SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke): A Randomized Controlled Phase 2 Trial.

BACKGROUND AND PURPOSE: The proinflammatory cytokine IL-1 (interleukin-1) has a deleterious role in cerebral ischemia, which is attenuated by IL-1 receptor antagonist (IL-1Ra). IL-1 induces peripheral inflammatory mediators, such as interleukin-6, which are associated with worse prognosis after ischemic stroke. We investigated whether subcutaneous IL-1Ra reduces the peripheral inflammatory response in acute ischemic stroke. METHODS: SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke) was a single-center, double-blind, randomized, placebo-controlled phase 2 trial of subcutaneous IL-1Ra (100 mg administered twice daily for 3 days) in patients presenting within 5 hours of ischemic stroke onset. Randomization was stratified for baseline National Institutes of Health Stroke Scale score and thrombolysis. Measurement of plasma interleukin-6 and other peripheral inflammatory markers was undertaken at 5 time points. The primary outcome was difference in concentration of log(interleukin-6) as area under the curve to day 3. Secondary outcomes included exploratory effect of IL-1Ra on 3-month outcome with the modified Rankin Scale. RESULTS: We recruited 80 patients (mean age, 72 years; median National Institutes of Health Stroke Scale, 12) of whom 73% received intravenous thrombolysis with alteplase. IL-1Ra significantly reduced plasma interleukin-6 (P<0.001) and plasma C-reactive protein (P<0.001). IL-1Ra was well tolerated with no safety concerns. Allocation to IL-1Ra was not associated with a favorable outcome on modified Rankin Scale: odds ratio (95% confidence interval)=0.67 (0.29-1.52), P=0.34. Exploratory mediation analysis suggested that IL-1Ra improved clinical outcome by reducing inflammation, but there was a statistically significant, alternative mechanism countering this benefit. CONCLUSIONS: IL-1Ra reduced plasma inflammatory markers which are known to be associated with worse clinical outcome in ischemic stroke. Subcutaneous IL-1Ra is safe and well tolerated. Further experimental studies are required to investigate efficacy and possible interactions of IL-1Ra with thrombolysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: ISRCTN74236229.

Bespoke versus off-the-shelf ankle-foot orthosis for people with stroke: randomized controlled trial.

OBJECTIVE: The aim of the study was to compare the effect of two designs of ankle-foot orthosis on people with stroke. DESIGN: The study design was an assessor-blind, multicentre randomized controlled trial. SETTING: The setting was community stroke services. PARTICIPANTS: A total of 139 community-dwelling stroke survivors with limited mobility were recruited. INTERVENTIONS: The two most commonly used types of ankle-foot orthosis (bespoke and off-the-shelf) were chosen. MAIN MEASURES: The main measures of the study were as follows: short- (6 weeks) and long-term (12 weeks) effects on stroke survivors' satisfaction; adverse events; mobility (Walking Handicap Scale); fear of falling (Falls Efficacy Scale-International (FES-I)) and walking impairments (gait speed and step length using the 5-m walk test). RESULTS: Long-term satisfaction was non-significantly higher in the off-the-shelf group: 72% versus 64%; OR (95% CI) = 0.64 (0.31 to 1.3); P = 0.21. No statistically significant differences were found between the orthoses except that the off-the-shelf group had less fear of falling at short-term follow-up than the bespoke group: mean difference (95% CI) = -4.6 (-7.6 to -1.6) points on the FES-I; P = 0.003. CONCLUSION: No differences between off-the-shelf and bespoke ankle-foot orthoses were found except that participants in the off-the-shelf orthosis group had less fear of falling at short-term follow-up.

The potential role of cost-utility analysis in the decision to implement major system change in acute stroke services in metropolitan areas in England.

