Observer Agreement on Computed Tomography Perfusion Imaging in Acute Ischemic Stroke.

Background and Purpose- Computed tomography (CT) perfusion (CTP) provides potentially valuable information to guide treatment decisions in acute stroke. Assessment of interobserver reliability of CTP has, however, been limited to small, mostly single center studies. We performed a large, internet-based study to assess observer reliability of CTP interpretation in acute stroke. Methods- We selected 24 cases from the IST-3 (Third International Stroke Trial), ATTEST (Alteplase Versus Tenecteplase for Thrombolysis After Ischaemic Stroke), and POSH (Post Stroke Hyperglycaemia) studies to illustrate various perfusion abnormalities. For each case, observers were presented with noncontrast CT, maps of cerebral blood volume, cerebral blood flow, mean transit time, delay time, and thresholded penumbra maps (dichotomized into penumbra and core), together with a short clinical vignette. Observers used a structured questionnaire to record presence of perfusion deficit, its extent compared with ischemic changes on noncontrast CT, and an Alberta Stroke Program Early CT Score for noncontrast CT and CTP. All images were viewed, and responses were collected online. We assessed observer agreement with Krippendorff-α. Intraobserver agreement was assessed by inviting observers who reviewed all scans for a repeat review of 6 scans. Results- Fifty seven observers contributed to the study, with 27 observers reviewing all 24 scans and 17 observers contributing repeat readings. Interobserver agreement was good to excellent for all CTP. Agreement was higher for perfusion maps compared with noncontrast CT and was higher for mean transit time, delay time, and penumbra map (Krippendorff-α =0.77, 0.79, and 0.81, respectively) compared with cerebral blood volume and cerebral blood flow (Krippendorff-α =0.69 and 0.62, respectively). Intraobserver agreement was fair to substantial in the majority of readers (Krippendorff-α ranged from 0.29 to 0.80). Conclusions- There are high levels of interobserver and intraobserver agreement for the interpretation of CTP in acute stroke, particularly of mean transit time, delay time, and penumbra maps.

Microbiological Etiologies of Pneumonia Complicating Stroke: A Systematic Review.

BACKGROUND AND PURPOSE: Identifying the causal pathogens of pneumonia complicating stroke is challenging, and antibiotics used are often broad spectrum, without recourse to the microbiological cause. We aimed to review existing literature to identify organisms responsible for pneumonia complicating stroke, before developing a consensus-based approach to antibiotic treatment. METHODS: A systematic literature review of multiple electronic databases using predefined search criteria was undertaken, in accordance with Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance. Published studies of hospitalized adults with ischemic stroke, intracerebral hemorrhage, or both, which identified microbiological etiologies for pneumonia complicating stroke up to January 1, 2017, were considered. Analysis included summary statistics and random-effects meta-analysis where appropriate. RESULTS: Fifteen studies (40% ischemic stroke, 60% ischemic stroke and intracerebral hemorrhage) involving 7968 patients were included. Reported occurrence of pneumonia varied considerably between studies (2%-63%) with a pooled frequency of 23% (95% confidence interval, 14%-34%; I2=99%). Where reported (60%), the majority of pneumonia occurred within 1 week of stroke (78%). Reported frequency of positive culture data (15%-88%) varied widely. When isolated, aerobic Gram-negative bacilli (38%) and Gram-positive cocci (16%) were most frequently cultured; commonly isolated organisms included Enterobacteriaceae (21.8%: Klebsiella pneumoniae, 12.8% and Escherichia coli, 9%), Staphylococcus aureus (10.1%), Pseudomonas aeruginosa (6%), Acinetobacter baumanii (4.6%), and Streptococcus pneumoniae (3.5%). Sputum was most commonly used to identify pathogens, in isolation (40%) or in conjunction with tracheal aspirate (15%) or blood culture (20%). CONCLUSIONS: Although the analysis was limited by small and heterogeneous study populations, limiting determination of microbiological causality, this review suggests aerobic Gram-negative bacilli and Gram-positive cocci are frequently associated with pneumonia complicating stroke. This supports the need for appropriately designed studies to determine microbial cause and a consensus-based approach in antibiotic usage and further targeted antibiotic treatment trials for enhanced antibiotic stewardship.

Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial.

