Abstract P467: Clinical Effectiveness of Endovascular Stroke Treatment in the Early and Extended Time Windows

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Raul Nogueira ◽  
Diogo C Haussen ◽  
David S Liebeskind ◽  
Tudor G Jovin ◽  
Rishi Gupta ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Time Windows ◽  
Clinical Effectiveness ◽  
Inclusion Criteria ◽  
Open Label ◽  
Time To Treatment ◽  
Stroke Treatment ◽  
Real World Setting ◽  
Lower Baseline ◽  
Iv Tpa

Background and Purpose: The clinical efficacy of mechanical thrombectomy (MT) has been unequivocally demonstrated in multiple randomized clinical trials (RCTs). However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. We aim to assess the clinical effectiveness of MT by comparing the specific RCT populations with corresponding patient cohorts derived from a prospective registry. Methods: A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label MT registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials based on the age, baseline NIHSS, occlusion site, IV tPA use, pre-morbid mRS and time to treatment criteria used in the RCTs 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 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 (mRS 0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding RCTs (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 RCT controls (ordinal mRS shift 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 RCTs and strict guidelines.

scholarly journals EXPRESS: Clinical Effectiveness of Endovascular Stroke Treatment in the Early and Extended Time Windows

2021 ◽  
pp. 174749302110057
Author(s):  
Raul Nogueira ◽  
Diogo C. Haussen ◽  
David S. Liebeskind ◽  
Tudor G Jovin ◽  
Rishi Gupta ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Mechanical Thrombectomy ◽  
Time Windows ◽  
Clinical Effectiveness ◽  
Inclusion Criteria ◽  
Open Label ◽  
Stroke Treatment ◽  
Clinical Criteria ◽  
Lower Baseline ◽  
Iv Tpa

Background The clinical efficacy of mechanical thrombectomy (MT) has been unequivocally demonstrated in multiple randomized clinical trials (RCTs). However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. Aim We aimed to assess the clinical effectiveness of MT in a prospective registry. Methods A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label MT 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 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 RCTs (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 RCT controls (ordinal mRS shift 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 RCTs.

EXPRESS: Influence of Time to Endovascular Stroke Treatment on Outcomes in the Early versus Extended Window Paradigms

2021 ◽  
pp. 174749302110063
Author(s):  
Raul Nogueira ◽  
Tudor G Jovin ◽  
Diogo C. Haussen ◽  
Rishi Gupta ◽  
ashutosh Jadhav ◽  
...  
Keyword(s):  
Functional Disability ◽  
Time Window ◽  
Time Windows ◽  
Extended Time ◽  
Primary Analysis ◽  
Anterior Circulation ◽  
Time To Treatment ◽  
Stroke Treatment ◽  
The Impact ◽  
The Relationship

Background The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized. Aim We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows. Methods Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6-hours) or extended (>6-24-hours) treatment window. Patients with baseline NIHSS≥10 and intracranial ICA or MCA-M1-segment occlusion and pre-morbid mRS0-1 (“DAWN-like” cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS0-2) fashion, was compared within and across the extended and early-windows. Results A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7-13.9]vs.3.4[2.5-4.3] hours,p<0.001), extended-window patients (n=257) had similar rates of symptomatic intracranial hemorrhage (0.8%vs.1.7%,p=0.293) and 90-day-mortality (10.5%vs.9.6%,p=0.714) with only slightly lower rates of 90-day good outcomes (50.4%vs.57.6%,p=0.047) versus early-window patients (n=709). Time to treatment was associated with 90-day disability in both ordinal (aOR,≥1-point mRS shift:0.75;95%CI[0.66-0.86],p<0.001) and dichotomized (aOR,mRS0-2:0.73;95%CI[0.62-0.86],p<0.001) analyses in the early- but not in the extended-window (aOR, mRS shift:0.96;95%CI[0.90-1.02],p=0.15; aOR,mRS0-2:0.97;95%CI[0.90-1.04],p=0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift:1.533;95%CI[1.138-2.065],p=0.005) and a trend towards higher rates of good outcomes (aOR,mRS0-2:1.391;95%CI[0.972-1.990],p=0.071). Conclusions The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration.

scholarly journals Assessing Durability of Vaccine Effect Following Blinded Crossover in COVID-19 Vaccine Efficacy Trials

2020 ◽  
Author(s):  
Dean Follmann ◽  
Jonathan Fintzi ◽  
Michael P. Fay ◽  
Holly E. Janes ◽  
Lindsey Baden ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Clinical Effectiveness ◽  
Late Enhancement ◽  
Open Label ◽  
Term Efficacy ◽  
Efficacy Trials ◽  
Timely Access ◽  
Over Time

