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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., From the 225 patients fulfilling RAPID‐based mismatch criteria randomized in EXTEND, 196 patients met revised mismatch criteria. Of the patients who met revised mismatch criteria, the alteplase group has a higher chance of achieving an excellent outcome than the placebo. Our study reinforces the benefit of alteplase in the later time window in patients selected with perfusion imaging and indicates that differences in automated perfusion imaging software outputs may be clinically relevant.

© 2019 AMPCo Pty Ltd Objectives: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). Design, setting, participants: Men and women aged 55–60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. Methods: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55–60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. Main outcome: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. Results: 21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. Conclusions: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.

Many stroke patients are discharged home due to advances in treatment approaches and reduced residual disability. The aim of this study was to understand health professionals' perspectives on the discharge process and continuity of care during the transition between hospital and home for stroke survivors. In this qualitative, descriptive study, we used focus groups with 25 health professionals involved in discharge processes for transition from hospital to home in 2014, in a regional area of Australia. Discontinuity in the discharge process was affected by pressure to discharge patients, discharge medications and associated risks, inadequate or late discharge summaries, and challenges involving carers. Discontinuity in post-discharge services and follow up was affected by availability of post-discharge services, number of services arranged at the time of discharge, general practitioner follow up after discharge, delays and waiting lists, carer problems, and long-term follow up. There were complex organizational barriers to the continuity of care for stroke survivors discharged home. It is important to address these deficits so that stroke survivors and their carers can make the transition home with minimal risk and adequate support following a stroke.

In this cross-sectional study, we evaluated the quality of discharge documentation for stroke patients discharged home. Participants were stroke patients discharged from a regional tertiary acute and rehabilitation hospital in Australia from 2014 to 2015. Compliance with expected discharge documentation and its relationship with readmission was measured using an audit instrument for stroke patients (n = 54), and a post-discharge survey of carers was conducted. There were deficits in the documentation of the mechanism of stroke (70%), functional assessments (58%), pending test results (39%), types of support services required after discharge (35%), and patient/carer meetings with the multi-disciplinary stroke team (20%). Readmission was associated with lower compliance scores for information provided to patients or their carer. The survey results suggested that carer burden was high for carers of stroke patients discharged home. Documentation of carer/family meetings with the stroke team, functional assessments, medications, and adequate support services needs to be improved. General practitioners and carers need this information, so that they can address the post-discharge needs of these vulnerable patients.

Objectives Identification of a biomarker for acute recanalization could have significant clinical impact. Methods We prospectively collected baseline, 24-h, and 90-day clinical and imaging data from consecutive ischemic stroke patients who fulfilled standard clinical eligibility criteria for treatment with intravenous recombinant tissue plasminogen activator (rtPA). Computed tomography angiography was acquired at 24 h and assessed using the thrombolysis is myocardial infarction (TIMI) scale with a score of 2b/3 indicating recanalization. Blood samples collected at 24 h after stroke symptom onset were used to measure the inflammatory biomarkers of glycoprotein IIb (CD41) expressing microparticles (MP), C-reactive protein (CRP), COX 2, APOE, and Angiopoietin 1. Analysis was performed using linear regression and Pearson's correlation coefficient. Results A total of 57 patients met study eligibility criteria and had sufficient data and sample quality to be analyzed. Circulating levels of platelet derived CD41 + MP were significantly related to reperfusion (Pearson correlation, PC: 0.554, P < 0.001) and recanalization (PC: 0.495, P < 0.001) as well as related with 3-month modified Rankin Score (PC: 0.483, P < 0.001). CRP was significantly negatively correlated with recanalization on 24 h CTA (PC: −0.292, P = 0.041). Backward logistic regression with CRP and CD41 + MP increased the association with reperfusion (r2 = 0.357 P < 0.001). Interpretation There is a significant relationship between the inflammatory biomarkers CD41 + MP and CRP and recanalization.

Task-switching performance relies on a broadly distributed frontoparietal network and declines in older adults. In this study, they investigated whether this age-related decline in task switching performance was mediated by variability in global or regional white matter microstructural health. Seventy cognitively intact adults (43-87 years) completed a cued-trials task switching paradigm. Microstructural white matter measures were derived using diffusion tensor imaging (DTI) analyses on the diffusion-weighted imaging (DWI) sequence. Task switching performance decreased with increasing age and radial diffusivity (RaD), a measure of white matter microstructure that is sensitive to myelin structure. RaD mediated the relationship between age and task switching performance. However, the relationship between RaD and task switching performance remained significant when controlling for age and was stronger in the presence of cardiovascular risk factors. Variability in error and RT mixing cost were associated with RaD in global white matter and in frontoparietal white matter tracts, respectively. These findings suggest that age-related increase in mixing cost may result from both global and tract-specific disruption of cerebral white matter linked to the increased incidence of cardiovascular risks in older adults. Hum Brain Mapp 38:1588-1603, 2017. © 2016 Wiley Periodicals, Inc.

