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1.
Chemosphere ; 242: 125143, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31675585

RESUMO

Ochratoxin A (OTA), a mycotoxin widely found in foodstuffs, reportedly damages multiple brain regions in developing rodents, but the corresponding mechanisms have not been elucidated. In this study, zebrafish embryos at 6 h post fertilization (hpf) were exposed to various concentrations of OTA and the phenomenon associated with intracerebral hemorrhage was observed at 72 hpf. Exposure of embryos to OTA significantly increased their hemorrhagic rate in a dose-dependent manner. Large numbers of extravagated erythrocytes were observed in the midbrain/hindbrain areas of Tg(fli-1a:EGFP; gata1:DsRed) embryos following exposure to OTA. OTA also disrupted the vascular patterning, especially the arch-shaped central arteries (CtAs), in treated embryos. Histological analysis revealed a cavity-like pattern in their hindbrain ventricles, implying the possibility of cerebral edema. OTA-induced intracerebral hemorrhage and CtA vessel defects were partially reversed by the presence of miR-731 antagomir or the overexpression of prolactin receptor a (prlra); prlra is a downstream target of miR-731. These results suggest that exposure to OTA has a negative effect on cerebral vasculature development by interfering with the miR-731/PRLR axis in zebrafish.


Assuntos
Hemorragia Cerebral/induzido quimicamente , Ocratoxinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/fisiologia , Eritrócitos/efeitos dos fármacos , MicroRNAs , Micotoxinas , Receptores da Prolactina/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/fisiologia
2.
J Stroke Cerebrovasc Dis ; 29(2): 104474, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784381

RESUMO

OBJECTIVE: To study the rate of symptomatic intracerebral hemorrhage (SxICH) and major systemic hemorrhage (MSH) after acute stroke treatments among different ethnicities/races. BACKGROUND: Studies have reported ethnic/racial disparities in intravenous tPA treatment (IV tPA). The adverse outcome of tPA and/or intra-arterial intervention (IA) among different ethnicities/races requires investigation. METHODS: We retrospectively reviewed all patients from an IRB-approved registry between June 2004 and June 2018. Patients who received IV tPA, IA, or both for acute stroke were identified and classified into 2 ethnic groups: non-Hispanics or Hispanics (NH/H) and 4 racial groups: Asian, Black, Other (Native Americans and Pacific Islanders), and White (A/B/O/W). RESULTS: We identified 916 patients that received acute therapy (A/B/O/W: n = 50/104/16/746, H/NH: n = 184/730). For those received IV tPA only (n = 759), IA only (n = 85), and IV tPA+IA (n = 72), the SxICH rate was 4.3%, 4.7%, and 6.9%; the MSH rate was 1.3%, 0%, and 0%, respectively. No significant difference in the rate of SxICH or MSH among different racial or ethnic groups was found after either therapy. Asian race (OR 14.17, P = .01), in association with age, international normalized value (INR), and Partial thromboplastin time (PTT) (OR 1.06, 46.52, and 1.18, P = .020, 0.037, and 0.042, respectively), was predictive of SxICH after IV tPA. There was a significant correlation between age and National Institute of Health Stroke Scale with SxICH (P < .01, P = .02, respectively). Age, INR, and PTT were independent predictors of SxICH after IV tPA (OR 1.06, 46.52, and 1.18, P = .02, 0.04, and 0.04, respectively). CONCLUSIONS: There was no significant difference in the rate of SxICH or MSH after IV tPA, IA, or IV tPA+IA among different racial or ethnic groups. Larger studies are needed to elucidate the race specific causes of SxICH and MSH after acute stroke treatment.


