Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 (RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: COVID-19 is associated with acute respiratory distress and cytokine release syndrome. The Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib reduces inflammatory cytokine concentrations in disorders characterised by cytokine dysregulation, including graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis. We assessed whether treatment with the JAK1/JAK2 inhibitor ruxolitinib would be beneficial in patients with COVID-19 admitted to hospital. Methods: RUXCOVID was an international, randomised, double-blind, phase 3 trial of ruxolitinib plus standard of care versus placebo plus standard of care in patients with COVID-19. Patients who were hospitalised but not on mechanical ventilation or in the intensive care unit [ICU] were randomly assigned (2:1) to oral ruxolitinib 5 mg twice per day or placebo for 14 days (14 additional days were allowed if no improvement). The primary endpoint was a composite of death, respiratory failure (invasive ventilation), or ICU care by day 29, analysed by logistic regression including region, treatment, baseline clinical status, age, and sex as covariates. This trial is registered with ClinicalTrials.gov, NCT04362137. Findings: Between May 4 and Sept 19, 2020, 432 patients were randomly assigned to ruxolitinib (n=287) or placebo (n=145) plus standard of care; the mean age was 56·5 years (SD 13·3), 197 (46%) were female, and 235 (54%) were male. The primary objective was not met: the composite endpoint occurred in 34 (12%) of 284 ruxolitinib-treated patients versus 17 (12%) of 144 placebo-treated patients (odds ratio 0·91, 95% CI 0·48-1·73; p=0·77). By day 29, nine (3%) of 286 ruxolitinib-treated patients had died compared with three (2%) of 145 placebo-treated patients; 22 (8%) of 286 ruxolitinib-treated patients had received invasive ventilation compared with ten (7%) of 145 placebo-treated patients; and 30 (11%) of 284 ruxolitinib-treated patients had received ICU care compared with 17 (12%) of 144 placebo-treated patients. In an exploratory analysis, median time to recovery was 1 day faster with ruxolitinib versus placebo (8 days vs 9 days; hazard ratio 1·10, 95% CI 0·89-1·36). Adverse events included headache (23 [8%] of 281 on ruxolitinib vs 11 [8%] of 143 on placebo) and diarrhoea (21 [7%] vs 12 [8%]). Interpretation: Ruxolitinib 5 mg twice per day showed no benefit in the overall study population. A larger sample is required to determine the clinical importance of trends for increased efficacy in patient subgroups. Funding: Novartis and Incyte.

Evaluation of a Spanish language version of the Asthma Trigger Inventory.

Background: Perceptions of asthma triggers provide important guidance for patients' disease management. A psychometrically valid instrument, the Asthma Trigger Inventory (ATI), is available in English and German language versions, however, a version in Spanish as major world language has been missing.Method: A Spanish-language version of the ATI was evaluated in 339 adult patients with asthma, 223 of these in Peru and 107 in the USA. Principal Component analysis (PCA) with Varimax rotation was used to identify coherent trigger domains across and within samples. Resulting subscales were evaluated for internal consistency.Results: PCA suggested differences in factor structures between sites. Whereas the USA sample largely replicated original factors for animal allergens, pollen allergens, physical activity, air pollution/irritants, infections, and psychology, the initial analysis of the Peru sample suggested substantial overlap of air pollution/irritant, infection, and allergen items. Subsequent analysis of an expanded research form of the ATI for the Peru site culminated in extraction of five factors related to psychology, climate/temperature, combined pollen and animal allergens, physical activity, and infection. Internal consistencies were in an acceptable to excellent range (α = 0.74 to 0.94). Additional free trigger responses confirmed the importance of climate variables for patients in Peru. Psychological triggers were reported by 26% (Peru) and 31% (USA) of patients.Conclusion: Coherent trigger domains are readily identified and measured reliably by a Spanish-language ATI version. However, factor structures vary between samples from different Hispanic/Latino cultural and geographic domains. Culturally adapted versions of this instrument are therefore required for Hispanic/Latino population studies.

[Surveillance, prevention, and control of influenza virus in Peru]. / Vigilancia, prevención y control del virus de la influenza en Perú.

The importance of surveilling the circulation of the influenza virus and timely vaccination of different populations in Peru was analyzed in three sessions by a group of clinical experts from different specialties. The Peruvian national influenza surveillance system has many selected establishments that have become currently ineffective in terms of a timely report. Most of the samples come from Lima. The viral distribution is inadequately analyzed. The northern and jungle areas of the country have weather and season conditions different to those in Lima and on the southern highlands. This lack of coordination is accentuated by the opportunity of arrival of the influenza vaccine in the country. The Ministry of Health uses a trivalent vaccine but the possibility of a tetravalent vaccine with the two type-B lineages must be analyzed from a cost-benefit standpoint. The appropriateness of vaccinating two times a year, regionally, should be assessed.

