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1.
JAMA Netw Open ; 4(2): e2037438, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33591368

RESUMO

Importance: Although the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor-associated intracerebral hemorrhage (ICH). Objective: To investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH. Design, Setting, and Participants: This is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines-Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019. Exposures: Anticoagulation therapy before ICH. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge. Results: Of 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors. Conclusions and Relevance: In this cohort study, FXa inhibitor-associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.


Assuntos
Hemorragia Cerebral/mortalidade , Inibidores do Fator Xa/efeitos adversos , Mortalidade Hospitalar , Inibidores da Agregação de Plaquetas/uso terapêutico , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos de Casos e Controles , Hemorragia Cerebral/induzido quimicamente , Estudos de Coortes , Deambulação com Auxílio , Quimioterapia Combinada , Terapia Antiplaquetária Dupla/estatística & dados numéricos , Feminino , Hospitais para Doentes Terminais , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Alta do Paciente , Sistema de Registros , Fatores de Risco
2.
J Stroke Cerebrovasc Dis ; 30(4): 105654, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33578352

RESUMO

BACKGROUND: About 15% of patients with non-valvular atrial fibrillation might require percutaneous coronary interventions (PCIs) with stent placement to treat obstructive coronary artery disease. Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (aspirin) and P2Y12 antagonist is recommended after PCI. Patients requiring DAPT also require treatment with oral anticoagulation for atrial fibrillation. We conducted a meta-analysis to identify the antithrombotic regimen associated with the lowest rate of bleeding and thromboembolic events in non-valvular atrial fibrillation after PCI. METHODS: We searched PubMed, Embase, Scopus and Cochrane databases to identify randomized trials that investigated the use of dual antiplatelet therapy and vitamin K antagonist and/or Non-vitamin K antagonist oral anticoagulants (NOAC) (triple antithrombotic therapy (TAT)) against single antiplatelet agent and NOAC (dual antithrombotic therapy (DAT)) in the setting of coronary artery disease (CAD) requiring PCI and non-valvular atrial fibrillation. Random-effect models were used to pool data. We used the I2 statistic to measure heterogeneity between trials. RESULTS: We found 4 randomized clinical trials (ENTRUST, AUGUSTUS, PIONEER, REDUAL) using different NOACs. Overall, 9241 patients (median age 70 years, 41.4% female, mean CHADS2VASC Score 3.5) were included. We excluded patients in the very low dose rivaroxaban group from the PIONEER AF-PCI trial and low dose dabigatran group from the REDUAL PCI trial as these are not available in the United States. Our metanalysis showed that dual therapy was associated with less risk of intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.99; p = 0.045; I2 = 42%) and major bleeding (RR 0.66; 95% CI 0.55-0.79; p < 0.0001; I2 = 27%) as compared to triple therapy. Further risk of ischemic stroke (RR 0.94, 95% CI 0.63-1.39; p = 0.75; I2=0%), myocardial infarction (RR 1.18, 95% CI 0.94-1.47; p = 0.16; I2 = 0), or stent thrombosis (RR 0.50, 95% CI 0.93-2.41; p = 0.10; I2 = 0%) were unchanged. Similar findings were also noted on analysis of NOAC specific DAT vs VKA based TAT. CONCLUSIONS: The combination of an antiplatelet and NOACs (dual therapy) is associated with less risk of major bleeding and intracranial hemorrhage, with no significant difference in ischemic events (stroke myocardial infarction or stent thrombosis).


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Hemorragia Cerebral/induzido quimicamente , Doença da Artéria Coronariana/mortalidade , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/mortalidade , Feminino , Humanos , /mortalidade , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Stents , Resultado do Tratamento
3.
Ecotoxicol Environ Saf ; 208: 111613, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396133

RESUMO

The environmental effects of additives have attracted increasing attention. Sodium dehydroacetate (DHA-S), as an approved preservative, is widely added in processed foods, cosmetics and personal care products. However, DHA-S has been recently reported to induce hemorrhage and coagulation aberration in rats. Yet little is known about the ecotoxicological effect and underlying mechanisms of DHA-S. Here, we utilized the advantage of zebrafish model to evaluate such effects. DHA-S induced cerebral hemorrhage, mandibular dysplasia and pericardial edema in zebrafish after 24 h exposure (48-72 hpf) at 50 mg/L. We also observed the defective heart looping and apoptosis in DHA-S-treated zebrafish through o-dianisidine and acridine orange staining. Meanwhile, DHA-S induced the deficiency of Ca2+ and vitamin D3 in zebrafish. We further demonstrated that DHA-S stimulated Ca2+ influx resulting in Ca2+-dependent mitochondrial damage in cardiomyocytes. Additionally, DHA-S inhibited glucose uptake and repressed the biosynthesis of amino acids. Finally, we identified that sodium bicarbonate could rescue zebrafish from DHA-S induced cardiovascular toxicity. Altogether, our results suggest that DHA-S is a potential risk for cardiovascular system.


