scholarly journals Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm

2020 ◽  
pp. 174749301989785 ◽  
Author(s):  
Xiaoying Chen ◽  
Jingwei Li ◽  
Craig S Anderson ◽  
Richard I Lindley ◽  
Maree L Hackett ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Logistic Regression ◽  
Outcome Measurement ◽  
Demographic Data ◽  
Weighted Kappa ◽  
Alternative Measure ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Quality Of Life Scale

Background and aims The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. Methods Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. Results SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78–0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91–1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87–1.11; P = 0.02 for non-inferiority), similar to those using mRS. Conclusions This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke. Clinical Trial registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616.

scholarly journals Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis

Circulation ◽  
2019 ◽  
Vol 140 (18) ◽  
pp. 1451-1459 ◽  
Author(s):  
John W. Eikelboom ◽  
Stuart J. Connolly ◽  
Jacqueline Bosch ◽  
Olga Shestakovska ◽  
Victor Aboyans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gastrointestinal Bleeding ◽  
Cancer Diagnosis ◽  
Minor Bleeding ◽  
Antithrombotic Drugs ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Risk Of Bleeding ◽  
Genitourinary Cancer

Background: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer. Methods: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites. Results: Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2–27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20–2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7–42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0–142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32–3.91]). Conclusions: In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.

scholarly journals Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage

Stroke ◽  
2019 ◽  
Vol 50 (11) ◽  
pp. 3064-3071 ◽  
Author(s):  
Philip M. Bath ◽  
Lisa J. Woodhouse ◽  
Kailash Krishnan ◽  
Jason P. Appleton ◽  
Craig S. Anderson ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Glyceryl Trinitrate ◽  
Global Analysis ◽  
Mass Effect ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Prehospital Treatment ◽  
Acute Intracerebral Hemorrhage

Background and Purpose— Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods— We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results— Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45–110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98–3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01–0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions— Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN26986053.

scholarly journals Novel Supreme TM DES with Early Synchronized Antiproliferative Drug Delivery to Inhibit Smooth Muscle Cell Proliferation after DES implantation in Coronary Artery Disease: Results of the PIONEER III Randomized Clinical Trial

Circulation ◽  
2021 ◽  
Author(s):  
Alexandra J. Lansky ◽  
Dean J. Kereiakes ◽  
Andreas Baumbach ◽  
Stephan Windecker ◽  
Yasin Hussain ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Trial ◽  
Absolute Risk ◽  
Target Lesion ◽  
Base Layer ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Durable Polymer ◽  
Coronary Syndromes

Background: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug eluting stents (DES). The novel Supreme TM DES (Supreme) is designed to synchronize early drug delivery within 4-6 weeks of implantation, leaving behind a pro-healing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long term clinical outcomes is not known. Methods: In an international 2:1 randomized single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-DES) in patients with acute and chronic coronary syndromes. The primary endpoint was target lesion failure (TLF) - a composite of cardiac death, target vessel myocardial infarction, or clinically-driven target lesion revascularisation (TLR). The trial was designed to demonstrate non-inferiority (margin of 3.58%) of the Supreme DES at 12 months compared to DP-DES (clinicaltrials.gov-NCT03168776). Results: From October 2017 to July 2019, a total of 1629 patients were randomly assigned (2:1) to the Supreme DES (N=1086) or DP-DES (N=543). At 12 months, TLF occurred in 57 of 1057 patients (5.4%) in the Supreme DES group and in 27 of 532 patients (5.1%) in the DP-DES group (Absolute Risk Difference 0.32%, 95%CI [-1.87%, 2.5%]; p non-inferiority =0.002]. There were no significant differences in rates of device success, clinically driven TLR or stent thrombosis at 12 months, and the safety composite of CV Death and TV MI was 3.5% vs 4.6%; HR [95.0% CI] 0.76 [0.46, 1.25] with Supreme DES compared to DP-DES, though rates of combined clinical and non-clinical driven TLR at 12 months were higher with Supreme DES. Conclusions: Among patients with acute and chronic coronary syndromes undergoing percutaneous coronary intervention, the Supreme DES proved to be non-inferior to the standard DP-DES. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03168776

scholarly journals Tenecteplase Versus Alteplase Between 3 and 4.5 Hours in Low National Institutes of Health Stroke Scale

Stroke ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 498-500 ◽  
Author(s):  
Ole Morten Rønning ◽  
Nicola Logallo ◽  
Bente Thommessen ◽  
Håkon Tobro ◽  
Vojtech Novotny ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Scale Score ◽  
Odds Ratio ◽  
National Institutes Of Health ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Intention To Treat ◽  
Good Functional Outcome

Background and Purpose— Thrombolysis with alteplase has beneficial effect on outcome and is safe within 4.5 hours. The present study compares the efficacy and safety of tenecteplase and alteplase in patients treated 3 to 4.5 hours after ischemic stroke. Methods— The data are from a prespecified substudy of patients included in The NOR-TEST (Norwegian Tenecteplase Stroke Trial), a randomized control trial comparing tenecteplase with alteplase. Results— The median admission National Institutes of Health Stroke Scale for this study population was 3 (interquartile range, 2–6). In the intention-to-treat analysis, 57% of patients that received tenecteplase and 53% of patients that received alteplase reached good functional outcome (modified Rankin Scale score of 0–1) at 3 months (odds ratio, 1.19; 95% CI, 0.68–2.10). The rates of intracranial hemorrhage in the first 48 hours were 5.7% in the tenecteplase group and 6.7% in the alteplase group (odds ratio, 0.84; 95% CI, 0.26–2.70). At 3 months, mortality was 5.7% and 4.5%, respectively. After excluding stroke mimics and patients with modified Rankin Scale score of >1 before stroke, the proportion of patients with good functional outcome was 61% in the tenecteplase group and 57% in the alteplase group (odds ratio, 1.24; 95% CI, 0.65–2.37). Conclusions— Tenecteplase is at least as effective as alteplase to achieve a good clinical outcome in patients with mild stroke treated between 3 and 4.5 hours after ischemic stroke. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

scholarly journals Inter-method reliability of the modified Rankin Scale in patients with subarachnoid hemorrhage

2021 ◽  
Author(s):  
E. Nobels-Janssen ◽  
E. N. Postma ◽  
I. L. Abma ◽  
J. M. C. van Dijk ◽  
R. Haeren ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Weighted Kappa ◽  
Structured Interview ◽  
Assessment Methods ◽  
The Self ◽  
Modified Rankin Scale ◽  
Self Assessment ◽  
Unique Identifier ◽  
Kappa Score

Abstract Background and objectives The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS. Methods This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire. Results The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible. Discussion The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials. Trial registration www.trialregister.nl; Unique identifier: NL7859.

scholarly journals The association of novel inflammatory marker GlycA and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA)

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248644
Author(s):  
Sunyoung Jang ◽  
Oluseye Ogunmoroti ◽  
Di Zhao ◽  
Oluwaseun E. Fashanu ◽  
Martin Tibuakuu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Individual Variability ◽  
Cvd Risk ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Link Type ◽  
The Mean

Background Emerging evidence has implicated that inflammation contributes to the pathogenesis of atrial fibrillation (AF). GlycA is a novel marker of systemic inflammation with low intra-individual variability and high analytic precision. GlycA has been associated with incident cardiovascular disease (CVD) independent of other inflammatory markers. However, whether GlycA is associated with AF, specifically, has yet to be established. We examined the association between GlycA and AF in a multi-ethnic cohort. Methods We studied 6,602 MESA participants aged 45–85, with no clinical CVD at baseline, with data on GlycA and incident AF. We used multivariable-adjusted Cox models to evaluate the association between GlycA and incident AF. We also examined other inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and fibrinogen] and incident AF for comparison. Results The mean (SD) age was 62 (10) years, 53% women. The mean plasma GlycA was 381 (62) μmol/L. Over median follow-up of 12.9 years, 869 participants experienced AF. There was no statistically significant association between GlycA and incident AF after adjusting for sociodemographics, CVD risk factors, and other inflammatory markers [Hazard Ratio (95% CI) per 1 SD increment in GlycA: 0.97 (0.88–1.06)]. Neither hsCRP nor fibrinogen was associated with incident AF in same model. In contrast, IL-6 was independently associated with incident AF [HR 1.12 per 1 SD increment (1.05–1.19)]. Conclusions Although GlycA has been associated with other CVD types, we found that GlycA was not associated with AF. More research will be required to understand why IL-6 was associated with AF but not GlycA. Clinical trial registration MESA is not a clinical trial. However, the cohort is registered at: URL: https://clinicaltrials.gov/ct2/show/NCT00005487 Unique identifier: NCT00005487.

scholarly journals A Randomized Clinical Trial of a Functional Electrical Stimulation Mimic to Gait Promotes Motor Recovery and Brain Remodeling in Acute Stroke

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiuyuan Zheng ◽  
Danfeng Chen ◽  
Tiebin Yan ◽  
Dongmei Jin ◽  
Zhiqiang Zhuang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Electrical Stimulation ◽  
Placebo Group ◽  
Functional Electrical Stimulation ◽  
Gait Pattern ◽  
Motor Recovery ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Dual Channel ◽  
Brain Fmri

Functional electrical stimulation can improve motor function after stroke. The mechanism may involve activity-dependent plasticity and brain remodeling. The aim of our study was to investigate the effectiveness of a patterned electrical stimulation FES mimic to gait in motor recovery among stroke survivors and to investigate possible mechanisms through brain fMRI. Forty-eight subjects were recruited and randomly assigned to a four-channel FES group (n=18), a placebo group (n=15), or a dual-channel FES group (n=15). Stimulation lasted for 30 minutes in each session for 3 weeks. All of the subjects were assessed at baseline and after weeks 1, 2, and 3. The assessments included the Fugl-Meyer Assessment, the Postural Assessment Scale for Stroke Patients, Brunel’s Balance Assessment, the Berg Balance Scale, and the modified Barthel Index. Brain fMRI were acquired before and after the intervention. All of the motor assessment scores significantly increased week by week in all the three groups. The four-channel group showed significantly better improvement than the dual-channel group and placebo groups. fMRI showed that fractional anisotropy was significantly increased in both the four-channel and dual-channel groups compared with the placebo group and fiber bundles had increased significantly on the ipsilateral side, but not on the contralateral side in the group given four-channel stimulation. In conclusion, when four-channel FES induces cycling movement of the lower extremities based on a gait pattern, it may be more effective in promoting motor recovery and induce more plastic changes and brain remodeling than two-channel stimulation. This trial is registered with clinical trial registration unique identifier ChiCTR-TRC-11001615.

