Browsing by Subject "Brain Ischemia"
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Item Open Access A Randomized, Placebo-Controlled, Phase II Trial of Intravenous Allogeneic Non-HLA Matched, Unrelated Donor, Cord Blood Infusion for Ischemic Stroke.(Stem cells translational medicine, 2024-02) Laskowitz, Daniel T; Troy, Jesse; Poehlein, Emily; Bennett, Ellen R; Shpall, Elizabeth J; Wingard, John R; Freed, Brian; Belagaje, Samir R; Khanna, Anna; Jones, William; Volpi, John J; Marrotte, Eric; Kurtzberg, JoanneStroke remains a leading cause of death and disability in the US, and time-limited reperfusion strategies remain the only approved treatment options. To address this unmet clinical need, we conducted a phase II randomized clinical trial to determine whether intravenous infusion of banked, non-HLA matched unrelated donor umbilical cord blood (UCB) improved functional outcome after stroke. Participants were randomized 2:1 to UCB or placebo within strata of National Institutes of Health Stroke Scale Score (NIHSS) and study center. Study product was infused 3-10 days following index stroke. The primary endpoint was change in modified Rankin Scale (mRS) from baseline to day 90. Key secondary outcomes included functional independence, NIHSS, the Barthel Index, and assessment of adverse events. The trial was terminated early due to slow accrual and logistical concerns associated with the COVID-19 pandemic, and a total of 73 of a planned 100 participants were included in primary analyses. The median (range) of the change in mRS was 1 point (-2, 3) in UCB and 1 point (-1,4) in Placebo (P = 0.72). A shift analysis comparing the mRS at day 90 utilizing proportional odds modeling showed a common odds ratio of 0.9 (95% CI: 0.4, 2.3) after adjustment for baseline NIHSS and randomization strata. The distribution of adverse events was similar between arms. Although this study did not suggest any safety concerns related to UCB in ischemic stroke, we did not show a clinical benefit in the reduced sample size evaluated.Item Open Access A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.(J Am Heart Assoc, 2013-01-28) Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee HBACKGROUND: We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS AND RESULTS: Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. CONCLUSIONS: A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.Item Open Access Absence of July Phenomenon in Acute Ischemic Stroke Care Quality and Outcomes.(Journal of the American Heart Association, 2018-01-31) Gonzalez-Castellon, Marco; Ju, Christine; Xian, Ying; Hernandez, Adrian; Fonarow, Gregg C; Schwamm, Lee; Smith, Eric E; Bhatt, Deepak L; Reeves, Matthew; Willey, Joshua ZBACKGROUND:Lower care quality and an increase in adverse outcomes as a result of new medical trainees is a concept well rooted in popular belief, termed the "July phenomenon." Whether this phenomenon occurs in acute ischemic stroke has not been well studied. METHODS AND RESULTS:We analyzed data from patients admitted with ischemic stroke in 1625 hospitals participating in the Get With The Guidelines-Stroke program for the 5-year period between January 2009 and December 2013. We compared acute stroke treatment processes and in-hospitals outcomes among the 4 quarters (first quarter: July-September, last quarter: April-June) of the academic year. Multivariable logistic regression models were used to evaluate the relationship between academic year transition and processes measures. A total of 967 891 patients were included in the study. There was a statistically significant, but modest (<4 minutes or 5 percentage points) difference in distribution of or quality and clinical metrics including door-to-computerized tomography time, door-to-needle time, the proportion of patients with symptomatic intracranial hemorrhage within 36 hours of admission, and the proportion of patients who received defect-free care in stroke performance measures among academic year quarters (P<0.0001). In multivariable analyses, there was no evidence that quarter 1 of the academic year was associated with lower quality of care or worse in-hospital outcomes in teaching and nonteaching hospitals. CONCLUSIONS:We found no evidence of the "July phenomenon" in patients with acute ischemic stroke among hospitals participating in the Get With The Guidelines-Stroke program.Item Open Access Anesthesia in Experimental Stroke Research.