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RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was ranked easy to address and very important, "variability in usual care" was ranked hard to address and of low importance, and "understanding the content of the control and how it differs from the experimental intervention" was ranked very important but not easy to address. The CONtrol DeSIGN (CONSIGN) decision support tool was developed to address the identified challenges and enhance comparator selection, description, and reporting. CONSIGN is a web-based tool inclusive of seven steps that guide the user through control comparator design. The tool was refined through multiple rounds of pilot testing that included more than 130 people working in neurorehabilitation research. Four hypothetical exemplar trials, which span preclinical, mood, aphasia, and motor recovery, demonstrate how the tool can be applied in practice. Six consensus recommendations are defined that span research domains, professional disciplines, and international borders.

BACKGROUND: Mobility is a key priority for stroke survivors. Worldwide consensus of standardized outcome instruments for measuring mobility recovery after stroke is an essential milestone to optimize the quality of stroke rehabilitation and recovery studies and to enable data synthesis across trials. METHODS: Using a standardized methodology, which involved convening of 13 worldwide experts in the field of mobility rehabilitation, consensus was established through an a priori defined survey-based approach followed by group discussions. The group agreed on balance- and mobility-related definitions and recommended a core set of outcome measure instruments for lower extremity motor function, balance and mobility, biomechanical metrics, and technologies for measuring quality of movement. RESULTS: Selected measures included the Fugl-Meyer Motor Assessment lower extremity subscale for motor function, the Trunk Impairment Scale for sitting balance, and the Mini Balance Evaluation System Test (Mini-BESTest) and Berg Balance Scale (BBS) for standing balance. The group recommended the Functional Ambulation Category (FAC, 0-5) for walking independence, the 10-meter Walk Test (10 mWT) for walking speed, the 6-Minute Walk Test (6 MWT) for walking endurance, and the Dynamic Gait Index (DGI) for complex walking. An FAC score of less than three should be used to determine the need for an additional standing test (FAC < 3, add BBS to Mini-BESTest) or the feasibility to assess walking (FAC < 3, 10 mWT, 6 MWT, and DGI are "not testable"). In addition, recommendations are given for prioritized kinetic and kinematic metrics to be investigated that measure recovery of movement quality of standing balance and walking, as well as for assessment protocols and preferred equipment to be used. CONCLUSIONS: The present recommendations of measures, metrics, technology, and protocols build on previous consensus meetings of the International Stroke Recovery and Rehabilitation Alliance to guide the

Introduction: Little is known about the cost-effectiveness of government policies that support primary care physicians to provide comprehensive chronic disease management (CDM). This paper aimed to estimate the potential cost-effectiveness of CDM policies over a lifetime for long-time survivors of stroke. Methods: A Markov model, using three health states (stable, hospitalised, dead), was developed to simulate the costs and benefits of CDM policies over 30 years (with 1-year cycles). Transition probabilities and costs from a health system perspective were obtained from the linkage of data between the Australian Stroke Clinical Registry (cohort n = 12,368, 42% female, median age 70 years, 45% had CDM claims) and government-held hospital, Medicare, and pharmaceutical claims datasets. Quality-adjusted life years (QALYs) were obtained from a comparable cohort (n = 512, 34% female, median age 69.6 years, 52% had CDM claims) linked with Medicare claims and death data. A 3% discount rate was applied to costs in Australian dollars (AUD, 2016) and QALYs beyond 12 months. Probabilistic sensitivity analyses were used to understand uncertainty. Results: Per-person average total lifetime costs were AUD 142,939 and 8.97 QALYs for those with a claim, and AUD 103,889 and 8.98 QALYs for those without a claim. This indicates that these CDM policies were costlier without improving QALYs. The probability of cost-effectiveness of CDM policies was 26.1%, at a willingness-to-pay threshold of AUD 50,000/QALY. Conclusion: CDM policies, designed to encourage comprehensive care, are unlikely to be cost-effective for stroke compared to care without CDM. Further research to understand how to deliver such care cost-effectively is needed.

RATIONALE: Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models. OBJECTIVE: The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task. METHODS: NL3R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed. RESULTS: In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3R451C mice. CONCLUSIONS: NL3R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes.

INTRODUCTION: Concerns exist that a potential mechanism for harm from upright activity (sitting, standing, and walking) early after an acute ischaemic stroke could be the reduction of cerebral perfusion during this critical phase. We aimed to estimate the effects of upright positions (sitting and standing) on cerebral hemodynamics within 48 h and later, 3-7 days post-stroke, in patients with strokes with and without occlusive disease and in controls. METHODS: We investigated MCAv using transcranial Doppler in 0° head position, then at 30°, 70°, 90° sitting, and 90° standing, at <48 h post-stroke, and later at 3-7 days post-stroke. Mixed-effect linear regression modeling was used to estimate differences in MCAv between the 0° and other positions and to compare MCAv changes across groups. RESULTS: A total of 42 stroke participants (anterior and posterior circulation) (13 with occlusive disease, 29 without) and 22 controls were recruited. Affected hemisphere MCAv decreased in strokes with occlusive disease (<48 h post-stroke): from 0° to 90° sitting (-9.9 cm/s, 95% CI[-16.4, -3.4]) and from 0° to 90° standing (-7.1 cm/s, 95%CI[-14.3, -0.01]). Affected hemisphere MCAv also decreased in strokes without occlusive disease: from 0° to 90° sitting (-3.3 cm/s, 95%CI[-5.6, -1.1]) and from 0° to 90° standing (-3.6 cm/s, 95%CI [-5.9, -1.3]) (p-value interaction stroke with vs. without occlusive disease = 0.07). A decrease in MCAv when upright was also observed in controls: from 0° to 90° sitting (-3.8 cm/s, 95%CI[-6.0, -1.63]) and from 0° to 90° standing (-3 cm/s, 95%CI[-5.2, -0.81]) (p-value interaction stroke vs. controls = 0.85). Subgroup analysis of anterior circulation stroke showed similar patterns of change in MCAv in the affected hemisphere, with a significant interaction between those with occlusive disease (n = 11) and those without (n = 26) (p = 0.02). Changes in MCAv from 0° to upright at <48 h post-stroke were similar to 3-7 days. No association between changes in M

Contains fulltext : 304883.pdf (Publisher’s version ) (Closed access), BACKGROUND: Mobility is a key priority for stroke survivors. Worldwide consensus of standardized outcome instruments for measuring mobility recovery after stroke is an essential milestone to optimize the quality of stroke rehabilitation and recovery studies and to enable data synthesis across trials. METHODS: Using a standardized methodology, which involved convening of 13 worldwide experts in the field of mobility rehabilitation, consensus was established through an a priori defined survey-based approach followed by group discussions. The group agreed on balance- and mobility-related definitions and recommended a core set of outcome measure instruments for lower extremity motor function, balance and mobility, biomechanical metrics, and technologies for measuring quality of movement. RESULTS: Selected measures included the Fugl-Meyer Motor Assessment lower extremity subscale for motor function, the Trunk Impairment Scale for sitting balance, and the Mini Balance Evaluation System Test (Mini-BESTest) and Berg Balance Scale (BBS) for standing balance. The group recommended the Functional Ambulation Category (FAC, 0-5) for walking independence, the 10-meter Walk Test (10 mWT) for walking speed, the 6-Minute Walk Test (6 MWT) for walking endurance, and the Dynamic Gait Index (DGI) for complex walking. An FAC score of less than three should be used to determine the need for an additional standing test (FAC < 3, add BBS to Mini-BESTest) or the feasibility to assess walking (FAC < 3, 10 mWT, 6 MWT, and DGI are "not testable"). In addition, recommendations are given for prioritized kinetic and kinematic metrics to be investigated that measure recovery of movement quality of standing balance and walking, as well as for assessment protocols and preferred equipment to be used. CONCLUSIONS: The present recommendations of measures, metrics, technology, and protocols build on previous consensus meetings of the International Stroke Recovery and Rehabilitation Alliance to guide the

Implementation of evidence-informed rehabilitation of the upper limb is variable, and outcomes for stroke survivors are often suboptimal. We established a national partnership of clinicians, survivors of stroke, researchers, healthcare organizations, and policy makers to facilitate change. The objectives of this study are to increase access to best-evidence rehabilitation of the upper limb and improve outcomes for stroke survivors. This prospective pragmatic, knowledge translation study involves four new specialist therapy centers to deliver best-evidence upper-limb sensory rehabilitation (known as SENSe therapy) for survivors of stroke in the community. A knowledge-transfer intervention will be used to upskill therapists and guide implementation. Specialist centers will deliver SENSe therapy, an effective and recommended therapy, to stroke survivors in the community. Outcomes include number of successful deliveries of SENSe therapy by credentialled therapists; improved somatosensory function for stroke survivors; improved performance in self-selected activities, arm use, and quality of life; treatment fidelity and confidence to deliver therapy; and for future implementation, expert therapist effect and cost-effectiveness. In summary, we will determine the effect of a national partnership to increase access to evidence-based upper-limb sensory rehabilitation following stroke. If effective, this knowledge-transfer intervention could be used to optimize the delivery of other complex, evidence-based rehabilitation interventions.