Assuntos
Grupos de Populações Continentais , Procedimentos Endovasculares , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Afro-Americanos , Fatores Etários , Americanos Asiáticos , California/epidemiologia , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/etnologia , Terapia Combinada , Procedimentos Endovasculares/efeitos adversos , Grupo com Ancestrais do Continente Europeu , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Coeficiente Internacional Normatizado , Tempo de Tromboplastina Parcial , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
3.
Rinsho Shinkeigaku ; 59(11): 699-706, 2019 Nov 08.
Artigo em Japonês | MEDLINE | ID: mdl-31656268

RESUMO

Tissue plasminogen activator (t-PA) treatment is beneficial for patients with ischemic stroke within 4.5 h of stroke onset, because the risk of intracerebral hemorrhagic transformation (HT) increases with delayed t-PA treatment. The benefits of t-PA thrombolysis are heavily dependent on time to treatment. Development of vasoprotective drugs that attenuate HT after delayed t-PA treatment might improve the prognosis of stroke patients and extend the therapeutic time window of t-PA and endovascular thrombolysis. An angiogenic factor, vascular endothelial growth factor (VEGF), might be associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia. By using a rat thromboembolic model, delayed t-PA treatment at 4 h after ischemia promoted expression of VEGF in BBB, matrix metalloproteinase-9 (MMP-9) activation, degradation of BBB components, and HT. We demonstrated that HT was inhibited by intravenous administration of an anti-VEGF neutralizing antibody/VEGF receptor antagonist. In addition, for clinical application, reverse translation studies, a path from bedside to bench, are necessary.


Assuntos
Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/prevenção & controle , Infarto Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Terapia de Alvo Molecular , Prognóstico , Ratos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
J Stroke Cerebrovasc Dis ; 28(12): 104329, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31607439

RESUMO

BACKGROUND AND PURPOSE: The timely administration of thrombolytic therapy for acute ischemic stroke has been associated with good functional outcomes. Current guidelines recommend alteplase administration within 60 minutes in 75% of eligible patients and within 45 minutes in 50% of patients. There is limited evidence guiding these measures and their effect on outcomes. We report a single-center, retrospective assessment of the safety and efficacy of alteplase treatment within 45 minutes. METHODS: Five hundred and eighty-six patients were treated with alteplase in our emergency departments (EDs) between January 2014 and October 2016; 368 patients were included for analysis. Multivariate regression analysis was used to assess the association between door-to-alteplase (DTA) times and 90-day modified Rankin scale (mRS) scores. Incidence of intracerebral hemorrhage (ICH) was also documented. RESULTS: The median DTA time was 29 minutes versus 64 minutes in the DTA less than or equal to 45 minutes arm and more than 45 minutes arm, respectively. The primary outcome of 90-day mRS 0-1 was achieved in 56% of patients in the less than or equal to 45 minutes group versus 58% in more than 45 minutes group (P = .67). Odds of achieving mRS 0-1 were not significantly impacted by DTA times. In the multivariate regression analysis, patient characteristics associated with achieving mRS 0-1 were: younger age, male sex, not requiring intubation in the ED, and without prior history of hypertension, atrial fibrillation, or stroke. There was no significant difference in rates of ICH for patients less than or equal to 45 minutes versus more than 45 minutes. CONCLUSIONS: Rapid administration of alteplase was not associated with significantly better outcomes nor increased risk of ICH. Conclusions about efficacy are limited due to the retrospective nature of the study, small sample size, and incomplete data points.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Hemorragia Cerebral/induzido quimicamente , Avaliação da Deficiência , Esquema de Medicação , Serviço Hospitalar de Emergência , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
5.
J Stroke Cerebrovasc Dis ; 28(11): 104360, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31501036