Assuntos
Cálcio/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Coração/efeitos dos fármacos , Pironas/toxicidade , Peixe-Zebra , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade , Linhagem Celular , Hemorragia Cerebral/induzido quimicamente , Relação Dose-Resposta a Droga , Edema Cardíaco/induzido quimicamente , Coração/embriologia , Miocárdio/metabolismo , Miocárdio/patologia , Pericárdio/efeitos dos fármacos , Pericárdio/patologia , Ratos , Peixe-Zebra/crescimento & desenvolvimento
4.
Am J Emerg Med ; 42: 31-37, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33440328

RESUMO

INTRODUCTION: Alteplase is an approved treatment for acute ischemic stroke. Tenecteplase is a genetically modified form of alteplase, with lower cost and a more favourable pharmacokinetic profile allowing bolus injection. The aim of this study was to compare both drugs in adult patients with acute ischemic stroke undergoing thrombolysis. MATERIAL AND METHODS: PubMed and CENTRAL were searched for observational and experimental studies comparing both drugs in the population of interest. Additional studies were sought in clinical trial registries and by means of reference check. The efficacy outcomes of interest were functional status at 3 months, recanalization and early neurological improvement (ENI). The safety outcomes of interest were cerebral haemorrhage (ICH), symptomatic ICH and mortality. The effect measure of interest was the absolute risk difference (ARD). Effect measures for each outcome were pooled across studies using random effect models. RESULTS: Eight studies were included, involving 2031 patients. Overall, there were no differences in terms of good or excellent functional outcome (ARR = 0.07 and 0.03 respectively, p > 0.05 for both comparisons) but tenecteplase patients showed higher rates of recanalization (ARD = 0.11, 95% CI [0.01;0.20]) and ENI (ARD = 0.10, 95% CI [0.02;0.17]). There were no differences between groups in terms of ICH (ARD = -0.02, 95% CI [-0.06;0.01]), symptomatic ICH (ARD = 0.00, 95% CI [-0.01;0.02]) or death (ARD = 0.00, 95% CI [-0.03;0.03]). CONCLUSION: Tenecteplase is an alternative to alteplase for stroke thrombolysis, with lower cost and a more favourable pharmacokinetic profile.


Assuntos
Fibrinolíticos/uso terapêutico , Tenecteplase/uso terapêutico , Terapia Trombolítica/métodos , /tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Fibrinolíticos/efeitos adversos , Fibrinolíticos/farmacocinética , Humanos , Tenecteplase/efeitos adversos , Tenecteplase/farmacocinética , Ativador de Plasminogênio Tecidual/farmacocinética , Ativador de Plasminogênio Tecidual/uso terapêutico
5.
J Stroke Cerebrovasc Dis ; 30(2): 105527, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33310072

RESUMO

We report herein a case of intraventricular silicone oil migration, a rare complication of intraocular silicone oil tamponade, mimicking a hemorrhage during antithrombotic therapy for ischemic stroke. A 62-year-old male patient with a history of diabetic retinopathy was admitted for right hemiparesis and dysarthria. Brain magnetic resonance imaging on admission showed an acute left-sided ventral medullary infarction, and antithrombotic therapy was started. Head computed tomography done on the next day after admission showed an area of high-density resembling a hematoma in the lateral ventricle. Additional magnetic resonance imaging in the supine and lateral recumbent positions confirmed migration of the lesion within the ventricles by position, indicating intraventricular silicone oil migration. Several facilities in Japan perform magnetic resonance imaging instead of computed tomography as the first step in assessing stroke in the emergency clinical setting. While the silicone oil used in internal tamponade appears high-density on computed tomography, it does not register as an abnormality on diffusion-weighted imaging, thus creating a pitfall to diagnosis based on this modality.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Fibrinolíticos/administração & dosagem , Migração de Corpo Estranho/diagnóstico por imagem , Óleos de Silicone/efeitos adversos , Tomografia Computadorizada por Raios X , Hemorragia Cerebral/induzido quimicamente , Erros de Diagnóstico , Fibrinolíticos/efeitos adversos , Migração de Corpo Estranho/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Óleos de Silicone/administração & dosagem , Resultado do Tratamento
6.
J Cancer Res Ther ; 16(3): 686-689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719293

