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1.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(8. Vyp. 2): 49-57, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33016677

RESUMO

AIM: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification. MATERIAL AND METHODS: The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60-65 years, 76-90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. RESULTS: The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0.001). The decrease in mean mRS score (Visit 1-5) was more prominent in patients aged 60-65 years (p=0.025), including patients with diabetes mellitus (DM). Patients aged 76-90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0.049 and p=0.02) and an increase in patients without problems with everyday activities (p=0.007 and p=0.02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0.023) and quality of life (p=0.045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. CONCLUSION: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Picolinas/efeitos adversos , Picolinas/uso terapêutico , Qualidade de Vida
2.
Medicine (Baltimore) ; 99(38): e22305, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957391

RESUMO

RATIONALE: A developmental venous anomaly (DVA) is the most common intracranial congenital anomaly and is mostly asymptomatic. Thrombosis rarely develops in a DVA due to hypercoagulation. We report a case of ischemic stroke in the area of a DVA after minor head trauma in a patient with DVA and without a predisposition thrombosis. PATIENT CONCERNS: A healthy 17-year-old male was admitted to the emergency room due to left hemiparesis, which was caused by a ball hitting the right side of his head during a soccer game. DIAGNOSIS: Brain magnetic resonance (MR) susceptibility-weighted image showed several small veins draining to the central vein in the area from the right posterior putamen to the periventricular white matter. INTERVENTIONS: We diagnosed the patient with an ischemic stroke associated with a DVA and administered antiplatelet agents. The patient's autoantibodies (including antiphospholipid antibody) and factors of blood coagulation were normal. OUTCOMES: The left hemiparesis of the patient worsened by the second day of admission. Moreover, high signal intensity was observed in the DVA region of the diffusion weighted image of brain MR. The patient's symptoms gradually improved afterward, and left hemiparesis recovered fully 3 weeks after the onset. LESSONS: DVAs may predispose to ischemic stroke due to thrombosis and hypercoagulation, although it is rare. It is necessary to consider the possibility of ischemic stroke due to minor head trauma, even without factors causing hypercoagulation.


Assuntos
Concussão Encefálica/complicações , Acidente Vascular Cerebral/etiologia , Adolescente , Concussão Encefálica/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Ventrículos Cerebrais/patologia , Imagem de Difusão por Ressonância Magnética , Humanos , Angiografia por Ressonância Magnética , Masculino , Inibidores da Agregação de Plaquetas/uso terapêutico , Futebol/lesões , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico
3.
Medicine (Baltimore) ; 99(36): e21958, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899031

RESUMO

INTRODUCTION: Wake up stroke starts in sleep and is a more common form of ischemic stroke. At present, it is still controversial whether wake up stroke can be treated with thrombolytic therapy. Therefore, this study will combine imaging techniques to assess the onset time of wake up stroke patients, and to analyze the imaging characteristics of wake up stroke patients and patients suitable for thrombolytic therapy within the time window. METHODS/DESIGN: This study will be a single-blinded, randomized controlled trial with 2 parallel groups. It will be conducted at North China University of science and technology affiliated hospital. DISCUSSION: There is no consistent conclusion about the pathogenesis of wake up stroke. Wake up stroke is more likely to manifest as small vessel disease. The incidence of wake up stroke patients is relatively high, and the effectiveness and safety of intravenous thrombolysis under the guidance of multimode imaging therapy in wake up stroke need to be further explored by prospective, large-scale studies. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000034402, Registered on 05 July 2020.


Assuntos
Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Ativador de Plasminogênio Tecidual/efeitos adversos
4.
BMJ Case Rep ; 13(9)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32907873

RESUMO

A 71-year-old man presented to the emergency department (ED) with low oxygen saturations and symptoms consistent with COVID-19 infection. Apart from a small left-sided ischaemic stroke 10 years prior with very minor residual deficit, he had been well and in full-time employment until development of symptoms. Within minutes of commencing non-invasive ventilation (NIV) in the ED, he developed a complete left-sided paralysis and hemineglect. This case highlights the significance of the prothrombotic complications associated with COVID-19 infection. It also raises the question whether pressure changes upon commencing NIV could lead to clot migration.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Ventilação não Invasiva/métodos , Pneumonia Viral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Doença Aguda , Idoso , Infecções por Coronavirus/terapia , Evolução Fatal , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pandemias , Pneumonia Viral/terapia , Respiração com Pressão Positiva/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X/métodos
5.
J Stroke Cerebrovasc Dis ; 29(10): 105047, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912511

