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BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is a pivotal clinical tool used to assess patients with acute stroke. However, substantial heterogeneity in the application and interpretation of stroke scale items can occur. This systematic review aimed to elucidate heterogeneity in measuring the NIHSS. MATERIAL AND METHODS: A literature search was performed on PubMed/OVID/Cochran's CENTRAL from inception to 2023. The references of the included papers were reviewed for further eligible articles. Clinical characteristic, NIHSS values, and sources of heterogeneity were recorded. Non-human and non-English language articles were excluded. The study quality was assessed using MINORS and GRADE. Meta-analysis and meta-regression were performed using a random-effects model to explore the sources of heterogeneity. RESULTS: Twenty-one papers for a total of 818 patients (mean per study: 39 ± 37) and 9696 NIHSS examinations (median per study: 8 [CI95% 2 to 42]) were included. Motor function had a higher ICC agreement (ranging from 0.85 ["Right Leg"] to 0.90 ["Right Arm"]) compared to the remaining items (ranging from 0.58 ["Facial Palsy"] to 0.85 ["Level of consciousness commands"]. The meta-regression showed a low effect size of covariates such as language version, remote evaluation, and retrospective analysis on NIHSS items (e.g., for "Level of consciousness commands," language effect was 0.30 [CI95% 0.20 to 0.48] and for "Visual", the retrospective assessment effect was -0.27 [CI95% -0.51 to -0.03]). CONCLUSION: The NIHSS scores showed moderate to excellent inter-rater agreement, with the highest heterogeneity in non-motor function evaluation. Using a non-English version, remote evaluation and retrospective analysis had small effects in terms of heterogeneity in the NIHSS scores.
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BACKGROUND: Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs fall under several overarching design groups, including adaptive designs (AD) and multi-arm (MA) designs. Factorial clinical trials designs represent a combination of factorial and MAMS trial designs and can provide increased efficiency relative to fixed, traditional designs. We explore design choices associated with Factorial Adaptive Multi-Arm Multi-Stage (FAST) designs, which represent the combination of factorial and MAMS designs. METHODS: Simulation studies were conducted to assess the impact of the type of analyses, the timing of analyses, and the effect size observed across multiple outcomes on trial operating characteristics for a FAST design. Given multiple outcomes types assessed within the hypothetical trial, the primary analysis approach for each assessment varied depending on data type. RESULTS: The simulation studies demonstrate that the proposed class of FAST trial designs can offer a framework to potentially provide improvements relative to other trial designs, such as a MAMS or factorial trial. Further, we note that the design implementation decisions, such as the timing and type of analyses conducted throughout trial, can have a great impact on trial operating characteristics. CONCLUSIONS: Motivated by a trial currently under design, our work shows that the FAST category of trial can potentially offer benefits similar to both MAMS and factorial designs; however, the chosen design aspects which can be included in a FAST trial need to be thoroughly explored during the planning phase.
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Ensayos Clínicos como Asunto , Simulación por Computador , Proyectos de Investigación , Humanos , Ensayos Clínicos como Asunto/métodos , Interpretación Estadística de Datos , Factores de Tiempo , Resultado del Tratamiento , Determinación de Punto Final , Tamaño de la Muestra , Modelos EstadísticosRESUMEN
Heart failure (HF) is an important comorbidity for patients with ischemic stroke, present in 11 %-18 % of patients, and may also independently increase the risk of first-ever and recurrent ischemic stroke. HF is categorized based on ejection fraction (EF) into HF with reduced (HFrEF), mildly-reduced (HFmrEG) and preserved ejection fraction (HFpEF), with the efficacy of HF therapies differing between the three subcategories. Despite this classification, the incidence, recurrence rates and outcomes of ischemic stroke do not appear to differ significantly between the three subtypes, even when considering the concurrent presence of atrial fibrillation. However, several randomized-controlled clinical trials of anticoagulation defined HF based on reduced EF, inevitably excluding a large proportion of patients with HFpEF. This exclusion is significant considering marked differences between heart failure phenotypes. Such discrepancies raise concerns about the broad applicability of the results of these studies, including those of primary or secondary stroke prevention in HF. Future trials should include both patients with HFrEF and HFpEF to evaluate the safety and efficacy of antiocoagulation therapies in primary and secondary stroke prevention across the spectrum of the EF.