RESUMO

Central nervous damage related to intra-arterial infusion chemotherapy (IAC) for head and neck cancer reported to date are cerebral infarction, transient ischemic attack, and neuropathy. There have been no reports of cerebral hemorrhage as an IAC-related complication for head and neck cancer. Authors report a case that underwent intra-arterial infusion chemoradiotherapy for advanced sphenoid sinus cancer which extended to the left cavernous sinus and cranium, subsequently suffered cerebral hemorrhage thought to have been caused by IAC. Treatment should be performed with greater caution when the head and neck cancer involves the cavernous sinus or cranium, as in the present case.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hemorragia Cerebral/etiologia , Neoplasias dos Seios Paranasais/tratamento farmacológico , Seio Esfenoidal/patologia , Idoso , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/patologia , Quimiorradioterapia , Docetaxel/administração & dosagem , Feminino , Humanos , Infusões Intra-Arteriais , Compostos Organoplatínicos/administração & dosagem , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/radioterapia , Prognóstico
7.
Stroke ; 51(7): 2139-2147, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32517582

RESUMO

BACKGROUND AND PURPOSE: Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source. METHODS: Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily. RESULTS: During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7-4.3]), East Asia region (HR, 2.5 [95% CI, 1.6-3.9]), systolic blood pressure ≥160 mm Hg (HR, 2.2 [95% CI, 1.2-3.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL/min per 1.73 m2 decrease, [95% CI, 1.0-1.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2-18.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin. CONCLUSIONS: Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.


Assuntos
Hemorragia Cerebral/induzido quimicamente , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Método Duplo-Cego , Extremo Oriente , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Embolia Intracraniana/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Stroke ; 51(7): 2153-2160, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32517581

RESUMO

BACKGROUND AND PURPOSE: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E (APOE) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. METHODS: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE-MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. RESULTS: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P<0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P=0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. CONCLUSIONS: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE-MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.


Assuntos
Anticoagulantes/efeitos adversos , Apolipoproteína E4/genética , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/genética , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Recidiva
9.
Stroke Vasc Neurol ; 5(1): 29-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411405

RESUMO

As intracerebral hemorrahge becomes more frequent as a result of an aging population with greater comorbidities, rapid identification and reversal of precipitators becomes increasingly paramount. The aformentioned population will ever more likely be on some form of anticoagulant therapy. Understanding the mechanisms of these agents and means by which to reverse them early on is critical in managing the acute intracerebral hemorrhage.


Assuntos
Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/terapia , Coagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Plasma , Varfarina/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia Cerebral/sangue , Hemorragia Cerebral/induzido quimicamente , Coagulantes/efeitos adversos , Fator VIIa/uso terapêutico , Fator Xa/uso terapêutico , Humanos , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
10.
Cerebrovasc Dis ; 49(2): 177-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32320990

RESUMO

BACKGROUND: Prevention of hematoma enlargement in oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) focuses on blood pressure (BP) reduction and OAC reversal. We investigated whether treatment efficiency and clinical outcomes differ between OAC-ICH patients admitted outside versus during regular working hours. METHODS: Based on pooled data of multicenter cohort studies, we grouped OAC-ICH patients (vitamin K antagonist [VKA], non-vitamin K oral anticoagulant [NOAC]) according to on- vs. off-hour admission. Primary outcome was the functional outcome using the modified Rankin scale (mRS) dichotomized into favorable (mRS 0-3) and unfavorable (mRS 4-6) and mortality at 3 months. Secondary outcome measures included the occurrence of hematoma enlargement, the proportions of patients with systolic BP <140 mm Hg and with anticoagulation treatment achieving international normalized ratio (INR) levels <1.3 at 4 h. Propensity score matching (PSM) was performed to account for imbalances in baseline characteristics. RESULTS: The study population consisted of 76/126 NOAC-ICH patients and 1,005/1,470 VKA patients presenting during off-hours. Functional outcome and mortality rates were not significantly different among PSM patients with VKA-ICH and NOAC-ICH during on- vs. off-hours (mRS 4-6 VKA-ICH: on-hour: 239/357 [66.9%] vs. 253/363 [69.7%] off-hour; p = 0.43; NOAC-ICH: on-hour 26/42 [61.9%] vs. off-hour: 37/57 [64.9%]; p = 0.76; mRS 6 VKA-ICH: on-hour: 127/357 [35.6%] vs. off-hour: 148/363 [40.8%]; p = 0.15; -NOAC-ICH: on-hour 17/42 [40.5%] vs. off-hour: 16/57 [28.1%]; p = 0.20). There were no differences detectable regarding the secondary outcome measures (i.e., hematoma enlargement, the proportion of patients who achieved systolic BP levels <140 mm Hg at 4 h as well as anticoagulation treatment achieving INR levels <1.3 at 4 h) in OAC patients. CONCLUSION: Our study implies that BP reduction and anticoagulation reversal management are well established and associated with similar rates of hematoma enlargement and clinical outcomes in on- vs. off-hour admitted OAC-ICH patients.


