Predicting outcome in acute stroke with large vessel occlusion:application and validation of MR PREDICTS in the ESCAPE-NA1 population

Background: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. Patients and methods: MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. Results: Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0–2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71–0.81). Conclusion: Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.</p

Defining Optimal Brain Health in Adults A Presidential Advisory From the American Heart Association/American Stroke Association

Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA's Life's Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index < 25 kg/m(2)) and 3 ideal health factors (untreated blood pressure < 120/< 80 mm Hg, untreated total cholesterol < 200 mg/dL, and fasting blood glucose < 100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimer's Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA's Life's Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA's Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention

Expanding the evidence of endovascular treatment for acute ischemic stroke: patient–centered outcomes, population–level impact, and patients presenting with mild stroke symptoms

Endovascular treatment (EVT) for anterior circulation acute ischemic stroke due to large?vessel occlusion is the new standard of care resulting in reduced disability compared to medical treatment. Practice guidelines recommend the use of EVT but can only speak to the evidence provided by clinical trials and might not be appropriate when complex medical decisions need to consider the heterogeneity of patients in routine clinical care. Brought about by the limitations of the clinical trials, the work described in this doctoral thesis aimed to assess the long–term sustainability of efficacy of EVT, the utilization of post–stroke outcomes that are patient–centered and more meaningful to affected individuals, and the effectiveness of EVT in patient populations that have not been part of clinical trial cohorts. These are commonly older patients with comorbidities and patients presenting with mild stroke symptoms. The miFUNCTION scale was shown to display greater granularity in the mild to moderately–severe disability range post–stroke compared to the modified Rankin Scale and thus provide more insight into the patient's ability and capacity to engage in meaningful life roles after EVT. In a population–based analysis, adult patients undergoing EVT spent on average more than one week longer at home within the first 90 days compared with patients receiving medical treatment. Home?time was used as a novel, health?economic, and patient?centered outcome. For patients presenting with mild symptoms, EVT resulted in similar 90–day outcomes compared to medical management despite an increased risk of neurological deterioration at 24 hours. Due to uncertainty regarding the risk–benefit–ratio, a well–designed clinical trial will need to establish how best to treat these patients. Overall, the work described here provides greater understanding of how the benefits and risks of EVT might vary across the population and differ from the rather homogenous patient cohort that has been assessed in the clinical trials. The results of this research will be meaningful to patients who experience acute ischemic strokes caused by large vessel occlusion and also aid with economic and regulatory decisions to more broadly offer and organize EVT across Alberta and beyond

Expanding the evidence of endovascular treatment for acute ischemic stroke: patient–centered outcomes, population–level impact, and patients presenting with mild stroke symptoms

Endovascular treatment (EVT) for anterior circulation acute ischemic stroke due to large‐vessel occlusion is the new standard of care resulting in reduced disability compared to medical treatment. Practice guidelines recommend the use of EVT but can only speak to the evidence provided by clinical trials and might not be appropriate when complex medical decisions need to consider the heterogeneity of patients in routine clinical care. Brought about by the limitations of the clinical trials, the work described in this doctoral thesis aimed to assess the long–term sustainability of efficacy of EVT, the utilization of post–stroke outcomes that are patient–centered and more meaningful to affected individuals, and the effectiveness of EVT in patient populations that have not been part of clinical trial cohorts. These are commonly older patients with comorbidities and patients presenting with mild stroke symptoms. The miFUNCTION scale was shown to display greater granularity in the mild to moderately–severe disability range post–stroke compared to the modified Rankin Scale and thus provide more insight into the patient's ability and capacity to engage in meaningful life roles after EVT. In a population–based analysis, adult patients undergoing EVT spent on average more than one week longer at home within the first 90 days compared with patients receiving medical treatment. Home‐time was used as a novel, health‐economic, and patient‐centered outcome. For patients presenting with mild symptoms, EVT resulted in similar 90–day outcomes compared to medical management despite an increased risk of neurological deterioration at 24 hours. Due to uncertainty regarding the risk–benefit–ratio, a well–designed clinical trial will need to establish how best to treat these patients. Overall, the work described here provides greater understanding of how the benefits and risks of EVT might vary across the population and differ from the rather homogenous patient cohort that has been assessed in the clinical trials. The results of this research will be meaningful to patients who experience acute ischemic strokes caused by large vessel occlusion and also aid with economic and regulatory decisions to more broadly offer and organize EVT across Alberta and beyond

Comprehensive assessment of disability post-stroke using the newly developed miFUNCTION scale

Background and Purpose: The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability impairs outcome assessment as well as reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health, we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the modified Rankin Scale and deliver a more thorough understanding of disability following stroke. Methods: The initial construct validity of miFUNCTION was established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the modified Rankin Scale and other outcome measures within the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the beneficial effect of endovascular treatment. Results: The pilot study showed moderate inter-observer agreement (k = 0.585, p < 0.005) but near perfect correlation between miFUNCTION and modified Rankin Scale (ρ = 0.821, p < 0.05). The correlation of miFUNCTION and modified Rankin Scale was near perfect again in the ESCAPE trial (ρ = 0.944). Effect size of the multivariable models using modified Rankin Scale (adjusted odds ratio: 3.45, 95% confidence interval: 2.05–5.78) and miFUNCTION (adjusted odds ratio: 3.32, 95% confidence interval: 1.99–5.55) as an outcome measure for the ESCAPE trial patients was similar. Conclusions: miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and a clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.</p

Association of time on outcome after intravenous thrombolysis in the elderly in a telestroke network

Background: Recent studies showed that the safety and benefit of early intravenous (IV) thrombolysis on favourable outcomes in acute ischemic stroke are also seen in the elderly. Furthermore, it has shown that age increases times for pre- and in-hospital procedures. We aimed to assess the applicability of these findings to telestroke. Methods: We retrospectively analysed 542 of 1659 screened consecutive stroke patients treated with IV thrombolysis in our telestroke network in East-Saxony, Germany from 2007 to 2012. Outcome data were symptomatic intracranial hemorrhage (sICH) by ECASS-2-criteria, survival at discharge and favourable outcome, defined as a modified Rankin scale (mRS) of 0–2 at discharge. Results: Thirty-three percent of patients were older than 80 years (elderly). Being elderly was associated with higher risk of sICH (p¼0.003), less favourable outcomes (p¼0.02) and higher mortality (p¼0.01). Using logistic regression analysis, earlier onsetto-treatment time was associated with favourable outcomes in not elderly patients (adjusted odds ratio (OR) 1.18; 95% CI 1.03–1.34; p¼0.01), and tended to be associated with favourable outcomes (adjusted OR 1.13; 95% CI 0.92–1.38; p¼0.25) and less sICH (adjusted OR 0.88; 95% CI 0.76–1.03; p¼0.11) in elderly patients. Age caused no significant differences in onset-to-doortime (p¼0.25), door-to-treatment-time (p¼0.06) or onset-to-treatment-time (p¼0.29). Conclusion: Treatment time seems to be critical for favourable outcome after acute ischemic stroke in the elderly. Age is not associated with longer delivery times for thrombolysis in telestroke

Comprehensive assessment of disability post-stroke using the newly developed miFUNCTION scale

Background and Purpose: The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability impairs outcome assessment as well as reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health, we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the modified Rankin Scale and deliver a more thorough understanding of disability following stroke. Methods: The initial construct validity of miFUNCTION was established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the modified Rankin Scale and other outcome measures within the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the beneficial effect of endovascular treatment. Results: The pilot study showed moderate inter-observer agreement (k = 0.585, p < 0.005) but near perfect correlation between miFUNCTION and modified Rankin Scale (ρ = 0.821, p < 0.05). The correlation of miFUNCTION and modified Rankin Scale was near perfect again in the ESCAPE trial (ρ = 0.944). Effect size of the multivariable models using modified Rankin Scale (adjusted odds ratio: 3.45, 95% confidence interval: 2.05–5.78) and miFUNCTION (adjusted odds ratio: 3.32, 95% confidence interval: 1.99–5.55) as an outcome measure for the ESCAPE trial patients was similar. Conclusions: miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and a clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale