Medicine (Austin & Northern Health) - Research Publications
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ItemTrends in direct oral anticoagulant use in patients presenting with acute stroke(WILEY, 2022-09)Acute ischaemic strokes occur despite the use of direct oral anticoagulants (DOACs). A retrospective review was conducted at a high-volume primary stroke centre over a 3-year period to assess the acute management of stroke presentations in patients prescribed DOACs. During the time period of the study, 103 of 195 anticoagulated stroke patients presented within the timeframe for thrombolysis and only 15 patients had DOAC plasma level assays performed. Of these 103, 5 received thrombolysis; however, DOAC level was not a factor in these cases.
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ItemA mixed-methods feasibility study of a new digital health support package for people after stroke: the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) intervention(BMC, 2022-11-19)BACKGROUND: Evidence for digital health programmes to support people living with stroke is growing. We assessed the feasibility of a protocol and procedures for the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial. METHODS: We conducted a mixed-method feasibility study. Participants with acute stroke were recruited from three hospitals (Melbourne, Australia). Eligibility: Adults with stroke discharged from hospital to home within 10 days, modified Rankin Score 0-4 and prior use of Short Message System (SMS)/email. While in hospital, recruited participants contributed to structured person-centred goal setting and completed baseline surveys including self-management skills and health-related quality of life. Participants were randomised 7-14 days after discharge via REDCap® (1:1 allocation). Following randomisation, the intervention group received a 12-week programme of personalised electronic support messages (average 66 messages sent by SMS or email) aligned with their goals. The control group received six electronic administrative messages. Feasibility outcomes included the following: number of patients screened and recruited, study retainment, completion of outcome measures and acceptability of the ReCAPS intervention and trial procedures (e.g. participant satisfaction survey, clinician interviews). Protocol fidelity outcomes included number of goals developed (and quality), electronic messages delivered, stop messages received and engagement with messages. We undertook inductive thematic analysis of interview/open-text survey data and descriptive analysis of closed survey questions. RESULTS: Between November 2018 and October 2019, 312 patients were screened; 37/105 (35%) eligible patients provided consent (mean age 61 years; 32% female); 33 were randomised (17 to intervention). Overall, 29 (88%) participants completed the12-week outcome assessments with 12 (41%) completed assessments in the allocated timeframe and 16 also completing the satisfaction survey (intervention=10). Overall, trial participants felt that the study was worthwhile and most would recommend it to others. Six clinicians participated in one of three focus group interviews; while they reported that the trial and the process of goal setting were acceptable, they raised concerns regarding the additional time required to personalise goals. CONCLUSION: The study protocol and procedures were feasible with acceptable retention of participants. Consent and goal personalisation procedures should be centralised for the phase III trial to reduce the burden on hospital clinicians. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618001468213 (date 31/08/2018); Universal Trial Number: U1111-1206-7237.
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ItemNo Preview AvailablePrevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow)(LIPPINCOTT WILLIAMS & WILKINS, 2022-02-22)BACKGROUND AND OBJECTIVES: The relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging. METHODS: In a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA; ClinicalTrials.gov NCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion. RESULTS: Regions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%-70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%-32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%-28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median -3.3%, interquartile range -11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32-15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22-16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = -4.06, 95% CI 6.78-1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35-10.20, p = 0.011) in multivariable analysis. DISCUSSION: Cerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.
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ItemNo Preview AvailableEndovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies(WILEY, 2022-05)OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.
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ItemTelemedicine for Stroke: Quantifying the Long-Term National Costs and Health Benefits(FRONTIERS MEDIA SA, 2022-06-20)OBJECTIVE: Few countries have established national programs to maximize access and reduce operational overheads. We aimed to use patient-level data up to 12 months to model the potential long-term costs and health benefits attributable to implementing such a program for Australia. METHODS: A Markov model was created for Australia with an inception population of 10,000 people with stroke presenting to non-urban or suburban hospitals without stroke medical specialists that could receive stroke telemedicine under a national program. Seven Markov states represented the seven modified Rankin Scale (mRS) scores (0 no disability to 6 dead) plus an absorbing state for all other causes of death. The literature informed inputs for the model; for the telemedicine program (including program costs and effectiveness) and patients, these were extrapolated from the Victorian Stroke Telemedicine (VST) program with the initial status of patients being their health state at day 365 as determined by their mRS score. Costs (2018 Australian dollars, healthcare, non-medical, and nursing home) and benefits were reported for both the societal and healthcare perspectives for up to a 25 years (lifetime) time horizon. RESULTS: We assumed 4,997 to 12,578 ischemic strokes would arrive within 4.5 h of symptom onset at regional hospitals in 2018. The average per person lifetime costs were $126,461 and $127,987 from a societal perspective or $76,680 and $75,901 from a healthcare system perspective and benefits were 4.43 quality-adjusted life years (QALYs) and 3.98 QALYs gained, respectively, for the stroke telemedicine program and practice without such program. The stroke telemedicine program was associated with a cost saving of $1,526 (from the societal perspective) or an additional $779 (from the healthcare system perspective) and an additional 0.45 QALY gained per patient over the lifetime. The incremental costs of the stroke telemedicine program ($2,959) and management poststroke ($813) were offset by cost savings from rehospitalization (-$552), nursing home care (-$2178), and non-medical resource use (-$128). CONCLUSION: The findings from this long-term model provide evidence to support ongoing funding for stroke telemedicine services in Australia. Our estimates are conservative since other benefits of the service outside the use of intravenous thrombolysis were not included.