Assuntos
Plantão Médico , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/tratamento farmacológico , Hematoma/tratamento farmacológico , Hemostáticos/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/fisiopatologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Alemanha , Hematoma/induzido quimicamente , Hematoma/mortalidade , Hematoma/fisiopatologia , Hemostáticos/efeitos adversos , Humanos , Coeficiente Internacional Normatizado , Masculino , Estudos Multicêntricos como Assunto , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
11.
Stroke ; 51(4): 1135-1141, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32126942

RESUMO

Background and Purpose- Selective serotonin reuptake inhibitors (SSRIs) have a well-established association with bleeding complications and conflicting reports on outcome after stroke. We sought to evaluate whether pre-intracerebral hemorrhage (ICH) SSRI use increased ICH risk and post-ICH SSRI use improved ICH outcome. Methods- Through post hoc analysis of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage), SSRI use was categorized into no use, pre-ICH only, pre- and post-ICH use (termed "continuous"), and post-ICH only (termed "new"). Using multivariable modeling, associations were sought between pre-ICH SSRI use and ICH risk in the case-control set, and associations between post-ICH SSRI use and 3-month outcome were analyzed in the ICH case set. Exploratory analyses sought to assess influence of race/ethnicity in models. Results- The final study cohort consisted of 2287 ICH cases and 2895 controls. Pre-ICH SSRI use was not associated with ICH risk (odds ratio, 0.824 [95% CI, 0.632-1.074]) nor potentiation of ICH risk with anticoagulant or antiplatelet use. New post-ICH SSRI use was associated with unfavorable modified Rankin Scale score at 3 months after ICH (odds ratio, 1.673 [95% CI, 1.162-2.408]; P=0.006) in multivariable analyses. Additional propensity score analysis indicated a similar trend but did not reach statistical significance (P=0.107). When stratified by race/ethnicity, multivariable modeling demonstrated reduced ICH risk with pre-ICH SSRI use in Hispanics (odds ratio, 0.513 [95% CI, 0.301-0.875]; P=0.014), but not non-Hispanic whites or blacks, and no associations between post-ICH SSRI use and 3-month outcome in any racial/ethnic group. Conclusions- In a large multiethnic cohort, pre-ICH SSRI use was not associated with increased ICH risk, but post-ICH SSRI use was associated with unfavorable 3-month neurological outcome after ICH. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01202864.


Assuntos
Afro-Americanos/etnologia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etnologia , Grupo com Ancestrais do Continente Europeu/etnologia , Hispano-Americanos , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Idoso , Estudos de Casos e Controles , Hemorragia Cerebral/induzido quimicamente , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Inibidores de Captação de Serotonina/efeitos adversos , Resultado do Tratamento
12.
J Stroke Cerebrovasc Dis ; 29(5): 104742, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32127258

RESUMO

BACKGROUND: Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies available for patients with known-onset stroke (KOS). Whether rt-PA treatment would improve functional outcomes in patients with stroke with unknown time of onset (UTOS) is undetermined, we aimed to systematically assess the efficacy and safety of thrombolysis for UTOS patients in this meta-analysis. METHODS: A systematic literature search of Medline, Embase, and Cochrane Library was conducted. We considered the relevant data comparing thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients or thrombolyzed UTOS patients versus thrombolyzed KOS patients. Treatment efficacy and safety were measured according to modified Rankin Scale scores of 0-2 (mRS 0-2), and the presence of spontaneous intracerebral hemorrhage (SICH) or mortality at 90 days respectively. RESULTS: A total of 11 studies with 2581 patients meeting the inclusion criteria were included in the meta-analysis. All the patients had an ischemic lesion that was assessed by imaging including computed tomography or magnetic resonance imaging. Among these studies, 6 compared the thrombolytic efficacy in thrombolyzed UTOS patients with that in nonthrombolyzed UTOS patients (mRS 0-2: odds ratio [OR] =1.76, 95% confidence interval [CI] 1.11-2.81, P = .02), and 8 studies compared thrombolyzed UTOS patients with thrombolyzed KOS patients (mRS 0-2: OR = 0.87, 95% CI 0.66-1.15, P = .33). The incidence of SICH and mortality at 90 days had no difference between thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients and thrombolyzed UTOS patients versus thrombolyzed KOS patients (all P > .05). CONCLUSIONS: Data from observational studies suggest that thrombolysis for UTOS patients had significantly favorable outcomes at 90 days compared with nonthrombolyzed patients.


