Cross-education of lower limb muscle strength following resistance exercise training in males and females: A systematic review and meta-analysis.

Cross-education describes the training of one limb that leads to performance enhancements in the contralateral untrained limb, driven by neural changes rather than muscle adaptation. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of cross-education (vs. a control group) via resistance exercise training (RET) for improving muscle strength in the untrained lower limb of healthy males and females. A literature search from inception to September 2023 was conducted using MEDLINE (via PubMed), the Cochrane Library (CENTRAL), Web of Science (Core Database), Scopus, EBSCO-host, and Ovid-EMBASE. Independent screening, data extraction and quality assessment were conducted. The measured outcomes were change in one-repetition maximum (1-RM) load, maximum voluntary contraction (MVC), and concentric, eccentric and isometric peak torque. Change in muscle structure (pennation angle and muscle thickness) was also analysed. A total of 29 studies were included. The pooled effect size from the random-effects model shows that cross-education significantly increased 1-RM compared to the control group (standardised mean difference (SMD): 0.59, 95% CI: 0.22-0.97; P = 0.002). Cross-education also significantly improved MVC (SMD: 0.55, 95% CI: 0.16-0.94; P = 0.006), concentric (SMD: 0.61, 95% CI: 0.39-0.84; P < 0.00001), eccentric (SMD: 0.39, 95% CI: 0.13-0.64; P = 0.003) and isometric (SMD: 0.45, 95% CI: 0.26-0.64; P < 0.00001) peak torque, each compared to the control group. When RET was categorised as eccentric or concentric, subgroup analysis showed that only eccentric training was associated with significantly increased isometric peak torque via cross-education (SMD: 0.37, 95% CI: 0.13-0.61; P = 0.003) (concentric, SMD: 0.33, 95% CI: -0.09 to 0.74; P = 0.12). This systematic review and meta-analysis emphasise the potency of cross-education for improving lower limb muscle strength. These findings have potential implications for clinical situations of impaired unilateral limb function (e.g., limb-casting or stroke). Future work exploring the mechanisms facilitating these enhancements will help to develop optimised rehabilitation protocols.

Pre-hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT-2 trial.

BACKGROUND AND PURPOSE: Ambulance trials assessing interventions in suspected stroke patients will recruit patients with currently active symptoms that will resolve into transient ischaemic attack (TIA). The safety and efficacy of glyceryl trinitrate (GTN) in the pre-specified subgroup of patients with TIA in the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial 2 (RIGHT-2) was assessed. METHODS: RIGHT-2 was a pre-hospital-initiated multicentre randomized sham-controlled blinded-endpoint trial that randomized patients with presumed ultra-acute stroke within 4 h of symptom onset to transdermal GTN or sham. Final diagnosis was determined by site investigators. The primary outcome was a shift in modified Rankin Scale (mRS) scores at 90 days analysed using ordinal logistic regression reported as adjusted common odds ratio with 95% confidence intervals (CIs). Secondary outcomes included death or dependence (mRS >2). RESULTS: In all, 109 of 1149 (9.5%) patients had a final diagnosis of TIA (GTN 57, sham 52) with mean age 73 (SD 13) years, 19 (17.4%) had pre-morbid mRS >2, and onset to randomization was 80 min (interquartile range 49, 105). GTN lowered blood pressure by 7.4/5.2 mmHg compared with sham by hospital arrival. At day 90, GTN had no effect on shift in mRS scores (common odds ratio for increased dependence 1.47, 95% CI 0.70-3.11) but was associated with increased death or dependence (mRS >2): GTN 29 (51.8%) versus sham 23 (46.9%), odds ratio 3.86 (95% CI 1.09-13.59). CONCLUSIONS: Pre-hospital ultra-acute transdermal GTN did not improve overall functional outcome in patients with investigator-diagnosed TIA compared with sham treatment.

