Browsing by Subject "ischemic stroke"

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    A Neuroprotective Locus Modulates Ischemic Stroke Infarction Independent of Collateral Vessel Anatomy.
    (Frontiers in neuroscience, 2021-01) Lee, Han Kyu; Wetzel-Strong, Sarah E; Aylor, David L; Marchuk, Douglas A
    Although studies with inbred strains of mice have shown that infarct size is largely determined by the extent of collateral vessel connections between arteries in the brain that enable reperfusion of the ischemic territory, we have identified strain pairs that do not vary in this vascular phenotype, but which nonetheless exhibit large differences in infarct size. In this study we performed quantitative trait locus (QTL) mapping in mice from an intercross between two such strains, WSB/EiJ (WSB) and C57BL/6J (B6). This QTL mapping revealed only one neuroprotective locus on Chromosome 8 (Chr 8) that co-localizes with a neuroprotective locus we mapped previously from F2 progeny between C3H/HeJ (C3H) and B6. The allele-specific phenotypic effect on infarct volume at the genetic region identified by these two independent mappings was in the opposite direction of the parental strain phenotype; namely, the B6 allele conferred increased susceptibility to ischemic infarction. Through two reciprocal congenic mouse lines with either the C3H or B6 background at the Chr 8 locus, we verified the neuroprotective effects of this genetic region that modulates infarct volume without any effect on the collateral vasculature. Additionally, we surveyed non-synonymous coding SNPs and performed RNA-sequencing analysis to identify potential candidate genes within the genetic interval. Through these approaches, we suggest new genes for future mechanistic studies of infarction following ischemic stroke, which may represent novel gene/protein targets for therapeutic development.
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    Hospital Factors Associated With Interhospital Transfer Destination for Stroke in the Northeast United States.
    (Journal of the American Heart Association, 2020-01) Zachrison, Kori S; Onnela, Jukka-Pekka; Reeves, Mathew J; Hernandez, Adrian; Camargo, Carlos A; Zhao, Xin; Matsouaka, Roland A; Goldstein, Joshua N; Metlay, Joshua P; Schwamm, Lee H
    Background We aimed to determine if there is an association between hospital quality and the likelihood of a given hospital being a preferred transfer destination for stroke patients. Methods and Results Data from Medicare claims identified acute ischemic stroke transferred between 394 northeast US hospitals from 2007 to 2011. Hospitals were categorized as transferring (n=136), retaining (n=241), or receiving (n=17) hospitals based on the proportion of acute ischemic stroke encounters transferred or received. We identified all 6409 potential dyads of sending and receiving hospitals, and categorized dyads as connected if ≥5 patients were transferred between the hospitals annually (n=82). We used logistic regression to identify hospital characteristics associated with establishing a connected dyad, exploring the effect of adjusting for different quality measures and outcomes. We also adjusted for driving distance between hospitals, receiving hospital stroke volume, and the number of hospitals in the receiving hospital referral region. The odds of establishing a transfer connection increased when rate of alteplase administration increased at the receiving hospital or decreased at the sending hospital, however this finding did not hold after applying a potential strategy to adjust for clustering. Receiving hospital performance on 90-day home time was not associated with likelihood of transfer connection. Conclusions Among northeast US hospitals, we found that differences in hospital quality, specifically higher levels of alteplase administration, may be associated with increased likelihood of being a transfer destination. Further research is needed to better understand acute ischemic stroke transfer patterns to optimize stroke transfer systems.
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    Patterns of care quality and prognosis among hospitalized ischemic stroke patients with chronic kidney disease.
    (J Am Heart Assoc, 2014-06-05) Ovbiagele, Bruce; Schwamm, Lee H; Smith, Eric E; Grau-Sepulveda, Maria V; Saver, Jeffrey L; Bhatt, Deepak L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C
    BACKGROUND: Relatively little is known about the quality of care and outcomes for hospitalized ischemic stroke patients with chronic kidney disease (CKD). We examined quality of care and in-hospital prognoses among patients with CKD in the Get With The Guidelines-Stroke (GWTG-Stroke) program METHODS AND RESULTS: We analyzed 679 827 patients hospitalized with ischemic stroke from 1564 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. Use of 7 predefined ischemic stroke performance measures, composite "defect-free" care compliance, and in-hospital mortality were examined based on glomerular filtration rate (GFR) categorized as a dichotomous (+CKD as <60) or rank-ordered variable: normal (≥ 90), mild (≥ 60 to <90), moderate (≥ 30 to <60), severe (≥ 15 to <30), and kidney failure (<15 or dialysis). There were 236 662 (35%) ischemic stroke patients with CKD. Patients with severe renal dysfunction or failure were significantly less likely to receive guideline-based therapies. Compared with patients with normal kidney function (≥ 90), those with CKD (adjusted OR 0.91 [95% CI: 0.89 to 0.92]), moderate dysfunction (adjusted OR 0.94 [95% CI: 0.92 to 0.97]), severe dysfunction (adjusted OR 0.80 [95% CI: 0.77 to 0.84]), or failure (adjusted OR 0.72 [95% CI: 0.68 to 0.0.76]), were less likely to receive 100% defect-free care measure compliance. Inpatient mortality was higher for patients with CKD (adjusted odds ratio 1.44 [95% CI: 1.40 to 1.47]), and progressively rose with more severe renal dysfunction. CONCLUSIONS: Despite higher in-hospital mortality rates, ischemic stroke patients with CKD, especially those with greater severity of renal dysfunction, were less likely to receive important guideline-recommended therapies.
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    Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs.
    (Frontiers in neurology, 2020-01) Naidech, Andrew M; Lawlor, Patrick N; Xu, Haolin; Fonarow, Gregg C; Xian, Ying; Smith, Eric E; Schwamm, Lee; Matsouaka, Roland; Prabhakaran, Shyam; Marinescu, Ioana; Kording, Konrad P
    Randomized Controlled Trials (RCTs) are considered the gold standard for measuring the efficacy of medical interventions. However, RCTs are expensive, and use a limited population. Techniques to estimate the effects of stroke interventions from observational data that minimize confounding would be useful. We used regression discontinuity design (RDD), a technique well-established in economics, on the Get With The Guidelines-Stroke (GWTG-Stroke) data set. RDD, based on regression, measures the occurrence of a discontinuity in an outcome (e.g., odds of home discharge) as a function of an intervention (e.g., alteplase) that becomes significantly more likely when crossing the threshold of a continuous variable that determines that intervention (e.g., time from symptom onset, since alteplase is only given if symptom onset is less than e.g., 3 h). The technique assumes that patients near either side of a threshold (e.g., 2.99 and 3.01 h from symptom onset) are indistinguishable other than the use of the treatment. We compared outcomes of patients whose estimated onset to treatment time fell on either side of the treatment threshold for three cohorts of patients in the GWTG-Stroke data set. This data set spanned three different treatment thresholds for alteplase (3 h, 2003-2007, N = 1,869; 3 h, 2009-2016, N = 13,086, and 4.5 h, 2009-2016, N = 6,550). Patient demographic characteristics were overall similar across the treatment thresholds. We did not find evidence of a discontinuity in clinical outcome at any treatment threshold attributable to alteplase. Potential reasons for failing to find an effect include violation of some RDD assumptions in clinical care, large sample sizes required, or already-well-chosen treatment threshold.
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    Relationship of national institutes of health stroke scale to 30-day mortality in medicare beneficiaries with acute ischemic stroke.
    (J Am Heart Assoc, 2012-02) Fonarow, Gregg C; Saver, Jeffrey L; Smith, Eric E; Broderick, Joseph P; Kleindorfer, Dawn O; Sacco, Ralph L; Pan, Wenqin; Olson, Daiwai M; Hernandez, Adrian F; Peterson, Eric D; Schwamm, Lee H
    BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS), a well-validated tool for assessing initial stroke severity, has previously been shown to be associated with mortality in acute ischemic stroke. However, the relationship, optimal categorization, and risk discrimination with the NIHSS for predicting 30-day mortality among Medicare beneficiaries with acute ischemic stroke has not been well studied. METHODS AND RESULTS: We analyzed data from 33102 fee-for-service Medicare beneficiaries treated at 404 Get With The Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS documented. The 30-day mortality rate by NIHSS as a continuous variable and by risk-tree determined or prespecified categories were analyzed, with discrimination of risk quantified by the c-statistic. In this cohort, mean age was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There was a strong graded relation between increasing NIHSS score and higher 30-day mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to 42, 53.5%. A model with NIHSS alone provided excellent discrimination whether included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to 0.79]). CONCLUSIONS: The NIHSS provides substantial prognostic information regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic stroke. This index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information, whether used as a continuous or categorical risk determinant. (J Am Heart Assoc. 2012;1:42-50.).