RESUMO

COVID-19 is a pandemic disease which predominantly affects the respiratory system, however it also causes multi-organ dysfunction in a subset of patients. There is a growing evidence that it increases the propensity of strokes in younger patients. Besides producing a prothrombotic state, arterial dissection could be one of its many manifestations, increasing the risks of stroke. Herein, we report the first case of spontaneous bilateral vertebral artery dissection in a patient with COVID-19. 39-year female presented with spontaneous bilateral vertebral artery dissections without any instigating traumatic events and no history of connective tissue disorders. Whether this patient's vertebral artery dissections were triggered by exaggerated inflammatory response or arteriopathy secondary to COVID-19 remains speculative. Nonetheless, arterial dissection could be one of it's complications. It is important for the physicians to be aware of different clinical manifestations of COVID-19 as we manage these patients with no historical experience, to provide adequate care.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Acidente Vascular Cerebral/etiologia , Dissecação da Artéria Vertebral/etiologia , Adulto , Anticoagulantes/administração & dosagem , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/virologia , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/tratamento farmacológico , Dissecação da Artéria Vertebral/virologia
6.
Yakugaku Zasshi ; 140(8): 1007-1012, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741858

RESUMO

We previously showed that increased permeability of the blood-brain barrier (BBB) after ischemic stroke enables extravasation of nano-sized liposomes and accumulation in the ischemic region, and that delivery of neuroprotective agents using liposomal drug delivery systems (DDS) is applicable for treating cerebral ischemia/reperfusion (I/R) injury. However, entry of liposomes into the brain parenchyma was limited in the early stages after I/R possibly due to microvascular dysfunction induced by pathological progression. As such, new approaches to overcome the BBB are needed. Leukocytes can pass through inflamed BBB in I/R region due to membrane proteins displayed on their surface. We thus hypothesized that incorporation of leukocyte membrane proteins onto liposomal membranes would impart leukocyte-mimicking functions to liposomes and that leukocyte-mimetic liposomes (LM-Lipo) may pass through inflamed endothelial cells and BBB, similar to leukocytes. LM-Lipo prepared using intermembrane protein transfer from human leukemia cells showed significantly increased association to inflamed human umbilical vein endothelial cells relative to plain liposomes. Moreover, LM-Lipo passed through inflamed endothelial cell layer by regulating intercellular junctions. These results suggest that imparting leukocyte-like properties to liposomes via intermembrane protein transfer would be an effective strategy to overcome inflamed endothelial barriers. In this review, we describe our findings on ischemic stroke treatment using liposomal DDS and the potential of LM-Lipo to overcome inflamed endothelial barriers.


Assuntos
Barreira Hematoencefálica/metabolismo , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Leucócitos , Lipossomos/metabolismo , Proteínas de Membrana/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Humanos , Permeabilidade , Transporte Proteico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
8.
N Z Med J ; 133(1519): 41-54, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32777794

