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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 6 ( 2009-06), p. 2079-2084
    Abstract: Background and Purpose— To make informed treatment decisions, patients and physicians need to be aware of the benefits and risks of a proposed treatment. The number needed to treat (NNT) for benefit and harm are intuitive and statistically valid measures to describe a treatment effect. The aim of this study is to calculate treatment time-specific NNT estimates based on shifts over the entire spectrum of clinically relevant functional outcomes. Methods— The pooled data set of the first 6 major randomized acute stroke trials of intravenous tissue plasminogen activator was used for this study. The data were stratified by 90-minute treatment time windows. NNT for benefit and NNT for harm estimates were determined based on expert generation of joint outcome distribution tables. NNT for benefit estimates were also calculated based on joint outcome distribution tables generated by a computer model. Results— NNT for benefit estimates based on the expert panel were 3.6 for patients treated between 0 and 90 minutes, 4.3 with treatment between 91 and 180 minutes, 5.9 with treatment between 181 and 270 minutes, and 19.3 with treatment between 271 and 360 minutes. The computer simulation yielded very similar results. The NNT for harm estimates for the corresponding time intervals are 65, 38, 30, and 14. Conclusions— Up to 4½ hours after symptom onset, tissue plasminogen activator therapy is associated with more benefit than harm, whereas there is no evidence of a net benefit in the 4½- to 6-hour time window. The NNT estimates for each 90-minute epoch provide useful and intuitive information based on which patients may be able to make better informed treatment decisions.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 3 ( 2023-01-17), p. e336-e347
    Abstract: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) – Tmax 〉 10 seconds/Tmax 〉 6 seconds (good collaterals – HIR 〈 0.4, poor collaterals – HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. Results Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13–22] , non-GA: 16 [11–20], p 〈 0.001) and ischemic core volume (GA: 15.0 mL [3.2–38.0] vs non-GA: 9.0 mL [0.0–31.0] , p 〈 0.001). In addition, GA was associated with longer last known well to arterial access (203 minutes [157–267] vs 186 minutes [138–252] , p = 0.002), but similar procedural time (35.5 minutes [23–59] vs 34 minutes [22–54] , p = 0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the propensity score–matched pairs, GA was independently associated with worse functional outcomes (adjusted common odds ratio [adj. cOR]: 0.64, 95% CI: 0.44–0.93, p = 0.021) and higher neurologic worsening (GA: 14.9% vs non-GA: 8.9%, aOR: 2.10, 95% CI: 1.02–4.33, p = 0.045). Patients with poor collaterals had worse functional outcomes with GA (adj. cOR: 0.47, 95% CI: 0.29–0.76, p = 0.002), whereas no difference was observed in those with good collaterals (adj. cOR: 0.93, 95% CI: 0.50–1.74, p = 0.82), p interaction : 0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate ( p interaction : 0.020). Discussion GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score–matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. Classification of Evidence This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. Trial Registration Information EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587).
