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  • 1
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. Suppl_1 ( 2022-03)
    Kurzfassung: Background: Conflicting data exists surrounding whether or not the effect of clopidogrel on risk reduction of cardiovascular outcomes, including stroke, is more pronounced in smokers. The aim of this study was to determine the effect of smoking status on subsequent stroke risk in all patients with minor ischemic stroke or TIA, as well as subgroups that may be particularly impacted by an effect, and determine whether smoking improves the effect of clopidogrel treatment on subsequent stroke risk reduction. Subgroup analysis included those of older age, black race, and female gender, as these groups may have higher risk of clopidogrel non-response and subsequently poor outcomes. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. The POINT trial compared clopidogrel plus aspirin (DAPT) to aspirin alone for prevention of recurrent stroke, myocardial infarction, or vascular death within 3 months of a high-risk TIA or minor ischemic stroke. We used multivariable cox-regression models to determine the effect of smoking on the efficacy of DAPT in reducing the risk of subsequent ischemic stroke in all patients and prespecified subgroups stratified based on age, sex, race, and diabetes. We also performed interaction analyses to determine whether the effect of clopidogrel on subsequent ischemic stroke differed with respect to smoking status. Results: Data from 4,877 participants enrolled in the POINT trial were analyzed. Among these, 1,004 were current smokers and 3,873 were non-smokers. Smoking was associated with a non-significantly increased risk of recurrent ischemic stroke during follow up (hazard ratio, 1.31 [95% CI, 0.97 - 1.78], P=0.076). The effect of clopidogrel on ischemic stroke was not significantly different in non-smokers (hazard ratio, 0.74 [95% CI, 0.56 - 0.98] , P=0.03) compared to smokers (adjusted hazard ratio, 0.63 [95% CI, 0.37 - 1.05], P=0.078), P for interaction = 0.572. In addition, the effect of clopidogrel on major hemorrhage was not significantly different in current smokers (hazard ratio, 2.59 [95% CI, 1.08 - 6.21] , P=0.032) compared to non-smokers (hazard ratio, 1.67 [95% CI, 0.40 - 7.00], P=0.481), P for interaction = 0.613. This finding was maintained across different subgroups: males, females, blacks, whites, those with and without diabetes, and those aged 〈 60 and ≥ 60 years. Conclusions: Cigarette smoking was associated with a non-significantly higher risk of subsequent ischemic stroke and smoking did not modify the effect of clopidogrel-based dual antiplatelet therapy on subsequent ischemic stroke risk reduction, even in the subgroups of stratified based on age, sex, race, and diabetes, where greater likelihood of effect was theorized. Every effort should be made to encourage tobacco dependence treatment and cessation in patients with minor ischemic stroke and TIA.
    Materialart: Online-Ressource
    ISSN: 0009-7322 , 1524-4539
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    ZDB Id: 1466401-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Kurzfassung: Background: Recent data suggest that in patients with acute myocardial infarction (MI), the effect of clopidogrel on risk reduction of cardiovascular outcomes is more pronounced in smokers. The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and determine whether smoking improves the effect of clopidogrel treatment on subsequent stroke risk reduction. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. The POINT trial compared clopidogrel plus aspirin (DAPT) to aspirin alone for prevention of recurrent stroke, myocardial infarction, or vascular death within 3 months of a high-risk TIA or minor ischemic stroke. We used multivariable cox-regression models to determine the effect of smoking on the risk of subsequent ischemic stroke. We also performed interaction analyses to determine whether the effect of clopidogrel on subsequent ischemic stroke differed with respect to smoking status. Results: Data from 4,877 participants enrolled in the POINT trial were analyzed. Among these, 1,004 were current smokers and 3,873 were non-smokers. Smoking was associated with a non-significantly increased risk of recurrent ischemic stroke during follow up (hazard ratio, 1.31 [95% CI, 0.97 - 1.78], P=0.076). The effect of clopidogrel on ischemic stroke was not significantly different in non-smokers (hazard ratio, 0.74 [95% CI, 0.56 - 0.98] , P=0.03) compared to smokers (adjusted hazard ratio, 0.63 [95% CI, 0.37 - 1.05], P=0.078), P for interaction = 0.572. In addition, the effect of clopidogrel on major hemorrhage was not significantly different in current smokers (hazard ratio, 2.59 [95% CI, 1.08 - 6.21] , P=0.032) compared to non-smokers (hazard ratio, 1.67 [95% CI, 0.40 - 7.00], P=0.481), P for interaction = 0.613. Conclusions: Cigarette smoking was associated with a non-significantly higher risk of subsequent ischemic stroke and smoking did not modify the effect of clopidogrel-based dual antiplatelet therapy on subsequent ischemic stroke risk reduction. Every effort should be made to encourage tobacco dependence treatment and cessation in patients with minor ischemic stroke and TIA.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Kurzfassung: Background: Prognostication following cerebral venous thrombosis (CVT) remains challenging. Mortality is an uncommon yet catastrophic outcome after CVT. We sought to externally validate the SI 2 NCAL 2 C score for mortality in an international cohort. Methods: The SI 2 NCAL 2 C score was developed from the International CVT Consortium Registry to predict mortality by 30 days and one year using the factors: female- s ex-specific risk factors, i ntracerebral hemorrhage, CNS i nfection, n eurological focal deficits, c oma, a ge, hemoglobin l evel, glucose l evel, and c ancer. ACTION-CVT was an international retrospective study that enrolled consecutive patients with CVT across 27 centers. Model performance was evaluated using the area under the curve (AUC) of the time-dependent receiver operating characteristic curve and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. Results: After exclusion of one site which contributed data to the derivation cohort, 950 of 1,025 patients enrolled in ACTION-CVT were analyzed. Compared to the derivation cohort, the ACTION-CVT cohort was older (median 44 vs 40 years), less female (63.4% vs 69.8%), and with milder clinical presentation (focal deficits 38.6% vs 57.1%; seizures 22.6% vs 36.7%). Mortality was 2.5% by 30 days and 6.0% by one year. The SI 2 NCAL 2 C score achieved an AUC of 0.716 [95% CI 0.603-0.823] for mortality by 30 days and 0.820 [0.761-0.878] for mortality by one year. Calibration plots demonstrated an overestimation of predicted risk among patients with low observed mortality, concordant with score derivation (Fig 1, A-D). Conclusions: The SI 2 NCAL 2 C score had acceptable performance in an international validation cohort despite differences in baseline characteristics between cohorts. The SI 2 NCAL 2 C score warrants additional validation studies in diverse populations and clinical implementation studies.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2024
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Kurzfassung: Introduction: Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, though it is unclear whether this reduction occurs due to blood pressure control or antihypertensive class-specific pleotropic effects. The goal of this study was to investigate the influence of antihypertensive medication class on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. Methods: Using the SPRINT-MIND dataset, we completed a post-hoc analysis of participants who completed a baseline and 4-year follow-up brain MRI with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the MRIs. A percentage of follow-up time participants were prescribed each of the eleven classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between two scans and, to address skew, dichotomized into a top tertile (greatest) accumulation and combined middle and bottom tertiles (slowest) accumulation. Results: Among 448 individuals included in this study, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 years versus 65.7±7.3 years, p 〈 0.001) and systolic blood pressure (128.3±11.0 mmHg versus 126.2±9.4 mmHg, p=0.039). The high had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL for the slowest progressors (p 〈 0.001). Only angiotensin converting enzyme inhibitors (ACE-I) (OR 0.34, 95% CI 0.15-0.75, p=0.008) and dihydropyridine calcium channel blockers (d-CCB) (OR 0.39, 95% CI 0.19-0.81, p=0.012) were independently associated with lower odds of being in the greatest progression grouping. Conclusions: Amongst hypertensive participants in the SPRINT-MIND trial, ACE-I and d-CCB antihypertensive medications were associated with significantly lower odds of being in the highest tertile of WMH progression compared with other antihypertensive classes, independent of blood pressure control.