BACKGROUND: Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in patients with dysphagia after acute stroke. METHODS: We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com, number ISRCTN37118456. FINDINGS: Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 [13%] of 564 patients in antibiotics group vs 52 [10%] of 524 in control group; marginal adjusted odds ratio [OR] 1·21 [95% CI 0·71-2·08], p=0·489, intraclass correlation coefficient [ICC] 0·06 [95% CI 0·02-0·17]. Algorithm-defined post-stroke pneumonia could not be established in 129 (10%) patients because of missing data. Additionally, we noted no differences in physician-diagnosed post-stroke pneumonia between groups (101 [16%] of 615 patients vs 91 [15%] of 602, adjusted OR 1·01 [95% CI 0·61-1·68], p=0·957, ICC 0·08 [95% CI 0·03-0·21]). The most common adverse events were infections unrelated to post-stroke pneumonia (mainly urinary tract infections), which were less frequent in the antibiotics group (22 [4%] of 615 vs 45 [7%] of 602; OR 0·55 [0·32-0·92], p=0·02). Diarrhoea positive for Clostridium difficile occurred in two patients (<1%) in the antibiotics group and four (<1%) in the control group, and meticillin-resistant Staphylococcus aureus colonisation occurred in 11 patients (2%) in the antibiotics group and 14 (2%) in the control group. INTERPRETATION: Antibiotic prophylaxis cannot be recommended for prevention of post-stroke pneumonia in patients with dysphagia after stroke managed in stroke units. FUNDING: UK National Institute for Health Research.

Higher cough flow is associated with lower risk of pneumonia in acute stroke.

UNLABELLED: There is little available evidence to demonstrate how cough strength mediates the risk of aspiration-related pneumonia in acute stroke. Our secondary analysis of trial data indicates that risk of pneumonia reduces with increasing peak cough flow (PCF) of voluntary cough (OR 0.994 for each 1 L/min increase in PCF, 95% CI 0.988 to 1.0, p=0.035); and to a lesser degree with increasing PCF of reflex cough (OR 0.998 for each 1 L/min increase in PCF, 95% CI 0.992 to 1.004, p=0.475). These data serve hypothesis generation. Further studies are needed to confirm these findings and validate their clinical utility. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN40298220 (post-results).

Differences in the distribution of stroke subtypes in a UK black stroke population - final results from the South London Ethnicity and Stroke Study.

BACKGROUND: Stroke incidence is increased in Black individuals but the reasons for this are poorly understood. Exploring the differences in aetiological stroke subtypes, and the extent to which they are explained by conventional and novel risk factors, is an important step in elucidating the underlying mechanisms for this increased stroke risk. METHODS: Between 1999 and 2010, 1200 black and 1200 white stroke patients were prospectively recruited from a contiguous geographical area in South London in the UK. The Trial of Org 10172 (TOAST) classification was used to classify stroke subtype. Age- and sex-adjusted comparisons of socio-demographics, traditional vascular risk factors and stroke subtypes were performed between black and white stroke patients and between Black Caribbean and Black African stroke patients using age-, sex-, and social deprivation-adjusted univariable and multivariable logistic regression analyses. RESULTS: Black stroke patients were younger than white stroke patients (mean (SD) 65.1 (13.7) vs. 74.8 (13.7) years). There were significant differences in the distribution of stroke subtypes. Small vessel disease stroke was increased in black patients versus white patients (27 % vs. 12 %; OR, 2.74; 95 % CI, 2.19-3.44), whereas large vessel and cardioembolic stroke was less frequent in black patients (OR, 0.59; 95 % CI, 0.45-0.78 and OR, 0.61; 95 % CI, 0.50-0.74, respectively). These associations remained after controlling for traditional vascular risk factors and socio-demographics. Black Caribbean patients appeared to have an intermediate risk factor and stroke subtype profile between that found in Black African and white stroke patients. Cardioembolic stroke was more strongly associated with Black Caribbean ethnicity versus Black African ethnicity (OR, 1.48; 95 % CI, 1.04-2.10), whereas intracranial large vessel disease was less frequent in Black Caribbean patients versus Black African subjects (OR, 0.44; 95 % CI, 0.24-0.83). CONCLUSIONS: Clear differences exist in stroke subtype distribution between black and white stroke patients, with a marked increase in small vessel stroke. These could not be explained by differences in the assessed traditional risk factors. Possible explanations for these differences might include variations in genetic susceptibility, differing rates of control of vascular risk factors, or as yet undetermined environmental risk factors.

Comparison of the diagnostic utility of physician-diagnosed with algorithm-defined stroke-associated pneumonia.

OBJECTIVE: Diagnosing stroke-associated pneumonia (SAP) is challenging and may result in inappropriate antibiotic use or confound research outcomes. This study evaluates the diagnostic accuracy of algorithm-defined versus physician-diagnosed SAP in 1088 patients who had dysphagic acute stroke from 37 UK stroke units between 21 April 2008 and 17 May 2014. METHODS: SAP in the first 14 days was diagnosed by a criteria-based algorithm applied to blinded patient data and independently by treating physicians. Patients in whom diagnoses differed were reassigned following blinded adjudication of individual patient records. The sensitivity, specificity, positive predictive value (PPV) and diagnostic OR of algorithmic and physician diagnosis of SAP were assessed using adjudicated SAP as the reference standard. Agreement was assessed using the κ statistic. RESULTS: Physicians diagnosed SAP in 176/1088 (16%) and the algorithm in 123/1088 (11.3%) patients. Diagnosis agreed in 885/1088 (81.3%) patients (κ 0.22 (95% CI 0.14 to 0.29)). On a blinded review, 129/1088 (11.8%) patients were adjudicated as patients with SAP. The algorithm and the physicians had high specificity (97% (95% CI 96% to 98%) and 90% (95% CI 88% to 92%), respectively) but only moderate sensitivity (72% (95% CI 64% to 80%) and 65% (95% CI 56% to 73%), respectively) in diagnosing SAP. The algorithm showed better PPV (76% (95% CI 67% to 83%) vs 48% (95% CI 40% to 55%)), diagnostic OR (80 (95% CI 42 to 136) vs 18 (95% CI 12 to 27)) and agreement (κ 0.70 (95% CI 0.63 to 0.78) vs 0.48 (95% CI 0.41 to 0.54)) than physician diagnosis with adjudicated SAP. CONCLUSIONS: Algorithm-based approaches can standardise SAP diagnosis for clinical practice and research. TRIAL REGISTRATION NUMBER: ISRCTN37118456; Post-results.

Admission avoidance hospital at home.

BACKGROUND: Admission avoidance hospital at home provides active treatment by healthcare professionals in the patient's home for a condition that otherwise would require acute hospital inpatient care, and always for a limited time period. This is the third update of the original review. OBJECTIVES: To determine the effectiveness and cost of managing patients with admission avoidance hospital at home compared with inpatient hospital care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, two other databases, and two trials registers on 2 March 2016. We checked the reference lists of eligible articles. We sought unpublished studies by contacting providers and researchers who were known to be involved in the field. SELECTION CRITERIA: Randomised controlled trials recruiting participants aged 18 years and over. Studies comparing admission avoidance hospital at home with acute hospital inpatient care. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data, requested individual patient data from trialists, and relied on published data when this was not available. We used the GRADE approach to assess the certainty of the body of evidence for the most important outcomes. MAIN RESULTS: We included 16 randomised controlled trials with a total of 1814 participants; three trials recruited participants with chronic obstructive pulmonary disease, two trials recruited participants recovering from a stroke, six trials recruited participants with an acute medical condition who were mainly elderly, and the remaining trials recruited participants with a mix of conditions. We assessed the majority of the included studies as at low risk of selection, detection, and attrition bias, and unclear for selective reporting and performance bias. Admission avoidance hospital at home probably makes little or no difference on mortality at six months' follow-up (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.60 to 0.99; P = 0.04; I2 = 0%; 912 participants; moderate-certainty evidence), little or no difference on the likelihood of being transferred (or readmitted) to hospital (RR 0.98, 95% CI 0.77 to 1.23; P = 0.84; I2 = 28%; 834 participants; moderate-certainty evidence), and may reduce the likelihood of living in residential care at six months' follow-up (RR 0.35, 95% CI 0.22 to 0.57; P < 0.0001; I2 = 78%; 727 participants; low-certainty evidence). Satisfaction with healthcare received may be improved with admission avoidance hospital at home (646 participants, low-certainty evidence); few studies reported the effect on caregivers. When the costs of informal care were excluded, admission avoidance hospital at home may be less expensive than admission to an acute hospital ward (287 participants, low-certainty evidence); there was variation in the reduction of hospital length of stay, estimates ranged from a mean difference of -8.09 days (95% CI -14.34 to -1.85) in a trial recruiting older people with varied health problems, to a mean increase of 15.90 days (95% CI 8.10 to 23.70) in a study that recruited patients recovering from a stroke. AUTHORS' CONCLUSIONS: Admission avoidance hospital at home, with the option of transfer to hospital, may provide an effective alternative to inpatient care for a select group of elderly patients requiring hospital admission. However, the evidence is limited by the small randomised controlled trials included in the review, which adds a degree of imprecision to the results for the main outcomes.