BACKGROUND: The economic implications of major system change are an important component of the decision to implement health service reconfigurations. Little is known about how best to report the results of economic evaluations of major system change to inform decision-makers. Reconfiguration of acute stroke care in two metropolitan areas in England, namely London and Greater Manchester (GM), was used to analyse the economic implications of two different implementation strategies for major system change. METHODS: A decision analytic model was used to calculate difference-in-differences in costs and outcomes before and after the implementation of two major system change strategies in stroke care in London and GM. Values in the model were based on patient level data from Hospital Episode Statistics, linked mortality data from the Office of National Statistics and data from two national stroke audits. Results were presented as net monetary benefit (NMB) and using Programme Budgeting and Marginal Analysis (PBMA) to assess the costs and benefits of a hypothetical typical region in England with approximately 4000 strokes a year. RESULTS: In London, after 90 days, there were nine fewer deaths per 1000 patients compared to the rest of England (95% CI -24 to 6) at an additional cost of £770,027 per 1000 stroke patients admitted. There were two additional deaths (95% CI -19 to 23) in GM, with a total costs saving of £156,118 per 1000 patients compared to the rest of England. At a £30,000 willingness to pay the NMB was higher in London and GM than the rest of England over the same time period. The results of the PBMA suggest that a GM style reconfiguration could result in a total greater health benefit to a region. Implementation costs were £136 per patient in London and £75 in GM. CONCLUSIONS: The implementation of major system change in acute stroke care may result in a net health benefit to a region, even one functioning within a fixed budget. The choice of what model of stroke reconfiguration to implement may depend on the relative importance of clinical versus cost outcomes.

Weekly variation in health-care quality by day and time of admission: a nationwide, registry-based, prospective cohort study of acute stroke care.

BACKGROUND: Studies in many health systems have shown evidence of poorer quality health care for patients admitted on weekends or overnight than for those admitted during the week (the so-called weekend effect). We postulated that variation in quality was dependent on not only day, but also time, of admission, and aimed to describe the pattern and magnitude of variation in the quality of acute stroke care across the entire week. METHODS: We did this nationwide, registry-based, prospective cohort study using data from the Sentinel Stroke National Audit Programme. We included all adult patients (aged >16 years) admitted to hospital with acute stroke (ischaemic or primary intracerebral haemorrhage) in England and Wales between April 1, 2013, and March 31, 2014. Our outcome measure was 30 day post-admission survival. We estimated adjusted odds ratios for 13 indicators of acute stroke-care quality by fitting multilevel multivariable regression models across 42 4-h time periods per week. FINDINGS: The study cohort comprised 74,307 patients with acute stroke admitted to 199 hospitals. Care quality varied across the entire week, not only between weekends and weekdays, with different quality measures showing different patterns and magnitudes of temporal variation. We identified four patterns of variation: a diurnal pattern (thrombolysis, brain scan within 12 h, brain scan within 1 h, dysphagia screening), a day of the week pattern (stroke physician assessment, nurse assessment, physiotherapy, occupational therapy, and assessment of communication and swallowing by a speech and language therapist), an off-hours pattern (door-to-needle time for thrombolysis), and a flow pattern whereby quality changed sequentially across days (stroke-unit admission within 4 h). The largest magnitude of variation was for door-to-needle time within 60 min (range in quality 35-66% [16/46-232/350]; coefficient of variation 18·2). There was no difference in 30 day survival between weekends and weekdays (adjusted odds ratio 1·03, 95% CI 0·95-1·13), but patients admitted overnight on weekdays had lower odds of survival (0·90, 0·82-0·99). INTERPRETATION: The weekend effect is a simplification, and just one of several patterns of weekly variation occurring in the quality of stroke care. Weekly variation should be further investigated in other health-care settings, and quality improvement should focus on reducing temporal variation in quality and not only the weekend effect. FUNDING: None.

The association between delays in screening for and assessing dysphagia after acute stroke, and the risk of stroke-associated pneumonia.

BACKGROUND: There is no robust evidence that screening patients with acute stroke for dysphagia reduces the risk of stroke-associated pneumonia (SAP), or of how quickly it should be done after admission. We aimed to identify if delays in bedside dysphagia screening and comprehensive dysphagia assessments by a speech and language therapist (SALT) were associated with patients' risk of SAP. METHODS: Nationwide, registry-based, prospective cohort study of patients admitted with acute stroke in England and Wales. Multilevel multivariable logistic regression models were fitted, adjusting for patient variables and stroke severity. The exposures were time from (1) admission to bedside dysphagia screen, and (2) admission to comprehensive dysphagia assessment. RESULTS: Of 63 650 patients admitted with acute stroke, 55 838 (88%) had a dysphagia screen, and 24 542 (39%) a comprehensive dysphagia assessment. Patients with the longest delays in dysphagia screening (4th quartile adjusted OR 1.14, 1.03 to 1.24) and SALT dysphagia assessment (4th quartile adjusted OR 2.01, 1.76 to 2.30) had a higher risk of SAP. The risk of SAP increased in a dose-response manner with delays in SALT dysphagia assessment, with an absolute increase of pneumonia incidence of 1% per day of delay. CONCLUSIONS: Delays in screening for and assessing dysphagia after stroke, are associated with higher risk of SAP. Since SAP is one of the main causes of mortality after acute stroke, early dysphagia assessment may contribute to preventing deaths from acute stroke and could be implemented even in settings without access to high-technology specialist stroke care.