RESUMO

OBJECTIVE: Thrombolytic therapy with intravenous alteplase (IV-rtPA) has a known risk of symptomatic intracerebral hemorrhage (sICH). We aim to identify factors with a significant association with the development of sICH post-IV-rtPA. We also aim to perform an external validation of sICH predicting scores in our patient population. MATERIAL AND METHODS: We performed a retrospective chart review of patients who received IV-rtPA at our tertiary care hospital. We excluded patients who underwent mechanical thrombectomy. We analyzed various factors recorded at presentation such as presenting mean arterial pressure (MAP), blood glucose, National Institutes of Health Stroke Scale (NIHSS) score, verify Aspirin, verify Plavix, age, sex, platelet count, international normalized ratio, prothrombin time, partial thromboplastin time, hemoglobin A1c, low-density lipoprotein, onset to treatment time, weight, sex, and early infarct signs on computed tomography (CT) head and compared them between sICH and non-sICH groups. For validation of sICH scores, we used documented variables to calculate the following scores for each patient: stroke prognostication using age and NIH stroke scale-100 (SPAN-100), DRAGON, CUCCHIARA, hemorrhage after thrombolysis (HAT), SEDAN, totaled health risks in vascular events, and safe implementation of thrombolysis in stroke-symptomatic intracerebral hemorrhage. RESULTS: sICH rate in our cohort of 89 patients was 5.62% according to the European-Australasian Cooperative Acute Stroke Study-II (ECASS-II) criteria and 7.86% according to the National Institute of Neurological Disorders and Stroke (NINDS) criteria. In the multivariate regression analysis, MAP (95% CI, .001-.01; P .002), blood glucose greater than or equal to 185 mg/dL (95% CI, .12-.45; P .001) and presence of early infarct signs (95% CI, .06-.25; P .002) had a significant association with the development of sICH with the ECASS-II definition of sICH post-IV-rtPA, whereas, only MAP (95% CI, 1.01-1.18; P .025) and verify Aspirin less than 500 (95% CI, .01-.80; P .032) had a significant association with the development of sICH with the NINDS definition of sICH post-IV-rtPA. Our study found that HAT (95% CI, .58-.96; P .044) and DRAGON (95% CI, .61-.96; P .012) scores had the highest area under the curve (AUC) with respect to ECASS-II and NINDS criteria of sICH, respectively. CONCLUSIONS: We found that presenting MAP, presence of early infarct signs on CT Head and blood glucose greater than or equal to 185 mg/dL upon a patient's presentation have a significant association with sICH post-IV-rtPA when the ECASS-II definition was used, while presenting MAP and verify Aspirin less than 500 upon a patient's presentation have a significant association with sICH post-IV-rtPA when the NINDS definition was used. Our study found that HAT and DRAGON scores had the highest AUC, and they were the most valid in predicting the development of sICH in our independent cohort. Patients with these risk factors should receive more intensive neurological monitoring.


Assuntos
Hemorragia Cerebral/induzido quimicamente , Técnicas de Apoio para a Decisão , Fibrinolíticos/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia , Feminino , Fibrinolíticos/administração & dosagem , Nível de Saúde , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento , Adulto Jovem
6.
BMC Res Notes ; 12(1): 497, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405369

RESUMO

OBJECTIVE: Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized European Medicines Agency database of suspected adverse reactions related to medicinal products (EudraVigilance) for fatal adverse events associated with treatment with alemtuzumab (Lemtrada®) for multiple sclerosis. Four independent reviewers with expertise on MS, clinical immunology, infectious diseases and clinical pharmacology reviewed the reports, and scored the likelihood for causality. RESULTS: We identified nine cases with a probable and one case with a possible causal relationship between alemtuzumab treatment and a fatal adverse event. Six of these patients died within one month after treatment; one from intracerebral hemorrhage, two from acute multiple organ failure and septic shock, one from listeriosis, one from pneumonia and one from agranulocytosis. Four patients died several months after administration of alemtuzumab from either autoimmune hepatitis, immune-mediated thrombocytopenia, autoimmune hemolytic anemia or agranulocytosis. Four of the 10 cases had been published previously in case reports or congress abstracts. Fatal adverse events related to treatment with alemtuzumab occur more frequently than previously published in the literature. A significant proportion occurs in the first month after treatment.