OBJECTIVE Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients for acute reperfusion therapy. In this study, we tested the hypothesis that a small acute perfusion lesion predicts good clinical outcome regardless of thrombolysis administration. METHODS We used a prospectively collected cohort of acute ischemic stroke patients being assessed for treatment with IV-alteplase, who had CTP before a treatment decision. Volumetric CTP was retrospectively analyded to identify patients with a small perfusion lesion (

Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age.

Background The Quality in Acute Stroke Care (QASC) trial evaluated systematic implementation of clinical treatment protocols to manage fever, sugar, and swallow (FeSS protocols) in acute stroke care. This cluster-randomised controlled trial was conducted in 19 stroke units in Australia. Aim To describe perceived barriers and enablers preimplementation to the introduction of the FeSS protocols and, postimplementation, to determine which of these barriers eventuated as actual barriers. Methods Preimplementation: Workshops were held at the intervention stroke units (n = 10). The first workshop involved senior clinicians who identified perceived barriers and enablers to implementation of the protocols, the second workshop involved bedside clinicians. Postimplementation, an online survey with stroke champions from intervention sites was conducted. Results A total of 111 clinicians attended the preimplementation workshops, identifying 22 barriers covering four main themes: (a) need for new policies, (b) limited workforce (capacity), (c) lack of equipment, and (d) education and logistics of training staff. Preimplementation enablers identified were: support by clinical champions, medical staff, nursing management and allied health staff; easy adaptation of current protocols, care-plans, and local policies; and presence of specialist stroke unit staff. Postimplementation, only five of the 22 barriers identified preimplementation were reported as actual barriers to adoption of the FeSS protocols, namely, no previous use of insulin infusions; hyperglycaemic protocols could not be commenced without written orders; medical staff reluctance to use the ASSIST swallowing screening tool; poor level of engagement of medical staff; and doctors' unawareness of the trial. Linking Evidence to Action The process of identifying barriers and enablers preimplementation allowed staff to take ownership and to address barriers and plan for change. As only five of the 22 barriers identified preimplementation were reported to be actual barriers at completion of the trial, this suggests that barriers are often overcome whilst some are only ever perceived rather than actual barriers.

Objectives: Hospital data used to assess regional variability in disease management and outcomes, including mortality, lack information on disease severity. We describe variance between hospitals in 30-day risk-adjusted mortality rates (RAMRs) for stroke, comparing models that include or exclude stroke severity as a covariate. Design: Cohort design linking Australian Stroke Clinical Registry data with national death registrations. Multivariable models using recommended statistical methods for calculating 30-day RAMRs for hospitals, adjusted for demographic factors, ability to walk on admission, stroke type, and stroke recurrence. Setting: Australian hospitals providing at least 200 episodes of acute stroke care, 2009–2014. Main outcome measures: Hospital RAMRs estimated by different models. Changes in hospital rank order and funnel plots were used to explore variation in hospital-specific 30-day RAMRs; that is, RAMRs more than three standard deviations from the mean. Results: In the 28 hospitals reporting at least 200 episodes of care, there were 16 218 episodes (15 951 patients; median age, 77 years; women, 46%; ischaemic strokes, 79%). RAMRs from models not including stroke severity as a variable ranged between 8% and 20%; RAMRs from models with the best fit, which included ability to walk and stroke recurrence as variables, ranged between 9% and 21%. The rank order of hospitals changed according to the covariates included in the models, particularly for those hospitals with the highest RAMRs. Funnel plots identified significant deviation from the mean overall RAMR for two hospitals, including one with borderline excess mortality. Conclusions: Hospital stroke mortality rates and hospital performance ranking may vary widely according to the covariates included in the statistical analysis.

