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Information Systems | Information Systems Development Methodologies | Simulation And Modelling | Decision Support And Group Support Systems
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2022
DOI: 10.1161/STROKEAHA.122.038576
Abstract: In patients with acute stroke who undergo endovascular thrombectomy, the relative prognostic power of computed tomography perfusion (CTP) parameters compared with multiphase CT angiogram (mCTA) is unknown. We aimed to compare the predictive accuracy of mCTA and CTP parameters on clinical outcomes. We included patients with acute ischemic stroke who had anterior circulation large vessel occlusion within 24 hours of onset in Melbourne Brain Centre at the Royal Melbourne Hospital. All patients underwent CTP for endovascular thrombectomy, and the mCTA collateral score was determined using CTP-reconstructed mCTA images. The primary outcome was 90-day functional outcomes defined by modified Rankin Scale. Multivariable logistic regression models analyzed associations between mCTA and CTP parameters and 90-day functional outcomes. The ability to discriminate 90 days-functional outcomes was compared between mCTA collateral score and CTP parameters using receiver operating curve analysis and C statistics. One hundred and twenty patients were included. The median age was 69 years (interquartile range, 60–79), the median baseline National Institutes of Health Stroke Scale score was 14 (interquartile range, 9–19). The baseline ischemic core volume, defined by CTP-based relative cerebral blood flow %, was associated with excellent functional outcome (modified Rankin Scale score 0–1 odds ratio, 0.942 [−0.897 to −0.989] P =0.015) and poor functional outcome (modified Rankin Scale score 5–6 odds ratio, 1.032 [1.007–1.056] P =0.010) at 90 days in the analysis of multivariable regression. There was no significant association between the mCTA score and excellent functional outcome ( P =0.58) or poor functional outcome ( P =0.155). The relative cerebral blood flow %-based regression model best fit the data for the 90-day poor functional outcome (C statistic, 0.834). The CTP-based ischemic core volume may provide better discrimination for 90-day functional outcomes for patients with acute stroke undergoing endovascular thrombectomy than the mCTA collateral score.
Publisher: Informa UK Limited
Date: 16-07-2022
DOI: 10.1080/09638288.2020.1789229
Abstract: To investigate the safety and efficacy of early mobilisation (EM) compared to usual care by meta-analysing in idual participant data (IPD). IPD were sought from randomised controlled trials comparing out-of-bed mobilisation starting within 48 h from stroke onset to usual care for acute stroke patients. Six trials were sourced from a recent Cochrane review. Favourable outcome (modified Rankin Scale 0-2) and death at 3 months post-stroke were compared between both groups using mixed-effect logistic regression modelling. Adjusted odds ratios (aORs) with respective 95% confidence intervals (95%CI) were reported. Out of 2630 participants, 1437 (54.6%) were assigned to EM and 1193 (45.4%) to usual care. Intervention protocols varied considerably between trials. The median (interquartile range) delay to starting mobilisation post-stroke onset was 20 h (14.5-23.8) for EM and 23 h (16.7-34.3) for usual care group. Fewer EM participants had a favourable outcome at 3 months post-stroke compared to the usual care group (678 [48%] vs. 611 [52%] aOR = 0.75, 95%CI: 0.62-0.92, The commencement of mobilisation should only be considered after 24 h post-stroke. Further research is required to identify safe, optimal dose, and timing of EM post-stroke.IMPLICATIONS FOR REHABILITATIONPatients who commenced mobilisation early after stroke had worse outcome than usual care.Insufficient detail about mobilisation interventions or usual care in many studies limits any further interpretation.The commencement of mobilisation should only be considered after 24-h post-stroke.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2022
DOI: 10.1161/STROKEAHA.121.036670
