Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial

Background. Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting β2 agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. Trial design. A multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Methods. Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 μg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 μg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0–4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV1) (23–24 h postdose; day 29) and wm FEV1 (0–4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 μg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment. Results. 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV1 per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0–4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI −3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV1 (mean difference 183 ml) and 0–4 h postdose wm FEV1 (mean difference 236 ml). Conclusion. FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD.publishedVersio

Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight : a meta-analysis of individual participant data

Background Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at 2499 g) or at term. Methods We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF25-75%]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. Findings Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3.4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV1 (-0.06 [SD 1.03] vs -0.81 [1.33], mean difference -0.78 [95% CI -0.96 to -0.61], p Interpretation Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Tuberculosis screening and follow-up of asylum seekers in Norway: a cohort study

<p>Abstract</p> <p>Background</p> <p>About 80% of new tuberculosis cases in Norway occur among immigrants from high incidence countries. On arrival to the country all asylum seekers are screened with Mantoux test and chest x-ray aimed to identify cases of active tuberculosis and, in the case of latent tuberculosis, to offer follow-up or prophylactic treatment.</p> <p>We assessed a national programme for screening, treatment and follow-up of tuberculosis infection and disease in a cohort of asylum seekers.</p> <p>Methods</p> <p>Asylum seekers ≥ 18 years who arrived at the National Reception Centre from January 2005 to June 2006, were included as the total cohort. Those with a Mantoux test ≥ 6 mm or positive x-ray findings were included in a study group for follow-up.</p> <p>Data were collected from public health authorities in the municipality to where the asylum seekers had moved, and from hospital based internists in case they had been referred to specialist care.</p> <p>Individual subjects included in the study group were matched with the Norwegian National Tuberculosis Register which receive reports of everybody diagnosed with active tuberculosis, or who had started treatment for latent tuberculosis.</p> <p>Results</p> <p>The total cohort included 4643 adult asylum seekers and 97.5% had a valid Mantoux test. At least one inclusion criterion was fulfilled by 2237 persons. By end 2007 municipal public health authorities had assessed 758 (34%) of them. Altogether 328 persons had been seen by an internist. Of 314 individuals with positive x-rays, 194 (62%) had seen an internist, while 86 of 568 with Mantoux ≥ 15, but negative x-rays (16%) were also seen by an internist. By December 31^st2006, 23 patients were diagnosed with tuberculosis (prevalence 1028/100 000) and another 11 were treated for latent infection.</p> <p>Conclusion</p> <p>The coverage of screening was satisfactory, but fewer subjects than could have been expected from the national guidelines were followed up in the community and referred to an internist. To improve follow-up of screening results, a simplification of organisation and guidelines, introduction of quality assurance systems, and better coordination between authorities and between different levels of health care are all required.</p

The role of entry screening in case finding of tuberculosis among asylum seekers in Norway

<p>Abstract</p> <p>Background</p> <p>Most new cases of active tuberculosis in Norway are presently caused by imported strains and not transmission within the country. Screening for tuberculosis with a Mantoux test of everybody and a chest X-ray of those above 15 years of age is compulsory on arrival for asylum seekers.</p> <p>We aimed to assess the effectiveness of entry screening of a cohort of asylum seekers. Cases detected by screening were compared with cases detected later. Further we have characterized cases with active tuberculosis.</p> <p>Methods</p> <p>All asylum seekers who arrived at the National Reception Centre between January 2005 - June 2006 with an abnormal chest X-ray or a Mantoux test ≥ 6 mm were included in the study and followed through the health care system. They were matched with the National Tuberculosis Register by the end of May 2008.</p> <p>Cases reported within two months after arrival were defined as being detected by screening.</p> <p>Results</p> <p>Of 4643 eligible asylum seekers, 2237 were included in the study. Altogether 2077 persons had a Mantoux ≥ 6 mm and 314 had an abnormal chest X-ray. Of 28 cases with tuberculosis, 15 were detected by screening, and 13 at 4-27 months after arrival. Abnormal X-rays on arrival were more prevalent among those detected by screening. Female gender and Somalian origin increased the risk for active TB.</p> <p>Conclusion</p> <p>In spite of an imperfect follow-up of screening results, a reasonable number of TB cases was identified by the programme, with a predominance of pulmonary TB.</p

