Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-α2b in Healthy Adults: The IN2COVID Phase I Randomized Trial.

BACKGROUND AND OBJECTIVES: Interferons 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-α2b (IFN)-α2b in healthy adults. METHODS: A 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-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b 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 IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments. RESULTS: Exposure to inhaled IFN-α2b 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-α 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). CONCLUSIONS: Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects. CLINICAL TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.

[Nosocomial infections after cardiac surgery in infants and children with congenital heart disease]. / Infecciones asociadas a la atención en salud (IAAS) en pacientes pediátricos post-operados de cardiopatías congénitas.

INTRODUCTION: Nosocomial infections generate high morbidity and mortality in children undergoing cardiac surgery. OBJECTIVE: To determine risk factors for nosocomial infections in children after congenital heart surgery. METHODS: A retrospective case-control study, in patients younger than 15 years undergoing surgery for congenital heart disease from January 2007 to December 2011 admitted to the Pediatric Critical Patient Unit (UPC-P) in a university hospital. For cases, the information was analyzed from the first episode of infection. RESULTS: 39 patients who develop infections and 39 controls who did not develop infection were enrolled. The median age of cases was 2 months. We identified a number of factors associated with the occurrence of infections, highlighting in univariate analysis: age, weight, univentricular heart physiology, complexity of the surgical procedure according to RACHS-1 and cardiopulmonary bypass (CPB) time ≥ 200 minutes. Multivariate analysis identified CPB time ≥ 200 minutes as the major risk factor, with an OR of 11.57 (CI: 1.04 to 128.5). CONCLUSION: CPB time ≥ 200 minutes was the mayor risk factor associated with the development of nosocomial infections.

Infecciones asociadas a la atención en salud (IAAS) en pacientes pediátricos post-operados de cardiopatías congénitas / Nosocomial infections after cardiac surgery in infants and children with congenital heart disease

Introduction: Nosocomial infections generate high morbidity and mortality in children undergoing cardiac surgery. Objective: To determine risk factors for nosocomial infections in children after congenital heart surgery. Methods: A retrospective case-control study, in patients younger than 15 years undergoing surgery for congenital heart disease from January 2007 to December 2011 admitted to the Pediatric Critical Patient Unit (UPC-P) in a university hospital. For cases, the information was analyzed from the first episode of infection. Results: 39 patients who develop infections and 39 controls who did not develop infection were enrolled. The median age of cases was 2 months. We identified a number of factors associated with the occurrence of infections, highlighting in univariate analysis: age, weight, univentricular heart physiology, complexity of the surgical procedure according to RACHS-1 and cardiopulmonary bypass (CPB) time ≥ 200 minutes. Multivariate analysis identified CPB time ≥ 200 minutes as the major risk factor, with an OR of 11.57 (CI: 1.04 to 128.5). Conclusion: CPB time ≥ 200 minutes was the mayor risk factor associated with the development of nosocomial infections.

Introducción: Las infecciones asociadas a la atención en salud (IAAS) generan elevada morbilidad y mortalidad en niños sometidos a cirugía cardíaca. Objetivo: Determinar factores de riesgo que inciden en la ocurrencia de IAAS en niños operados de cardiopatías congénitas. Métodos: Estudio retrospectivo de casos y controles, en pacientes menores de 15 años sometidos a cirugía por cardiopatías congénitas desde enero 2007 a diciembre 2011 admitidos en la Unidad de Paciente Crítico Pediátrico (UPC-P) de un hospital universitario. Para los casos, se analizó la información del primer episodio de infección. Resultados: Se enrolaron 39 pacientes con IAAS y 39 controles operados que no desarrollaron infección. La mediana de edad de los casos fue 2 meses. Se identificó una serie de factores asociados a la ocurrencia de IAAS, destacando en el análisis univariado: edad, peso, fisiología cardíaca tipo univentricular, complejidad del procedimiento quirúrgico según RACHS-1 y tiempo de circulación extracorpórea (CEC) ≥ 200 min. El análisis multivariado identificó al tiempo de CEC ≥ 200 min como el principal factor de riesgo, con un OR de 11,57 (IC: 1,04-128,5). Conclusión: El tiempo de CEC ≥ 200 min fue el factor de riesgo más asociado al desarrollo de IAAS en niños operados de cardiopatías congénitas.