RESUMO

BACKGROUND: Concomitant atrial fibrillation (AF) and acute coronary syndrome (ACS) present the difficult therapeutic dilemma of balancing bleeding, cardio-embolic and coronary thrombotic risks with appropriate combinations of antithrombotic medications. We aim to evaluate current New Zealand practice by identifying the incidence of AF in ACS; describe the population characteristics; and assess our antithrombotic management. METHODS: Consecutive patients ≥18y presenting with ACS who had coronary angiography (2017-2018) were identified from the All New Zealand ACS Quality Improvement (ANZACS-QI) registry. The cohort was divided into three groups: 1) patients with pre-existing AF; 2) new-onset AF; and 3) no AF. Antithrombotic regimens included dual antiplatelet therapy (DAPT), dual antithrombotic therapy (DAT-single antiplatelet plus an oral anticoagulant (OAC)) and triple antithrombotic therapy (TAT). RESULTS: There were 9,489 patients, 9.6% with pre-existing AF, 4.4% new AF and 86% without AF. Both AF groups were older (median 74 vs 71 vs 65y, p=0.001), had poorer renal function, were more likely to present with heart failure (16% vs 19% vs 8%, p=0.001) and have left ventricular ejection fraction <40% (22% vs 28% vs 13%, p<0.001). They received less percutaneous coronary intervention (PCI) (53% vs 59% vs 70%, p=0.001). In the cohort, 25 different combinations of antithrombotic agents were utilised. Ninety-six percent of patients with any AF had a CHA2DS2VASC stroke risk score of ≥2, of whom 48% did not receive OAC. Twenty-four percent received TAT and 19% DAT. OAC use increased slightly with increasing stroke risk but were independent of CRUSADE bleeding risk. Of patients with AF treated with PCI, 53% received DAPT, 11% DAT and 35% TAT. 51% of those at high stroke risk were discharged on DAPT only. In contrast, 19% at low stroke risk received TAT. CONCLUSION: In New Zealand, one in seven patients presenting with ACS have AF, a third being new-onset AF. Antithrombotic management is inconsistent, with underutilisation of anticoagulants, particularly the DAT regimen, and is inadequately informed by stroke and bleeding risk scores.


Assuntos
Síndrome Coronariana Aguda , Fibrilação Atrial , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
9.
Cochrane Database Syst Rev ; 8: CD013066, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32860632

RESUMO

BACKGROUND: Stroke is one of the leading causes of long-lasting disability and mortality and its global burden has increased in the past two decades. Several therapies have been proposed for the recovery from, and treatment of, ischemic stroke. One of them is citicoline. This review assessed the benefits and harms of citicoline for treating patients with acute ischemic stroke. OBJECTIVES: To assess the clinical benefits and harms of citicoline compared with placebo or any other control for treating people with acute ischemic stroke. SEARCH METHODS: We searched in the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS until 29 January 2020. We searched the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. Additionally, we also reviewed reference lists of the retrieved publications and review articles, and searched the websites of the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). SELECTION CRITERIA: We included randomized controlled trials (RCTs) in any setting including participants with acute ischemic stroke. Trials were eligible for inclusion if they compared citicoline versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: We selected RCTs, assessed the risk of bias in seven domains, and extracted data by duplicate. Our primary outcomes of interest were all-cause mortality and the degree of disability or dependence in daily activities at 90 days. We estimated risk ratios (RRs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed-effect and random-effects model meta-analyses. We assessed the overall quality of evidence for six pre-specified outcomes using the GRADE approach. MAIN RESULTS: We identified 10 RCTs including 4281 participants. In all these trials, citicoline was given either orally, intravenously, or a combination of both compared with placebo or standard care therapy. Citicoline doses ranged between 500 mg and 2000 mg per day. We assessed all the included trials as having high risk of bias. Drug companies sponsored six trials. A pooled analysis of eight trials indicates there may be little or no difference in all-cause mortality comparing citicoline with placebo (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07; I² = 0%; low-quality evidence due to risk of bias). Four trials found no difference in the proportion of patients with disability or dependence in daily activities according to the Rankin scale comparing citicoline with placebo (21.72% versus 19.23%; RR 1.11, 95% CI 0.97 to 1.26; I² = 1%; low-quality evidence due to risk of bias). Meta-analysis of three trials indicates there may be little or no difference in serious cardiovascular adverse events comparing citicoline with placebo (8.83% versus 7.77%; RR 1.04, 95% CI 0.84 to 1.29; I² = 0%; low-quality evidence due to risk of bias). Overall, either serious or non-serious adverse events - central nervous system, gastrointestinal, musculoskeletal, etc. - were poorly reported and harms may have been underestimated. Four trials assessing functional recovery with the Barthel Index at a cut-off point of 95 points or more did not find differences comparing citicoline with placebo (32.78% versus 30.70%; RR 1.03, 95% CI 0.94 to 1.13; I² = 24%; low-quality evidence due to risk of bias). There were no differences in neurological function (National Institutes of Health Stroke Scale at a cut-off point of ≤ 1 points) comparing citicoline with placebo according to five trials (24.31% versus 22.44%; RR 1.08, 95% CI 0.96 to 1.21; I² = 27%, low-quality evidence due to risk of bias). A pre-planned Trial Sequential Analysis suggested that no more trials may be needed for the primary outcomes but no trial provided information on quality of life. AUTHORS' CONCLUSIONS: This review assessed the clinical benefits and harms of citicoline compared with placebo or any other standard treatment for people with acute ischemic stroke. The findings of the review suggest there may be little to no difference between citicoline and its controls regarding all-cause mortality, disability or dependence in daily activities, severe adverse events, functional recovery and the assessment of the neurological function, based on low-certainty evidence. None of the included trials assessed quality of life and the safety profile of citicoline remains unknown. The available evidence is of low quality due to either limitations in the design or execution of the trials.


Assuntos
Citidina Difosfato Colina/uso terapêutico , Nootrópicos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Atividades Cotidianas , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Viés , Isquemia Encefálica/complicações , Causas de Morte , Citidina Difosfato Colina/efeitos adversos , Humanos , Pessoa de Meia-Idade , Nootrópicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
10.
Medicine (Baltimore) ; 99(32): e21594, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769914

RESUMO

BACKGROUND: To evaluate the effect of dl-3-N-butylphthalide (NBP) on new cerebral microbleeds (CMBs) in patients with acute ischemic stroke (AIS). METHODS: We will prospectively enroll patients with AIS admitted to the stroke center of Jingjiang People's Hospital. Qualified participants will be randomly assigned to either the NBP group (NBP injection) or the control group (NBP injection placebo) in a ratio of 1:1. Patients will complete the brain magnetic resonance imaging within 48 hours and 14 days after stroke onset to observe the CMBs through susceptibility weighted imaging, and evaluate whether the use of NBP will affect the new CMBs in AIS patients. SPSS 20.0 will be used for statistical analyses. RESULT: We will provide practical and targeted results assessing the safety of NBP for AIS patients, to provide reference for clinical use of NBP. CONCLUSION: The stronger evidence about the effect of NBP on new CMBs in AIS patients will be provided for clinicians.


Assuntos
Benzofuranos/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Protocolos Clínicos , Acidente Vascular Cerebral/tratamento farmacológico , Benzofuranos/normas , Hemorragia Cerebral/complicações , Humanos , Isquemia/complicações , Isquemia/tratamento farmacológico , Imagem por Ressonância Magnética/métodos , Inibidores da Agregação de Plaquetas/normas , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Prospectivos
13.
Neurology ; 95(4): e362-e373, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32601121

RESUMO

OBJECTIVE: To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis. METHODS: Data from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET. RESULTS: Of 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET-). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0-4.0] vs 3 [IQR 1.0-4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups. CONCLUSIONS: Patients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.


Assuntos
Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/métodos
14.
Neurology ; 95(4): e353-e361, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32611631

RESUMO

OBJECTIVE: We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology. METHODS: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH). RESULTS: Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not ß-blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for calcium channel blockers showed particularly strong associations with small vessel stroke and the related radiologic phenotype of WMH. CONCLUSIONS: This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP-lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/complicações , Hipertensão/genética , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Pressão Sanguínea/genética , Doenças de Pequenos Vasos Cerebrais/etiologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana
16.
Lancet Neurol ; 19(8): 661-669, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702335