Objective This paper identified barriers which prevent rural health care providers from utilising rt-PA in acute ischaemic stroke and proposes possible support mechanisms to increase its utilisation. Methods This descriptive study uses data from anonymous surveys distributed to health care providers involved in acute stroke patient care in three rural hospitals with rt-PA pathways. Saturation sampling was used. Surveys gathered self assessed ratings of experience, practice environment, attitudes, existing support, barriers and possible enablers regarding rt-PA use in acute stroke. Results Physicians reported the strongest barriers to the use of rt-PA in acute stroke as pre-hospital delays (91%), risk of intracerebral haemorrhage (ICH) (73%) and clinical diagnostic uncertainty (60%). They reported high levels of confidence in the support received from their stroke units (90%). Nurses identified a poor level of stroke education and knowledge on rt-PA utilisation in acute stroke. A third of nurses could correctly list six different stroke signs. The risk of ICH following rt-PA administration in stroke was also a significant barrier for nurses. Response rate from physicians was 26% (10/38) and 19% (13/69) for nurses. Conclusions To reduce barriers to rt-PA utilisation in rural facilities physicians require education on the calculated risk of ICH as well as exposure and experience to improve their ability to confidently diagnose stroke patients who are eligible for rt-PA treatment. Education for nurses on symptoms of stroke and rt-PA utilisation and administration is recommended.

Objective This audit of activity reports on current rates of recombinant tissue plasminogen activator (rt-PA) use within specialised stroke care units in rural New South Wales (NSW). It measures stroke onset-to-treatment time and morbidity outcomes for patients treated with rt-PA and aims to establish the safety and effectiveness of rt-PA use in rural NSW. Design, setting and participants Medical records reviews of patients admitted with acute ischaemic stroke at two rural NSW hospitals between 1 July 2008 and 30 June 2010. Main outcome measures Treatment with rt-PA, morbidity scores 5 days post-stroke or discharge, incidence of intracranial haemorrhage and mortality rate 6 months post-stroke were recorded. Treatment protocol violations were assessed and time to treatment from stroke onset and hospital admission. Results Of 605 patients admitted with acute ischaemic stroke, 20 (3.3%) received rt-PA treatment. Of these two, 10% had symptomatic intracranial haemorrhage and one died within 6 months. Morbidity scores for those treated with rt-PA were similar to those not treated. The median onset-to-needle time was 2 hours and 34 min, and the median door-to-needle time was 1 hour and 40 min. There were no treatment protocol violations. Conclusion Recombinant tissue plasminogen activator can be delivered in rural Australian hospitals in a timely manner within recommended implementation guidelines. Acute stroke thrombolytic services in rural Australian facilities had comparable outcomes to metropolitan facilities. Small numbers of thrombolysed patients prevented a validation study of the well-defined outcome benefits from rt-PA. The need for ongoing data collection in regional settings is supported.

Objective Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. Methods The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p 8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. Interpretation VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion. ANN NEUROL 2013;73:510–519

Background: Stroke care across Australian hospitals is variable. The impact on health outcomes, in particular levels of disability for patients in rural areas, is unclear. The aim of this study was to determine whether geographic location and access to stroke units are associated with differences in health outcomes in patients with acute stroke. Methods: Retrospective cohort study of consecutive eligible admissions from 32 hospitals (12 rural) in New South Wales between 2003 and 2007. Health status measured at discharge included level of independence (modified Rankin score: mRS) and frequency of severe complications during hospitalization. Multivariable analyses included adjustment for patient casemix and clustering. Results: Among 2254 eligible patients, 55% were treated in metropolitan hospitals. Stroke unit treatment varied significantly (rural 3%; metropolitan 77%). Age, gender and stroke type did not differ by location (mean age 74, 50% female). After adjusting for age, gender, ethnicity, important risk factors and validated stroke prognostic variables, patients treated in rural hospitals had a greater odds of dying during hospitalization compared with those treated in metropolitan hospitals (adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI) 1.03–2.05). There were no differences in mortality or frequency of severe complications between patients treated in rural and metropolitan hospitals when we adjusted for access to stroke units (aOR 1.00, 95% CI 0.62–1.61). Nevertheless, patients treated in rural hospitals were more dependent (mRS 3–5) at discharge (aOR 1.82, 95% CI 1.23–2.70) despite adjusting for stroke unit status. Conclusion: Patients with stroke treated in rural hospitals have poorer health outcomes, especially if not managed in stroke units.

