RESUMO
OBJECTIVES: To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. METHODS: This phase 2a, double-blind, multicentre study randomly assigned RSV-positive adult outpatients ≤5 days from symptom onset 1:1:1 to receive rilematovir 500 mg, 80 mg, or placebo once-daily for 7 days. Antiviral effect was assessed by RSV RNA viral load (VL), measured by quantitative RT-PCR, and Kaplan-Meier (KM) estimates of time to undetectable VL. Clinical course was assessed by KM estimates of median time to resolution of key RSV symptoms assessed through patient-reported outcomes. RESULTS: RSV-positive patients (n = 72) were randomly assigned; 66 had confirmed RSV infection and received rilematovir 500 mg (n = 23), 80 mg (n = 21) or placebo (n = 22). Differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5 and 8, respectively, were 0.09 (-0.837; 1.011), -0.10 (-2.171; 1.963), and -1.03 (-4.746; 2.682) log10 copies.day/mL for rilematovir 500 mg, and 1.25 (0.291; 2.204), 2.53 (0.430; 4.634), and 3.85 (0.097; 7.599) log10 copies.day/mL for rilematovir 80 mg. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90), 8.0 (6.86; 12.80) and 7.0 (6.62; 10.88) days and 5.7 (2.93; 7.01), 8.1 (6.74; 12.80) and 7.9 (6.62; 11.74) days in patients with symptom onset ≤3 days, for rilematovir 500 mg, 80 mg, and placebo, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43), 7.6 (5.93; 8.32), and 9.6 (5.95; 14.00) days for rilematovir 500 mg, 80 mg, and placebo, respectively; and in patients with symptom onset ≤3 days, median 8.0, 7.6, and 11.8 days, respectively. DISCUSSION: Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov (NCT03379675).
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Adulto , Humanos , Antivirais/efeitos adversos , Método Duplo-Cego , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , RNARESUMO
La Rehabilitación Respiratoria (RR), dirigida a las personas con enfermedad respiratoria crónica, reduce las exacerbaciones y hospitalizaciones, mejora los síntomas, la tolerancia al ejercicio y calidad de vida. Miembros de la Sección de RR de la Asociación Argentina de Medicina Respiratoria, se reunieron con el objetivo de preguntarse cuáles son los temas principales de controversia para dar respuesta desde la medicina basada en evidencia (sistema GRADE). Se eligieron diez preguntas. Resultados: La RR se debe indicar en pacientes con EPOC estadio GOLD 1 (1C). La adherencia es fundamental y se relaciona a sus beneficios (1C). La actividad física debe ser evaluada y estimulada (1B). Los beneficios de la RR dentro del mes posterior a una exacerbación de EPOC, reduce los síntomas y exacerbaciones y mejora la calidad de vida (1B). La RR está indicada en algunas enfermedades respiratorias crónicas no-EPOC (1B). Se deben indicar estrategias de entrenamiento especiales en desnutridos (3B) y obesos (3C). Los pacientes deben ser evaluados con prueba de ejercicio, escalas de disnea y calidad de vida (1A). El rol del entrenador de salud es novedoso ya que disminuye hospitalizaciones y mejora la calidad de vida (2C). Las comorbilidades afectan el resultado de la RR (3B). La RR reduce la mortalidad (1B) y la ansiedad-depresión (2B). La RR domiciliaria es efectiva (1A). La RR es fundamental en el tratamiento de enfermedades respiratorias crónicas. Se han actualizado las recomendaciones en RR en base a la evidencia científica con el objetivo que la RR pueda aplicarse en nuestro país.
Respiratory Rehabilitation (RR) is indicated in patients with chronic pulmonary diseases to reduce exacerbations and hospitalizations, and to improve symptoms, exercise tolerance and quality of life. Members of RR Section of the Asociación Argentina de Medicina Respiratoria, joined to review critical issues and controversies by an evidence-based system (GRADE). Ten questions were elected.213 Results: RR must be indicated in GOLD 1 COPD (1C). Adherence in RR is critical and related to benefits (1C). Physical activity must be evaluated and stimulated (1B). RR implemented after one month of COPD exacerbation hospitalization, reduces symptoms and exacerbations and improves quality of life(1B). RR is indicated in some no-COPD chronic respiratory diseases (1B). Special training strategies must be used in undernourished (3B) and obeses patients (3C). Exercise tests, dyspnea and quality of life questionnaires must be used to evaluate patients (1A). Health trainer is an original strategy to reduce hospitalizations and improve quality of life (2C). Comorbilities impacts on RR outcomes (3B). RR reduces mortality (1B) and ansiety-depression (2B). Domiciliary RR is efective (1A). RR is a key component of chronic pulmonary diseases treatment. Based in new scientific evidence, local recomendations have been done regarding to improve access in our country.
