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Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay protocols and primer sequences become widely known, many laboratories perform diagnostic tests using methods such as RT-PCR or reverse transcription loop mediated isothermal amplification (RT-LAMP). Here, we report an RT-LAMP isothermal assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and demonstrate the assay on clinical samples using a simple and accessible point-of-care (POC) instrument. We characterized the assay by dipping swabs into synthetic nasal fluid spiked with the virus, moving the swab to viral transport medium (VTM), and sampling a volume of the VTM to perform the RT-LAMP assay without an RNA extraction kit. The assay has a limit of detection (LOD) of 50 RNA copies per μL in the VTM solution within 30 min. We further demonstrate our assay by detecting SARS-CoV-2 viruses from 20 clinical samples. Finally, we demonstrate a portable and real-time POC device to detect SARS-CoV-2 from VTM samples using an additively manufactured three-dimensional cartridge and a smartphone-based reader. The POC system was tested using 10 clinical samples, and was able to detect SARS-CoV-2 from these clinical samples by distinguishing positive samples from negative samples after 30 min. The POC tests are in complete agreement with RT-PCR controls. This work demonstrates an alternative pathway for SARS-CoV-2 diagnostics that does not require conventional laboratory infrastructure, in settings where diagnosis is required at the point of sample collection.

IMPORTANCE: Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel. OBJECTIVE: To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. DESIGN, SETTING, AND PARTICIPANTS: Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012. INTERVENTIONS: Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome. RESULTS: Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction). CONCLUSIONS AND RELEVANCE: Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00979589.

Immersive learning environments that use virtual simulation (VS) technology are increasingly relevant as medical learners train in an environment of restricted clinical training hours and a heightened focus on patient safety. We conducted a consensus process with a breakout group of the 2017 Academic Emergency Medicine Consensus Conference "Catalyzing System Change Through Health Care Simulation: Systems, Competency, and Outcomes." This group examined the current uses of VS in training and assessment, including limitations and challenges in implementing VS into medical education curricula. We discuss the role of virtual environments in formative and summative assessment. Finally, we offer recommended areas of focus for future research examining VS technology for assessment, including high-stakes assessment in medical education. Specifically, we discuss needs for determination of areas of focus for VS training and assessment, development and exploration of virtual platforms, automated feedback within such platforms, and evaluation of effectiveness and validity of VS education.

IMPORTANCE: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE: To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS: Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS: Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE: Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01608490.

BACKGROUND AND PURPOSE: Little is known about intravenous recombinant tissue plasminogen activator (rtPA) use in China. By accessing the Chinese National Stroke Registry (CNSR), the rate of intravenous rtPA use was reviewed. We specifically examined the issues of prehospital and in-emergency department delay and compared them with the published data from developed countries. METHODS: Funded by Chinese government, CNSR is the only nationwide stroke registry that includes 132 urban hospitals. All patients eligible for intravenous rtPA were included for analysis. We then compared the onset-to-needle time and door-to-needle time in the emergency department in China with those in developed countries. RESULTS: From September 2007 to August 2008, 14,702 patients with ischemic stroke were entered into CNSR. Among 11,675 patients with known time of stroke onset, 2514 (21.5%) presented to the emergency department within 3 hours, 1469 (12.6%) were eligible for thrombolytic treatment, and 284 (2.4%) were finally treated, 181 (1.6%) of them with intravenous rtPA. The median onset-to-needle time was 180 (interquartile range, 150 to 228) minutes; the median door-to-needle time was 116 (interquartile range, 70 to 150) minutes; the median imaging-to-needle time was 90 (interquartile range, 60 to 129) minutes. Patients who were younger, presented to the emergency department quicker, with higher National Institutes of Health Stroke Scale scores, having higher income, and better education had a better chance of receiving intravenous rtPA. CONCLUSIONS: Approximately 1 in 5 patients with stroke presenting within 3 hours received thrombolytic therapy. The onset-to-needle time, door-to-needle time, and especially imaging-to-needle time were significantly longer than those in developed countries. Reducing prehospital and in-emergency department response time would help increase intravenous rtPA use in China.

