Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample.

BACKGROUND: Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. METHODS AND RESULTS: We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). CONCLUSIONS: IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results from the Nationwide Inpatient Sample.

Background: Despite its approval for use in acute ischemic stroke (AIS) >25 years ago, intravenous thrombolysis (IVT) remains underutilized, with inequities by age, sex, race/ethnicity, and geography. Little is known about IVT rates by insurance status. We aimed to assess temporal trends in the inequities in IVT use. Methods: We assessed trends from 2002 to 2015 in IVT for AIS in the Nationwide Inpatient Sample by sex, age, race/ethnicity, hospital location/teaching status, and insurance, using survey-weighted logistic regression, adjusting for sociodemographics, comorbidities, and hospital characteristics. We calculated odds ratios for IVT for each category in 2002-2008 (Period 1) and 2009-2015 (Period 2). Results: Among AIS patients (weighted N=6,694,081), IVT increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio (AARR) 1.15, 95% CI 1.14-1.16). Individuals ≥85 years had the most pronounced increase from 2002 to 2015 (AARR 1.18, 1.17-1.19), but were less likely to receive IVT compared to those aged 18-44 years in both Period 1 (adjusted odds ratio (aOR) 0.23, 0.21-0.26) and Period 2 (aOR 0.36, 0.34-0.38). Women were less likely than men to receive IVT, but the disparity narrowed over time (Period 1 aOR 0.81, 0.78-0.84, Period 2 aOR 0.94, 0.92-0.97). Inequities in IVT by race/ethnicity resolved for Hispanic individuals in Period 2 but not for Black individuals (Period 2 aOR 0.81, 0.78-0.85). The disparity in IVT for Medicare patients, compared to privately insured patients, lessened over time (Period 1 aOR 0.59, 0.56-0.52, Period 2 aOR 0.75, 0.72-0.77). Patients treated in rural hospitals were less likely to receive IVT than those treated in urban hospitals; a more dramatic increase in urban areas widened the inequity (Period 2 urban non-teaching vs. rural aOR 2.58, 2.33-2.85, urban teaching vs. rural aOR 3.90, 3.55-4.28). Conclusion: From 2002 through 2015, IVT for AIS increased among adults. Despite encouraging trends, only 1 in 15 AIS patients received IVT and persistent inequities remained for Black individuals, women, government-insured, and those treated in rural areas, highlighting the need for intensified efforts at addressing inequities.

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.

Effect of Magnesium on Deterioration and Symptomatic Hemorrhagic Transformation in Cerebral Ischemia: An Ancillary Analysis of the FAST-MAG Trial.

BACKGROUND: Magnesium (Mg) is a neuroprotectant in preclinical models. Lower serum Mg levels have been associated with symptomatic hemorrhagic transformation (HT) in patients with ischemic stroke. Early treatment of acute ischemic stroke with Mg may reduce rates of symptomatic HT. METHODS: In this post hoc study of the Field Administration of Stroke Therapy Magnesium (FAST-MAG) trial, 1,245 participants with a diagnosis of cerebral ischemia received 20 g of Mg or placebo initiated in the prehospital setting. Posttreatment serum Mg level was measured for 809 participants. Cases of clinical deterioration, defined as worsening by ≥4 points on the National Institute of Health Stroke Scale (NIHSS), were imaged and evaluated for etiology. Symptomatic HT was defined as deterioration with imaging showing new hemorrhage. RESULTS: Clinical deterioration occurred in 187 and symptomatic HT in 46 of 1,245 cases of cerebral ischemia. Rates of deterioration and symptomatic HT were not significantly lower in those who received Mg (15.7% vs. 14.4%, p = 0.591; 2.8% vs. 4.6%, p = 0.281). In cases where serum Mg level was obtained posttreatment, lower serum Mg level (<1.7 mg/dL) was associated with significantly higher rates of deterioration and symptomatic HT (27.5% vs. 15.5%, p = 0.0261; 11.6% vs. 3.65%, p = 0.00819). CONCLUSIONS: Treatment with Mg did not significantly reduce rates of clinical deterioration or symptomatic HT. Future analysis should address whether treatment with Mg could have influenced the subgroup with low serum Mg at baseline.