Assuntos
Agranulocitose/induzido quimicamente , Alemtuzumab/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Fatores Imunológicos/efeitos adversos , Listeriose/induzido quimicamente , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Pneumonia/induzido quimicamente , Adulto , Agranulocitose/mortalidade , Agranulocitose/patologia , Alemtuzumab/administração & dosagem , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/patologia , Evolução Fatal , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Listeriose/microbiologia , Listeriose/mortalidade , Listeriose/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Pneumonia/microbiologia , Pneumonia/mortalidade , Pneumonia/patologia
7.
Neurology ; 93(9): e851-e863, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31366724

RESUMO

OBJECTIVE: To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke. METHODS: We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum. RESULTS: Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score (p = 2.02 × 10-6, p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C (p = 0.012, p = 0.034, p = 5.32 × 10-4). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, p = 0.009). CONCLUSION: The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.


Assuntos
Hemorragia Cerebral/epidemiologia , Valor Preditivo dos Testes , Ativador de Plasminogênio Tecidual/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Fator XII/genética , Feminino , Finlândia/epidemiologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia/efeitos adversos , Trombectomia/estatística & dados numéricos , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/uso terapêutico , alfa-Macroglobulinas/genética
8.
J Stroke Cerebrovasc Dis ; 28(10): 104292, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31375402

RESUMO

BACKGROUND: Decisions regarding whether and when to resume direct oral anticoagulants (DOAC) after acute intracerebral hemorrhage (ICH) are challenging. We examined the timing of DOAC resumption and factors that influence decision-making in DOAC resumption. METHODS: We retrospectively analyzed 43 patients with ICH who were treated with DOAC for nonvalvular atrial fibrillation before ICH onset. All patients were divided into 2 groups (resumption of DOAC and no resumption of DOAC) during hospitalization. Clinical backgrounds, laboratory data, and stroke severity were compared between the groups. RESULTS: DOAC were resumed in 19 of 39 (49%) acute ICH survivors and were not resumed in 24 patients, including 4 deceased patients. The National Institutes of Health Stroke Scale score at admission tended to be higher in the no resumption group (median, 17) than in the resumption group (median, 6) (P = .119). The modified Rankin Scale score was slightly poorer in the no resumption group (median, 4) than in the resumption group (median, 3) (P = .070). In the resumption group, DOAC were resumed at a median of 11 days (interquartile range, 5-21 days) after ICH onset. The modified Rankin Scale score at discharge was positively correlated with the days of DOAC resumption (R2 = .31, P = .013). CONCLUSIONS: In half of patients, DOAC were resumed relatively early after ICH onset. Early resumption of DOAC for ICH in patients with nonvalvular atrial fibrillation is considered to be safe. The functional outcome was associated with not only resumption of DOAC but also the timing of resumption.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Administração Oral , Idoso , Fibrilação Atrial/diagnóstico , Hemorragia Cerebral/diagnóstico por imagem , Esquema de Medicação , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
J Biomed Sci ; 26(1): 53, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307481

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades that contribute to secondary neuronal damage. Tropomyosin-related kinase receptor B (TrkB) signaling plays a crucial role in promoting neuronal survival following brain damage. METHODS: The present study investigated the protective effects and underlying mechanisms of TrkB activation by the specific TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), in a model of collagenase-induced ICH and in neuronal cultures. Mice subjected to collagenase-induced ICH were intraperitoneally injected with either 7,8-DHF or vehicle 10 min after ICH and, subsequently, daily for 3 days. Behavioral studies, brain edema measurement, and histological analysis were conducted. Levels of TrkB signaling-related molecules and apoptosis-related proteins were analyzed by western blots. RESULTS: Treatment with 20 mg/kg 7,8-DHF significantly improved functional recovery and reduced brain damage up to 28 days post-ICH. Reduction in neuronal death, apoptosis, and brain edema were also observed in response to 7,8-DHF treatment at 3 days post-ICH. These changes were accompanied by a significant increase in the phosphorylation of TrkB and Akt (Ser473/Thr308) at 1 and 3 days, but had no effect on Erk 44/42 phosphorylation. 7,8-DHF also enhanced the phosphorylation of Ask-1 Ser967 and FOXO-1, downstream targets of Akt at 1 and 3 days. Moreover, 7,8-DHF increased brain-derived neurotrophic factor levels at 1 day. In primary cultured neurons stimulated with hemin, 7,8-DHF promoted survival and reduced apoptosis. Furthermore, delaying the administration of 7,8-DHF to 3 h post-ICH reduced brain tissue damage and neuronal death. CONCLUSIONS: Our findings demonstrate that the activation of TrkB signaling by 7,8-DHF protects against ICH via the Akt, but not the Erk, pathway. These data provide new insights into the role of TrkB signaling deficit in the pathophysiology of ICH and highlight TrkB/Akt as possible therapeutic targets in this disease.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Flavonas/farmacologia , Glicoproteínas de Membrana/agonistas , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Hemorragia Cerebral/induzido quimicamente , Colagenases/toxicidade , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
10.
J Clin Neurosci ; 66: 33-37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160199

RESUMO

Antiplatelet therapy at the time of spontaneous intracerebral hemorrhage (sICH) may increase risk for hemorrhage expansion and mortality. Current guidelines recommend considering a single dose of desmopressin in sICH associated with cyclooxygenase-1 inhibitors or adenosine diphosphate receptor inhibitors. Adult subjects with sICH and concomitant antiplatelet therapy admitted to a large, tertiary care center were included. We sought to compare the risk of hematoma expansion in patients that received desmopressin for antiplatelet reversal in the setting of sICH to similar patients that did not receive desmopressin. The primary outcomes were the incidence of relative and absolute hematoma expansion. In total, 71 patients (29 received desmopressin, 42 did not receive desmopressin) were analyzed. All patients in the desmopressin group received a 0.3 mcg/kg intravenous dose prior to hematoma expansion assessment. Relative hematoma expansion occurred in 5/29 (17%) with desmopressin compared to 11/42 (26%) without desmopressin (OR 0.59 [95% CI 0.18-1.92]). Absolute hematoma expansion occurred in 9/29 (30%) with desmopressin compared to 12/42 (28%) without desmopressin (OR 1.13 [95% CI 0.40-3.16]). Multiple logistic regression controlling for significant covariates did not reveal a significant effect of desmopressin on relative or absolute hematoma expansion (OR 0.65 [95% CI 0.18-2.43] and OR 1.55 [0.48-4.99], respectively). We failed to find evidence that desmopressin administration for antiplatelet reversal in sICH reduces the incidence of hematoma expansion. Larger studies, focusing on the early phase of sICH, are needed to characterize the clinical efficacy and safety of desmopressin for antiplatelet reversal before widespread implementation.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/epidemiologia , Desamino Arginina Vasopressina/administração & dosagem , Hematoma/tratamento farmacológico , Hematoma/epidemiologia , Hemostáticos/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Estudos de Coortes , Feminino , Hematoma/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
11.
BMJ Case Rep ; 12(6)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31175112

RESUMO

Anabolic steroid use is prevalent among athletes and bodybuilders. There are known cardiovascular, reproductive, musculoskeletal and neuropsychiatric risks associated with their prolonged use. Although there have been very few documented cases of strokes associated with anabolic steroid use, cardiomyopathy and secondary erythropoiesis can increase the risk of strokes in users with no other risk factors. We present a 49-year-old man with left parietal ischaemic stroke with haemorrhagic conversion resulting in Gerstmann syndrome secondary to a hypercoagulable state from chronic anabolic steroid use.


Assuntos
Anabolizantes/efeitos adversos , Síndrome de Gerstmann/diagnóstico , Esteroides/efeitos adversos , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/diagnóstico por imagem , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/terapia , Síndrome de Gerstmann/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Flebotomia , Policitemia/induzido quimicamente , Policitemia/diagnóstico por imagem , Levantamento de Peso
12.
N Engl J Med ; 380(19): 1795-1803, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31067369

RESUMO

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Fibrinolíticos/uso terapêutico , Imagem de Perfusão , Acidente Vascular Cerebral/tratamento farmacológico , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Angiografia por Tomografia Computadorizada , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/prevenção & controle , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/mortalidade , Equipolência Terapêutica , Ativador de Plasminogênio Tecidual/efeitos adversos
13.
J Stroke Cerebrovasc Dis ; 28(7): 1853-1859, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31072698

RESUMO

BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR) is suggested as a readily available and inexpensive biomarker to predict prognosis of acute stroke. Experience with intravenous (IV) tissue plasminogen activator (tPA) treatment is limited. METHODS: Total 142 (80 female, age: 69 ± 13 yearr) consecutive acute stroke patients treated with IV tPA were evaluated. Admission and 24th hour lymphocyte, neutrophil, and monocyte counts were measured and the NLR was calculated. RESULTS: Average NLR elevated (by 3.47 ± 6.75) significantly from admission to 24th hour (P< .001). Total 52% of patients exerted good response to IV tPA (NIHSS ≤1 or decrease in NIHSS ≥4 at end of 24 hour), while 27% showed dramatic response (decrease in NIHSS ≥8 at end of 24 hour). The patients with "thrombolysis resistance" had significantly higher 24 hour Neutrophil-to-Lymphocyte Ratio (24h NLR) (P= .001). At the end of 3rd month, 46.5% of patients had favorable (modified Rankin's score, mRS 0-2) and 32.4% had excellent (mRS 0-1) outcome. Patients without favorable/excellent outcome had significantly higher 24h NLRs. Regression analysis indicated that post-tPA, but not admission NLR, was an independent negative predictor of excellent (ß =-.216, P= .006) and favorable (ß = -.179, P= .034) outcome after adjustment for age, hypertension, and admission NIHSS. Nine patients who developed symptomatic intracerebral hemorrhage had elevated pre-tPA (7.6 ± 7.39 versus 3.33 ± 3.07, P< .001) and 24h NLR (26.2 ± 18.6 versus 5.78 ± 4.47, P< .001). Of note, receiver operating characteristics analysis failed to detect any reliable NLR threshold for absence of tPA effectiveness/dramatic response, 3rd month good/excellent outcome or any type tPA-induced hemorrhage. CONCLUSIONS: As a marker of stroke-associated acute stress response, the NLR, which increases during the first 24 hours, is an epiphenomenon of poor prognosis. However, pretreatment NLR values have no importance in predicting IV tPA response.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Linfócitos , Neutrófilos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Hemorragia Cerebral/sangue , Hemorragia Cerebral/induzido quimicamente , Avaliação da Deficiência , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Neuropharmacology ; 155: 162-172, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132437

RESUMO

This study aims at determining the ability of clinical-based doses of four oral anticoagulants to transform the onset of a cerebral microhemorrhages (CMH) burden into a symptomatic intracerebral hemorrhage (ICH) in the healthy brain, and precipitate cognitive impairment. Wild-type mice were anticoagulated for 10 days using apixaban, rivaroxaban or dabigatran as direct oral anticoagulants (DOACs), or warfarin as vitamin K-antagonist. Meanwhile, a burden of ∼20 CMHs was induced in the Sylvian territory by intra-carotid injection of cyclodextrin nanoparticles. At bleeding onset, only warfarin provoked deadly hematoma, and dramatically increased mortality (+45%). All the DOACs enhanced CMH burden through a greater number of intermediate-sized microhemorrhages (+80% to +180%). Although silent at onset, both baseline- and anticoagulant-enhanced CMH burdens increased mortality (+11% to +58%) along the following year without statistical difference among groups, and despite cessation of anticoagulation and absence of CMH progression or transformation into ICH. All survivor mice exhibited reduction in visual recognition memory from 9 months. In the healthy brain, DOACs preserve the onset of microhemorrhages from transformation into ICH, and do not precipitate cognitive impairment despite enhancement of CMH burden. High CMH burdens should however be considered for early detection and preventive memory care apart from anticoagulation decisions.


Assuntos
Anticoagulantes/administração & dosagem , Hemorragia Cerebral/fisiopatologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Administração Oral , Animais , Anticoagulantes/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/prevenção & controle , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL
15.
Lancet ; 394(10193): 139-147, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-31128925

RESUMO

BACKGROUND: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. METHODS: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FINDINGS: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66). INTERPRETATION: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. FUNDING: None.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Tempo para o Tratamento , Hemorragia Cerebral/induzido quimicamente , Imagem de Difusão por Ressonância Magnética , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Humanos , Imagem de Perfusão , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
Lancet ; 393(10191): 2613-2623, 2019 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-31128924

RESUMO

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation.


Assuntos
Hemorragia Cerebral/epidemiologia , Inibidores da Agregação de Plaquetas/administração & dosagem , Acidente Vascular Cerebral/complicações , Doenças Vasculares/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Feminino , Humanos , Masculino , Cooperação do Paciente , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Reino Unido
17.
Herz ; 44(4): 315-323, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-30941474

RESUMO

The incidence of intracerebral hemorrhage (ICH) in patients using oral anticoagulation (OAC) will continue to increase with the demographic change of an aging population. As compared to primary spontaneous ICH, OAC-ICH is characterized by larger hematoma volumes, more frequent hematoma enlargement and intraventricular hemorrhage resulting in an even worse prognosis. Specific treatment should focus on immediate reversal of anticoagulation in addition to the basic acute management of ICH. In ICH patients using vitamin K antagonists (VKA), complete anticoagulant reversal with an international normalized ratio (INR) <1.3 should be achieved as quickly as possible using prothrombin complex concentrate (PCC) with additional substitution of vitamin K. Patients with ICH under dabigatran treatment should receive idarucizumab. In ICH patients using factor-Xa inhibitors, andexanet should be administered as soon as approved in Europe or within clinical studies and if unavailable alternatively high-dose PCC administration. Regarding OAC resumption, results from randomized trials are pending. In comprehensive observational studies and meta-analyses ICH patients resuming OAC showed a reduced incidence of thromboembolic events and mortality without significantly increased rates of hemorrhagic complications. Non-vitamin K dependent oral anticoagulants (NOAC) might further increase the safety of OAC resumption, which should be initiated after 4-8 weeks for patients with atrial fibrillation. In contrast, VKA resumption in patients with mechanical heart valves should not take place earlier than 1 week after ICH. Generally, safety of OAC resumption appears to be affected by ICH localization along with the presence of cerebral microbleeding, cortical superficial siderosis and cortical/convexity subarachnoid hemorrhage, making it crucial to weigh up the individual patient risk with respect to thromboembolic versus hemorrhagic events.


Assuntos
Anticoagulantes , Fibrilação Atrial , Hemorragia Cerebral , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Europa (Continente) , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina K
18.
J Stroke Cerebrovasc Dis ; 28(6): 1703-1709, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878368

RESUMO

BACKGROUND: The association of lipid lowering therapy and intracerebral hemorrhage risk is controversial. METHODS: We performed a cumulative meta-analysis of lipid lowering trials that reported intracerebral hemorrhage. Statin, fibrate, ezetimibe, PCSK9, and CETP trials were included. We explored whether the association of lipid lowering therapy and risk of intracerebral hemorrhage may vary by baseline low-density lipoprotein (LDL) level, mean change in LDL or baseline cardiovascular risk of population. RESULTS: Among 39 trials (287,651 participants), lipid lowering therapy was not associated with a statistically significant increased risk of intracerebral hemorrhage (ICH) in primary and secondary prevention trials combined (odds ratio [OR], 1.12; 95% confidence interval [CI], .98-1.28). Lipid lowering was associated with an increased risk of ICH in secondary prevention trials (OR, 1.18; 95% CI, 1.00-1.38), but not in primary prevention trials (OR, 1.01; 95% CI, .78-1.30), but the test for interaction was not significant (P for interaction = .31). Meta-regression of baseline LDL or difference in LDL reduction between active and control did not explain significant heterogeneity between studies for ICH risk. Of 1000 individuals treated for 1 year for secondary prevention, we estimated 9.17 (95% CI, 5.78-12.66) fewer ischemic strokes and .48 (95% CI, .06-1.02) more ICH, and a net reduction of 8.69 in all stroke per 1000 person-years. CONCLUSIONS: The benefits of lipid lowering therapy in prevention of ischemic stroke greatly exceed the risk of ICH. Concern about ICH should not discourage stroke clinicians from prescribing lipid lowering therapy for secondary prevention of ischemic stroke.