Abstract: Emerging data suggest tissue within the infarct lesion is not homogenously damaged following ischemic stroke but has a gradient of injury. Using blood-brain-barrier (BBB) disruption as a marker of tissue injury, we tested whether therapeutic reperfusion improves clinical outcome by reducing the severity of tissue injury within the infarct in patients with ischemic stroke. In a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) and EXTEND-IA part-2 (Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke) trials, post-treatment BBB permeability at 24 hours was calculated based on the extent of T1-brightening by extravascular gadolinium on T2* perfusion-weighted imaging and measured within the diffusion-weighted-imaging lesion. First, to determine the clinical significance of BBB disruption as a marker of severity of tissue injury, we examined the association between post-treatment BBB permeability and functional outcome. Second, we performed an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis to estimate the proportion of the reperfusion-outcome relationship that is mediated by change in BBB permeability. In the 238 patients analyzed, an increased BBB permeability measured within the infarct at 24 hours was associated with a reduced likelihood of favorable outcome (90-day modified Rankin Scale score of ≤2) after adjusting for age, baseline National Institutes of Health Stroke Scale, premorbid modified Rankin Scale, infarct topography, laterality, thrombolytic agent, sex, parenchymal hematoma, and follow-up infarct volume (adjusted odds ratio, 0.86 [95% CI, 0.75–0.98] P =0.023). Mediation analysis suggested reducing the severity of tissue injury (as estimated by BBB permeability) accounts for 18.2% of the association between reperfusion and favorable outcome, as indicated by a reduction in the regression coefficient of reperfusion after addition of BBB permeability as a covariate. In patients with ischemic stroke, reduced severity of tissue injury within the infarct, as determined by assessing the integrity of the BBB, is independently associated with improved functional outcome. In addition to reducing diffusion-weighted imaging-defined infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.
Publisher: Informa UK Limited
Date: 26-05-2023
DOI: 10.1080/09638288.2022.2076935
Abstract: Identifying personal needs of young stroke survivors is crucial for their recovery. Identify factors, burden, and significance of unmet needs of young community-living stroke survivors. We used online advertising and word-of-mouth snowballing to recruit participants for an English language online questionnaire constructed for this purpose. Eligible participants aged 18-55 at time of stroke. Needs were classified into seven domains: Healthcare Experience, Impairments from Stroke, Everyday Activities, Work/Study, Finances, Relationships, and Social Participation. Random-effects logistic regression was used to determine the probability of unmet needs and X Out of 137 responses recorded: 32 did not meet inclusion criteria, 29 duplicates identified were discarded, and 76 eligible participants were analysed. Respondents were median 37 (IQR 32-47) years at time of stroke, and median 3 (1-5) years since stroke. Fifty-eight (76%) females. Modified Rankin Scale median score of 1 (1-3). Of 48 identified potential needs, 25 (IQR 19-30) were rated unmet. Twenty (IQR 15-25) considered of high significance. Unmet needs most frequently occurred in the domains: Impairments from Stroke, Finances, and Social Participation. There is high burden of unmet needs in community-living young stroke survivors which are spread disproportionately across the identified domains.IMPLICATIONS FOR REHABILITATIONIdentifying personal needs of young stroke survivors is crucial for their recovery.Impairments after Stroke, Finances, and Social Participation were often selected as being high burden unmet needs for community-living young people after stroke.Employing a post-stroke checklist to guide exploration of needs in young stroke may better capture which needs are unmet.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-03-2021
DOI: 10.1212/WNL.0000000000011647