scholarly journals Accuracy of a smartwatch based single-lead electrocardiogram device in detection of atrial fibrillation

Heart ◽  
2020 ◽  
Vol 106 (9) ◽  
pp. 665-670 ◽  
Author(s):  
Kevin Rajakariar ◽  
Anoop N Koshy ◽  
Jithin K Sajeev ◽  
Sachin Nair ◽  
Louise Roberts ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Predictive Value ◽  
Cardiac Rhythm ◽  
Hospital Setting ◽  
Automated Diagnosis ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Automated Algorithms ◽  
Improved Accuracy

ObjectiveThe AliveCor KardiaBand (KB) is an Food and Drug Administration-approved smartwatch-based cardiac rhythm monitor that records a lead-Intelligent ECG (iECG). Despite the appeal of wearable integrated ECG devices, there is a paucity of data evaluating their accuracy in diagnosing atrial fibrillation (AF). We evaluated whether a smartwatch-based device for AF detection is an accurate tool for diagnosing AF when compared with 12-lead ECG.MethodsA prospective, multi-centre, validation study was conducted in an inpatient hospital setting. The KB paired with a smartwatch, generated an automated diagnosis of AF or sinus rhythm (SR). This was compared with a 12-lead ECG performed immediately after iECG tracing. Where an unclassified or no-analysis tracing was generated, repeat iECG was performed.Results439 ECGs (iECGs (n=239) and 12-lead ECG (n=200)) were recorded in 200 patients (AF: n=38; SR: n=162) from three tertiary centres. Sensitivity and specificity using KB was 94.4% and 81.9% respectively, with a positive predictive value of 54.8% and negative predictive value of 98.4%. Agreement between 12-lead ECG and KB diagnosis was moderate when unclassified tracings were included (κ=0.60, 95% CI 0.47 to 0.72). Combining the automated device diagnosis with blinded electrophysiologists (EP) interpretation of unclassified tracings improved overall agreement (EP1: κ=0.76, 95% CI 0.65 to 0.87; EP2: κ=0.74, 95% CI 0.63 to 0.86).ConclusionThe KB demonstrated moderate diagnostic accuracy when compared with a 12-lead ECG. Combining the automated device diagnosis with EP interpretation of unclassified tracings yielded improved accuracy. However, even with future improvements in automated algorithms, physician involvement will likely remain an essential component when exploring the utility of these devices for arrhythmia screening.Clinical trial registrationURL: https://www.anzctr.org.au/ Unique identifier: ACTRN12616001374459.

Abstract WMP24: Collateral Status Contributes to Differences Between Observed and Predicted 24-Hour Infarct Volumes in DEFUSE 3

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Vaishnavi Rao ◽  
Michael Mlynash ◽  
Søren Christensen ◽  
Amarnath Yennu ◽  
Stephanie Kemp ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cerebral Blood Volume ◽  
Ct Perfusion ◽  
Infarct Volume ◽  
Volume Index ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Volume Estimate ◽  
The Difference

Background and Purpose: We have previously shown that in the DEFUSE 3 trial, the infarct volume 24 hours after randomization was predicted by the union of the baseline core and the 24-hour Tmax>6s perfusion lesion. We determined if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume index (CBV) accounts for the variance in infarct volume predictions. Methods: DEFUSE 3 patients underwent MRI with perfusion or CT perfusion at baseline and 24 hours after randomization. We used RAPID software to determine ischemic core and Tmax>6s lesion volumes as well as HIR and CBV Index at baseline and 24 hours. Patients were stratified by the difference between the predicted and the observed infarct volume at 24 hours. We compared baseline and follow-up HIR and CBV Index, as well as several other imaging and clinical outcomes in subgroups based on the accuracy of the infarct volume estimate. Results: Out of 123 eligible patients, 34 had 24-hour infarcts larger than predicted and these patients had less favorable collaterals (HIR 0.43 vs 0.32, p=0.006 and CBV Index 0.78 vs 0.85, p=0.001) at baseline, as well as at 24-hour follow-up (HIR 0.56 vs 0.07, p=0.004 and CBV Index 0.47 vs 0.73, p=0.006) compared to the 71 patients with more accurate infarct volume prediction. The remaining 18 patients had 24-hour infarct volumes smaller than predicted. These patients had similar baseline collateral scores but a more favorable CBV Index at 24 hours (0.81 vs 0.73, p=0.040) compared to patients with more accurate infarct prediction. Conclusions: Patients with 24-hour infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24 hours, while patients with 24-hour infarcts smaller than predicted typically had favorable collaterals that persisted for at least 24 hours. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02586415

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