Prevalence and Predictors of Food Insecurity Among Stroke Survivors in the United States.

BACKGROUND: Food insecurity (FI)-lack of consistent access to food due to poor financial resources-limits the ability to eat a healthy diet, which is essential for secondary stroke prevention. Yet, little is known about FI in stroke survivors. METHODS: Using data from the US National Health and Nutrition Examination Survey from 1999 to 2015, we analyzed the prevalence, predictors, and temporal trends in FI among adults with and without self-reported prior stroke in this cross-sectional study. Age-standardized prevalence estimates were computed by self-reported history of stroke over survey waves. Multivariable logistic regression models were performed for the National Health and Nutrition Examination Survey participants who had a prior stroke to identify independent predictors of FI by self-reported history of stroke. RESULTS: Among 48 242 adults ≥20 years of age, 1877 self-reported history of stroke. FI was more prevalent among people with prior stroke (17%) versus those without prior stroke (12%; P<0.001). Prevalence of FI increased over time from 7.8% in 1999 to 42.1% in 2015 among stroke survivors and from 8% to 17% among individuals without prior stroke (P<0.001). The age-standardized prevalence of FI over the entire time was 24% among stroke survivors versus 11% among individuals without prior stroke (P<0.001). In the adjusted model, younger age (adjusted odds ratio [aOR], 0.96 [0.95-0.97]; P<0.01), Hispanic ethnicity (aOR, 2.12 [1.36-3.31]; P<0.01), lower education (aOR, 1.67 [1.17-2.38]; P<0.01), nonmarried status (aOR, 1.49 [1.01-2.19]; P=0.04), and poverty income ratio <130% (aOR, 3.78 [2.55-5.59]; P<0.01) were associated with FI in those with prior stroke. CONCLUSIONS: One in 3 stroke survivors reported FI in 2015, nearly double the prevalence in those without stroke. Addressing the fundamental drivers of FI and targeting vulnerable demographic groups may have a profound influence on stroke prevalence.

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.

Minocycline decreases blood-brain barrier permeability following aneurysmal subarachnoid hemorrhage: a randomized, double-blind, controlled trial.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH)-induced vasospasm is linked to increased inflammatory cell trafficking across a permeable blood-brain barrier (BBB). Elevations in serum levels of matrix metalloprotease 9 (MMP9), a BBB structural protein, have been implicated in the pathogenesis of vasospasm onset. Minocycline is a potent inhibitor of MMP9. The authors sought to detect an effect of minocycline on BBB permeability following aSAH. METHODS: Patients presenting within 24 hours of symptom onset with imaging confirmed aSAH (Fisher grade 3 or 4) were randomized to high-dose (10 mg/kg) minocycline or placebo. The primary outcome of interest was BBB permeability as quantitated by contrast signal intensity ratios in vascular regions of interest on postbleed day (PBD) 5 magnetic resonance permeability imaging. Secondary outcomes included serum MMP9 levels and radiographic and clinical evidence of vasospasm. RESULTS: A total of 11 patients were randomized to minocycline (n = 6) or control (n = 5) groups. No adverse events or complications attributable to minocycline were reported. High-dose minocycline administration was associated with significantly lower permeability indices on imaging analysis (p < 0.01). There was no significant difference with respect to serum MMP9 levels between groups, although concentrations trended upward in both cohorts. Radiographic vasospasm was noted in 6 patients (minocycline = 3, control = 3), with only 1 patient developing symptoms of clinical vasospasm in the minocycline cohort. There was no difference between cohorts with respect to Lindegaard ratios, transcranial Doppler values, or onset of vasospasm. CONCLUSIONS: Minocycline at high doses is well tolerated in the ruptured cerebral aneurysm population. Minocycline curtails breakdown of the BBB following aSAH as evidenced by lower permeability indices, though minocycline did not significantly alter serum MMP9 levels. Larger randomized clinical trials are needed to assess minocycline as a neuroprotectant against aSAH-induced vasospasm. Clinical trial registration no.: NCT04876638 (clinicaltrials.gov).

National Institutes of Health Stroke Scale Correlates Well with Initial Intracerebral Hemorrhage Volume.

OBJECTIVES: The US Centers for Medicare and Medicaid Services (CMS) currently publicly reports hospital-quality, risk-adjusted mortality measure for ischemic stroke but not intracerebral hemorrhage (ICH). The NIHSS, which is captured in CMS administrative claims data, is a candidate metric for use in ICH risk adjustment and has been shown to predict clinical outcome with accuracy similar to the ICH Score. Correlation between early NIHSS and initial ICH volume would further support use of the NIHSS for ICH risk adjustment. MATERIALS AND METHODS: Among 372 ICH patients enrolled in a large multicenter trial (FAST-MAG), the relation between early NIHSS and early ICH volume was assessed with correlation and linear trend analysis. RESULTS: Overall, there was strong correlation between NIHSS and ICH volume, r = 0.77 (p < 0.001), and for every 10cc increase in ICH the NIHSS increased by 4.5 points. Correlation coefficients were comparable in all subgroups, but magnitude of NIHSS increase with ICH unit volume increase was greater with left than right hemispheric ICH, with presence rather than absence of IVH, with imaging done within the first hour than second hour after last known well, with men than women, and with younger than older patients. CONCLUSION: Early NIHSS neurologic deficit severity values correlate strongly with initial ICH hematoma volume. As with ischemic stroke, lesion volume increases produce greater NIHSS change in the left than right hemisphere, reflecting greater NIHSS sensitivity to left hemisphere function. These findings provide further support for the use of NIHSS in risk-adjusted mortality measures for intracerebral hemorrhage.

Perceptions Regarding the SARS-CoV-2 Pandemic's Impact on Neurocritical Care Delivery: Results From a Global Survey.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic has impacted many facets of critical care delivery. METHODS: An electronic survey was distributed to explore the pandemic's perceived impact on neurocritical care delivery between June 2020 and March 2021. Variables were stratified by World Bank country income level, presence of a dedicated neurocritical care unit (NCCU) and experiencing a COVID-19 patient surge. RESULTS: Respondents from 253 hospitals (78.3% response rate) from 47 countries (45.5% low/middle income countries; 54.5% with a dedicated NCCU; 78.6% experienced a first surge) participated in the study. Independent of country income level, NCCU and surge status, participants reported reductions in NCCU admissions (67%), critical care drug shortages (69%), reduction in ancillary services (43%) and routine diagnostic testing (61%), and temporary cancellation of didactic teaching (44%) and clinical/basic science research (70%). Respondents from low/middle income countries were more likely to report lack of surge preparedness (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.8-5.8) and struggling to return to prepandemic standards of care (OR, 12.2; 95% CI, 4.4-34) compared with respondents from high-income countries. Respondents experiencing a surge were more likely to report conversion of NCCUs and general-mixed intensive care units (ICUs) to a COVID-ICU (OR 3.7; 95% CI, 1.9-7.3), conversion of non-ICU beds to ICU beds (OR, 3.4; 95% CI, 1.8-6.5), and deviations in critical care and pharmaceutical practices (OR, 4.2; 95% CI 2.1-8.2). Respondents from hospitals with a dedicated NCCU were less likely to report conversion to a COVID-ICU (OR, 0.5; 95% CI, 0.3-0.9) or conversion of non-ICU to ICU beds (OR, 0.5; 95% CI, 0.3-0.9). CONCLUSION: This study reports the perceived impact of the COVID-19 pandemic on global neurocritical care delivery, and highlights shortcomings of health care infrastructures and the importance of pandemic preparedness.

Association Between Glycemic Gap and In-hospital Outcomes in Aneurysmal Subarachnoid Hemorrhage.