Development and feasibility testing of an oral hygiene intervention for stroke unit care.

OBJECTIVE: To develop an oral hygiene complex intervention and evaluate its feasibility in a single UK stroke centre. BACKGROUND: Oral hygiene interventions might improve clinical outcomes after stroke but evidence-based practice is lacking. MATERIALS AND METHODS: We used a sequential mixed methods approach and developed an oral hygiene complex intervention comprising: (i) web-based education and 'hands-on' practical training for stroke unit nursing staff, (ii) a pragmatic oral hygiene protocol consisting of twice-daily powered (or manual if preferred) brushing with chlorhexidine gel (or non-foaming toothpaste) ± denture care. We evaluated feasibility of (i) the staff education and training and (ii) the oral hygiene protocol in consenting inpatients with confirmed stroke, requiring assistance with at least one aspect of personal care. RESULTS: The staff education and training were feasible, acceptable and raised knowledge and awareness. Several barriers to completing the education and training were identified. The oral hygiene protocol was feasible and well-tolerated. 22% of eligible patients screened declined participation in the study. Twenty-nine patients (median age = 78 year; National Institutes of Health Stroke Scale score = 8.5; 73% dentate) were recruited at a median of 7 days from stroke onset. 97% of participants chose the default chlorhexidine-based protocol; the remainder chose the non-foaming toothpaste-based protocol. The mouth hygiene protocol was administered as prescribed on 95% of occasions, over a median duration of 28 days. There were no adverse events attributed to the oral hygiene protocol. CONCLUSION: Our oral hygiene complex intervention was feasible in a single UK stroke centre. Further studies to optimise patient selection, model health economics and explore efficacy are now required.

Interleukin-1 and neuronal injury.

Interleukin-1 is a pro-inflammatory cytokine that has numerous biological effects, including activation of many inflammatory processes (through activation of T cells, for example), induction of expression of acute-phase proteins, an important function in neuroimmune responses and direct effects on the brain itself. There is now extensive evidence to support the direct involvement of interleukin-1 in the neuronal injury that occurs in both acute and chronic neurodegenerative disorders. This article discusses the key evidence of a role for interleukin-1 in acute neurodegeneration - for example, stroke and brain trauma - and provides a rationale for targeting the interleukin-1 system as a therapeutic strategy.

Effects of Centralizing Acute Stroke Services on Stroke Care Provision in Two Large Metropolitan Areas in England.

BACKGROUND AND PURPOSE: In 2010, Greater Manchester and London centralized acute stroke care into hyperacute units (Greater Manchester=3, London=8), with additional units providing ongoing specialist stroke care nearer patients' homes. Greater Manchester patients presenting within 4 hours of symptom onset were eligible for hyperacute unit admission; all London patients were eligible. Research indicates that postcentralization, only London's stroke mortality fell significantly more than elsewhere in England. This article attempts to explain this difference by analyzing how centralization affects provision of evidence-based clinical interventions. METHODS: Controlled before and after analysis was conducted, using national audit data covering Greater Manchester, London, and a noncentralized urban comparator (38 623 adult stroke patients, April 2008 to December 2012). Likelihood of receiving all interventions measured reliably in pre- and postcentralization audits (brain scan; stroke unit admission; receiving antiplatelet; physiotherapist, nutrition, and swallow assessments) was calculated, adjusting for age, sex, stroke-type, consciousness, and whether stroke occurred in-hospital. RESULTS: Postcentralization, likelihood of receiving interventions increased in all areas. London patients were overall significantly more likely to receive interventions, for example, brain scan within 3 hours: Greater Manchester=65.2% (95% confidence interval=64.3-66.2); London=72.1% (71.4-72.8); comparator=55.5% (54.8-56.3). Hyperacute units were significantly more likely to provide interventions, but fewer Greater Manchester patients were admitted to these (Greater Manchester=39%; London=93%). Differences resulted from contrasting hyperacute unit referral criteria and how reliably they were followed. CONCLUSIONS: Centralized systems admitting all stroke patients to hyperacute units, as in London, are significantly more likely to provide evidence-based clinical interventions. This may help explain previous research showing better outcomes associated with fully centralized models.