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BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. CONCLUSION: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05757869.
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Fibrilación Atrial , Inhibidores del Factor Xa , Pirazoles , Piridonas , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Piridonas/efectos adversos , Método Doble Ciego , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Masculino , Femenino , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Aleteo Atrial/complicaciones , Hemorragia/inducido químicamente , Persona de Mediana Edad , Anciano , Factor XIa/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversosRESUMEN
Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.
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Aspirina , Inhibidores del Factor Xa , Accidente Cerebrovascular Isquémico , Neoplasias , Pirazoles , Piridonas , Humanos , Piridonas/uso terapéutico , Piridonas/efectos adversos , Masculino , Femenino , Aspirina/uso terapéutico , Aspirina/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Anciano , Persona de Mediana Edad , Método Doble Ciego , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/epidemiología , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Hemorragia/inducido químicamenteAsunto(s)
Fibrilación Atrial , Cardiopatías Congénitas , Accidente Cerebrovascular Isquémico , Humanos , Fibrilación Atrial/epidemiología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/prevención & control , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/complicaciones , Factores de Riesgo , Medición de RiesgoRESUMEN
BACKGROUND: ARCADIA compared apixaban to aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. One possible explanation for the neutral result is that biomarkers used did not optimally identify atrial cardiopathy. We examined the relationship between biomarker levels and subsequent detection of AF, the hallmark of atrial cardiopathy. METHODS: Patients were randomized if they met criteria for atrial cardiopathy, defined as P-wave terminal force >5000 µV*ms in ECG lead V1 (PTFV1), NT-proBNP >250 pg/mL, or left atrial diameter index (LADI) ⩾3 cm/m2. For this analysis, the outcome was AF detected per routine care. RESULTS: Of 3745 patients who consented to screening for atrial cardiopathy, 254 were subsequently diagnosed with AF; 96 before they could be randomized and 158 after randomization. In unadjusted analyses, ln(NT-proBNP) (RR per SD, 1.99; 95% CI, 1.85-2.13), PTFV1 (RR per SD, 1.15; 95% CI, 1.03-1.28) and LADI (RR per SD, 1.34; 95% CI, 1.20-1.50) were associated with AF. In a model containing all 3 biomarkers, demographics, and AF risk factors, age (RR per 10 years, 1.24; 95% CI, 1.09-1.41), ln(NT-proBNP) (RR per SD, 1.88; 95% CI, 1.67-2.11) and LADI (RR per SD, 1.25; 95% CI, 1.14-1.37) were associated with AF. These three variables together had a c-statistic of 0.82 (95% CI, 0.79-0.85) but only modest calibration. Discrimination was attenuated in sensitivity analyses of patients eligible for randomization who may have been more closely followed for AF. CONCLUSIONS: Biomarkers used to identify atrial cardiopathy in ARCADIA were moderately predictive of subsequent AF.
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Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden.