BACKGROUND: Hyperglycemia in acute ischemic stroke reduces the efficacy of stroke thrombolysis and thrombectomy, with worse clinical outcomes. Insulin-based therapies are difficult to implement and may cause hypoglycemia. We investigated whether exenatide, a GLP-1 (glucagon-like peptide-1) receptor agonist, would improve stroke outcomes, and control poststroke hyperglycemia with minimal hypoglycemia. METHODS: The TEXAIS trial (Treatment With Exenatide in Acute Ischemic Stroke) was an international, multicenter, phase 2 prospective randomized clinical trial (PROBE [Prospective Randomized Open Blinded End-Point] design) enrolling adult patients with acute ischemic stroke ≤9 hours of stroke onset to receive exenatide (5 µg BID subcutaneous injection) or standard care for 5 days, or until hospital discharge (whichever sooner). The primary outcome (intention to treat) was the proportion of patients with ≥8-point improvement in National Institutes of Health Stroke Scale score (or National Institutes of Health Stroke Scale scores 0-1) at 7 days poststroke. Safety outcomes included death, episodes of hyperglycemia, hypoglycemia, and adverse event. RESULTS: From April 2016 to June 2021, 350 patients were randomized (exenatide, n=177, standard care, n=173). Median age, 71 years (interquartile range, 62-79), median National Institutes of Health Stroke Scale score, 4 (interquartile range, 2-8). Planned recruitment (n=528) was stopped early due to COVID-19 disruptions and funding constraints. The primary outcome was achieved in 97 of 171 (56.7%) in the standard care group versus 104 of 170 (61.2%) in the exenatide group (adjusted odds ratio, 1.22 [95% CI, 0.79-1.88]; P=0.38). No differences in secondary outcomes were observed. The per-patient mean daily frequency of hyperglycemia was significantly less in the exenatide group across all quartiles. No episodes of hypoglycemia were recorded over the treatment period. Adverse events of mild nausea and vomiting occurred in 6 (3.5%) e

BACKGROUND: Identifying personal needs of young stroke survivors is crucial for their recovery. PURPOSE: Identify factors, burden, and significance of unmet needs of young community-living stroke survivors. MATERIALS AND METHODS: We used online advertising and word-of-mouth snowballing to recruit participants for an English language online questionnaire constructed for this purpose. Eligible participants aged 18-55 at time of stroke. Needs were classified into seven domains: Healthcare Experience, Impairments from Stroke, Everyday Activities, Work/Study, Finances, Relationships, and Social Participation. Random-effects logistic regression was used to determine the probability of unmet needs and X2 test to determine significance of distribution across domains. RESULTS: Out of 137 responses recorded: 32 did not meet inclusion criteria, 29 duplicates identified were discarded, and 76 eligible participants were analysed. Respondents were median 37 (IQR 32-47) years at time of stroke, and median 3 (1-5) years since stroke. Fifty-eight (76%) females. Modified Rankin Scale median score of 1 (1-3). Of 48 identified potential needs, 25 (IQR 19-30) were rated unmet. Twenty (IQR 15-25) considered of high significance. Unmet needs most frequently occurred in the domains: Impairments from Stroke, Finances, and Social Participation. CONCLUSIONS: There is high burden of unmet needs in community-living young stroke survivors which are spread disproportionately across the identified domains.IMPLICATIONS FOR REHABILITATIONIdentifying personal needs of young stroke survivors is crucial for their recovery.Impairments after Stroke, Finances, and Social Participation were often selected as being high burden unmet needs for community-living young people after stroke.Employing a post-stroke checklist to guide exploration of needs in young stroke may better capture which needs are unmet.

The effect of treatment dose on recovery of post-stroke aphasia is not well understood. Inconsistent conceptualization, measurement, and reporting of the multiple dimensions of dose hinders efforts to evaluate dose-response relations in aphasia rehabilitation research. We review the state of dose conceptualization in aphasia rehabilitation and compare the applicability of 3 existing dose frameworks to aphasia rehabilitation research-the Frequency, Intensity, Time, and Type (FITT) principle, the Cumulative Intervention Intensity (CII) framework, and the Multidimensional Dose Articulation Framework (MDAF). The MDAF specifies dose in greater detail than the CII framework and the FITT principle. On this basis, we selected the MDAF to be applied to 3 diverse examples of aphasia rehabilitation research. We next critically examined applicability of the MDAF to aphasia rehabilitation research and identified the next steps needed to systematically conceptualize, measure, and report the multiple dimensions of dose, which together can progress understanding of the effect of treatment dose on outcomes for people with aphasia after stroke. Further consideration is required to enable application of this framework to aphasia interventions that focus on participation, personal, and environmental interventions and to understand how the construct of episode difficulty applies across therapeutic activities used in aphasia interventions.

Background and Aims: Mobile Stroke Units (MSU) have been shown to reduce time to treatment and improve patient outcomes.There is an opportunity to improve the efficacy of stroke reperfusion treatment provided by MSUs. In the MSU environment, tenecteplase (TNK) offers practical benefits as it is administered as a single bolus rather than a one-hour infusion like alteplase (tPA). In the present study, we test the hypothesis that treatment with TNK in the MSU results in superior reperfusion on hospital arrival compared with tPA. Method(s): The Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit- TASTE-A) is a PROBE, phase II superiority RCT of TNK (0.25mg/kg) versus tPA (0.9mg/ kg) for patients presenting within 4.5 hours of symptom onset to the Melbourne MSU. The primary outcome is the volume of the perfusion lesion post treatment, on computed tomography perfusion imaging performed on arrival at the receiving hospital ED, adjusted for pre-treatment NIHSS and time from initiation of MSU treatment to ED imaging. Secondary outcomes include time for MSU arrival to treatment, NIHSS change from MSU to ED assessments and 90 day modified Rankin Score. Result(s): The trial was conducted on one MSU in Melbourne Australia which transferred enrolled patients to one of five participating hospitals. The last patient was recruited on November 16, 2021 after recruitment of the prespecified adaptive sample size of 104 patients, and the final results will be presented at the conference. Conclusion(s): To be Determined.

RationaleHaematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.Methods and designStopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.HypothesisIn patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimatesA sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.InterventionParticipants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.Primary efficacy measureThe primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.DiscussionWe describe the rationale and protocol of STOP-MSU, a phase II trial of

Background The optimal treatment for acute stroke attributable to isolated cervical internal carotid artery occlusion without intracranial target is unclear. The purpose of our study was to examine whether endovascular therapy for acute stroke attributable to isolated cervical internal carotid artery occlusion was associated with improved clinical outcome. Methods We identified patients from 2 comprehensive stroke centers during the period January 2009 to December 2019, with acute ischemic stroke attributable to cervical internal carotid artery occlusion without an intracranial occlusion. We categorized patients into 2 groups: endovascular therapy and medical therapy. Clinical outcome (modified Rankin scale score at 90 days poststroke) was compared between the 2 groups. Results Seventy‐three patients were included (26 women [36%]; median age, 69 [interquartile range (IQR), 60–80] years; median National Institutes of Health Stroke Scale score, 11 [IQR, 5–16]). Of these, 40 patients received endovascular therapy, and 33 patients were managed with medical therapy alone. The endovascular therapy group had a significantly higher median National Institutes of Health Stroke Scale score on presentation (13 versus 3; P <0.0001). Rates of thrombolysis were also significantly higher in the endovascular group (50% versus 15%; P =0.002). There were no other significant differences in baseline characteristics between the 2 groups. Good clinical outcome (modified Rankin scale score 0–2 at 90 days or no decline in modified Rankin scale score from baseline at 90 days) was seen in 73% of the endovascular therapy group compared with the 61% of the medical management group (odds ratio [OR] for good outcome, 1.7 [95% CI, 0.64–4.6]), despite the large discrepancy in baseline stroke severity. When restricted to patients with presenting National Institutes of Health Stroke Scale score ≥6, endovascular therapy was associated with higher rates of good clinical outcome (66% versus 18%; OR

