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1.
J Neurol Sci ; : 117224, 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33183779

RESUMO

Although statins have been associated with increased risk of spontaneous intracerebral hemorrhage, their relationship with cerebral microbleeds (CMBs) formation is poorly understood. We systematically reviewed previously published studies reporting on the association between CMBs presence and current statin use. We performed a systematic search in MEDLINE and SCOPUS databases on October 24, 2019 to identify all cohorts from randomized-controlled clinical trials or observational studies reporting on CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Random effects model was used to calculate the pooled estimates. We included 7 studies (n = 3734 participants): unselected general population [n = 1965], ischemic stroke [n = 849], hemorrhagic stroke [n = 252] and patients with hypertension over the age of 60 [n = 668]. Statin use was not associated with CMBs presence in either unadjusted (OR = 1.15, 95%CI: 0.76-1.74) or adjusted analyses (OR = 1.09, 95%CI: 0.64-1.86). Statin use was more strongly related to lobar CMB presence (OR = 2.01, 95%CI: 1.48-2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR = 2.26, 95%CI: 0.86-5.91). Except for the analysis on the unadjusted probability of lobar CMBs presence, considerable heterogeneity was present in all other analyses (I2 > 60%). Our findings suggest that statin treatment seems not to be associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.

2.
Can J Cardiol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33191198

RESUMO

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, by 2020 a large number of developments had accumulated in a wide range of areas, motivating the committee to create a complete guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations system was used to grade recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.

3.
J Stroke Cerebrovasc Dis ; 29(11): 105228, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066882

RESUMO

BACKGROUND: This report aims to describe changes that centres providing transient ischaemic attack (TIA) pathway services have made to stay operational in response to the SARS-CoV-2 pandemic. METHODS: An international cross-sectional description of the adaptions of TIA pathways between 30th March and 6th May 2020. Experience was reported from 18 centres with rapid TIA pathways in seven countries (Australia, France, UK, Canada, USA, New Zealand, Italy, Canada) from three continents. RESULTS: All pathways remained active (n = 18). Sixteen (89%) had TIA clinics. Six of these clinics (38%) continued to provide in-person assessment while the majority (63%) used telehealth exclusively. Of these, three reported PPE use and three did not. Five centres with clinics (31%) had adopted a different vascular imaging strategy. CONCLUSION: The COVID pandemic has led TIA clinics around the world to adapt and move to the use of telemedicine for outpatient clinic review and modified investigation pathways. Despite the pandemic, all have remained operational.


Assuntos
Infecções por Coronavirus/terapia , Procedimentos Clínicos/tendências , Prestação Integrada de Cuidados de Saúde/tendências , Equipe de Respostas Rápidas de Hospitais/tendências , Ataque Isquêmico Transitório/terapia , Pneumonia Viral/terapia , Padrões de Prática Médica/tendências , Telemedicina/tendências , Austrália , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Estudos Transversais , Diagnóstico por Imagem/tendências , Europa (Continente) , Humanos , Ataque Isquêmico Transitório/diagnóstico , Nova Zelândia , América do Norte , Pandemias , Equipamento de Proteção Individual/tendências , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Tempo
4.
BMJ Open ; 10(10): e040466, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33055122

RESUMO

INTRODUCTION: Cerebral small vessel disease (cSVD) accounts for 20%-25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response. METHODS AND ANALYSIS: This prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60-85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13-24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests. ETHICS AND DISSEMINATION: Research Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings. TRIAL REGISTRATION NUMBER: NCT04109963.

5.
JAMA Neurol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074284

RESUMO

Importance: The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging. Objective: To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy. Design, Setting, and Participants: Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial. Interventions: Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. Main Outcomes and Measures: The primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality. Results: Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI, 1.54-3.15), multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P > .99). Conclusions and Relevance: Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.

6.
Stroke ; 51(10): 2901-2909, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32951537

RESUMO

BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.


Assuntos
Aspirina/uso terapêutico , Infarto Encefálico/prevenção & controle , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Quimioterapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento
7.
Can J Neurol Sci ; : 1-7, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32741386

RESUMO

BACKGROUND: We investigated the impact of regionally imposed social and healthcare restrictions due to coronavirus disease 2019 (COVID-19) to the time metrics in the management of acute ischemic stroke patients admitted at the regional stroke referral site for Central South Ontario, Canada. METHODS: We compared relevant time metrics between patients with acute ischemic stroke receiving intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy (EVT) before and after the declared restrictions and state of emergency imposed in our region (March 17, 2020). RESULTS: We identified a significant increase in the median door-to-CT times for patients receiving intravenous tPA (19 min, interquartile range (IQR): 14-27 min vs. 13 min, IQR: 9-17 min, p = 0.008) and/or EVT (20 min, IQR: 15-33 min vs. 11 min, IQR: 5-20 min, p = 0.035) after the start of social and healthcare restrictions in our region compared to the previous 12 months. For patients receiving intravenous tPA treatment, we also found a significant increase (p = 0.005) in the median door-to-needle time (61 min, IQR: 46-72 min vs. 37 min, IQR: 30-50 min). No delays in the time from symptom onset to hospital presentation were uncovered for patients receiving tPA and/or endovascular reperfusion treatments in the first 1.5 months after the establishment of regional and institutional restrictions due to the COVID-19 pandemic. CONCLUSION: We detected an increase in our institutional time to treatment metrics for acute ischemic stroke patients receiving tPA and/or endovascular reperfusion therapies, related to delays from hospital presentation to the acquisition of cranial CT imaging for both tPA- and EVT-treated patients, and an added delay to treatment with tPA.

8.
JAMA Neurol ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32628266

RESUMO

Importance: The concept of embolic stroke of undetermined source (ESUS) unifies a subgroup of cryptogenic strokes based on neuroimaging, a defined minimum set of diagnostic tests, and exclusion of certain causes. Despite an annual stroke recurrence rate of 5%, little is known about the etiology underlying recurrent stroke after ESUS. Objective: To identify the stroke subtype of recurrent ischemic strokes after ESUS, to explore the interaction with treatment assignment in each category, and to examine the consistency of cerebral location of qualifying ESUS and recurrent ischemic stroke. Design, Setting, and Participants: The NAVIGATE-ESUS trial was a randomized clinical trial conducted from December 23, 2014, to October 5, 2017. The trial compared the efficacy and safety of rivaroxaban and aspirin in patients with recent ESUS (n = 7213). Ischemic stroke was validated in 309 of the 7213 patients by adjudicators blinded to treatment assignment and classified by local investigators into the categories ESUS or non-ESUS (ie, cardioembolic, atherosclerotic, lacunar, other determined cause, or insufficient testing). Five patients with recurrent strokes that could not be defined as ischemic or hemorrhagic in absence of neuroimaging or autopsy were excluded. Data for this secondary post hoc analysis were analyzed from March to June 2019. Interventions: Patients were randomly assigned to receive rivaroxaban, 15 mg/d, or aspirin, 100 mg/d. Main Outcomes and Measures: Association of recurrent ESUS with stroke characteristics. Results: A total of 309 patients (205 men [66%]; mean [SD] age, 68 [10] years) had ischemic stroke identified during the median follow-up of 11 (interquartile range [IQR], 12) months (annualized rate, 4.6%). Diagnostic testing was insufficient for etiological classification in 39 patients (13%). Of 270 classifiable ischemic strokes, 156 (58%) were ESUS and 114 (42%) were non-ESUS (37 [32%] cardioembolic, 26 [23%] atherosclerotic, 35 [31%] lacunar, and 16 [14%] other determined cause). Atrial fibrillation was found in 27 patients (9%) with recurrent ischemic stroke and was associated with higher morbidity (median change in modified Rankin scale score 2 [IQR, 3] vs 0 (IQR, 1]) and mortality (15% vs 1%) than other causes. Risk of recurrence did not differ significantly by subtype between treatment groups. For both the qualifying and recurrent strokes, location of infarct was more often in the left (46% and 54%, respectively) than right hemisphere (40% and 37%, respectively) or brainstem or cerebellum (14% and 9%, respectively). Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, most recurrent strokes after ESUS were embolic and of undetermined source. Recurrences associated with atrial fibrillation were a minority but were more often disabling and fatal. More extensive investigation to identify the embolic source is important toward an effective antithrombotic strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.

