Abstract 100: Reperfusion Improves Clinical Outcome Across the 4.5-9h and Wake-Up Stroke Time Continuum in EXTEND and EPITHET

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Bruce C Campbell ◽  
Henry Ma ◽  
Mark W Parsons ◽  
Leonid Churilov ◽  
Nawaf Yassi ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Randomized Trials ◽  
Time Window ◽  
Functional Improvement ◽  
Lesion Volume ◽  
Common Odds Ratio ◽  
Shift Analysis ◽  
Intravenous Alteplase ◽  
Interaction Term ◽  
Time Continuum

Introduction: Intravenous alteplase reduces disability after ischemic stroke in patients 4.5-9h after onset and with wake-up onset stroke who have favorable perfusion imaging. We examined the benefit of reperfusion in reducing disability, including by onset to randomization time strata in the EXTEND and EPITHET randomized trials. Methods: Patients were randomized to alteplase or placebo after perfusion mismatch imaging. Reperfusion was defined as >90% reduction in Tmax>6s lesion volume at 24h. Ordinal logistic regression adjusted for baseline age and NIHSS was used to analyze functional improvement in day 90 modified Rankin scale overall, including a reperfusion*time to randomization interaction term, and in the 4.5-6h, 6-9h and wake-up time strata. Symptomatic hemorrhage was defined as large parenchymal hematoma with ≥4 point NIHSS increase (SITS). Results: Reperfusion was assessable in 270/294 (92%) patients, 68/133 (51%) alteplase and 38/137 (28%) placebo reperfused (p<0.001). Median age 76 (IQR 66-81) in reperfused vs 74 (IQR 64.5-81) in non-reperfused, median baseline NIHSS 10 (IQR 7-15) in reperfused vs 12 (IQR 8-17.5) in non-reperfused. Overall, reperfusion was associated with common odds ratio 7.7 (95%CI 4.6-12.8, p<0.0001) in ordinal “shift” analysis. There was no heterogeneity in the beneficial effect of reperfusion effect by time to randomization (p=0.63). Reperfusion was associated with significantly improved functional outcome in each of the 4.5-6h, 6-9h and wake-up time strata (figure). Symptomatic hemorrhage, assessed in all 294 patients, occurred in 3/51 (5.9%) 4.5-6h, 2/28 (7.1%) 6-9h, 4/73 (5.5%) wake-up stroke in the alteplase-treated patients (van Elteren p=0.66). Conclusions: Strong benefits of reperfusion in all time strata without differential risk in symptomatic hemorrhage support the durable treatment effect of alteplase in perfusion mismatch-selected patients throughout the 4.5-9h and wake-up stroke time window.

scholarly journals Comparative effectiveness of pharmacological interventions to prevent postoperative delirium: a network meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sun-Kyung Park ◽  
Taeyoon Lim ◽  
Hyeyeon Cho ◽  
Hyun-Kyu Yoon ◽  
Ho-Jin Lee ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Atypical Antipsychotics ◽  
Postoperative Delirium ◽  
Randomized Trials ◽  
Time Window ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Cochrane Central Register ◽  
Pharmacological Interventions ◽  
Diagnostic Time

AbstractMany pharmacologic agents were investigated for the effect to prevent delirium. We aimed to comprehensively compare the effect of the pharmacological interventions to prevent postoperative delirium. A Bayesian network meta-analysis of randomized trials was performed using random effects model. PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched on 20 January 2021. Randomized trials comparing the effect of a drug to prevent postoperative delirium with another drug or placebo in adult patients undergoing any kind of surgery were included. Primary outcome was the postoperative incidence of delirium. Eighty-six trials with 26,992 participants were included. Dexmedetomidine, haloperidol, and atypical antipsychotics significantly decreased the incidence of delirium than placebo [dexmedetomidine: odds ratio 0.51, 95% credible interval (CrI) 0.40–0.66, moderate quality of evidence (QOE); haloperidol: odds ratio 0.59, 95% CrI 0.37–0.95, moderate QOE; atypical antipsychotics: odds ratio 0.27, 95% CrI 0.14–0.51, moderate QOE]. Dexmedetomidine and atypical antipsychotics had the highest-ranking probabilities to be the best. However, significant heterogeneity regarding diagnostic time window as well as small study effects precludes firm conclusion.

scholarly journals Association of Time of Day When Endovascular Therapy for Stroke Starts and Functional Outcome

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011449
Author(s):  
Steven D Hajdu ◽  
Johannes Kaesmacher ◽  
Prof Patrik Michel ◽  
Gaia Sirimarco ◽  
Jean-Francois Knebel ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Odds Ratio ◽  
Primary Outcome ◽  
Time Of Day ◽  
Start Time ◽  
Common Odds Ratio ◽  
Shift Analysis ◽  
Baseline Factors ◽  
Working Day ◽  
Stroke Center

Objective:To investigate the association between EVT start time in acute ischemic stroke (AIS) and mid-term functional outcome.Methods:This retrospective cohort study included all AIS cases treated with EVT from two stroke center registries from January 2012 to December 2018. The primary outcome was the score on the modified Rankin Scale (mRS) and the utility-weighted mRS (uw-mRS) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention at a given EVT start time would lead to lower scores on the mRS (shift analysis).Results:One thousand five hundred fifty-eight cases were equally allotted into twelve EVT-start-time periods. The primary outcome favored EVT start times in the morning at 08:00-10:20 and 10:20-11:34 (common odds ratio (OR), 0.53; 95% confidence interval (CI), 0.38 to 0.75; P<0.001; OR, 0.62; 95% CI, 0.44 to 0.87; P=0.006, respectively), while it disfavored EVT start times at the end of the working day at 15:55-17:15 and 18:55-20:55 (OR, 1.47; 95% CI, 1.03 to 2.09; P=0.034; OR, 1.49; 95% CI, 1.03 to 2.15; P=0.033). Symptom onset-to-EVT start time was significantly higher and use of IV t-PA significantly lower between 10:20-11:34 (P<0.004 and P=0.012, respectively).Conslusion:EVT for AIS in the morning leads to better mid-term functional outcome, while EVT at the end of the work day leads to poorer mid-term functional outcome. Neither difference in baseline factors, standard workflow and technical efficacy metrics could be identified as potential mediators of this effect.

scholarly journals Cerebral Edema in Patients With Large Hemispheric Infarct Undergoing Reperfusion Treatment: A HERMES Meta-Analysis

Stroke ◽  
2021 ◽  
Author(s):  
Felix C. Ng ◽  
Nawaf Yassi ◽  
Gagan Sharma ◽  
Scott B. Brown ◽  
Mayank Goyal ◽  
...  
Keyword(s):  
Cerebral Edema ◽  
Odds Ratio ◽  
Ct Perfusion ◽  
Meta Analysis ◽  
National Institutes Of Health ◽  
Functional Improvement ◽  
Common Odds Ratio ◽  
Core Volume ◽  
Hemispheric Infarction

Background and Purpose: Whether reperfusion into infarcted tissue exacerbates cerebral edema has treatment implications in patients presenting with extensive irreversible injury. We investigated the effects of endovascular thrombectomy and reperfusion on cerebral edema in patients presenting with radiological evidence of large hemispheric infarction at baseline. Methods: In a systematic review and individual patient-level meta-analysis of 7 randomized controlled trials comparing thrombectomy versus medical therapy in anterior circulation ischemic stroke published between January 1, 2010, and May 31, 2017 (Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration), we analyzed the association between thrombectomy and reperfusion with maximal midline shift (MLS) on follow-up imaging as a measure of the space-occupying effect of cerebral edema in patients with large hemispheric infarction on pretreatment imaging, defined as diffusion-magnetic resonance imaging or computed tomography (CT)-perfusion ischemic core 80 to 300 mL or noncontrast CT-Alberta Stroke Program Early CT Score ≤5. Risk of bias was assessed using the Cochrane tool. Results: Among 1764 patients, 177 presented with large hemispheric infarction. Thrombectomy and reperfusion were associated with functional improvement (thrombectomy common odds ratio =2.30 [95% CI, 1.32–4.00]; reperfusion common odds ratio =4.73 [95% CI, 1.66–13.52]) but not MLS (thrombectomy β=−0.27 [95% CI, −1.52 to 0.98]; reperfusion β=−0.78 [95% CI, −3.07 to 1.50]) when adjusting for age, National Institutes of Health Stroke Score, glucose, and time-to-follow-up imaging. In an exploratory analysis of patients presenting with core volume >130 mL or CT-Alberta Stroke Program Early CT Score ≤3 (n=76), thrombectomy was associated with greater MLS after adjusting for age and National Institutes of Health Stroke Score (β=2.76 [95% CI, 0.33–5.20]) but not functional improvement (odds ratio, 1.71 [95% CI, 0.24–12.08]). Conclusions: In patients presenting with large hemispheric infarction, thrombectomy and reperfusion were not associated with MLS, except in the subgroup with very large core volume (>130 mL) in whom thrombectomy was associated with increased MLS due to space-occupying ischemic edema. Mitigating cerebral edema-mediated secondary injury in patients with very large infarcts may further improve outcomes after reperfusion therapies.

scholarly journals Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials

2017 ◽  
Vol 13 (2) ◽  
pp. 175-189 ◽  
Author(s):  
Werner Hacke ◽  
Patrick Lyden ◽  
Jonathan Emberson ◽  
Colin Baigent ◽  
Lisa Blackwell ◽  
...  
Keyword(s):  
United States ◽  
European Union ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Randomized Trials ◽  
Individual Patient Data ◽  
Time Window ◽  
Meta Analysis ◽  
Hazard Ratios ◽  
Intravenous Alteplase

Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

Does Locoregional Radiation Therapy Improve Survival in Breast Cancer? A Meta-Analysis