INTRODUCTION: We describe the demographic, preoperative, surgical, anesthetic, and postoperative characteristics of patients who required a rapid response team (RRT) activation after major hip surgery. We determined the characteristics and outcomes of patients that require RRTs after major hip surgery, and their associations with mortality. PRESENTATION OF CASES: We retrospectively reviewed adult patients undergoing major hip surgery in a university teaching hospital. We included patients who had an RRT or "code blue" activation post-surgery and within the index hospital admission. We extracted patient, surgical, anesthetic, and postoperative variables. We explored differences between patients who survived their index hospital stay and those who died. DISCUSSION: 187 (9%) patients had a postoperative RRT activation. The median age was 84.0 (78-90) years; 125 (67%) were female, and most patients had significant comorbidities. The median Charlson Comorbidity Index (CCI) was 5.0 (4.0-7.0). Patients were frail (68%), ASA physical status ≥Class 3 (91%) and underwent emergency surgery (88%). Death after RRT activation occurred in 1 in 7 patients. Compared to patients who survived RRT activation, those who died had a higher mean CCI (6.5 [1.8] vs. 5.5 [2.1], P = 0.02), were more frail (80.1% vs. 56.5%, OR = 3.2, 95% CI: 1.2,8.1; P = 0.03), and received less intraoperative opioids (intravenous morphine equi-analgesia: median = 5.8 (0.1-8.20 vs. 11.7 (3.7-19.0) mg, P = 0.03). CONCLUSION: Mortality after RRT activation is associated with non-modifiable patients factors rather than surgical or anesthesia factors. Our findings provide opportunities for the implementation of strategies aimed at improving postoperative outcomes.

BACKGROUND AND PURPOSE: Pre-hospital severity-based triaging using the Ambulance Clinical Triage For Acute Stroke Treatment (ACT-FAST) algorithm has been demonstrated to substantially reduce time to endovascular thrombectomy in Melbourne, Australia. We aimed to model the cost-effectiveness of an ACT-FAST bypass system from the healthcare system perspective. METHODS: A simulation model was developed to estimate the long-term costs and health benefits associated with diagnostic accuracy of the ACT-FAST algorithm. Three-month post stroke functional outcome was projected to the lifetime horizon to estimate the long-term cost-effectiveness between two strategies (ACT-FAST vs. standard care pathways). For ACT-FAST screened true positives (i.e., screened positive and eligible for EVT), a 52 mins time saving was applied unanimously to the onset to arterial time for EVT, while 10 mins delay in thrombolysis was applied for false-positive (i.e., screened positive but was ineligible for EVT) thrombolysis-eligible infarction. Quality-adjusted life year (QALY) was employed as the outcome measure to calculate the incremental cost-effectiveness ratio (ICER) between the ACT-FAST algorithm and the current standard care pathway. RESULTS: Over the lifetime, ACT-FAST was associated with lower costs (-$45) and greater QALY gains (0.006) compared to the current standard care pathway, resulting in it being the dominant strategy (less costly but more health benefits). Implementing ACT-FAST triaging led to higher proportion of patients received EVT procedure (30 more additional EVT performed per 10,000 patients). The total Net Monetary Benefit from ACT-FAST care estimated at A$0.76 million based on its implementation for a single year. CONCLUSIONS: An ACT-FAST severity-triaging strategy is associated with cost-saving and increased benefits when compared to standard care pathways. Implementing ACT-FAST triaging increased the proportion of patients who received EVT procedure due to more patien

INTRODUCTION: Mobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients' prehospital with thrombolysis and transfer them to the most appropriate hospital for ongoing stroke care and thrombectomy when indicated. The effect of MSUs in both reducing the time to reperfusion treatment and improving patient outcomes is now established. There is now an opportunity to improve the efficacy of treatment provided by the MSU. Tenecteplase is a potent plasminogen activator, which may have benefits over the standard of care stroke lytic alteplase. Specifically, in the MSU environment tenecteplase presents practical benefits since it is given as a single bolus and does not require an infusion over an hour like alteplase. OBJECTIVE: In this trial, we seek to investigate if tenecteplase, given to patients with acute ischaemic stroke as diagnosed on the MSU, improves the rate of early reperfusion. METHODS AND ANALYSIS: TASTE-A is a prospective, randomised, open-label, blinded endpoint (PROBE) phase II trial of patients who had an ischaemic stroke assessed in an MSU within 4.5 hours of symptom onset. The primary endpoint is early reperfusion measured by the post-lysis volume of the CT perfusion lesion performed immediately after hospital arrival. ETHICS AND DISSEMINATION: The study was approved by the Royal Melbourne Hospital Human Ethics committee. The findings will be published in peer-reviewed journals, presented at academic conferences and disseminated among consumer and healthcare professional audiences. TRIAL REGISTRATION NUMBER: NCT04071613.