BACKGROUND: The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. METHODS AND RESULTS: The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). CONCLUSIONS: The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

BACKGROUND AND PURPOSE: The association between hypertension (HTN) and stroke recurrence is unclear, but may be influenced by different subtypes of stroke. This study aims to explore whether HTN contributes to the recurrence of certain subtypes of ischemic stroke (IS). METHODS: Data from the China National Stroke Registry was examined and 1-year follow-up data for stroke recurrence was analyzed. Trial of Org 10172 in Acute Stroke Treatment criteria was used to classify the subtypes of all IS. HTN was defined when resting blood pressure was ≥ 140/90 mm Hg on repeated measurements during hospitalization or a patient had been on antihypertensive medication. Recurrent stroke was defined as a new neurological deficit compatible to IS or intracerebral hemorrhage. The association between HTN and stroke recurrence in patients with different IS subtypes was analyzed by using univariable and multivariable logistic regression models. RESULTS: Of 11 560 patients with IS, 8409 (72.7%) had HTN and 2050 (17.7%) experienced a recurrent stroke within 1 year. Patients with HTN had an insignificantly higher stroke recurrence rate than those without (18.0% versus 17.0%; P=0.21). After stratification by Trial of Org 10172 in Acute Stroke Treatment subtypes, multivariable analysis revealed a significant association between HTN and stroke recurrence in small-artery occlusion subtype (odds ratio, 1.52; 95% confidence interval, 1.03-2.31), but not in the other subtypes (large-artery atherosclerosis: odds ratio, 0.99; 95% confidence interval, 0.81-1.21; cardioembolic: odds ratio, 1.14; 95% confidence interval, 0.75-1.73; other: odds ratio, 0.88; 95% confidence interval, 0.71-1.09). CONCLUSIONS: Our results showed that HTN is specifically related to the recurrent strokes in patients with small-vessel diseases, not other subtypes of IS.

Ischemic stroke classification is critical in conducting basic research and clinical practice. A precise analysis of stroke subtypes requires the integration of clinical features, findings from diagnostic tests, and knowledge about potential etiologic factors by competent diagnostic investigators. We performed a literature review of the published stroke classification systems and examined each for its benefits and limitations in the evaluation of the stroke etiology. Two major approaches to etiologic classifications of ischemic stroke are currently being used: the causative and phenotypic subtyping. The most widely used causative system is the Trial of Org 10172 in acute stroke treatment (TOAST) classification. With the advances in modern diagnostic technology, new stroke subclassification systems, such as the causative classification system (CCS) and Chinese ischemic stroke subclassification (CISS) system, have been developed to enhance the accuracy of TOAST. The A-S-C-O (Atherosclerosis, Small-vessel disease, Cardiac source, Other cause) phenotypic classification system makes efforts to identify the most likely etiology but not neglecting the possibility of other potential multiple causes. We conclude that the ideal stroke classification system needs to be valid, easy to use, evidence-based, and incorporate new information as it emerges.

Abstract Objective To test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis. Design Open label, blinded endpoint, randomised controlled phase II trial. Setting Prospective studies conducted at 26 centres in China, August 2015 to March 2017. Participants 675 patients with acute minor stroke or transient ischaemic attack. Intervention Ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset. Main outcome measures Primary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year. Results At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P&lt;0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P&lt;0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42). Conclusion Patients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations. Trial registration Clinicaltrials.gov NCT02506140 .

Importance: In China and other parts of the world, hospital personnel adherence to evidence-based stroke care is limited. Objective: To determine whether a multifaceted quality improvement intervention can improve hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke (AIS) in China. Design, Setting, and Participants: A multicenter, cluster-randomized clinical trial among 40 public hospitals in China that enrolled 4800 patients hospitalized with AIS from August 10, 2014, through June 20, 2015, with 12-month follow-up through July 30, 2016. Interventions: Twenty hospitals received a multifaceted quality improvement intervention (intervention group; 2400 patients), including a clinical pathway, care protocols, quality coordinator oversight, and performance measure monitoring and feedback. Twenty hospitals participated in the stroke registry with usual care (control group; 2400 patients). Main Outcomes and Measures: The primary outcome was hospital personnel adherence to 9 AIS performance measures, with co-primary outcomes of a composite of percentage of performance measures adhered to, and as all-or-none. Secondary outcomes included in-hospital mortality and long-term outcomes (a new vascular event, disability [modified Rankin Scale score, 3-5], and all-cause mortality) at 3, 6, and 12 months. Results: Among 4800 patients with AIS enrolled from 40 hospitals and randomized (mean age, 65 years; women, 1757 [36.6%]), 3980 patients (82.9%) completed the 12-month follow-up of the trial. Patients in intervention group were more likely to receive performance measures than those in the control groups (composite measure, 88.2% vs 84.8%, respectively; absolute difference, 3.54% [95% CI, 0.68% to 6.40%], P = .02). The all-or-none measure did not significantly differ between the intervention and control groups (53.8% vs 47.8%, respectively; absolute difference, 6.69% [95% CI, -0.41% to 13.79%], P = .06). New clinical vascular events were significantly reduced in the intervention group compared with the control group at 3 months (3.9% vs 5.3%, respectively; difference, -2.03% [95% CI, -3.51% to -0.55%]; P = .007), 6 months (6.3% vs 7.8%, respectively; difference, -2.18% [95% CI, -4.0% to -0.35%]; P = .02) and 12 months (9.1% vs 11.8%, respectively; difference, -3.13% [95% CI, -5.28% to -0.97%]; P = .005). Conclusions and Relevance: Among 40 hospitals in China, a multifaceted quality improvement intervention compared with usual care resulted in a statistically significant but small improvement in hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke when assessed as a composite measure, but not as an all-or-none measure. Further research is needed to understand the generalizability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02212912.

Background: In June 2015, the Chinese Stroke Association (CSA) initiated the Chinese Stroke Center Alliance (CSCA) to establish the national hospital-based stroke care quality assessment and improvement platform. This article outlines its objectives, operational structure, patient population, quality improvement (QI) intervention tools, data elements, data collection methodology and current patient and hospital data. Methods: The CSCA is a national, hospital-based, multicentre, voluntary, multifaceted intervention and continuous QI initiative. This multifaceted intervention includes stroke centre development, written care protocols, workshops and a monitoring/feedback system of evidence-based performance measures. The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital. Results: As of July 2017, 1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433 264 patients with acute stroke/transient ischaemic attacks (TIA), including 352 572 (81.38%) acute ischaemic stroke, 30 362 (7.01%) TIA, 42 080 (9.71%) spontaneous intracranial haemorrhage, 5505 (1.27%) subarachnoid haemorrhage and 2745 (0.63%) not specified stroke. Conclusion: The CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and, ultimately, improve patient outcomes. It supports the CSA mission to reduce stroke burden in China.

BACKGROUND AND PURPOSE: Stroke is a leading cause of death in China. Yet the adherence to guideline-recommended ischemic stroke performance metrics in the past decade has been previously shown to be suboptimal. Since then, several nationwide stroke quality management initiatives have been conducted in China. We sought to determine whether adherence had improved since then. METHODS: Data were obtained from the 2 phases of China National Stroke Registries, which included 131 hospitals (12 173 patients with acute ischemic stroke) in China National Stroke Registries phase 1 from 2007 to 2008 versus 219 hospitals (19 604 patients) in China National Stroke Registries phase 2 from 2012 to 2013. Multiple regression models were developed to evaluate the difference in adherence to performance measure between the 2 study periods. RESULTS: The overall quality of care has improved over time, as reflected by the higher composite score of 0.76 in 2012 to 2013 versus 0.63 in 2007 to 2008. Nine of 13 individual performance metrics improved. However, there were no significant improvements in the rates of intravenous thrombolytic therapy and anticoagulation for atrial fibrillation. After multivariate analysis, there remained a significant 1.17-fold (95% confidence interval, 1.14-1.21) increase in the odds of delivering evidence-based performance metrics in the more recent time periods versus older data. The performance metrics with the most significantly increased odds included stroke education, dysphagia screening, smoking cessation, and antithrombotics at discharge. CONCLUSIONS: Adherence to stroke performance metrics has increased over time, but significant opportunities remain for further improvement. Continuous stroke quality improvement program should be developed as a national priority in China.

