Browsing by Author "Matsouaka, Roland"

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    A paradoxical relationship between hemoglobin A1C and in-hospital mortality in intracerebral hemorrhage patients.
    (Heliyon, 2019-05-06) Dandapat, Sudeepta; Siddiqui, Fazeel M; Fonarow, Gregg C; Bhatt, Deepak L; Xu, Haolin; Matsouaka, Roland; Heidenreich, Paul A; Xian, Ying; Schwamm, Lee H; Smith, Eric E
    Objectives:The relationship between prior glycemic status and outcomes in intracerebral hemorrhage (ICH) is not established. We hypothesized that higher hemoglobin (Hb) A1c is associated with worse outcomes in ICH. Patients and methods:Using the GWTG-Stroke registry, data on patients with ICH between April 1, 2003 and September 30, 2015 were harvested. Patients were divided into four ordinal groups based on HbA1c values of <5.7%, 5.7-6.4%, 6.5-8.0% and >8.0%. Outcomes (mortality, modified Rankin Scale (mRS), home discharge and independent ambulatory status) were analyzed for patients overall and separately for patients with or without history of diabetes using multivariable regression models. Results:Among 75,455 patients with ICH (with available HbA1c data), patients with lower HbA1c (<5.7%) had higher rates of in-hospital mortality in the entire cohort (15.5%; 3947/25473); as well as those with history of diabetes (19.0%; 542/2852). Among those without history of diabetes, both lower HbA1c (15.1%; 3405/22621) and higher HbA1c (>8.0%), (15.0%; 205/1364) were associated with higher in-hospital mortality. Lower HbA1c was also associated with higher mRS, less chance of going home, and lower likelihood of having independent ambulatory status in patients with prior history of diabetes. Conclusions:Among patients with no reported history of diabetes, both very low and very high HbA1c were directly associated with higher in-hospital mortality. Only very low HbA1c was associated with higher mortality in known diabetic patients. Further studies are needed to better define the relationship between HbA1c and outcomes, for it may have important implications for care of ICH patients.
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    Calcineurin activation causes retinal ganglion cell degeneration.
    (Mol Vis, 2012) Qu, Juan; Matsouaka, Roland; Betensky, Rebecca A; Hyman, Bradley T; Grosskreutz, Cynthia L
    PURPOSE: We previously reported that calcineurin, a Ca(2+)/calmodulin-dependent serine/threonine phosphatase, is activated and proposed that it participates in retinal ganglion cell (RGC) apoptosis in two rodent ocular hypertension models. In this study, we tested whether calcineurin activation by itself, even in the absence of ocular hypertension, is sufficient to cause RGC degeneration. METHODS: We compared RGC and optic nerve morphology after adeno-associated virus serotype 2 (AAV2)-mediated transduction of RGCs with constitutively active calcineurin (CaNCA) or unactivated, wild-type calcineurin (CaNwt). Retinas and optic nerves were harvested 7-16 weeks after injection of the AAV into mouse vitreous. In flatmounted retinas, the transduced RGCs were identified with immunohistochemistry. The morphology of the RGCs was revealed by immunostaining for neurofilament SMI32 or by using GFP-M transgenic mice. A modified Sholl analysis was applied to analyze the RGC dendritic morphology. Optic nerve damage was assessed with optic