Healthcare facilities are among the most expensive buildings to construct, maintain, and operate. How building design can best support healthcare services, staff, and patients is important to consider. In this narrative review, we outline why the healthcare environment matters and describe areas of research focus and current built environment evidence that supports healthcare in general and stroke care in particular. Ward configuration, corridor design, and staff station placements can all impact care provision, staff and patient behavior. Contrary to many new ward design approaches, single-bed rooms are neither uniformly favored, nor strongly evidence-based, for people with stroke. Green spaces are important both for staff (helping to reduce stress and errors), patients and relatives, although access to, and awareness of, these and other communal spaces is often poor. Built environment research specific to stroke is limited but increasing, and we highlight emerging collaborative multistakeholder partnerships (Living Labs) contributing to this evidence base. We believe that involving engaged and informed clinicians in design and research will help shape better hospitals of the future.

Minimal sufficient balance (MSB) is a recently suggested method for adaptively controlling covariate imbalance in randomized controlled trials in a manner which reduces the impact on randomness of allocation over other approaches by only intervening when the imbalance is sufficiently significant. Despite its improvements, the approach is unable to consider the relative clinical importance or magnitude of imbalance in each covariate weight, and ignores any imbalance which is not statistically significant, even when these imbalances may collectively justify intervention. We propose the common scale MSB (CS-MSB) method which addresses these limitations, and present simulation studies comparing our proposed method to MSB. We demonstrate that CS-MSB requires less intervention than MSB to achieve the same level of covariate balance, and does not adversely impact either statistical power or Type-I error.

OBJECTIVE: Prior uncontrolled studies have reported seizure reductions following deep brain stimulation (DBS) in patients with Lennox-Gastaut syndrome (LGS), but evidence from randomized controlled studies is lacking. We aimed to formally assess the efficacy and safety of DBS to the centromedian thalamic nucleus (CM) for the treatment of LGS. METHODS: We conducted a prospective, double-blind, randomized study of continuous, cycling stimulation of CM-DBS, in patients with LGS. Following pre- and post-implantation periods, half received 3 months of stimulation (blinded phase), then all received 3 months of stimulation (unblinded phase). The primary outcome was the proportion of participants with ≥50% reduction in diary-recorded seizures in stimulated versus control participants, measured at the end of the blinded phase. A secondary outcome was the proportion of participants with a ≥50% reduction in electrographic seizures on 24-hour ambulatory electroencephalography (EEG) at the end of the blinded phase. RESULTS: Between November 2017 and December 2019, 20 young adults with LGS (17-37 years;13 women) underwent bilateral CM-DBS at a single center in Australia, with 19 randomized (treatment, n = 10 and control, n = 9). Fifty percent of the stimulation group achieved ≥50% seizure reduction, compared with 22% of controls (odds ratio [OR] = 3.1, 95% confidence interval [CI] = 0.44-21.45, p = 0.25). For electrographic seizures, 59% of the stimulation group had ≥50% reduction at the end of the blinded phase, compared with none of the controls (OR= 23.25, 95% CI = 1.0-538.4, p = 0.05). Across all patients, median seizure reduction (baseline vs study exit) was 46.7% (interquartile range [IQR] = 28-67%) for diary-recorded seizures and 53.8% (IQR = 27-73%) for electrographic seizures. INTERPRETATION: CM-DBS in patients with LGS reduced electrographic rather than diary-recorded seizures, after 3 months of stimulation. Fifty percent of all participants had diary-recorded seizures

