Introduction: High blood pressure (BP) is associated with a poor outcome after stroke. Trials of transdermal glyceryl trinitrate (GTN), a nitric oxide donor, have suggested that treatment between 3 and 5 h might improve functional outcome. Methods: We randomly assigned hospitalised patients with an acute ischaemic or haemorrhagic stroke to 2 days of transdermal GTN (5 mg/day) or sham, started between 3 and 5 h after onset. The primary feasibility outcome was recruitment rate; proof-of-concept (PoC) was assessed at 90 days by central observers blinded to treatment assignment using the modified Rankin Scale (mRS). Data are number (%), median [interquartile range], or mean (standard deviation). Comparisons were assessed by multiple linear regression. Results: Thirty-nine of an intended 120 participants were recruited. A total of 3,314 people were excluded, commonly related to presentation >5 h of onset or outside of researcher working hours, no eligible symptoms/signs or an unclear onset time. Mean age was 72 (SD 13) years, females were 41%, BP was 161.8 (18.4)/80.8 (14.9) mm Hg, and time from onset at baseline was 216 [186, 251] minutes. The fall in BP over 24 h did not differ between GTN versus sham. mRS at 3 months did not differ between the groups (difference in means, DIM -0.20, 95% confidence intervals -1.30, 0.90; p = 0.72). GTN was associated with improved cognition on the telephone interview of cognition scale (DIM 8.0, 95% CI 1.3, 14.8; p = 0.020). Although headache was more common, GTN was associated with fewer serious adverse events (p = 0.020). Conclusion: Recruitment limitations in this small single-centre trial prevented demonstration of feasibility for patients in the time window of 3-5 h post ictus. GTN demonstrated some evidence of PoC and was safe. A multicentre trial needs to further test this hypothesis.

Background High blood pressure is associated with a poor outcome after stroke. Trials of transdermal glyceryl trinitrate (GTN), a nitric oxide donor, have suggested that treatment between 3 and 5 hours might improve functional outcome. Methods We randomly assigned hospitalised patients with an acute ischaemic or haemorrhagic stroke to 2 days of transdermal glyceryl trinitrate (GTN, 5 mg/day) or sham, started between 3 and 5 hours after onset. The primary feasibility outcome was recruitment rate; proof of concept was assessed by central observers blinded to treatment assignment at 90 days using the modified Rankin Scale (mRS). Data are number (%), median [interquartile range] or mean (standard deviation). Comparisons by adjusted multiple linear regression. Findings 39 of an intended 120 participants were recruited; common exclusions were presentation >5 hours of onset or out of researcher working hours, no eligible symptoms/signs or an unclear onset time. Mean age 72 (13) years, female 41%, blood pressure 161.8(18.4)/80.8(14.9) mmHg, time from onset at baseline 216 [186, 251] minutes. The fall in blood pressure over 24 hours did not differ between GTN versus sham. Headache was more common with GTN but there was no difference in serious adverse events. mRS at 3 months did not differ between the groups. Interpretation Recruitment limitations prevented demonstration of feasibility for patients in the time window of 3-5 hours post ictus. GTN appeared safe and showed some evidence of proof-of-concept. A multicentre trial needs to further test this hypothesis. Registration ISRCTN17654248 Date: 31/3/2021

BACKGROUND: Nurses often carry out swallow screening when patients are admitted to hospital following a stroke, some receive further training to conduct more comprehensive tests. Little is known about how they perceive their role. The aim of this study was to understand the experiences of Dysphagia Trained Nurses (DTNs) in acute stroke who conduct the comprehensive tests. METHODS: Nine DTNs were recruited from one UK hospital. They were identified by maximum variation and convenience sampling ensuring a broad demographic. Semi-structured interviews were carried out during usual shift patterns, in a quiet room on the acute stroke unit by a research and clinical SLT. Thematic analysis was conducted by two researchers and a summary of themes was verified by the participants. RESULTS: Four main themes were identified relating to the role, screening tool, training and pathway. The role was highly regarded, bringing professional benefits such as job satisfaction and career development. Nurses also identified that it was an essential role in acute stroke for the health and wellbeing of patients. The tool was easy to use but needed adaptations at times and the pathway was difficult to adhere to during busy periods when the use of the test with certain patients was questioned. Training and support was deemed crucial for the role and confidence developed with experience. CONCLUSIONS: Dysphagia Trained Nurses who conduct comprehensive dysphagia screening tests in acute stroke value the role. Further research is needed to quantify the impact that the nurses have on patient outcomes and stroke pathways.

Remote ischaemic per‐conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. The effect of RIC on plasma biomarkers was assessed using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST‐1).

Post stroke dysphagia (PSD) is common and associated with poor outcome. The Dysphagia Severity Rating Scale (DSRS), which grades how severe dysphagia is based on fluid and diet modification and supervision requirements for feeding, is used for clinical research but has limited published validation information. Multiple approaches were taken to validate the DSRS, including concurrent- and predictive criterion validity, internal consistency, inter- and intra-rater reliability and sensitivity to change. This was done using data from four studies involving pharyngeal electrical stimulation in acute stroke patients with dysphagia, an individual patient data meta-analysis and unpublished studies (NCT03499574, NCT03700853). In addition, consensual- and content validity and the Minimal Clinically Important Difference (MCID) were assessed using anonymous surveys sent to UK-based Speech and Language Therapists (SLTs). Scores for consensual validity were mostly moderate (62.5-78%) to high or excellent (89-100%) for most scenarios. All but two assessments of content validity were excellent. In concurrent criterion validity assessments, DSRS was most closely associated with measures of radiological aspiration (penetration aspiration scale, Spearman rank rs = 0.49, p < 0.001) and swallowing (functional oral intake scale, FOIS, rs = -0.96, p < 0.001); weaker but statistically significant associations were seen with impairment, disability and dependency. A similar pattern of relationships was seen for predictive criterion validity. Internal consistency (Cronbach's alpha) was either "good" or "excellent". Intra and inter-rater reliability were largely "excellent" (intraclass correlation >0.90). DSRS was sensitive to positive change during recovery (medians: 7, 4 and 1 at baseline and 2 and 13 weeks respectively) and in response to an intervention, pharyngeal electrical stimulation, in a published meta-analysis. The MCID was 1.0 and DSRS and FOIS scores may be estimated from each other. The DSRS appears to be a valid tool for grading the severity of swallowing impairment in patients with post stroke dysphagia and is appropriate for use in clinical research and clinical service delivery.

Background Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may protect the brain from ischemic reperfusion injury. Methods and Results We performed a phase IIb blinded dose‐escalation sham‐controlled trial in patients with hyperacute stroke, randomized 1:1 to receive RIC (four 5‐minute cycles) or sham to the nonparetic upper limb, in 3 blocks of increasing dose, starting within 6 hours of ictus. The primary outcome was trial feasibility (recruitment, attrition). Secondary outcomes included adherence, tolerability, safety (serious adverse events), plasma biomarkers at days 1 and 4 (S100‐ß protein, matrix metalloproteinase‐9, and neuron‐specific enolase), and functional outcome. Sixty participants were recruited from 2 centers (3 per month) with no loss to follow‐up: time to randomization 4 hours 5 minutes (SD 72 minutes), age 72 years (12), men 60%, blood pressure 154/80 mm Hg (25/12), National Institutes of Health Stroke Scale 8.4 (6.9), and 55% thrombolyzed. RIC was well tolerated with adherence not differing between RIC and sham, falling in both groups on day 3 (P=0.001, repeated measures ANOVA) because of discharge or transfer. S100ß increased in the sham group (mean rise 111 pg/mL [302], P=0.041, repeated measures ANCOVA) but not the RIC group. There were no differences in matrix metalloproteinase‐9, neuron‐specific enolase, number with serious adverse events (RIC 10 versus sham 10, P=0.81), deaths (2 versus 4, P=0.36), or modified Rankin Scale score (2 [interquartile range 1–4], 2 [interquartile range, 1–3]; P=0.85). Conclusions RIC in hyperacute stroke is feasible when given twice daily for 2 days and appears safe in a small population with hyperacute stroke. A larger phase III trial is warranted. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02779712.

(1) Vascular Medicine, Division of Medical Sciences and GEM, School of Medicine, University of Nottingham, UK (2) Stroke, Royal Derby Hospital, University Hospitals of Derby and Burton, NHS Foundation Trust, UK (3) Stroke Trials Unit, Division of Clinical Neuroscience, City Hospital campus, University of Nottingham NG5 1PB, UK (4) Stroke, Nottingham University Hospitals NHS Trust, City Hospital campus, Nottingham NG5 1PB

Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH.