Magnesium and Hematoma Expansion in Intracerebral Hemorrhage: A FAST-MAG Randomized Trial Analysis.

BACKGROUND: Observational studies suggest that magnesium may have hemostatic effects. FAST-MAG (Field Administration of Stroke Therapy-Magnesium) was a pragmatic clinical trial of magnesium sulfate administered prehospital for acute clinical stroke syndromes and included patients with intracerebral hemorrhage. Exploratory secondary analysis by the treatment group found no reduction in hematoma expansion (HE) associated with magnesium treatment in intracerebral hemorrhage but did not consider serum magnesium levels achieved. We analyzed FAST-MAG intracerebral hemorrhage data for associations between serum magnesium level, HE, and early neurological deterioration, accounting for groupwise biases. METHODS: HE was defined as hematoma volume increase ≥3 mL within 24 hours and early neurological deterioration as ≥1-point Glasgow Coma Scale decline from arrival to hospital day 4. Comparing treatment and placebo groups confirmed biased availability of neuroimaging data. Therefore, HE and neurological deterioration were analyzed and stratified by treatment and placebo groups using univariate tests and adjusted logistic regression. RESULTS: Spontaneous intracerebral hemorrhage was present in 381 patients. Placebo patients had fewer serial neuroimaging studies available (123 [65.4%] versus 145 [75.1%]; P=0.038). Necessary data were available in 104 magnesium- and 85 placebo-treated patients (age, 64.9 [13.0] years; 67.7% male). In the magnesium group, higher magnesium level was associated with less HE (adjusted odds ratio, 0.64 per mg/dL [95% CI, 0.42-0.93]) and less neurological deterioration (adjusted odds ratio, 0.54 per mg/dL [95% CI, 0.33-0.82]). In the placebo group, magnesium level was not associated with either HE or neurological deterioration. CONCLUSIONS: Magnesium may exhibit a hemostatic effect that was only observable in the FAST-MAG magnesium treatment group. Equipoise should be maintained, and specific trials are needed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00059332.

Circadian variation in stroke onset: Differences between ischemic and hemorrhagic stroke and weekdays versus weekends.

OBJECTIVES: To delineate diurnal variation onset distinguishing ischemic from hemorrhagic stroke, wake from sleep onset, and weekdays from weekends/holidays. MATERIALS AND METHODS: We analyzed patients enrolled in the FAST-MAG trial of field-initiated neuroprotective agent in patients with hyperacute stroke within 2h of symptoms onset. Stroke onset times were analyzed in 1h, 4h, and 12h time blocks throughout the 24h day-night cycle. Patient demographic, clinical features, stroke severity, and prehospital workflow were evaluated for association with onset times. RESULTS: Among 1615 acute cerebrovascular disease patients, final diagnoses were acute cerebral ischemia in 76.5% and Intracerebral hemorrhage in 23.5%. Considering all acute cerebrovascular disease patients, frequency of wake onset times showed a bimodal pattern, with peaks on onsets at 09:00-13:59 and 17:00-18:59 and early morning (00:00-05:59) onset in only 3.8%. Circadian rhythmicity differed among stroke subtypes: in acute cerebral ischemia, a single broad plateau of elevated incidences was seen from 10:00-21:59; in Intracerebral hemorrhage, bimodal peaks occurred at 09:00 and 19:00. The ratio of Intracerebral hemorrhage to acute cerebral ischemia occurrence was highest in early morning, 02:00-06:59. Marked weekday vs weekends pattern variation was noted for acute cerebral ischemia, with a broad plateau between 09:00 and 21:59 on weekdays but a unimodal peak at 14:00-15:59 on weekends. CONCLUSIONS: Wake onset of acute cerebrovascular disease showed a marked circadian variation, with distinctive patterns of a broad elevated plateau among acute cerebral ischemia patients; a bimodal peak among intracerebral hemorrhage patients; and a weekend change in acute cerebral ischemia pattern to a unimodal peak.

Magnesium Sulfate and Hematoma Expansion: An Ancillary Analysis of the FAST-MAG Randomized Trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is the deadliest form of stroke. In observational studies, lower serum magnesium has been linked to more hematoma expansion (HE) and intracranial hemorrhage, implying that supplemental magnesium sulfate is a potential acute treatment for patients with ICH and could reduce HE. FAST-MAG (Field Administration of Stroke Therapy - Magnesium) was a clinical trial of magnesium sulfate started prehospital in patients with acute stroke within 2 hours of last known well enrolled. CT was not required prior to enrollment, and several hundred patients with acute ICH were enrolled. In this ancillary analysis, we assessed the effect of magnesium sulfate treatment upon HE in patients with acute ICH. METHODS: We retrospectively analyzed data that were prospectively collected in the FAST-MAG study. Patients received intravenous magnesium sulfate or matched placebo within 2 hours of onset. We compared HE among patients allocated to intravenous magnesium sulfate or placebo with a Mann-Whitney U. We used the same method to compare neurological deficit severity (National Institutes of Health Stroke Scale) and global disability (modified Rankin Scale) at 3 months. RESULTS: Among 268 patients with ICH meeting study entry criteria, mean 65.4±13/4 years, 33% were female, and 211 (79%) had a history of hypertension. Initial deficit severities were median (interquartile range) of 4 (3-5) on the Los Angeles Motor Scale in the field and National Institutes of Health Stroke Scale score of 16 (9.5-25.5) early after hospital arrival. Follow-up brain imaging was performed a median of 17.1 (11.3-22.7) hours after first scan. The magnesium and placebo groups did not statistically differ in hematoma volume on arrival, 10.1 (5.6-28.7) versus 12.4 (5.6-28.7) mL (P=0.6), or HE, 2.0 (0.1-7.4) versus 1.5 (-0.2 to 8) mL (P=0.5). There was no difference in functional outcomes (modified Rankin Scale score of 3-6), 59% versus 50% (P=0.5). CONCLUSIONS: Magnesium sulfate did not reduce HE or improve functional outcomes at 90 days. A benefit for patients with initial hypomagnesemia was not addressed. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00059332.

Beyond the Golden Hour: Treating Acute Stroke in the Platinum 30 Minutes.

BACKGROUND: To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized. METHODS: In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy-Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients. RESULTS: Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25-30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57-79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3-5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3-18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0-1) in 35.5%, functional independence (modified Rankin Scale score, 0-2) in 53.2%, and mortality in 17.7%. CONCLUSIONS: Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.

Paramedic Global Impression of Change During Prehospital Evaluation and Transport for Acute Stroke.

Background and Purpose- The prehospital setting is a promising site for therapeutic intervention in stroke, but current stroke screening tools do not account for the evolution of neurological symptoms in this early period. We developed and validated the Paramedic Global Impression of Change (PGIC) Scale in a large, prospective, randomized trial. Methods- In the prehospital FAST-MAG (Field Administration of Stroke Therapy-Magnesium) randomized trial conducted from 2005 to 2013, EMS providers were asked to complete the PGIC Scale (5-point Likert scale values: 1-much improved, 2-mildly improved, 3-unchanged, 4-mildly worsened, 5-much worsened) for neurological symptom change during transport for consecutive patients transported by ambulance within 2 hours of onset. We analyzed PGIC concurrent validity (compared with change in Glasgow Coma Scale, Los Angeles Motor Scale), convergent validity (compared with National Institutes of Health Stroke Scale severity measure performed in the emergency department), and predictive validity (of neurological deterioration after hospital arrival and of final 90-day functional outcome). We used PGIC to characterize differential prehospital course among stroke subtypes. Results- Paramedics completed the PGIC in 1691 of 1700 subjects (99.5%), among whom 635 (37.5%) had neurological deficit evolution (32% improvement, 5.5% worsening) during a median prehospital care period of 33 (IQR, 27-39) minutes. Improvement was associated with diagnosis of cerebral ischemia rather than intracranial hemorrhage, milder stroke deficits on emergency department arrival, and more frequent nondisabled and independent 3-month outcomes. Conversely, worsening on the PGIC was associated with intracranial hemorrhage, more severe neurological deficits on emergency department arrival, more frequent treatment with thrombolytic therapy, and poor disability outcome at 3 months. Conclusions- The PGIC scale is a simple, validated measure of prehospital patient course that has the potential to provide information useful to emergency department decision-making. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00059332.

A Prehospital Acute Stroke Trial has Only Modest Impact on Enrollment in Concurrent, Post-arrival-Recruiting Stroke Trials.

BACKGROUND: Because "time is brain," acute stroke trials are migrating to the prehospital setting. The impact upon enrollment in post-arrival trials of earlier recruitment in a prehospital trial requires delineation. METHODS: We analyzed all patients recruited into acute and prevention stroke trials during an 8-year period when an academic medical center (AMC) was participating in a prehospital treatment trial - the NIH Field Administration of Stroke Treatment - Magnesium (FAST-MAG) study. RESULTS: During the study period, in addition to FAST-MAG, the AMC participated in 33 post-arrival stroke trials: 27 for acute cerebral ischemia, one for intracerebral hemorrhage, and 5 secondary prevention trials. Throughout the study period, the AMC was recruiting for at least 3 concurrent post-arrival acute trials. Among 199 patients enrolled in acute stroke trials, 98 (49%) were in FAST-MAG and 101 (51%) in concurrent, post-arrival acute trials. Among FAST-MAG patients, 67% were not eligible for any concurrent acute, post-arrival trial. Of 134 patients eligible for post-arrival acute trials, 101 (76%) were enrolled in post-arrival trials and 32 (24%) in FAST-MAG. Leading reasons FAST-MAG patients were ineligible for post-arrival acute trials were: NIHSS too low (23.4%), intracranial hemorrhage (17.9%), IV tPA used in standard management (9.0%), NIHSS too high (7.1%), and age too high (5.2%). CONCLUSIONS: A prehospital hyperacute stroke trial with wide entry criteria reduced only modestly, by one-fourth, enrollment into concurrently active, post-arrival stroke trials. Simultaneous performance of prehospital and post-arrival acute and secondary prevention stroke trials in research networks is feasible.

Evolution of a US County System for Acute Comprehensive Stroke Care.

BACKGROUND AND PURPOSE: In Orange County, California, patients with suspected acute stroke are taken to stroke neurology receiving centers that are designated by County Emergency Medical Services authorities as either hubs or spokes based on endovascular treatment capability. We examined relationships between stroke details, reperfusion therapies, hospital transfers, and their change over time. METHODS: All patients from January 1, 2013, to December 31, 2015, for whom 911 was called within 7 hours of onset in whom Emergency Medical Services personnel suspected acute stroke were evaluated. RESULTS: Among 6132 patients, 3924 (64%) had confirmed diagnosis of stroke (74% ischemic/26% hemorrhagic), yielding diagnostic precision of 64% in the field. Of the 2892 patients with acute ischemic stroke, acute reperfusion therapy was given to 29.2% (21.7% intravenous tPA [tissue-type plasminogen activator] only and 7.5% endovascular treatment). Rates of endovascular treatment of patients with ischemic stroke increased over time, more than doubling from 5.6% in 2013 to 12.5% (odds ratio per 3-month quarter=1.09; 95% confidence interval, 1.04-1.14; P<0.0001). Only 3.4% of patients with acute ischemic stroke were transferred from a spoke to a hub hospital; transfer rates were inversely related to age (P<0.0001), and reperfusion therapy rates did not vary according to transfer status. CONCLUSIONS: Favorable features of this acute stroke care system include reperfusion therapy in 29.2% of patients with ischemic stroke and substantial increases in endovascular treatment rates over time. Continued efforts to optimize acute stroke systems of care can be directed toward improving access to best acute stroke therapies.

Los Angeles Motor Scale to Identify Large Vessel Occlusion: Prehospital Validation and Comparison With Other Screens.

BACKGROUND AND PURPOSE: Prehospital scales have been developed to identify patients with acute cerebral ischemia (ACI) because of large vessel occlusion (LVO) for direct routing to Comprehensive Stroke Centers (CSCs), but few have been validated in the prehospital setting, and their impact on routing of patients with intracranial hemorrhage has not been delineated. The purpose of this study was to validate the Los Angeles Motor Scale (LAMS) for LVO and CSC-appropriate (LVO ACI and intracranial hemorrhage patients) recognition and compare the LAMS to other scales. METHODS: The performance of the LAMS, administered prehospital by paramedics to consecutive ambulance trial patients, was assessed in identifying (1) LVOs among all patients with ACI and (2) CSC-appropriate patients among all suspected strokes. Additionally, the LAMS administered postarrival was compared concurrently with 6 other scales proposed for paramedic use and the full National Institutes of Health Stroke Scale. RESULTS: Among 94 patients, age was 70 (±13) and 49% female. Final diagnoses were ACI in 76% (because of LVO in 48% and non-LVO in 28%), intracranial hemorrhage in 19%, and neurovascular mimic in 5%. The LAMS administered by paramedics in the field performed moderately well in identifying LVO among patients with ACI (C statistic, 0.79; accuracy, 0.72) and CSC-appropriate among all suspected stroke transports (C statistic, 0.80; accuracy, 0.72). When concurrently performed in the emergency department postarrival, the LAMS showed comparable or better accuracy versus the 7 comparator scales, for LVO among ACI (accuracies LAMS, 0.70; other scales, 0.62-0.68) and CSC-appropriate (accuracies LAMS, 0.73; other scales, 0.56-0.73). CONCLUSIONS: The LAMS performed in the field by paramedics identifies LVO and CSC-appropriate patients with good accuracy. The LAMS performs comparably or better than more extended prehospital scales and the full National Institutes of Health Stroke Scale.

Prehospital use of magnesium sulfate as neuroprotection in acute stroke.

BACKGROUND: Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents. METHODS: We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient's arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). RESULTS: Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P=0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P=1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P=0.95) or all serious adverse events. CONCLUSIONS: Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days. (Funded by the National Institute of Neurological Disorders and Stroke; FAST-MAG ClinicalTrials.gov number, NCT00059332.).

Paramedic Initiation of Neuroprotective Agent Infusions: Successful Achievement of Target Blood Levels and Attained Level Effect on Clinical Outcomes in the FAST-MAG Pivotal Trial (Field Administration of Stroke Therapy - Magnesium).

BACKGROUND AND PURPOSE: Paramedic use of fixed-size lumen, gravity-controlled tubing to initiate intravenous infusions in the field may allow rapid start of neuroprotective therapy for acute stroke. In a large, multicenter trial, we evaluated its efficacy in attaining target serum levels of candidate neuroprotective agent magnesium sulfate and the relation of achieved magnesium levels to outcome. METHODS: The FAST-MAG phase 3 trial (Field Administration of Stroke Therapy - Magnesium) randomized 1700 patients within 2 hours of onset to paramedic-initiated, a 15-minute loading intravenous infusion of magnesium or placebo followed by a 24-hour maintenance dose. The drug delivery strategy included fixed-size lumen, gravity-controlled tubing for field drug administration, and a shrink-wrapped ambulance kit containing both the randomized field loading and hospital maintenance doses for seamless continuation. RESULTS: Among patient randomized to active treatment, magnesium levels in the first 72 hours were assessed 987 times in 572 patients. Mean patient age was 70 years (SD±14 years), and 45% were women. During the 24-hour period of active infusion, mean achieved serum level was 3.91 (±0.8), consistent with trial target. Mg levels were increased by older age, female sex, lower weight, height, body mass index, and estimated glomerular filtration rate, and higher blood urea nitrogen, hemoglobin, and higher hematocrit. Adjusted odds for clinical outcomes did not differ by achieved Mg level, including disability at 90 days, symptomatic hemorrhage, or death. CONCLUSIONS: Paramedic infusion initiation using gravity-controlled tubing permits rapid achievement of target serum levels of potential neuroprotective agents. The absence of association of clinical outcomes with achieved magnesium levels provides further evidence that magnesium is not biologically neuroprotective in acute stroke.

