labelling the LD coat protein perilipin 2 (PLIN2) with tdTomato, enabling staining-free fluorescent LD visualisation in living and fixed tissues and cells. Here we validate this model under standard and high-fat diet conditions and demonstrate that LDs are present in various cells in the healthy brain, including neurons, astrocytes, ependymal cells, neural stem/progenitor cells and microglia. Furthermore, we show that LDs are abundant during brain development and can be visualized using live-imaging of embryonic slices. Taken together, our tdTom-Plin2 mouse serves as a novel tool to study LDs and their dynamics under both physiological and diseased conditions in all tissues expressing Plin2

Statistical analysis plan for the stepped wedge clinical trial Healing Right Way—enhancing rehabilitation services for Aboriginal Australians after brain injury

Background Aboriginal Australians are known to suffer high levels of acquired brain injury (stroke and traumatic brain injury) yet experience significant barriers in accessing rehabilitation services. The aim of the Healing Right Way trial is to evaluate a culturally secure intervention for Aboriginal people with newly acquired brain injury to improve their rehabilitation experience and quality of life. Following publication of the trial protocol, this paper outlines the statistical analysis plan prior to locking the database. Methods The trial involves a stepped wedge design with four steps over 3 years. Participants were 108 adult Aboriginal Australians admitted to one of eight hospitals (four rural, four urban) in Western Australia within 6 weeks of onset of a new stroke or traumatic brain injury who consented to follow-up for 26 weeks. All hospital sites started in a control phase, with the intervention assigned to pairs of sites (one metropolitan, one rural) every 26 weeks until all sites received the intervention. The two-component intervention involves training in culturally safe care for hospital sites and enhanced support provided to participants by Aboriginal Brain Injury Coordinators during their hospital stay and after discharge. The primary outcome is quality of life as measured by the Euro QOL–5D-3L VAS. A mixed effects linear regression model will be used to assess the between-group difference at 26 weeks post-injury. The model will control for injury type and severity, age at recruitment and time since commencement of the trial, as fixed effects. Recruitment site and participant will be included as random effects. Secondary outcomes include measurements of function, independence, anxiety and depression, carer strain, allied health occasions of service received and hospital compliance with minimum processes of care based on clinical guidelines and best practice models of care. Discussion The trial will provide the first data surrounding the effectiveness of an intervention package for Aboriginal people with brain injury and inform future planning of rehabilitation services for this population. The statistical analysis plan outlines the analyses to be undertaken. Trial registration Australia New Zealand Clinical Trials Registry ACTRN12618000139279. Registered 30 January, 2018

Statistical analysis plan for the COMPARE trial: a 3-arm randomised controlled trial comparing the effectiveness of Constraint-induced Aphasia Therapy Plus and Multi-modality Aphasia Therapy to usual care in chronic post-stroke aphasia (COMPARE)

BackgroundWhile high-quality meta-analyses have confirmed the effectiveness of aphasia therapy after stroke, there is limited evidence for the comparative effectiveness of different aphasia interventions. Two commonly used interventions, Constraint-induced Aphasia Therapy Plus (CIAT Plus) and Multi-modality Aphasia Therapy (M-MAT), are hypothesised to rely on diverse underlying neural mechanisms for recovery and may be differentially responsive to aphasia severity. COMPARE is a prospective randomised open-blinded end-point trial designed to determine whether, in people with chronic post-stroke aphasia living in the community, CIAT Plus and M-MAT provide greater therapeutic benefit compared to usual care, are differentially effective according to aphasia severity, and are cost-effective. This paper details the statistical analysis plan for the COMPARE trial developed prior to data analysis.MethodsParticipants (n = 216) are randomised to one of three arms, CIAT Plus, M-MAT or usual care, and undertake therapy with a study trained speech pathologist in groups of three participants stratified by aphasia severity. Therapy occurs for 3 h blocks per day for 10 days across 2 weeks. The primary clinical outcome is aphasia severity as measured by the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ) immediately post intervention. Secondary outcomes include WAB-R-AQ at 12-week follow-up, and functional communication, discourse efficiency, multimodal communication, and health-related quality of life immediately post intervention and at 12-week follow-up.ResultsLinear mixed models (LMMs) will be used to analyse differences between M-MAT and UC, and CIAT-Plus and UC on each outcome measure immediately and at 12 weeks post-intervention. The LMM for WAB-R-AQ will assess the differences in efficacy between M-MAT and CIAT-Plus. All analyses will control for baseline aphasia severity (fixed effect) and for the clustering effect of treatment groups (random effect).DiscussionThis trial will provide relative effectiveness data for two common interventions for people with chronic post-stroke aphasia, and highlight possible differential effects based on aphasia severity. Together with the health economic analysis data, the results will enable more informed personalised prescription for aphasia therapy after stroke.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN 12615000618550 . Registered on 15 June 2016

The International comparison of Systems of care and patient outcomes In minor Stroke and Tia (InSIST) study: A community-based cohort study

This is the author accepted manuscript. The final version is available from Sage Publications via the DOI in this record.Rationale: Rapid response by health-care systems for transient ischemic attack and minor stroke (TIA/mS) is recommended to maximize the impact of secondary prevention strategies. The applicability of this evidence to Australian non-hospital-based TIA/mS management is uncertain. Aims: Within an Australian community setting we seek to document processes of care, establish determinants of access to care, establish attack rates and determinants of recurrent vascular events and other clinical outcomes, establish the performance of ABC2-risk stratification, and compare the processes of care and outcomes to those in the UK and New Zealand for TIA/mS. Sample size estimates: Recruiting practices containing approximately 51 full-time-equivalent general practitioners to recruit 100 TIA/mS per year over a four-year study period will provide sufficient power for each of our outcomes. Methods and design: An inception cohort study of patients with possible TIA/mS recruited from 16 general practices in the Newcastle-Hunter Valley-Manning Valley region of Australia. Potential TIA/mS will be ascertained by multiple overlapping methods at general practices, after-hours collaborative, and hospital in-patient and outpatient services. Participants’ index and subsequent clinical events will be adjudicated as TIA/mS or mimics by an expert panel. Study outcomes: Process outcomes—whether the patient was referred for secondary care; time from event to first patient presentation to a health professional; time from event to specialist acute-access clinic appointment; time from event to brain and vascular imaging and relevant prescriptions. Clinical outcomes—recurrent stroke and major vascular events; and health-related quality of life. Discussion: Community management of TIA/mS will be informed by this study.Nationale Health and Medical Research Council (NHMRC