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COVID-19 , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/terapia , COVID-19/complicaciones , Ensayos Clínicos Pragmáticos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Teorema de Bayes , Proyectos de Investigación , SARS-CoV-2 , Lagunas en las EvidenciasRESUMEN
BACKGROUND: Previous cohort studies of hospitalized patients with a delayed diagnosis of ischemic stroke found that these patients often had an initial emergency department (ED) diagnosis of a fall. We sought to evaluate whether ED visits for a fall resulting in discharge to home (ie, treat-and-release visits) were associated with increased short-term ischemic stroke risk. METHODS: A case-crossover design was used to compare ED visits for falls during case periods (0-15, 16-30, 31-90, and 91-180 days before stroke) and control periods (equivalent time periods exactly 1 year before stroke) using administrative data from the Healthcare Cost and Utilization Project on all hospital admissions and ED visits across 10 states from 2016 to 2020. To identify ED treat-and-release visits for a fall and patients hospitalized for acute ischemic stroke, we used previously validated International Classification of Diseases, Tenth Revision, Clinical Modification codes. Odds ratios and 95% CIs were calculated using conditional logistic regression. RESULTS: Among 90â 592 hospitalized patients with ischemic stroke, 5230 (5.8%) had an ED treat-and-release visit for a fall within 180 days before their stroke. Patients with an ED treat-and-release visit for a fall were older (mean age, 74.7 [SD, 14.6] versus 70.8 [SD, 15.1] years), more often female (61.9% versus 53.4%), and had higher rates of vascular comorbidities than other patients with stroke. ED treat-and-release visits for a fall were significantly more common in the 15 days before stroke compared with the 15-day control period 1 year earlier (odds ratio, 2.7 [95% CI, 2.4-3.1]). The association between stroke and a preceding ED treat-and-release visit for a fall decreased in magnitude with increasing temporal distance from stroke. CONCLUSIONS: ED treat-and-release visits for a fall are associated with significantly increased short-term ischemic stroke risk. These visits may be opportunities to improve stroke diagnostic accuracy and treatment in the ED.
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Accidentes por Caídas , Servicio de Urgencia en Hospital , Humanos , Femenino , Masculino , Servicio de Urgencia en Hospital/estadística & datos numéricos , Anciano , Accidentes por Caídas/estadística & datos numéricos , Persona de Mediana Edad , Anciano de 80 o más Años , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/terapia , Factores de Riesgo , Estudios Cruzados , Alta del Paciente/estadística & datos numéricos , Hospitalización/estadística & datos numéricosRESUMEN
INTRODUCTION: Among stroke patients with atrial fibrillation (AF), it is not uncommon to identify carotid atherosclerosis. This study aimed to estimate the prevalence of, and factors associated with, carotid atherosclerosis among patients with AF and acute ischemic stroke. PATIENTS AND METHODS: Prospectively collected data from consecutive patients with anterior ischemic stroke and AF who underwent carotid imaging from 10 stroke registries were categorized retrospectively according to the degree of stenosis in: no atherosclerosis, stenosis <50%, stenosis ≥50%, and occlusion. Logistic regression analysis was used to identify factors associated with ipsilateral carotid atherosclerosis. RESULTS: Among 2,955 patients with ischemic stroke and AF, carotid atherosclerosis was evident in 1,022 (34.6%) patients, while carotid stenosis ≥50% and occlusion were identified in 204 (6.9%) and 168 (5.7%) patients, respectively. Ipsilateral carotid stenosis ≥50% or occlusion was associated with higher age (OR: 1.15, 95% CI: 1.01-1.32, per decade), previous ischemic stroke or transient ischemic attack (OR: 1.70, 95% CI: 1.29-2.25), peripheral artery disease (OR: 1.85, 95% CI: 1.23-2.78), coronary artery disease (OR: 1.53, 95% CI: 1.16-2.04), and statin treatment on admission (OR: 1.30, 95% CI: 1.01-1.67). Patients with lacunar stroke had a lower likelihood of stenosis ≥50% or occlusion (OR: 0.29, 95% CI: 0.13-0.68). Compared to the absence of atherosclerotic disease, atherosclerosis in one and two arterial beds was associated with the identification of ipsilateral carotid stenosis (OR: 1.49, 95% CI: 1.22-2.98 and OR: 3.18, 95% CI: 1.85-5.49, respectively). CONCLUSION: Among acute ischemic stroke patients with AF, 1 out of 3 had ipsilateral carotid atherosclerosis, and 1 out of 8 had ipsilateral carotid stenosis ≥50% or occlusion. Atherosclerosis in two arterial beds was the most important predictor for the identification of ipsilateral carotid stenosis. Among ischemic stroke patients with AF, carotid atherosclerosis is common, while carotid imaging should not be overlooked, especially in those with coronary or/and peripheral artery disease.