Endovascular thrombectomy vs best medical management for late presentation acute ischaemic stroke with large vessel occlusion without CT perfusion or MR imaging selection: A systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of endovascular thrombectomy (EVT) beyond 6 hours from stroke onset for patients with large vessel occlusion (LVO) selected without CT perfusion(CTP) or MR imaging(MRI) is undetermined. We conducted a systematic review and meta-analysis of the current literature comparing outcomes for late presenting patients with LVO treated by best medical management (BMM) with those selected for EVT based only on non-contrast CT(NCCT)/CT angiography(CTA) (without CTP or MRI). METHODS: PRISMA guidelines were employed. The primary outcome was functional independence (modified Rankin Scale 0-2) at 3 months. Secondary outcomes were symptomatic intracranial haemorrhage (sICH) and mortality at 3 months. Data were analysed using the random-effects model. RESULTS: Six studies of 2083 patients, including three randomised controlled trials, were included; 1271 patients were treated with EVT and 812 patients with BMM. Compared to BMM, patients treated with EVT demonstrated higher odds of achieving functional independence (39.0 % EVT vs 22.0 % BMM; OR = 2.55, 95 %CI 1.61-4.05,p < 0.0001, I2 = 74 %). The rates of sICH (OR = 2.09, 95 %CI 0.86-5.04,p = 0.10) and mortality (OR = 0.62, 95 %CI 0.35-1.10,p = 0.10) were not significantly different between each cohort. CONCLUSION: Compared to BMM, late presenting stroke patients selected for EVT eligibility with NCCT/CTA only and treated with EVT achieved significantly higher rates of functional independence at 90 days, without increasing the incidence of sICH or mortality. Whilst these findings indicate that NCCT/CTA only may be used for EVT eligibility selection for patients who present beyond 6 hours from stroke onset, the results should be interpreted with caution due to the substantial heterogeneity between studies.

Randomized controlled feasibility trial of swallow strength and skill training with surface electromyographic biofeedback in acute stroke patients with dysphagia.

BACKGROUND & OBJECTIVES: Swallow strength and skill training with surface electromyography (sEMG) biofeedback may improve dysphagia but little is known about the feasibility and efficacy of this intervention in acute stroke. METHODS: We conducted a randomized controlled feasibility study in acute stroke patients with dysphagia. Participants were randomized to either usual care or usual care plus swallow strength and skill training with sEMG biofeedback. Primary outcomes were feasibility and acceptability. Secondary measures included swallowing and clinical outcomes, safety and swallow physiology. RESULTS: Twenty-seven patients (13 biofeedback, 14 control) with average age of 73.3 (SD 11.0) and National Institute of Health Stroke Scale (NIHSS) of 10.7 (5.1) were recruited 22.4 (9.5) days post stroke. About 84.6% of participants completed >80% of sessions; failed sessions were mainly due to participant availability, drowsiness or refusal. Sessions lasted for an average of 36.2 (7.4) min. Although 91.7% found the intervention comfortable with satisfactory administration time, frequency and time post stroke, 41.7% found it challenging. There were no treatment-related serious adverse events. The biofeedback group had a lower Dysphagia Severity Rating Scale (DSRS) score at 2 weeks compared to control (3.2 vs. 4.3), but the difference did not reach statistical significance. CONCLUSIONS: Swallow strength and skill training with sEMG biofeedback appears feasible and acceptable to acute stroke patients with dysphagia. Preliminary data suggests it is safe and further research refining the intervention and investigating treatment dose and efficacy is warranted.

Incidence and predictors of poor functional outcome despite complete recanalisation following endovascular thrombectomy for acute ischaemic stroke.