(Translational stroke research, 2016-10) Hoffmann, Ulrike; Sheng, Huaxin; Ayata, Cenk; Warner, David SAnesthetics have enabled major advances in development of experimental models of human stroke. Yet, their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have species-, drug-, and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both preconditioning and postconditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke.Item Open Access Anticoagulation in Acute Neurological Disease.(Seminars in neurology, 2021-10) Sasannejad, Cina; Sheth, Kevin NWhile anticoagulation and its reversal have been of clinical relevance for decades, recent academic and technological advances have expanded the repertoire of its application in neurological disease. The advent of direct oral anticoagulants provides effective, mechanistically elegant, and relatively safer therapeutic options than warfarin for eligible patients at risk for neurological sequelae of prothrombotic states, particularly given the recent availability of corresponding reversal agents. In this review, we examine the provenance, indications, safety, and reversal tools for anticoagulant medications in the context of neurological disease, with specific attention to acute ischemic stroke, cerebral venous sinus thrombosis, and intracerebral hemorrhage. We will use specific clinical scenarios to illustrate the complex factors that must be considered in the use of anticoagulation, including intracranial pathology such as intracerebral hemorrhage, traumatic brain injury, or malignancy; metabolic complications such as chronic kidney disease; pregnancy; and advanced age.Item Open Access Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome.(Critical care medicine, 2019-08) Ma, Shuang; Chu, Dongmei; Li, Litao; Creed, Jennifer A; Ryang, Yu-Mi; Sheng, Huaxin; Yang, Wei; Warner, David S; Turner, Dennis A; Hoffmann, UlrikeObjectives
We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days.Design
Controlled, randomized, double-blinded laboratory study.Setting
Animal research laboratories.Subjects
Adult Wistar male rats (n = 110).Interventions
Rats were subjected to permanent or temporary focal cerebral ischemia via middle cerebral artery occlusion, followed by inhalation of 70% argon or nitrogen in 30% oxygen for 24 hours. On postoperative day 7, a 48-point neuroscore and histologic lesion size were assessed.Measurements and main results
After argon inhalation for 24 hours immediately following "severe permanent ischemia" induction, neurologic outcome (neuroscore, p = 0.034), overall recovery (body weight, p = 0.02), and infarct volume (total infarct volume, p = 0.0001; cortical infarct volume, p = 0.0003; subcortical infarct volume, p = 0.0001) were significantly improved. When 24-hour argon treatment was delayed for 2 hours after permanent stroke induction or until after postischemic reperfusion treatment, neurologic outcomes remained significantly improved (neuroscore, p = 0.043 and p = 0.014, respectively), as was overall recovery (body weight, p = 0.015), compared with nitrogen treatment. However, infarct volume and 7-day mortality were not significantly reduced when argon treatment was delayed.Conclusions
Neurologic outcome (neuroscore), overall recovery (body weight), and infarct volumes were significantly improved after 24-hour inhalation of 70% argon administered immediately after severe permanent stroke induction. Neurologic outcome and overall recovery were also significantly improved even when argon treatment was delayed for 2 hours or until after reperfusion.Item Open Access Association between stroke center hospitalization for acute ischemic stroke and mortality.(JAMA, 2011-01) Xian, Ying; Holloway, Robert G; Chan, Paul S; Noyes, Katia; Shah, Manish N; Ting, Henry H; Chappel, Andre R; Peterson, Eric D; Friedman, BruceAlthough stroke centers are widely accepted and supported, little is known about their effect on patient outcomes.To examine the association between admission to stroke centers for acute ischemic stroke and mortality.Observational study using data from the New York Statewide Planning and Research Cooperative System. We compared mortality for patients admitted with acute ischemic stroke (n = 30,947) between 2005 and 2006 at designated stroke centers and nondesignated hospitals using differential distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. Patients were followed up for mortality for 1 year after the index hospitalization through 2007. To assess whether our findings were specific to stroke, we also compared mortality for patients admitted with gastrointestinal hemorrhage (n = 39,409) or acute myocardial infarction (n = 40,024) at designated stroke centers and nondesignated hospitals.Thirty-day all-cause mortality.Among 30,947 patients with acute ischemic stroke, 15,297 (49.4%) were admitted to designated stroke centers. Using the instrumental variable analysis, admission to designated stroke centers was associated with lower 30-day all-cause mortality (10.1% vs 12.5%; adjusted mortality difference, -2.5%; 95% confidence interval [CI], -3.6% to -1.4%; P < .001) and greater use of thrombolytic therapy (4.8% vs 1.7%; adjusted difference, 2.2%; 95% CI, 1.6% to 2.8%; P < .001). Differences in mortality also were observed at 1-day, 7-day, and 1-year follow-up. The outcome differences were specific for stroke, as stroke centers and nondesignated hospitals had similar 30-day all-cause mortality rates among those with gastrointestinal hemorrhage (5.0% vs 5.8%; adjusted mortality difference, +0.3%; 95% CI, -0.5% to 1.0%; P = .50) or acute myocardial infarction (10.5% vs 12.7%; adjusted mortality difference, +0.1%; 95% CI, -0.9% to 1.1%; P = .83).Among patients with acute ischemic stroke, admission to a designated stroke center was associated with modestly lower mortality and more frequent use of thrombolytic therapy.Item Open Access Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke.(JAMA, 2020-06) Man, Shumei; Xian, Ying; Holmes, DaJuanicia N; Matsouaka, Roland A; Saver, Jeffrey L; Smith, Eric E; Bhatt, Deepak L; Schwamm, Lee H; Fonarow, Gregg CImportance:Earlier administration of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is associated with reduced mortality by the time of hospital discharge and better functional outcomes at 3 months. However, it remains unclear whether shorter door-to-needle times translate into better long-term outcomes. Objective:To examine whether shorter door-to-needle times with intravenous tPA for acute ischemic stroke are associated with improved long-term outcomes. Design, Setting, and Participants:This retrospective cohort study included Medicare beneficiaries aged 65 years or older who were treated for acute ischemic stroke with intravenous tPA within 4.5 hours from the time they were last known to be well at Get With The Guidelines-Stroke participating hospitals between January 1, 2006, and December 31, 2016, with 1-year follow-up through December 31, 2017. Exposures:Door-to-needle times for intravenous tPA. Main Outcomes and Measures:The primary outcomes were 1-year all-cause mortality, all-cause readmission, and the composite of all-cause mortality or readmission. Results:Among the 61 426 patients treated with tPA within 4.5 hours, the median age was 80 years and 43.5% were male. The median door-to-needle time was 65 minutes (interquartile range, 49-88 minutes). The 48 666 patients (79.2%) who were treated with tPA and had door-to-needle times of longer than 45 minutes, compared with those treated within 45 minutes, had significantly higher all-cause mortality (35.0% vs 30.8%, respectively; adjusted HR, 1.13 [95% CI, 1.09-1.18]), higher all-cause readmission (40.8% vs 38.4%; adjusted HR, 1.08 [95% CI, 1.05-1.12]), and higher all-cause mortality or readmission (56.0% vs 52.1%; adjusted HR, 1.09 [95% CI, 1.06-1.12]). The 34 367 patients (55.9%) who were treated with tPA and had door-to-needle times of longer than 60 minutes, compared with those treated within 60 minutes, had significantly higher all-cause mortality (35.8% vs 32.1%, respectively; adjusted hazard ratio [HR], 1.11 [95% CI, 1.07-1.14]), higher all-cause readmission (41.3% vs 39.1%; adjusted HR, 1.07 [95% CI, 1.04-1.10]), and higher all-cause mortality or readmission (56.8% vs 53.1%; adjusted HR, 1.08 [95% CI, 1.05-1.10]). Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause mortality (adjusted HR, 1.04 [95% CI, 1.02-1.05]) within 90 minutes after hospital arrival, but not after 90 minutes (adjusted HR, 1.01 [95% CI, 0.99-1.03]), higher all-cause readmission (adjusted HR, 1.02; 95% CI, 1.01-1.03), and higher all-cause mortality or readmission (adjusted HR, 1.02 [95% CI, 1.01-1.03]). Conclusions and Relevance:Among patients aged 65 years or older with acute ischemic stroke who were treated with tissue plasminogen activator, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year. These findings support efforts to shorten time to thrombolytic therapy.Item Open Access Association of body mass index with mortality and functional outcome after acute ischemic stroke.(Scientific reports, 2017-05-31) Sun, Weiping; Huang, Yining; Xian, Ying; Zhu, Sainan; Jia, Zhirong; Liu, Ran; Li, Fan; Wei, Jade W; Wang, Ji-Guang; Liu, Ming; Anderson, Craig SThe relation between obesity and stroke outcome has been disputed. This study was aimed to determine the association of body mass index (BMI) with mortality and functional outcome in patients with acute ischemic stroke. Data were from a national, multi-centre, prospective, hospital-based register: the ChinaQUEST (Quality Evaluation of Stroke Care and Treatment) study. Of 4782 acute ischemic stroke patients, 282 were underweight (BMI < 18.5 kg/m2), 2306 were normal-weight (BMI 18.5 to < 24 kg/m2), 1677 were overweight (BMI 24 to <28 kg/m2) and 517 were obese (BMI ≥ 28 kg/m2). The risks of death at 12 months and death or high dependency at 3 and 12 months in overweight (HR: 0.97, 95% CI: 0.78-1.20; OR: 0.93, 95% CI: 0.80-1.09; OR: 0.95, 95% CI: 0.81-1.12) and obese patients (HR: 1.07, 95% CI: 0.78-1.48; OR: 0.96, 95% CI: 0.75-1.22; OR: 1.06, 95% CI: 0.83-1.35) did not differ from normal-weight patients significantly after adjusting for baseline characteristics. Underweight patients had significantly increased risks of these three outcomes. In ischemic stroke patients, being overweight or obese was not associated with decreased mortality or better functional recovery but being underweight predicted unfavourable outcomes.Item Open Access Bone morphogenetic protein 10: a novel risk marker of ischaemic stroke in patients with atrial fibrillation.(European heart journal, 2023-01) Hijazi, Ziad; Benz, Alexander P; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Granger, Christopher B; Kastner, Peter; Lopes, Renato D; Ziegler, André; Oldgren, Jonas; Siegbahn, Agneta; Wallentin, LarsAims
Biomarkers specifically related to atrial tissue may increase the understanding of the pathophysiology of atrial fibrillation (AF) and further improve risk prediction in this setting. Bone morphogenetic protein 10 (BMP10) is a protein expressed in the atrial myocardium. We evaluated the association between BMP10 and the risk of ischaemic stroke and other cardiovascular events in large cohorts of patients with AF, treated with and without oral anticoagulation (OAC).Methods and results
BMP10 was measured in plasma samples collected at randomisation in patients with AF without OAC in the ACTIVE A and AVERROES trials (n = 2974), and with OAC in the ARISTOTLE trial (n = 13 079). BMP10 was analysed with a prototype Elecsys immunoassay. Associations with outcomes were evaluated by Cox-regression models adjusted for clinical characteristics, kidney function, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median concentrations of BMP10 were 2.47 and 2.44 ng/mL, in the non-OAC and OAC cohort, respectively. Increasing BMP10 was associated with lower body mass index, older age, female sex, kidney dysfunction, and AF rhythm. BMP10 was consistently associated with ischaemic stroke. In the non-OAC cohort, BMP10 increased the concordance index of the multivariable model from 0.713 to 0.733 (P = 0.004) and in the OAC cohort from 0.673 to 0.694 (P < 0.001). Additionally, BMP10 maintained a significant prognostic value after additionally adjusting for NT-proBNP. BMP10 was not independently associated with bleeding or with death.Conclusion
The novel atrial biomarker BMP10 was independently associated with ischaemic stroke in patients with AF irrespective of OAC treatment. BMP10 seems to be more specifically related to the risk of ischaemic stroke in AF.One-sentence summary