9.
Neurology ; 95(5): e480-e487, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32651298

RESUMO

OBJECTIVE: Subdural hematomas (SDHs) are an uncommon, but important, complication of anticoagulation therapy. We hypothesized that the risks of SDH would be similar during treatment with oral factor Xa inhibitors compared with aspirin. METHODS: We assessed the frequency and the effects of antithrombotic treatments on SDHs in the recent international Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial comparing aspirin 100 mg daily, rivaroxaban 5 mg twice daily, and rivaroxaban 2.5 mg twice daily plus aspirin. A systematic review/meta-analysis of randomized trials comparing oral factor Xa inhibitors vs aspirin on SDH risk was undertaken. RESULTS: Among 27,395 COMPASS participants, 28 patients with SDHs were identified (mean age 72 years). SDH-associated mortality was 7%. Incidence was 0.06 per 100 patient-years (11 SDH/17,492 years observation) during the mean 23-month follow-up among aspirin-assigned patients and did not differ significantly between treatments. Three additional randomized controlled trials including 16,177 participants reported a total of 14 SDHs with an incidence ranging from 0.06 to 0.1 per 100 patient-years. Factor Xa inhibitor use was not associated with an increased risk of SDH compared to aspirin (odds ratio, 0.97; 95% confidence interval, 0.52-1.81; I2 = 0%). CONCLUSION: The frequency of SDH was similar in all 3 treatment arms of the COMPASS trial. The COMPASS trial results markedly increase the available evidence from randomized comparisons of oral factor Xa inhibitors with aspirin regarding SDH. From available, albeit limited, evidence from 4 randomized trials, therapeutic dosages of factor Xa inhibitors do not appear to increase the risk of SDH compared with aspirin. CLINICAL TRIAL IDENTIFIER NUMBER: NCT01776424.


Assuntos
Inibidores do Fator Xa/efeitos adversos , Hematoma Subdural Intracraniano/induzido quimicamente , Rivaroxabana/efeitos adversos , Idoso , Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Feminino , Hematoma Subdural Intracraniano/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Stroke ; 51(8): 2386-2394, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640945

RESUMO

BACKGROUND AND PURPOSE: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. METHODS: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. RESULTS: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41-1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25-0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification (P=0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment (P=0.3). CONCLUSIONS: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.


Assuntos
Embolia Intracraniana/sangue , Embolia Intracraniana/diagnóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Troponina T/sangue , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Biomarcadores/sangue , Método Duplo-Cego , Inibidores do Fator Xa/administração & dosagem , Feminino , Seguimentos , Humanos , Internacionalidade , Embolia Intracraniana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Medição de Risco , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico
11.
Stroke ; 51(6): 1797-1804, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295509

RESUMO

Background and Purpose- Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods- We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results- In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0-3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions- A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Embolia Intracraniana , Inibidores da Agregação de Plaquetas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Embolia Intracraniana/tratamento farmacológico , Embolia Intracraniana/mortalidade , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Prevalência , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Taxa de Sobrevida
12.
Stroke ; 51(3): 938-943, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31893985

RESUMO

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.