nerve grading according to the Morrison standard. RESULTS: CaNwt and CaNCA were highly expressed in the injected eyes. Compared to the CaNwt-expressing RGCs, the CaNCA-expressing RGCs had smaller somas, smaller dendritic field areas, shorter total dendrite lengths, and simpler dendritic branching patterns. At 16 weeks, the CaNCA-expressing eyes had greater optic nerve damage than the CaNwt-expressing eyes. CONCLUSIONS: Calcineurin activation is sufficient to cause RGC dendritic degeneration and optic nerve damage. These data support the hypothesis that calcineurin activation is an important mediator of RGC degeneration, and are consistent with the hypothesis that calcineurin activation may contribute to RGC neurodegeneration in glaucoma.
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    Initiation, Continuation, or Withdrawal of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers and Outcomes in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction.
    (J Am Heart Assoc, 2017-02-11) Gilstrap, Lauren G; Fonarow, Gregg C; Desai, Akshay S; Liang, Li; Matsouaka, Roland; DeVore, Adam D; Smith, Eric E; Heidenreich, Paul; Hernandez, Adrian F; Yancy, Clyde W; Bhatt, Deepak L
    BACKGROUND: Guidelines recommend continuation or initiation of guideline-directed medical therapy, including angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), in hospitalized patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: Using the Get With The Guidelines-Heart Failure Registry, we linked clinical data from 16 052 heart failure with reduced ejection fraction (ejection fraction ≤40%) patients with Medicare claims data. We divided ACEi/ARB-eligible patients into 4 categories based on admission and discharge ACEi/ARB use: continued (reference group), started, discontinued, or not started on therapy. A multivariable Cox proportional hazard model was used to determine the association between ACEi/ARB category and outcomes. Most, 90.5%, were discharged on ACEi/ARB (59.6% continued and 30.9% newly started). Of those discharged without ACEi/ARB, 1.9% were discontinued, and 7.5% were eligible but not started. Thirty-day mortality was 3.5% for patients continued and 4.1% for patients started on ACEi/ARB. In contrast, 30-day mortality was 8.8% for patients discontinued (adjusted hazard ratio [HRadj] 1.92; 95% CI 1.32-2.81; P<0.001) and 7.5% for patients not started (HRadj 1.50; 95% CI 1.12-2.00; P=0.006). The 30-day readmission rate was lowest among patients continued or started on therapy. One-year mortality was 28.2% for patients continued and 29.7% for patients started on ACEi/ARB compared to 41.6% for patients discontinued (HRadj 1.35; 95% CI 1.13-1.61; P<0.001) and 41.7% (HRadj 1.28; 95% CI 1.14-1.43; P<0.001) for patients not started on therapy. CONCLUSIONS: Compared with continuation, withdrawal of ACEi/ARB during heart failure hospitalization is associated with higher rates of postdischarge mortality and readmission, even after adjustment for severity of illness.
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    Outcomes After Endovascular Thrombectomy With or Without Alteplase in Routine Clinical Practice.
    (JAMA neurology, 2022-08) Smith, Eric E; Zerna, Charlotte; Solomon, Nicole; Matsouaka, Roland; Mac Grory, Brian; Saver, Jeffrey L; Hill, Michael D; Fonarow, Gregg C; Schwamm, Lee H; Messé, Steven R; Xian, Ying