BACKGROUND: Vitamin K antagonists are the only oral anticoagulants approved to prevent valve thrombosis and valve-related thromboembolism in patients with mechanical heart valves. Whether patients with an On-X mechanical aortic valve can be safely anticoagulated with apixaban is unknown. METHODS: Patients with an On-X aortic valve implanted at least 3 months before enrollment were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalized ratio 2.0 to 3.0). The primary efficacy end point was the composite of valve thrombosis or valve-related thromboembolism with coprimary analyses comparing apixaban with warfarin for noninferiority and comparing the apixaban event rate with an objective performance criterion (OPC). RESULTS: The trial was stopped after 863 participants were enrolled owing to an excess of thromboembolic events in the apixaban group. Most (94%) participants took aspirin. A total of 26 primary end-point events occurred, 20 (in 16 participants) in the apixaban group (4.2%/patient-year; 95% confidence interval [CI], 2.3 to 6.0) and 6 (in 6 participants) in the warfarin group (1.3%/patient-year; 95% CI, 0.3 to 2.3). The difference in primary end-point rates between the apixaban and warfarin groups was 2.9 (95% CI, 0.8 to 5.0); noninferiority and OPC success criteria were not met. Major bleeding rates were 3.6%/patient-year with apixaban and 4.5%/patient-year with warfarin. CONCLUSIONS: Apixaban did not demonstrate noninferiority to warfarin and is less effective than warfarin for the prevention of valve thrombosis or thromboembolism in patients with an On-X mechanical aortic valve. (Funded by Artivion; ClinicalTrials.gov number, NCT04142658.)

<h3>Objective</h3> Evidence about whether neutrophil counts or neutrophil ratio is associated with new stroke is scant. The aim of this study is to assess the association of neutrophil counts or neutrophil ratio with a new stroke in patients with minor stroke or TIA. <h3>Methods</h3> We derived data from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events trial. Patients with a minor stroke or TIA were categorized into 4 groups according to the quartile of neutrophil counts or neutrophil ratio. The primary outcome was a new stroke (ischemic or hemorrhagic), and secondary outcomes included a new composite vascular event (stroke, myocardial infarction, or death resulting from cardiovascular causes) and ischemic stroke during the 90-day follow-up. We assessed the association between neutrophil counts, neutrophil ratio, and risk of new stroke. <h3>Results</h3> A total of 4,854 participants were enrolled, among whom 495 had new strokes at 90 days. Compared with the first quartile, the second, third, and fourth quartiles of neutrophil counts were associated with increased risk of new stroke (adjusted hazard ratio 1.40 [95% confidence interval (CI) 1.05–1.87], 1.55 [95% CI 1.17–2.05], and 1.69 [95% CI 1.28–2.23], respectively, <i>p</i> for trend &lt;0.001). Similar results were observed for the endpoint of composite events and ischemic stroke. Parallel results were found for neutrophil ratio. <h3>Conclusion</h3> High levels of both neutrophil counts and neutrophil ratio were associated with an increased risk of new stroke, composite events, and ischemic stroke in patients with a minor ischemic stroke or TIA.

BACKGROUND: The last update of the consensus statement on intravenous recombinant tissue plasminogen activator (IV rt-PA) for acute ischemic stroke (AIS) by the Chinese Stroke Therapy Expert Panel was published in 2006. Great progress has been made since then. AIM: To provide another update on the new knowledge of IV rt-PA for AIS since 7 years ago. METHOD: In summer of 2012, the Chinese Stroke Therapy Expert Panel was reconvened. New publications on the use of IV rt-PA for AIS were reviewed. In addition, all newly published consensus and guidelines from other countries were reviewed. The 2006 version of Chinese Consensus was then updated. RESULTS: There is now clinical evidence to support the use of IV rt-PA between 3 and 4.5 h after the onset with several exclusion criteria. More studies are needed to provide the evidence for IV rt-PA use beyond 4.5 h. There is benefit giving IV rt-PA within 3 h to patients who are older than 80 and in patients with ongoing atrial fibrillation. Patients with INR<1.7 while on warfarin, minor strokes, rapid improving strokes and severe strokes should be treated and can all be benefited from IV rt-PA. DISCUSSION: Since IV rt-PA was initially recommended in 1996, there is now more evidence support its use, efficacy and safety. The treatment time window is also being expanded. More public education on stroke recognition are needed so many stroke patients may benefit from the treatment. CONCLUSION: The 2013 version of Chinese IV rt-PA consensus contains the most up-to-date information on the use of IV rt-PA for AIS. It will be a useful tool and guideline to provide appropriate thrombolytic therapy to stroke patients who meet the criteria.

