Implementation of an optimised tele-medicine platform for stroke in South Australia improves patient care.

Background: Patients with a large vessel occlusion require a transfer from a primary stroke centre to access thrombectomy, often over significant distances in regional areas. We sought to optimise stroke care access in the regional South Australian Tele-Strokeservice (SATS) to improve patient access to thrombectomy. Methods: We undertook a 24-month interventional historically controlled cohort study comparing acute stroke care metrics in the SATS. This consisted of a 12-month control period and a 12-month intervention monitoring period. The study intervention considered of an education package provided to the regional hospitals, a stroke neurologist roster to receive consultations and the intervention of a centralised tele-stroke system to provide treatment advice and organise patient transfers where needed. The SATS services 61 rural hospitals in South Australia, and Alice Springs in the Northern Territory. Suspected acute stroke patients presenting to the participating regional hospitals in SATS network where a telehealth consultation took place. Results: Over the study period, there were 919 patient referrals, with 449 consultations in the pre-intervention phase and 470 in the post-intervention phase. Demographic features in both epochs were similar. The post-intervention phase was associated with shorter door-to-scan time (35 min, IQR: 18,70; vs. 49 min, IQR:25,102, p < 0.0001), faster door-to-thrombolysis time (58 min, IQR: 39,91, vs.83 min, IQR: 55,100, p = 0.0324) and a higher portion of patients treated with thrombectomy (54, 11.5% vs. 26, 5.8%, p = 0.002). Conclusion: An optimised implementation of a streamlined telehealth platform with ongoing education and feedback to referring sites was associated with improved stroke workflow metrics and higher thrombectomy rates.

First stroke incidence, causes, treatments, and outcomes for Aboriginal Peoples in South Australia and the Northern Territory: a pilot prospective study.

OBJECTIVE: We performed a pilot stroke incidence study, focused on feasibility and inclusion of the CONSIDER reporting guidelines, to model the design of a future population-based study aiming to definitively determine stroke incidence, antecedents, treatment, and outcomes. STUDY DESIGN: Prospective stroke incidence study (pilot study). SETTING, PARTICIPANTS: All people aged 15 years or older who lived in postcode-defined areas of South Australia and Northern Territory (885 472 people, including 45 127 Aboriginal people [5.1%]) diagnosed with stroke for the first time during 1 October - 31 December 2015 and admitted to public hospitals or stroke and transient ischaemic attack clinics. MAIN OUTCOME MEASURES: Feasibility of a prospective population-based stroke incidence study. RESULTS: Of the 123 participants with first strokes, ten were Aboriginal (8%); the median age of Aboriginal people was 45 years (interquartile range [IQR], 33-55 years), of non-Indigenous people 73 years (IQR, 62-84 years). For Aboriginal people, the age-standardised incidence of stroke was 104 (95% confidence interval [CI], 84-124) per 100 000 person-years, for non-Indigenous people 33 (95% CI, 22-44) per 100 000 person-years. We found that a prospective population-based stroke incidence study in Aboriginal people was feasible, including with respect to establishing an adequate sample size, diagnostic confirmation, identification of incident stroke, confirming stroke subtypes, establishing a stable statistical population, standardising data reporting for comparison with other stroke incidence studies, and ethical research reporting that conforms to CONSIDER guidelines. CONCLUSIONS: A larger, population-based study of the incidence of stroke in Aboriginal people is both feasible and needed to provide robust estimates of stroke incidence, antecedents, treatments and outcomes to help guide strategies for reducing the risk of and outcomes of stroke in Aboriginal people.

Predictions for functional outcome and mortality in acute ischaemic stroke following successful endovascular thrombectomy.

Background: Accurate outcome predictions for patients who had ischaemic stroke with successful reperfusion after endovascular thrombectomy (EVT) may improve patient treatment and care. Our study developed prediction models for key clinical outcomes in patients with successful reperfusion following EVT in an Australian population. Methods: The study included all patients who had ischaemic stroke with occlusion in the proximal anterior cerebral circulation and successful reperfusion post-EVT over a 7-year period. Multivariable logistic regression and Cox regression models, incorporating bootstrap and multiple imputation techniques, were used to identify predictors and develop models for key clinical outcomes: 3-month poor functional status; 30-day, 1-year and 3-year mortality; survival time. Results: A total of 978 patients were included in the analyses. Predictors associated with one or more poor outcomes include: older age (ORs for every 5-year increase: 1.22-1.40), higher premorbid functional modified Rankin Scale (ORs: 1.31-1.75), higher baseline National Institutes of Health Stroke Scale (ORs: 1.05-1.07) score, higher blood glucose (ORs: 1.08-1.19), larger core volume (ORs for every 10 mL increase: 1.10-1.22), pre-EVT thrombolytic therapy (ORs: 0.44-0.56), history of heart failure (outcome: 30-day mortality, OR=1.87), interhospital transfer (ORs: 1.42 to 1.53), non-rural/regional stroke onset (outcome: functional dependency, OR=0.64), longer onset-to-groin puncture time (outcome: 3-year mortality, OR=1.08) and atherosclerosis-caused stroke (outcome: functional dependency, OR=1.68). The models using these predictors demonstrated moderate predictive abilities (area under the receiver operating characteristic curve range: 0.752-0.796). Conclusion: Our models using real-world predictors assessed at hospital admission showed satisfactory performance in predicting poor functional outcomes and short-term and long-term mortality for patients with successful reperfusion following EVT. These can be used to inform EVT treatment provision and consent.

Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial.

BACKGROUND: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. METHODS: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. FINDINGS: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). INTERPRETATION: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. FUNDING: Australian National Health Medical Research Council; Boehringer Ingelheim.

External Validation of a Model for Persistent Perfusion Deficit in Patients With Incomplete Reperfusion After Thrombectomy: EXTEND-PROCEED.

BACKGROUND AND OBJECTIVES: We recently developed a model (PROCEED) that predicts the occurrence of persistent perfusion deficit (PPD) at 24 hours in patients with incomplete angiographic reperfusion after thrombectomy. This study aims to externally validate the PROCEED model using prospectively acquired multicenter data. METHODS: Individual patient data for external validation were obtained from the Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection, Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke part 1 and 2 trials, and a prospective cohort of the Medical University of Graz. The model's primary outcome was the occurrence of PPD, defined as a focal, wedge-shaped perfusion delay on 24-hour follow-up perfusion imaging that corresponds to the capillary phase deficit on last angiographic series in patients with

Incidence of thrombocytopenia-associated cerebral venous sinus thrombosis: a population-based study.

Objectives: The identification of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia (VITT) followed the recognition of a hitherto uncommon clinical syndrome frequently associated with cerebral venous sinus thrombosis (CVST), termed 'thrombosis with thrombocytopenia' syndrome (TTS). While anecdotally recognised as rare, the background incidence of TTS is unknown. We therefore aimed to investigate the background incidence of CVST with TTS in a large, well-defined population-based CVST cohort. Methods: We performed an analysis of our previously obtained retrospective population-based cohort of patients with CVST from Adelaide, Australia (2005-2011, comprising an adult population of 953 390) to identify the background incidence of CVST associated with TTS. Results: Among 105 people with CVST, the background population-based incidence of TTS-associated CVST was 1.2 per million per year (95% CI 0.5 to 2.4). A single case of a severe CVST VITT-like syndrome with multiorgan thrombosis was identified, occurring 3 weeks postrotavirus infection. Conclusions: In our population-based study, the background incidence of CVST with associated TTS was very low, and the sole clinically severe case with multiorgan thrombosis occurred following a rotaviral precipitant. Our study establishes a benchmark against which to measure future potential 'TTS' clusters and suggests that viruses other than adenovirus may trigger this syndrome.

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke with Proven Occlusion (TEMPO-2): Rational and design of a multicenter, randomized open-label clinical trial.

BACKGROUND: Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials. DESIGN: TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) is a prospective, open label with blinded outcome assessment, randomized controlled trial, designed to test the superiority of intravenous tenecteplase (0.25 mg/kg) over nonthrombolytic standard of care, with an estimated sample size of 1274 patients. Adult patients presenting with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) ⩽ 5 and visible arterial occlusion or perfusion deficit within 12 h of onset are randomized to receive either tenecteplase (0.25 mg/kg) or standard of care. The primary outcome is return to baseline neurological functioning, measured by the modified Rankin scale (mRS) at 90 days. Safety outcomes include death and symptomatic hemorrhage (intra or extra-cranial). Other secondary outcomes include mRS 0-1, mRS 0-2, ordinal shift analysis of the mRS, partial, and full recanalization on follow-up computed tomography angiogram. CONCLUSION: Results of this trial will aid in determining whether there is benefit of using tenecteplase (0.25 mg/kg) in treating patients presenting with minor stroke who are at high risk of developing poor outcomes due to presence of an intracranial occlusion. DATA ACCESS STATEMENT: Data will be available upon reasonable request.

Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial.