    Importance

    The effectiveness and safety of intravenous alteplase given before or concurrently with endovascular thrombectomy (EVT) is uncertain. Randomized clinical trials suggest there is little difference in outcomes but with only modest precision and insufficient power to analyze uncommon outcomes including symptomatic intracranial hemorrhage (sICH).

    Objective

    To determine whether 8 prespecified outcomes are different in patients with acute ischemic stroke treated in routine clinical practice with EVT with alteplase compared with patients treated with EVT alone without alteplase. It was hypothesized that alteplase would be associated with higher risk of sICH.

    Design, setting, and participants

    This was an observational cohort study conducted from February 1, 2019, to June 30, 2020, that included adult patients with acute ischemic stroke treated with EVT within 6 hours of time last known well, after excluding patients without information on discharge destination and patients with in-hospital stroke. Participants were recruited from Get With The Guidelines-Stroke, a large nationwide registry of patients with acute ischemic stroke from 555 hospitals in the US.

    Exposures

    Intravenous alteplase or no alteplase.

    Main outcomes and measures

    Prespecified outcomes were discharge destination, independent ambulation at discharge, modified Rankin score at discharge, discharge mortality, cerebral reperfusion according to modified Thrombolysis in Cerebral Infarction grade, and sICH.

    Results

    There were 15 832 patients treated with EVT (median [IQR] age, 72.0 [61.0-82.0] years; 7932 women [50.1%]); 10 548 (66.7%) received alteplase and 5284 (33.4%) did not. Patients treated with alteplase were younger, arrived via Emergency Medical Services sooner, were less likely to have certain comorbidities, including atrial fibrillation, hypertension, and diabetes, but had similar National Institutes of Health Stroke Severity (NIHSS) scores. Compared with patients who did not receive alteplase treatment, patients treated with alteplase were less likely to die (11.1% [1173 of 10 548 patients] vs 13.9% [734 of 5284 patients]; adjusted odds ratio [aOR] 0.83; 95% CI, 0.77-0.89; P < .001), more likely to have no major disability based on modified Rankin scale of 2 or less at discharge (28.5% [2415 of 8490 patients] vs 20.7% [894 of 4322 patients]; aOR, 1.36; 95% CI, 1.28-1.45; P < .001), and to have better reperfusion based on modified Thrombolysis in Cerebral Infarction grade 2b or greater (90.9% [8474 of 9318 patients] vs 88.0% [4140 of 4705 patients]; aOR, 1.39; 95% CI, 1.28-1.50; P < .001). However, alteplase treatment was associated with higher risk of sICH (6.5% [685 of 10 530 patients] vs 5.3% [279 of 5249 patients]; OR, 1.28; 95% CI, 1.16-1.42; P < .001).

    Conclusions and relevance

    In this observational cohort study of patients treated with EVT, intravenous alteplase treatment was associated with better in-hospital survival and functional outcomes but higher sICH risk after adjusting for other covariates.
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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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    Quality of Care and Outcomes for Patients With Stroke in the United States Admitted During the International Stroke Conference.
    (Journal of the American Heart Association, 2018-11) Messé, Steven R; Mullen, Michael T; Cox, Margueritte; Fonarow, Gregg C; Smith, Eric E; Saver, Jeffrey L; Reeves, Mathew J; Bhatt, Deepak L; Matsouaka, Roland; Schwamm, Lee H
    Background Patients presenting to hospitals during non-weekday hours experience worse outcomes, often attributed to reduced staffing. The American Heart Association International Stroke Conference ( ISC ) is well attended by stroke clinicians. We sought to determine whether patients with acute ischemic stroke ( AIS ) admitted during the ISC receive less guideline-adherent care and experience worse outcomes. Methods and Results We performed a retrospective cohort study of US hospitals participating in Get With The Guidelines-Stroke and assessed use of intravenous tissue plasminogen activator, other quality measures, and outcomes for patients with AIS admitted during the ISC compared with those admitted the weeks before and after the conference. A total of 69 738 patients with AIS were included: mean age, 72 years; 52% women; 29% nonwhite. There was no difference between the average weekly number of AIS cases admitted during ISC weeks versus non- ISC weeks (1984 versus 1997; P=0.95). Patient and hospital characteristics were similar between ISC and non- ISC time periods. There were no significant differences in 14 quality metrics and 5 clinical outcomes between patients with AIS treated during the ISC versus non- ISC weeks. Patients with AIS who presented within 2 hours of onset had no difference in the likelihood of receiving intravenous tissue plasminogen activator within 3 hours (adjusted odds ratio, 0.89; 95% confidence interval, 0.77-1.03; P=0.13) or the likelihood of receiving intravenous tissue plasminogen activator within 60 minutes of arrival (adjusted odds ratio, 0.92; 95% confidence interval, 0.83-1.02; P=0.13). Conclusions Patients with acute stroke admitted to Get With The Guidelines-Stroke hospitals during ISC received the same quality care and had similar outcomes as patients admitted at other times.
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    Race-Ethnic Disparities in Rates of Declination of Thrombolysis for Stroke.
    (Neurology, 2022-04) Mendelson, Scott J; Zhang, Shuaiqi; Matsouaka, Roland; Xian, Ying; Shah, Shreyansh; Lytle, Barbara L; Solomon, Nicole; Schwamm, Lee H; Smith, Eric E; Saver, Jeffrey L; Fonarow, Gregg; Holl, Jane; Prabhakaran, Shyam

    Background and objectives

    Prior regional or single-center studies have noted that 4% to 7% of eligible patients with acute ischemic stroke (AIS) decline IV tissue plasminogen activator (tPA). We sought to determine the prevalence of tPA declination in a nationwide registry of patients with AIS and to investigate differences in declination by race/ethnicity.