Assuntos
Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Segurança do Paciente , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Resultado do Tratamento
13.
Stroke ; 51(4): 1111-1119, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114928

RESUMO

Background and Purpose- It has been suggested that statins increase the risk of intracerebral hemorrhage in individuals with a history of stroke, which has led to a precautionary principle of avoiding statins in patients with prior intracerebral hemorrhage. However, such prescribing reticence may be unfounded and potentially harmful when considering the well-established benefits of statins. This study is so far the largest to explore the statin-associated risk of intracerebral hemorrhage in individuals with prior stroke. Methods- We conducted a population-based, propensity score-matched cohort study using information from Danish national registers. We included all individuals initiating statin treatment after a first-time stroke diagnosis (intracerebral hemorrhage, N=2728 or ischemic stroke, N=52 964) during 2002 to 2016. For up to 10 years of follow-up, they were compared with a 1:5 propensity score-matched group of statin nonusers with the same type of first-time stroke. The difference between groups was measured by adjusted hazard ratios for intracerebral hemorrhage calculated by type of first-time stroke as a function of time since statin initiation. Results- Within the study period, 118 new intracerebral hemorrhages occurred among statin users with prior intracerebral hemorrhage and 319 new intracerebral hemorrhages in users with prior ischemic stroke. The risk of intracerebral hemorrhage was similar for statin users and nonusers when evaluated among those with prior intracerebral hemorrhage, and it was reduced by half in those with prior ischemic stroke. These findings were consistent over time since statin initiation and could not be explained by concomitant initiation of other medications, by dilution of treatment effect (due to changes in exposure status over time), or by healthy initiator bias. Conclusions- This large study found no evidence that statins increase the risk of intracerebral hemorrhage in individuals with prior stroke; perhaps the risk is even lower in the subgroup of individuals with prior ischemic stroke.


Assuntos
Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Sistema de Registros , Projetos de Pesquisa , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico
14.
J Stroke Cerebrovasc Dis ; 29(5): 104747, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151478

RESUMO

OBJECTIVES: Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH. METHODS: At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be "cryptogenic" (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data. RESULTS: All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups. CONCLUSIONS: In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient's pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.


Assuntos
Hemorragia Cerebral/induzido quimicamente , Suplementos Nutricionais/envenenamento , Acidente Vascular Cerebral/induzido quimicamente , Vitaminas/envenenamento , alfa-Tocoferol/envenenamento , Idoso , Hemorragia Cerebral/sangue , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral Intraventricular/sangue , Hemorragia Cerebral Intraventricular/induzido quimicamente , Hemorragia Cerebral Intraventricular/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Recomendações Nutricionais , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico por imagem , Vitaminas/sangue , alfa-Tocoferol/sangue
15.
J Stroke Cerebrovasc Dis ; 29(4): 104683, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32059925