Assuntos
Infarto Encefálico , Cardiomegalia , Embolia Intracraniana , Placa Aterosclerótica , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral , Idoso , Biomarcadores/sangue , Infarto Encefálico/sangue , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/fisiopatologia , Cardiomegalia/sangue , Cardiomegalia/tratamento farmacológico , Cardiomegalia/fisiopatologia , Feminino , Átrios do Coração/fisiopatologia , Humanos , Embolia Intracraniana/sangue , Embolia Intracraniana/tratamento farmacológico , Embolia Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/fisiopatologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia
15.
JAMA Neurol ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31524941

RESUMO

Importance: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized clinical trial was stopped early owing to the efficacy of low-dose rivaroxaban plus aspirin in preventing major cardiovascular events. The main reason for early trial termination was the effect of combination therapy on reducing ischemic strokes. Objective: To analyze the association between low-dose rivaroxaban with or without aspirin and different ischemic stroke subtypes. Design, Setting, and Participants: This is a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study that was performed in 33 countries from March 12, 2013, to May 10, 2016. Patients with stable atherosclerotic vascular disease were eligible, and a total of 27 395 participants were randomized and followed up to February 6, 2017. All first ischemic strokes and uncertain strokes that occurred by this date were adjudicated using TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. The analysis of ischemic stroke subtypes was evaluated using an intention-to-treat principle. Statistical analysis was performed from March 12, 2013, to February 6, 2017. Interventions: Participants received rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban (5 mg twice a day), or aspirin (100 mg once a day). Main Outcomes and Measures: Risk of ischemic stroke subtypes during follow-up. Results: A total of 291 patients (66 women; mean [SD] age, 69.4 [8.5] years; 43 [14.8%] had a previous nonlacunar stroke) experienced an ischemic stroke. During the study, 49 patients (16.8%) received a diagnosis of atrial fibrillation. Applying TOAST criteria, 59 strokes (20.3%) were cardioembolic, 54 strokes (18.6%) were secondary to greater than 50% stenosis of the ipsilateral internal carotid artery, 42 strokes (14.4%) had a negative evaluation that met criteria for embolic stroke of undetermined source, and 21 strokes (7.2%) were secondary to small vessel disease. There were significantly fewer cardioembolic strokes (hazard ratio [HR], 0.40 [95% CI, 0.20-0.78]; P = .005) and embolic strokes of undetermined source (HR, 0.30 [95% CI, 0.12-0.74]; P = .006) in the combination therapy group compared with the aspirin-only group. A trend for reduction in strokes secondary to small vessel disease (HR, 0.36 [95% CI, 0.12-1.14]; P = .07) was not statistically significant. No significant difference was observed between the 2 groups in strokes secondary to greater than 50% carotid artery stenosis (HR, 0.85 [95% CI, 0.45-1.60]; P = .61). Rivaroxaban, 5 mg, twice daily showed a trend for reducing cardioembolic strokes compared with aspirin (HR, 0.57 [95% CI, 0.31-1.03]; P = .06) but was not associated with reducing other stroke subtypes. Conclusions and Relevance: For patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin was associated with large, significant reductions in cardioembolic strokes and embolic strokes of undetermined source. However, these results of exploratory analysis need to be independently confirmed before influencing clinical practice. Trial Registration: ClinicalTrials.gov identifier: NCT01776424.

16.
Indian J Dermatol ; 64(4): 285-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516137

RESUMO

Background: Currently, the studies related to hair loss in children showed the variable prevalence of different clinical patterns and causes of scalp hair loss, that had regional variation. Aims: The aim of this study is to evaluate the epidemiology and clinical pattern of scalp hair loss in children (0-18 years age group). Materials and Methods: A total of 300 children presenting with scalp hair loss were studied during a period of 1 year from April 2015 to March 2016. The results were recorded and analyzed. Results: The most common disorder found in this study was tinea capitis seen in 166 (55.33%) cases followed by alopecia areata, seborrheic dermatitis, pediculosis with secondary infection. Other uncommon causes were lichen planopilaris, tractional alopecia, telogen effluvium, nevus sebaceous, occipital neonatal alopecia, ectodermal dysplasia, scalp psoriasis, trichotillomania, and alopecia due to nutritional deficiency. Several other rare causes were identified in this study. Conclusion: This study showed that hair loss in children in our region is not an uncommon problem and results from a variety of causes. Early diagnosis and treatment are needed to prevent further hair loss and to avoid irreversible hair loss and scarring alopecia. As has been observed in this study, hair problem may be due to important nutritional deficiency. We should be aware of such presentation. These may be a clue to the diagnosis of systemic illness.