Introduction: Glycemic gap (GG), as determined by the difference between glucose and the hemoglobin A1c (HbA1c)-derived estimated average glucose (eAG), is associated with poor outcomes in various clinical settings. There is a paucity of data describing GG and outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Our main objectives were to evaluate the association of admission glycemic gap (aGG) with in-hospital mortality and with poor composite outcome and to compare aGG's predictive value to admission serum glucose. Secondary outcomes were the associations between aGG and neurologic complications including vasospasm and delayed cerebral ischemia following aSAH. Methods: We retrospectively reviewed 119 adult patients with aSAH admitted to a single tertiary care neuroscience ICU. Spearman method was used for correlation for non-normality of data. Area under the curve (AUC) for Receiver Operating Characteristic (ROC) curve was used to estimate prediction accuracy of aGG and admission glucose on outcome measures. Multivariable analyses were conducted to assess the value of aGG in predicting in-hospital poor composite outcome and death. Results: Elevated aGG at or above 30 mg/dL was identified in 79 (66.4%) of patients. Vasospasm was not associated with the elevated aGG. Admission GG correlated with admission serum glucose (r = 0.94, p < 0.01), lactate (r = 0.41, p < 0.01), procalcitonin (r = 0.38, p < 0.01), and Hunt and Hess score (r = 0.51, p < 0.01), but not with HbA1c (r = 0.02, p = 0.82). Compared to admission glucose, aGG had a statistically significantly improved accuracy in predicting inpatient mortality (AUC mean ± SEM: 0.77 ± 0.05 vs. 0.72 ± 0.06, p = 0.03) and trended toward statistically improved accuracy in predicting poor composite outcome (AUC: 0.69 ± 0.05 vs. 0.66 ± 0.05, p = 0.07). When controlling for aSAH severity, aGG was not independently associated with delayed cerebral ischemia, poor composite outcome, and in-hospital mortality. Conclusion: Admission GG was not independently associated with in-hospital mortality or poor outcome in a population of aSAH. An aGG ≥30 mg/dL was common in our population, and further study is needed to fully understand the clinical importance of this biomarker.

Admission glycemic gap in the assessment of patients with intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke. Glycemic gap, determined by the difference between glucose and the HbA1c-derived average glucose, predicts poor outcomes in various clinical settings. Our main objective was to evaluate association of some admission factors and outcomes in relation to admission glycemic gap (AGG) in patients with ICH. METHODS: We retrospectively analyzed 506 adult patients with ICH between 2014 and 2019. AGG was defined as A1c-derived average glucose (28.7×HbA1c-46.7) subtracted from admission glucose. Admission factors and hospital outcomes indicative of poor outcome (i.e. death, gastrostomy tube, tracheostomy, and discharge status) were compared between patients with elevated (greater than 80 mg/dL) vs. non-elevated (less than or equal-to 80 mg/dL) AGG. Pearson chi-square test was used for independence, and multivariate analysis was used for association. SPSS and excel were used for all data analysis. RESULTS: We found that 67 of 506 (13%) ICH patients had elevated AGG with a mean of 137.3 mg/dL compared to 439 (87%) non-elevated AGG with a mean of 12.6 mg/dL. While mean and standard deviation values for age, weight,and body mass index were comparable between groups, the elevated AGG group had significantly higher admission glucose (286.1 ± 84.3 vs. 140.1 ± 42.5, p < 0.001), higher lactic acid (3.26 ± 2.04 mmol/L vs. 1.99 ± 1.33 mmol/L, p < 0.001), lower Glasgow Coma Scale (GCS) scores (7.70 ± 4.28 vs. 11.24 ± 4.14, p < 0.001), and higher ICH score (median 3, IQR 2-4 vs. median 1, IQR 0-3, p < 0.001). Higher AGG was associated with an increased likelihood of mechanical ventilation, and in-hospital mortality (74.6% vs. 38.3% and 47.8% vs. 15.0% respectively, p < 0.001). Placements of tracheostomy and gastrostomy were similar between the two groups (13.4% vs. 11.8%, p = 0.69% and 1.5% and 4.6%, p = 0.34 respectively). The higher AGG group had a more common poor discharge outcome to either long-term acute care, skilled nursing facility, and/or hospice (65.7% vs. 42.6%, p < 0.001). Hospital cost and length of hospitalization did not differ significantly. Although AGG was not an independent predictor of poor outcome, multivariate analysis showed it was significantly associated with poor outcome while admission glucose was not (p < 0.001 vs. p = 0.167). CONCLUSION: Elevated AGG was associated with worse GCS and ICH scores on admission, as well as need for mechanical ventilation, in hospital mortality and poor discharge status. Elevated AGG has value in prediction of outcome, but existing understanding is limited.