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BACKGROUND: Cirrhosis is associated with an increased risk of hemorrhagic stroke. Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. The objective of this study was to test the hypothesis that elevated Fibrosis-4 (FIB-4) index, indicating a high probability of liver fibrosis, is associated with an increased risk of hemorrhagic stroke. METHODS: We performed a cohort analysis of the prospective United Kingdom Biobank cohort study. Participants 40-69 years old were enrolled between 2007 and 2010 and had available follow-up data until March 1, 2018. We excluded participants with prevalent hemorrhagic stroke or thrombocytopenia. High probability of liver fibrosis was defined as having a value >2.67 of the validated FIB-4 index. The primary outcome was hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), defined based on hospitalization and death registry data. Secondary outcomes were intracerebral and subarachnoid hemorrhage, separately. We used Cox proportional hazards models to evaluate the association of FIB-4 index >2.67 with hemorrhagic stroke while adjusting for potential confounders including hypertension, alcohol use, and antithrombotic use. RESULTS: Among 452,994 participants (mean age, 57 years; 54% women), approximately 2% had FIB-4 index >2.67, and 1241 developed hemorrhagic stroke. In adjusted models, FIB-4 index >2.67 was associated with an increased risk of hemorrhagic stroke (HR, 2.0; 95% CI, 1.6-2.6). Results were similar for intracerebral hemorrhage (HR, 2.0; 95% CI, 1.5-2.7) and subarachnoid hemorrhage (HR, 2.2; 95% CI, 1.5-3.5) individually. CONCLUSIONS: Elevated FIB-4 index was associated with an increased risk of hemorrhagic stroke.
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INTRODUCTION: Atrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on outcomes of cancer-related stroke. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study using the 2016-2019 National Inpatient Sample, identifying all hospitalizations with diagnosis codes for cancer and AIS. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge to non-home locations. We used multiple logistic and linear regression models, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes. RESULTS: Among 150,200 hospitalizations with diagnoses of cancer and AIS (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% [95% CI, 14.0%-15.6%] vs 12.1% [95% CI, 11.6%-12.5%]) and non-home discharge disposition (83.5% [95% CI, 82.7%-84.3%] vs 75.1% [95% CI, 74.5%-75.7%]) as well as longer mean length-of-stay (8.4 days [95% CI, 8.2-8.6 days] vs 8.2 days [95% CI, 8.0-8.3 days]). In multivariable analyses, AF remained independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR], 1.34; 95% CI, 1.24-1.46), non-home discharge disposition (aOR, 1.32; 95% CI, 1.23-1.42), and longer length-of-stay (adjusted mean difference, 13.7%; 95% CI, 10.9%-16.7%). DISCUSSION AND CONCLUSION: In cancer-related AIS, comorbid AF is associated with worse short-term outcomes, including higher odds for in-hospital mortality, poor discharge disposition, and longer hospital stays.