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Kurzfassung: Background: Prior research has shown that increased blood pressure variability (BPV) after ischemic stroke is associated with lower odds of good functional outcome, but the number, intervals between, and epochs of blood pressure measurements have not been standardized. Methods: We include patients enrolled in the FAST-MAG trial with a final diagnosis of ischemic stroke, premorbid modified Rankin Scale (mRS) of 0, 4 “early” blood pressure measurements (prehospital and 3 in the hour after arrival), and 9 “later” measurements (q4 hours from hours 4-24 and q8 hours from hours 24-48). The primary outcome was 90-day mRS of 0-1 (good outcome). The BPV exposure was the top tertile (highest level) of systolic standard deviation (SD). We fit logistic regression models adjusted for patient age, race, sex, baseline NIH Stroke Scale, tPA, endovascular therapy, mean systolic blood pressure, smoking, atrial fibrillation, hypertension, and diabetes. Results: We included 455 patients, with a mean age of 70.8 years, 46.8% female, 50.8% had tPA, 6.4% had endovascular therapy, the median baseline NIH Stroke Scale was 12 (5-19) and good outcome occurred in 152/455 (33.4%). The mean early SD was not significantly lower in patients with good outcome (p=0.12), but later SD was lower in patients with good outcome (13.5±5.6 vs. 15.1±5.6, p 〈 0.01). The adjusted odds ratio for good outcome in the top tertile of early BPV was 1.09 (95% CI 0.63-1.89), while for the top tertile of later BPV it was 0.54 (95% CI 0.30-0.95). The predicted probability of good outcome for a range of later BPV values is seen in Figure 1. Conclusion: Increased BPV in the hours after ischemic stroke onset was not associated with 90-day good outcome, but increased BPV during hours 4-48 after hospital arrival had a significant association with lower odds of good outcome. While these results are hypothesis-generating, the rigor of outcome adjudication and standardization of blood pressure measurements strengthens the findings.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Kurzfassung: Introduction: Midlife hypertension is associated with an increased later-life ischemic stroke risk. However, temporal trends of blood pressure have not been fully explored. Methods: We performed a post hoc analysis of the ARIC study and included participants with four systolic blood pressures (SBP) at Visits 1-4 (1987-1999). Patients who had an ischemic stroke, died, or were lost to follow-up before 1999 were excluded from the analysis. We used group-based trajectory modeling to define six distinct SBP trajectories during Visits 1-4 (Figure 1). We report unadjusted and adjusted hazard ratios from Cox models fit to the primary outcome of ischemic stroke during follow-up from 1999-2017. We confirmed the proportional hazards assumptions of our models. Results: We included 9,689 participants, of which 758 (7.8%) had an ischemic stroke during follow-up. The mean±SD age at Visit 1 was 54±6 years and at Visit 4 was 63±6 years. The adjusted Cox models, Table 1, show the highest risk of ischemic stroke with increasing hypertension or stable severe hypertension. Comparing trajectories with similar baseline hypertension confirmed that increasing hypertension and stable severe hypertension had a higher risk than decreasing trajectories with the same starting point. Conclusion: Midlife blood pressure trajectory is associated with later-life ischemic stroke risk. Patients with hypertension who achieved a midlife reduction in systolic blood pressure were less likely to have a later-life stroke than those who did not.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. Suppl_1 ( 2021-03)
    Kurzfassung: Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p 〈 0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size ( 〈 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2021
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. Suppl_1 ( 2020-02)
    Kurzfassung: Background: Increased blood pressure variability (BPV) has been associated with stroke risk, but never specifically in patients with diabetes. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the long term follow-up extension of ACCORD. Visit-to-visit BPV was analyzed using all BP readings during the first 36 months. The primary outcome was incident ischemic or hemorrhagic stroke after 36 months. Differences in mean BPV was tested with Student’s t-test. We fit Cox proportional hazards models to estimate the adjusted risk of stroke across lowest vs. highest quintile of BPV and report hazard ratios along with 95% confidence intervals (CI). Results: Our analysis included 9,241 patients, with a mean (SD) age of 62.7 (6.6) years and 61.7% were male. Mean (SD) follow-up was 5.7 (2.4) years and number of BP readings per patient was 12.0 (4.3). Systolic, but not diastolic, BPV was higher in patients who developed stroke (Table 1). The highest quintile of SBP SD was associated with increased risk of incident stroke, independent of mean blood pressure or other potential confounders. (Table 2, Figure 1). There was no interaction between SBP SD and treatment arm assignment, although the interaction for glucose approached significance (Table 2). Conclusion: Higher systolic BPV was associated with incident stroke in a large cohort of diabetic patients. Future trials of stroke prevention may benefit from interventions targeting BPV reduction.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2020
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. Suppl_1 ( 2021-03)
    Kurzfassung: Background: The combination of aspirin and clopidogrel for 90 days after minor stroke or transient ischemic attack (TIA) reduced the risk of recurrent stroke in the POINT trial. The risk reduction was greater in patients with infarct on CT or MRI compared to those without infarct. Objective: To investigate the effect of DAPT on minor stroke and TIA in the POINT trial based on (1) the presence or absence of infarct attributed to the index event (“index infarct”) and (2) whether the index event was classified as stroke or TIA. Design/Methods: Patients were divided into two groups based on whether they had an “index infarct” or not. Baseline demographics and clinical variables were compared between groups using standard statistical tests. We used univariate and multivariable cox-regression models to determine associations between presence of infarct on imaging and primary and secondary outcomes, and interaction analyses to determine whether the presence of “index infarct” modifies the effect of DAPT on study outcomes. We also explored whether the association of “index-infarct” with primary and secondary outcomes varied by index diagnosis (TIA vs. minor stroke). Results: Amongst 4881 enrolled in POINT, 4876 patients had data on whether there was an “index-infarct”; 1793 (36.8%) had “index-infarct”. In adjusted cox-regression analyses, the presence of “index infarct” was associated with the primary efficacy outcome (HR 3.02 95% CI 2.34-3.89, p 〈 0.01) and subsequent ischemic stroke (HR 3.10 95% CI 2.39-4.02, p 〈 0.01). The effect of DAPT vs. aspirin on primary efficacy outcome was more pronounced in patients with “index infarct” (HR 0.58 95% CI 0.43-0.79, p 〈 0.01) vs. those without (HR 1.16 95% CI 0.79-1.71, p=0.44) (p for interaction = 0.01). In a secondary analysis based on final diagnosis, the effect of “index infarct” on primary outcome was only significant in those with minor stroke at the time of randomization (p for interaction=0.01) but not TIA at the time of randomization (p for interaction=0.36). Conclusions: In the POINT trial, efficacy of DAPT was greater in patients with infarct on imaging attributed to the index event. Future work should focus on determining clinical factors associated with this group to help identify patients most likely to benefit from acute DAPT.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2021
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Kurzfassung: Background: Patients with symptomatic intracranial stenosis (ICAS) face elevated risks of recurrent cerebrovascular events (RCE) despite optimal medical therapy. Borderzone infarcts (BZI) indirectly correlate with impaired distal perfusion, a known mechanism of recurrence. Studies assessing associations between borderzone infarcts and recurrence rates are observational and have relatively small sample size. We therefore performed a meta-analysis of published studies investigating this association. Methods: We performed a Medline and Web of Science search using the key words (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Borderzone OR Infarct Pattern) to identify studies reporting associations between index infarct pattern and RCE, defined as recurrent ischemic stroke or neurological deterioration, or new infarct on follow up neuroimaging in patients with symptomatic ICAS. We included relevant papers and scientific abstracts with more than 20 patients included. For all outcome events we calculated the corresponding risk ratios (RRs) and 95% confidence intervals (95% CI). Results: We identified 178 studies using Web of Science and 384 studies using Medline with only 6 studies (591 patients) meeting our inclusion criteria (2 prospective and 4 retrospective). The weighted proportion of patients with BZI was 32.5% (28.7%-36.4%). During a follow-up period of 7-950 days, 33.1% (26.3%-40.5%) of patients with BZI had RCE and 63.6% (30.8%-89.1%) had new infarction on a 6-8 week follow up brain MRI. In meta-analysis, BZI was associated with increased rates of RCE (RR 2.40 95% CI 1.71-3.37) and new infarct(s) on follow up brain MRI (RR 2.55 95% CI 1.31-4.94). The findings were unchanged when the analysis was limited to 90-day RCE risks only (RR 2.22 95% 1.49-3.29). Conclusions: BZI are associated with over 2-fold increased risk of RCE and recurrent infarct in patients with symptomatic ICAS. Prospective studies are needed to validate these findings.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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