Tuberculosis screening and follow-up of asylum seekers in Norway: a cohort study

Background: About 80% of new tuberculosis cases in Norway occur among immigrants from high incidence countries. On arrival to the country all asylum seekers are screened with Mantoux test and chest x-ray aimed to identify cases of active tuberculosis and, in the case of latent tuberculosis, to offer follow-up or prophylactic treatment. We assessed a national programme for screening, treatment and follow-up of tuberculosis infection and disease in a cohort of asylum seekers. Methods: Asylum seekers ≥ 18 years who arrived at the National Reception Centre from January 2005 to June 2006, were included as the total cohort. Those with a Mantoux test ≥ 6 mm or positive x-ray findings were included in a study group for follow-up. Data were collected from public health authorities in the municipality to where the asylum seekers had moved, and from hospital based internists in case they had been referred to specialist care. Individual subjects included in the study group were matched with the Norwegian National Tuberculosis Register which receive reports of everybody diagnosed with active tuberculosis, or who had started treatment for latent tuberculosis. Results: The total cohort included 4643 adult asylum seekers and 97.5% had a valid Mantoux test. At least one inclusion criterion was fulfilled by 2237 persons. By end 2007 municipal public health authorities had assessed 758 (34%) of them. Altogether 328 persons had been seen by an internist. Of 314 individuals with positive x-rays, 194 (62%) had seen an internist, while 86 of 568 with Mantoux ≥ 15, but negative x-rays (16%) were also seen by an internist. By December 31st 2006, 23 patients were diagnosed with tuberculosis (prevalence 1028/100 000) and another 11 were treated for latent infection. Conclusion: The coverage of screening was satisfactory, but fewer subjects than could have been expected from the national guidelines were followed up in the community and referred to an internist. To improve follow-up of screening results, a simplification of organisation and guidelines, introduction of quality assurance systems, and better coordination between authorities and between different levels of health care are all required

Continuous monitoring of the bronchial epithelial lining fluid by microdialysis-1

<p><b>Copyright information:</b></p><p>Taken from "Continuous monitoring of the bronchial epithelial lining fluid by microdialysis"</p><p>http://respiratory-research.com/content/8/1/78</p><p>Respiratory Research 2007;8(1):78-78.</p><p>Published online 1 Nov 2007</p><p>PMCID:PMC2169243.</p><p></p> excluded as an outlier due to extreme deviation in the arterial microdialysis value. The accuracy of bronchial microdialysis with a continuous lactate infusion was mean 0.26 ± 0.08 with a coefficient of variation of 62.6%. The accuracy of bronchial microdialysis with a continuous lactate infusion and a correction by the arteriobronchial urea gradient was mean 0.81 ± 0.06 with a coefficient of variation of 17.0%. The reduced coefficient of variation after correction by the arteriobronchial ureagradient sustains the ureacorrection as useful correction factor to estimate the absolute concentrations of molecules in the epithelial lining fluid as measured by microdialysis

Continuous monitoring of the bronchial epithelial lining fluid by microdialysis-3

<p><b>Copyright information:</b></p><p>Taken from "Continuous monitoring of the bronchial epithelial lining fluid by microdialysis"</p><p>http://respiratory-research.com/content/8/1/78</p><p>Respiratory Research 2007;8(1):78-78.</p><p>Published online 1 Nov 2007</p><p>PMCID:PMC2169243.</p><p></p>en circles and dotted line, number three closed triangles and medium dashed line, number four open triangles and dash-dot-dot line, and number five closed squares and long dashed line. Plot A and B show arterial lactate along the X-axis and bronchial (R0.82 ± 0.18) and ureacorrected bronchial lactate (R0.91 ± 0.11) along the Y-axis respectively. Paired t-test of Rfor the individual bronchial and ureacorrected bronchial lactate XY-plots showed significant difference (p < 0.05). Plot C and D show arterial fluorescein isothiocyanate dextran 4000 Da (FD-4) along the X-axis and bronchial (R0.53 ± 0.38) and ureacorrected bronchial FD-4 (R0.72 ± 0.34) along the Y-axis. Paired t-test of Rfor the individual bronchial and ureacorrected bronchial FD-4 XY-plots was not significant

Continuous monitoring of the bronchial epithelial lining fluid by microdialysis-2

<p><b>Copyright information:</b></p><p>Taken from "Continuous monitoring of the bronchial epithelial lining fluid by microdialysis"</p><p>http://respiratory-research.com/content/8/1/78</p><p>Respiratory Research 2007;8(1):78-78.</p><p>Published online 1 Nov 2007</p><p>PMCID:PMC2169243.</p><p></p> dextran 4000 Da (FD-4) values by corrected bronchial microdialysis are corrected by the arteriobronchial urea gradient. * Paired t-test showed significant difference from arterial microdialysis at low steady state (FD-4 5 μg/kg/hour) (p < 0.05). † Paired t-test showed significant difference from arterial microdialysis at high steady state (FD-4 10 μg/kg/hour) (p < 0.05)

Continuous monitoring of the bronchial epithelial lining fluid by microdialysis-0

<p><b>Copyright information:</b></p><p>Taken from "Continuous monitoring of the bronchial epithelial lining fluid by microdialysis"</p><p>http://respiratory-research.com/content/8/1/78</p><p>Respiratory Research 2007;8(1):78-78.</p><p>Published online 1 Nov 2007</p><p>PMCID:PMC2169243.</p><p></p>d bronchial microdialysis are corrected by the arteriobronchial urea gradient. * Paired T-test showed significant difference from arterial microdialysis at low steady state (arterial blood lactate ~5 mmol/L) (p < 0.05). † Paired t-test showed significant difference from arterial microdialysis at high steady state (arterial blood lactate ~10 mmol/L) (p < 0.05). ns Non significant from arterial microdialysis at high steady state (arterial blood lactate ~10 mmol/L)