Medicine (RMH) - Research Publications
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ItemPerfusion computed tomography to assist decision making for stroke thrombolysis(OXFORD UNIV PRESS, 2015-07-01)The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.
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ItemGoogling Boundaries for Operating Mobile Stroke Unit for Stroke Codes(FRONTIERS MEDIA SA, 2019-04-04)Background: Mobile stroke units (MSU) have been proposed to expedite delivery of recombinant tissue plasminogen activator (tPA) and expedite endovascular clot retrieval (ECR). Unexplored questions in the use of MSU include: maximal distance from base, time limit with regards to the use CT imaging, CT Angiography, CT Perfusion, and Telemedicine. We developed a computational model as an app (https://gntem3.shinyapps.io/ambmc/), taking into account traveling time to explore this issue. The aim of this study was to define the operating parameters for an MSU in a large metropolitan city, based on the geography of Melbourne. Methods: There are 2 hospitals (Royal Melbourne Hospital/RMH, Monash Medical Center/MMC) designated to provide state-wide ECR services. In these spatial simulations, the MSU is based at RMH and delivers tPA at the patient's pick-up address and then takes the patient to the nearest ECR center. We extracted the geocode of suburbs in Melbourne and travel time to each hospital using ggmap, an interface to Google Map API. The app contains widgets for varying the processing time at the patient location (default = 30 min), performing CT angiography (default = 10 min), performing telemedicine consultation (default = 15 min). The data were compared against those for usual ambulance metrics (default traveling time = 15 min, processing time at patient's location = 20 min, door to tPA = 60 min, door to groin = 90 min). Varying the widgets allow the viewer to explore the trade-off between the variable of interest and time to therapy at a suburb level. Results: The MSU was superior for delivering tPA to all Melbourne suburbs (up to 76 min from RMH). If the CTA times or processing time at location increased by 20 min then it was superior for providing ECR to only 74.9% of suburbs if the return base was RMH. Addition of CT Perfusion or telemedicine consultation affect the ability of a single hospital to provide ECR but not tPA if these additions can be limited to 20 min. Conclusion: The app can help to define how best to deploy the MSU across Melbourne. This app can be modified and used to optimize operating characteristics of MSU in other centers around the world.
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ItemEndovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost(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).
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ItemNo Preview AvailableComparison of Computed Tomography Perfusion and Magnetic Resonance Imaging Perfusion-Diffusion Mismatch in Ischemic Stroke(LIPPINCOTT WILLIAMS & WILKINS, 2012-10)BACKGROUND AND PURPOSE: Perfusion imaging has the potential to select patients most likely to respond to thrombolysis. We tested the correspondence of computed tomography perfusion (CTP)-derived mismatch with contemporaneous perfusion-diffusion magnetic resonance imaging (MRI). METHODS: Acute ischemic stroke patients 3 to 6 hours after onset had CTP and perfusion-diffusion MRI within 1 hour, before thrombolysis. Relative cerebral blood flow (relCBF) and time to peak of the deconvolved tissue residue function (Tmax) were calculated. The diffusion lesion (diffusion-weighted imaging) was registered to the CTP slabs and manually outlined to its maximal visual extent. Volumetric accuracy of CT-relCBF infarct core (compared with diffusion-weighted imaging) was tested. To reduce false-positive low CBF regions, relCBF core was restricted to voxels within a relative time-to-peak (relTTP) >4 seconds for lesion region of interest. The MR-Tmax >6 seconds perfusion lesion was automatically segmented and registered to CTP. Receiver-operating characteristic analysis determined the optimal CT-Tmax threshold to match MR-Tmax >6 seconds. Agreement of these CT parameters with MR perfusion-diffusion mismatch in coregistered slabs was assessed (mismatch ratio >1.2, absolute mismatch >10 mL, infarct core <70 mL). RESULTS: In analysis of 49 patients (mean onset to CT, 213 minutes; mean CT to MR, 31 minutes), constraining relCBF <31% within the automated relTTP perfusion lesion region of interest reduced the median magnitude of volumetric error (vs diffusion-weighted imaging) from 47.5 mL to 15.8 mL (P<0.001). The optimal CT-Tmax threshold to match MR-Tmax >6 seconds was 6.2 seconds (95% confidence interval, 5.6-7.3 seconds; sensitivity, 91%; specificity, 70%; area under the curve, 0.87). Using CT-Tmax >6 seconds "penumbra" and relTTP-constrained relCBF "core," CT-based and MRI-based mismatch status was concordant in 90% (kappa=0.80). CONCLUSIONS: Quantitative CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. The greater accessibility of CTP may facilitate generalizability of mismatch-based selection in clinical practice and trials.
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ItemTime to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials(ELSEVIER SCIENCE INC, 2010-05-15)BACKGROUND: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. METHODS: We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. FINDINGS: Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. INTERPRETATION: Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. FUNDING: None.