Does respiratory muscle training improve cough flow in acute stroke? Pilot randomized controlled trial.

BACKGROUND AND PURPOSE: Cough protects the lungs from aspiration. We investigated whether respiratory muscle training may improve respiratory muscle and cough function, and potentially reduce pneumonia risk in acute stroke. METHODS: We conducted a single-blind randomized placebo-controlled trial in 82 patients with stroke (mean age, 64±14 years; 49 men) within 2 weeks of stroke onset. Participants were masked to treatment allocation and randomized to 4 weeks of daily expiratory (n=27), inspiratory (n=26), or sham training (n=25), using threshold resistance devices. Primary outcome was the change in peak expiratory cough flow of maximal voluntary cough. Intention-to-treat analyses were conducted using ANCOVA, adjusting for baseline prognostic covariates. RESULTS: There were significant improvements in the mean maximal inspiratory (14 cmH2O; P<0.0001) and expiratory (15 cmH2O; P<0.0001) mouth pressure and peak expiratory cough flow of voluntary cough (74 L/min; P=0.0002) between baseline and 28 days in all groups. Peak expiratory cough flow of capsaicin-induced reflex cough was unchanged. There were no between-group differences that could be attributed to respiratory muscle training. There were also no differences in the 90-day incidence of pneumonia between the groups (P=0.65). CONCLUSIONS: Respiratory muscle function and cough flow improve with time after acute stroke. Additional inspiratory or expiratory respiratory muscle training does not augment or expedite this improvement. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN40298220.

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.

Anatomical predictors of aphasia recovery: a tractography study of bilateral perisylvian language networks.

Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. For patients and clinicians the possibility of relying on valid predictors of recovery is an important asset in the clinical management of stroke-related impairment. Age, level of education, type and severity of initial symptoms are established predictors of recovery. However, anatomical predictors are still poorly understood. In this prospective longitudinal study, we intended to assess anatomical predictors of recovery derived from diffusion tractography of the perisylvian language networks. Our study focused on the arcuate fasciculus, a language pathway composed of three segments connecting Wernicke's to Broca's region (i.e. long segment), Wernicke's to Geschwind's region (i.e. posterior segment) and Broca's to Geschwind's region (i.e. anterior segment). In our study we were particularly interested in understanding how lateralization of the arcuate fasciculus impacts on severity of symptoms and their recovery. Sixteen patients (10 males; mean age 60 ± 17 years, range 28-87 years) underwent post stroke language assessment with the Revised Western Aphasia Battery and neuroimaging scanning within a fortnight from symptoms onset. Language assessment was repeated at 6 months. Backward elimination analysis identified a subset of predictor variables (age, sex, lesion size) to be introduced to further regression analyses. A hierarchical regression was conducted with the longitudinal aphasia severity as the dependent variable. The first model included the subset of variables as previously defined. The second model additionally introduced the left and right arcuate fasciculus (separate analysis for each segment). Lesion size was identified as the only independent predictor of longitudinal aphasia severity in the left hemisphere [beta = -0.630, t(-3.129), P = 0.011]. For the right hemisphere, age [beta = -0.678, t(-3.087), P = 0.010] and volume of the long segment of the arcuate fasciculus [beta = 0.730, t(2.732), P = 0.020] were predictors of longitudinal aphasia severity. Adding the volume of the right long segment to the first-level model increased the overall predictive power of the model from 28% to 57% [F(1,11) = 7.46, P = 0.02]. These findings suggest that different predictors of recovery are at play in the left and right hemisphere. The right hemisphere language network seems to be important in aphasia recovery after left hemispheric stroke.

The development and implementation of the structured training programme for caregivers of inpatients after stroke (TRACS) intervention: the London Stroke Carers Training Course.

OBJECTIVE: To describe the content and delivery of the adapted London Stroke Carers Training Course intervention evaluated in the Training Caregivers after Stroke (TRACS) trial. SETTING: The London Stroke Carers Training Course is a structured training programme for caregivers of inpatients who are likely to return home after their stroke. The course was delivered by members of the multidisciplinary team while the patient was in the stroke unit with one recommended 'follow through' session after discharge home. INTERVENTION: The intervention consists of 14 training components (six mandatory) that were identified as important knowledge/skills that caregivers would need to be able to care for the stroke patient after discharge home. Following national training days, the London Stroke Carers Training Course was disseminated to intervention sites by the cascade method of implementation. RESULTS: The intervention was adapted for implementation across a range of stroke units. Training days were well attended (median 2.5 and 2.0 attendees per centre for the first and second days, respectively) and the feedback positive, demonstrating 'face validity' for the intervention. However cascading of this training to other members of the multidisciplinary team was not consistent, with 7/18 centres recording no cascade training. CONCLUSION: The adapted London Stroke Carers Training Course provided a training programme that could be delivered in a standardised, structured way in a variety of stroke unit settings throughout the UK. The intervention was well received by stroke unit staff, however, the cascade method of implementation was not as effective as we would have wished.

A structured training programme for caregivers of inpatients after stroke (TRACS): a cluster randomised controlled trial and cost-effectiveness analysis.

BACKGROUND: Most patients who have had a stroke are dependent on informal caregivers for activities of daily living. The TRACS trial investigated a training programme for caregivers (the London Stroke Carers Training Course, LSCTC) on physical and psychological outcomes, including cost-effectiveness, for patients and caregivers after a disabling stroke. METHODS: We undertook a pragmatic, multicentre, cluster randomised controlled trial with a parallel cost-effectiveness analysis. Stroke units were eligible if four of five criteria used to define a stroke unit were met, a substantial number of patients on the unit had a diagnosis of stroke, staff were able to deliver the LSCTC, and most patients were discharged to a permanent place of residence. Stroke units were randomly assigned to either LSCTC or usual care (control group), stratified by geographical region and quality of care, and using blocks of size 2. Patients with a diagnosis of stroke, likely to return home with residual disability and with a caregiver providing support were eligible. The primary outcome for patients was self-reported extended activities of daily living at 6 months, measured with the Nottingham Extended Activities of Daily Living (NEADL) scale. The primary outcome for caregivers was self-reported burden at 6 months, measured with the caregivers burden scale (CBS). We combined patient and caregiver costs with primary outcomes and quality-adjusted life-years (QALYs) to assess cost-effectiveness. This trial is registered with controlled-trials.com, number ISRCTN 49208824. FINDINGS: We assessed 49 stroke units for eligibility, of which 36 were randomly assigned to either the intervention group or the control group. Between Feb 27, 2008, and Feb 9, 2010, 928 patient and caregiver dyads were registered, of which 450 were in the intervention group, and 478 in the control group. Patients' self-reported extended activities of daily living did not differ between groups at 6 months (adjusted mean NEADL score 27·4 in the intervention group versus 27·6 in the control group, difference -0·2 points [95% CI -3·0 to 2·5], p value=0·866, ICC=0·027). The caregiver burden scale did not differ between groups either (adjusted mean CBS 45·5 in the intervention group versus 45·0 in the control group, difference 0·5 points [95% CI -1·7 to 2·7], p value=0·660, ICC=0·013). Patient and caregiver costs were similar in both groups (length of the initial stroke admission and associated costs were £13,127 for the intervention group and £12,471 for the control group; adjusted mean difference £1243 [95% CI -1533 to 4019]; p value=0·380). Probabilities of cost-effectiveness based on QALYs were low. INTERPRETATION: In a large scale, robust evaluation, results from this study have shown no differences between the LSCTC and usual care on any of the assessed outcomes. The immediate period after stroke might not be the ideal time to deliver structured caregiver training. FUNDING: Medical Research Council.

Health professionals' knowledge of driving restrictions following stroke and TIA: experience from a hyperacute stroke centre.