17.
J Water Health ; 17(4): 622-632, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313999

RESUMO

Drinking water quality plays a remarkable role in human infections and diseases. This study used polymerase chain reaction (PCR) techniques to detect bacterial pathogens. In addition, a physicochemical analysis was performed on drinking water samples from several sources. A total of 123 drinking water samples were collected from different areas in the Jazan region in Saudi Arabia: ground water (40 samples), bottled water (15 samples), tap water (52 samples), and water purification shops (16 samples). To isolate the bacterial pathogens, the water samples were spread on Nutrient and MacConkey agar media, and the grown pathogens were then identified by the 16S ribosomal RNA technique. In 87 (70.7%) of the 123 drinking water samples, there was no pathogen growth on the two-culture medium. However, 36 (29.3%) of the samples were found to be contaminated with bacteria. The physicochemical analysis indicated that the water samples were within the Saudi drinking water standards. The bacteria were resistant to Cefotaxime, Cefotaxime/Clavulanic acid, Erythromycin, Penicillin G, Rifampin and Sulfamethoxazole-Trimethoprim, respectively. The findings suggest that in Jazan, bottled water is a safer source of potable water than tap water. The contamination in the water may be occurring at the reservoirs rather than the water sources.


Assuntos
Água Potável , Humanos , Arábia Saudita , Microbiologia da Água , Qualidade da Água , Recursos Hídricos
18.
J Stroke Cerebrovasc Dis ; 28(8): 2273-2279, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160218

RESUMO

BACKGROUND: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Embolia Intracraniana/tratamento farmacológico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
19.
Trials ; 20(1): 313, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151483

RESUMO

BACKGROUND: Successful stroke trials require adequate recruitment. In this observational study, we assessed reasons for refusal to provide informed consent in eligible patients approached for clinical trial participation at the Vancouver Stroke Program. METHODS: We assessed screening logs from four trials that were actively recruiting at our center: three randomized trials, two of which investigated different antithrombotic strategies for secondary prevention (NAVIGATE-ESUS, NCT02313909 12/2014; DATAS-II, NCT02295826 11/2014) and one that investigated surgery plus medical management versus medical management alone for primary prevention (CREST-2, NCT02089217 03/2014). The fourth study was observational and non-randomized; all participants received an external monitoring device (PROPHECY, NCT03712865 10/2018). Screening logs from June 2015 to April 2017 were reviewed retrospectively. Subsequently, we used a prospective structured case report form for screening (May 2017-March 2018). We assessed and compared refusal rates between trials, demographics of those refusing consent, and their reasons for doing so. We used descriptive statistics, chi-square and Fisher's exact tests as appropriate for non-parametric data, and t-tests for parametric data. We examined likelihood of refusal by sex using multivariable logistic regression models including age and trial intervention as co-variables. RESULTS: A total of 235 patients (43% women) were approached for consent. More patients refused the surgical (59%) and antithrombotic trials (53%) compared with the non-randomized external monitoring device study (13%) (p < 0.001). Surgical trial refusals were primarily due to a desire for certainty in receiving a particular intervention (39%), with the majority of those patients wanting surgery. Refusals for the antithrombotic trials were mainly due to concerns with the potential side effects of the study drug (41%); refusals in the device trial were mainly due to disinterest (46%). Women refused participation more often than men (48% vs 33%). Women remained less likely to consent than men, even after adjustment for age and trial intervention (OR 0.46, 95% CI 0.26-0.82, p = 0.009). CONCLUSIONS: Concern surrounding drug safety, randomization, and disinterest were the chief deterrents to enrolment; there were also differences in rates of consent by gender. A better understanding of why patients refuse participation in stroke trials may help to develop future patient-directed communication strategies to improve enrolment. Further research is required to better understand the reasons underlying gender disparities in consent rates.


Assuntos
Ensaios Clínicos como Assunto , Recusa de Participação/estatística & dados numéricos , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
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