CT perfusion core and ASPECT score prediction of outcomes in DEFUSE 3.

BACKGROUND: The role of Alberta Stroke Program Early CT Score (ASPECTS) for thrombectomy patient selection and prognostication in late time windows is unknown. AIMS: We compared baseline ASPECTS and core infarction determined by CT perfusion (CTP) as predictors of clinical outcome in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE) 3 trial. METHODS: We included all DEFUSE 3 patients with baseline non-contrast CT and CTP imaging. ASPECTS and core infarction were determined by the DEFUSE 3 core laboratory. Primary outcome was functional independence (modified Rankin Scale (mRS) ≤2). Secondary outcomes included ordinal mRS shift at 90 days and final core infarction volume. RESULTS: Of the 142 patients, 85 patients (60%) had ASPECTS 8-10 and 57 (40%) had ASPECTS 5-7. Thirty-one patients (36%) with ASPECTS 8-10 and 11 patients (19%) with ASPECTS 5-7 were functionally independent at 90 days (p = 0.03). In the primary and secondary logistic regression analysis, there was no difference in ordinal mRS shift (p = 0.98) or functional independence (mRS ≤ 2; p = 0.36) at 90 days between ASPECTS 8-10 and ASPECTS 5-7 patients. Similarly, primary and secondary logistic regression analyses found no difference in ordinal mRS shift (p = 1.0) or functional independence (mRS ≤ 2; p = 0.87) at 90 days between patients with baseline small core ( < 50 ml) versus medium core (50-70 ml). CONCLUSIONS: Higher ASPECTS (8-10) correlated with functional independence at 90 days in the DEFUSE trial. ASPECTS and core infarction volume did not modify the thrombectomy treatment effect, which indicates that patients with a target mismatch profile on perfusion imaging should undergo thrombectomy regardless of ASPECTS or core infarction volume in late time windows.

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.

Older Age Is Not Associated with Worse Outcomes Following Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Decompressive hemicraniectomy (DHC) is commonly offered after large spontaneous intracerebral hemorrhage (ICH) as a life-saving measure. Based on limited available evidence, surgery is sometimes avoided in the elderly. The association between age and outcomes following DHC in spontaneous ICH remains largely understudied. OBJECTIVE: The goal of this study is to investigate the influence of older age on outcomes of patients who undergo DHC for spontaneous ICH. METHODS: In this retrospective cohort study, inpatient data were obtained from the United States Nationwide Inpatient Sample from 2000 to 2011. Using International Classification of Diseases, ninth revision designations, patients with a primary diagnosis of nontraumatic ICH who underwent DHC were identified. The primary outcome of interest was the association of age to inpatient mortality and poor outcome. Subjects were grouped by age: 18-50, 51-60, 61-70, and more than 70 years. Sample characteristics were compared across age groups using χ2 testing, and univariate and multivariate Poisson Regression was performed using a generalized equation to estimate rate ratios for primary and secondary outcomes. RESULTS: One thousand one hundred and forty four patient cases were isolated. Death occurred in an estimated 28.9% and poor outcome in 86.4%. In multivariate Poisson regression models, there was no difference in hospital mortality or poor outcome by age group. Although younger patients were more likely to be diagnosed with herniation, total complication rate was similar between age groups. CONCLUSIONS: Our study results do not provide evidence that age independently predicts in-hospital mortality or poor outcomes. The true influence of age on outcomes is unclear, and further study is needed to determine which factors may be best in selecting candidates for DHC following spontaneous ICH.