Abstract: To determine how young stroke survivors want their unmet needs to be addressed, we undertook an international online survey of people living with stroke. Participants self-selected to complete an online survey that included a questionnaire on demographics and stroke-related characteristics, the Young Stroke Needs Screening Tool, and a questionnaire on how they wanted their needs to be met. One hundred seventy-one responses were received (68% female respondents, mean age 45 years, interquartile range 36–51 years). Preferences for methods of meeting needs varied depending on the domain of need and participants' demographic and stroke-related characteristics. Face-to-face contact with a health care professional was a popular means of meeting needs, but methods outside of a traditional health care setting such as a succinct list of tips or peer support were widely acceptable and sometimes preferred. This work provides the impetus for developing alternative methods of meeting young stroke survivors' needs, many of which are not resource intensive or do not require an appointment with a health care professional.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2023
Publisher: Elsevier BV
Date: 03-2021
Publisher: BMJ
Date: 17-03-2021
Abstract: Past studies have inconsistently identified factors associated with independent walking post-stroke. We investigated the relationship between pre-stroke factors and factors collected acutely after stroke and number of days to walking 50 m unassisted using data from A Very Early Rehabilitation Trial (AVERT). The outcome was recovery of 50 m independent walking, tested from 24 hours to 3 months post-stroke. A set of a priori defined factors (participant demographics: age, sex, handedness pre-stroke: hypertension, ischaemic heart disease, hypercholesterolaemia, diabetes mellitus, atrial fibrillation stroke-related: stroke severity, stroke type, ischaemic stroke location, stroke hemisphere, thrombolysis) were investigated for association with independent walking using a cause-specific competing risk Cox proportional hazards model. Respective effect sizes are reported as cause-specific adjusted HR (caHR) adjusted for age, stroke severity and AVERT intervention. A total of 2100 participants (median age 73 years, National Institutes of Health Stroke Scale 7, % missing data) with stroke were included. The median time to walking 50 m unassisted was 6 days (IQR 2–63) and 75% achieved independent walking by 3 months. Adjusted Cox regression indicated that slower return to independent walking was associated with older age (caHR 0.651, 95% CI 0.569 to 0.746), diabetes (caHR 0.836, 95% CI 0.740 to 0.945), severe stroke (caHR 0.094, 95% CI 0.072 to 0.122), haemorrhagic stroke (caHR 0.790, 95% CI 0.675 to 0.925) and right hemisphere stroke (caHR 0.796, 95% CI 0.714 to 0.887). Our analysis provides robust evidence for important factors associated with independent walking recovery. These findings highlight the need for tailored mobilisation programmes that target subgroups, in particular people with haemorrhagic and severe stroke.
Publisher: JMIR Publications Inc.
Date: 07-06-2019
DOI: 10.2196/13986
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2021
DOI: 10.1161/STROKEAHA.120.030455
Abstract: Lacunar syndromes correlate with a lacunar stroke on imaging in 50% to 60% of cases. Computed tomography perfusion (CTP) is becoming the preferred imaging modality for acute stroke triage. We aimed to estimate the sensitivity, specificity, and predictive values for noncontrast computed tomography and CTP in lacunar syndromes, and for cortical, subcortical, and posterior fossa regions. A retrospective analysis of confirmed ischemic stroke patients who underwent acute CTP and follow-up magnetic resonance imaging between 2010 and 2018 was performed. Brain noncontrast computed tomography and CTP were assessed independently by 2 stroke neurologists. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and area under the curve (AUC) for the detection of strokes in patients with lacunar syndromes using different CTP maps. We found 106 clinical lacunar syndromes, but on diffusion-weighted imaging, these consisted of 59 lacunar, 33 cortical, and 14 posterior fossa strokes. The discrimination of ischemia identification was very poor using noncontrast computed tomography in all 3 regions, but good for cortical (AUC, 0.82) and poor for subcortical and posterior regions (AUCs, 0.55 and 0.66) using automated core-penumbra maps. The addition of delay time and mean transient time maps substantially increased subcortical (AUC, 0.80) and slightly posterior stroke detection (AUC, 0.69). Analysis of mean transient time and delay time maps in combination with core-penumbra maps improves detection of subcortical and posterior strokes.
