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1.
Clin Infect Dis ; 74(10): 1812-1820, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34409431

RESUMO

BACKGROUND: The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19. METHODS: In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC). Patients hospitalized between 28 February and 28 May 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were included with the development of COVID-19 pneumonia on chest radiography and hypoxia requiring supplemental oxygen or oxygen saturation ≤94% with room air. The primary outcome was overall survival, assessed with time-dependent Cox proportional hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use, and random effects for hospital. RESULTS: A total of 1138 patients were enrolled, including 286 who received RDV and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). Comparing persons receiving RDV with those receiving BSC, the hazard ratio (95% confidence interval) for death was 0.46 (.31-.69) in the univariate model (P < .001) and 0.60 (.40-.90) in the risk-adjusted model (P = .01). In the subgroup of persons with baseline use of low-flow oxygen, the hazard ratio (95% confidence interval) for death in RDV compared with BSC was 0.63 (.39-1.00; P = .049). CONCLUSION: Treatment with RDV was associated with lower mortality rates than BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen.


Assuntos
Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Humanos , Oxigênio , Estudos Retrospectivos , SARS-CoV-2
2.
Crit Care ; 25(1): 70, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596975

RESUMO

BACKGROUND: The early months of the COVID-19 pandemic were fraught with much uncertainty and some resource constraint. We assessed the change in survival to hospital discharge over time for intensive care unit patients with COVID-19 during the first 3 months of the pandemic and the presence of any surge effects on patient outcomes. METHODS: Retrospective cohort study using electronic medical record data for all patients with laboratory-confirmed COVID-19 admitted to intensive care units from February 25, 2020, to May 15, 2020, at one of 26 hospitals within an integrated delivery system in the Western USA. Patient demographics, comorbidities, and severity of illness were measured along with medical therapies and hospital outcomes over time. Multivariable logistic regression models were constructed to assess temporal changes in survival to hospital discharge during the study period. RESULTS: Of 620 patients with COVID-19 admitted to the ICU [mean age 63.5 years (SD 15.7) and 69% male], 403 (65%) survived to hospital discharge and 217 (35%) died in the hospital. Survival to hospital discharge increased over time, from 60.0% in the first 2 weeks of the study period to 67.6% in the last 2 weeks. In a multivariable logistic regression analysis, the risk-adjusted odds of survival to hospital discharge increased over time (biweekly change, adjusted odds ratio [aOR] 1.22, 95% CI 1.04-1.40, P = 0.02). Additionally, an a priori-defined explanatory model showed that after adjusting for both hospital occupancy and percent hospital capacity by COVID-19-positive individuals and persons under investigation (PUI), the temporal trend in risk-adjusted patient survival to hospital discharge remained the same (biweekly change, aOR 1.18, 95% CI 1.00-1.38, P = 0.04). The presence of greater rates of COVID-19 positive/PUI as a percentage of hospital capacity was, however, significantly and inversely associated with survival to hospital discharge (aOR 0.95, 95% CI 0.92-0.98, P < 0.01). CONCLUSIONS: During the early COVID-19 pandemic, risk-adjusted survival to hospital discharge increased over time for critical care patients. An association was also seen between a greater COVID-19-positive/PUI percentage of hospital capacity and a lower survival rate to hospital discharge.


Assuntos
COVID-19/epidemiologia , COVID-19/terapia , Pandemias , Alta do Paciente/estatística & dados numéricos , Idoso , COVID-19/mortalidade , Cuidados Críticos , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Análise de Sobrevida , Estados Unidos/epidemiologia
3.
Curr Atheroscler Rep ; 20(3): 14, 2018 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-29455255

RESUMO

PURPOSE OF REVIEW: Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD); however, lipid testing for risk assessment and treatment surveillance has been underutilized. Several factors likely account for this, including the common practice of measuring lipid levels in the fasting state, which often necessitates that patients return for an additional visit. In this review, we evaluate potential advantages and cautions associated with measuring lipids in the non-fasting state. RECENT FINDINGS: There is similar performance with the use of either fasting or non-fasting total cholesterol and HDL cholesterol in ASCVD risk assessment. Observational studies demonstrate that in comparison to fasting levels, non-fasting triglycerides are approximately 20% higher on average, although the magnitude of difference is subject to substantial inter-patient variability. Higher triglycerides can lead to the under-estimation of low-density lipoprotein cholesterol (LDL-C) by approximately 10 mg/dL or more when calculated using the Friedewald equation. This is especially clinically relevant at low LDL-C levels, although a novel validated algorithm for LDL-C estimation largely overcomes this limitation. Non-fasting lipid assessment is reasonable in many clinical circumstances given that ASCVD risk prediction is similar using fasting or non-fasting lipid values and because LDL-C can be accurately estimated using modern methods. Allowing the option for non-fasting lipid assessment can reduce a barrier to lipid testing and can facilitate a more convenient assessment of ASCVD risk with the ultimate potential effect of reducing the global burden of ASCVD. However, certain patients such as those with severe hypertriglyceridemias or high-risk patients being treated to low LDL-C levels may still need fasting lipid panels performed for precise diagnosis and to standardize therapeutic monitoring.


Assuntos
Aterosclerose/sangue , Aterosclerose/diagnóstico , Jejum/sangue , Lipídeos/sangue , Aterosclerose/terapia , Humanos , Estudos Observacionais como Assunto , Medição de Risco , Fatores de Risco
5.
J Am Heart Assoc ; 6(11)2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29097390

RESUMO

BACKGROUND: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome. METHODS AND RESULTS: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11-dehydrothromboxane B2 (11-dhTXB2), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, and death alone. 11-dhTXB2 measured 3 days after surgery did not independently predict outcome, whereas 11-dhTXB2 >450 pg/mg creatinine measured 6 months after surgery predicted the composite end point (adjusted hazard ratio, 1.79; P=0.02) and death (adjusted hazard ratio, 2.90; P=0.01) at 5 years compared with lower values. Additional modeling revealed 11-dhTXB2 measured early after surgery associated with several markers of inflammation, in contrast to 11-dhTXB2 measured 6 months later, which highly associated with oxidative stress. CONCLUSIONS: Long-term nonplatelet thromboxane generation after coronary artery bypass graft surgery is a novel risk factor for 5-year adverse outcome, including death. In contrast, nonplatelet thromboxane generation in the early postoperative period appears to be driven predominantly by inflammation and did not independently predict long-term clinical outcome.


Assuntos
Aspirina/administração & dosagem , Ponte de Artéria Coronária , Inibidores da Agregação Plaquetária/administração & dosagem , Tromboxano A2/sangue , Tromboxano B2/análogos & derivados , Idoso , Aspirina/efeitos adversos , Biomarcadores/sangue , Biomarcadores/urina , Causas de Morte , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/urina , Inibidores da Agregação Plaquetária/efeitos adversos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/urina , Tromboxano B2/urina , Fatores de Tempo , Resultado do Tratamento , Urinálise
6.
Future Cardiol ; 12(5): 539-44, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27539057

RESUMO

AIM: To propose a method for estimating the lifetime advantage of statins. METHODS: Kaplan-Meier survival curves from published 4S and LIPID studies with 5.8- and 6.1-year follow-up were digitized. Gompertz distributions were fit up to the end of the trials, and then extrapolated out to the end of the patients' predicted lifetimes for each study. RESULTS: The method results in a 9.9 (95% CI: 8.7-11.9) and 2.8 (95% CI: 2.3-3.3) years' increases for the statin groups for 4S and LIPID studies, respectively. CONCLUSION: Previous analysis of the same data was limited by the trials' relatively short run time. As such, we propose a method for correctly estimating the true effect of statin therapy in terms of total lifetime extension.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estimativa de Kaplan-Meier , Longevidade/efeitos dos fármacos , Humanos , Expectativa de Vida , Pravastatina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Sinvastatina/uso terapêutico , Fatores de Tempo
7.
Am J Cardiol ; 95(6): 744-7, 2005 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-15757601

RESUMO

The incidence of antiplatelet factor-4/heparin antibody formation in patients who receive contemporary doses of unfractionated heparin in the setting of percutaneous coronary revascularization is unknown. Also unknown is the ability of these antibodies to activate platelets or adversely affect clinical outcome in the absence of clinically recognized heparin-induced thrombocytopenia. To address these questions, we serially measured antiplatelet factor-4/heparin antibody levels and performed serotonin release assays in patients who underwent percutaneous coronary intervention. Correlations were then made across antibody induction, heparin exposure, and clinical outcome at 6 months.


Assuntos
Angina Pectoris/imunologia , Angioplastia Coronária com Balão , Formação de Anticorpos/imunologia , Doença das Coronárias/imunologia , Heparina/imunologia , Infarto do Miocárdio/imunologia , Fator Plaquetário 4/imunologia , Idoso , Angina Pectoris/mortalidade , Angina Pectoris/terapia , Formação de Anticorpos/efeitos dos fármacos , Doença das Coronárias/mortalidade , Doença das Coronárias/terapia , Feminino , Seguimentos , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Doenças do Complexo Imune/induzido quimicamente , Doenças do Complexo Imune/imunologia , Doenças do Complexo Imune/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Ativação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/imunologia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/mortalidade , Recidiva , Fatores de Risco , Serotonina/sangue , Taxa de Sobrevida
8.
J Am Coll Cardiol ; 57(9): 1069-77, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21349398

RESUMO

OBJECTIVES: The purpose of this study was to determine if an incomplete response to or inadequate antiplatelet effect of aspirin, or both, contribute to saphenous vein graft (SVG) occlusion after coronary artery bypass graft (CABG) surgery. BACKGROUND: Thrombosis is the predominant cause of early SVG occlusion. Aspirin, which inhibits cyclooxygenase-1 activity and thromboxane generation in platelets, reduces early SVG occlusion by one-half. METHODS: Aspirin responsiveness and platelet reactivity were characterized 3 days and 6 months after coronary artery bypass graft surgery in 229 subjects receiving aspirin monotherapy by platelet aggregation to arachidonic acid, adenosine diphosphate, collagen and epinephrine, Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Newark, Delaware) closure time (CT) using collagen/epinephrine agonist cartridge and collagen/adenosine diphosphate (CADP) agonist cartridge, VerifyNow Aspirin assay (Accumetrics, Inc., San Diego, California), and urine levels of 11-dehydro-thromboxane B(2) (UTXB(2)). SVG patency was determined 6 months after surgery by computed tomography coronary angiography. RESULTS: Inhibited arachidonic acid-induced platelet aggregation, indicative of aspirin-mediated cyclooxygenase-1 suppression, occurred in 95% and >99% of subjects 3 days and 6 months after surgery, respectively. Despite this, 73% and 31% of subjects at these times had elevated UTXB(2). Among tested parameters, only UTXB(2) and CADP CT measured 6 months after surgery correlated with outcome. By multivariate analysis, CADP CT of ≤88 s (odds ratio: 2.85, p = 0.006), target vessel diameter of ≤1.5 mm (odds ratio: 2.38, p = 0.01), and UTXB(2) of ≥450 pg/mg creatinine (odds ratio: 2.59, p = 0.015) correlated with SVG occlusion. CADP CT and UTXB(2) in combination further identified subjects at particularly high and low risk for SVG occlusion. CONCLUSIONS: Aspirin-insensitive thromboxane generation measured by UTXB(2) and shear-dependent platelet hyper-reactivity measured by Platelet Function Analyzer-100 CADP CT are novel independent risk factors for early SVG thrombosis after coronary artery bypass graft surgery.


Assuntos
Aspirina/uso terapêutico , Oclusão de Enxerto Vascular/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Veia Safena/transplante , Idoso , Angiografia Coronária , Ponte de Artéria Coronária/efeitos adversos , Feminino , Seguimentos , Oclusão de Enxerto Vascular/sangue , Oclusão de Enxerto Vascular/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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