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1.
Hepatology ; 58(2): 777-87, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23390034

RESUMO

UNLABELLED: Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. CONCLUSION: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Proteína HMGB1/sangue , Hospitalização , Queratina-18/sangue , MicroRNAs/sangue , Adulto , Alanina Transaminase/metabolismo , Biomarcadores/sangue , Gerenciamento Clínico , Feminino , Glutamato Desidrogenase/metabolismo , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de Tempo
2.
N Engl J Med ; 359(2): 142-51, 2008 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-18614781

RESUMO

BACKGROUND: Noninvasive ventilation (continuous positive airway pressure [CPAP] or noninvasive intermittent positive-pressure ventilation [NIPPV]) appears to be of benefit in the immediate treatment of patients with acute cardiogenic pulmonary edema and may reduce mortality. We conducted a study to determine whether noninvasive ventilation reduces mortality and whether there are important differences in outcome associated with the method of treatment (CPAP or NIPPV). METHODS: In a multicenter, open, prospective, randomized, controlled trial, patients were assigned to standard oxygen therapy, CPAP (5 to 15 cm of water), or NIPPV (inspiratory pressure, 8 to 20 cm of water; expiratory pressure, 4 to 10 cm of water). The primary end point for the comparison between noninvasive ventilation and standard oxygen therapy was death within 7 days after the initiation of treatment, and the primary end point for the comparison between NIPPV and CPAP was death or intubation within 7 days. RESULTS: A total of 1069 patients (mean [+/-SD] age, 77.7+/-9.7 years; female sex, 56.9%) were assigned to standard oxygen therapy (367 patients), CPAP (346 patients), or NIPPV (356 patients). There was no significant difference in 7-day mortality between patients receiving standard oxygen therapy (9.8%) and those undergoing noninvasive ventilation (9.5%, P=0.87). There was no significant difference in the combined end point of death or intubation within 7 days between the two groups of patients undergoing noninvasive ventilation (11.7% for CPAP and 11.1% for NIPPV, P=0.81). As compared with standard oxygen therapy, noninvasive ventilation was associated with greater mean improvements at 1 hour after the beginning of treatment in patient-reported dyspnea (treatment difference, 0.7 on a visual-analogue scale ranging from 1 to 10; 95% confidence interval [CI], 0.2 to 1.3; P=0.008), heart rate (treatment difference, 4 beats per minute; 95% CI, 1 to 6; P=0.004), acidosis (treatment difference, pH 0.03; 95% CI, 0.02 to 0.04; P<0.001), and hypercapnia (treatment difference, 0.7 kPa [5.2 mm Hg]; 95% CI, 0.4 to 0.9; P<0.001). There were no treatment-related adverse events. CONCLUSIONS: In patients with acute cardiogenic pulmonary edema, noninvasive ventilation induces a more rapid improvement in respiratory distress and metabolic disturbance than does standard oxygen therapy but has no effect on short-term mortality. (Current Controlled Trials number, ISRCTN07448447.)


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Ventilação com Pressão Positiva Intermitente , Oxigenoterapia , Edema Pulmonar/terapia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Cardiopatias/complicações , Humanos , Ventilação com Pressão Positiva Intermitente/métodos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Estudos Prospectivos , Edema Pulmonar/etiologia , Edema Pulmonar/mortalidade
3.
Emerg Med J ; 28(6): 477-82, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20921019

RESUMO

BACKGROUND: The aim of this study was to measure health utility and survival in patients with acute cardiogenic pulmonary oedema (ACPO), identify predictors of outcome and determine the effect of initial treatment with non-invasive ventilation (NIV) upon outcomes. METHODS: A randomised controlled trial was conducted at 26 hospitals in the UK. 1069 adults with ACPO were randomised to continuous positive airway pressure (CPAP), non-invasive positive pressure ventilation (NIPPV) or standard oxygen therapy. The main outcome measures were survival to 1-5 years, health utility measured using the EQ-5D survey at 1, 3 and 6 months, and quality-adjusted life years (QALYs). RESULTS: Median survival was 771 days (95% CI 669 to 875), with no difference between the three treatment groups (p = 0.827). Age (HR 1.042, 95% CI 1.031 to 1.052), chronic obstructive pulmonary disease (HR 1.13, 95% CI 1.06 to 1.62), cerebrovascular disease (HR 1.41, 95% CI 1.14 to 1.73) and diabetes mellitus (HR 1.31, 95% CI 1.01 to 1.63) independently predicted mortality. Mean EQ-5D scores were 0.578, 0.576 and 0.582 at 1, 3 and 6 months, respectively, with no significant difference between the treatment groups. Male gender (+0.045 QALYs, 95% CI 0.009 to 0.081) and cerebrovascular disease (-0.080 QALYs, 95% CI -0.131 to -0.029) independently predicted health utility. CONCLUSION: Patients with ACPO have high mortality and reduced health utility. Initial treatment with CPAP or NIPPV does not alter subsequent survival or health utility.


Assuntos
Doenças Cardiovasculares/epidemiologia , Causas de Morte , Pressão Positiva Contínua nas Vias Aéreas/mortalidade , Mortalidade Hospitalar/tendências , Oxigenoterapia/mortalidade , Edema Pulmonar/mortalidade , Edema Pulmonar/terapia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Intervalos de Confiança , Pressão Positiva Contínua nas Vias Aéreas/métodos , Estado Terminal/mortalidade , Estado Terminal/terapia , Serviço Hospitalar de Emergência , Tratamento de Emergência/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Admissão do Paciente/estatística & dados numéricos , Respiração com Pressão Positiva/mortalidade , Modelos de Riscos Proporcionais , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco , Análise de Sobrevida , Reino Unido/epidemiologia
4.
Circ Heart Fail ; 3(1): 111-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19880805

RESUMO

BACKGROUND: Acute cardiogenic pulmonary edema is a common medical emergency with high early mortality. Initial clinical assessment would benefit from accurate mortality prediction. We aimed to develop a simple clinical score based on presenting characteristics that would predict 7-day mortality in patients with acute cardiogenic pulmonary edema. METHODS AND RESULTS: We used data from patients recruited to the 3CPO trial (a pragmatic multicenter trial comparing continuous positive airway pressure, noninvasive positive pressure ventilation, and standard oxygen therapy in emergency department patients with acute cardiogenic pulmonary edema) to investigate the association between baseline characteristics and 7-day mortality. Factors associated with mortality (P<0.1) were entered into a multivariable model. Independent predictors of mortality from the multivariable model (P<0.05) were assigned integer weights based on their coefficients and incorporated into a risk score. The discriminant ability of the score was tested by receiver operator characteristic analysis. Data from 1069 patients (78+/-10 years; 43% men; 7-day mortality, 9.6%) were analyzed. Multivariable analysis identified age (P=0.003), systolic blood pressure (P<0.001), and Glasgow Coma Scale motor component dichotomized and simplified to the ability to obey commands or not (P=0.02) as the only independent predictors of 7-day mortality. These were weighted and used to develop a risk score ranging from 0 (7-day mortality, 1.9%; 95% CI, 0.8 to 4.5) to 7 (7-day mortality, 100%; 95% CI, 34.2 to 100). Receiver operator characteristic analysis demonstrated good risk prediction with a c-statistic of 0.794 (95% CI, 0.745 to 0.843). A simplified 3-point score with no weighting had a c-statistic of 0.754 (95% CI, 0.701 to 0.807). CONCLUSIONS: A simple clinical score based on age, systolic blood pressure, and the ability to obey commands predicts early mortality in patients with acute cardiogenic pulmonary edema. Clinical Trial Registration- clinicaltrials.gov Identifier: ISRCTN077448447.


Assuntos
Edema Pulmonar/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
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