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 49, No. 4 ( 2018-04), p. 952-957
    Abstract: This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke. Methods— We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax 〉 10s lesion volume (target mismatch, 〈 100 mL; malignant mismatch, 〉 100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0–2) at day 90 and radiographic outcomes at day 5. Results— Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence ( P =0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P =0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49–166] versus 43 [18–81] mL; P =0.006) and larger final infarct volumes (110 [61–155] versus 48 [21–99] mL; P =0.001). Conclusions— Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: International Journal of Stroke, SAGE Publications, Vol. 17, No. 4 ( 2022-04), p. 389-399
    Abstract: The clinical efficacy of mechanical thrombectomy has been unequivocally demonstrated in multiple randomized clinical trials. However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. Aim We aimed to assess the clinical effectiveness of mechanical thrombectomy in a prospective registry. Methods A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label mechanical thrombectomy registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials according to the basic demographic and clinical criteria without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups. Results As compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of intravenous tissue plasminogen activator (IV-tPA) and general anesthesia were higher in DAWN- and DEFUSE-3 registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding randomized clinical trials (SWIFT-Prime, 64.5% vs. 60.2%; DAWN, 50.4% vs. 48.6%; Beyond-DAWN: 52.4% vs. 48.6%; DEFUSE 3, 52% vs. 44.6%, respectively; all P  〉  0.05). Registry-derived patients had significant less disability than the corresponding randomized clinical trial controls (ordinal modified Rankin Scale (mRS) shift odds ratio (OR), P  〈  0.05 for all). Conclusion Our study provides favorable generalizability data for the safety and efficacy of thrombectomy in the “real-world” setting and supports that patients may be safely treated outside the constraints of randomized clinical trials.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2211666-7
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. suppl_1 ( 2016-02)
    Abstract: Introduction: Intra-arterial therapy has become standard-of-care for stroke patients with large vessel occlusions presenting within 6 hours of symptom onset. Treatment effectiveness at later times is currently unknown. Using data from the CT Perfusion (CTP) to predict Response to recanalization in Ischemic Stroke Project (CRISP), we assessed the effect of time to treatment on the probability of good outcomes. Hypothesis: Symptom onset-to-reperfusion time is not associated with probability of favorable outcomes in patients with target mismatch who achieve reperfusion. Methods: All patients enrolled underwent baseline CTP. For this analysis, we included data from patients with target mismatch (ratio of Tmax 〉 6s lesion to core volume of 〉 1.8) who achieved endovascular reperfusion. We determined reperfusion status by early follow-up MRI or CTP, or final TICI score 2b-3 if early follow-up perfusion imaging is unavailable. We defined good functional outcome (GFO) as mRS 0-2 at day 90. We assessed the probability of good outcome as a function of onset-to-reperfusion time using logistic regression, with prespecified adjustment for age and baseline NIHSS. Results: Following intra-arterial intervention performed within 18 hours, 102 patients with target mismatch achieved reperfusion. Median onset-to-reperfusion time was 6.6 hours (IQR 5.2-9.5). In univariate analysis, onset-to-reperfusion time was not associated with GFO (p=0.19), whereas age and NIHSS were. Similarly, in multivariate analysis, age and NIHSS were associated with GFO, while onset-to-reperfusion time was not. The adjusted relative risk per hour of delay is 0.994 (95% CI 0.97-1.02). GFO was achieved in 71.4% of patients treated within 6 hours, and in 61.7% of patients treated after 6 hours. Conclusion: The lack of significant association between onset-to-reperfusion time and GFO, and the high proportion of patients achieving good outcomes at 6-18 hours, suggest that endovascular interventions may be beneficial beyond 6 hours with a CTP target mismatch profile, supporting randomized controlled trials of endovascular therapy in the extended time window in selected patients.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods: In a pooled patient level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II and SELECT, EVT Functional outcomes (mRS distribution) were compared between general anesthesia (GA) vs non-general anesthesia (non-GA). Further, we assessed the impact of collateral flow on perfusion imaging evaluated by hypoperfusion intensity ratio (HIR) - Tmax10 sec/Tmax6 sec) on the association between anesthesia type and EVT outcomes. Results: Of 731 treated with EVT, 305 (42%) received GA and 426 (58%) non-GA. The baseline characteristics were similar, except for presentation NIHSS (median [IQR] GA 18 [13-22] , non-GA 16[11-20], p 〈 0.001) and ischemic core volume (GA 14.1mL [3-37] vs non-GA 9mL [0-31] , p=0.002). GA was associated with longer LKW to arterial access (203min [158-267] vs 186min [138-252] , p=0.002), but similar procedural time (36min [23-59] vs 34min [22-54] , p=0.36). Non-GA was independently associated with improved functional outcomes (adj cOR 1.42, 95%CI 1.05-1.93, p=0.024) and lower mortality (17% vs 11.3%, p=0.025). Patients with poor collaterals (HIR≥0.4) had improved functional outcomes with non-GA (adj cOR 1.53, 95%CI 1.02-2.29, p=0.038), while no difference was observed in those with good collaterals-HIR 〈 0.4 (adj cOR 1.38, 95% CI 0.84-2.27, p=0.21). Conclusion: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals. These findings have implications for randomized trials of GA vs non-GA.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 10 ( 2021-10), p. 3399-3403
    Abstract: Reperfusion therapy with intravenous alteplase and endovascular therapy are effective treatments for selected patients with acute ischemic stroke. Guidelines for treatment are based upon randomized trials demonstrating substantial treatment effects for highly selected patients based on time from stroke onset and imaging features. However, patients beyond the current established guidelines might benefit with lesser but still clinically significant treatment effects. The STAIR (Stroke Treatment Academic Industry Roundtable) XI meeting convened a workgroup to consider the “outer limits” of reperfusion therapy by defining the current boundaries, and exploring optimal parameters and methodology for determining the outer limits. In addition to statistical significance, the minimum clinically important difference should be considered in exploring the limits of reperfusion therapy. Societal factors and quality of life considerations should be incorporated into assessment of treatment efficacy. The threshold for perception of benefit in the medical community may differ from that necessary for the Food and Drug Administration approval. Data from alternative sources such as platform trials, registries and large pragmatic trials should supplement randomized controlled trials to improve generalizability to routine clinical practice. Further interactions between industry and academic centers should be encouraged.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 8
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 13, No. 10 ( 2021-10), p. 875-882
    Abstract: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. Methods In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS 〈 6 or computed tomography perfusion (CTP) ischemic core volume (rCBF 〈 30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials. Results From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0–2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. Conclusions In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. Clinical trial registration NCT02446587
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2506028-4
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. suppl_1 ( 2016-02)
    Abstract: Introduction: ASPECTS and CT perfusion (CTP) lesion volumes have been used to triage patients with large artery occlusions to endovascular therapy. Specifically, ASPECTS ≤5 and CTP infarct core 〉 50 mL excluded patients from some recent endovascular trials. It is unclear how well these criteria select patients who will have poor functional outcomes despite reperfusion and if the criteria are interchangeable. Hypothesis: ASPECTS and CTP infarct volumes are correlated and both predict clinical outcome. Methods: Patients with anterior circulation strokes were enrolled in a prospective multi-center study (CRISP) if CTP could be obtained 〈 90 minutes before endovascular treatment, and intervention performed 〈 18h from onset. Reperfusion was defined as 〉 50% reduction from baseline Tmax 〉 6s volume on early follow-up MRI ( 〈 36h from baseline CT) or final TICI 2b/3 if follow-up MRI unavailable. A single blinded reader at the core imaging facility determined ASPECTS on baseline CT. Baseline ischemic core volumes were assessed using automated software (RAPID). Good outcome was defined as mRS 0-2 and poor outcome as mRS 5-6. Results: This analysis includes 165 patients with reperfusion after endovascular therapy. Baseline ASPECTS and infarct core volume are inversely associated (p=0.009). Lower ASPECTS and larger infarct core were associated with a lower chance of good outcome in univariate analysis: OR for good outcome was 0.8 (95% CI 0.7-1.0) per point decrease in ASPECTS and 0.8 (95% CI 0.6-0.9) per 10mL increase in infarct core. Adjusted for baseline NIHSS and age, core remained a predictor of good outcomes (p=0.025) while ASPECTS showed a strong trend (p=0.072). The PPV for poor outcome despite reperfusion was 38% (5/13) for infarct core 〉 50 mL and 0% (0/7) for ASPECTS ≤5 (p=0.1 for difference in PPV). No patient met both criteria. Conclusions: The ASPECTS and ischemic core volume criteria used to exclude patients from some endovascular therapy trials, did not agree in identifying patients with presumed poor outcomes. Neither criterion had a high specificity for identifying patients destined to have a poor outcome despite reperfusion. Randomized trials are warranted to assess the efficacy of endovascular therapy in patients with ischemic core lesions 〉 50 ml and ASPECTS ≤5.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: The Lancet Neurology, Elsevier BV, Vol. 11, No. 10 ( 2012-10), p. 860-867
    Type of Medium: Online Resource
    ISSN: 1474-4422
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2012
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