Mechanical thrombectomy: can it be safely delivered out of hours in the UK?

BACKGROUND: Mechanical thrombectomy was approved by NICE as a treatment for stroke in 2016. However, most of the evidence is from studies conducted during working hours. Only few centres in the UK perform thrombectomies out-of-hours. The Royal Stoke University Hospital (RSUH) has offered thrombectomies over 24 h (24/7) since 2010. The aim of this service review is to compare the outcomes for patients treated in regular working hours to those treated outside normal working hours within this unit. METHODS: This retrospective service analysis includes all patients treated with mechanical thrombectomy at RSUH since the start of the service in January 2010 to June 2019. Data on key demographics, timings, procedural complications, and long-term outcomes including death and disability at 90 days were collected. In-hours was defined as the time between 8:00-17:00 h, Monday to Friday; out-of-hours was defined as any time outside this period. RESULTS: In total, 516 mechanical thrombectomies were performed in this time period; data were available on 501 of these. Successful recanalization (TICI 2b/3) was achieved in 86% of patients. By 90 days 96 (19%) had died and 234 (47%) were functionally independent (modified Rankin Scale score ≤ 2). 211 (42%) of the procedures were performed in-hours and 290 (58%) out-of-hours. Door-to-CT and door-to-groin times were significantly longer out-of-hours than in-hours, but thrombectomy duration was significantly shorter. There were no significant differences in complications and short- and long-term outcomes. CONCLUSION: Mechanical thrombectomy was delivered safely and effectively 24/7 in this UK hospital, with no difference in clinical outcomes.

Pharyngeal Electrical Stimulation for Treatment of Dysphagia in Subacute Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke dysphagia that has shown promise in 3 pilot randomized controlled trials. METHODS: We randomly assigned 162 patients with a recent ischemic or hemorrhagic stroke and dysphagia, defined as a penetration aspiration score (PAS) of ≥3 on video fluoroscopy, to PES or sham treatment given on 3 consecutive days. The primary outcome was swallowing safety, assessed using the PAS, at 2 weeks. Secondary outcomes included dysphagia severity, function, quality of life, and serious adverse events at 6 and 12 weeks. RESULTS: In randomized patients, the mean age was 74 years, male 58%, ischemic stroke 89%, and PAS 4.8. The mean treatment current was 14.8 (7.9) mA and duration 9.9 (1.2) minutes per session. On the basis of previous data, 45 patients (58.4%) randomized to PES seemed to receive suboptimal stimulation. The PAS at 2 weeks, adjusted for baseline, did not differ between the randomized groups: PES 3.7 (2.0) versus sham 3.6 (1.9), P=0.60. Similarly, the secondary outcomes did not differ, including clinical swallowing and functional outcome. No serious adverse device-related events occurred. CONCLUSIONS: In patients with subacute stroke and dysphagia, PES was safe but did not improve dysphagia. Undertreatment of patients receiving PES may have contributed to the neutral result. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25681641.

Safety and effect of metoclopramide to prevent pneumonia in patients with stroke fed via nasogastric tubes trial.

BACKGROUND AND PURPOSE: Pneumonia is a major cause of mortality and morbidity in patients with stroke fed via nasogastric tubes and may be because of vomiting and gastro-oesophageal regurgitation. The aim of the study was to assess whether regular treatment with metoclopramide, a D2-receptor antagonist with antiemetic and gastric prokinetic actions, could reduce the rate of aspiration and pneumonia. METHODS: Patients with no signs of pneumonia within 7 days of stroke onset and 48 hours of insertion of a nasogastric tube were recruited into a double-blind randomized placebo-controlled trial. Participants received metoclopramide 10 mg or placebo 3× daily via the nasogastric tube for 21 days or until nasogastric feeds were discontinued. Clinical signs of pneumonia were recorded daily. Pneumonia was diagnosed if the patient had relevant clinical signs, high inflammatory markers, and new infiltrates on the chest radiograph. RESULTS: Sixty patients (mean age, 78 years; 38 women; mean National Institutes for Health Stroke Scale score, 19.25) were randomized in a 1:1 ratio. There were significantly more episodes of pneumonia in the placebo group than in the metoclopramide group (rate ratio, 5.24; P<0.001). There were also significant differences in favor of metoclopramide in the rate of aspiration, oxygen saturation, highest inflammatory markers, and National Institutes for Health Stroke Scale. There was no significant difference in mortality between the groups. CONCLUSIONS: This study suggests that metoclopramide may reduce the rate of pneumonia and may improve other clinical outcomes in patients with subacute stroke fed via nasogastric tube. These findings need to be confirmed in larger randomized and blinded trials. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrialsregister.eu. EudraCT no: 2006-002570-22, URL: http://www.controlled-trials.com/ISRCTN18034911/18034911.

Pharyngeal electrical stimulation for neurogenic dysphagia following stroke, traumatic brain injury or other causes: Main results from the PHADER cohort study.

BACKGROUND: Neurogenic dysphagia is common and has no definitive treatment. We assessed whether pharyngeal electrical stimulation (PES) is associated with reduced dysphagia. METHODS: The PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry (PHADER) was a prospective single-arm observational cohort study. Participants were recruited with neurogenic dysphagia (comprising five groups - stroke not needing ventilation; stroke needing ventilation; ventilation acquired; traumatic brain injury; other neurological causes). PES was administered once daily for three days. The primary outcome was the validated dysphagia severity rating scale (DSRS, score best-worst 0-12) at 3 months. FINDINGS: Of 255 enrolled patients from 14 centres in Austria, Germany and UK, 10 failed screening. At baseline, mean (standard deviation) or median [interquartile range]: age 68 (14) years, male 71%, DSRS 11·4 (1·7), time from onset to treatment 32 [44] days; age, time and DSRS differed between diagnostic groups. Insertion of PES catheters was successfully inserted in 239/245 (98%) participants, and was typically easy taking 11·8 min. 9 participants withdrew before the end of treatment. DSRS improved significantly in all dysphagia groups, difference in means (95% confidence intervals, CI) from 0 to 3 months: stroke (n = 79) -6·7 (-7·8, -5·5), ventilated stroke (n = 98) -6·5 (-7·6, -5·5); ventilation acquired (n = 35) -6·6 (-8·4, -4·8); traumatic brain injury (n = 24) -4·5 (-6·6, -2·4). The results for DSRS were mirrored for instrumentally assessed penetration aspiration scale scores. DSRS improved in both supratentorial and infratentorial stroke, with no difference between them (p = 0·32). In previously ventilated participants with tracheotomy, DSRS improved more in participants who could be decannulated (n = 66) -7·5 (-8·6, -6·5) versus not decannulated (n = 33) -2·1 (-3·2, -1·0) (p<0·001). 74 serious adverse events (SAE) occurred in 60 participants with pneumonia (9·2%) the most frequent SAE. INTERPRETATION: In patients with neurogenic dysphagia, PES was safe and associated with reduced measures of dysphagia and penetration/aspiration. FUNDING: Phagenesis Ltd.

Early Diagnosis of Pneumonia in Severe Stroke: Clinical Features and the Diagnostic Role of C-Reactive Protein.

BACKGROUND: Accurate diagnosis of pneumonia complicating severe stroke is challenging due to difficulties in physical examination, altered immune responses and delayed manifestations of radiological changes. The aims of this study were to describe early clinical features and to examine C-reactive protein (CRP) as a diagnostic marker of post-stroke pneumonia. METHODS: Patients who required nasogastric feeding and had no evidence of pneumonia within 7 days of stroke onset were included in the study and followed-up for 21 days with a daily clinical examination. Pneumonia was diagnosed using modified British Thoracic Society criteria. RESULTS: 60 patients were recruited (mean age 77 years, mean National Institutes of Health Stroke Scale Score 19.47). Forty-four episodes of pneumonia were identified. Common manifestations on the day of the diagnosis were new onset crackles (43/44, 98%), tachypnoea>25/min (42/44, 95%), and oxygen saturation <90% (41/44, 93%). Cough, purulent sputum, and pyrexia >38°C were observed in 27 (61%), 25 (57%) and 15 (34%) episodes respectively. Leucocytosis (WBC>11,000/ml) and raised CRP (>10 mg/l) were observed in 38 (86%) and 43 (97%) cases of pneumonia respectively. The area under the ROC curve for CRP was 0.827 (95% CI 0.720, 0.933). The diagnostic cut-off for CRP with an acceptable sensitivity (>0.8) was 25.60 mg/L (Youden index (J) 0.515; sensitivity 0.848; specificity 0.667). A cut-off of 64.65 mg/L had the highest diagnostic accuracy (J 0.562; sensitivity 0.636; specificity 0.926). CONCLUSION: Patients with severe stroke frequently do not manifest key diagnostic features of pneumonia such as pyrexia, cough and purulent sputum early in their illness. The most common signs in this group are new-onset crackles, tachypnoea and hypoxia. Our results suggest that a CRP >25 mg/L should prompt investigations for pneumonia while values >65 mg/L have the highest diagnostic accuracy to justify consideration of this threshold as a diagnostic marker of post-stroke pneumonia.

Post-stroke dysphagia: A review and design considerations for future trials.

Post-stroke dysphagia (a difficulty in swallowing after a stroke) is a common and expensive complication of acute stroke and is associated with increased mortality, morbidity, and institutionalization due in part to aspiration, pneumonia, and malnutrition. Although most patients recover swallowing spontaneously, a significant minority still have dysphagia at six months. Although multiple advances have been made in the hyperacute treatment of stroke and secondary prevention, the management of dysphagia post-stroke remains a neglected area of research, and its optimal management, including diagnosis, investigation and treatment, have still to be defined.

The stroke oxygen pilot study: a randomized controlled trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months.

INTRODUCTION: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. METHODS: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p ≤ 0.05. RESULTS: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p = 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p = 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. CONCLUSIONS: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-41.

The SOS pilot study: a RCT of routine oxygen supplementation early after acute stroke--effect on recovery of neurological function at one week.

UNLABELLED: Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke. METHODS: Patients with a clinical diagnosis of acute stroke were recruited within 24 h of hospital admission between October 2004 and April 2008. Participants were randomized to oxygen via nasal cannulae (72 h) or control (room air, oxygen given only if clinically indicated). Clinical outcomes were assessed by research team members at 1 week. Baseline data for oxygen (n = 148) and control (n = 141) did not differ between groups. RESULTS: The median (interquartile range) National Institutes of Health Stroke Scale (NIHSS) score for the groups at baseline was 6 (7) and 5 (7) respectively. The median Nocturnal Oxygen Saturation during treatment was 1.4% (0.3) higher in the oxygen than in the control group (p<0.001) during the intervention. At 1 week, the median NIHSS score had reduced by 2 (3) in the oxygen and by 1 (2) in the control group. 31% of participants in the oxygen group and 14% in the control group had an improvement of ≥4 NIHSS points at 1 week doubling the odds of improvement in the oxygen group (OR: 2.9). CONCLUSION: Our data show that routine oxygen supplementation started within 24 hours of hospital admission with acute stroke led to a small, but statistically significant, improvement in neurological recovery at 1 week. However, the difference in NIHSS improvement may be due to baseline imbalance in stroke severity between the two groups and needs to be confirmed in a larger study and linked to longer-term clinical outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN12362720; European Clinical Trials Database 2004-001866-41.