Background: Stroke is an Australian health priority area causing considerable levels of disability. We report 90-day outcomes for a cohort of acute stroke patients in New South Wales (NSW), Australia prior to randomization to a large cluster randomized controlled trial (CRCT), the Quality in Acute Stroke Care (QASC) trial. Aims: This paper describes prospectively collected, 90-day outcome data for a cohort of NSW stroke patients, providing pre-intervention data for the QASC trial. Methods: A consecutive sample of patients from acute stroke units in NSW was recruited. We measured patient death, disability (modified Rankin Score (mRS)), dependency (Barthel Index (BI)) and Health Status (Medical Outcomes Short-Form Health Survey (SF-36)) 90 days post-hospital admission. We also collected self-reported healthcare utilization and patient satisfaction with health professionals' advice and management to reduce risk of subsequent stroke. Results: Ninety-day outcome data were obtained for 687 patients, of which, 335 (49%) had an mRS ≥2; 44 patients (6.4%) had died. For the 643 surviving patients, the mean BI was 87.2 (SD 21.9) and the mean scores for SF-36 Physical Component Summary score and Mental Component Summary score were 46.2 (SD 10.1) and 46.3 (SD 12.6) respectively. Conclusions: In this pre-intervention cohort of selected acute stroke inpatients, stroke severity was mild to moderate and subsequent clinical outcomes were favourable in the majority. The findings from this study provide a comprehensive description of 90-day health outcomes of patients who have experienced a mild–moderate stroke managed in stroke care units across metropolitan NSW and provide valuable data to inform the subsequent cluster trial.

Stroke is Australia's second single greatest killer with 53 000 new events each year at a rate of 1 every 10 min. Stroke services should be organized to enable people to access proven therapies, such as stroke unit care and thrombolysis, to reduce the impact of stroke. Timely, efficient and coordinated care from ambulance services, emergency services and stroke services will maximize recovery and prevent costly complications and subsequent strokes. Efficient management of patients with transient ischaemic attack can produce significant reductions in subsequent stroke events and risk stratification using the ABCD2 tool can aid management decisions. Evidence for acute stroke care continues to evolve and it is crucial that health professionals are aware of, and implement, best practice clinical guidelines for stroke care.

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) has not been previously applied to perfusion CT (CTP). Five raters assigned ASPECTS to baseline noncontrast CT (NCCT), CT angiography source images (CTA-SI), CTP source images (CTP-SI), and CTP maps of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) from 37 consecutive patients with less than 6-hour anterior circulation ischemic stroke. Major reperfusion was identified on follow-up imaging. Mean baseline ASPECTS was compared with follow-up imaging ASPECTS. Rates of favorable outcome were compared for dichotomized baseline ASPECTS. In patients with major reperfusion, mean CBV and CTP-SI ASPECTS closely predicted final infarct ASPECTS. In patients without major reperfusion, mean CBF and MTT ASPECTS best predicted final infarct ASPECTS. There were significant increases in rates of favorable outcome for CTP-SI and CBV ASPECTS of greater than 6, versus less than or equal to 6, but not for other baseline CT modalities. ASPECTS applied to CTP is more accurate at identifying the extent of reversible and irreversible ischemia and at predicting final clinical outcome than NCCTor CTA-SI.

One hundred fifty patients undergoing carotid endarterectomy were randomly assigned to receive intravenous 10% dextran 40 or placebo. Transcranial Doppler monitoring of the ipsilateral middle cerebral artery 0 to 1 hour postoperatively detected embolic signals in 57% of placebo and 42% of dextran patients, with overall embolic signal counts 46% less for dextran (p = 0.052). Two to 3 hours postoperatively, embolic signals were present in 45% of placebo and 27% of dextran patients, with embolic signal counts 64% less for dextran (p = 0.040). We conclude that dextran reduces embolic signals within 3 hours of CEA.

The perinatal period remains a time of significant risk of death or disability. Increasing evidence suggests that this depends on microcirculatory behavior. Sidestream dark‐field orthogonal polarized light videomicroscopy (OPS) has emerged as a useful assessment of adult microcirculation but the values derived are not delineated for the newborn. We aimed to define these parameters in well term newborn infants. Demographic details were collected prospectively on 42 healthy term neonates (n = 20 females, n = 22 males). OPS videomicroscopy (Microscan) was used to view ear conch skin microcirculation at 6, 24, and 72 h of age. Stored video was analyzed by a masked observer using proprietary software. There were no significant differences between the sexes for any structural parameters at any time point. There was a significant increase over time in small vessel perfusion in female infants only (P = 0.009). A number of 6‐ and 72‐h measurements were significantly correlated, but differed from the 24‐h values. These observations confirm the utility of the ear conch for neonatal microvascular videomicroscopy. They provide a baseline for studies into the use of OPS videomicroscopy in infants. The changes observed are comparable with previous studies of term infants using these and other microvascular techniques. It is recommended that studies for examining the mature neonatal microvascular structure be delayed until 72 h of life, but studies of the physiology of cardiovascular transition should include the 24‐h time point after delivery.