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ItemThe quest to reduce stroke treatment delays at a Melbourne metropolitan primary stroke centre over the past two decades(WILEY, 2022-11)BACKGROUND: Reducing door-to-needle time (DNT) for intravenous thrombolysis in acute ischaemic stroke can lead to improved patient outcomes. Long-term reports on DNT trends in Australia are lacking in the setting of extension of the thrombolysis time window, addition of mechanical thrombectomy and increasing presentations. AIMS: To examine 17-year trends of DNT and identify factors associated with improved DNT at a high-volume, metropolitan primary stroke centre. METHOD: Retrospective study between 2003 and 2019 of all thrombolysis cases using departmental stroke database. Since most strategies were implemented from 2012 onwards, intervention period has been defined as period 2012-2019. Factors associated with DNT reduction were examined by regression modelling. RESULTS: Fifteen strategies were identified including alterations to 'Code Stroke' processes. One thousand, two hundred and fifty patients were thrombolysed, with 737 (58.8%) treated during the intervention period. The proportion of DNT ≤60-min rose from average of 22.5% during 2003-2012 to 63% during 2015-2018 and 71% in 2019. However, median DNT has only marginally improved from 58 to 51 min between 2015 and 2019. Faster DNT was independently associated with two modifiable workflow factors, 'Direct-to-CT' protocol (P < 0.001) and acute stroke nurse presence (P < 0.005). Over time, treated patients were older and less independent (P < 0.001), and the number of annual stroke admissions and 'Code Stroke' activations have risen by fourfold and 10-fold to 748 and 1298 by 2019 respectively. CONCLUSIONS: Targeted quality improvement initiatives are key to reducing thrombolysis treatment delays in the Australian metropolitan setting. Relative stagnation in DNT improvement is concerning and needs further investigation.
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ItemNo Preview AvailableHealthy 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(AMER MEDICAL ASSOC, 2021-06)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.
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ItemThe economic and health burden of stroke among younger adults in Australia from a societal perspective(BMC, 2022-02-03)BACKGROUND: To estimate the short term (5 years) and long term (30 years) economic burden of stroke among younger adults (18-64 years), and to calculate the loss of health-related quality of life in these individuals, in Australia. METHODS: A Markov microsimulation model was built to simulate incidence of stroke among younger adults in Australia. Younger adults with stroke commenced in the model via health states defined by the modified Rankin Scale at 12 months from the AVERT study (A Very Early Rehabilitation Trial), and transitioned through these health states. Costs in Australian dollars (AUD) were measured from a societal perspective for a 2018 reference year and categorised into medical, non-medical and indirect costs. Probabilistic sensitivity analyses were performed to test the robustness around the cost of illness estimates. The loss of health-related quality of life due to stroke among younger adults was calculated by determining the difference in estimated quality-adjusted life years (QALYs) between the stroke population and the general population. This was determined by multiplying the predicted remaining life years for the modelled stroke cohort and the age-matched general population, by their corresponding age-dependent utilities. RESULTS: The economic burden of stroke among younger adults was estimated to be AUD2.0 billion over 5 years, corresponding to a mean of $149,180 per stroke patient. Over 30 years, the economic impact was AUD3.4 billion, equating to a mean of $249,780 per case. Probabilistic sensitivity analyses revealed a mean cost per patient of $153,410 in the short term, and a mean cost per patient of $273,496 in the long term. Compared to the age-matched general population, younger adults with stroke experienced a loss of 4.58 life years and 9.21 QALYs. CONCLUSIONS: The results of our study suggests high economic and health burden of stroke among younger adults and highlights the need for preventive interventions targeting this age group. TRIAL REGISTRATION: ACTRN12606000185561 , retrospectively registered.
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ItemCarotid endarterectomy: the change in practice over 11years in a stroke centre(WILEY, 2019-04)BACKGROUND: Recent research evidence has impacted the practice of carotid endarterectomy (CEA). We aim to characterize changes in the practice and outcome of CEA over time in a single large-volume stroke centre. METHODS: All patients who underwent CEA from 2004 to 2014 and carotid angioplasty and stenting (CAS) from 2003 to 2008 at an Australian metropolitan tertiary stroke centre hospital were included. Clinical data were analysed to identify time trends in choice of intervention, patient selection, preoperative imaging utilization, surgical timing and outcome. RESULTS: There were 510 CEAs performed during 2004-2014 and 95 CASs during 2003-2008. The proportion of patients undergoing CEA compared to CAS increased from 60% to 90% from 2004 to 2008 (P < 0.001). CAS patients were more likely to have cardiac co-morbidities. From 2004 to 2014, the proportion of CEA patients aged ≥80 years increased (P = 0.001) and the proportion of asymptomatic patients decreased (P = 0.003) over time. Median time from symptom onset to surgery decreased from 52 days (Q1: 25, Q3: 74) in 2004 to 8 days (Q1: 5, Q3: 37) in 2014 (P < 0.001). Use of preoperative ultrasonography decreased whilst CT angiography and the number of imaging modalities applied to each patient increased over time (P < 0.001). Overall, 5.9% of CEAs were complicated by death, stroke or acute myocardial infarction with no significant change over time. CONCLUSION: The trends in CEA practice at our centre align with international trends and guidelines. This study provides a representative indicator of Australian hospital practice, and illustrates how evidence from research is translated into clinical care.