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

BACKGROUND AND PURPOSE: Subject 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. METHODS: All 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. RESULTS: There 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%. CONCLUSION: There was a high rate of retention when subjects were enrolled into prehospital stroke research using a phone-based method to obtain explicit consent.

Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome

Background and Purpose- The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods- This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin Scale score of ≤2). Additional outcomes include the full range of the modified Rankin Scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results- Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26-1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant ( P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions- In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Quality of Acute Stroke Care at Primary Stroke Centers Before and After Certification in Comparison to Never-Certified Hospitals.

Background and Purpose: Primary stroke center (PSC) certification is associated with improvements in stroke care and outcome. However, these improvements may reflect a higher baseline level of care delivery in hospitals eventually achieving certification. This study examines whether advancements in acute stroke care at PSCs are due to certification or factors intrinsic to the hospital. Methods: Data was obtained from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial with participation of 40 Emergency Medical System agencies, 315 ambulances, and 60 acute receiving hospitals in Los Angeles and Orange Counties. Subjects were transported to one of three types of destinations: PSC certified hospitals (PSCs), hospitals that were not PSCs at time of enrollment but would later become certified (pre-PSCs), and hospitals that would never be certified (non-PSCs). Metrics of acute stroke care quality included time arrival to imaging, use of intravenous tPA, and arrival to treatment. Results: Of 1,700 cases, 856(50%) were at certified PSCs, 529(31%) were at pre-PSCs, and 315 (19%) were at non-PSCs. Mean (SD) was 33min (±76.1) at PSCs, 47(±86.6) at pre-PSCs, and 49(±71.7) at non-PSCs. Of 1,223 cerebral ischemia cases, rate of tPA utilization was 43% at PSCs, 27% at pre-PSCs, and 28% at non-PSCs. Mean ED arrival to thrombolysis was 71(±32.7) at PSC, 98(±37.6) at pre-PSC, and 95(±45.0) at non-PSCs. PSCs had improved time to imaging (p = 0.014), percent tPA use (p < 0.001), and time to treatment (p = 0.003). Conclusions: Stroke care at hospitals prior to PSC certification is equivalent to care at non-PSCs. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

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.

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging.

BACKGROUND: Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. METHODS: We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. RESULTS: The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18). CONCLUSIONS: Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

Impact of the 2003 ACGME Resident Duty Hour Reform on Hospital-Acquired Conditions: A National Retrospective Analysis.

BACKGROUND: The Accreditation Council for Graduate Medical Education reforms in 2003 instituted an 80-hour weekly limit for resident physicians. Critics argue that these restrictions have increased handoffs among residents and the potential for a decline in patient safety. "Never events" hospital-acquired conditions (HACs) are a set of preventable events used as a quality metric in hospital safety analyses. OBJECTIVE: This analysis evaluated post-work hour reform effects on HAC incidence for US hospital inpatients, using the National Inpatient Sample. METHODS: Data were collected from 2000-2002 (pre-2003) and 2004-2006 (post-2003) time periods. HAC incidence in academic and non-academic centers was evaluated in multivariate analysis assessing for likelihood of HAC occurrence, prolonged length of stay (pLOS), and increased total charges. RESULTS: The data encompassed approximately 111 million pre-2003 and 117 million post-2003 admissions. Patients were 10% more likely to incur a HAC in the post-2003 versus pre-2003 era (odds ratio [OR] = 1.10; 95% confidence interval [CI] 1.06-1.14; P < .01). Teaching hospitals exhibited an 18% (OR = 1.18; 95% CI 1.11-1.27; P < .01) increase in HAC likelihood, with no change in nonteaching settings (OR = 1.03; 95% CI 1.00-1.06; P > .05). Patients with ≥ 1 HAC were associated with a 60% likelihood of elevated charges (OR = 1.60; 95% CI 1.50-1.72; P < .01) and 65% likelihood of pLOS (OR = 1.65; 95% CI 1.60-1.70; P < .01). CONCLUSIONS: Post-2003 era patients were associated with 10% increased likelihood of HAC, with effects noted primarily at teaching hospitals.