BACKGROUND AND PURPOSE: Assessment of fitness to drive (FTD) is important after stroke or transient ischaemic attack (TIA) to ensure that neither patients nor public are at risk. This is particularly important in patients with TIAs or minor stroke as many are discharged directly from emergency departments by a range of health professionals. We assessed stroke-related FTD knowledge among physicians' and allied health professionals' (AHPs) treating patients with stroke at a hyperacute stroke centre. METHODS: Knowledge of FTD restrictions following a stroke or TIA for domestic and commercial use was assessed in 195 physicians and 45 AHPs using a multiple-choice questionnaire between January and December 2009. The effect of discipline, seniority, previous instruction in FTD restrictions and experience in stroke medicine on FTD was assessed. RESULTS: The correct driving restriction following stroke with domestic and commercial license was known to 29% and 73% of physicians, respectively. For AHPs, these figures were 36% and 20%. For TIA with domestic and commercial license, this was 37% and 43% for physicians, and 44% and 11% for AHPs. 25% of physicians and 11% of AHPs believed that no driving restrictions applied after a TIA. The correct office for reporting FTD was known to 180 (92%) doctors and 31 (69%) AHPs (p=0.0001); 160 (82%) physicians and 27 (60%) AHPs correctly identified that reporting was the patients' responsibility (p=0.001). FTD knowledge correlated with post in stroke (OR 3.2 (95% CI 1.6 to 6.2, p=0.001)) but not with seniority or previous FTD education. CONCLUSIONS: Health professionals providing stroke care showed limited knowledge of FTD regulations after minor stroke or TIA. Imparting accurate information on driving restrictions is an important but neglected part of stroke management.

Influence of age on thrombolysis outcome in wake-up stroke.

BACKGROUND AND PURPOSE: Thrombolysis in patients >80 years remains controversial; we hypothesized that >80-year-old patients with wake-up ischemic stroke (WUIS) will benefit from thrombolysis despite risks because of poor outcomes with no treatment. METHODS: The study included 68 thrombolysed patients with WUIS (33 [48%] >80 years), 54 nonthrombolysed patients with WUIS (21 [39%] >80 years), and 117 patients (>80 years old) thrombolysed within 4.5 hours of symptom onset (reference group). Mortality and modified Rankin Scale (mRS) were assessed at 90 days. RESULTS: Baseline characteristics of thrombolysed and nonthrombolysed >80 and ≤80-year-old patients with WUIS were comparable. Thrombolysis outcomes in >80-year-old patients with WUIS were better than in nonthrombolysed >80-year-old patients with WUIS (90-day mortality: 24% versus 47%, P=0.034; mRS 0-2: 30% versus 5%, P=0.023; mRS 0-1: 15% versus 5%, P=0.24) and comparable with thrombolysed ≤80-year-old patients with WUIS. Thrombolysis was associated with odds ratio 0.27 (95% confidence interval, 0.05-0.97) for mortality and odds ratio 28.6 (95% confidence interval, 1.8-448) for mRS 0 to 2 at 90 days in >80-year-old patients with WUIS after adjusting for stroke severity and risk factors. CONCLUSIONS: Thrombolysis may be associated with greater benefit in >80-year-old patients with WUIS but a selection bias favoring thrombolysis in those most likely to benefit may significantly reduce interpretability of these findings.

An observational study of thrombolysis outcomes in wake-up ischemic stroke patients.

BACKGROUND AND PURPOSE: Wake-up ischemic stroke (WUIS) patients are not eligible for thrombolysis; the a priori hypothesis was that thrombolysis of selected WUIS patients who meet clinical and imaging criteria for treatment is associated with better outcomes. METHODS: The sample consisted of consecutive WUIS patients who fulfilled predefined criteria: (1) were last seen normal >4.5 hours and <12 hours before presentation; (2) National Institute of Health Stroke Scale score ≥ 5; (3) No or early ischemic changes <1/3 middle cerebral artery territory on computed tomography imaging; (4) No absolute contraindications to thrombolysis. The primary outcome measure was the modified Rankin Scale of 0 to 2 at 90 days. Other outcome measures were mortality and symptomatic intracerebral hemorrhage. RESULTS: WUIS patients constituted 10.5% (193/1836) of all stroke admissions. Inclusion criteria were fulfilled by 122 (63%) patients, of whom 68 (56%) were thrombolysed. Thrombolysed and nonthrombolysed patients were comparable for baseline characteristics, but the median baseline National Institute of Health Stroke Scale score was higher in thrombolysed patients (9 versus 11.5; P=0.034). There was no difference in modified Rankin Scale 0 to 2 (25 [37%] versus 14 [26%]; P=0.346), death (10 [15%] versus 14 [26%]; P=0.122), and symptomatic intracerebral hemorrhage (2 versus 0; P=0.204) between thrombolysed and nonthrombolysed patients. After adjusting for age, sex, and baseline National Institute of Health Stroke Scale score thrombolysis was associated with odds ratio of 5.2 (95% confidence interval 1.3-20.3), P=0.017 for modified Rankin Scale 0 to 2 at 90 days and odds ratio of 0.09 (95% confidence interval 0.02-0.44), P=0.003 for death. CONCLUSIONS: Thrombolysis in selected WUIS patients is feasible and may have potential of benefit.