Publisher: Informa UK Limited
Date: 24-09-2019
Publisher: BMJ
Date: 05-2020
DOI: 10.1136/BMJOQ-2020-000954
Abstract: Hand and arm activity after stroke improves with evidence-based rehabilitation. Therapists face known barriers when providing evidence-based rehabilitation and require support to implement guidelines. The aim of this study was to investigate the feasibility of two implementation packages on guideline adherence by occupational therapists and physiotherapists, and explore effect on patient upper limb outcomes. This was a non-randomised clustered feasibility study of occupational and physiotherapy rehabilitation services (n=3 inpatient and n=3 outpatient services). Services were allocated to one of three groups: (group A) facilitator-mediated implementation package, (group B) self-directed implementation package or (group C) usual care (control) we recruited n=1 inpatient and n=1 outpatient service per group. Outcomes of feasibility, adherence to guidelines (medical file audits) and patient upper limb impairment (Fugl-Meyer Upper Extremity Assessment), activity (Box and Block Test) and practice (minutes/week) were collected at baseline and after 3 months of intervention. 29 therapists (8 in group A, 13 in groups B and 8 in group C) and 55 patients participated. Both the facilitator-mediated and the self-directed implementation packages were feasible to deliver in the rehabilitation setting. Therapists in group A improved with respect to guideline adherence (medical file audits median within-group proportion difference of 0.29 (95% CI 0.22 to 0.36, p .0001) preintervention to postintervention). No significant within-group differences from baseline to postintervention were found in group B or group C, and no between-group differences were found for upper limb outcomes. A facilitator-mediated package was acceptable to therapists working in stroke rehabilitation, and feasibility data suggest increased guideline uptake following implementation. An adequately powered study is planned to understand how to support therapists to provide evidence-based upper limb rehabilitation after stroke. Australian New Zealand Clinical Trials Registry (ACTRN12619000596101).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2021
DOI: 10.1161/STROKEAHA.120.032496
Abstract: Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose reporting guidelines (2) inadequate conceptualization of dose, which is multidimensional and (3) unclear and inconsistent terminology that incorporates the multiple dose dimensions. To address these challenges, we need a well-conceptualized and consistent approach to dose articulation that can be applied across stroke recovery domains to stimulate critical thinking about dose during intervention development, as well as promote reporting of planned intervention dose versus actually delivered dose. We followed the Design Research Paradigm to develop a framework that guides how to articulate dose, conceptualizes the multidimensional nature and systemic linkages between dose dimensions, and provides reference terminology for the field. Our framework recognizes that dose is multidimensional and comprised of a duration of days that contain in idual sessions and episodes that can be active (time on task) or inactive (time off task), and each in idual episode can be made up of information about length, intensity, and difficulty. Clinical utility of this framework was demonstrated via hypothetical application to preclinical and clinical domains of stroke recovery. The suitability of the framework to address dose articulation challenges was confirmed with an international expert advisory group. This novel framework provides a pathway for better articulation of nonpharmacological dose that will enable transparent and accurate description, implementation, monitoring, and reporting, in stroke recovery research.
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2023
DOI: 10.1101/2023.06.05.23291002
Abstract: Patients with large vessel occlusion (LVO) stroke of milder baseline clinical severity are often missed by pre-hospital severity-based triage tools. We examined whether these patients had differences in 1) markers of collateral circulation and 2) the relative harm of transfer delays on outcome, compared to patients with clinically more severe baseline deficits. Registry data from two large Australian thrombectomy centers was used to identify all directly presenting and transferred LVO patients undergoing endovascular thrombectomy, ided into those with milder baseline deficits (NIHSS ) and severe baseline deficits (NIHSS ≥10). Baseline CT-perfusion markers of collateral circulation and the association between transfer status and functional outcome (using the 90-day modified Rankin Scale) were compared. Of 1210 included LVO patients, 273 (22.6%) had milder severity. Milder LVO patients showed smaller median ischemic core volumes (12.6 [IQR 0.0-17.9] vs 27.5 [IQR 6.5-37.1] mL, p .001)), higher median perfusion mismatch ratio (148.3 [IQR 5.0-500.0] vs 66.2 [IQR 3.6-17.2], p .001) and lower median hypoperfusion intensity ratio (0.25 [IQR 0.18-0.38] vs 0.40 [IQR 0.22-0.57], p .001). Transferred patients had a lower odd of excellent outcome than primary presenters, when deficits were severe deficits (aOR 0.759 [95% CI 0.576-0.999]) but not when deficits were milder (aOR 1.357 [95% CI 0.764-2.409], pinteraction=0.122). Patients with LVO stroke of milder clinical severity have significantly better imaging markers of collateral circulation compared to high-severity patients. Despite high rates of thrombolytics, secondary transfer to thrombectomy-center was only associated with poorer 90-day functional outcomes in higher-severity patients. Failure of pre-hospital screening tools to detect lower-severity LVO patients for immediate pre-hospital bypass to a thrombectomy center may not deleteriously affect their outcome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2023
