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STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.
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Objective: Protocols to evaluate for myocardial infarction (MI) using high-sensitivity cardiac troponin (hs-cTn) have the potential to drive costs upward due to the added sensitivity. We performed an economic evaluation of an accelerated protocol (AP) to evaluate for MI using hs-cTn to identify changes in costs of treatment and length of stay compared with conventional testing. Methods: We performed a planned secondary economic analysis of a large, cluster randomized trial across nine emergency departments (EDs) from July 2020 to April 2021. Patients were included if they were 18 years or older with clinical suspicion for MI. In the AP, patients could be discharged without further testing at 0 h if they had a hs-cTnI < 4 ng/L and at 1 h if the initial value were 4 ng/L and the 1-h value ≤7 ng/L. Patients in the standard of care (SC) protocol used conventional cTn testing at 0 and 3 h. The primary outcome was the total cost of treatment, and the secondary outcome was ED length of stay. Results: Among 32,450 included patients, an AP had no significant differences in cost (+$89, CI: -$714, $893 hospital cost, +$362, CI: -$414, $1138 health system cost) or ED length of stay (+46, CI: -28, 120 min) compared with the SC protocol. In lower acuity, free-standing EDs, patients under the AP experienced shorter length of stay (-37 min, CI: -62, 12 min) and reduced health system cost (-$112, CI: -$250, $25). Conclusion: Overall, the implementation of AP using hs-cTn does not result in higher costs.
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Chronic refractory angina remains a common and debilitating condition for millions of people, with up to 30% of patients experiencing persistent angina despite successful revascularization. We share our experience with the implantation of a coronary sinus reducer in two complex CAD patients with refractory angina despite multiple revascularization strategies and maximally tolerated medical therapy.
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Seno Coronario , Angina de Pecho/diagnóstico , Angina de Pecho/terapia , Seno Coronario/diagnóstico por imagen , Seno Coronario/cirugía , Humanos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the relationship between maximal exercise capacity measured before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalization due to coronavirus disease 2019 (COVID-19). METHODS: We identified patients (≥18 years) who completed a clinically indicated exercise stress test between January 1, 2016, and February 29, 2020, and had a test for SARS-CoV-2 (ie, real-time reverse transcriptase polymerase chain reaction test) between February 29, 2020, and May 30, 2020. Maximal exercise capacity was quantified in metabolic equivalents of task (METs). Logistic regression was used to evaluate the likelihood that hospitalization secondary to COVID-19 is related to peak METs, with adjustment for 13 covariates previously identified as associated with higher risk for severe illness from COVID-19. RESULTS: We identified 246 patients (age, 59±12 years; 42% male; 75% black race) who had an exercise test and tested positive for SARS-CoV-2. Among these, 89 (36%) were hospitalized. Peak METs were significantly lower (P<.001) among patients who were hospitalized (6.7±2.8) compared with those not hospitalized (8.0±2.4). Peak METs were inversely associated with the likelihood of hospitalization in unadjusted (odds ratio, 0.83; 95% CI, 0.74-0.92) and adjusted models (odds ratio, 0.87; 95% CI, 0.76-0.99). CONCLUSION: Maximal exercise capacity is independently and inversely associated with the likelihood of hospitalization due to COVID-19. These data further support the important relationship between cardiorespiratory fitness and health outcomes. Future studies are needed to determine whether improving maximal exercise capacity is associated with lower risk of complications due to viral infections, such as COVID-19.