Assuntos
Reabilitação , Doenças Respiratórias , Doença Pulmonar Obstrutiva CrônicaRESUMO
Respiratory rehabilitation (RR) is a multidisciplinary program of care for patients with chronic respiratory impairment, individually tailored, designed to optimize physical and social performance and patient autonomy. It is particularly indicated in chronic obstructive pulmonary disease (COPD) patients with exercise intolerance. The objectives of respiratory rehabilitation are: reduction in symptoms and exercise intolerance, improvement of health-related quality of life, and reduction of health costs. A group of neumonologists, nutritionists and physical therapists performed a systematic review of the evidence in RR to update previous local guidelines. Inclusion and exclusion criteria, guidelines for initial evaluation and follow up and resources needed are defined. Training characteristics are recommended regarding frequency of the visits, intensity, progression and duration of the exercise training. Aerobic training was recommended for lower limb (1A), upper limb (1B). Strength training must be added (1B). Respiratory muscle training and other physiotherapy techniques were recommended only for specific patients (1C). In addition recommendations have been made for educational objectives of the program including smoking cessation, nutritional and psychological support. The positive impact of RR on reductions of health care costs and reductions on hospitalizations (Evidence A) and mortality (Evidence B) were analized. Respiratory rehabilitation is a key component in the modern treatment of COPD patients. This consensus statement was prepared based on the most recent scientific evidence and adjusted to the local environment with the aim of being implemented nationally.
Assuntos
Terapia por Exercício/normas , Tolerância ao Exercício/fisiologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Argentina , Avaliação da Deficiência , Controle de Formulários e Registros , Humanos , Educação de Pacientes como Assunto , Qualidade de VidaRESUMO
La rehabilitación respiratoria (RR) es un tratamiento multidisciplinario para pacientes con enfermedad respiratoria crónica, adaptado individualmente y diseñado para optimizar la capacidad física, la actividad social y la autonomía de los mismos. Está especialmente indicado en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Los objetivos de la RR son: reducir los síntomas, mejorar la tolerancia al ejercicio físico y la calidad de vida. Un grupo de neumonólogos, nutricionistas y kinesiólogos realizó un análisis sistemàtico de la evidencia científica con el objetivo de actualizar las normativas anteriores de RR. Se definieron los criterios de inclusión y exclusión, la evaluación inicial y de seguimiento como así también los elementos y material necesarios. Las características del entrenamiento en cuanto a la frecuencia de las visitas, la intensidad, progresión y duración del ejercicio han sido revisadas. Se recomendó el entrenamiento de los miembros inferiores (1A), miembros superiores (1B), complementando el entrenamiento de fuerza (1B). El entrenamiento de músculos respiratorios, otras técnicas kinesiológicas y pautas nutricionales se recomiendan sólo para casos particulares (1C). Se fijan también objetivos educativos para los programas de rehabilitación que incluyen la cesación de fumar, aspectos nutricionales y apoyo psicológico. La RR ha demostrado reducir las exacerbaciones, hospitalizaciones y costos (Evidencia A), y mejoraría la sobrevida (Evidencia B). La RR es un componente fundamental en el tratamiento moderno de la EPOC. Estas pautas basadas en la más reciente evidencia científica, adaptadas al medio local tienen por objetivo que la RR pueda aplicarse en todo el país.
Respiratory rehabilitation (RR) is a multidisciplinary program of care for patients with chronic respiratory impairment, individually tailored, designed to optimize physical and social performance and patient autonomy. It is particularly indicated in chronic obstructive pulmonary disease (COPD) patients with exercise intolerance. The objectives of respiratory rehabilitation are: reduction in symptoms and exercise intolerance, improvement of health-related quality of life, and reduction of health costs. A group of neumonologists, nutritionists and physical therapists performed a systematic review of the evidence in RR to update previous local guidelines. Inclusion and exclusion criteria, guidelines for initial evaluation and follow up and resources needed are defined. Training characteristics are recommended regarding frequency of the visits, intensity, progression and duration of the exercise training. Aerobic training was recommended for lower limb (1A), upper limb (1B). Strength training must be added (1B). Respiratory muscle training and other physiotherapy techniques were recommended only for specific patients (1C). In addition recommendations have been made for educational objectives of the program including smoking cessation, nutritional and psychological support. The positive impact of RR on reductions of health care costs and reductions on hospitalizations (Evidence A) and mortality (Evidence B) were analized. Respiratory rehabilitation is a key component in the modern treatment of COPD patients. This consensus statement was prepared based on the most recent scientific evidence and adjusted to the local environment with the aim of being implemented nationally.