DOI: 10.1161/STROKEAHA.122.041260
Abstract: Several methods for conducting power analysis of studies with outcomes across the full ordinal modified Rankin Scale are proposed in the literature. No systematic comparison of accuracy, agreement, and sensitivity to small changes in hypothesized effect sizes for these methods is available. Our aim is to conduct such a systematic comparative analysis and to introduce a comprehensive freely available online tool to facilitate appropriate power analyses for ordinal outcomes. We performed simulation studies utilizing the control arm modified Rankin Scale distributions from the AVERT (A Very Early Rehabilitation Trial), EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits), and HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) studies, as well as a uniform distribution, in combination with hypothetical treatment effects. We systematically evaluated published power formulas for Ordinal Logistic Regression and Tournament Methods (generalized odds ratio Win Probability Win Ratio and Wilcoxon-Mann-Whitney U test). We also developed an online and downloadable Shiny R app facilitating s le size calculation for, and ordinal analysis of, modified Rankin Scale data. Power formulas for Tournament Methods performed well, while the formula for ordinal logistic regression was inaccurate. Tang’s Wilcoxon-Mann-Whitney U test s le size formula exhibited the highest accuracy. All methods, including ordinal logistic regression, had almost identical empirical power for a given s le size. All power methods exhibited sensitivity to small changes in hypothesized effect size. The developed freely available online app supports analytical and visualization requirements for all investigated methods for power and statistical analyses of ordinal modified Rankin Scale outcomes. As Tournament Method s le size formulas are assumption-free and accurately calculate power, stroke researchers should use these methods when designing studies with outcomes measured on the full or partially collapsed modified Rankin Scale as well as other ordinal scales, even if they intend to use ordinal logistic regression for analysis. Conducting sensitivity analyses of the effect size assumptions are essential for appropriate s le size estimation. Our developed tool supports both of these recommendations ( www.thembc.com.au/tournamentmethods ).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2023
DOI: 10.1161/STROKEAHA.122.041061
Abstract: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or % reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06] P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03] P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83] P interaction =0.16). Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.REHAB.2021.101487
Abstract: To enable development of effective interventions, there is a need to complete systematic early-phase dose articulation research. This scoping review aimed to synthesize dose articulation research of behavioral motor interventions for stroke recovery. MEDLINE and EMBASE were systematically searched for dose articulation studies. Preclinical experiments and adult clinical trials were classified based on the discovery pipeline and analyzed to determine which dose dimensions were articulated (time, scheduling or intensity) and how they were investigated (unidimensional vs multidimensional approach). Reporting of dose, safety and efficacy outcomes were summarized. The intervention description, risk of bias, and quality was appraised. We included 41 studies: 3 of preclinical dose preparation (93 rodents), 2 Phase I dose ranging (21 participants), 9 Phase IIA dose screening (198 participants), and 27 Phase IIB dose finding (1879 participants). All studies adopted a unidimensional approach. Time was the most frequent dimension investigated (53%), followed by intensity (29%), and scheduling (18%). Overall, 95% studies reported an efficacy outcome however, only 65% reported dose and 45% reported safety. Across studies, 61% were at high risk of bias, and the average percentage reporting of intervention description and quality was 61% and 67%, respectively. This review highlights a need to undertake more high-quality, early-phase studies that systematically articulate intervention doses from a multidimensional perspective in the field of behavioral motor stroke recovery. To address this gap, we need to invest in adapting early phase trial designs, especially Phase I, to support multidimensional dose articulation.