BACKGROUND AND PURPOSE: The evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. METHODS: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI data to the first month after stroke was assessed using unified segmentation in SPM12. We hypothesized that age, ischemic brain lesion size, and white matter (WM) changes were associated with larger brain volume change. Enlarged perivascular spaces (EPVSs) and white matter hyperintensities (WMHs) were rated visually and the presence of lacunes was assessed. RESULTS: We enrolled 173 patients with a mean age of 67 ± 11 years, 44% were women. There was a median 6 ml decrease in volume (25th percentile -1 ml to 75th percentile 21 ml) over time, equivalent to a median 0.5% (interquartile range [IQR], -0.07%-1.4%), decrease in brain volume. Age was associated with larger brain volume loss (per 10 years of age, 5 ml 95% CI 2-8 ml). Baseline diffusion weighted imaging (DWI) lesion volume was not associated with greater volume loss per 10 ml of lesion volume, change by 0 ml (95% CI -0.1 to 0.1 ml). Increasing Fazekas scores of deep WMH were associated with greater tissue loss (5 ml, 95% CI 1-10 ml). CONCLUSIONS: Total brain volume changes in a heterogenous fashion after stroke. Volume loss occurs over 1 month after stroke and is associated with age and deep WM disease. We did not find evidence that more severe strokes lead to increased early tissue loss.

AIMS: We reprocessed the Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) perfusion imaging with a different automated software with the aim of comparing mismatch eligibility and outcomes. METHODS: EXTEND baseline perfusion imaging data were reprocessed using autoMIStar software to identify patients who were eligible based on the same target mismatch criteria as per the original trial. RESULTS: From the 225 patients fulfilling RAPID-based mismatch criteria randomized in the EXTEND study, 196 (87%) patients met the revised mismatch criteria. Most common reasons for not meeting revised criteria were core >70 ml (n = 9), and no perfusion lesion/lack of penumbral tissue (n = 20). The revised perfusion lesion volumes were significantly smaller compared to the original RAPID volumes (median 68 ml IQR 34-102 ml vs. 42 ml 16-92 ml, p = 0.036). Of the patients who met the revised mismatch criteria, 40% receiving alteplase had modified Rankin Scale (mRS) 0-1 at 3-month compared to 28% with placebo (Adjusted Odds Ratio (OR) = 2.23, CI 1.08-4.58, p = 0.028). In contrast, in the original mismatch cohort, 35% receiving alteplase had mRS 0-1 at 3-month compared to 30% with placebo (adjusted OR = 1.88, p = 0.056). CONCLUSIONS: These data reinforce the benefit of alteplase in the later time window, and suggest that differences in automated perfusion imaging software outputs may be clinically relevant.

BACKGROUND AND PURPOSE: The benefit regarding co-treatment with intravenous (IV) thrombolysis before mechanical thrombectomy in acute ischemic stroke with large vessel occlusion remains unclear. To test the hypothesis that clinical outcome of ischemic stroke patients with intracranial internal carotid artery, middle cerebral artery or basilar artery occlusion treated with direct endovascular thrombectomy within 4.5 hours will be non-inferior compared with that of standard bridging IV thrombolysis followed by endovascular thrombectomy. METHODS: To randomize 780 patients 1:1 to direct thrombectomy or bridging IV thrombolysis with thrombectomy. An international-multicenter prospective randomized open label blinded endpoint trial (PROBE) (ClincalTrials.gov identifier: NCT03494920). RESULTS: Primary endpoint is functional independence defined as modified Rankin Scale (mRS) 0-2 or return to baseline at 90 days. Secondary end points include ordinal mRS analysis, good angiographic reperfusion (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b-3), safety endpoints include symptomatic intracerebral hemorrhage and death. CONCLUSION: s DIRECT-SAFE will provide unique information regarding the impact of direct thrombectomy in patients with large vessel occlusion, including patients with basilar artery occlusion, with comparison across different ethnic groups.

Continuous glucose monitoring (CGM) is rapidly becoming a vital tool in the management of type 1 diabetes. Its use has been shown to improve glycaemic management and reduce the risk of hypoglycaemic events. The cost of CGM remains a barrier to its widespread application. We aimed to identify and synthesize evidence about the cost-effectiveness of utilizing CGM in patients with type 1 diabetes. Studies were identified from MEDLINE, Embase and Cochrane Library from January 2010 to February 2022. Those that assessed the cost-effectiveness of CGM compared to self-monitored blood glucose (SMBG) in patients with type 1 diabetes and reported lifetime incremental cost-effectiveness ratio (ICER) were included. Studies on critically ill or pregnant patients were excluded. Nineteen studies were identified. Most studies compared continuous subcutaneous insulin infusion and SMBG to a sensor-augmented pump (SAP). The estimated ICER range was [$18,734-$99,941] and the quality-adjusted life year (QALY) gain range was [0.76-2.99]. Use in patients with suboptimal management or greater hypoglycaemic risk revealed more homogenous results and lower ICERs. Limited studies assessed CGM in the context of multiple daily injections (MDI) (n = 4), MDI and SMBG versus SAP (n = 2) and three studies included hybrid closed-loop systems. Most studies (n = 17) concluded that CGM is a cost-effective tool. This systematic review suggests that CGM appears to be a cost-effective tool for individuals with type 1 diabetes. Cost-effectiveness is driven by reducing short- and long-term complications. Use in patients with suboptimal management or at risk of severe hypoglycaemia is most cost-effective.