In this study, BMP10 may be a novel specific biomarker of ischaemic stroke in patients with atrial fibrillation, irrespective of oral anticoagulation.Item Open Access Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.(Nature chemical biology, 2005-07) Degterev, Alexei; Huang, Zhihong; Boyce, Michael; Li, Yaqiao; Jagtap, Prakash; Mizushima, Noboru; Cuny, Gregory D; Mitchison, Timothy J; Moskowitz, Michael A; Yuan, JunyingThe mechanism of apoptosis has been extensively characterized over the past decade, but little is known about alternative forms of regulated cell death. Although stimulation of the Fas/TNFR receptor family triggers a canonical 'extrinsic' apoptosis pathway, we demonstrated that in the absence of intracellular apoptotic signaling it is capable of activating a common nonapoptotic death pathway, which we term necroptosis. We showed that necroptosis is characterized by necrotic cell death morphology and activation of autophagy. We identified a specific and potent small-molecule inhibitor of necroptosis, necrostatin-1, which blocks a critical step in necroptosis. We demonstrated that necroptosis contributes to delayed mouse ischemic brain injury in vivo through a mechanism distinct from that of apoptosis and offers a new therapeutic target for stroke with an extended window for neuroprotection. Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies.Item Open Access Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke.(JAMA neurology, 2019-04) Song, Sarah; Liang, Li; Fonarow, Gregg C; Smith, Eric E; Bhatt, Deepak L; Matsouaka, Roland A; Xian, Ying; Schwamm, Lee H; Saver, Jeffrey LImportance:Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals. Objective:To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke. Design, Setting, Participants:Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association. Main Outcomes and Measures:Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures. Results:The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008). Conclusions and Relevance:Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.Item Open Access Comparison of performance achievement award recognition with primary stroke center certification for acute ischemic stroke care.(J Am Heart Assoc, 2013-10-14) Fonarow, Gregg C; Liang, Li; Smith, Eric E; Reeves, Mathew J; Saver, Jeffrey L; Xian, Ying; Hernandez, Adrian F; Peterson, Eric D; Schwamm, Lee H; GWTG-Stroke Steering Committee & InvestigatorsBACKGROUND: Hospital 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 RESULTS: The 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. CONCLUSIONS: While 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.Item Open Access Contemporary trends and predictors of postacute service use and routine discharge home after stroke.(J Am Heart Assoc, 2015-02-23) Prvu Bettger, Janet; McCoy, Lisa; Smith, Eric E; Fonarow, Gregg C; Schwamm, Lee H; Peterson, Eric DBACKGROUND: Returning home after the hospital is a primary aim for healthcare; however, additional postacute care (PAC) services are sometimes necessary for returning stroke patients to their pre-event status. Recent trends in hospital discharge disposition specifying PAC use have not been examined across age groups or health insurance types. METHODS AND RESULTS: We examined trends in discharge to inpatient rehabilitation facilities (IRFs), skilled nursing facilities (SNFs), home with home health (HH), and home without services for 849 780 patients ≥18 years of age with ischemic or hemorrhagic stroke at 1687 hospitals participating in Get With The Guidelines-Stroke. Multivariable analysis was used to identify factors associated with discharge to any PAC (IRF, SNF, or HH) versus discharge home without services. From 2003 to 2011, there was a 2.1% increase (unadjusted P=0.001) in PAC use after a stroke hospitalization. Change was greatest in SNF use, an 8.3% decrease over the period. IRF and HH increased 6.9% and 3.6%, respectively. The 2 strongest clinical predictors of PAC use after acute care were patients not ambulating on the second day of their hospital stay (ambulation odds ratio [OR], 3.03; 95% confidence interval [CI], 2.86 to 3.23) and those who failed a dysphagia screen or had an order restricting oral intake (OR, 2.48; 95% CI, 2.37 to 2.59). CONCLUSIONS: Four in 10 stroke patients are discharged home without services. Although little has changed overall in PAC use since 2003, further research is needed to explain the shift in service use by type and its effect on outcomes.Item Open Access Cost efficiency of anticoagulation with warfarin to prevent stroke in medicare beneficiaries with nonvalvular atrial fibrillation.(Stroke, 2011-01) Mercaldi, Catherine J; Ciarametaro, Mike; Hahn, Beth; Chalissery, George; Reynolds, Matthew W; Sander, Stephen D; Samsa, Gregory P; Matchar, David BBackground and purpose