ABSTRACTBackgroundSeveral candidate vaccines to prevent COVID-19 disease have entered large-scale phase 3 placebo-controlled randomized clinical trials and some have demonstrated substantial short-term efficacy. Efficacious vaccines should, at some point, be offered to placebo participants, which will occur before long-term efficacy and safety are known.MethodsFollowing vaccination of the placebo group, we show that placebo-controlled vaccine efficacy can be derived by assuming the benefit of vaccination over time has the same profile for the original vaccine recipients and the placebo crossovers. This reconstruction allows estimation of both vaccine durability and potential vaccine-associated enhanced disease.ResultsPost-crossover estimates of vaccine efficacy can provide insights about durability, identify waning efficacy, and identify late enhancement of disease, but are less reliable estimates than those obtained by a standard trial where the placebo cohort is maintained. As vaccine efficacy estimates for post-crossover periods depend on prior vaccine efficacy estimates, longer pre-crossover periods with higher case counts provide better estimates of late vaccine efficacy. Further, open-label crossover may lead to riskier behavior in the immediate crossover period for the unblinded vaccine arm, confounding vaccine efficacy estimates for all post-crossover periods.ConclusionsWe advocate blinded crossover and continued follow-up of trial participants to best assess vaccine durability and potential delayed enhancement of disease. This approach allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain participants on placebo, yet still allows important insights about immunological and clinical effectiveness over time.

scholarly journals Acute reperfusion therapies for acute ischemic stroke patients with unknown time of symptom onset or in extended time windows: an individualized approach

2021 ◽  
Vol 14 ◽  
pp. 175628642110211
Author(s):  
Georgios Magoufis ◽  
Apostolos Safouris ◽  
Guy Raphaeli ◽  
Odysseas Kargiotis ◽  
Klearchos Psychogios ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Time Windows ◽  
Intravenous Thrombolysis ◽  
Inclusion Criteria ◽  
Stroke Patients ◽  
Treatment Algorithms ◽  
Late Presenters

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.

scholarly journals Non-operative orthobiologic use for rotator cuff disorders and glenohumeral osteoarthritis: A systematic review

2020 ◽  
pp. 1-16
Author(s):  
David M. Robinson ◽  
Christine Eng ◽  
Steven Makovitch ◽  
Joshua B. Rothenberg ◽  
Stephanie DeLuca ◽  
...  
Keyword(s):  
Systematic Review ◽  
Rotator Cuff ◽  
Cohort Studies ◽  
Randomized Clinical Trials ◽  
Platelet Rich Plasma ◽  
Inclusion Criteria ◽  
Serious Adverse Events ◽  
Bias Risk ◽  
Glenohumeral Osteoarthritis ◽  
Functional Outcome Measures

BACKGROUND: Shoulder pain from rotator cuff pathology and glenohumeral osteoarthritis is a common entity encountered in musculoskeletal practices. Orthobiologic agents are being increasingly used as a treatment option and understanding their safety and efficacy is necessary. OBJECTIVE: To systematically evaluate the available evidence for orthobiologic use in rotator cuff and glenohumeral pathology. METHODS: A systematic review was undertaken following PRISMA guidelines. Randomized clinical trials (RCTs) and prospective cohort studies evaluating non-operative treatment with prolotherapy, platelet-rich plasma (PRP), or medicinal signaling cells (MSCs) for rotator cuff pathology and glenohumeral osteoarthritis were included. Bias risk assessments used were the Cochrane tool and Newcastle-Ottawa score. RESULTS: The search yielded 852 potential articles, of which 20 met the inclusion criteria with a breakdown of 5 prolotherapy, 13 PRP, and 2 MSC. Sixteen studies were RCTs and 4 were cohort studies. Six studies were deemed “low risk of bias or good quality”. Efficacy results were mixed, and no serious adverse events were reported from orthobiologic treatment. CONCLUSIONS: Orthobiologics offer a relatively safe management option with inconclusive evidence for or against its use for rotator cuff pathology. No studies on glenohumeral osteoarthritis met the inclusion criteria. Adoption of standardized preparation reporting and consistent use of functional outcome measures is imperative for future studies to consider.

scholarly journals Association between Anxiety Levels and Weight Change in the Multiethnic Study of Atherosclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Katherine Rieke ◽  
Ramon Durazo-Arvizu ◽  
Kiang Liu ◽  
Erin D. Michos ◽  
Amy Luke ◽  
...  
Keyword(s):  
Weight Change ◽  
Inclusion Criteria ◽  
Mixed Effect ◽  
Effect Model ◽  
Lower Baseline ◽  
Multiethnic Cohort ◽  
Baseline Weight ◽  
Study Population ◽  
The Relationship

Objective. To examine the association between anxiety and weight change in a multiethnic cohort followed for approximately 10 years.Methods. The study population consisted of participants of the multiethnic study of atherosclerosis who met specified inclusion criteria (n= 5,799). Weight was measured at baseline and four subsequent follow-up exams. Anxiety was analyzed as sex-specific anxiety quartiles (QANX). The relationship between anxiety level and weight change was examined using a mixed-effect model with weight as the dependent variable, anxiety and time as the independent variables, and adjusted for covariates.Results. Average annual weight change (range) was −0.17 kg (−6.04 to 4.38 kg) for QANX 1 (lowest anxiety), −0.16 kg (−10.71 to 4.45 kg) for QANX 2, −0.15 kg (−8.69 to 6.39 kg) for QANX 3, and −0.20 kg (−7.12 to 3.95 kg) for QANX 4 (highest anxiety). No significant association was noted between QANX and weight change. However, the highest QANX was associated with a −2.48 kg (95% CI = −3.65, −1.31) lower baseline weight compared to the lowest QANX after adjustment for all covariates.Conclusions. Among adults, age 45–84, higher levels of anxiety, defined by the STPI trait anxiety scale, are associated with lower average baseline weight but not with weight change.

scholarly journals Efficacy and Safety of Adalimumab in Canadian Patients with Moderate to Severe Crohn’s Disease: Results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn’s DiseaSe (ACCESS) Trial

2011 ◽  
Vol 25 (8) ◽  
pp. 419-425 ◽  
Author(s):  
Remo Panaccione ◽  
Edward V Loftus ◽  
David Binion ◽  
Kevin McHugh ◽  
Shamsul Alam ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Patient Reported Outcomes ◽  
Activity Index ◽  
Work Productivity ◽  
Clinical Effectiveness ◽  
Open Label ◽  
Adalimumab Therapy ◽  
Patient Reported ◽  
Fistula Healing

OBJECTIVE: To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy.METHODS: Patients with moderate to severe CD (CD activity index [CDAI] score of greater than 220, or Harvey-Bradshaw index [HBI] of 7 or greater) were eligible. Patients received open-label adalimumab as induction (160 mg and 80 mg subcutaneously [sc]) at weeks 0 and 2, respectively and maintenance (40 mg sc every other week) therapy. At or after eight weeks, patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly. Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada.RESULTS: Of the 304 patients enrolled, 160 were infliximab experienced, while 144 were anti-TNF naive. HBI remission (HBI score of 4 or lower) at week 24 was achieved by 53% of anti-TNF-naive and 36% of infliximab-experienced patients (P<0.01; P<0.001 for both groups for all visits versus baseline). Fistula healing rates at week 12 were 48% for anti-TNF-naive patients, and 26% for infliximab-experienced patients. At week 24, fistula healing rates were significantly greater for the anti-TNF-naive group (60% versus 28%; P<0.01). Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients. Serious infections occurred in 2% of patients.CONCLUSIONS: Adalimumab therapy induced and sustained steroid-free remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.

Abstract W P48: Marked Regional Variation in Acute Stroke Treatment in Medicare Beneficiaries

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
James F Burke ◽  
Lesli E Skolarus ◽  
Eric E Adelman ◽  
Phillip A Scott ◽  
William J Meurer
Keyword(s):  
Population Density ◽  
Acute Stroke ◽  
Census Data ◽  
Combined Therapy ◽  
Local Health ◽  
Median Income ◽  
Medicare Beneficiaries ◽  
Stroke Treatment ◽  
Acute Stroke Treatment ◽  
Iv Tpa

Objective: Regionalization of stroke care has occurred sporadically across the U.S, so determining realistic goal treatment rates for individual regions or the nation as a whole is challenging. Studies of a single hospital or region vary widely in estimates of eligibility for acute therapy and may have limited generalizability or biases. We hypothesized that the proportion of U.S. Medicare beneficiaries receiving acute stroke therapy varies by region. Treatment rates in high performing regions may represent realistic national goals and inform policy to increase treatment rates. Methods: All Medicare beneficiaries with a principal diagnosis of ischemic stroke (ICD-9 433.x1, 434.x1, 436) admitted through the emergency department were identified using MEDPAR files from 2007-2010. Receipt of IV tPA (DRG 559, MS-DRG 61-63, ICD-9 procedure code 99.10) or IA thrombolysis (CPT code 37184-6, 37201, 75896 via linked Medicare Carrier files) was determined. Patients were assigned to one of 3,436 Hospital Service Areas (HSA; local health care markets for hospital care) by zip code. Regional acute stroke treatment rates were calculated and the lowest and highest quintiles were compared. Multi-level logistic regression was used to adjust for individual demographics as well as regional population density, education, median income, and unemployment using linked census data. Model-based adjusted regional acute stroke treatment rates were estimated. Results: Of 916,232 stroke admissions 3.6% received IV tPA only and 0.6% received IA or combined therapy. Unadjusted treatment rates by region ranged from 0.8% (minimum) to 14.8% (maximum). Regional rates ranged from 1.7% (quintile 1) to 5.4% (quintile 5). Regions with higher education, population density and income had higher treatment rates (p <= 0.001). After adjustment, regional differences were attenuated slightly _ 1.9% (quintile 1) to 5.1% (quintile 5). Conclusions: Marked variation exists in acute stroke treatment rates by region, even after adjusting for patient and regional characteristics, supporting the perception that a major opportunity exists to improve acute stroke treatment within many HSAs.

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