Objective: To conduct a per-protocol analysis on thigh muscle volume outcomes from the Spinal Cord Injury and Physical Activity (SCIPA) Switch-On Trial.Design: Secondary analysis from an assessor-blind randomized, controlled trial.Setting: Four acute/sub-acute hospitals in Australia and New Zealand.Participants: 24 adults (1 female) within four weeks of motor complete or incomplete spinal cord injury (SCI)Intervention: Functional electrical stimulation-assisted cycling (FESC) or passive cycling (PC) 4x/week for 12 weeks.Outcome Measures: Whole thigh and muscle group volumes calculated from manually segmented MR images.Results: 19/24 participants completed ≥ twelve weeks of the intervention. Five participants experienced hypertrophy (4 FESC; 1 PC) and eight attenuation of atrophy (<20% volume loss) (3 FESC; 5 PC) in thigh muscle volume. Six participants were non-responders, exhibiting atrophy >20% (3 FESC; 3 PC). Mean (SD) change for FESC was -2.3% (25.3%) and PC was -14.0% (12.3%). After controlling for baseline muscle volumes, a strong significant correlation was found between mean weekly exercise frequency and quadriceps and hamstring volumes (r=6.25, P=0.006), regardless of mode. Average watts was highly correlated to quadriceps volumes only (r=5.92, P=0.01), while total number of sessions was strongly correlated with hamstring volumes only (r=5.91, P=0.01).Conclusion: This per-protocol analysis of FESC and PC early after SCI reports a partial response in 42% and a beneficial response in 25% of patients who completed 12 weeks intervention, regardless of mode. Strong correlations show a dose-response according to exercise frequency. Characteristics of non-responders are discussed to inform clinical decision-making.

BACKGROUND: Understanding cultural differences between geographical regions is essential in delivering culturally appropriate healthcare. We aimed to describe the characteristics and outcomes of diverse clients using the Far North Mental Health and Wellbeing Service (FNS) and the Central West Health and Wellbeing Service (CWS). METHODS: We conducted a cohort study within Queensland, Australia, on all clients who received a mental health therapy session at either the FNS or the CWS. Patient data was prospective data collected form July 2019 to December 2020. FINDINGS: There were1202 clients, with a median number of individual contacts per-client of 3.0 (IQR 2.0-6.0). There was 428 (35.6% 95% CI 32.90-38.39) males and 772 (64.2% 95% CI 61.44-66.94) females with a median age across the genders of 38.0 (IQR 28.0-51.0). There was 505 (42.0% 95% CI 39.20-44.86) identifying as Indigenous and 697 (58.0% 95% CI 55.14-60.80) as non-Indigenous Australians. The FNS had a significantly higher proportion of Indigenous clients (n=484; 54.8% 95% CI 51.46-58.13) as compared to the CWS (n=21; 6.6% 95% CI 4.12-9.89). Of the 1202 clients, 946 (78.7% 95% CI 76.28-80.99) had a socio-economic classification of 'most disadvantaged', consisting of 740 (83.8%) clients from the FNS and 206 (64.6%) clients from the CWS. The majority of presentations were for neurotic, stress-related and somatoform disorders (n=568; 47.3%), followed by mood affective disorders (n=310; 25.8%). The overall number of treatments strategies employed was 10798, equalling a median of 6.0 (IQR 4.0-9.0) strategies per-client, with the leading strategies being counselling/psychosocial (n=1394; 12.9%), reflective listening (n=1191; 11.0%), and strengths based reasoning (n=1116; 10.3%). There were 511 (42.5%) clients who completed the Kessler Psychological Distress Scale (K10/K5), with 493 (41.0%) clients not offered as deemed not culturally appropriate by the treating team. The mean initial K10/K5 score was 23.7 (SD 9.4)