Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator.

BACKGROUND: Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist ß2-agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients with moderate to severe COPD. METHODS: This was a randomized, five-way complete cross-over study. Patients received single doses of navafenterol 400 µg, navafenterol 1800 µg and placebo (all double-blind) and indacaterol 150 µg and tiotropium 18 µg (both open-label active comparators). The primary pharmacodynamic endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 2. Safety and tolerability were monitored throughout. RESULTS: Thirty-eight patients were randomized and 28 (73.7%) completed the study. Navafenterol 400 µg and 1800 µg demonstrated statistically significant improvements vs placebo in change from baseline in trough FEV1 (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P < .0001). The changes were significantly greater with navafenterol 1800 µg vs the active comparators (least squares mean treatment difference: 0.065-0.069 L, both P < .05). The frequency of treatment-emergent adverse events was similar for placebo and the active comparators (range 34.4-37.5%), slightly higher for navafenterol 400 µg (52.9%), and lowest for navafenterol 1800 µg (22.6%). CONCLUSIONS: Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised. TRIAL REGISTRY: ClinicalTrials.gov ; No.: NCT02573155 ; URL: www.clinicaltrials.gov . Registered 9th October, 2015.

Navafenterol (AZD8871) in patients with mild asthma: a randomised placebo-controlled phase I study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of this novel inhaled long-acting dual-pharmacology bronchodilator.

BACKGROUND: Navafenterol (AZD8871) is an inhaled long-acting dual-pharmacology muscarinic antagonist/ß2-adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma. METHODS: This was a randomised, single-blind, placebo-controlled, single-ascending-dose study. Patients were randomly assigned to one of two cohorts which evaluated escalating doses of navafenterol (50-2100 µg) in an alternating manner over three treatment periods. The primary pharmacodynamic endpoint was the change from pre-dose baseline in trough forced expiratory volume in 1 s (FEV1) for each treatment period. RESULTS: Sixteen patients were randomised; 15 completed treatment. Data from all 16 patients were analysed. The maximum tolerated dose was not identified, and all doses of navafenterol were well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were headache (n = 10, 62.5%) and nasopharyngitis (n = 7, 43.8%). No TEAEs were serious, fatal, or led to discontinuation, and no dose dependency was identified. Navafenterol demonstrated a dose-ordered bronchodilatory response with a rapid onset of action (within 5 min post-dose). Doses ≥200 µg resulted in improvements in trough FEV1 (mean change from baseline range 0.186-0.463 L) with sustained bronchodilation for 24-36 h. Plasma concentrations increased in a dose-proportional manner, peaking ~ 1 h post-dose, with a derived terminal elimination half-life of 15.96-23.10 h. CONCLUSIONS: In this study navafenterol was generally well tolerated with a rapid onset of action which was sustained over 36 h. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02573155.

Occupational fatigue and work absenteeism in female assistant nurses of a high-complexity hospital, Chile. / Fatiga laboral y ausentismo en el trabajo en mujeres auxiliares de enfermería de un hospital de alta complejidad, Chile.

This research examined the association between occupational fatigue and work absenteeism in 110 female assistant nurses of a high-complexity hospital in Chile. A sociodemographic questionnaire and the Checklist Individual Strength (CIS) scale were used. The results showed that the predominant absenteeism range was 11-29 days. The highest means of fatigue occurred in those with seniority above 2 years, with more than 10 patients in charge and an annual contract. No significant difference was observed between the fatigue means concerning absenteeism, but a significant association was observed between physical fatigue (p = 0.040, OR = 1.054) and service seniority (p = 0.001, OR = 1.084) with work absenteeism. Finally, we can conclude that physical fatigue and seniority in the clinical service are significant risk factors for the occurrence of absenteeism.

Esta investigación ignifi la asociación entre la fatiga y el absentismo en el trabajo en 110 asistentes de enfermería de un hospital altamente complejo en Chile. Se ignifi un cuestionario sociodemográfico y la escala Check Strength Individual Strength. Los resultados mostraron que el ignific de absentismo predominante fue de 11 a 29 días. Los mayores promedios de fatiga se presentaron en los mayores de 2 años, con más de 10 pacientes en el consultorio y con contrato annual. No hubo diferencias significativas entre la fatiga media en relación con el absentismo, pero hubo una asociación ignificative entre la fatiga física (p = 0,040; OR = 1,054) y la antigüedad en el trabajo (p = 0,001; OR = 1,084) con el absentismo laboral. Finalmente, se concluye que la fatiga física y la antigüedad en el servicio clínico representaron un factor de riesgo significativo para el absentismo.

[Treatment of atrial fibrillation at different levels of health care]. / Tratamiento de la fibrilación auricular en los distintos niveles asistenciales de un área sanitaria.

BACKGROUND AND OBJECTIVE: Atrial fibrillation is managed in multiple settings by different specialists. We sought to analyze treatment and compliance of the prevailing guidelines of patients with atrial fibrillation attended at different levels of health care and to quantify interventions to correct treatment inadequacies. PATIENTS AND METHOD: We included all adult patients with atrial fibrillation who presented during a 14 day-period to different levels of health care of a tertiary hospital and a related primary care clinic (family physician, cardiologist, emergency department, hospitalization). In all of them, clinical and epidemiological data in relation to atrial fibrillation, and all data referring to treatment and compliance of guidelines, were recorded prospectively. RESULTS: 293 patients were included. Clinical and epidemiological data were similar in the different settings. A great diversity in atrial fibrillation treatment was observed. In 30 and 33% of the patients, antiarrhythmic and antithrombotic treatment, respectively, did not meet the recommendations of the prevailing guidelines. The adequacy was inferior in primary care. The adequacy percentages increased slightly after the medical attention (2 and 3% respectively, p non significant) with no differences in this increase between the different settings. CONCLUSIONS: There are no epidemiological differences between patients with atrial fibrillation treated at different levels of health care. An important number of patients do not follow the recommendations of the prevailing guidelines. There is a clear medical abstention in incorrectly treated cases.

Fatiga laboral y ausentismo en el trabajo en mujeres auxiliares de enfermería de un hospital de alta complejidad, Chile / Occupational fatigue and work absenteeism in female assistant nurses of a high-complexity hospital, Chile

Resumen Esta investigación ignifi la asociación entre la fatiga y el absentismo en el trabajo en 110 asistentes de enfermería de un hospital altamente complejo en Chile. Se ignifi un cuestionario sociodemográfico y la escala Check Strength Individual Strength. Los resultados mostraron que el ignific de absentismo predominante fue de 11 a 29 días. Los mayores promedios de fatiga se presentaron en los mayores de 2 años, con más de 10 pacientes en el consultorio y con contrato annual. No hubo diferencias significativas entre la fatiga media en relación con el absentismo, pero hubo una asociación ignificative entre la fatiga física (p = 0,040; OR = 1,054) y la antigüedad en el trabajo (p = 0,001; OR = 1,084) con el absentismo laboral. Finalmente, se concluye que la fatiga física y la antigüedad en el servicio clínico representaron un factor de riesgo significativo para el absentismo.

Abstract This research examined the association between occupational fatigue and work absenteeism in 110 female assistant nurses of a high-complexity hospital in Chile. A sociodemographic questionnaire and the Checklist Individual Strength (CIS) scale were used. The results showed that the predominant absenteeism range was 11-29 days. The highest means of fatigue occurred in those with seniority above 2 years, with more than 10 patients in charge and an annual contract. No significant difference was observed between the fatigue means concerning absenteeism, but a significant association was observed between physical fatigue (p = 0.040, OR = 1.054) and service seniority (p = 0.001, OR = 1.084) with work absenteeism. Finally, we can conclude that physical fatigue and seniority in the clinical service are significant risk factors for the occurrence of absenteeism.

Tratamiento de la fibrilación auricular en los distintos niveles asistenciales de un área sanitaria / Treatment of atrial fibrillation at different levels of health care

Fundamento y objetivo: La fibrilación auricular se trata en múltiples niveles asistenciales por distintos especialistas. El objetivo del estudio fue analizar el tratamiento de esta arritmia y su adecuación a las guías clínicas vigentes en los distintos niveles de atención sanitaria, así como cuantificar las intervenciones correctoras en los mismos niveles cuando el tratamiento era inadecuado. Pacientes y método: Se incluyó a todos los pacientes adultos con fibrilación auricular (FA) que consultaron a los distintos niveles de atención sanitaria de un hospital de tercer nivel y de un centro de atención primaria (CAP) relacionado (CAP, cardiólogo ambulatorio, urgencias, hospitalización) durante 14 días consecutivos. En todos ellos se registraron las características clínico-epidemiológicas, los datos referentes al tratamiento de la fibrilación auricular y su adecuación a las guías clínicas vigentes antes y después de la visita. Resultados: Se incluyó a 293 pacientes. Las características clínico-epidemiológicas fueron similares entre los distintos niveles asistenciales. Se objetivó una gran variabilidad en el tratamiento de la FA. En un 30 y un 33% de los pacientes el tratamiento antiarrítmico y antitrombótico, respectivamente, no se adecuaba a las recomendaciones de las guías clínicas vigentes. La adecuación fue inferior en las consultas del médico de familia. Estos porcentajes de adecuación se incrementaron mínimamente tras la visita (el 2 y el 3%, respectivamente; p no significativas), sin diferencias en este incremento entre los distintos niveles asistenciales. Conclusiones: No hay diferencias epidemiológicas entre los pacientes con fibrilación auricular tratados en los distintos niveles de la atención sanitaria. Un porcentaje importante de los pacientes no siguen las recomendaciones de las guías clínicas vigentes. Hay un claro nihilismo médico ante los pacientes con FA incorrectamente tratados

Background and objective: Atrial fibrillation is managed in multiple settings by different specialists. We sought to analyze treatment and compliance of the prevailing guidelines of patients with atrial fibrillation attended at different levels of health care and to quantify interventions to correct treatment inadequacies. Patients and method: We included all adult patients with atrial fibrillation who presented during a 14 day-period to different levels of health care of a tertiary hospital and a related primary care clinic (family physician, cardiologist, emergency department, hospitalization). In all of them, clinical and epidemiological data in relation to atrial fibrillation, and all data referring to treatment and compliance of guidelines, were recorded prospectively. Results: 293 patients were included. Clinical and epidemiological data were similar in the different settings. A great diversity in atrial fibrillation treatment was observed. In 30 and 33% of the patients, antiarrhythmic and antithrombotic treatment, respectively, did not meet the recommendations of the prevailing guidelines. The adequacy was inferior in primary care. The adequacy percentages increased slightly after the medical attention (2 and 3% respectively, p non significant) with no differences in this increase between the different settings. Conclusions: There are no epidemiological differences between patients with atrial fibrillation treated at different levels of health care. An important number of patients do not follow the recommendations of the prevailing guidelines. There is a clear medical abstention in incorrectly treated cases