in controlled trials, anticoagulation with warfarin reduces stroke risk by nearly two thirds, but the benefit has been less pronounced in clinical practice. This report describes the extent of warfarin use, its effectiveness, and its impact on medical costs among Medicare patients with nonvalvular atrial fibrillation.Methods
using claims from >2 million beneficiaries in the Centers for Medicare and Medicaid Services 5% Sample Standard Analytic Files, we identified patients with nonvalvular atrial fibrillation from 2004 to 2005. Warfarin use was inferred from 3 or more tests of the international normalized ratio within 1 year. Incidence of ischemic/hemorrhagic stroke and major bleeding was evaluated. Adjusted risk was calculated by Cox proportional-hazards regression. Medical costs (reimbursed amounts in 2006 US dollars) were estimated by multivariate linear regression.Results
of patients with nonvalvular atrial fibrillation (N=119 764, mean age=79.3 years), 58.5% were categorized as warfarin users based on the study definition. During an average of 2.1 years' follow-up, the rate of ischemic stroke was 3.9 per 100 patient-years. After multivariate adjustment, ischemic stroke incidence was 27% lower in patients taking warfarin than in patients not taking warfarin (P<0.0001), with no increase in hemorrhagic stroke and a slightly elevated risk of a major bleed. Use of warfarin was independently associated with lower total medical costs, averaging $9836 per patient per year.Conclusions
these results indicate that 41.5% of Medicare patients with nonvalvular atrial fibrillation are not anticoagulated with warfarin. The incidence of stroke and overall medical costs were significantly lower in patients treated with warfarin.Item Open Access Effect of a Multifaceted Quality Improvement Intervention on Hospital Personnel Adherence to Performance Measures in Patients With Acute Ischemic Stroke in China: A Randomized Clinical Trial.(JAMA, 2018-07) Wang, Yilong; Li, Zixiao; Zhao, Xingquan; Wang, Chunjuan; Wang, Xianwei; Wang, David; Liang, Li; Liu, Liping; Wang, Chunxue; Li, Hao; Shen, Haipeng; Bettger, Janet; Pan, Yuesong; Jiang, Yong; Yang, Xiaomeng; Zhang, Changqing; Han, Xiujie; Meng, Xia; Yang, Xin; Kang, Hong; Yuan, Weiqiang; Fonarow, Gregg C; Peterson, Eric D; Schwamm, Lee H; Xian, Ying; Wang, Yongjun; GOLDEN BRIDGE—AIS InvestigatorsIn China and other parts of the world, hospital personnel adherence to evidence-based stroke care is limited.To determine whether a multifaceted quality improvement intervention can improve hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke (AIS) in China.A multicenter, cluster-randomized clinical trial among 40 public hospitals in China that enrolled 4800 patients hospitalized with AIS from August 10, 2014, through June 20, 2015, with 12-month follow-up through July 30, 2016.Twenty hospitals received a multifaceted quality improvement intervention (intervention group; 2400 patients), including a clinical pathway, care protocols, quality coordinator oversight, and performance measure monitoring and feedback. Twenty hospitals participated in the stroke registry with usual care (control group; 2400 patients).The primary outcome was hospital personnel adherence to 9 AIS performance measures, with co-primary outcomes of a composite of percentage of performance measures adhered to, and as all-or-none. Secondary outcomes included in-hospital mortality and long-term outcomes (a new vascular event, disability [modified Rankin Scale score, 3-5], and all-cause mortality) at 3, 6, and 12 months.Among 4800 patients with AIS enrolled from 40 hospitals and randomized (mean age, 65 years; women, 1757 [36.6%]), 3980 patients (82.9%) completed the 12-month follow-up of the trial. Patients in intervention group were more likely to receive performance measures than those in the control groups (composite measure, 88.2% vs 84.8%, respectively; absolute difference, 3.54% [95% CI, 0.68% to 6.40%], P = .02). The all-or-none measure did not significantly differ between