BACKGROUND: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. METHODS: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. FINDINGS: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). INTERPRETATION: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. FUNDING: Australian Government Medical Research Future Fund.

Determining the Optimal Methodology for Identifying Incident Stroke Deaths Using Administrative Datasets Within Australia.

BACKGROUND AND AIM: Quantifying stroke incidence and mortality is crucial for disease surveillance and health system planning. Administrative data offer a cost-effective alternative to "gold standard" population-based studies. However, the optimal methodology for establishing stroke deaths from administrative data remains unclear. We aimed to determine the optimal method for identifying stroke-related deaths in administrative datasets as the fatal component of stroke incidence, comparing counts derived using underlying and all causes of death (CoD). METHOD: Using whole-population multijurisdictional person-level linked data from hospital and death datasets from South Australia, the Northern Territory, and Western Australia, we identified first-ever stroke events between 2012 and 2015, using underlying CoD and all CoD to identify fatal stroke counts. We determined the 28-day case fatality for both counts and compared results with gold standard Australian population-based stroke incidence studies. RESULTS: The total number of incident stroke events was 16,150 using underlying CoD and 18,074 using all CoD. Case fatality was 24.7% and 32.7% using underlying and all CoD, respectively. Case fatality using underlying CoD was similar to that observed in four Australian "gold standard" population-based studies (20%-24%). CONCLUSIONS: Underlying CoD generates fatal incident stroke estimates more consistent with population-based studies than estimates based on stroke deaths identified from all-cause fields in death registers.

Disseminated Aspergillosis with Mediastinal Invasion Causing Fatal Stroke in an Immunocompetent Young Man.

Introduction: Aspergillus flavus is a common cause of aspergillosis. Case Presentation: A previously fit and well, immunocompetent 27-year-old male living in Australia developed disseminated A. flavus complex infection with mediastinal and cardiac invasion, superior vena cava obstruction and stroke, with fatal haemorrhagic transformation. Conclusion: Aspergillus Flavus is a rare but important cause of serious disease in the immunocompetent.

Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial.

BACKGROUND: The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. METHODS: SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. RESULTS: Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (Pinteraction=0.77). CONCLUSIONS: ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

Large vessel occlusive stroke with milder baseline severity shows better collaterals and reduced harm from thrombectomy transfer delays.

BACKGROUND: Patients with large vessel occlusion (LVO) stroke presenting with milder baseline clinical severity are common and require endovascular thrombectomy. However, such patients are difficult to recognize using pre-hospital severity-based triage tools and therefore are likely to require a secondary inter-hospital transfer if transported to a non-thrombectomy center. Given the potential for milder severity to represent better underlying cerebrovascular collateral circulation, it is unknown whether transfer delays are still associated with poorer post-stroke outcomes in this patient group. AIMS: We primarily aimed to examine whether the harmful effect of inter-hospital transfer delay for thrombectomy was different for LVO patients with mild or severe deficits. Secondarily, we also investigated whether imaging markers of collateral circulation were different between severity groups. METHODS: Registry data from two large Australian thrombectomy centers were used to identify all directly presenting and secondarily transferred LVO patients undergoing thrombectomy, divided into those with lower (NIHSS < 10) and higher (NIHSS ⩾ 10) baseline deficits. The primary outcome was the functional independence or return to baseline defined as modified Rankin Scale 0-2 or baseline at 90 days. Patients with complete baseline CT-perfusion data were analyzed for imaging markers of collateral circulation by baseline severity group. RESULTS: A total of 1210 LVO patients undergoing thrombectomy were included, of which 273 (22.6%) had lower baseline severity. Despite similar thrombolysis and recanalization rates, transferred patients had lower odds of achieving the primary outcome compared to the primary presentation to a thrombectomy center, where baseline severity was higher (adjusted odds ratio (aOR) 0.759 (95% CI 0.576-0.999)), but not when severity was lower (aOR 1.357 (95% CI 0.764-2.409), p-interaction = 0.122). In the imaging analysis of 436 patients, those with milder severity showed smaller median ischemic core volumes (12.6 (IQR 0.0-17.9) vs 27.5 (IQR 6.5-37.1) mL, p < 0.001)), higher median perfusion mismatch ratio (10.8 (IQR 4.8-54.5) vs 6.6 (IQR 3.5-16.5), p < 0.001), and lower median hypoperfusion intensity ratio (0.25 (IQR 0.18-0.38) vs 0.40 (IQR 0.22-0.57), p < 0.001). DISCUSSION: Patients receiving secondary inter-hospital transfer for thrombectomy had poorer outcomes compared to those presenting directly to a thrombectomy center if baseline deficits were severe, but this difference was not observed when baseline deficits were milder. This result may potentially be due to our secondary findings of significantly improved collateral circulation markers in lower-severity LVO patients. As such, failure of pre-hospital screening tools to detect lower-severity LVO patients for pre-hospital bypass to a thrombectomy center may not necessarily deleteriously affect outcome. DATA ACCESS STATEMENT: Anonymized data not published within this article will be made available on request from any qualified investigator.