A case-controlled comparison of thrombolysis outcomes between wake-up and known time of onset ischemic stroke patients.

BACKGROUND AND PURPOSE: Wake-up ischemic stroke (WUIS) patients are not thrombolysed even if they meet other criteria for treatment. We hypothesized that patients with WUIS showing no or early ischemic changes on brain imaging will have thrombolysis outcomes comparable with those with known time of symptom onset. METHODS: Consecutive sampling of a prospective registry of patients with stroke between January 2009 and December 2010 identified 394 thrombolysed patients meeting predefined inclusion criteria, 326 presenting within 0 to 4.5 hours of symptom onset (Reference Group) and 68 WUIS patients. Inclusion criteria were last seen normal<12 hours or >4.5 hours (WUIS) or presented <4.5 hours (Reference Group), had National Institutes of Health Stroke Scale score ≥5, and no or early ischemic changes on imaging at presentation. The primary outcome measure was the modified Rankin Scale of 0 to 2 at 90 days measured by trained assessors blinded to patient grouping. Other outcome measures were symptomatic intracerebral hemorrhage, modified Rankin Scale 0 to 1, and mortality at 90 days. RESULTS: The groups were comparable for mean age (72.8 versus 73.9 years; P=0.58) and baseline median National Institutes of Health Stroke Scale score (median 13 versus 12; P=0.34). The proportions of patients with modified Rankin Scale 0 to 2 (38% versus 37%; P=0.89) and modified Rankin Scale 0 to 1 (24% versus 16%; P=0.18) at 90 days, any ICH (20% versus 22%; P=0.42) and symptomatic intracerebral hemorrhage (3.4% versus 2.9%; P=1.0) were comparable after adjusting for age, stroke severity, and imaging changes. Only 9/394 (2%) patients were lost to follow-up. CONCLUSIONS: Thrombolysis in selected patients with WUIS is feasible, and its outcomes are comparable with those thrombolysed with 0 to 4.5 hours.

Stroke unit care benefits patients with intracerebral hemorrhage: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Patients with any type of stroke managed in organized inpatient (stroke unit) care are more likely to survive, return home, and regain independence. However, it is uncertain whether these benefits apply equally to patients with intracerebral hemorrhage and ischemic stroke. METHODS: We conducted a secondary analysis of a systematic review of controlled clinical trials comparing stroke unit care with general ward care, including only trials published after 1990 that could separately report outcomes for patients with intracerebral hemorrhage and ischemic stroke. We performed random-effects meta-analyses and tested for subgroup interactions by stroke type. RESULTS: We identified 13 trials (3570 patients) of modern stroke unit care that recruited patients with intracerebral hemorrhage and ischemic stroke, of which 8 trials provided data on 2657 patients. Stroke unit care reduced death or dependency (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.471-0.92; P=0.0009; I2=60%) with no difference in benefits for patients with intracerebral hemorrhage (RR, 0.79; 95% CI, 0.61-1.00) than patients with ischemic stroke (RR, 0.82; 95% CI, 0.70-0.97; Pinteraction=0.77). Stroke unit care reduced death (RR, 0.79; 95% CI, 0.64-0.97; P=0.02; I2=49%) to a greater extent for patients with intracerebral hemorrhage (RR, 0.73; 95% CI, 0.54-0.97) than patients with ischemic stroke (RR, 0.82; 95%, CI 0.61-1.09), but this difference was not statistically significant (Pinteraction=0.58). CONCLUSIONS: Patients with intracerebral hemorrhage seem to benefit at least as much as patients with ischemic stroke from organized inpatient (stroke unit) care.