RESUMO

BACKGROUND: Studies have suggested that fluoxetine could improve neurological recovery after stroke. The Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke (EFFECTS) trial aimed to assess whether administration of oral fluoxetine for 6 months after acute stroke improves functional outcome. METHODS: EFFECTS was an investigator-led, multicentre, randomised, placebo-controlled, double-blind, parallel group trial that enrolled patients aged 18 years or older between 2 and 15 days after stroke onset in 35 stroke and rehabilitation centres in Sweden. Eligible patients had a clinical diagnosis of ischaemic or intracerebral haemorrhage, brain imaging that was consistent with intracerebral haemorrhage or ischaemic stroke, and had at least one persisting focal neurological deficit. A web-based randomisation system that incorporated a minimisation algorithm was used to randomly assign (1:1) participants to receive oral fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Patients, care providers, investigators, and outcomes assessors were masked to the allocation. The primary outcome was functional status, measured with the modified Rankin Scale (mRS) at 6 months, analysed in all patients with available mRS data at the 6-month follow-up; we did an ordinal analysis adjusted for the minimisation variables used in the randomisation. This trial is registered with EudraCT, 2011-006130-16; ISRCTN, 13020412; and ClinicalTrials.gov, NCT02683213. FINDINGS: Between Oct 20, 2014, and June 28, 2019, 1500 patients were enrolled, of whom 750 were randomly assigned to fluoxetine and 750 were randomly assigned to placebo. At 6 months, mRS data were available for 737 (98%) patients in the fluoxetine group and 742 (99%) patients in the placebo group. There was no effect of fluoxetine on the primary outcome-distribution across mRS score categories-compared with placebo (adjusted common odds ratio 0·94 [95% CI 0·78 to 1·13]; p=0·42). The proportion of patients with a new diagnosis of depression was lower with fluoxetine than with placebo (54 [7%] patients vs 81 [11%] patients; difference -3·60% [-6·49 to -0·71]; p=0·015), but fluoxetine was associated with more bone fractures (28 [4%] vs 11 [2%]; difference 2·27% [0·66 to 3·87]; p=0·0058) and hyponatraemia (11 [1%] vs one [<1%]; difference 1·33% [0·43 to 2·23]; p=0·0038) at 6 months. INTERPRETATION: Functional outcome after acute stroke did not improve with oral fluoxetine 20 mg once daily for 6 months. Fluoxetine reduced the occurrence of depression but increased the risk of bone fractures and hyponatraemia. Our results do not support the use of fluoxetine after acute stroke. FUNDING: The Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Brain Foundation, the Swedish Society of Medicine, King Gustav V and Queen Victoria's Foundation of Freemasons, and the Swedish Stroke Association (STROKE-Riksförbundet).


Assuntos
Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
17.
Lancet Neurol ; 19(8): 651-660, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702334

RESUMO

BACKGROUND: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. METHODS: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2-15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. FINDINGS: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76-1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. INTERPRETATION: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke. FUNDING: National Health and Medical Research Council of Australia.


Assuntos
Fluoxetina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
18.
Cochrane Database Syst Rev ; 7: CD007026, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32662068

RESUMO

BACKGROUND: Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain that has potential neuroprotective properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. This is an update of a review first published in 2010 and last updated in 2017. OBJECTIVES: To assess the benefits and harms of Cerebrolysin for treating acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian databases in October 2019. We also searched reference lists, ongoing trials registers, and conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing Cerebrolysin, started within 48 hours of stroke onset and continued for any length of time, with placebo or no treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, extracted data, and applied GRADE criteria to the evidence. MAIN RESULTS: Seven RCTs (1601 participants) met the inclusion criteria of the review. In this update we re-evaluated risk of bias through identification, examination, and evaluation of study protocols and judged it to be low, unclear, or high across studies: unclear for all domains in one study, and unclear for selective outcome reporting across all studies; low for blinding of participants and personnel in four studies and unclear in the remaining three; low for blinding of outcome assessors in three studies and unclear in four studies. We judged risk of bias to be low in two studies and unclear in the remaining five studies for generation of allocation sequence; low in one study and unclear in six studies for allocation concealment; and low in one study, unclear in one study, and high in the remaining five studies for incomplete outcome data. The manufacturer of Cerebrolysin supported four multicentre studies, either totally, or by providing Cerebrolysin and placebo, randomisation codes, research grants, or statisticians. We judged three studies to be at high risk of other bias and the remaining four studies to be at unclear risk of other bias. All-cause death: we extracted data from six trials (1517 participants). Cerebrolysin probably results in little to no difference in all-cause death: risk ratio (RR) 0.90, 95% confidence interval (CI) 0.61 to 1.32 (6 trials, 1517 participants, moderate-quality evidence). None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset), or time to restoration of capacity for work and quality of life. Only one trial clearly reported on the cause of death: cerebral infarct (four in the Cerebrolysin and two in the placebo group), heart failure (two in the Cerebrolysin and one in the placebo group), pulmonary embolism (two in the placebo group), and pneumonia (one in the placebo group). Serious adverse events (SAEs): Cerebrolysin probably results in little to no difference in the total number of people with SAEs (RR 1.15, 95% CI 0.81 to 1.65, 4 RCTs, 1435 participants, moderate-quality evidence). This comprised fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38) and an increase in the total number of people with non-fatal SAEs (RR 2.15, 95% CI 1.01 to 4.55, P = 0.047, 4 trials, 1435 participants, moderate-quality evidence). In the subgroup of dosing schedule 30 mL for 10 days (cumulative dose 300 mL), the increase was more prominent: RR 2.86, 95% CI 1.23 to 6.66, P = 0.01 (2 trials, 1189 participants). Total number of people with adverse events: four trials reported on this outcome. Cerebrolysin may result in little to no difference in the total number of people with adverse events: RR 0.97, 95% CI 0.85 to 1.10, P = 0.90, 4 trials, 1435 participants, low-quality evidence. Non-death attrition: evidence from six trials involving 1517 participants suggests that Cerebrolysin results in little to no difference in non-death attrition, with 96 out of 764 Cerebrolysin-treated participants and 117 out of 753 placebo-treated participants being lost to follow-up for reasons other than death (very low-quality evidence). AUTHORS' CONCLUSIONS: Moderate-quality evidence indicates that Cerebrolysin probably has little or no beneficial effect on preventing all-cause death in acute ischaemic stroke, or on the total number of people with serious adverse events. Moderate-quality evidence also indicates a potential increase in non-fatal serious adverse events with Cerebrolysin use.


Assuntos
Aminoácidos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Doença Aguda , Aminoácidos/efeitos adversos , Viés , Isquemia Encefálica/complicações , Causas de Morte , Humanos , Fármacos Neuroprotetores/efeitos adversos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
19.
Neurology ; 95(5): e499-e507, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32631920

RESUMO

OBJECTIVE: To compare the efficacy and safety of oral anticoagulants vs antiplatelets in patients with stroke and atherosclerotic plaques in the aortic arch or cervical or intracranial arteries, collectively described as supracardiac atherosclerosis. METHODS: We searched PubMed and Scopus until August 28, 2019, for randomized trials comparing oral anticoagulants vs antiplatelets in patients with stroke and supracardiac atherosclerosis using the terms "anticoagulant or anticoagulation" and "antiplatelet or aspirin" and "randomized controlled trial or RCT" and "stroke or cerebral ischemia" and "aortic or carotid or vertebrobasilar or intracranial or atherosclerosis or stenosis or arterial." Four outcomes were assessed: recurrent ischemic stroke, major ischemic event or death, major bleeding, and intracranial bleeding. Treatment effects (relative risk [RR] and 95% confidence interval [CI]) were estimated by meta-analysis using random-effects models. RESULTS: Among 1,117 articles identified in the literature search, results from 10 randomized controlled trials involving 6,068 patients with stroke/TIA with supracardiac atherosclerosis were included in the meta-analysis. Recurrent ischemic stroke rates were 2.94 per 100 patient-years in the anticoagulant-assigned patients vs 3.30 per 100 patient-years in the antiplatelet-assigned patients (RR, 0.91; 95% CI, 0.70-1.18 for the SJ estimator, I2 = 26%). Major ischemic event or death rates were 4.39 per 100 patient-years in anticoagulant-assigned patients vs 4.32 in antiplatelet-assigned patients (RR, 1.03; 95% CI, 0.79-1.35; I2 = 54.5%). Major bleeding rates were 2.88 per 100 patient-years in anticoagulant-assigned patients vs 0.82 in antiplatelet-assigned patients (RR, 3.21; 95% CI, 1.96-5.24; I2 = 46%). CONCLUSION: This systematic review and meta-analysis showed that anticoagulant-assigned patients with stroke and supracardiac atherosclerosis were not at different risk of ischemic stroke recurrence and increased risk of major bleeding compared to antiplatelet-assigned patients.


Assuntos
Anticoagulantes/uso terapêutico , Arteriosclerose Intracraniana/complicações , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Doenças da Aorta/complicações , Aterosclerose/complicações , Humanos
20.
Neurol Sci ; 41(9): 2325-2329, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32656711

RESUMO

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend.


Assuntos
Betacoronavirus , Isquemia Encefálica/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Proteínas Recombinantes/administração & dosagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
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