Publisher: Cold Spring Harbor Laboratory
Date: 21-08-2019
DOI: 10.1101/742494
Abstract: Executive function deficits in Alzheimer’s disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APP/PS1 mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2022
DOI: 10.1161/STROKEAHA.120.034019
Abstract: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NIHSS may be considered ineligible for reperfusion therapies. This study aimed to develop a modified version of the NIHSS, the Posterior NIHSS (POST-NIHSS), to improve NIHSS prognostic accuracy for posterior circulation stroke patients with mild-moderate symptoms. Clinical data of consecutive posterior circulation stroke patients with mild-moderate symptoms (NIHSS ), who were conservatively managed, were retrospectively analyzed from the Basilar Artery Treatment and Management registry. Clinical features were assessed within 24 hours of symptom onset dysphagia was assessed by a speech therapist within 48 hours of symptom onset. Random forest classification algorithm and constrained optimization were used to develop the POST-NIHSS in the derivation cohort. The POST-NIHSS was then validated in a prospective cohort. Poor outcome was defined as modified Rankin Scale score ≥3 at 3 months. We included 202 patients (mean [SD] age 63 [14] years, median NIHSS 3 [interquartile range, 1–5]) in the derivation cohort and 65 patients (mean [SD] age 63 [16] years, median NIHSS 2 [interquartile range, 1–4]) in the validation cohort. In the derivation cohort, age, NIHSS, abnormal cough, dysphagia and gait/truncal ataxia were ranked as the most important predictors of functional outcome. POST-NIHSS was calculated by adding 5 points for abnormal cough, 4 points for dysphagia, and 3 points for gait/truncal ataxia to the baseline NIHSS. In receiver operating characteristic analysis adjusted for age, POST-NIHSS area under receiver operating characteristic curve was 0.80 (95% CI, 0.73–0.87) versus NIHSS area under receiver operating characteristic curve, 0.73 (95% CI, 0.64–0.83), P =0.03. In the validation cohort, POST-NIHSS area under receiver operating characteristic curve was 0.82 (95% CI, 0.69–0.94) versus NIHSS area under receiver operating characteristic curve 0.73 (95% CI, 0.58–0.87), P =0.04. POST-NIHSS showed higher prognostic accuracy than NIHSS and may be useful to identify posterior circulation stroke patients with NIHSS at higher risk of poor outcome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
DOI: 10.1161/STROKEAHA.121.036537
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has presented unique challenges to stroke care and research internationally. In particular, clinical trials in stroke are vulnerable to the impacts of the pandemic at multiple stages, including design, recruitment, intervention, follow-up, and interpretation of outcomes. A carefully considered approach is required to ensure the appropriate conduct of stroke trials during the pandemic and to maintain patient and participant safety. This has been recently addressed by the International Council for Harmonisation which, in November 2019, released an addendum to the Statistical Principles for Clinical Trials guidelines entitled Estimands and Sensitivity Analysis in Clinical Trials. In this article, we present the International Council for Harmonisation estimand framework for the design and conduct of clinical trials, with a specific focus on its application to stroke clinical trials. This framework aims to align the clinical and scientific objectives of a trial with its design and end points. It also encourages the prospective consideration of potential postrandomization intercurrent events which may occur during a trial and either impact the ability to measure an end point or its interpretation. We describe the different categories of such events and the proposed strategies for dealing with them, specifically focusing on the COVID-19 pandemic as a source of intercurrent events. We also describe potential practical impacts posed by the COVID-19 pandemic on trials, health systems, study groups, and participants, all of which should be carefully reviewed by investigators to ensure an adequate practical and statistical strategy is in place to protect trial integrity. We provide ex les of the implementation of the estimand framework within hypothetical stroke trials in intracerebral hemorrhage and stroke recovery. While the focus of this article is on COVID-19 impacts, the strategies and principles proposed are well suited for other potential events or issues, which may impact clinical trials in the field of stroke.
Publisher: Wiley
Date: 14-07-2017
Abstract: Home visits by occupational therapists are a routine part of practice, but there remains little understanding about factors that are associated with the decision to complete a home visit. The aim of this study was to investigate the rate of pre-discharge home visits by occupational therapists for patients following hip fracture and explore factors associated with their occurrence. A retrospective cohort study including 293 patients admitted to a metropolitan health service following hip fracture. Multi-variate logistic regression was used to identify significant variables associated with receiving a home visit. Home visits were conducted by occupational therapists for 28% of patients admitted from a private residence, and for less than 5% of patients admitted from low-level residential care facilities. The variables significantly associated with receiving a home visit at a private residence were older age and being admitted to a rehabilitation ward, but the model only explained between 9% and 13% of the variance. Other clinical and socio-demographic variables evaluated were not associated with the provision of a home visit. About one in four people admitted to hospital from a private residence following hip fracture receive a home visit. The results suggest that whether or not a patient receives a home visit has little to do with socio-demographic or clinical factors at the time of admission to hospital. There remains much unexplained variation in whether or not a patient receives a home visit and this study highlights the ersity that exists in clinical practice.