Field Validation of the Los Angeles Motor Scale as a Tool for Paramedic Assessment of Stroke Severity.

BACKGROUND AND PURPOSE: The Los Angeles Motor Scale (LAMS) is a 3-item, 0- to 10-point motor stroke-deficit scale developed for prehospital use. We assessed the convergent, divergent, and predictive validity of the LAMS when performed by paramedics in the field at multiple sites in a large and diverse geographic region. METHODS: We analyzed early assessment and outcome data prospectively gathered in the FAST-MAG trial (Field Administration of Stroke Therapy-Magnesium phase 3) among patients with acute cerebrovascular disease (cerebral ischemia and intracranial hemorrhage) within 2 hours of onset, transported by 315 ambulances to 60 receiving hospitals. RESULTS: Among 1632 acute cerebrovascular disease patients (age 70±13 years, male 57.5%), time from onset to prehospital LAMS was median 30 minutes (interquartile range 20-50), onset to early postarrival (EPA) LAMS was 145 minutes (interquartile range 119-180), and onset to EPA National Institutes of Health Stroke Scale was 150 minutes (interquartile range 120-180). Between the prehospital and EPA assessments, LAMS scores were stable in 40.5%, improved in 37.6%, and worsened in 21.9%. In tests of convergent validity, against the EPA National Institutes of Health Stroke Scale, correlations were r=0.49 for the prehospital LAMS and r=0.89 for the EPA LAMS. Prehospital LAMS scores did diverge from the prehospital Glasgow Coma Scale, r=-0.22. Predictive accuracy (adjusted C statistics) for nondisabled 3-month outcome was as follows: prehospital LAMS, 0.76 (95% confidence interval 0.74-0.78); EPA LAMS, 0.85 (95% confidence interval 0.83-0.87); and EPA National Institutes of Health Stroke Scale, 0.87 (95% confidence interval 0.85-0.88). CONCLUSIONS: In this multicenter, prospective, prehospital study, the LAMS showed good to excellent convergent, divergent, and predictive validity, further establishing it as a validated instrument to characterize stroke severity in the field.

A Dedicated Spanish Language Line Increases Enrollment of Hispanics Into Prehospital Clinical Research.

BACKGROUND AND PURPOSE: Novel methods are needed to reduce the disparity of Hispanic enrollment in stroke clinical trials. Prehospital enrollment using a dedicated Spanish language line may help overcome this bias. METHODS: Subjects or legally authorized representatives provided information on race and ethnicity for all cases enrolled in the FAST-MAG clinical trial (Field Administration of Stroke Therapy-Magnesium), a prehospital phase 3 randomized study of intravenous magnesium for neuroprotection. One of 2 in-ambulance cell phones (in English or Spanish) was used to obtain informed content in the field. We describe the yield and characteristics of subjects enrolled via Spanish line. RESULTS: There were 1700 subjects enrolled from 2005 to 2012, of which 402 (24%) identified as Hispanic ethnicity. Study racial makeup was 1325 (78%) white, 219 (13%) black, and 139 (8%) Asian. The dedicated Spanish line was used for 195 (12%) enrollments. Spanish-line enrollments were younger (65 versus 70 years old; P<0.001), more likely to identify as Hispanic (98% versus 14%; P<0.001), and more likely to present with intracerebral hemorrhage (36% versus 21%; P<0.001). CONCLUSIONS: The use of a dedicated Spanish language enrollment line allowed for greater enrollment of Hispanics, a population with significantly different baseline characteristics. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

Enrollment Yield and Reasons for Screen Failure in a Large Prehospital Stroke Trial.