BACKGROUND AND PURPOSE: We aimed to determine the association between stress hyperglycemia and risk of new stroke in patients with a minor ischemic stroke or transient ischemic attack. METHODS: A subgroup of 3026 consecutive patients from 73 prespecified sites of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Stress hyperglycemia was measured by glucose/glycated albumin (GA) ratio. Glucose/GA ratio was calculated by fasting plasma glucose divided by GA and categorized into 4 even groups according to the quartiles. The primary outcome was a new stroke (ischemic or hemorrhagic) at 90 days. We assessed the association between glucose/GA ratio and risk of stroke by multivariable Cox regression models adjusted for potential covariates. RESULTS: Among 3026 patients included, a total of 299 (9.9%) new stroke occurred at 3 months. Compared with patients with the lowest quartile, patients with the highest quartile of glucose/GA ratio was associated with an increased risk of stroke at 3 months after adjusted for potential covariates (12.0% versus 9.2%; adjusted hazard ratio, 1.46; 95% confidence interval, 1.06-2.01). Similar results were observed after further adjusted for fasting plasma glucose. We also observed that higher level of glucose/GA ratio was associated with an increased risk of stroke with a threshold of 0.29 using a Cox regression model with restricted cubic spline. CONCLUSIONS: Stress hyperglycemia, measured by glucose/GA ratio, was associated with an increased risk of stroke in patients with a minor ischemic stroke or transient ischemic attack. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

This article describes OSF Healthcare's recent journey in patient safety. It discusses the involvement of its 6 hospitals in collaboration with each other and the Institute for Healthcare Improvement. OSF focused on a strategy for decreasing adverse drug events (ADEs). They worked on impacting 4 major areas: safety culture, high-risk medication, dispensing of medication, and medication reconciliation. By doing this, OSF decreased its rate of ADEs per 1000 units of medication administered from 3.84 to 1.39 over the course of 20 months.

Stroke is The first two authors contributed equally. the leading cause of death and adult disability in China. Although evidence-based clinical interventions have been identified to improve care and outcomes in stroke, significant gaps still exist between guideline recommendations and clinical practice in China. Regional and national stroke registries have been used to assess the benchmark of stroke care quality, provide feedback on compliance with evidence-based performance measures to health care providers, and continuously improve stroke care quality without increasing additional medical costs in the past several decades worldwide. In China, stroke care has become a national priority. A series of stroke care quality assessment and improvement actions was initiated by the Ministry of Health to increase the detection of high-risk populations with stroke, rate of adherence to evidence-based process performance measures of stroke care, and stroke care organization development, aiming to decrease the burden of stroke. China National Stroke Registries have been started in 2007, and they are conducted every 3 to 5 years. A carotid disease screen and intervention project for communities was initiated in 2009. The Chinese Stroke Association, founded in 2015, launched the Chinese Stroke Center Alliance to increase the stroke center design in the near future. In this article, we described these stroke care actions and progression, summarized the benchmark and improvement of stroke care quality, and outlined the future plans in China.

BACKGROUND AND PURPOSE: Several retrospective studies suggested that contrast extravasation on CT angiography predicts hematoma expansion, poor outcome, and mortality in primary intracerebral hemorrhage. We aimed to determine the predictive value of contrast extravasation on multidetector CT angiography for clinical outcome in a prospective study. METHODS: In 160 consecutive patients with spontaneous intracerebral hemorrhage admitted within 6 hours of symptom onset, noncontrast CT and multidetector CT angiography were performed on admission. A follow-up noncontrast CT was done at 24 hours. Multidetector CT angiography images were analyzed to identify the presence of contrast extravasation. Clinical outcome was assessed by modified Rankin Scale on discharge and at 90 days. RESULTS: A total of 139 patients with primary intracerebral hemorrhage were included in the final analysis. Contrast extravasation occurred in 30 (21.6%) patients. The presence of contrast extravasation was associated with increased hematoma expansion (P<0.0001), in-hospital mortality (P=0.008), prolonged hospital stay (P=0.006), poor outcome on discharge (P=0.025), increased 3-month mortality (P=0.009), and poor clinical outcome (P<0.0001). In multivariate analysis, contrast extravasation was a promising independent predictor (OR, 10.5; 95% CI, 3.2-34.7; P<0.0001) for 90-day poor clinical outcome followed by the presence of intraventricular hemorrhage (OR, 3.4; 95% CI, 1.5-7.7; P=0.003) and initial hematoma volume (OR, 1.0; 95% CI, 1.0-1.1; P=0.013). CONCLUSIONS: The presence of contrast extravasation on multidetector CT angiography in patients with hyperacute-stage intracerebral hemorrhage is an independent and strong factor associated with poor outcome. Any patient with intracerebral hemorrhage with such sign on multidetector CT angiography should be monitored intensely and treated accordingly.