La importancia de la vigilancia de la circulación del virus de influenza y la vacunación oportuna a las diferentes poblaciones del Perú, fue analizada en tres sesiones por un grupo de clínicos expertos de diferentes especialidades. En Perú, en los últimos años, el sistema nacional de vigilancia de influenza tiene muchos establecimientos seleccionados que son ineficaces en la notificación oportuna. La mayoría de las muestras provienen de Lima. La distribución viral es inadecuadamente analizada. El norte y la selva tienen estaciones climáticas diferentes a Lima y la sierra sur. Esta descoordinación se acentúa con la oportunidad de la llegada de la vacuna de influenza al país. El Ministerio de Salud utiliza una vacuna trivalente pero la posibilidad de una vacuna tetravalente con los dos linajes de tipo B, debe ser analizada desde el punto de vista de costo-beneficio. Se debería evaluar la pertinencia de vacunar en dos momentos anuales, regionalmente.

Vigilancia, prevención y control del virus de la influenza en Perú / Surveillance, prevention, and control of influenza virus in Peru

RESUMEN La importancia de la vigilancia de la circulación del virus de influenza y la vacunación oportuna a las diferentes poblaciones del Perú, fue analizada en tres sesiones por un grupo de clínicos expertos de diferentes especialidades. En Perú, en los últimos años, el sistema nacional de vigilancia de influenza tiene muchos establecimientos seleccionados que son ineficaces en la notificación oportuna. La mayoría de las muestras provienen de Lima. La distribución viral es inadecuadamente analizada. El norte y la selva tienen estaciones climáticas diferentes a Lima y la sierra sur. Esta descoordinación se acentúa con la oportunidad de la llegada de la vacuna de influenza al país. El Ministerio de Salud utiliza una vacuna trivalente pero la posibilidad de una vacuna tetravalente con los dos linajes de tipo B, debe ser analizada desde el punto de vista de costo-beneficio. Se debería evaluar la pertinencia de vacunar en dos momentos anuales, regionalmente.

ABSTRACT The importance of surveilling the circulation of the influenza virus and timely vaccination of different populations in Peru was analyzed in three sessions by a group of clinical experts from different specialties. The Peruvian national influenza surveillance system has many selected establishments that have become currently ineffective in terms of a timely report. Most of the samples come from Lima. The viral distribution is inadequately analyzed. The northern and jungle areas of the country have weather and season conditions different to those in Lima and on the southern highlands. This lack of coordination is accentuated by the opportunity of arrival of the influenza vaccine in the country. The Ministry of Health uses a trivalent vaccine but the possibility of a tetravalent vaccine with the two type-B lineages must be analyzed from a cost-benefit standpoint. The appropriateness of vaccinating two times a year, regionally, should be assessed.

[Characteristics of chronic obstructive pulmonary disease due to tobacco consumption in pneumology patients in lima and callao]. / Características de enfermedad pulmonar obstructiva crónica por consumo de tabaco en pacientes de servicios de neumología de Lima y Callao.

The aim of the study was to describe the clinical characteristics of patients with COPD receiving treatment at the pneumology units of specialized care centers in Lima and Callao. A cross-sectional study was performed on 196 patients, with a mean age of 69 years, interquartile range of 63-75 years. Of these patients, 31.1% was classified in the GOLD 1/ mild group (FEV1 ≥80%); 41.8% in the GOLD 2/moderate group (50%≤FEV1<80%); 22.5% in the GOLD 3/severe group (30%≤FEV1<50%), and 4.6% in the GOLD 4/very severe group (FEV1 <30%). A 93.9% of patients used some type of medication for COPD. The most-frequently used therapy was the combination of long-acting beta agonists and inhaled corticosteroids (LABA/ICS) (31.1%). A preliminary characterization has been obtained for COPD patients treated in these centers, but it is essential to complement these findings with longitudinal studies.

El objetivo del estudio fue describir las características clínicas de pacientes con enfermedad pulmonar obstructiva crónica (EPOC), atendidos en los servicios de Neumología de centros especializados de Lima y Callao. Se realizó un estudio transversal en 196 pacientes, con una mediana de edad de 69 años, rango intercuartil 63-75 años. El 31,1 % de los pacientes se encontró en el grupo GOLD 1/leve (VEF1 ≥80 %), el 41,8 % en el grupo GOLD 2/moderado (50 %≤VEF1<80 %), el 22,5 % en el grupo GOLD 3/severo (30 %≤VEF1<50 %), y el 4,6 % en el grupo GOLD 4/muy severo (VEF1 <30 %). El 93,9 % usaba algún tipo de medicación para EPOC, la terapia más usada fue la combinación de beta agonistas de acción larga/corticoides inhalados (LABA/ICS) con 31,1 %. Se ha obtenido una primera caracterización de pacientes con EPOC atendidos en estos centros. Es imprescindible complementar lo encontrado con estudios longitudinales.

