***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: Objective : To assess the cost-effectiveness of 3 treatments ( tiotropium , salmeterol , and no treatment ) in patients with moderate chronic obstructive pulmonary disease ( COPD ) . Methods : A Markov model with a time horizon of 1 year was developed . A hypothetical cohort of 100,000 subjects with moderate COPD with mean age of 65 years , smoking history of 50 pack-years , and disease duration of 9.5 years were included in the model . The efficacy and withdrawal data were taken from published r and omized clinical trials . The effectiveness measure was exacerbations avoided per patient per year . Incremental cost-effectiveness ratio ( ICER ) was calculated as additional cost per patient to prevent 1 exacerbation , compared with the next most expensive option . A payer ’s perspective was used and only direct costs were included in the study . Sensitivity analyses were conducted to test the robustness of the baseline estimates and study assumptions . Results : The mean annual costs for the no treatment , salmeterol , and tiotropium groups were $ 392.1 , $ 1268.7 , and $ 1408.6 , respectively . The ICER of tiotropium compared with no treatment was $ 1817.36 per exacerbation avoided , while the ICER of salmeterol compared with no treatment was $ 2454.48 per exacerbation avoided . Thus , in patients with moderate COPD , tiotropium is more cost-effective than salmeterol and no treatment RATIONALE OM-85 BV , an immunostimulant made from bacterial extracts , has been shown to reduce the risk of hospitalization for acute exacerbation in patients with chronic obstructive pulmonary disease , as well as to reduce the length of stay for all hospitalizations . METHODS In conjunction with a placebo controlled , r and omized clinical trial , a cost effectiveness analysis was carried out to assess the economic impact of using OM-85 BV . In the analysis , effectiveness was defined as the difference in the number of severe acute exacerbations , assessed by the number of hospitalizations for a respiratory problem , between the  placebo and OM-85 BV-treated groups . RESULTS The median cost to prevent one day of hospitalization for a respiratory condition was CDN$45 , with a 95 % CI of CDN$18 to CDN$210 . Bootstrap of the study population and sensitivity analyses showed that the results were robust and not likely due to r and om fluctuation ; 98.8 % of the cost effectiveness and 96.8 % of the cost-benefit ratios favoured the use of OM-85 BV .  Indirect costs , defined as a need for help , were reduced by 36 % in the group treated with OM-85 BV : 779 h of help compared with 1212 h in the placebo group . This trend , while not significant , is consistent with other results and suggests a decrease in the severity of exacerbations in the OM-85 BV-treated group . CONCLUSION Given the high prevalence of chronic obstructive pulmonary disease worldwide and the high cost of acute exacerbations , immunostimulants may become a key element in the improved control of this condition BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is debilitating and costly to manage . A recent clinical trial concluded that formoterol , a long-acting beta(2)-adrenoceptor agonist , was more clinical ly effective than inpratropium bromide in the management of COPD . OBJECTIVE The aim of this study was to perform an economic assessment of the management of COPD with formeterol versus ipratropium bromide . METHODS Assessment were based on the results of a previously published 12-week , multicenter , double-masked , r and omized , parallel-group , placebo-controlled clinical trial comparing inhaled formoterol dry powder 12 and 24 microg BID with ipratropium bromide 40 microg QID pressurized metered dose inhaler and with placebo in 780 COPD patients .  Treatment costs for study drugs and rescue medications were estimated from re source utilization and average wholesale prices . Costs were assessed with respect to forced expiratory lung volume in 1 second ( FEV(1 ) ) and patient-reported quality of life ( QOL ) as assessed via the St. George 's Respiratory Question naire . Cost-effectiveness ratios were calculated for each treatment arm and incremental cost-effectiveness ratios ( ICERs ) were calculated for each treatment relative to the next best alternative . Economic efficiency frontiers were identified . Sensitivity analysis was conducted . RESULTS Cost analysis with respect to FEV(1 ) revealed an economic efficiency frontier formed by placebo , ipratropium bromide 40 microg , and formoterol 12 microg at their respective FEV(1 ) levels , with cost-effectiveness ratios of $ 30.18 , $ 53.50 , and $ 142.04 , respectively , per FEV(1 ) . The ICER for ipratropium over placebo was $ 273.03 ; for formoterol 12 microg over ipratropium , $ 1611.32 . Cost analysis with respect to QOL showed an economic efficiency frontier formed by placebo and formoterol 12 microg at their respective QOL outcomes , with cost-effectiveness ratios of $ 25.96 and $ 32.56 , respectively , per QOL score change . The cost-effectiveness ratio for ipratropium was $ 69.40,which was not on the QOL economic efficiency frontier . The ICER for formoterol 12 microg over placebo was $ 34.51 per QOL score point . CONCLUSIONS Formoterol 12 microg provided greater QOL outcome than ipratropium bromide at an additional cost of $ 554.28 per year . Further research would be necessary to assess whether the differences in outcomes , particularly QOL , observed in the short term with formoterol would lead to favorable long-term health and economic outcomes The Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) serves as a guide to treat and manage different severity classes of patients with COPD . It was suggested that the five categories of FEV1 % predicted ( GOLD 0–4 ) , can be applied for selecting different therapeutic approaches . However , validation of these selective properties is very poor . To determine the relevance of the GOLD staging system for estimating the severity of clinical problems , GOLD 2 ( n=70 ) and GOLD 3 ( n=65 ) patients were drawn from a prospect i ve cohort of patients with COPD and evaluated crosssectionally by a newly developed Nijmegen Integral Assessment Framework ( NIAF ) . The NIAF is a detailed assessment of a wide range of aspects of health status ( HS ) . Significant , though small , differences were found in Static Lung Volumes , Exercise Capacity , Subjective Pulmonary Complaints , Subjective Impairment , and Health-Related QoL , besides Airflow of course . Moreover , overlap between scores of these five HS sub-domains was substantial , indicating small clinical relevance for discernment . No significant differences were found in nine other aspects of HS . It is concluded that GOLD stages do not discriminate in any aspect of HS other than airflow obstruction , and therefore do not help the clinician in deciding which treatment modalities are appropriate Objective : To estimate the cost-effectiveness of fluticasone propionate – salmeterol combination ( FSC ) compared to salmeterol for maintenance therapy in severe chronic obstructive pulmonary disease ( COPD ) . Study design : Pooled economic analysis . Methods : We performed an economic analysis of pooled data from two r and omized clinical trials ( combined N = 1554 ) that evaluated the effect of maintenance therapy with FSC ( 250/50 μg twice daily ) or salmeterol ( 50 μg twice daily ) on exacerbation rates in patients with severe COPD . We calculated exacerbation rates and applied st and ardized costs to exacerbation-related health care utilization reported in the trials ( office , urgent care , and emergency department visits ; hospitalizations ; and oral corticosteroids and antibiotics ) to determine cost differences between FSC and salmeterol treatment outcomes . Results : Annual rates of any exacerbation and moderate/severe exacerbation were lower in the FSC group than the salmeterol group ( 4.91 vs 5.78 and 1.32 vs 2.00 respectively , both P < 0.05 ) . Total adjusted annual COPD related exacerbation and therapeutic costs were $ 4,842 ( 95 % CI ; $ 4,731–$4,952 ) in the FSC group and $ 5,066 ( 95 % CI ; $ 4,937–$5,195 ) in the salmeterol group . Conclusions : FSC combination therapy is associated with reduced risk of any exacerbation and moderate/severe exacerbation , and incurs lower annual COPD -related health care costs compared to treatment with salmeterol . This analysis demonstrates that FSC therapy may be advantageous from both a clinical and cost-benefit st and point for patients with severe COPD Background : Little is known about the combination of different medications in chronic obstructive pulmonary disease ( COPD ) . This study determined the cost effectiveness of adding salmeterol ( S ) or fluticasone/salmeterol ( FS ) to tiotropium ( T ) for COPD . Methods : This concurrent , prospect i ve , economic analysis was based on costs and health outcomes from a 52 week r and omised study comparing : ( 1 ) T 18 µg once daily + placebo twice daily ( TP group ) ; ( 2 ) T 18 µg once daily + S 25 µg/puff , 2 puffs twice daily ( TS group ) ; and ( 3 ) T 18 µg once daily + FS 250/25 µg/puff , 2 puffs twice daily ( TFS group ) . The incremental cost effectiveness ratios ( ICERs ) were defined as incremental cost per exacerbation avoided , and per additional quality adjusted life year ( QALY ) between treatments . A combination of imputation and bootstrapping was used to quantify uncertainty , and extensive sensitivity analyses were performed . Results : The average patient in the TP group generated CAN$2678 in direct medical costs compared with $ 2801 ( TS group ) and $ 4042 ( TFS group ) . The TS strategy was dominated by TP and TFS . Compared with TP , the TFS strategy result ed in ICERs of $ 6510 per exacerbation avoided , and $ 243 180 per QALY gained . In those with severe COPD , TS result ed in equal exacerbation rates and slightly lower costs compared with TP . Conclusions : TFS had significantly better quality of life and fewer hospitalisations than patients treated with TP but these improvements in health outcomes were associated with increased costs . Neither TFS nor TS are economically attractive alternatives compared with monotherapy with The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new , once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease ( COPD ) . This prospect i ve cost-effectiveness analysis was performed alongside two 1‐yr r and omised , double-blind clinical trials in the Netherl and s and Belgium . Patients had a diagnosis of COPD and a forced expiratory volume in one second ( FEV1 ) ≤65 % predicted normal . Patients were r and omised to tiotropium ( 18 µg once daily ) or ipratropium ( 2 puffs of 20 µg administered four times daily ) in a ratio of 2:1 . The mean number of exacerbations was reduced from 1.01 in the ipratropium group ( n=175 ) to 0.74 in the tiotropium group ( n=344 ) . The percentages of patients with a relevant improvement on the St. George 's Respiratory Question naire ( SGRQ ) were 34.6 % and 51.2 % respectively . Compared to ipratropium , the number of hospital admissions , hospital days and unscheduled visits to healthcare providers was reduced by 46 % , 42 % and 36 % respectively . Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 ( sem 160 ) in the tiotropium group and 1,541 ( SEM 163 ) in the ipratropium group ( difference 180 ) . Incremental cost-effectiveness ratios were 667 per exacerbation avoided and 1084 per patient with a relevant improvement on the SGRQ . Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 per patient per year Exacerbations of chronic obstuctive pulmonary disease ( COPD ) are associated with worse health status . The Inhaled Steroids in Obstructive Lung Disease in Europe ( ISOLDE ) study showed that treatment with fluticasone propionate ( FP ) reduced exacerbation frequency and the rate of deterioration in health status as compared with placebo . The present study analysed these data to test whether the effect of FP on health status was attributable to its effect on exacerbations . Rates of deterioration in St George 's Respiratory Question naire ( SGRQ ) total score were obtained for 613 patients with moderate to severe COPD followed for a maximum of 3 yrs . Exacerbation rates were skewed and could not be normalised , therefore , patients were stratified into three exacerbation groups : none , infrequent ( < 1.65 exac 
    Output:
    
The few studies on combining short-acting bronchodilators were consistent in finding net cost savings compared with monotherapy .
Studies comparing fluticasone with salmeterol consistently found salmeterol to be more cost effective .
All of these studies reported additional health benefits of tiotropium .
The cost-per-QALY estimates of this combination treatment vary widely and are very sensitive to the assumptions on mortality benefit and time horizon .