BACKGROUND: Numerous ischaemic stroke patients experience poor functional outcome despite successful recanalisation following endovascular thrombectomy (EVT). We aimed to identify the incidence and predictors of futile complete recanalisation (FCR) in a national stroke registry. METHODS: Patients who achieved complete recanalisation (mTICI 3) following EVT, between October 2015 and March 2020, were included from a United Kingdom national stroke registry. Modified Rankin Scale of 4-6 at discharge was defined as a 'poor/futile outcome'. Backward stepwise multivariable logistic regression analysis was performed with FCR as the dependent variable, incorporating all baseline characteristics, procedural time metrics and post-procedural events. RESULTS: We included 2132 of 4383 patients (48.8%) with complete recanalisation post-EVT, of which 948 patients (44.4%) developed FCR. Following multivariable regression analysis adjusted for potential confounders, patients with FCR were associated with multiple baseline patient, imaging and procedural factors: age (p=0.0001), admission NIHSS scores (p=0.0001), pre-stroke disability (p=0.007), onset-to-puncture (p=0.0001) and procedural times (p=0.0001), presence of diabetes (p=0.005), and use of general anaesthesia (p=0.0001). Although not predictive of outcome, post-procedural events including development of any intracranial haemorrhage (ICH) (p=0.0001), symptomatic ICH (sICH) (p=0.0001) and early neurological deterioration (END) (p=0.007) were associated with FCR. CONCLUSION: Nearly half of patients in this national registry experienced FCR following EVT. Significant predictors of FCR included increasing age, admission NIHSS scores, pre-stroke disability, onset-to-puncture and procedural times, presence of diabetes, atrial fibrillation, and use of general anaesthesia. Post procedural development of any ICH, sICH, and END were associated with FCR.

Perfusion Imaging for Endovascular Thrombectomy in Acute Ischemic Stroke Is Associated With Improved Functional Outcomes in the Early and Late Time Windows.

BACKGROUND: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice. METHODS: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (<6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2). RESULTS: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; P=0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P=0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage (P=0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P=0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; P=0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; P=0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; P=0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; P=0.047). CONCLUSIONS: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.

Brief Consent Methods Enable Rapid Enrollment in Acute Stroke Trial: Results From the TICH-2 Randomized Controlled Trial.

BACKGROUND: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial. METHODS: Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours. RESULTS: Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557; 68%) or 2-stage consent (260; 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%]; 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38-93) minutes for doctor consent, 55 (37-95) minutes for 2-stage patient, 69 (43-110) minutes for 2-stage relative, 75 (48-124) minutes for 1-stage patient, and 90 (56-155) minutes for 1-stage relative consents (P<0.001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5-2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5-3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03-0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up. CONCLUSIONS: The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.

Pre-hospital transdermal glyceryl trinitrate in patients with stroke mimics: data from the RIGHT-2 randomised-controlled ambulance trial.

BACKGROUND: Prehospital stroke trials will inevitably recruit patients with non-stroke conditions, so called stroke mimics. We undertook a pre-specified analysis to determine outcomes in patients with mimics in the second Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT-2). METHODS: RIGHT-2 was a prospective, multicentre, paramedic-delivered, ambulance-based, sham-controlled, participant-and outcome-blinded, randomised-controlled trial of transdermal glyceryl trinitrate (GTN) in adults with ultra-acute presumed stroke in the UK. Final diagnosis (intracerebral haemorrhage, ischaemic stroke, transient ischaemic attack, mimic) was determined by the hospital investigator. This pre-specified subgroup analysis assessed the safety and efficacy of transdermal GTN (5 mg daily for 4 days) versus sham patch among stroke mimic patients. The primary outcome was the 7-level modified Rankin Scale (mRS) at 90 days. RESULTS: Among 1149 participants in RIGHT-2, 297 (26%) had a final diagnosis of mimic (GTN 134, sham 163). The mimic group were younger, mean age 67 (SD: 18) vs 75 (SD: 13) years, had a longer interval from symptom onset to randomisation, median 75 [95% CI: 47,126] vs 70 [95% CI:45,108] minutes, less atrial fibrillation and a lower systolic blood pressure and Face-Arm-Speech-Time tool score than the stroke group. The three most common mimic diagnoses were seizure (17%), migraine or primary headache disorder (17%) and functional disorders (14%). At 90 days, the GTN group had a better mRS score as compared to the sham group (adjusted common odds ratio 0.54; 95% confidence intervals 0.34, 0.85; p = 0.008), a difference that persisted at 365 days. There was no difference in the proportion of patients who died in hospital, were discharged to a residential care facility, or suffered a serious adverse event. CONCLUSIONS: One-quarter of patients suspected by paramedics to have an ultra-acute stroke were subsequently diagnosed with a non-stroke condition. GTN was associated with unexplained improved functional outcome observed at 90 days and one year, a finding that may represent an undetected baseline imbalance, chance, or real efficacy. GTN was not associated with harm. TRIAL REGISTRATION: This trial is registered with International Standard Randomised Controlled Trials Number ISRCTN 26986053 .

Diagnostic accuracy of the Dysphagia Trained Nurse Assessment tool in acute stroke.

BACKGROUND AND PURPOSE: Comprehensive swallow screening assessments to identify dysphagia and make early eating and drinking recommendations can be used by trained nurses. This study aimed to validate the Dysphagia Trained Nurse Assessment (DTNAx) tool in acute stroke patients. METHODS: Participants with diagnosed stroke were prospectively and consecutively recruited from an acute stroke unit. Following a baseline DTNAx on admission, participants underwent a speech and language therapist (SLT) bedside assessment of swallowing (speech and language therapist assessment [SLTAx]), videofluoroscopy (VFS) and a further DTNAx by the same or a different nurse. RESULTS: Forty-seven participants were recruited, of whom 22 had dysphagia. Compared to SLTAx in the identification of dysphagia, DTNAx had a sensitivity of 96.9% (95% confidence interval [CI] 83.8-99.9) and specificity of 89.5% (95% CI 75.2-97.1). Compared to VFS in the identification of aspiration, DTNAx had a sensitivity of 77.8% (95% CI 40.0-97.2) and a specificity of 81.6% (95% CI 65.7-92.3). Over 81% of the diet and fluid recommendations made by the dysphagia trained nurses were in absolute agreement compared to SLTAx. Both DTNAx and SLTAx had low diagnostic accuracy compared to the VFS-based definition of dysphagia. CONCLUSIONS: Nurses trained in DTNAx showed good diagnostic accuracy in identifying dysphagia compared to SLTAx and in identifying aspiration compared to VFS. They made appropriate diet and fluid recommendations in line with SLTs in the early management of dysphagia.

Blood markers in remote ischaemic conditioning for acute ischaemic stroke: data from the REmote ischaemic Conditioning After Stroke Trial.

BACKGROUND AND PURPOSE: 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). METHODS: RECAST-1 was a pilot sham-controlled blinded trial in 26 patients with ischaemic stroke, randomized to receive four 5-min cycles of RIC within 24 h of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) using chemiluminescence and all other biomarkers by multiplex analysis. Biomarkers were correlated with clinical outcome (day 90 National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel index). RESULTS: Remote ischaemic per-conditioning reduced serum amyloid protein (SAP) and tissue necrosis factor α (TNF-α) levels from pre- to post-intervention (n = 13, two-way ANOVA, p < 0.05). Overall (n = 26), increases in SAP pre- to post-intervention and pre-intervention to day 4 were moderately correlated with worse day 90 clinical outcomes. No consistent significant changes over time, or by treatment, or correlations with outcome were seen for other biomarkers. CONCLUSIONS: Remote ischaemic per-conditioning reduced SAP and TNF-α levels from pre- to post-intervention. Increases in plasma levels of SAP were associated with worse clinical outcomes after ischaemic stroke. Larger studies assessing biomarkers and the safety and efficacy of RIC in acute ischaemic stroke are warranted to further understand these relationships.

Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome, and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage.

Background and Purpose- Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage. Methods- The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome. Results- Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16-2.03]; P=0.003), black hole (aOR, 2.03 [1.34-3.08]; P=0.001), and hypodensities (aOR, 2.06 [1.48-2.89]; P<0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10-2.11]; P=0.012), hypodensities (aOR, 1.37 [1.05-1.78]; P=0.019), and island sign (aOR, 2.59 [1.21-5.55]; P=0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63-0.94]; P=0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome (P interaction all >0.05). Conclusions- Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid. Clinical Trial Registration- URL: https://www.isrctn.com. Unique identifier: ISRCTN93732214.

The effects of acute and sustained cannabidiol dosing for seven days on the haemodynamics in healthy men: A randomised controlled trial.

BACKGROUND: In vivo studies show that cannabidiol (CBD) acutely reduces blood pressure (BP) in men. The aim of this study was to assess the effects of repeated CBD dosing on haemodynamics. METHODS: Twenty-six healthy males were given CBD (600 mg) or placebo orally for seven days in a randomised, placebo-controlled, double-blind, parallel study (n = 13/group). Cardiovascular parameters were assessed at rest and in response to isometric exercise after acute and repeated dosing using Finometer®, Vicorder® and Duplex ultrasound. RESULTS: Compared to placebo, CBD significantly reduced resting mean arterial pressure (P = .04, two-way ANOVA, mean difference (MD) -2 mmHg, 95% CI -3.6 to -0.3) after acute dosing, but not after repeated dosing. In response to stress, volunteers who had taken CBD had lower systolic BP after acute (P = .001, two-way ANOVA, MD -6 mmHg, 95% CI -10 to -1) and repeated (P = .02, two-way ANOVA, MD -5.7 mmHg, 95% CI -10 to -1) dosing. Seven days of CBD increased internal carotid artery diameter (MD +0.55 mm, P = .01). Within the CBD group, repeated dosing reduced arterial stiffness by day 7 (pulse wave velocity; MD -0.44 m/s, P = .05) and improved endothelial function (flow mediation dilatation, MD +3.5%, P = .02, n = 6 per group), compared to day 1. CONCLUSION: CBD reduces BP at rest after a single dose but the effect is lost after seven days of treatment (tolerance); however, BP reduction during stress persists. The reduction in arterial stiffness and improvements in endothelial function after repeated CBD dosing are findings that warrant further investigation in populations with vascular diseases.

Accuracy and clinical utility of comprehensive dysphagia screening assessments in acute stroke: A systematic review and meta-analysis.

INTRODUCTION: Nurses and other nonspecialists in dysphagia are often trained to screen swallowing poststroke. There are many basic tools that test water only, they are usually conservative, and patients that fail the test remain nil by mouth until a speech and language therapy assessment. More comprehensive tests also allow nonspecialists to recommend modified oral intake. Little is known about the accuracy, clinical utility and cost-effectiveness of these tests. METHODS: Following PRISMA guidelines, a systematic review was conducted to describe comprehensive swallowing tests that are available for use in acute stroke by nurses or other nonspecialists in dysphagia. A meta-analysis was performed to evaluate accuracy and the clinical utility of the tests was considered. Searches and analyses, conducted by two reviewers, included MEDLINE, Embase, trial registries and grey literature up to December 2018. Validated studies were assessed for quality and risk of bias using QUADAS-2. RESULTS: Twenty studies were included, describing five different tests, three of which had undergone validation. The tests varied in content, recommendations and use. There was no test superior in accuracy and clinical utility. Three studies validating the Gugging Swallow Screen provided sufficient data for meta-analysis, demonstrating high sensitivity; 96% (95% CI 0.90-0.99), but low specificity, 65% (95% CI 0.47-0.79), in line with many water swallow tests. Results should be interpreted with caution as study quality and applicability to the acute stroke population was poor. CONCLUSIONS: There is no comprehensive nurse dysphagia assessment tool that has robustly demonstrated good accuracy, clinical utility and cost-effectiveness in acute stroke. RELEVANCE TO CLINICAL PRACTICE: Nurses and other clinicians can develop competencies in screening swallowing and assessing for safe oral intake in those with poststroke dysphagia. It is important to use a validated assessment tool that demonstrates good accuracy, clinical utility and cost-effectiveness.

Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage: Data From the RIGHT-2 Trial.

Background and Purpose- Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods- We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results- Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45-110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98-3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01-0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN26986053.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

BACKGROUND: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. METHODS: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. FINDINGS: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001). INTERPRETATION: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. FUNDING: National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial.

BACKGROUND: Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage. METHODS: We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214. FINDINGS: We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77-1·10, p=0·37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]). INTERPRETATION: Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect. FUNDING: National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.

Does Therapy With Biofeedback Improve Swallowing in Adults With Dysphagia? A Systematic Review and Meta-Analysis.

OBJECTIVE: To describe and systematically review the current evidence on the effects of swallow therapy augmented by biofeedback in adults with dysphagia (PROSPERO 2016:CRD42016052942). DATA SOURCES: Two independent reviewers conducted searches that included MEDLINE, EMBASE, trial registries, and gray literature up to December 2016. STUDY SELECTION: Randomized controlled trials (RCTs) and non-RCTs were assessed, including for risk of bias and quality. DATA EXTRACTION: Data were extracted by 1 reviewer and verified by another on biofeedback type, measures of swallow function, physiology and clinical outcome, and analysed using Cochrane Review Manager (random effects models). Results are expressed as weighted mean difference (WMD) and odds ratio (OR). DATA SYNTHESIS: Of 675 articles, we included 23 studies (N=448 participants). Three main types of biofeedback were used: accelerometry, surface electromyography (sEMG), and tongue manometry. Exercises included saliva swallows, maneuvers, and strength exercises. Dose varied between 6 and 72 sessions for 20-60 minutes. Five controlled studies (stroke n=95; head and neck cancer n=33; mixed etiology n=10) were included in meta-analyses. Compared to control, biofeedback augmented dysphagia therapy significantly enhanced hyoid displacement (3 studies, WMD=0.22cm; 95% confidence interval [CI] [0.04, 0.40], P=.02) but there was no significant difference in functional oral intake (WMD=1.10; 95% CI [-1.69, 3.89], P=.44) or dependency on tube feeding (OR =3.19; 95% CI [0.16, 62.72], P=.45). Risk of bias was high and there was significant statistical heterogeneity between trials in measures of swallow function and number tube fed (I2 70%-94%). Several nonvalidated outcome measures were used. Subgroup analyses were not possible due to a paucity of studies. CONCLUSIONS: Dysphagia therapy augmented by biofeedback using sEMG and accelerometry enhances hyoid displacement but functional improvements in swallowing are not evident. However, data are extremely limited and further larger well-designed RCTs are warranted.

RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. METHODS: We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. RESULTS: Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group (P=0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P=0.04); RIC augmented plasma HSP27 (heat shock protein 27; P<0.05, repeated 2-way ANOVA) and phosphorylated HSP27 (P<0.001) but not plasma S100-ß, matrix metalloproteinase-9, endocannabinoids, or arterial compliance. CONCLUSIONS: RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015.

Neurocysticercosis presenting as a 'Stroke Mimic'.

A 62 year old Nepalese gentleman presented with left sided weakness and sensory loss. Initial brain CT scanning was suggestive of acute infarction but a subsequent MRI scan showed cysts with oedema. Cysticercosis serology was positive and a diagnosis of neurocysticercosis was made. The patient made almost a complete recovery after treatment with albendazole, praziquantel and steroids. Neurocysticercosis should be considered in the diffierential diagnosis when patients originating from endemic areas present with focal neurological deficit.

Remote ischemic conditioning for stroke: A critical systematic review.

Remote ischemic conditioning (RIC) is the application of brief periods of ischemia to an organ or tissue with the aim of inducing protection from ischemia in a distant organ. It was first developed as a cardioprotective strategy but has been increasingly investigated as a neuroprotective intervention. The mechanisms by which RIC achieves neuroprotection are incompletely understood. Preclinical studies focus on the hypothesis that RIC can protect the brain from ischemia reperfusion (IR) injury following the restoration of blood flow after occlusion of a large cerebral artery. However, increasingly, a role of chronic RIC (CRIC) is being investigated as a means of promoting recovery following an ischemic insult to the brain. The recent publication of two large, randomized control trials has provided promise that RIC could improve functional outcomes after acute ischemic stroke, and that there may be a role for CRIC in the prevention of recurrent stroke. Although less developed, there is also proof-of-concept to suggest that RIC may be used to reduce vasospasm after subarachnoid hemorrhage or improve cognitive outcomes in vascular dementia. As a cheap, well-tolerated and almost universally applicable intervention, the motivation for investigating possible benefit of RIC in patients with cerebrovascular disease is great. In this review, we shall review the current evidence for RIC as applied to cerebrovascular disease.