How is pneumonia diagnosed in clinical stroke research? A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Diagnosis of pneumonia complicating stroke is challenging, and there are currently no consensus diagnostic criteria. As a first step in developing such consensus-based diagnostic criteria, we undertook a systematic review to identify the existing diagnostic approaches to pneumonia in recent clinical stroke research to establish the variation in diagnosis and terminology. METHODS: Studies of ischemic stroke, intracerebral hemorrhage, or both, which reported occurrence of pneumonia from January 2009 to March 2014, were considered and independently screened for inclusion by 2 reviewers after multiple searches using electronic databases. The primary analysis was to identify existing diagnostic approaches for pneumonia. Secondary analyses explored potential reasons for any heterogeneity where standard criteria for pneumonia had been applied. RESULTS: Sixty-four studies (56% ischemic stroke, 6% intracerebral hemorrhage, 38% both) of 639 953 patients were included. Six studies (9%) reported no information on the diagnostic approach, whereas 12 (19%) used unspecified clinician-reported diagnosis or initiation of antibiotics. The majority used objective diagnostic criteria: 20 studies (31%) used respiratory or other published standard criteria; 26 studies (41%) used previously unpublished ad hoc criteria. The overall occurrence of pneumonia was 14.3% (95% confidence interval 13.2%-15.4%; I(2)=98.9%). Occurrence was highest in studies applying standard criteria (19.1%; 95% confidence interval 15.1%-23.4%; I(2)=98.5%). The substantial heterogeneity observed was not explained by stratifying for other potential confounders. CONCLUSIONS: We found considerable variation in terminology and the diagnostic approach to pneumonia. Our review supports the need for consensus development of operational diagnostic criteria for pneumonia complicating stroke.

Diagnosis of Stroke-Associated Pneumonia: Recommendations From the Pneumonia in Stroke Consensus Group.

BACKGROUND AND PURPOSE: Lower respiratory tract infections frequently complicate stroke and adversely affect outcome. There is currently no agreed terminology or gold-standard diagnostic criteria for the spectrum of lower respiratory tract infections complicating stroke, which has implications for clinical practice and research. The aim of this consensus was to propose standardized terminology and operational diagnostic criteria for lower respiratory tract infections complicating acute stroke. METHODS: Systematic literature searches of multiple electronic databases were undertaken. An evidence review and 2 rounds of consensus consultation were completed before a final consensus meeting in September 2014, held in Manchester, United Kingdom. Consensus was defined a priori as ≥75% agreement between the consensus group members. RESULTS: Consensus was reached for the following: (1) stroke-associated pneumonia (SAP) is the recommended terminology for the spectrum of lower respiratory tract infections within the first 7 days after stroke onset; (2) modified Centers for Disease Control and Prevention (CDC) criteria are proposed for SAP as follows-probable SAP: CDC criteria met, but typical chest x-ray changes absent even after repeat or serial chest x-ray; definite SAP: CDC criteria met, including typical chest x-ray changes; (3) there is limited evidence for a diagnostic role of white blood cell count or C-reactive protein in SAP; and (4) there is insufficient evidence for the use of other biomarkers (eg, procalcitonin). CONCLUSIONS: Consensus operational criteria for the terminology and diagnosis of SAP are proposed based on the CDC criteria. These require prospective evaluation in patients with stroke to determine their reliability, validity, impact on clinician behaviors (including antibiotic prescribing), and clinical outcomes.

Incidence, predictors and clinical characteristics of orolingual angio-oedema complicating thrombolysis with tissue plasminogen activator for ischaemic stroke.

BACKGROUND: Orolingual angio-oedema is a recognised complication of tissue plasminogen activator (tPA) for ischaemic stroke. We investigated its incidence, clinical characteristics and relationship with other factors in patients receiving tPA at a UK centre. METHODS: 530 consecutive patients (median age 70 years) receiving tPA treatment for confirmed ischaemic stroke were included. Cases were defined as those developing angio-oedema within 24 h of initiation of tPA. Angio-oedema was retrospectively classified as mild, moderate or severe using predefined criteria. The primary analysis was the association between prior ACE inhibitor (ACE-I) treatment and angio-oedema. RESULTS: Orolingual angio-oedema was observed in 42 patients (7.9%; 95% CI 5.5% to 10.6%), ranging from 5 to 189 min after initiation of tPA (median 65 min). 12% of the angio-oedema cases were severe (1% of all patients treated with tPA), requiring urgent advanced airway management. 172 patients (33%) were taking ACE-I. In multifactorial analyses, only prior ACE-I treatment remained a significant independent predictor of angio-oedema (odds ratio (OR) 2.3; 95% CI 1.1 to 4.7). CONCLUSIONS: Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis.

Organisation, practice and experiences of mouth hygiene in stroke unit care: a mixed-methods study.

AIMS AND OBJECTIVES: To (1) investigate the organisation, provision and practice of oral care in typical UK stroke units; (2) explore stroke survivors', carers' and healthcare professionals' experiences and perceptions about the barriers and facilitators to receiving and undertaking oral care in stroke units. BACKGROUND: Cerebrovascular disease and oral health are major global health concerns. Little is known about the provision, challenges and practice of oral care in the stroke unit setting, and there are currently no evidence-based practice guidelines. DESIGN: Cross-sectional survey of 11 stroke units across Greater Manchester and descriptive qualitative study using focus groups and semi-structured interviews. METHODS: A self-report questionnaire was used to survey 11 stroke units in Greater Manchester. Data were then collected through two focus groups (n = 10) with healthcare professionals and five semi-structured interviews with stroke survivors and carers. Focus group and interview data were recorded, transcribed verbatim and analysed using framework approach. RESULTS: Eleven stroke units in Greater Manchester responded to the survey. Stroke survivors and carers identified a lack of oral care practice and enablement by healthcare professionals. Healthcare professionals identified a lack of formal training to conduct oral care for stroke patients, inconsistency in the delivery of oral care and no set protocols or use of formal oral assessment tools. CONCLUSION: Oral care post-stroke could be improved by increasing healthcare professionals' awareness, understanding and knowledge of the potential health benefits of oral care post-stroke. Further research is required to develop and evaluate the provision of oral care in stroke care to inform evidence-based education and practice. RELEVANCE TO CLINICAL PRACTICE: Development of staff training and education, and evidence-based oral care protocols may potentially benefit patient care and outcomes and be implemented widely across stroke care.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. METHODS: Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. RESULTS: A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. CONCLUSIONS: Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Derivation and external validation of a case mix model for the standardized reporting of 30-day stroke mortality rates.

BACKGROUND AND PURPOSE: Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data. METHODS: Models were derived (n=9000 patients) and internally validated (n=18 169 patients) using data from the Sentinel Stroke National Audit Program, the national register of acute stroke in England and Wales. External validation (n=1470 patients) was performed in the South London Stroke Register, a population-based longitudinal study. Models were fitted using general estimating equations. Discrimination and calibration were assessed using receiver operating characteristic curve analysis and correlation plots. RESULTS: Two final models were derived. Model A included age (<60, 60-69, 70-79, 80-89, and ≥90 years), National Institutes of Health Stroke Severity Score (NIHSS) on admission, presence of atrial fibrillation on admission, and stroke type (ischemic versus primary intracerebral hemorrhage). Model B was similar but included only the consciousness component of the NIHSS in place of the full NIHSS. Both models showed excellent discrimination and calibration in internal and external validation. The c-statistics in external validation were 0.87 (95% confidence interval, 0.84-0.89) and 0.86 (95% confidence interval, 0.83-0.89) for models A and B, respectively. CONCLUSIONS: We have derived and externally validated 2 models to predict mortality in unselected patients with acute stroke using commonly collected clinical variables. In settings where the ability to record the full NIHSS on admission is limited, the level of consciousness component of the NIHSS provides a good approximation of the full NIHSS for mortality prediction.

Associations between stroke mortality and weekend working by stroke specialist physicians and registered nurses: prospective multicentre cohort study.