the intervention and control groups (53.8% vs 47.8%, respectively; absolute difference, 6.69% [95% CI, -0.41% to 13.79%], P = .06). New clinical vascular events were significantly reduced in the intervention group compared with the control group at 3 months (3.9% vs 5.3%, respectively; difference, -2.03% [95% CI, -3.51% to -0.55%]; P = .007), 6 months (6.3% vs 7.8%, respectively; difference, -2.18% [95% CI, -4.0% to -0.35%]; P = .02) and 12 months (9.1% vs 11.8%, respectively; difference, -3.13% [95% CI, -5.28% to -0.97%]; P = .005).Among 40 hospitals in China, a multifaceted quality improvement intervention compared with usual care resulted in a statistically significant but small improvement in hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke when assessed as a composite measure, but not as an all-or-none measure. Further research is needed to understand the generalizability of these findings.ClinicalTrials.gov Identifier: NCT02212912.Item Open Access Emergency medical services use and its association with acute ischaemic stroke evaluation and treatment in Singapore.(Stroke and vascular neurology, 2020-06) Xu, Hanzhang; Xian, Ying; Woon, Fung Peng; Bettger, Janet Prvu; Laskowitz, Daniel T; Ng, Yih Yng; Ong, Marcus Eng Hock; Matchar, David Bruce; De Silva, Deidre AnneBackground
Emergency medical services (EMS) is a critical link in the chain of stroke survival. We aimed to assess EMS use for stroke in Singapore, identify characteristics associated with EMS use and the association of EMS use with stroke evaluation and treatment.Methods
The Singapore Stroke Registry combines nationwide EMS and public hospital data for stroke cases in Singapore. Multivariate regressions with the generalised estimating equations were performed to examine the association between EMS use and timely stroke evaluation and treatment.Results
Of 3555 acute ischaemic patients with symptom onset within 24 hours admitted to all five public hospitals between 2015 and 2016, 68% arrived via EMS. Patients who used EMS were older, were less likely to be female, had higher stroke severity by National Institute of Health Stroke Scale and had a higher prevalence of atrial fibrillation or peripheral arterial disease. Patients transported by EMS were more likely to receive rapid evaluation (door-to-imaging time ≤25 min 34.3% vs 11.1%, OR=2.74 (95% CI 1.40 to 5.38)) and were more likely to receive intravenous tissue plasminogen activator (tPA, 22.8% vs 4.6%, OR=4.61 (95% CI 3.52 to 6.03)). Among patients treated with tPA, patients who arrived via EMS were more likely to receive timely treatment than self-transported patients (door-to-needle time ≤60 min 52.6% vs 29.4%, OR=2.58 (95% CI 1.35 to 4.92)).Conclusions
EMS use is associated with timely stroke evaluation and treatment in Singapore. Seamless EMS-Hospital stroke pathways and targeted public campaigns to advocate for appropriate EMS use have the potential to improve acute stroke care.Item Open Access Haemiballism/haemichorea: an atypical presentation of ischaemic stroke.(BMJ case reports, 2021-06) Nohria, Raman; Bennett, Stacey; O'Keefe, Yasmin AliA 76-year-old man was admitted to the hospital with acute onset of involuntary movements of the left side of his body. His neurological examination revealed he was oriented only to himself, and aforementioned movements of his left arm and leg. CT head demonstrated old infarcts in his right aspect of his pons and basal ganglia. Cerebrospinal fluid analysis was unremarkable. He initially had a normal blood glucose with an elevated anion gap and elevated creatine kinase. Brain MRI showed a small lacunar-type ischaemic infarct within the anteromedial aspect of the right cerebral peduncle, which localised to his haemiballism. To prevent worsening rhabdomyolysis associated with his haemiballism, the primary team initiated both tetrabenazine and diazepam. His movements improved after 1 week of medication therapy. This report discusses a thorough workup for this movement disorder and when to intervene for this distressing condition.Item Open Access International Comparison of Patient Characteristics and Quality of Care for Ischemic Stroke: Analysis of the China National Stroke Registry and the American Heart Association Get With The Guidelines--Stroke Program.