Publisher: Informa UK Limited
Date: 24-09-2022
Publisher: Informa UK Limited
Date: 22-09-2022
DOI: 10.1080/09638288.2020.1815873
Abstract: In search of Kipling's six honest serving men in upper limb rehabilitation after stroke, we sought to investigate clinicians' perspective of In total, 225 Australian stroke clinicians responded: 53% occupational therapists, 61% working in acute/inpatient stroke setting. Most respondents indicated they did not have a protocol/expectation regarding when (62%), how much (84%) or what (60%) therapy to provide in their setting. Respondents ranked 24-h to 7-days post-stroke as the optimal time to commence therapy, and 30- to 60-min per day as the optimal dose to provide. Within-participant experiments demonstrated that greater motor recovery as time progressed increased the odds of offering therapy, while lack of motor recovery, shoulder pain, neurological decline and sole therapist reduced the odds. We need to develop an evidence base concerning Kipling's six honest serving men and equip clinicians with clinical decision-making skills aligned with this focus.IMPLICATIONS FOR REHABILITATIONMost clinicians did not have access to a protocol / clinical pathway which defines when, how much and what upper limb therapy to provide after stroke, which may be improved by providing in idual clinicians with organisational support to make therapy decisions.To improve the personalisation of upper limb rehabilitation in clinical practice, we need to understand
Publisher: MDPI AG
Date: 28-07-2023
Abstract: Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson’s disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2021
DOI: 10.1161/STROKEAHA.120.030661
Abstract: Distal clot migration is a recognized event following intravenous thrombolysis (IVT) in the setting of acute ischemic stroke. Of note, clots that were initially retrievable by endovascular thrombectomy may migrate to a distal nonretrievable location and compromise clinical outcome. We investigated the incidence of clot migration leading to clot inaccessibility following IVT in the time window of 4.5 to 9 hours. We performed a retrospective analysis of the EXTEND trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits) data. Baseline and 12- to 24-hour follow-up clot location was determined on computed tomography angiogram or magnetic resonance angiogram. The incidence of clot migration leading to a change from retrievable to nonretrievable location was identified and compared between the two treatment groups (IVT versus placebo). Two hundred twenty patients were assessed. Clot migration from a retrievable to nonretrievable location occurred in 37 patients: 21 patients (19.3%) in the placebo group and 16 patients (14.4%) in the IVT group. No significant difference was identified in the incidence of clot migration leading to inaccessibility between groups ( P =0.336). Our results did not show increased clot migration leading to clot inaccessibility in patients treated with IVT.
Publisher: Cold Spring Harbor Laboratory
Date: 19-08-2020
DOI: 10.1101/2020.08.16.20176230
Abstract: We aimed to compare the pre, lockdown, and post-lockdown aeromedical retrieval (AR) diagnostic reasons and patient demographics during a period of Coronavirus 2019 (COVID-19) social isolation. An observational study with retrospective data collection, consisting of Australians who received an AR between the 26 January to the 23 June 2020. The main outcome measures were patient diagnostic category proportions and trends prior (28 January to 15 March), during (16 March to 4 May), and following (5 May to 23 June 2020) social isolation restrictions. There were 16981 ARs consisting of 1959 (11.5) primary evacuations (PE) and 12724 (88.5) inter-hospital transfer (IHT), with a population median age of 52 years old (interquartile range [IQR] 29.0–69.0), with 49.0% (n = 8283) of the cohort being male and 38.0% (n = 6399) being female. There were a total of 6 confirmed and 209 suspected cases of COVID-19, with the majority of cases (n = 114 53.0%) in the social isolation period. As compared to pre-restriction, the odds of retrieval for the restriction and post-restriction period differed across time between the major diagnostic groups. This included, an increase in cardiovascular retrieval for both restriction and post-restriction periods (OR 1.12 95% CI 1.02-1.24 and OR 1.18 95% CI 1.08-1.30 respectively), increases in neoplasm in the post restriction period (OR 1.31 95% CI 1.04-1.64), and increases for congenital conditions in the restriction period (OR 2.56 95% CI 1.39-4.71). Cardiovascular and congenital conditions had increased rates of priority 1 