BACKGROUND: Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this "weekend effect" is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke. METHODS AND FINDINGS: We conducted a prospective cohort study of 103 stroke units (SUs) in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and 1 December 2012 were extracted from a national register of stroke care in England. SU characteristics and staffing levels were derived from cross-sectional survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) of 30-d post-admission mortality, adjusting for case mix, organisational, staffing, and care quality variables. After adjusting for confounders, there was no significant difference in mortality risk for patients admitted to a stroke service with stroke specialist physician rounds fewer than 7 d per week (adjusted HR [aHR] 1.04, 95% CI 0.91-1.18) compared to patients admitted to a service with rounds 7 d per week. There was a dose-response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in stroke services with the lowest nurse/bed ratios. In multivariable analysis, patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07-1.29) compared to 11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI 0.77-0.93), equivalent to one excess death per 25 admissions. The main limitation is the risk of confounding from unmeasured characteristics of stroke services. CONCLUSIONS: Mortality outcomes after stroke are associated with the intensity of weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke specialist physicians. The findings have implications for quality improvement and resource allocation in stroke care. Please see later in the article for the Editors' Summary.

The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial.

BACKGROUND: Interleukin-1 (IL-1) is a key mediator of ischaemic brain injury induced by stroke and subarachnoid haemorrhage (SAH). IL-1 receptor antagonist (IL-1Ra) limits brain injury in experimental stroke and reduces plasma inflammatory mediators associated with poor outcome in ischaemic stroke patients. Intravenous (IV) IL-1Ra crosses the blood-brain barrier (BBB) in patients with SAH, to achieve cerebrospinal fluid (CSF) concentrations that are neuroprotective in rats. METHODS: A small phase II, double-blind, randomised controlled study was carried out across two UK neurosurgical centres with the aim of recruiting 32 patients. Adult patients with aneurysmal SAH, requiring external ventricular drainage (EVD) within 72 hours of ictus, were eligible. Patients were randomised to receive IL-1Ra (500 mg bolus, then a 10 mg/kg/hr infusion for 24 hours) or placebo. Serial samples of CSF and plasma were taken and analysed for inflammatory mediators, with change in CSF IL-6 between 6 and 24 hours as the primary outcome measure. RESULTS: Six patients received IL-1Ra and seven received placebo. Concentrations of IL-6 in CSF and plasma were reduced by one standard deviation in the IL-1Ra group compared to the placebo group, between 6 and 24 hours, as predicted by the power calculation. This did not reach statistical significance (P = 0.08 and P = 0.06, respectively), since recruitment did not reach the target figure of 32. No adverse or serious adverse events reported were attributable to IL-1Ra. CONCLUSIONS: IL-1Ra appears safe in SAH patients. The concentration of IL-6 was lowered to the degree expected, in both CSF and plasma for patients treated with IL-1Ra.

Bigger, faster? Associations between hospital thrombolysis volume and speed of thrombolysis administration in acute ischemic stroke.

BACKGROUND AND PURPOSE: There is evidence that high-volume hospitals may produce better patient outcomes. We aimed to identify whether there were any associations between hospital thrombolysis volume and speed of thrombolysis (tissue-type plasminogen activator [tPA]) administration in patients with ischemic stroke. METHODS: Data were drawn from 2 national clinical audits in England: the Stroke Improvement National Audit Program and the 2012 Sentinel Stroke Audit. Hospitals were categorized into 3 groups based on the annualized volume of thrombolysis: 0 to 24, 25 to 49, and ≥50 cases per annum. Arrival-brain scan, onset-tPA, and arrival-tPA times were compared across groups and stratified by onset-arrival time. Multilevel logistic models were used to estimate the odds of receiving tPA within 60 minutes of arrival. RESULTS: Of the 42 024 patients with acute ischemic stroke admitted to 80 hospitals, 4347 received tPA (10.3%). Patients admitted to hospitals with an annual thrombolysis volume of ≥50 cases per annum had median arrival-tPA times that were 28 and 22 minutes shorter than patients admitted to hospitals with volumes of 0 to 24 and 25 to 49, respectively. Onset-tPA times were shorter by 24 to 32 minutes across strata of onset-arrival times. In multivariable analysis, patients admitted to hospitals with a volume of ≥50 cases per annum had 4.33 (2.21-8.50; P<0.0001) the odds of receiving tPA within 60 minutes of arrival. No differences in safety outcomes were observed, with similar 30-day mortality and complication rates across the groups. CONCLUSIONS: Hospitals with higher volumes of thrombolysis activity achieve statistically and clinically significant shorter delays in administering tPA to patients after arrival in hospital.

Accuracy and clinical usefulness of intracerebral hemorrhage grading scores: a direct comparison in a UK population.