Assuntos
Isquemia Encefálica/prevenção & controle , Hemorragia Cerebral/induzido quimicamente , Dislipidemias/tratamento farmacológico , Hipolipemiantes/efeitos adversos , Lipoproteínas LDL/sangue , Acidente Vascular Cerebral/prevenção & controle , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Humanos , Prevenção Primária/métodos , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Prevenção Secundária/métodos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
19.
Medicine (Baltimore) ; 98(9): e14685, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30817601

RESUMO

Cerebral microbleeds (CMBs) may be markers of intracerebral bleeding risk in patients receiving antithrombotic drugs. This study aimed to analyze CMBs and white matter hyperintensities (WMHs) in patients taking aspirin or clopidogrel.This retrospective study included patients with ischemic cardiovascular disease administered 75 mg/day aspirin (n = 150) or clopidogrel (n = 150, matched for age and gender) for >1 year (Affiliated Hospital of Inner Mongolia Medical University, China, from July, 2010 to July, 2015). Patients underwent T2-weighted imaging, T1-weighted imaging, diffusion-weighted imaging (DWI) and enhanced T2*-weighted angiography (ESWAN) imaging (3.0-Tesla scanner). Baseline vascular risk factors for CMBs and macroscopic bleeding (MB) were evaluated using univariate and multivariate analyses.The aspirin and clopidogrel groups did not differ significantly in baseline characteristics or prevalences of CMBs or MB. The odds of MB were higher in patients with CMBs than in patients without CMBs in both the aspirin (odds ratio, 95% confidence interval: 4.09, 1.93-8.68; P < .001) and clopidogrel (6.42, 2.83-14.57; P < .001) groups. The odds of WMHs were also higher in patients with CMBs in both the aspirin (3.28, 1.60-6.71; P = .001) and clopidogrel (4.09, 1.91-8.75; P < .001) groups. Patients receiving treatment for >5 years showed elevated risk of CMBs in the aspirin (0.17; 0.09-0.36; P < .001) and clopidogrel (0.15, 0.07-0.33; P < .001) groups as well as higher odds of MB in the aspirin (0.34, 0.16-0.71; P = .004) and clopidogrel (0.37, 0.17-0.80; P = .010) groups.The WMHs and MB were associated with CMBs in patients taking aspirin or clopidogrel for >1 year, and long-term use increased the risks of CMB and bleeding.


Assuntos
Aspirina/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Clopidogrel/efeitos adversos , Leucoencefalopatias/tratamento farmacológico , Isquemia Miocárdica/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Idoso , Aspirina/uso terapêutico , China , Clopidogrel/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
20.
Trials ; 20(1): 183, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30909946

RESUMO

BACKGROUND: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet therapy modifies the risks of recurrent ICH, major haemorrhagic events, major occlusive vascular events, or a composite of all major vascular events compared to avoiding antiplatelet therapy. METHODS/DESIGN: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, parallel group, open, assessor-blind, randomised trial comparing starting versus avoiding antiplatelet therapy for adults surviving antithrombotic-associated ICH. Recruitment began on 22 May 2013 and ended on 31 May 2018. Follow-up ended on 30 November 2018. This update to the protocol describes the statistical analysis plan (version 1.7, finalised on 25 January 2019). Database lock and un-blinding occurred on 29 January 2019, after which the un-masked trial statistician conducted the final analyses according to this statistical analysis plan. DISCUSSION: Final results of RESTART will be analysed and disseminated in May 2019. TRIAL REGISTRATION: ISRCTN registry 71907627 . Prospectively registered on 25 April 2013.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Prevenção Secundária/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico por imagem , Interpretação Estatística de Dados , Esquema de Medicação , Fibrinolíticos/efeitos adversos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Prevenção Secundária/estatística & dados numéricos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento
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