BACKGROUND AND PURPOSE: The enrollment yield and reasons for screen failure in prehospital stroke trials have not been well delineated. METHODS: The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial identified patients for enrollment using a 2 stage screening process-paramedics in person followed by physician-investigators by cell phone. Outcomes of consecutive screening calls from paramedics to enrolling physician-investigators were prospectively recorded. RESULTS: From 2005 to 2012, 4458 phone calls were made by paramedics to physician-investigators, an average of 1 call per vehicle every 135.7 days. A total of 1700 (38.1%) calls resulted in enrollments. The rate of enrollment of stroke mimics was 3.9%. Among the 2758 patients not enrolled, 3140 reasons for screen failure were documented. The most common reasons for nonenrollment were >2 hours from last known well (17.2%), having a prestroke condition causing disability (16.1%), and absence of a consent provider (9.5%). Novel barriers for phone informed consent specific to the prehospital setting were infrequent, but included: cell phone connection difficulties (3.2%), patient being hard of hearing (1.4%), insufficient time to complete consent (1.3%), or severely dysarthric (1.3%). CONCLUSIONS: In this large, multicenter prehospital trial, nearly 40% of every calls from the field to physician-investigators resulted in trial enrollments. The most common reasons for nonenrollment were out of window last known well time, prestroke confounding medical condition, and absence of a consent provider. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

Routing Ambulances to Designated Centers Increases Access to Stroke Center Care and Enrollment in Prehospital Research.

BACKGROUND AND PURPOSE: Emergency medical services routing of patients with acute stroke to designated centers may increase the proportion of patients receiving care at facilities meeting national standards and augment recruitment for prehospital stroke research. METHODS: We analyzed consecutive patients enrolled within 2 hours of symptom onset in a prehospital stroke trial, before and after regional Los Angeles County Emergency Medical Services implementation of preferentially routing patients with acute stroke to approved stroke centers (ASCs). From January 2005 to mid-November 2009, patients were transported to the nearest emergency department, whereas from mid-November 2009 to December 2012, patients were preferentially transported to first 9, and eventually 29, ASCs. RESULTS: There were 863 subjects enrolled before and 764 after emergency medical service preferential routing, with implementation leading to an increase in the proportion cared for at an ASC from 10% to 91% (P<0.0001), with a slight decrease in paramedic on-scene to emergency department arrival time (34.5 [SD, 9.1] minutes versus 33.5 [SD, 10.3] minutes; P=0.045). The effects of routing were immediate and included an increase in proportion of receiving ASC care (from 17% to 88%; P<0.001) and a greater number of enrollments (18.6% increase) when comparing 12 months before and after regional stroke system implementation. CONCLUSIONS: The establishment of a regionalized emergency medical services system of acute stroke care dramatically increased the proportion of patients with acute stroke cared for at ASCs, from 1 in 10 to >9 in 10, with no clinically significant increase in prehospital care times and enhanced recruitment of patients into a prehospital treatment trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

Research in prehospital and disaster health and medicine: developing a research objective statement.

A concise, well-designed research objective statement for proposed research is important for directing and coordinating a study.While often only a single or a few sentences in a manuscript, the research objective statement is usually the single most important element in the design and conduct of a research study.

Characteristics of hospitals diverting ambulances in a California EMS system.