BACKGROUND AND PURPOSE: Various grading scores to predict survival after intracerebral hemorrhage (ICH) have been described. We aimed to test the accuracy and clinical usefulness of 3 well-known scores (original ICH score, modified ICH score, and ICH grading scale) in a large unselected cohort of typical ICH patients. METHODS: A total of 1364 ICH cases were referred to our center from January 1, 2008, to October 17, 2010. Clinical details were prospectively recorded, and the first computed tomography brain scan was retrospectively reviewed to determine ICH volume and location and to identify intraventricular hemorrhage. The original ICH, ICH grading scale, and modified ICH score were calculated. Receiver operating characteristic and decision curves for 30-day mortality were generated. RESULTS: A total of 1175 patients were included in the final analysis. All 3 scores and the Glasgow Coma Scale (GCS) divided cases into groups with highly significant differences in mortality. The area under the receiver operating characteristic curve was very similar for original ICH (0.861), ICH grading scale (0.874), and GCS (0.872), but was less for modified ICH score (0.824). Age was much less predictive (0.565). Combining GCS with age, log ICH volume, and intraventricular hemorrhage to derive a multifactorial risk of death at 30 days significantly increased the area under the receiver operating characteristic curve (0.897). All scores and GCS demonstrated a similar net benefit for threshold probabilities of 10% to 95%. Above 95%, the net benefit of GCS became inferior to the prognostic scores. CONCLUSIONS: Although existing grading scores are highly predictive of 30-day mortality, GCS alone was as predictive in our cohort, but age was not.

Stroke thrombolysis in England: an age stratified analysis of practice and outcome.

INTRODUCTION: until very recently, only small numbers of older patients with stroke had been recruited into randomised controlled trials of thrombolysis with recombinant tissue plasminogen activator (rt-PA) and patients aged >80 are excluded in the European licence for this therapy. We aimed to estimate the use and outcome of stroke thrombolysis in England across age groups, including the oldest-old. METHODS: data were collected as part of the Stroke Improvement National Audit Programme. All adults receiving thrombolysis for acute ischaemic stroke as part of routine care between April 2010 and November 2011 were included. Multilevel multivariable logistic regression was used to analyse the associations between age, process of care and 30-day mortality. RESULTS: of 37,151 adults admitted with acute ischaemic stroke, 3,374 (9.1%) received rt-PA. Patients aged >80 accounted for 21% of the thrombolysis recipients and 4.8% of patients in this age group received rt-PA. Treatment times were similar across all age groups, but older thrombolysis recipients were more likely to have Total anterior circulation infarct strokes and less likely to be functionally independent prior to stroke. Similar rates of post-thrombolysis complications were observed between patients aged >80 and younger patients. Mortality was high among older patients whether they were treated with rt-PA or not. Among patients treated with rt-PA, those aged 81-90 and >90 had, respectively, 34 and 270% higher odds of 30-day mortality than patients aged 70-80. CONCLUSION: treatment with rt-PA is now carried out frequently for older stroke patients in England. Their care is as timely as younger patients with no higher risk of major complication but mortality rates in older patients with stroke remain high.

Feasibility of assessing the needs of stroke patients after six months using the GM-SAT.

OBJECTIVE: To investigate the feasibility of administering the Greater Manchester Stroke Assessment Tool (GM-SAT), a structured evidence-based needs assessment tool, in a community setting and its acceptability to stroke patients and their carers. SETTING: Community stroke services. SUBJECTS: One hundred and thirty-seven stroke patients at six months post hospital discharge with no communication or cognitive difficulties residing in their own homes. INTERVENTION: Patients' needs were assessed by information, advice and support (IAS) coordinators from the UK Stroke Association using the GM-SAT. MAIN MEASURES: Number and nature of unmet needs identified and actions required to address these; patient/carer feedback; and IAS coordinator feedback. RESULTS: The mean number of unmet needs identified was 3 (min 0, max 14; SD 2.5). The most frequently identified unmet needs related to fatigue (34.3%), memory, concentration and attention (25.5%), secondary prevention non-lifestyle (21.9%) and depression (19.0%). It was found that 50.4% of unmet needs could be addressed through the provision of information and advice. Patients/carers found the assessment process valuable and IAS coordinators found the GM-SAT easy to use. CONCLUSIONS: Results demonstrate that the GM-SAT is feasible to administer in the community using IAS coordinators and is acceptable to patients and their carers, as well as staff undertaking the assessments. Further research is needed to determine whether the application of the GM-SAT at six months improves outcomes for patients.