patients in the restriction and post restriction periods. There was a decrease in endocrine and metabolic disease retrievals in the restriction period (OR 0.72 95% CI 0.53-0.98). There were lower odds during the post-restriction period for a retrievals of the respiratory system (OR 0.78 95% CI 0.67-0.93), and disease of the skin (OR 0.78 95% CI 0.6-1.0). Distribution between the 2019 and 2020 time periods differed (p 0.05), with the lockdown period resulting in a significant reduction in activity. The lockdown period resulted in increased AR rates of circulatory and congenital conditions. However, this period also resulted in a reduction of overall activity, possibly due to a reduction in other infectious disease rates, such as influenza, due to social distancing.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2022
DOI: 10.1161/STROKEAHA.122.038829
Abstract: Evidence is growing on anticancer effects of statins. We investigated whether the effectiveness of treatment with statins after ischemic stroke on mortality is influenced by a history of cancer. Analyses of 90-day survivors of ischemic stroke (2012–2016 45 hospitals) using linked registry and administrative data. Dispense of statins within 90 days postdischarge was determined from pharmaceutical records. Participants were followed from 91 days postdischarge until death or June 30, 2018. History of cancer was determined from hospital data. Propensity score–adjusted Cox proportional hazards regression model was used to determine the association between being dispensed statins and survival. The influence of history of cancer on this association was assessed based on the concepts of (1) statistical interaction and (2) biological interaction using 3 indices: relative excess risk due to interaction , attributable proportion due to interaction , or synergy index . Among 9948 eligible participants (median age=72 years, 42% female), there were 1463 deaths. In adjusted analyses, there was no statistical interaction between being dispensed statins and history of cancer on mortality ( P =0.156). However, being dispensed statins had a significant positive biological interaction with having a history of cancer on mortality: relative excess risk due to interaction, 2.80 (95% CI, 1.56–5.05), attributable proportion due to interaction, 0.45 (95% CI, 0.23–0.66), and synergy index, 2.14 (95% CI, 1.32–3.49). Treatment with statins after ischemic stroke may confer additional survival benefits for people who also have had cancer.
Publisher: BMJ
Date: 30-11-2021
Abstract: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. A s le size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive s le size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours or matching placebo. The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.
Publisher: Informa UK Limited
Date: 11-06-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2022
DOI: 10.1161/STROKEAHA.121.036104
Abstract: Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24–72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy. We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible ( mm), mild (≥1 to mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere. Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00–1.028), 1.03 (IQR, 1.01–1.077), and 1.15 (IQR, 1.08–1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days ( P .002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 [95% CI, 1.03–1.20], P =0.005 rHV β, 0.39 [95% CI, 0.24–0.55], P .0001), as was reduced cerebral blood flow (MLS cOR, 0.25 [95% CI, 0.10–0.58], P =0.001 rHV β, −2.95 [95% CI, −4.61 to −11.29], P =0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 [95% CI, 0.14–0.98], P =0.045 rHV β, −2.59 [95% CI, −4.32 to −0.86], P =0.004). BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
DOI: 10.1161/STROKEAHA.121.034348
Abstract: This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22–66) and study s le size remains small (median n=30, IQR 20–48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute ( hours), 13 acute (1–7 days), 176 early subacute (8–90 days), 34 late subacute (91–180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600–1430) min/session, 1 (IQR, 1–1) session/d, 5 (IQR, 5–5) d/wk for 4 (IQR, 3–5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and s le size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2022
No related organisations have been discovered for Leonid Churilov.
Start Date: 07-2003
End Date: 12-2008
Amount: $69,099.00
Funder: Australian Research Council
View Funded ActivityStart Date: 12-2002
End Date: 12-2007
Amount: $67,635.00
Funder: Australian Research Council
View Funded Activity