Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial

<p><b>Background and Purpose:</b>Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth.</p> <p><b>Methods:</b> IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed.</p> <p><b>Results:</b> Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume.</p> <p><b>Conclusions:</b> Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.</p&gt

Statistical analysis of the primary outcome in acute stroke trials

Common outcome scales in acute stroke trials are ordered categorical or pseudocontinuous in structure but most have been analyzed as binary measures. The use of fixed dichotomous analysis of ordered categorical outcomes after stroke (such as the modified Rankin Scale) is rarely the most statistically efficient approach and usually requires a larger sample size to demonstrate efficacy than other approaches. Preferred statistical approaches include sliding dichotomous, ordinal, or continuous analyses. Because there is no best approach that will work for all acute stroke trials, it is vital that studies are designed with a full understanding of the type of patients to be enrolled (in particular their case mix, which will be critically dependent on their age and severity), the potential mechanism by which the intervention works (ie, will it tend to move all patients somewhat, or some patients a lot, and is a common hazard present), a realistic assessment of the likely effect size, and therefore the necessary sample size, and an understanding of what the intervention will cost if implemented in clinical practice. If these approaches are followed, then the risk of missing useful treatment effects for acute stroke will diminish

Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

Comparison of performance achievement award recognition with primary stroke center certification for acute ischemic stroke care.

BackgroundHospital certification and recognition programs represent 2 independent but commonly used systems to distinguish hospitals, yet they have not been directly compared. This study assessed acute ischemic stroke quality of care measure conformity by hospitals receiving Primary Stroke Center (PSC) certification and those receiving the American Heart Association's Get With The Guidelines-Stroke (GWTG-Stroke) Performance Achievement Award (PAA) recognition.Methods and resultsThe patient and hospital characteristics as well as performance/quality measures for acute ischemic stroke from 1356 hospitals participating in the GWTG-Stroke Program 2010-2012 were compared. Hospitals were classified as PAA+/PSC+ (hospitals n = 410, patients n = 169,302), PAA+/PSC- (n = 415, n = 129,454), PAA-/PSC+ (n = 88, n = 26,386), and PAA-/PSC- (n = 443, n = 75,565). A comprehensive set of stroke measures were compared with adjustment for patient and hospital characteristics. Patient characteristics were similar by PAA and PSC status but PAA-/PSC- hospitals were more likely to be smaller and nonteaching. Measure conformity was highest for PAA+/PSC+ and PAA+/PSC- hospitals, intermediate for PAA-/PSC+ hospitals, and lowest for PAA-/PSC- hospitals (all-or-none care measure 91.2%, 91.2%, 84.3%, and 76.9%, respectively). After adjustment for patient and hospital characteristics, PAA+/PSC+, PAA+/PSC-, and PAA-/PSC+ hospitals had 3.15 (95% CIs 2.86 to 3.47); 3.23 (2.93 to 3.56) and 1.72 (1.47 to 2.00), higher odds for providing all indicated stroke performance measures to patients compared with PAA-/PSC- hospitals.ConclusionsWhile both PSC certification and GWTG-Stroke PAA recognition identified hospitals providing higher conformity with care measures for patients hospitalized with acute ischemic stroke, PAA recognition was a more robust identifier of hospitals with better performance

Subject Retention in Prehospital Stroke Research Using a Telephone-Based Physician-Investigator Driven Enrollment Method.

Background and purposeSubject retention into clinical trials is vital, and prehospital enrollment may be associated with higher rates of subject withdrawal than more traditional methods of enrollment. We describe rates of subject retention in a prehospital trial of acute stroke therapy.MethodsAll subjects were enrolled into the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial. Paramedics screened eligible subjects and contacted the physician-investigator using a dedicated in-ambulance cellular phone. Physician-investigators obtained explicit informed consent from the subject or on-scene legally authorized representative (LAR) who reviewed and signed a consent form. Exception from informed consent (EFIC) was utilized in later stages of the study.ResultsThere were 1,700 subjects enrolled; 1,017 provided consent (60%), 662 were enrolled via LAR (39%), and 21 were enrolled via EFIC (1%). Of the 1,700 patients, 1,413 (83%) completed the 90-day visit, 265 (16%) died prior to the 90-day visit, and 22 (1.3%) withdrew from the study before completion. There were no differences in rates of withdrawal by method of study enrolment, i.e., self-consent (n = 14), 1.4%; LAR (n = 8), 1.2%; EFIC (n = 0) 0%.ConclusionThere was a high rate of retention when subjects were enrolled into prehospital stroke research using a phone-based method to obtain explicit consent

Emergency Stroke Calls: Obtaining Rapid Telephone Triage (ESCORTT) - a programme of research to facilitate recognition of stroke by emergency medical dispatchers