RESUMO

BACKGROUND AND AIM: The coexistence of cerebral venous thrombosis (CVT) and hematological neoplasms is rare. Currently available therapeutic options raise problems concerning the balance of thrombotic and hemorrhagic risks. Our purpose is to characterize a series of cases of CVT and concomitant hematological malignancy, focusing on predisposing factors and treatment strategies. METHODS: We performed a descriptive retrospective analysis of the cases of CVT and hematological neoplasms diagnosed in a tertiary center from 2006 to 2015. RESULTS: From the 111 CVT cases diagnosed, only 7 coexisted with hematological malignancy (lymphoma, leukemia, multiple myeloma, and myelodysplastic syndromes). These included 4 women; median age was 44 years old. Median follow-up time was 72 days. The hematological condition was already known in 5 cases. Besides malignancy, we identified other prothrombotic conditions in all cases. Several anticoagulant strategies were used during the acute phase, after which 5 patients remained on warfarin indefinitely. One patient died due to cerebral hemorrhage during the acute phase. In the remaining 6 patients, there was no recurrence of CVT or other complications of anticoagulation. CONCLUSIONS: Although these results reiterate the role of hematological malignancy as predisposing factor to CVT, in all cases other factors contributed to CVT etiology, potentiating the risk. We report 1 death directly attributable to a fatal hemorrhagic complication of anticoagulation, evidencing the delicate balance of thrombotic and hemorrhagic risk. Nevertheless, most patients benefited of long-term anticoagulation, which proved a reasonable option. A multidisciplinary approach is paramount in making decisions regarding the time and type of anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias Hematológicas/terapia , Trombose Intracraniana/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Adulto , Idoso , Anticoagulantes/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/mortalidade , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Humanos , Trombose Intracraniana/diagnóstico , Trombose Intracraniana/etiologia , Trombose Intracraniana/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Trombose Venosa/mortalidade
16.
J Neurol Neurosurg Psychiatry ; 91(4): 402-410, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32015090

RESUMO

BACKGROUND AND OBJECTIVE: Predictors of symptomatic haemorrhagic transformation (s-HT) of cerebral ischaemia after intravenous recombinant tissue-plasminogen activator (rt-PA) were identified in studies using CT scans. We evaluated whether MRI can identify other predictors. METHOD: We analysed predictors of s-HT in a cohort of consecutive patients who received intravenous rt-PA for cerebral ischaemia after MRI at baseline. We used receiver operating characteristic curves considering an area under the curve (AUC) of 0.70 or higher as indicating acceptable discrimination. RESULTS: Of 944 patients, 49 patients (5.2%) developed s-HT. Clinical factors independently associated with s-HT were age (adjusted OR (adjOR) 1.03 for 1 year increase; 95% CI 1.01 to 1.05), excessive alcohol consumption (adjOR 3.13; 95% CI 1.32 to 7.42), recent transient ischaemic attack (adjOR 2.88; 95% CI 1.04 to 7.95) and baseline national institutes of health stroke scale score (adjOR 1.06 for 1 point increase; 95% CI 1.02 to 1.10). MRI predictors were vascular hyperintensities (adjOR 3.89; 95% CI 1.50 to 10.08), old infarcts (adjOR 2.01; 95% CI 1.11 to 3.66) and volume of diffusion-weighted imaging (DWI) abnormality (adjOR 1.02 for 1 cm3 increase; 95% CI 1.01 to 1.03). The only variable with an acceptable discrimination was volume of DWI abnormality (AUC 0.72; 95% CI 0.64 to 0.79), a value of 4 cm3 predicting s-HT with a 78% sensitivity and 58% specificity. Variables that can be assessed only with MRI did not predict s-HT. CONCLUSION: Although the volume of DWI abnormality predicts s-HT, other imaging characteristics that can only be assessed with MRI were not significantly associated with s-HT. Trial registration number NCT01614080.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , 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/induzido quimicamente , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Ativador de Plasminogênio Tecidual/uso terapêutico
17.
Br J Hosp Med (Lond) ; 81(2): 1-6, 2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32097070

RESUMO

BACKGROUND/AIMS: Four-factor prothrombin complex concentrate is the first-line treatment in vitamin K antagonist-related intracerebral haemorrhage. Early administration is associated with improved patient outcomes. A quality improvement project investigated delays in prothrombin complex concentrate administration in vitamin K antagonist-related intracerebral haemorrhage in order to reduce the time from computed tomography scan confirming intracerebral haemorrhage to prothrombin complex concentrate administration (scan-to-needle time). METHOD: Twenty patients were identified by retrospective audit over a 3-year period. The median scan-to-needle time for prothrombin complex concentrate was 156 minutes. Several points of delay were identified, including contacting both haematology and transfusion departments for prothrombin complex concentrate dosing and dispensing. Following this audit, interventions were brought in which included the introduction of a protocol with a prothrombin complex concentrate dosing algorithm, negating the need to contact haematology before administration. A dedicated supply of prothrombin complex concentrate was given to the stroke unit avoiding the need to contact the transfusion service. RESULTS: A re-audit showed a 68% reduction in median scan-to-needle time from 156 minutes to 49 minutes. Prospective data collection is ongoing.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Fatores de Coagulação Sanguínea/administração & dosagem , Hemorragia Cerebral/diagnóstico por imagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Melhoria de Qualidade , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X
18.
World Neurosurg ; 137: 408-414, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32105874