Association of Time to Thrombolysis With Early Reperfusion After Alteplase and Tenecteplase in Patients With Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: Early treatment with intravenous alteplase increases the probability of lytic-induced reperfusion in large vessel occlusion (LVO) patients. The relationship of tenecteplase-induced reperfusion and the timing of thrombolytic administration has not been explored. In this study, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates and assessed their relationship to the time of thrombolytic administration. METHODS: Patients who were initially treated with a thrombolytic within 4.5 hours of symptom onset were pooled from the Royal Melbourne Stroke Registry, EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK part 2 trials. The primary outcome, thrombolytic-induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at initial angiographic assessment (or repeat CT perfusion/angiography). We compared the treatment effect of tenecteplase and alteplase through fixed-effects Poisson regression modelling. RESULTS: Among 846 patients included in the primary analysis, early reperfusion was observed in 173 (20%) patients (tenecteplase: 98/470 [21%], onset-to-thrombolytic time: 132 minutes [interquartile range (IQR): 99-170], and thrombolytic-to-assessment time: 61 minutes [IQR: 39-96]; alteplase: 75/376 [19%], onset-to-thrombolytic time: 143 minutes [IQR: 105-180], thrombolytic-to-assessment time: 92 minutes [IQR: 63-144]). Earlier onset-to-thrombolytic administration times were associated with an increased probability of thrombolytic-induced reperfusion in patients treated with either tenecteplase (adjusted risk ratio [aRR] 1.05 per 15 minutes [95% confidence interval (CI) 1.00-1.12] or alteplase (aRR 1.06 per 15 minutes [95% CI 1.00-1.13]). Tenecteplase remained associated with higher rates of reperfusion vs alteplase after adjustment for onset-to-thrombolytic time, occlusion site, thrombolytic-to-assessment time, and study as a fixed effect, (adjusted incidence rate ratio: 1.41 [95% CI 1.02-1.93]). No significant treatment-by-time interaction was observed (p = 0.87). DISCUSSION: In patients with LVO presenting within 4.5 hours of symptom onset, earlier thrombolytic administration increased successful reperfusion rates. Compared with alteplase, tenecteplase was associated with a higher probability of lytic-induced reperfusion, independent of onset-to-lytic administration times. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifiers: NCT02388061, NCT03340493. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with LVO receiving a thrombolytic, reperfusion was more likely with tenecteplase than alteplase.

The role of decompressive craniectomy following microsurgical repair of a ruptured aneurysm: Analysis of a South Australian cerebrovascular registry.

OBJECTIVE: Decompressive craniectomy (DC) remains a controversial intervention for intracranial hypertension among patients with aneurysmal subarachnoid haemorrhage (aSAH). METHODS: We identified aSAH patients who underwent DC following microsurgical aneurysm repair from a prospectively maintained registry and compared their outcomes with a propensity-matched cohort who did not. Logistic regression was used to identify predictors of undergoing decompressive surgery and post-operative outcome. Outcomes of interest were inpatient mortality, unfavourable outcome, NIS-Subarachnoid Hemorrhage Outcome Measure and modified Rankin Score (mRS). RESULTS: A total of 246 patients with aSAH underwent clipping of the culprit aneurysm between 01/09/2011 and 20/07/2020. Of these, 46 underwent DC and were included in the final analysis. Unsurprisingly, DC patients had a greater chance of unfavourable outcome (p < 0.001) and higher median mRS (p < 0.001) at final follow-up. Despite this, almost two-thirds (64.1 %) of DC patients had a favourable outcome at this time-point. When compared with a propensity-matched cohort who did not, patients treated with DC fared worse at all endpoints. Multivariable logistic regression revealed that the presence of intracerebral haemorrhage and increased pre-operative mid-line shift were predictive of undergoing DC, and WFNS grade ≥ 4 and a delayed ischaemic neurological deficit requiring endovascular angioplasty were associated with an unfavourable outcome. CONCLUSIONS: Our data suggest that DC can be performed with acceptable rates of morbidity and mortality. Further research is required to determine the superiority, or otherwise, of DC compared with structured medical management of intracranial hypertension in this context, and to identify predictors of requiring decompressive surgery and patient outcome.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Renal disease is not associated with delays in hyperacute stroke management in South Australia.

OBJECTIVE: The aims of the present study were to determine how renal disease is associated with the time to receive hyperacute stroke care. METHODS: The present study involved a 5-year cohort of all patients admitted to stroke units in South Australia. RESULTS: In those with pre-existing renal disease there were no significant differences in the time taken to receive a scan, thrombolysis or endovascular thrombectomy. CONCLUSIONS: The present study shows that in protocolised settings there were no significant delays in hyperacute stroke management for patients with renal disease.

Rapid outpatient transient ischemic attack clinic and stroke service activity during the SARS-CoV-2 pandemic: a multicenter time series analysis.

Background and aim: Rapid outpatient evaluation and treatment of TIA in structured clinics have been shown to reduce stroke recurrence. It is unclear whether short-term downtrends in TIA incidence and admissions have had enduring impact on TIA clinic activity. This study aims to measure the impact of the pandemic on hospitals with rapid TIA clinics. Methods: Relevant services were identified by literature search and contacted. Three years of monthly data were requested - a baseline pre-COVID period (April 2018 to March 2020) and an intra-COVID period (April 2020 to March 2021). TIA presentations, ischemic stroke presentations, and reperfusion trends inclusive of IV thrombolysis (IVT) and endovascular thrombectomy (EVT) were recorded. Pandemic impact was measured with interrupted time series analysis, a segmented regression approach to test an effect of an intervention on a time-dependent outcome using a defined impact model. Results: Six centers provided data for a total of 6,231 TIA and 13,191 ischemic stroke presentations from Australia (52.1%), Canada (35.0%), Italy (7.6%), and England (5.4%). TIA clinic volumes remained constant during the pandemic (2.9, 95% CI -1.8 to 7.6, p = 0.24), as did ischemic stroke (2.9, 95% CI -7.8 to 1.9, p = 0.25), IVT (-14.3, 95% CI -36.7, 6.1, p < 0.01), and EVT (0, 95% CI -16.9 to 16.9, p = 0.98) counts. Proportion of ischemic strokes requiring IVT decreased from 13.2 to 11.4% (p < 0.05), but those requiring EVT did not change (16.0 to 16.7%, p = 0.33). Conclusion: This suggests that the pandemic has not had an enduring effect on TIA clinic or stroke service activity for these centers. Furthermore, the disproportionate decrease in IVT suggests that patients may be presenting outside the IVT window during the pandemic - delays in seeking treatment in this group could be the target for public health intervention.

Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index: A Systematic Review.

BACKGROUND AND OBJECTIVES: Cardiovascular disease contributes significantly to disease burden among many Indigenous populations. However, data on stroke incidence in Indigenous populations are sparse. We aimed to investigate what is known of stroke incidence in Indigenous populations of countries with a very high Human Development Index (HDI), locating the research in the broader context of Indigenous health. METHODS: We identified population-based stroke incidence studies published between 1990 and 2022 among Indigenous adult populations of developed countries using PubMed, Embase, and Global Health databases, without language restriction. We excluded non-peer-reviewed sources, studies with fewer than 10 Indigenous people, or not covering a 35- to 64-year minimum age range. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. We assessed quality using "gold standard" criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and CONSIDER criteria for reporting of Indigenous health research. An Indigenous Advisory Board provided oversight for the study. RESULTS: From 13,041 publications screened, 24 studies (19 full-text articles, 5 abstracts) from 7 countries met the inclusion criteria. Age-standardized stroke incidence rate ratios were greater in Aboriginal and Torres Strait Islander Australians (1.7-3.2), American Indians (1.2), Sámi of Sweden/Norway (1.08-2.14), and Singaporean Malay (1.7-1.9), compared with respective non-Indigenous populations. Studies had substantial heterogeneity in design and risk of bias. Attack rates, male-female rate ratios, and time trends are reported where available. Few investigators reported Indigenous stakeholder involvement, with few studies meeting any of the CONSIDER criteria for research among Indigenous populations. DISCUSSION: In countries with a very high HDI, there are notable, albeit varying, disparities in stroke incidence between Indigenous and non-Indigenous populations, although there are gaps in data availability and quality. A greater understanding of stroke incidence is imperative for informing effective societal responses to socioeconomic and health disparities in these populations. Future studies into stroke incidence in Indigenous populations should be designed and conducted with Indigenous oversight and governance to facilitate improved outcomes and capacity building. REGISTRATION INFORMATION: PROSPERO registration: CRD42021242367.