    Methods

    We used the Get With The Guidelines-Stroke registry to identify patients with AIS eligible for tPA and admitted to participating hospitals between January 1, 2016, and March 28, 2019. We compared patient demographics and admitting hospital characteristics between tPA-eligible patients who received and those who declined tPA. Using multivariable logistic regression, we determined patient and hospital factors associated with tPA declination.

    Results

    Among 177,115 tPA-eligible patients with AIS at 1,976 sites, 6,545 patients (3.7%) had tPA declination as the sole documented reason for not receiving tPA. Patients declining treatment were slightly older, were more likely to be female, arrived more often at off-hours and earlier after symptom onset, and were more likely to present to Primary Stroke Centers. Compared with non-Hispanic White, non-Hispanic Black race/ethnicity was independently associated with increased (adjusted odds ratio [aOR] 1.21, 95% CI 1.11-1.31), Asian race/ethnicity with decreased (aOR 0.72, 95% CI 0.58-0.88), and Hispanic ethnicity (any race) with similar odds of tPA declination (OR 0.98, 95% CI 0.86-1.13) in multivariable analysis.

    Discussion

    Although the overall prevalence of tPA declination is low, eligible non-Hispanic Black patients are more likely and Asian patients less likely to decline tPA than non-Hispanic White patients. Reducing rates of tPA declinations among non-Hispanic Black patients may be an opportunity to address disparities in stroke care.
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    Thrombolysis in young adults with stroke: Findings from Get With The Guidelines-Stroke.
    (Neurology, 2019-06) Dodds, Jodi A; Xian, Ying; Sheng, Shubin; Fonarow, Gregg C; Bhatt, Deepak L; Matsouaka, Roland; Schwamm, Lee H; Peterson, Eric D; Smith, Eric E
    OBJECTIVE:To determine whether young adults (≤40 years old) with acute ischemic stroke are less likely to receive IV tissue plasminogen activator (tPA) and more likely to have longer times to brain imaging and treatment. METHODS:We analyzed data from the Get With The Guidelines-Stroke registry for patients with acute ischemic stroke hospitalized between January 2009 and September 2015. We used multivariable models with generalized estimating equations to evaluate tPA treatment and outcomes between younger (age 18-40 years) and older (age >40 years) patients with acute ischemic stroke. RESULTS:Of 1,320,965 patients with acute ischemic stroke admitted to 1,983 hospitals, 2.3% (30,448) were 18 to 40 years of age. Among these patients, 12.5% received tPA vs 8.8% of those >40 years of age (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.56-1.71). However, younger patients were less likely to receive brain imaging within 25 minutes (62.5% vs 71.5%, aOR 0.78, 95% CI 0.73-0.84) and to be treated with tPA within 60 minutes of hospital arrival (37.0% vs 42.8%, aOR 0.74, 95% CI 0.68-0.79). Compared to older patients, younger patients treated with tPA had a lower symptomatic intracranial hemorrhage rate (1.7% vs 4.5%, aOR 0.55, 95% CI 0.42-0.72) and lower in-hospital mortality (2.0% vs 4.3%, aOR 0.65, 95% CI 0.52-0.81). CONCLUSIONS:In contrast to our hypothesis, younger patients with acute ischemic stroke were more likely to be treated with tPA than older patients, but they were more likely to experience delay in evaluation and treatment. Compared with older patients, younger patients had better outcomes, including fewer intracranial hemorrhages.