INTRODUCTION: While several reports discuss controversies regarding ambulance diversion from acute care hospitals and the mortality, financial, and resource effects, there is scant literature related to the effect of hospital characteristics. HYPOTHESIS/PROBLEM: The objective of this study was to describe specific paramedic receiving center characteristics that are associated with ambulance diversion rates in an Emergency Medical Services system. METHODS: A retrospective observational study design was used. The study was performed in a suburban EMS system with 27 paramedic receiving centers studied; one additional hospital present at the beginning of the study period (2000-2008) was excluded due to lack of recent data. Hospital-level and population-level characteristics were gathered, including diversion rate (hours on diversion/total hours open), for-profit status, number of specialty services (including trauma, burn, cardiovascular surgery, renal transplant services, cardiac catheterization capability [both interventional and diagnostic], and burn surgery), average inpatient bed occupancy rate (total patient days/licensed bed days), annual emergency department (ED) volume (patients per year), ED admission rate (percent of ED patients admitted), and percent of patients leaving without being seen. Demographic characteristics included percent of persons in each hospital's immediate census tract below the 100% and 200% poverty lines (each considered separately), and population density within the census tract. Bivariate and regression analyses were performed. RESULTS: Diversion rates for the 27 centers ranged from 0.3%-14.5% (median 4.5%). Average inpatient bed occupancy rate and presence of specialty services were correlated with an increase in diversion rate; occupancy rate showed a 0.08% increase in diversion hours per 1% increase in occupancy rate (95% CI, 0.01%-0.16%), and hospitals with specialty services had, on average, a 4.1% higher diversion rate than other hospitals (95% CI, 1.6%-6.7%). Other characteristics did not show a statistically significant effect. When a regression was performed, only the presence of specialty services was related to the ambulance diversion rate. CONCLUSIONS: Hospitals in this study providing specialty services were more likely to have higher diversion rates. This may result in increased difficulty getting patients requiring specialty care to centers able to provide the needed level of service. Major limitations include the retrospective nature of the study, as well as reliance on multiple data systems.

Water and power reserve capacity of health facilities in the Greek islands.

INTRODUCTION: Geographically isolated islands are vulnerable during natural or technological disasters. During disasters, island health facilities should be able to secure power and water in order to continue operations. OBJECTIVE: This study sought to determine the existence of Greek island health facility backup systems for water and power. When such systems existed, reserve capacity was quantified and compared to the Pan American Health Organization (PAHO) Hospital Safety Index standards. METHODS: A standardized, self-administered questionnaire was sent to major health care facilities belonging to the national health system in all Greek islands. The biggest facility available in each island was included (hospital, health center, or health post). For Crete and Euboea, all hospitals were included. RESULTS: Fifty-four of 85 facilities queried (27 hospitals, 17 health centers and 41 health posts) responded, for a response rate of 64%. Responding to the survey were 16 hospitals, 12 health centers and 26 health posts. In 70% of responding facilities (all 16 hospitals, 10 health centers, and 12 health posts) a backup water tank was available, while 72% (all 16 hospitals, 11 health centers, and 12 health posts) had a backup power supply system. Twenty-seven facilities provided data on water reserve, with 15 (56%) reporting a reserve for three or more days. Twenty facilities provided data on fuel stock and power consumption; six (30%) had energy reserves for more than 72 hours, and eight (40%) had reserves for 24-72 hours. CONCLUSIONS: Greek state-supported island health facilities responding to the questionnaire had water and power reserves for use in an emergency. Health centers and health posts were less prepared than hospitals. Of the responding health facilities, half had a water backup system and approximately one-third had power backup systems with reserves that would last for at least 72 hours.

Purposeful Sampling: Advantages and Pitfalls.

This editorial monograph explores the advances and pitfalls of the common forms of purposeful sampling. Purposeful sampling is a common research design in qualitative research.

Modular switches shift monarch butterfly migratory flight behavior at their Mexican overwintering sites.

Eastern North American migratory monarch butterflies exhibit migratory behavioral states in fall and spring characterized by sun-dependent oriented flight. However, it is unclear how monarchs transition between these behavioral states at their overwintering site. Using a modified Mouritsen-Frost flight simulator, we confirm individual directionality and compass-based orientation (leading to group orientation) in fall migrants, and also uncover sustained flight propensity and direction-based flight reinforcement as distinctly migratory behavioral traits. By testing monarchs at their Mexican overwintering sites, we show that overwintering monarchs show reduced propensity for sustained flight and lose individual directionality, leading to the loss of group-level orientation. Overwintering fliers orient axially in a time-of-day dependent manner, which may indicate local versus long-distance directional heading. These results support a model of migratory flight behavior in which modular, state-dependent switches for flight propensity and orientation control are highly dynamic and are controlled in season- and location-dependent manners.