Medicine (Austin & Northern Health) - Research Publications

Permanent URI for this collection

Search Results

Now showing 1 - 9 of 9
  • Item
    No Preview Available
    Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials
    Almekhlafi, MA ; Goyal, M ; Dippel, DWJ ; Majoie, CBLM ; Campbell, BCV ; Muir, KW ; Demchuk, AM ; Bracard, S ; Guillemin, F ; Jovin, TG ; Mitchell, P ; White, P ; Hill, MD ; Brown, S ; Saver, JL (AMER MEDICAL ASSOC, 2021-05-03)
    Importance: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
  • Item
    Thumbnail Image
    Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit
    Bivard, A ; Zhao, H ; Coote, S ; Campbell, B ; Churilov, L ; Yassi, N ; Yan, B ; Valente, M ; Sharobeam, A ; Balabanski, A ; Dos Santos, A ; Ng, F ; Langenberg, F ; Stephenson, M ; Smith, K ; Bernard, S ; Thijs, V ; Cloud, G ; Choi, P ; Ma, H ; Wijeratne, T ; Chen, C ; Olenko, L ; Davis, SM ; Donnan, GA ; Parsons, M (BMJ PUBLISHING GROUP, 2022-04-01)
    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.
  • Item
    No Preview Available
    Fatal and Nonfatal Events Within 14 days After Early, Intensive Mobilization Poststroke
    Bernhardt, J ; Borschmann, K ; Collier, JM ; Thrift, AG ; Langhorne, P ; Middleton, S ; Lindley, RI ; Dewey, HM ; Bath, P ; Said, CM ; Churilov, L ; Ellery, F ; Bladin, C ; Reid, CM ; Frayne, JH ; Srikanth, V ; Read, SJ ; Donnan, GA (LIPPINCOTT WILLIAMS & WILKINS, 2021-02-23)
    OBJECTIVE: This tertiary analysis from AVERT examined fatal and non-fatal Serious Adverse Events (SAEs) at 14 days. METHOD: AVERT was a prospective, parallel group, assessor blinded, randomized international clinical trial comparing mobility training commenced <24 hours post stroke, termed very early mobilization (VEM) to usual care (UC). Primary outcome was assessed at 3 months. Included: Patients with ischaemic and haemorrhagic stroke within 24 hours of onset. Treatment with thrombolytics allowed. Excluded: Patients with severe premorbid disability and/or comorbidities. Interventions continued for 14 days or hospital discharge if less. The primary early safety outcome was fatal SAEs within 14 days. Secondary outcomes were non-fatal SAEs classified as neurologic, immobility-related, and other. Mortality influences were assessed using binary logistic regression adjusted for baseline stroke severity (NIHSS) and age. RESULTS: 2,104 participants were randomized to VEM (n = 1,054) or UC (n = 1,050) with a median age of 72 years (IQR 63-80) and NIHSS 7 (IQR 4-12). By 14 days, 48 had died in VEM, 32 in UC, age and stroke severity adjusted Odds Ratio of 1.76 (95% CI 1.06-2.92, p = 0.029). Stroke progression was more common in VEM. Exploratory subgroup analyses showed higher odds of death in intracerebral haemorrhage and >80 years subgroups, but there was no significant treatment by subgroup interaction. No difference in non-fatal SAEs found. CONCLUSION: While the overall case fatality at 14 days post-stroke was only 3.8%, mortality adjusted for age and stroke severity was increased with high dose, intensive training compared to usual care. Stroke progression was more common in VEM. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that very early mobilization increases mortality at 14 days post stroke. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12606000185561.
  • Item
    Thumbnail Image
    Patterns of Infarction on MRI in Patients With Acute Ischemic Stroke and Cardio-Embolism: A Systematic Review and Meta-Analysis
    Sharobeam, A ; Churilov, L ; Parsons, M ; Donnan, GA ; Davis, SM ; Yan, B (FRONTIERS MEDIA SA, 2020-12-08)
    Background: Cardioembolic strokes are common however atrial fibrillation, the most common cause, is often asymptomatic and difficult to detect. There is evidence that infarct topography and volume on magnetic resonance imaging may be associated with specific stroke etiologies. Aim: A systematic review and meta-analysis were undertaken to summarize the available evidence on the association between stroke etiology, infarct topography, and volume. Methods: A systematic review was conducted using Medline (OVID), Embase (OVID), and PubMed databases. Hand searches of the gray literature and of reference lists in relevant articles were also performed. A quality assessment was undertaken, based on the STROBE checklist. For each study, the number of patients with and without a CE source of stroke and infarct topography was collected and outcomes presented as odds ratios (OR) with 95% CI and p-values. Results: Four thousand eight hundred and seventy-three patients with ischemic stroke were included, of whom 1,559 were determined to have a CE source. Bilateral infarcts (OR 3.41; 95% CI 2.20-5.29; p < 0.0001) and multiple territory infarcts (OR 1.57; 95% CI 1.12-2.21; p = 0.009) were more common in patients with a CE source of stroke, than patients without a CE source. Lacunar infarcts (OR 0.49; 95% CI 0.31-0.80; p = 0.004) were more likely to occur in patients without a CE source. No significant difference between the frequency of multiple infarcts (OR 0.96; 95% CI 0.57-1.61; p = 0.87) anterior circulation (OR 1.45; 95% CI 0.83-2.53; p = 0.19) or posterior circulation infarcts (OR 1.06; 95% CI 0.72-1.57; p = 0.75), between the two groups were identified. Three out of four studies examining volume, found a significant association between increased infarct volume and CE source of stroke. A sensitivity analysis with cryptogenic and undetermined stroke sources assumed to be cardioembolic, did not alter the associations observed. Conclusion: The findings of this systematic review and meta-analysis are broadly consistent with previous literature and provide more robust evidence on the association between infarct topography, volume and stroke etiology. Our findings may assist with refining cardiac investigations for patients with cryptogenic stroke, based on infarct topography.
  • Item
    Thumbnail Image
    Differentiating Childhood Stroke From Mimics in the Emergency Department
    Mackay, MT ; Yock-Corrales, A ; Churilov, L ; Monagle, P ; Donnan, GA ; Babl, FE (LIPPINCOTT WILLIAMS & WILKINS, 2016-10-01)
    BACKGROUND AND PURPOSE: Clinical identification of stroke in the pediatric emergency department is critical for improving access to hyperacute therapies. We identified key clinical features associated with childhood stroke or transient ischemic attack compared with mimics. METHODS: Two hundred and eighty consecutive children presenting to the emergency department with mimics, prospectively recruited over 18 months from 2009 to 2010, were compared with 102 children with stroke or transient ischemic attack, prospectively/retrospectively recruited from 2003 to 2010. RESULTS: Cerebrovascular diagnoses included arterial ischemic stroke (55), hemorrhagic stroke (37), and transient ischemic attack (10). Mimic diagnoses included migraine (84), seizures (46), Bell's palsy (29), and conversion disorders (18). Being well in the week before presentation (odds ratio [OR] 5.76, 95% confidence interval [CI] 2.25-14.79), face weakness (OR 2.94, 95% CI 1.19-7.28), arm weakness (OR 8.66, 95% CI, 2.50-30.02), and inability to walk (OR 3.38, 95% CI 1.54-7.42) were independently associated with increased odds of stroke diagnosis. Other symptoms were independently associated with decreased odds of stroke diagnosis (OR 0.28, 95% CI 0.10-0.77). Associations were not observed between seizures or loss of consciousness. Factors associated with stroke differed by arterial and hemorrhagic subtypes. CONCLUSIONS: Being well in the week before presentation, inability to walk, face and arm weakness are associated with increased odds of stroke. The lack of positive or negative association between stroke and seizures or loss of consciousness is an important difference to adults. Pediatric stroke pathways and bedside tools need to factor in differences between children and adults and between stroke subtypes.
  • Item
    Thumbnail Image
    Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost
    Campbell, BCV ; Mitchell, PJ ; Churilov, L ; Keshtkaran, M ; Hong, K-S ; Kleinig, TJ ; Dewey, HM ; Yassi, N ; Yan, B ; Dowling, RJ ; Parsons, MW ; Wu, TY ; Brooks, M ; Simpson, MA ; Miteff, F ; Levi, CR ; Krause, M ; Harrington, TJ ; Faulder, KC ; Steinfort, BS ; Ang, T ; Scroop, R ; Barber, PA ; McGuinness, B ; Wijeratne, T ; Phan, TG ; Chong, W ; Chandra, RV ; Bladin, CF ; Rice, H ; de Villiers, L ; Ma, H ; Desmond, PM ; Meretoja, A ; Cadilhac, DA ; Donnan, GA ; Davis, SM (FRONTIERS MEDIA SA, 2017-12-14)
    BACKGROUND: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. METHODS: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). RESULTS: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. CONCLUSION: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life. CLINICAL TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).
  • Item
    Thumbnail Image
    Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study
    Patel, SK ; Restrepo, C ; Werden, E ; Churilov, L ; Ekinci, EI ; Srivastava, PM ; Ramchand, J ; Wai, B ; Chambers, B ; O'Callaghan, CJ ; Darby, D ; Hachinski, V ; Cumming, T ; Donnan, G ; Burrell, LM ; Brodtmann, A (BMC, 2017-04-07)
    BACKGROUND: Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. METHODS: The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. DISCUSSION: The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.
  • Item
    Thumbnail Image
    Positron Emission Tomographic Imaging in Stroke Cross-Sectional and Follow-Up Assessment of Amyloid in Ischemic Stroke
    Sahathevan, R ; Linden, T ; Villemagne, VL ; Churilov, L ; Ly, JV ; Rowe, C ; Donnan, G ; Brodtmann, A (LIPPINCOTT WILLIAMS & WILKINS, 2016-01-01)
    BACKGROUND AND PURPOSE: Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time. METHODS: Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ≤18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. RESULTS: Forty-seven patients were imaged with (11)C-PiB positron emission tomography. There was an increase in (11)C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, -0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of (11)C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, -0.02 to 0.10]; P=0.095). We repeated (11)C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of (11)C-PiB between regions of interest (median difference in standardized uptake value ratio, -0.08 [95% confidence interval, -0.23 to -0.03]; P=0.04). CONCLUSIONS: There was no significant increase in (11)C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric (11)C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased β-amyloid deposition ≤18 months after stroke.
  • Item
    No Preview Available
    Statistical analysis plan (SAP) for A Very Early Rehabilitation Trial (AVERT): an international trial to determine the efficacy and safety of commencing out of bed standing and walking training (very early mobilization) within 24 h of stroke onset vs. usual stroke unit care
    Bernhardt, J ; Churilov, L ; Dewey, H ; Lindley, RI ; Moodie, M ; Collier, J ; Langhorne, P ; Thrift, AG ; Donnan, G (SAGE PUBLICATIONS LTD, 2015-01-01)
    Currently, the acute stroke interventions for which there is evidence of efficacy are stroke unit care (a complex package), selected surgery , aspirin and thrombolysis. The stroke unit effect is powerful with a 20% relative reduction in mortality and similar reduction in disability. However the key components of this ‘black box’ are unknown. Starting out of bed sitting, standing and walking training early after stroke (early mobilization) have emerged as a component of care that may make an important contribution to the stroke unit care effect.