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Importance: Extracranial internal carotid artery stenosis (50-99% arterial narrowing) is an important risk factor for ischemic stroke. Yet, the benefits and harms of targeted screening for asymptomatic carotid artery stenosis (ACAS) have not been assessed in population-based studies. Objective: To estimate the cost-effectiveness of one-time, targeted ACAS screening stratified by atherosclerotic cardiovascular disease (ASCVD) risk using the American Heart Association's Pooled Cohort Equations. Design Setting and Participants: We developed a lifetime microsimulation model of ACAS and stroke for a hypothetical cohort representative of US adults aged 50-80 years without stroke history. We used the Cardiovascular Health Study to estimate the probability and severity of ACAS based on individual characteristics (e.g., age, sex, smoking status, blood pressure, and cholesterol). Stroke risks were functions of these characteristics and ACAS severity. In the model, individuals testing positive for >70% stenosis with Duplex ultrasound and a confirmatory diagnostic test undergo revascularization, which may reduce the risk of stroke but also introduces complication risks. Diagnostic performance parameters, revascularization benefits and risks, utility weights, and costs were estimated from published sources. Cost-effectiveness was assessed from the health care sector perspective using a $100,000/quality-adjusted life year (QALY) threshold. Main Outcomes and Measures: Estimated stroke events prevented, lifetime costs, QALYs, and incremental cost-effectiveness ratios (ICERs) associated with ACAS screening. Costs (2023 USD) and QALYs were discounted at 3% annually. Results: We found that screening individuals with a 10-year ASCVD risk >30% was the most cost-effective strategy, with an ICER of $89,000/QALY. This strategy would make approximately 11.9% of the population eligible for screening, averting an estimated 24,084 strokes. Results were sensitive to variations in the efficacy and complication risk of revascularization. In probabilistic sensitivity analysis, screening those in lower ASCVD risk groups (0-20%) only had a 0.6% chance of being cost-effective. Conclusion and Relevance: A one-time screening may only be cost-effective for adults at a relatively high ASCVD risk. Our findings provide a framework that can be adapted as future clinical trial data continue to improve our understanding of the role of revascularization and intensive medical therapy in contemporary stroke prevention secondary to carotid disease.
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Fibrilación Atrial , Inhibidores del Factor Xa , Accidente Cerebrovascular Isquémico , Pirazoles , Piridonas , Prevención Secundaria , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Inhibidores del Factor Xa/uso terapéutico , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/prevención & control , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Recurrencia , Accidente Cerebrovascular/prevención & control , Persona de Mediana Edad , Anciano , Negro o Afroamericano , Factores Sexuales , Masculino , Femenino , Biomarcadores/análisis , Péptido Natriurético Encefálico/análisis , ElectrocardiografíaRESUMEN
Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists' review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists' diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier's diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.
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BACKGROUND: Chronic hypertension is an established long-term risk factor for major adverse cardiovascular events (MACEs). However, little is known about short-term MACE risk after hypertensive urgency, defined as an episode of acute severe hypertension without evidence of target-organ damage. We sought to evaluate the short-term risk of MACE after an emergency department (ED) visit for hypertensive urgency resulting in discharge to home. METHODS: We performed a case-crossover study using deidentified administrative claims data. Our case periods were 1-week intervals from 0 to 12 weeks before hospitalization for MACE. We compared ED visits for hypertensive urgency during these case periods versus equivalent control periods 1 year earlier. Hypertensive urgency and MACE components were all ascertained using previously validated International Classification of Diseases, Tenth Revision Clinical Modification codes. We used McNemar test for matched data to calculate risk ratios. RESULTS: Among 2â 225â 722 patients with MACE, 1â 893â 401 (85.1%) had a prior diagnosis of hypertension. There were 4644 (0.2%) patients who had at least 1 ED visit for hypertensive urgency during the 12 weeks preceding their MACE hospitalization. An ED visit for hypertensive urgency was significantly more common in the first week before MACE compared with the same chronological week 1 year earlier (risk ratio, 3.5 [95% CI, 2.9-4.2]). The association between hypertensive urgency and MACE decreased in magnitude with increasing temporal distance from MACE and was no longer significant by 11 weeks before MACE (risk ratio, 1.2 [95% CI, 0.99-1.6]). CONCLUSIONS: ED visits for hypertensive urgency were associated with a substantially increased short-term risk of subsequent MACE.
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Servicio de Urgencia en Hospital , Hipertensión , Humanos , Hipertensión/epidemiología , Hipertensión/complicaciones , Masculino , Femenino , Servicio de Urgencia en Hospital/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/epidemiología , Estudios Cruzados , Hospitalización/estadística & datos numéricos , Factores de Riesgo , Medición de Riesgo/métodos , Adulto , Visitas a la Sala de Emergencias , Crisis HipertensivaRESUMEN
One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.
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Accidente Cerebrovascular Embólico , Humanos , Accidente Cerebrovascular Embólico/etiología , Accidente Cerebrovascular Embólico/diagnóstico , Consenso , Factores de Riesgo , Medición de Riesgo , Europa (Continente)RESUMEN
BACKGROUND: Cardiac point-of-care ultrasound (cPOCUS) can aid in the diagnosis and treatment of cardiac disorders. Such disorders can arise as complications of acute brain injury, but most neurologic intensive care unit (NICU) providers do not receive formal training in cPOCUS. Caption artificial intelligence (AI) uses a novel deep learning (DL) algorithm to guide novice cPOCUS users in obtaining diagnostic-quality cardiac images. The primary objective of this study was to determine how often NICU providers with minimal cPOCUS experience capture quality images using DL-guided cPOCUS as well as the association between DL-guided cPOCUS and change in management and time to formal echocardiograms in the NICU. METHODS: From September 2020 to November 2021, neurology-trained physician assistants, residents, and fellows used DL software to perform clinically indicated cPOCUS scans in an academic tertiary NICU. Certified echocardiographers evaluated each scan independently to assess the quality of images and global interpretability of left ventricular function, right ventricular function, inferior vena cava size, and presence of pericardial effusion. Descriptive statistics with exact confidence intervals were used to calculate proportions of obtained images that were of adequate quality and that changed management. Time to first adequate cardiac images (either cPOCUS or formal echocardiography) was compared using a similar population from 2018. RESULTS: In 153 patients, 184 scans were performed for a total of 943 image views. Three certified echocardiographers deemed 63.4% of scans as interpretable for a qualitative assessment of left ventricular size and function, 52.6% of scans as interpretable for right ventricular size and function, 34.8% of scans as interpretable for inferior vena cava size and variability, and 47.2% of scans as interpretable for the presence of pericardial effusion. Thirty-seven percent of screening scans changed management, most commonly adjusting fluid goals (81.2%). Time to first adequate cardiac images decreased significantly from 3.1 to 1.7 days (p < 0.001). CONCLUSIONS: With DL guidance, neurology providers with minimal to no cPOCUS training were often able to obtain diagnostic-quality cardiac images, which informed management changes and significantly decreased time to cardiac imaging.
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Lesiones Encefálicas , Ecocardiografía , Neurología , Sistemas de Atención de Punto , Humanos , Lesiones Encefálicas/diagnóstico por imagen , Masculino , Femenino , Neurología/educación , Neurología/normas , Persona de Mediana Edad , Competencia Clínica/normas , Inteligencia Artificial , Anciano , Aprendizaje Profundo , Adulto , Internado y Residencia/normas , Unidades de Cuidados Intensivos , Asistentes Médicos/educación , Asistentes Médicos/normasRESUMEN
BACKGROUND: Rates of dual antiplatelet therapy (DAPT) after high-risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost-effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS. METHODS AND RESULTS: We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost-effectiveness ratio <$100 000 per quality-adjusted life year was considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed. From the payer perspective, a QI intervention was associated with $9657 in lifetime cost savings and 0.18 more quality-adjusted life years compared with current national treatment rates. A QI intervention was cost-effective in 73% of probabilistic sensitivity analysis iterations. Results were similar from the societal perspective. The maximum acceptable, initial, 1-time payer cost of a QI intervention was $28 032 per patient. A QI intervention that increased DAPT use to at least 51% was cost-effective in the base case. CONCLUSIONS: Increasing DAPT use after TIAMIS with a QI intervention is cost-effective over a wide range of costs and proportion of patients with TIAMIS treated with DAPT after implementation of a QI intervention. Our results support the development of future interventions focused on increasing DAPT use after TIAMIS.
Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Análisis Costo-Beneficio , Análisis de Costo-Efectividad , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamenteRESUMEN
Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.