(Journal of the American Heart Association, 2018-10) Wangqin, Runqi; Laskowitz, Daniel T; Wang, Yongjun; Li, Zixiao; Wang, Yilong; Liu, Liping; Liang, Li; Matsouaka, Roland A; Saver, Jeffrey L; Fonarow, Gregg C; Bhatt, Deepak L; Smith, Eric E; Schwamm, Lee H; Prvu Bettger, Janet; Hernandez, Adrian F; Peterson, Eric D; Xian, YingBackground Adherence to evidence-based guidelines is an important quality indicator; yet, there is lack of assessment of adherence to performance measures in acute ischemic stroke for most world regions. Methods and Results We analyzed 19 604 patients with acute ischemic stroke in the China National Stroke Registry and 194 876 patients in the Get With The Guidelines--Stroke registry in the United States from June 2012 to January 2013. Compared with their US counterparts, Chinese patients were younger, had a lower prevalence of comorbidities, and had similar median, lower mean, and less variability in National Institutes of Health Stroke Scale (median 4 [25th percentile-75th percentile, 2-7], mean 5.4±5.6 versus median 4 [1-10], mean 6.8±7.7). Chinese patients were more likely to experience delays from last known well to hospital arrival (median 1318 [330-3209] versus 644 [142-2055] minutes), less likely to receive thrombolytic therapy (2.5% versus 8.1%), and more likely to experience treatment delays (door-to-needle time median 95 [72-112] versus 62 [49-85] minutes). Adherence to early and discharge antithrombotics, smoking cessation counseling, and dysphagia screening were relatively high (eg >80%) in both countries. Large gaps existed between China and the United States with regard to the administration of thrombolytics within 3 hours (18.3% versus 83.6%), door-to-needle time ≤60 minutes (14.6% versus 48.0%), deep venous thrombosis prophylaxis (65.0% versus 97.8%), anticoagulation for atrial fibrillation (21.0% versus 94.4%), lipid treatment (66.3% versus 95.8%), and rehabilitation assessment (58.8% versus 97.4%). Conclusions We found significant differences in clinical characteristics and gaps in adherence for certain performance measures between China and the United States. Additional efforts are needed for continued improvements in acute stroke care and secondary prevention in both nations, especially China.Item Open Access Lack of evidence for a remote effect of renal ischemia/reperfusion acute kidney injury on outcome from temporary focal cerebral ischemia in the rat.(Journal of cardiothoracic and vascular anesthesia, 2013-02) Yates, RB; Sheng, H; Sakai, H; Kleven, DT; Desimone, NA; Stafford Smith, M; Warner, DSObjective
Acute kidney injury (AKI) and ischemic stroke may occur in the same cardiac surgical patient. It is not known if an interaction exists between these organ injuries. Isolated renal ischemia/reperfusion is associated with dysfunction in remote, otherwise normal organs, including the brain. In a rat model of simultaneous bilateral renal artery occlusion (BRAO) and middle cerebral artery occlusion (MCAO), the authors tested the hypothesis that AKI would worsen experimental stroke outcome.Design
Sixty thermoregulated anesthetized rats were randomized to (1) 40-minute BRAO, (2) 80-minute MCAO, or (3) simultaneous BRAO + MCAO. Serum creatinine was measured at baseline and 2 and 7 days after organ reperfusion. Neurologic function and brain and kidney histologies were measured on day 7. In a parallel study, serum cytokines were measured over 16 hours.Setting
Laboratory.Participants
Male Wistar rats.Interventions
Combined or isolated BRAO and MCAO.Measurements and main results
AKI was similar between the BRAO and BRAO + MCAO groups, with greater 48-hour creatinine increases (p < 0.02) and renal histopathologic scores (p < 0.001) in these groups than with MCAO alone. Neurologic scores correlated with cerebral infarct size (p = 0.0001). There were no differences in neurologic score (p = 0.53) and cerebral infarct volume (p = 0.21) between the MCAO and BRAO + MCAO groups. There was no association between cerebral infarct size or neurologic score and 48-hour creatinine increase. Interleukin-6 was increased during reperfusion (p < 0.0001), but a difference among groups was absent (p = 0.41).Conclusions
In contrast to the effects reported for AKI on normal remote organs, AKI had no influence on infarct size or neurologic function after experimental ischemic cerebral stroke.