Características de enfermedad pulmonar obstructiva crónica por consumo de tabaco en pacientes de servicios de neumología de Lima y Callao / Characteristics of chronic obstructive pulmonary disease due to tobacco consumption in pneumology patients in lima and callao

RESUMEN El objetivo del estudio fue describir las características clínicas de pacientes con enfermedad pulmonar obstructiva crónica (EPOC), atendidos en los servicios de Neumología de centros especializados de Lima y Callao. Se realizó un estudio transversal en 196 pacientes, con una mediana de edad de 69 años, rango intercuartil 63-75 años. El 31,1 % de los pacientes se encontró en el grupo GOLD 1/leve (VEF1 ≥80 %), el 41,8 % en el grupo GOLD 2/moderado (50 %≤VEF1<80 %), el 22,5 % en el grupo GOLD 3/severo (30 %≤VEF1<50 %), y el 4,6 % en el grupo GOLD 4/muy severo (VEF1 <30 %). El 93,9 % usaba algún tipo de medicación para EPOC, la terapia más usada fue la combinación de beta agonistas de acción larga/corticoides inhalados (LABA/ICS) con 31,1 %. Se ha obtenido una primera caracterización de pacientes con EPOC atendidos en estos centros. Es imprescindible complementar lo encontrado con estudios longitudinales.

ABSTRACT The aim of the study was to describe the clinical characteristics of patients with COPD receiving treatment at the pneumology units of specialized care centers in Lima and Callao. A cross-sectional study was performed on 196 patients, with a mean age of 69 years, interquartile range of 63-75 years. Of these patients, 31.1% was classified in the GOLD 1/ mild group (FEV1 ≥80%); 41.8% in the GOLD 2/moderate group (50%≤FEV1<80%); 22.5% in the GOLD 3/severe group (30%≤FEV1<50%), and 4.6% in the GOLD 4/very severe group (FEV1 <30%). A 93.9% of patients used some type of medication for COPD. The most-frequently used therapy was the combination of long-acting beta agonists and inhaled corticosteroids (LABA/ICS) (31.1%). A preliminary characterization has been obtained for COPD patients treated in these centers, but it is essential to complement these findings with longitudinal studies.

Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d) or twice-daily (2, 25, 75 or 150 mg b.i.d) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 µg b.i.dFevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted.

Utilidad de broncofibroscopia flexible en el diagnóstico de las causas de hemoptisis / Utility of broncofibroscopia flex in the diagnosis of the reasons of hemoptisis

Se realizó estudio descriptivo prospectivo para evaluar la utilidad de la broncofibroscopia flexible en el diagnóstico de las causas de hemoptisis. Se realizaron 60 broncofibroscopias. Las hipótesis planteadas como primera posibilidad fueron de etiología Infecciosa 52 (86.7 por ciento), de etiología neoplßsica 6 (10 por ciento) y de otras causas 2 (3.3 por ciento). Resultados Bacteriológicos: de 48 pacientes con sospecha de tuberculosis 12 (25 por ciento) resultaron con baciloscopias positivas; obteniéndose el mejor rendimiento mediante el aspirado bronquial (100 por ciento). De 17 pacientes con sospecha de otra causa infecciosa 11 (64.7 por ciento) resultarón positivas para gérmenes comunes y hongos y 6 (35.3 por ciento) negativas. De 14 pacientes con estudio citológico de papanicolau (PAP)13 (92.9 por ciento) no presentaron Células Sospechosas de Neoplasias (NCSN) y en 1 (7.1 por ciento) se evidenciaron Células Sospechosas de Neoplasia (CSN). En 41 pacientes con biopsias bronquiales los resultados fueron: bronquitis crónica 25 (61 por ciento), bronquitis crónica y aguda 07 (17.1 por ciento), metaplasia epidermoide 02 (4.9 por ciento), granuloma tuberculoso 02 (4.9 por ciento), y 5 (12 por ciento) fueron informadas como muestra insuficiente. Conclusiones: Se demostró la importancia de la broncofibroscopía flexible en el diagnóstico de las causas de hemoptisis en nuestro medio, siendo el mayor aporte en la detección precoz de enfermedades infecciosas posibilitando su tratamiento oportuno con importantes beneficios epidemiológicos.

A descriptive and prospective study to evaluate utility of fiberoptic bronchoscopy in the diagnosis in hemoptisis was undertaken. Sixty fiberoptic bronchoscopy were done.The raised hypotheses as first possibility were of infectious etiology 52 (86.7 per cent) of neoplasic etiology 6 (10 per cent) and of other causes 2 (3,3 per cent). Bacteriological results: among 48 patients (with suspect tuberculosis), 12 patients (25 per cent) had positive acid fast bacilli smears. Among 17 samples that under went routine bacterial culture testing, 11 samples grew bacteria and fungal culture were positive, in 6(35.3 per cent) were negative. Cytological results: papanicolao smears were done in 14 patients, in 1 patients (7.1 per cent) suspicious neoplastic cells were detected. Histological results: In 41 patients, biopsy specimens were obtained, the following results were seen :: chronic inflammation in 25 (61 per cent), chronic and acute bronchitis in7 (17,1 per cent), epidermoid metaplasia 2 (4,9 per cent ), tuberculous granuloma in 2 (4,9 per cent), and 5 (12 per cent) were informed, as it shows insufficient specimens. Conclusions: The importance of the use of the flexible fiberoptic bronchoscopy was demoustrated in the diagnosis of the causes of hemoptisis, contributing the most to the early diagnosis of infectious diseases which results inopportune treatment and epidemiologic benefit.