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Supplemental Material for A randomized 500-subject open-label phase 3 clinical trial of minimally invasive surgery plus alteplase in intracerebral hemorrhage evacuation (MISTIE III) by Wendy C Ziai, Nichol McBee, Karen Lane, Kennedy R Lees, Jesse Dawson, Paul Vespa, Richard E Thompson, A David Mendelow, Carlos S Kase, J Ricardo Carhuapoma, Carol B Thompson, Steven W Mayo, Pat Reilly, Scott Janis, Craig S Anderson, Mark R Harrigan, Paul J Camarata, Jean-Louis Caron, Mario Zuccarello, Issam A Awad, Daniel F Hanley and On Behalf of the MISTIE III Investigators in International Journal of Stroke

Supplemental Material for Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke by Teresa J Kimberley, Cecília N Prudente, Navzer D Engineer, David Pierce, Brent Tarver, Steven C Cramer, David Alexander Dickie and Jesse Dawson in European Stroke Journal

Supplemental Material for Oedema extension distance in intracerebral haemorrhage: Association with baseline characteristics and long-term outcome by Robert Hurford, Andy Vail, Calvin Heal, Wendy C Ziai, Jesse Dawson, Santosh B Murthy, Xia Wang, Craig S Anderson, Daniel F Hanley, Adrian R Parry-Jones and on behalf of the VISTA-ICH Collaborators: the STRONG STAR Consortium in European Stroke Journal

Background:\ud \ud Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear.\ud Objective:\ud \ud The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses.\ud Design:\ud \ud A national record linkage cohort study.\ud Setting:\ud \ud All renal and stroke units in Scotland, UK.\ud Patients:\ud \ud All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015).\ud Measurements:\ud \ud Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records.\ud Methods:\ud \ud Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke.\ud Results:\ud \ud Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death.\ud Limitations:\ud \ud Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available.\ud Conclusions:\ud \ud The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.

Background and Purpose- We assessed safety, feasibility, and potential effects of vagus nerve stimulation (VNS) paired with rehabilitation for improving arm function after chronic stroke. Methods- We performed a randomized, multisite, double-blinded, sham-controlled pilot study. All participants were implanted with a VNS device and received 6-week in-clinic rehabilitation followed by a home exercise program. Randomization was to active VNS (n=8) or control VNS (n=9) paired with rehabilitation. Outcomes were assessed at days 1, 30, and 90 post-completion of in-clinic therapy. Results- All participants completed the course of therapy. There were 3 serious adverse events related to surgery. Average FMA-UE scores increased 7.6 with active VNS and 5.3 points with control at day 1 post-in-clinic therapy (difference, 2.3 points; CI, -1.8 to 6.4; P=0.20). At day 90, mean scores increased 9.5 points from baseline with active VNS, and the control scores improved by 3.8 (difference, 5.7 points; CI, -1.4 to 11.5; P=0.055). The clinically meaningful response rate of FMA-UE at day 90 was 88% with active VNS and 33% with control VNS ( P

Background:\ud \ud Allopurinol, a xanthine oxidase inhibitor, reduced progression of carotid-intima media thickness and lowered blood pressure in a small clinical trial in people with ischaemic stroke. Xanthine oxidase inhibition for improvement of long-term outcomes following ischaemic stroke and transient ischaemic attack (XILO-FIST) aims to assess the effect of allopurinol treatment on white matter hyperintensity progression and blood pressure after stroke. This paper describes the XILO-FIST protocol.\ud Methods:\ud \ud XILO-FIST is a multicentre randomised double-blind, placebo-controlled, parallel group clinical trial funded by the British Heart Foundation and the Stroke Association. The trial has been adopted by the Scottish Stroke Research Network and the UK Clinical Research Network. The trial is registered in clinicaltrials.gov (registration number NCT02122718). XILO-FIST will randomise 464 participants, aged greater than 50 years, with ischaemic stroke within the past month, on a 1:1 basis, to two years treatment with allopurinol 300 mg twice daily or placebo. Participants will undergo brain magnetic resonance imaging, cognitive assessment, ambulatory blood pressure monitoring and blood sampling at baseline and after two years treatment. The primary outcome will be white matter hyperintensity progression, measured using the Rotterdam progression scale. Secondary outcomes will include change in white matter hyperintensity volume, mean day-time systolic blood pressure and measures of cognitive function. Up to 100 will undergo additional cardiac magnetic resonance imaging in a sub-study of left ventricular mass.\ud Discussion:\ud \ud If white matter hyperintensity progression is reduced, allopurinol could be an effective preventative treatment for patients with ischaemic stroke and clinical endpoint studies would be needed. If allopurinol reduces blood pressure after stroke, then it could be used to help patients reach blood pressure targets.

Introduction:\ud Stroke rate and mortality are greater in people with end-stage renal disease (ESRD) than those without. We examined discrepancies in stroke-care in ESRD patients and its influence on mortality.\ud \ud Methods:\ud A national record-linkage cohort study of hospitalised stroke from 2005-2013. Presentation, measures of care quality (admission to stroke unit, swallow assessment, anti-thrombotic or thrombolysis use) and outcomes were compared in those with and without ESRD after propensity score matching (PSM). We examined the effect being admitted to a stroke unit on survival using Kaplan-Meier and Cox survival analyses.\ud \ud Results:\ud 8,757 people with ESRD and 61,367 people with stroke were identified. 486 ESRD patients experienced stroke over 34,551.9 years follow-up; incidence rates 25.3 (dialysis) and 4.5 (kidney transplant)/ 1000 patient-years. Following PSM, dialysis patients were less likely to be functionally independent (61.4 vs 77.7%, p

Supplemental material, Supplementary Data and Tables for A survey of opinion: When to start oral anticoagulants in patients with acute ischaemic stroke and atrial fibrillation? by David Munn, Azmil H Abdul-Rahim, Urs Fischer, David J Werring, Thompson G Robinson and Jesse Dawson in European Stroke Journal