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COVID-19/fisiopatología , Tolerancia al Ejercicio , Hospitalización/estadística & datos numéricos , Neumonía Viral/fisiopatología , Prueba de COVID-19 , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Viral/epidemiología , Neumonía Viral/virología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Accumulation of the synaptic protein alpha-synuclein (alpha-syn) is a hallmark of Parkinson's disease (PD) and Lewy body disease (LBD), a heterogeneous group of disorders with dementia and parkinsonism, where Alzheimer's disease and PD interact. Accumulation of alpha-syn in these patients might be associated with alterations in the autophagy pathway. Therefore, we postulate that delivery of beclin 1, a regulator of the autophagy pathway, might constitute a strategy toward developing a therapy for LBD/PD. Overexpression of alpha-syn from lentivirus transduction in a neuronal cell line resulted in lysosomal accumulation and alterations in autophagy. Coexpression of beclin 1 activated autophagy, reduced accumulation of alpha-syn, and ameliorated associated neuritic alterations. The effects of beclin 1 overexpression on LC3 and alpha-syn accumulation were partially blocked by 3-MA and completely blocked by bafilomycin A1. In contrast, rapamycin enhanced the effects of beclin 1. To evaluate the potential effects of activating autophagy in vivo, a lentivirus expressing beclin 1 was delivered to the brain of a alpha-syn transgenic mouse. Neuropathological analysis demonstrated that beclin 1 injections ameliorated the synaptic and dendritic pathology in the tg mice and reduced the accumulation of alpha-syn in the limbic system without any significant deleterious effects. This was accompanied by enhanced lysosomal activation and reduced alterations in the autophagy pathway. Thus, beclin 1 plays an important role in the intracellular degradation of alpha-syn either directly or indirectly through the autophagy pathway and may present a novel therapeutic target for LBD/PD.
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Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/fisiología , Enfermedad por Cuerpos de Lewy/fisiopatología , Degeneración Nerviosa/fisiopatología , Enfermedad de Parkinson/fisiopatología , alfa-Sinucleína/metabolismo , Animales , Beclina-1 , Encéfalo/citología , Encéfalo/patología , Encéfalo/fisiopatología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Técnicas de Transferencia de Gen , Humanos , Enfermedad por Cuerpos de Lewy/patología , Ratones , Ratones Transgénicos , Degeneración Nerviosa/patología , Neuronas/citología , Neuronas/patología , Neuronas/fisiología , Enfermedad de Parkinson/patología , Ratas , Transducción de Señal , alfa-Sinucleína/genéticaRESUMEN
INTRODUCTION: The purpose of the study is to develop an optimal TR-Band weaning strategy while minimizing vascular access site complications of hematoma or radial artery occlusion (RAO). METHODS: The trial was a randomized, prospective, single center study of 129 patients who underwent cardiac catheterization via the radial artery. Group A was an accelerated protocol in which weaning was initiated 20â¯min after sheath removal. Group B was an adjusted protocol, in which weaning was dependent on the amount of anti-platelet or anti-coagulation used. All patients underwent radial artery ultrasound to demonstrate arterial patency. RESULTS: Baseline characteristics were similar in both groups, and PCI was performed in 36.7% of patients in Group A and 37.7% of patients in Group B. RAO occurred in 7.7% of patients overall, with no statistical difference between groups (Group A 5% versus Group B 10.1%, p-valueâ¯=â¯0.337). Hematoma formation >5â¯cm in diameter occurred in 4.6% of patients in the overall cohort, without statistical difference between groups (Group A 5% versus Group B 4.3%, p-valueâ¯=â¯1). The TR-Band duration was significantly shorter in Group A compared to Group B (112.9⯱â¯50.7 versus 130.7⯱â¯51.1 in minutes, respectively, p-valueâ¯=â¯0.013). CONCLUSION: We have demonstrated an accelerated weaning protocol is simple to utilize for nursing staff without increased vascular site complications of RAO or hematoma formation.
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Cateterismo Cardíaco , Cateterismo Periférico , Hemorragia/prevención & control , Técnicas Hemostáticas/instrumentación , Arteria Radial , Anciano , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/fisiopatología , Cateterismo Periférico/efectos adversos , Femenino , Hematoma/etiología , Hemorragia/etiología , Técnicas Hemostáticas/efectos adversos , Humanos , Masculino , Michigan , Persona de Mediana Edad , Estudios Prospectivos , Punciones , Arteria Radial/diagnóstico por imagen , Arteria Radial/fisiopatología , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Management strategies to ensure medication adherence for patients following percutaneous coronary intervention have not changed in recent years despite the dismal rates of non-compliance with dual antiplatelet therapy. The goal of this review is to emphasis the importance of dual antiplatelet therapy in patients following percutaneous coronary intervention, discuss the clinical and economic ramifications of premature discontinuation and strategies for improvement.
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Cumplimiento de la Medicación , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Quimioterapia Combinada , Costos de la Atención en Salud , Humanos , Inhibidores de Agregación Plaquetaria/administración & dosificaciónRESUMEN
Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid ß-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aß, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD.