Browsing by Author "Severino Cuevas, Nicolás Felipe"

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    A cluster randomized trial of interferon ß-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19)
    (2021) Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Eiffler, Nat; Aniba, Rad; Pérez Mateluna, Guillermo; Meyer, Jessica K. V.; Severino Cuevas, Nicolás Felipe; Borzutzky Schachter, Arturo; Perret Pérez, Cecilia; Castro Rodríguez, José Antonio; García-Huidobro Munita, Diego Nicolás
    Abstract Background SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. Methods Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 μg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. Discussion The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. Trial Registration: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.
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    Cálculo de los Días de Terapia Antimicrobiana (DOT) en Cuidados Intensivos Pediátricos: una propuesta de metodología basada en el sistema informático de dispensación de medicamentos
    (2023) Gutiérrez Torres, Waldo; Gullone Bobadilla, Deborath; Severino Cuevas, Nicolás Felipe; Plaza Plaza, José Cristián; Pérez Pérez, Regina Elizabeth; Reyes Barros, Tomás Alejandro
    Introducción: El método recomendado para la medición de consumo de antimicrobianos (AMB) en pediatría es el cálculo del indicador Días de Terapia estandarizado por ocupación (DOT-std). Sin embargo, en hospitales que no cuentan con fichas electrónicas, obtener el numerador de los días de terapia (DOT) requiere revisión directa de las indicaciones del paciente, dificultando su aplicabilidad. Objetivos: Validar el sistema de registros electrónicos de dispensación de medicamentos desde farmacia como fuente para el cálculo de DOT y DOT-std en la Unidad de Cuidados Intensivos Pediátrica (UCIP). Materiales y Métodos: Se revisaron las prescripciones de AMB desde la ficha clínica (método manual) y se compararon con los registros de dispensación de AMB a la UCIP (método informático) obtenidos del sistema de medicamentos de farmacia. Se evaluó la concordancia entre los DOT obtenidos mediante el Coeficiente de Correlación Intraclase. Resultados: Los AMB más utilizados fueron vancomicina, meropenem y piperacilina/tazobactam. En 9 de 12 AMB se encontró concordancia significativa entre ambos métodos. Conclusiones: Tras un proceso de validación local, los registros del sistema informático de dispensación de medicamentos desde farmacia podrían utilizarse para el cálculo de DOT en pediatría en hospitales que no cuenten con una ficha electrónica que permita su cálculo directo.
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    Nefropatía aguda por fosfatos secundaria al uso de laxantes con fosfato de sodio: caso clínico-patológico
    (2021) Ávila Jiménez, Eduardo Rodolfo; Purto, Dalay; Kutscher Campero, Sofía; Cornejo Valenzuela, Cristina; Severino Cuevas, Nicolás Felipe; Méndez Olivieri, Gonzalo Patricio; Tagle Vargas, Rodrigo Jaime
    Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.
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    Population pharmacokinetics of amikacin in suspected cases of neonatal sepsis
    (Wiley, 2023) Severino Cuevas, Nicolás Felipe; Urzúa Baquedano, Maria Soledad; Ibacache Figueroa, Mauricio Enrique; Paulos Arenas, Claudio; Cortinez Fernandez, Luis Ignacio; Toso Milos, Alberto Antonio; Leguizamon Marino, Liliana Marcela; Inojosa Mackenzie, Fernanda; Maccioni Romero, Andrea Ana; Meza Cañas, Sebastián Jaime; Garcia, Andres; Ramirez, Marcelo; Von Mentlen Gutierrez, Catalina Paz; Ceballos Jorquera Javiera Nicol; Paredes Galvez, Noemi Saray
    Aims:This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin exposure. Methods: Newborns aged >= 3 days who received at least 1 dose of amikacin during their hospitalization period were eligible for the study. Amikacin was administered intravenously during a 60-min infusion period. Three venous blood samples were taken from each patient during the first 48 h. Population pharmacokinetic parameter estimates were obtained using a population approach with the programme NONMEM. ResultsData from 329 drug assay samples were obtained from 116 newborn patients (postmenstrual age [PMA] 38.3, range 32-42.4 weeks; weight 2.8, range 1.6-3.8 kg). Measured amikacin concentrations ranged from 0.8 to 56.4 mg/L. A 2-compartment model with linear elimination produced a good fit of the data. Estimated parameters for a typical subject (2.8 kg, 38.3 weeks) were clearance (Cl = 0.16 L/h), intercompartmental clearance (Q = 0.15 L/h), volume of distribution of the central compartment (Vc = 0.98 L) and peripheral volume of distribution (Vp = 1.23 L). Total bodyweight, PMA and the presence of sepsis positively influenced Cl. Plasma creatinine concentration and circulatory instability (shock) negatively influenced Cl. ConclusionOur main results confirm previous findings showing that weight, PMA and renal function are relevant factors influencing newborn amikacin pharmacokinetics. In addition, current results showed that pathophysiological states of critically ill neonates, such as sepsis and shock, were associated with opposite effects in amikacin clearance and should be considered in dose adjustments.
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    Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-& alpha;2b in Healthy Adults: The (INCOVID)-C-2 Phase I Randomized Trial
    (2023) García-Huidobro Munita, Diego Nicolás; Iturriaga, Carolina; Perez-Mateluna, Guillermo; Fajuri, Paula; Severino Cuevas, Nicolás Felipe; Urzua, Marcela; Fraga, Juan Pablo; Cruz, Javiera de la; Poli, Cecilia; Castro Rodríguez, José Antonio; Fish, Eleanor; Borzutzky, Arturo
    Background and ObjectivesInterferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-& alpha;2b (IFN)-& alpha;2b in healthy adults.MethodsA double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-& alpha;2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-& alpha;2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFN & alpha; concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments.ResultsExposure to inhaled IFN-& alpha;2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-& alpha; concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons).ConclusionsInhaled IFN-& alpha;2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects.