human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Evidence is scarce on the relative risk-benefit of inhaled triple therapy , consisting of inhaled corticosteroid , long-acting muscarinic antagonist , and long-acting β2-agonist , versus dual bronchodilation for chronic obstructive pulmonary disease ( COPD ) . We aim ed to compare a single-inhaler triple combination of beclometasone dipropionate , formoterol fumarate , and glycopyrronium ( BDP/FF/G ) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium ( IND/GLY ) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment . METHODS This r and omised , parallel-group , double-blind , double-dummy study was done at 187 sites across 17 countries . Eligible patients had symptomatic COPD , severe or very severe airflow limitation , at least one moderate or severe exacerbation in the previous year , and were receiving inhaled maintenance medication . After a 2 week run-in period with one inhalation per day of IND/GLY ( 85 μg/43 μg ) , patients were r and omly assigned ( 1:1 ) , via an interactive response technology system , to receive 52 weeks of treatment with two inhalations of extrafine BDP/FF/G ( 87 μg/5 μg/9 μg ) twice per day or one inhalation of IND/GLY ( 85 μg/43 μg ) per day . R and omisation was stratified by country and severity of airflow limitation . The primary endpoint was the rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment in all r and omised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment . Safety was assessed in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT02579850 . FINDINGS Between May , 29 2015 , and July 10 , 2017 , 1532 patients received BDP/FF/G ( n=764 ) or IND/GLY ( n=768 ) . Moderate-to-severe exacerbation rates were 0·50 per patient per year ( 95 % CI 0·45 - 0·57 ) for BDP/FF/G and 0·59 per patient per year ( 0·53 - 0·67 ) for IND/GLY , giving a rate ratio of 0·848 ( 0·723 - 0·995 , p=0·043 ) in favour of BDP/FF/G. Adverse events were reported by 490 ( 64 % ) of 764 patients receiving BDP/FF/G and 516 ( 67 % ) of 768 patients receiving IND/GLY . Pneumonia occurred in 28 ( 4 % ) patients receiving BDP/FF/G versus 27 ( 4 % ) patients receiving IND/GLY . One treatment-related serious adverse event occurred in each group : dysuria in a patient receiving BDP/FF/G and atrial fibrillation in a patient receiving IND/GLY . INTERPRETATION In patients with symptomatic COPD , severe or very severe airflow limitation , and an exacerbation history despite maintenance therapy , extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY , without increasing the risk of pneumonia . FUNDING Chiesi Farmaceutici BACKGROUND The benefits of triple therapy for chronic obstructive pulmonary disease ( COPD ) with an inhaled glucocorticoid , a long‐acting muscarinic antagonist ( LAMA ) , and a long‐acting β2‐agonist ( LABA ) , as compared with dual therapy ( either inhaled glucocorticoid – LABA or LAMA – LABA ) , are uncertain . METHODS In this r and omized trial involving 10,355 patients with COPD , we compared 52 weeks of a once‐daily combination of fluticasone furoate ( an inhaled glucocorticoid ) at a dose of 100 μg , umeclidinium ( a LAMA ) at a dose of 62.5 μg , and vilanterol ( a LABA ) at a dose of 25 μg ( triple therapy ) with fluticasone furoate – vilanterol ( at doses of 100 μg and 25 μg , respectively ) and umeclidinium – vilanterol ( at doses of 62.5 μg and 25 μg , respectively ) . Each regimen was administered in a single Ellipta inhaler . The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment . RESULTS The rate of moderate or severe exacerbations in the triple‐therapy group was 0.91 per year , as compared with 1.07 per year in the fluticasone furoate – vilanterol group ( rate ratio with triple therapy , 0.85 ; 95 % confidence interval [ CI ] , 0.80 to 0.90 ; 15 % difference ; P<0.001 ) and 1.21 per year in the umeclidinium – vilanterol group ( rate ratio with triple therapy , 0.75 ; 95 % CI , 0.70 to 0.81 ; 25 % difference ; P<0.001 ) . The annual rate of severe exacerbations result ing in hospitalization in the triple‐therapy group was 0.13 , as compared with 0.19 in the umeclidinium – vilanterol group ( rate ratio , 0.66 ; 95 % CI , 0.56 to 0.78 ; 34 % difference ; P<0.001 ) . There was a higher incidence of pneumonia in the inhaled‐glucocorticoid groups than in the umeclidinium – vilanterol group , and the risk of clinician‐diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium – vilanterol , as assessed in a time‐to‐first‐event analysis ( hazard ratio , 1.53 ; 95 % CI , 1.22 to 1.92 ; P<0.001 ) . CONCLUSIONS Triple therapy with fluticasone furoate , umeclidinium , and vilanterol result ed in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate – vilanterol or umeclidinium – vilanterol in this population . Triple therapy also result ed in a lower rate of hospitalization due to COPD than umeclidinium – vilanterol . ( Funded by GlaxoSmithKline ; IMPACT Clinical Trials.gov number , NCT02164513 . BACKGROUND The combination of tiotropium and fluticasone propionate/salmeterol ( FSC ) is commonly used to treat chronic obstructive pulmonary disease ( COPD ) , but no study had evaluated the effectiveness of tiotropium plus FSC with 250 μg of fluticasone propionate . Our aim was to assess whether tiotropium ( 18 μg once daily ) plus FSC ( 250/50 μg twice daily ) provides better clinical outcomes compared to tiotropium monotherapy . METHODS In this 24-week , r and omized , open label , multicenter two-arm parallel study , 479 patients received tiotropium plus FSC ( n = 237 ) or tiotropium alone ( n = 242 ) . RESULTS After 24 weeks of treatment , the triple-inhaled treatment group had a significant improvement in pre-bronchodilator FEV(1 ) ( L ) compared to the tiotropium-only group ( 0.090 L vs. 0.038 L ; P = 0.005 ) . Regarding health-related quality of life , the mean change in total score on the St. George 's Respiratory Question naire for COPD patients ( SGRQ-C ) was -6.6 points in the tiotropium plus FSC group , but -1.5 points in the tiotropium-only group ( P = 0.001 ) . In the subgroup of GOLD stage II patients with COPD , treatment with tiotropium plus FSC also improved FEV(1 ) compared to tiotropium alone ( 0.088 L vs. 0.030 L ; P = 0.011 ) and improved the total SGRQ-C score  than tiotropium alone ( -4.5 points vs. -1.0 points , respectively ) . This triple-inhaled treatment approach did not induce more adverse events , such as pneumonia . CONCLUSION Over the course of 24 weeks , FSC ( 250/50 μg twice daily ) added to tiotropium provided greater improvement in lung function and quality of life in patients with COPD ( FEV(1 ) ≤ 65 % ) than tiotropium alone Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : Triple inhalation therapy with tiotropium ( Tio ) and salmeterol/fluticasone propionate combination ( SFC ) is widely used in the treatment of chronic obstructive pulmonary disease ( COPD ) . However , the effects of triple therapy on airway structural changes remain unknown . Objective : The aim of the study was to assess the effects of Tio , salmeterol ( SM ) , SFC and Tio plus SFC on airway dimensions in COPD . Methods : A r and omized , open-label , 4-way study ( n = 60 ) was conducted comparing 16-week treatment periods of Tio ( 18 μg once daily ) , SM ( 50 μg twice daily ) , SFC ( 50/250 μg twice daily ) and Tio ( 18 μg once daily ) plus SFC ( 50/250 μg twice daily ) . Airway dimensions were assessed by a vali date d CT technique , and airway wall area ( WA ) corrected for body surface area ( BSA ) , percentage WA ( WA% ) , wall thickness/√BSA and luminal area (Ai)/BSA at the right apical segmental bronchus were measured . Pulmonary function and the St. George 's Respiratory Question naire ( SGRQ ) were evaluated . Results : Tio plus SFC result ed in a significant decrease in WA corrected for BSA and WA% compared with Tio , SM and SFC ( p < 0.05 for all ) . The changes in WA% and Ai/BSA were significantly correlated with changes in forced expiratory volume in 1 s ( r = -0.86 , p < 0.001 , and r = 0.48 , p < 0.05 , respectively ) . There were more significant improvements in SGRQ scores after treatment with triple therapy than after the 3 other treatments . Conclusions : Tio plus SFC therapy is more effective than Tio , SM and SFC for reducing airway wall thickness in COPD Introduction Chronic obstructive pulmonary disease is associated with a high healthcare re source and cost burden . Healthcare re source utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study . Patients received either once-daily , single inhaler triple therapy ( fluticasone furoate/umeclidinium/vilanterol ) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy ( budesonide/formoterol ) 400 µg/12 µg . Methods FULFIL was a phase III , r and omized , double-blind , double-dummy , multicenter study . Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary ; the costs of healthcare re source utilization were calculated post hoc using UK reference costs . Results Over 24 weeks , slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol ( 169/911 ; 18.6 % ) required contacts with healthcare providers compared with budesonide/formoterol ( 180/899 ; 20.0 % ) . Over 52 weeks in an extension population , fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol ( 25.2 % vs. 32.7 % ) . Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks ( £ 653.80 vs. £ 763.32 and £ 749.22 vs. £ 988.03 , respectively ) , with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol ( £ 1,289.35 vs. £ 1,267.45 ) . Conclusions This healthcare re source utilization evidence suggests that , in a clinical trial setting over a 24- or 52-week timeframe , non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vil 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Evidence is scarce on the relative risk-benefit of inhaled triple therapy , consisting of inhaled corticosteroid , long-acting muscarinic antagonist , and long-acting β2-agonist , versus dual bronchodilation for chronic obstructive pulmonary disease ( COPD ) . We aim ed to compare a single-inhaler triple combination of beclometasone dipropionate , formoterol fumarate , and glycopyrronium ( BDP/FF/G ) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium ( IND/GLY ) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment . METHODS This r and omised , parallel-group , double-blind , double-dummy study was done at 187 sites across 17 countries . Eligible patients had symptomatic COPD , severe or very severe airflow limitation , at least one moderate or severe exacerbation in the previous year , and were receiving inhaled maintenance medication . After a 2 week run-in period with one inhalation per day of IND/GLY ( 85 μg/43 μg ) , patients were r and omly assigned ( 1:1 ) , via an interactive response technology system , to receive 52 weeks of treatment with two inhalations of extrafine BDP/FF/G ( 87 μg/5 μg/9 μg ) twice per day or one inhalation of IND/GLY ( 85 μg/43 μg ) per day . R and omisation was stratified by country and severity of airflow limitation . The primary endpoint was the rate of moderate-to-severe COPD exacerbations across 52 weeks of treatment in all r and omised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment . Safety was assessed in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT02579850 . FINDINGS Between May , 29 2015 , and July 10 , 2017 , 1532 patients received BDP/FF/G ( n=764 ) or IND/GLY ( n=768 ) . Moderate-to-severe exacerbation rates were 0·50 per patient per year ( 95 % CI 0·45 - 0·57 ) for BDP/FF/G and 0·59 per patient per year ( 0·53 - 0·67 ) for IND/GLY , giving a rate ratio of 0·848 ( 0·723 - 0·995 , p=0·043 ) in favour of BDP/FF/G. Adverse events were reported by 490 ( 64 % ) of 764 patients receiving BDP/FF/G and 516 ( 67 % ) of 768 patients receiving IND/GLY . Pneumonia occurred in 28 ( 4 % ) patients receiving BDP/FF/G versus 27 ( 4 % ) patients receiving IND/GLY . One treatment-related serious adverse event occurred in each group : dysuria in a patient receiving BDP/FF/G and atrial fibrillation in a patient receiving IND/GLY . INTERPRETATION In patients with symptomatic COPD , severe or very severe airflow limitation , and an exacerbation history despite maintenance therapy , extrafine BDP/FF/G significantly reduced the rate of moderate-to-severe exacerbations compared with IND/GLY , without increasing the risk of pneumonia . FUNDING Chiesi Farmaceutici BACKGROUND The benefits of triple therapy for chronic obstructive pulmonary disease ( COPD ) with an inhaled glucocorticoid , a long‐acting muscarinic antagonist ( LAMA ) , and a long‐acting β2‐agonist ( LABA ) , as compared with dual therapy ( either inhaled glucocorticoid – LABA or LAMA – LABA ) , are uncertain . METHODS In this r and omized trial involving 10,355 patients with COPD , we compared 52 weeks of a once‐daily combination of fluticasone furoate ( an inhaled glucocorticoid ) at a dose of 100 μg , umeclidinium ( a LAMA ) at a dose of 62.5 μg , and vilanterol ( a LABA ) at a dose of 25 μg ( triple therapy ) with fluticasone furoate – vilanterol ( at doses of 100 μg and 25 μg , respectively ) and umeclidinium – vilanterol ( at doses of 62.5 μg and 25 μg , respectively ) . Each regimen was administered in a single Ellipta inhaler . The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment . RESULTS The rate of moderate or severe exacerbations in the triple‐therapy group was 0.91 per year , as compared with 1.07 per year in the fluticasone furoate – vilanterol group ( rate ratio with triple therapy , 0.85 ; 95 % confidence interval [ CI ] , 0.80 to 0.90 ; 15 % difference ; P<0.001 ) and 1.21 per year in the umeclidinium – vilanterol group ( rate ratio with triple therapy , 0.75 ; 95 % CI , 0.70 to 0.81 ; 25 % difference ; P<0.001 ) . The annual rate of severe exacerbations result ing in hospitalization in the triple‐therapy group was 0.13 , as compared with 0.19 in the umeclidinium – vilanterol group ( rate ratio , 0.66 ; 95 % CI , 0.56 to 0.78 ; 34 % difference ; P<0.001 ) . There was a higher incidence of pneumonia in the inhaled‐glucocorticoid groups than in the umeclidinium – vilanterol group , and the risk of clinician‐diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium – vilanterol , as assessed in a time‐to‐first‐event analysis ( hazard ratio , 1.53 ; 95 % CI , 1.22 to 1.92 ; P<0.001 ) . CONCLUSIONS Triple therapy with fluticasone furoate , umeclidinium , and vilanterol result ed in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate – vilanterol or umeclidinium – vilanterol in this population . Triple therapy also result ed in a lower rate of hospitalization due to COPD than umeclidinium – vilanterol . ( Funded by GlaxoSmithKline ; IMPACT Clinical Trials.gov number , NCT02164513 . BACKGROUND The combination of tiotropium and fluticasone propionate/salmeterol ( FSC ) is commonly used to treat chronic obstructive pulmonary disease ( COPD ) , but no study had evaluated the effectiveness of tiotropium plus FSC with 250 μg of fluticasone propionate . Our aim was to assess whether tiotropium ( 18 μg once daily ) plus FSC ( 250/50 μg twice daily ) provides better clinical outcomes compared to tiotropium monotherapy . METHODS In this 24-week , r and omized , open label , multicenter two-arm parallel study , 479 patients received tiotropium plus FSC ( n = 237 ) or tiotropium alone ( n = 242 ) . RESULTS After 24 weeks of treatment , the triple-inhaled treatment group had a significant improvement in pre-bronchodilator FEV(1 ) ( L ) compared to the tiotropium-only group ( 0.090 L vs. 0.038 L ; P = 0.005 ) . Regarding health-related quality of life , the mean change in total score on the St. George 's Respiratory Question naire for COPD patients ( SGRQ-C ) was -6.6 points in the tiotropium plus FSC group , but -1.5 points in the tiotropium-only group ( P = 0.001 ) . In the subgroup of GOLD stage II patients with COPD , treatment with tiotropium plus FSC also improved FEV(1 ) compared to tiotropium alone ( 0.088 L vs. 0.030 L ; P = 0.011 ) and improved the total SGRQ-C score  than tiotropium alone ( -4.5 points vs. -1.0 points , respectively ) . This triple-inhaled treatment approach did not induce more adverse events , such as pneumonia . CONCLUSION Over the course of 24 weeks , FSC ( 250/50 μg twice daily ) added to tiotropium provided greater improvement in lung function and quality of life in patients with COPD ( FEV(1 ) ≤ 65 % ) than tiotropium alone Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : Triple inhalation therapy with tiotropium ( Tio ) and salmeterol/fluticasone propionate combination ( SFC ) is widely used in the treatment of chronic obstructive pulmonary disease ( COPD ) . However , the effects of triple therapy on airway structural changes remain unknown . Objective : The aim of the study was to assess the effects of Tio , salmeterol ( SM ) , SFC and Tio plus SFC on airway dimensions in COPD . Methods : A r and omized , open-label , 4-way study ( n = 60 ) was conducted comparing 16-week treatment periods of Tio ( 18 μg once daily ) , SM ( 50 μg twice daily ) , SFC ( 50/250 μg twice daily ) and Tio ( 18 μg once daily ) plus SFC ( 50/250 μg twice daily ) . Airway dimensions were assessed by a vali date d CT technique , and airway wall area ( WA ) corrected for body surface area ( BSA ) , percentage WA ( WA% ) , wall thickness/√BSA and luminal area (Ai)/BSA at the right apical segmental bronchus were measured . Pulmonary function and the St. George 's Respiratory Question naire ( SGRQ ) were evaluated . Results : Tio plus SFC result ed in a significant decrease in WA corrected for BSA and WA% compared with Tio , SM and SFC ( p < 0.05 for all ) . The changes in WA% and Ai/BSA were significantly correlated with changes in forced expiratory volume in 1 s ( r = -0.86 , p < 0.001 , and r = 0.48 , p < 0.05 , respectively ) . There were more significant improvements in SGRQ scores after treatment with triple therapy than after the 3 other treatments . Conclusions : Tio plus SFC therapy is more effective than Tio , SM and SFC for reducing airway wall thickness in COPD Introduction Chronic obstructive pulmonary disease is associated with a high healthcare re source and cost burden . Healthcare re source utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study . Patients received either once-daily , single inhaler triple therapy ( fluticasone furoate/umeclidinium/vilanterol ) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy ( budesonide/formoterol ) 400 µg/12 µg . Methods FULFIL was a phase III , r and omized , double-blind , double-dummy , multicenter study . Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary ; the costs of healthcare re source utilization were calculated post hoc using UK reference costs . Results Over 24 weeks , slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol ( 169/911 ; 18.6 % ) required contacts with healthcare providers compared with budesonide/formoterol ( 180/899 ; 20.0 % ) . Over 52 weeks in an extension population , fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol ( 25.2 % vs. 32.7 % ) . Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks ( £ 653.80 vs. £ 763.32 and £ 749.22 vs. £ 988.03 , respectively ) , with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol ( £ 1,289.35 vs. £ 1,267.45 ) . Conclusions This healthcare re source utilization evidence suggests that , in a clinical trial setting over a 24- or 52-week timeframe , non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vil 
    Output:
    