Background: Rapid access to emergency stroke care can reduce death and disability by enabling immediate provision of interventions such as thrombolysis, physiological monitoring and stabilisation. One of the ways that access to services can be facilitated is through emergency medical service (EMS)dispatchers. The sensitivity of EMS dispatchers for identifying stroke is < 50%. Studies have shown that activation of the EMSs is the single most important factor in the rapid triage and treatment of acute stroke patients. Objectives: To facilitate recognition of stroke by emergency medical dispatchers (EMDs). Design: An eight-phase mixed-methods study. Phase 1: a retrospective cohort study exploring stroke diagnosis. Phase 2: semi-structured interviews exploring public and EMS interactions. Phases 3 and 4: a content analysis of 999 calls exploring the interaction between the public and EMDs. Phases 5–7: development and implementation of stroke-specific online training (based on phases 1–4). Phase 8: an interrupted time series exploring the impact of the online training. Setting: One ambulance service and four hospitals. Participants: Patients arriving at hospital by ambulance with stroke suspected somewhere on the stroke pathway (phases 1 and 8). Patients arriving at hospital by ambulance with a final diagnosis of stroke (phase 2). Calls to the EMSs relating to phase 1 patients (phases 3 and 4). EMDs (phase 7). Interventions: Stroke-specific online training package, designed to improve recognition of stroke for EMDs. Main outcome measures: Phase 1: symptoms indicative of a final and dispatch diagnosis of stroke. Phase 2: factors involved in the decision to call the EMSs when stroke is suspected. Phases 3 and 4: keywords used by the public when describing stroke and non-stroke symptoms to EMDs. Phase 8: proportion of patients with a final diagnosis of stroke correctly dispatched as stroke by EMDs. Results: Phase 1: for patients with a final diagnosis of stroke, facial weakness and speech problems were significantly associated with an EMD code of stroke. Phase 2: four factors were identified – perceived seriousness; seeking and receiving lay or professional advice; caller’s description of symptoms and emotional response to symptoms. Phases 3 and 4: mention of ‘stroke’ or one or more Face Arm Speech Test (FAST) items is much more common in stroke compared with non-stroke calls. Consciousness level was often difficult for callers to determine and/or communicate. Phase 8: there was a significant difference (p = 0.003) in proportions correctly dispatched as stroke – before the training was implemented 58 out of 92 (63%); during implementation of training 42 out of 48 (88%); and after training implemented 47 out of 59 (80%). Conclusions: EMDs should be aware that callers are likely to describe loss of function (e.g. unable to grip) rather than symptoms (e.g. weakness) and that callers using the word ‘stroke’ or describing facial weakness, limb weakness or speech problems are likely to be calling about a stroke. Ambiguities and contradictions in dialogue about consciousness level arise during ambulance calls for suspected and confirmed stroke. The online training package improved recognition of stroke by EMDs. Recommendations for future research include testing the effectiveness of the Emergency Stroke Calls: Obtaining Rapid Telephone Triage (ESCORTT) training package on the recognition of stroke across other EMSs in England; and exploring the impact of the early identification of stroke by call handlers on patient and process outcomes. Funding: The National Institute for Health Research Programme Grants for Applied Research programme

Relationship of national institutes of health stroke scale to 30-day mortality in medicare beneficiaries with acute ischemic stroke.

BackgroundThe National Institutes of Health Stroke Scale (NIHSS), a well-validated tool for assessing initial stroke severity, has previously been shown to be associated with mortality in acute ischemic stroke. However, the relationship, optimal categorization, and risk discrimination with the NIHSS for predicting 30-day mortality among Medicare beneficiaries with acute ischemic stroke has not been well studied.Methods and resultsWe analyzed data from 33102 fee-for-service Medicare beneficiaries treated at 404 Get With The Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS documented. The 30-day mortality rate by NIHSS as a continuous variable and by risk-tree determined or prespecified categories were analyzed, with discrimination of risk quantified by the c-statistic. In this cohort, mean age was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There was a strong graded relation between increasing NIHSS score and higher 30-day mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to 42, 53.5%. A model with NIHSS alone provided excellent discrimination whether included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to 0.79]).ConclusionsThe NIHSS provides substantial prognostic information regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic stroke. This index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information, whether used as a continuous or categorical risk determinant. (J Am Heart Assoc. 2012;1:42-50.)

Patterns, predictors, variations, and temporal trends in emergency medical service hospital prenotification for acute ischemic stroke.

BACKGROUND#ENTITYSTARTX02014;: Emergency medical services (EMS) hospital prenotification of an incoming stroke patient is guideline recommended as a means of increasing the timeliness with which stroke patients are evaluated and treated. Still, data are limited with regard to national use of, variations in, and temporal trends in EMS prenotification and associated predictors of its use. METHODS AND RESULTS#ENTITYSTARTX02014;: We examined 371 988 patients with acute ischemic stroke who were transported by EMS and enrolled in 1585 hospitals participating in Get With The Guidelines-Stroke from April 1, 2003, through March 31, 2011. Prenotification occurred in 249 197 EMS-transported patients (67.0%) and varied widely by hospital (range, 0% to 100%). Substantial variations by geographic regions and by state, ranging from 19.7% in Washington, DC, to 93.4% in Montana, also were noted. Patient factors associated with lower use of prenotification included older age, diabetes mellitus, and peripheral vascular disease. Prenotification was less likely for black patients than for white patients (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97, P&lt;0.0001). Hospital factors associated with greater EMS prenotification use were absence of academic affiliation, higher annual volume of tissue plasminogen activator administration, and geographic location outside the Northeast. Temporal improvements in prenotification rates showed a modest general increase, from 58.0% in 2003 to 67.3% in 2011 (P temporal trend &lt;0.0001). CONCLUSIONS#ENTITYSTARTX02014;: EMS hospital prenotification is guideline recommended, yet among patients transported to Get With The Guidelines-Stroke hospitals it is not provided for 1 in 3 EMS-arriving patients with acute ischemic stroke and varies substantially by hospital, state, and region. These results support the need for enhanced implementation of stroke systems of care. (J Am Heart Assoc. 2012;1:e002345 doi: 10.1161/JAHA.112.002345.)