RESUMO

OBJECTIVE: Cerebral venous thrombosis (CVT) is a rare type of stroke whose pathophysiology differs from arterial stroke. CVT is treated with systemic anticoagulant therapy even in the setting of intracerebral hemorrhage. Patients who do not respond adequately may require decompressive surgery. The study objective was to examine the timing of anticoagulation in patients with CVT who require decompressive surgery through systematic literature review and consecutive case series. METHODS: A review of the literature was performed through PubMed using key word search to identify case series and cohort studies examining timing of anticoagulation following decompressive surgery. Our case series included 4 patients who had decompressive surgery for hemorrhagic CVT between 1 January, 2015 and 31 December, 2016 at our comprehensive stroke center. RESULTS: The literature review summarizes 243 patients from 15 studies whose timing of anticoagulation varied. The review suggests anticoagulation can be safely resumed at 48 hours postoperatively based on larger series and as early as 12 hours in smaller series, especially when delivered as a half or prophylactic dose. In our case series, timing of anticoagulation varied slightly but was started or resumed within 38-44 hours postoperatively in 3 patients and was started at the time of decompressive surgery without interruption in 1 patient. No patient had worsening hemorrhage or new hemorrhage while 2 patients rethrombosed. CONCLUSIONS: Despite the lack of high-quality studies, this systematic review of patients with CVT requiring decompressive surgery indicates that anticoagulation can be safely initiated or resumed around 24-48 hours postoperatively; our series supports the existing literature.


Assuntos
Anticoagulantes/administração & dosagem , Craniectomia Descompressiva/métodos , Heparina/administração & dosagem , Trombose dos Seios Intracranianos/terapia , Adulto , Anticoagulantes/efeitos adversos , Angiografia Cerebral , Hemorragia Cerebral/induzido quimicamente , Procedimentos Endovasculares , Feminino , Heparina/efeitos adversos , Antagonistas de Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/induzido quimicamente , Período Pós-Operatório , Protaminas/uso terapêutico , Trombectomia , Terapia Trombolítica , Fatores de Tempo
19.
Cochrane Database Syst Rev ; 1: CD004213, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985838

RESUMO

BACKGROUND: Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants and increases the risk of adverse outcomes. Indomethacin has been the standard treatment to close a PDA but is associated with renal, gastrointestinal, and cerebral side effects. Ibuprofen has less effect on blood flow velocity to important organs. OBJECTIVES: Primary objectives To determine the effectiveness and safety of ibuprofen compared to placebo/no intervention, or other cyclo-oxygenase inhibitor drugs in the prevention of PDA in preterm infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 10), MEDLINE via PubMed (1966 to 17 October 2018), Embase (1980 to 17 October 2018), and CINAHL; 1982 to 17 October 2018). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing ibuprofen with placebo/no intervention or other cyclo-oxygenase inhibitor drugs to prevent PDA in preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted outcomes data including presence of PDA on day three or four of life (after 72 hours of treatment), need for surgical ligation or rescue treatment with cyclo-oxygenase inhibitors, mortality, cerebral, renal, pulmonary, and gastrointestinal complications. We performed meta-analyses and reported treatment estimates as typical mean difference (MD), risk ratio (RR), risk difference (RD) and, if statistically significant, number needed to treat to benefit (NNTB) or to harm (NNTH), along with their 95% confidence intervals (CI). We assessed between-study heterogeneity by the I-squared test (I²). We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: In this updated analysis, we included nine trials (N = 1070 infants) comparing prophylactic ibuprofen (IV or oral) with placebo/no intervention or indomethacin. Ibuprofen (IV or oral) probably decreases the risk of PDA on day 3 or 4 (typical RR 0.39, 95% CI 0.31 to 0.48; typical RD -0.26, 95% CI -0.31 to -0.21; NNTB 4, 95% CI 3 to 5; 9 trials; N = 1029) (moderate-quality evidence). In the control group, the spontaneous closure rate was 58% by day 3 to 4 of age. In addition, ibuprofen probably decreases the need for rescue treatment with cyclo-oxygenase inhibitors (typical RR 0.17, 95% CI 0.11 to 0.26; typical RD -0.27, 95% CI -0.32 to -0.22; NNTB 4; 95% CI 3 to 5),and the need for surgical ductal ligation (typical RR 0.46, 95% CI 0.22 to 0.96; typical RD -0.03, 95% CI -0.05 to -0.00; NNTB 33, 95% CI 20 to infinity; 7 trials; N = 925) (moderate-quality evidence). There was a possible decrease in the risk of grade 3 or 4 intraventricular haemorrhage (IVH) in infants receiving prophylactic ibuprofen (typical RR 0.67, 95% CI 0.45 to 1.00; I² = 34%; typical RD -0.04, 95% CI -0.08 to- 0.00; I² = 60%; 7 trials; N = 925) (moderate-quality evidence). High quality evidence showed increased risk for oliguria (typical RR 1.45, 95% CI 1.04 to 2.02; typical RD 0.06, 95% CI 0.01 to 0.11; NNTH 17, 95% CI 9 to 100; 4 trials; N = 747). Low quality results from four studies (N = 202) showed that administering oral ibuprofen may decrease the risk of PDA (typical RR 0.47, 95% CI 0.30 to 0.74) and may increase risk of gastrointestinal bleeding (NNTH 7, 95% CI 4 to 25). No evidence of a difference was identified for mortality, any intraventricular haemorrhage (IVH), or chronic lung disease. AUTHORS' CONCLUSIONS: This review shows that prophylactic use of ibuprofen, compared to placebo or no intervention, probably decreases the incidence of patent ductus arteriosus, the need for rescue treatment with cyclo-oxygenase inhibitors, and for surgical ductal closure. Adverse effects associated with ibuprofen (IV or oral) included increased risks for oliguria, increase in serum creatinine levels, and increased risk of gastrointestinal haemorrhage. There was a reduced risk for intraventricular haemorrhage (grade III - IV) but no evidence of a difference in mortality, chronic lung disease, necrotising enterocolitis, or time to reach full feeds. In the control group, the patent ductus arteriosus had closed spontaneously by day 3 or 4 in 58% of neonates. Prophylactic treatment exposes a large proportion of infants unnecessarily to a drug that has important side effects without conferring any important short-term benefits. Current evidence does not support the use of ibuprofen for prevention of patent ductus arteriosus. Until long-term follow-up results of the trials included in this review have been published, no further trials of prophylactic ibuprofen are recommended. A new approach to patent ductus arteriosus management is an early targeted treatment based on echocardiographic criteria within the first 72 hours of life, that have a high sensitivity for diagnosing a patent ductus arteriosus that is unlikely to close spontaneously. Such trials are currently ongoing in many parts of the world. Results of such trials will be included in updates of our "Ibuprofen for treatment of PDA" review.


Assuntos
Inibidores de Ciclo-Oxigenase/uso terapêutico , Permeabilidade do Canal Arterial/prevenção & controle , Ibuprofeno/efeitos adversos , Ibuprofeno/uso terapêutico , Hemorragia Cerebral/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Enterocolite Necrosante/induzido quimicamente , Inibidores Enzimáticos/uso terapêutico , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Indometacina/uso terapêutico , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Vasc Med ; 25(1): 55-59, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31928394

RESUMO

Following an anticoagulation-associated intracerebral hemorrhage (ICH), whether and when to resume anticoagulation is controversial. Patient-level recurrence risk is difficult to predict with accuracy, but time-based recurrence risk may be more predictable. To better inform clinical decisions, we set out to estimate the net clinical benefit of anticoagulation over time among patients with atrial fibrillation. Using a large administrative dataset with 5339 index ICH hospitalizations and 132 readmissions for ICH, we created a two-stage prediction model, first predicting patient-level risk of recurrence and then predicting timing, conditional on recurrence. A log-normal survival function best explained the declining risk of recurrent ICH over time. We then compared risk of recurrent ICH over time against ischemic stroke risk, weighting the two outcomes to compute the net clinical benefit on each day following an index discharge. Using a bootstrapping approach, we identified the first day following discharge on which anticoagulation would lead to net benefit rather than net harm. Anticoagulation remains harmful for at least 11 days following index discharge and, depending on desired confidence level and assumptions, may remain harmful for as long as 62 days after discharge. Results were sensitive to the overall ICH recurrence risk. Although patient-level risk of recurrent ICH is difficult to predict accurately, recurrence risk declines rapidly over time. The survival function presented herein can inform decision-analytic models regarding when patients should resume anticoagulation following ICH.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/prevenção & controle , Hemorragia Cerebral/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Tomada de Decisão Clínica , Bases de Dados Factuais , Técnicas de Apoio para a Decisão , Esquema de Medicação , Feminino , Humanos , Masculino , Readmissão do Paciente , Seleção de Pacientes , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
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