2000 ◽  
Vol 18 (6) ◽  
pp. 1220-1229 ◽  
Author(s):  
Timothy J. Whelan ◽  
Jim Julian ◽  
Jim Wright ◽  
Alejandro R. Jadad ◽  
Mark L. Levine
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Systemic Therapy ◽  
Odds Ratio ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Radical Mastectomy ◽  
Node Positive ◽  
Meta Analyses ◽  
Positive Breast Cancer

PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.

scholarly journals One-Year Outcome After Endovascular Treatment for Acute Basilar Artery Occlusion

Stroke ◽  
2021 ◽  
Author(s):  
Fengli Li ◽  
Hongfei Sang ◽  
Jiaxing Song ◽  
Zhangbao Guo ◽  
Shuai Liu ◽  
...  
Keyword(s):  
Treatment Group ◽  
Endovascular Treatment ◽  
Basilar Artery ◽  
Odds Ratio ◽  
Conventional Treatment ◽  
Artery Occlusion ◽  
Basilar Artery Occlusion ◽  
Modified Rankin Scale ◽  
Common Odds Ratio ◽  
One Year

Background and Purpose: The BASILAR registry, a nationwide prospective nonrandomized study conducted in China, enrolled consecutive patients with acute basilar artery occlusion receiving endovascular treatment or conventional-treatment from January 2014 to May 2019. This article aimed to report the results of clinical follow-up at one year among these patients. Methods: The primary outcome was the modified Rankin Scale at one year, assessed as a common odds ratio using ordinal logistic regression analysis adjusted for prespecified prognostic factors. Secondary outcomes included the modified Rankin Scale-based outcome group at one year (0–1, 0–2, or 0–3) and all-cause death. Results: Of the 829 patients enrolled in the original BASILAR registry, one-year data were available for 785 patients (94.7%). The distribution of outcomes on the modified Rankin Scale favored endovascular treatment over conventional-treatment (adjusted common odds ratio, 4.50 [95% CI, 2.81–7.29]; P <0.001). The cumulative one-year mortality rate was 54.6% in the endovascular treatment group versus 83.5% in the conventional-treatment group (adjusted odds ratio, 4.36 [95% CI, 2.69–7.29]; P <0.001). Conclusions: The beneficial effect of endovascular treatment on functional outcome at one year in patients with acute basilar artery occlusion is similar to that reported at 90 days in the original study. REGISTRATION: URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR1800014759.

scholarly journals A Systematic Review of Randomized Trials of Long-Term Opioid Management for Chronic Non-Cancer Pain

2011 ◽  
Vol 3;14 (2;3) ◽  
pp. 91-121
Author(s):  
Laxmaiah Manchikanti
Keyword(s):  
Systematic Review ◽  
Cancer Pain ◽  
Systematic Reviews ◽  
Randomized Trials ◽  
Opioid Therapy ◽  
Functional Improvement ◽  
Controlled Trials ◽  
Chronic Opioid Therapy ◽  
Level Of Evidence

Background: Even though opioids have been used for pain for thousands of years, opioid therapy for chronic non-cancer pain is controversial due to concerns regarding the long-term effectiveness and safety, particularly the risk of tolerance, dependance, or abuse. While the debate continues, the use of chronic opioid therapy for chronic non-cancer pain has increased exponentially. Even though evidence is limited, multiple expert panels have concluded that chronic opioid therapy can be effective therapy for carefully selected and monitored patients with chronic non-cancer pain. Study Design: A systematic review of randomized trials of opioid management for chronic noncancer pain. Objective: The objective of this systematic review is to evaluate the clinical efficacy of opioids in the treatment of chronic non-cancer pain. Methods: A comprehensive evaluation of the literature relating to opioids in chronic non-cancer pain was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs) and Jadad criteria. A literature search was conducted by using PubMed, EMBASE, Cochrane library, ECRI Institute Library, U.S. Food and Drug Administration (FDA) website, U.S. National Guideline Clearinghouse (NGC), Database of Abstracts of Reviews of Effectiveness (DARE), clinical trials, systematic reviews and cross references from systematic reviews. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) and used by other systematic reviews and guidelines. Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, withdrawals, and adverse effects. Results: Based on the USPSTF criteria, the indicated level of evidence was fair for Tramadol in managing osteoarthritis. For all the drugs assessed, including Tramadol, for all other conditions, the evidence was poor based on either weak positive evidence, indeterminate evidence, or negative evidence. Limitations: A paucity of literature, specifically with follow-up beyond 12 weeks for all types of opioids with controlled trials for various chronic non-cancer pain conditions. Conclusions: This systematic review illustrated fair evidence for Tramadol in managing osteoarthritis with poor evidence for all other drugs and conditions. Thus, recommendations must be based on non-randomized studies. Key words: Chronic non-cancer pain, opioids, opioid efficacy, opioid effectiveness, significant pain relief, functional improvement, adverse effects, morphine, hydrocodone, hydromorphone, fentanyl, tramadol, buprenorphine, methadone, tapentadol, oxycodone, oxymorphone, systematic reviews, randomized trials

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