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: Application of techniques such as cost-effectiveness analysis ( CEA ) is growing rapidly in health care . There are two general approaches to analysis : deterministic models based upon assumptions and secondary analysis of retrospective data , and prospect i ve stochastic analyses in which the design of a clinical experiment such as r and omised controlled trial is adapted to collect patient-specific data on costs and effects . An important method ological difference between these two approaches is in the quantification and analysis of uncertainty . Whereas the traditional CEA model utilizes sensitivity analysis , the mean-variance data on costs and effects from a prospect i ve trial presents the opportunity to analyze cost-effectiveness using conventional inferential statistical methods . In this study we explored some of the implication s of moving economic appraisal away from deterministic models and toward the experimental paradigm . Our specific focus was on the feasibility and desirability of constructing statistical tests of economic hypotheses and estimation of cost-effectiveness ratios with associated 95 % confidence intervals . We show how relevant variances can be estimated for this task and discuss the implication s for the design and analysis of prospect i ve economic studies Abstract Background and objective : Asthma is a chronic-episodic disease characterised by acute , symptomatic episodes of varying severity . We developed a Markov model that can be used to estimate the cost effectiveness of alternative asthma treatments . Because of the costs they incur , asthma exacerbations ( ‘ attacks ’ ) requiring intervention by a healthcare professional were a central consideration in the development of the model . Methods : Treatment success was assessed as asthma control , a composite measure based on goals defined in world-wide asthma management guidelines and in terms of quality -adjusted life-years ( QALYs ) . The data from which the transition probabilities were derived came from patients with asthma who received either salmeterol/fluticasone propionate combination ( SFC ) 50/100μg or fluticasone propionate ( FP ) 100μg , administered twice daily via an inhaler , in a 12-week , r and omised , double-blind , clinical trial . Costs were estimated from re source profiles defined for each of the model states . A key aspect of the model was the use of probabilistic sensitivity analysis techniques to examine the uncertainty in the cost-effectiveness results . Distributions were fitted to transition probabilities and to cost input parameters and values were sample d at r and om from these distributions using a second order Monte Carlo simulation technique . This produced a distribution for incremental cost effectiveness that was employed to construct 95 % uncertainty intervals and to construct cost effectiveness acceptability curves . Results : In this analysis , the model was run over a 12-week period using transition probabilities derived from the trial data . The results showed that treatment with SFC result ed in a higher proportion of successfully controlled weeks per patient than treatment with FP(66 vs 47 % ) , and higher mean weekly direct asthma management costs ( £ 15.77 vs £ 11.83 ; 2000 values ) . The average incremental cost per successfully controlled week with SFC was £ 20.83.Probabilistic sensitivity analysis showed that the 95 % uncertainty intervals for the incremental cost-effectiveness ratio was −£64.94 to £ 112.66 . In approximately 25 % of cases , SFC was dominant ( more effective and less costly ) , but in the remaining cases , it was both more effective and more costly . It was shown that if decision makers are willing to pay approximately £ 45 for an additional successfully controlled week , SFC will be the more cost-effective strategy in this patient population for 80 % of the time . Conclusions : This is one of the first decision-analytic models of asthma to incorporate probabilistic sensitivity analysis techniques to explore uncertainty . The model ’s flexible yet st and ardised framework permits the cost effectiveness of alternative asthma management strategies in different healthcare setting s to be established BACKGROUND Simplifying dosing regimens could improve both adherence and asthma-related morbidity . However , there is little information on the effectiveness of once-daily budesonide , administered through a metered dose inhaler ( MDI ) plus spacer , on asthma symptoms and pulmonary function in asthmatic children . METHODS The aim of this study was to compare the effect of once-daily versus twice-daily doses of inhaled budesonide on symptoms , lung function and bronchial hyperresponsiveness ( BHR ) in asthmatic children . This study was a r and omized , single-blind , parallel clinical trial . Patients received budesonide from an MDI either 800 microg as a daily dose or fractionated in 400 microg twice a day for 12 weeks . Statistical analysis was performed using tests for independent and paired sample s. RESULTS In both groups , asthma symptoms significantly decreased . However , the improvement in asthma symptoms , decrease in BHR and treatment adherence were significantly greater in the once-daily group than in the twice-daily group ( p < 0.05 ) . No significant differences were found between the two groups in spirometric parameters , morning peak expiratory flow or plasma cortisol values . CONCLUSIONS Once-daily administration of 800 microg of inhaled budesonide administered by MDI plus spacer was more effective in controlling symptoms and improving BHR than fractionating the dose to 400 microg twice daily . The differences observed in this study could have been due to the greater adherence to treatment in patients in the once-daily group This study is an extended follow‐up for 24 months of a 12‐week trial to study the long‐term clinical efficacy of low‐dose inhaled budesonide ( BUD ) once or twice daily in children with mild asthma . A total of 122 children ( mean age 9.7 years , girls/boys ; 42/80 ) with mild asthma ( FEV1 103.7 % of predicted , reversibility in FEV1 3.5 % , and fall in FEV1 afterexercise 12.2 % ) , not previously treated with inhaled steroids , were included in a double‐blind , r and omized , parallel‐group study . The children were treated with inhaled BUD 100 or 200 µg administered via Turbuhaler ® once daily in the morning , 100 µg twice daily , or placebo for 27 months . Exercise and methacholine challenges were performed at 3‐month intervals the first year and at 6‐month intervals the second year , in a total of seven visits . A significant dose‐response effect favoring BUD 200 µg daily ( vs 100 µg daily ) was found when comparing changes in FEV1 , FEF25 % , and FEV50 % ; the fall in FEV1 after an exercise test ; and the effect on blood eosinophils . Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 µg daily compared to placebo . Growth rate was not significantly affected except in children aged 7–11 years at baseline after 12 months of treatment . In conclusion , 100 or 200 µg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise‐induced asthma and achieving nearly normal lung function . Baseline lung function was not significantly affected in this group of children with mild asthma BACKGROUND --Inhaled steroids are widely used in the treatment of mild to moderate asthma . However , long term compliance with inhaled steroids is poor and administration of a single daily dose may improve compliance . METHODS --A double blind , r and omised study was performed to determine whether inhaled steroids given once daily at bedtime are as efficacious as a twice daily regimen in the long term maintenance of moderate asthmatic patients . Forty adults of mean age 37 years with moderate asthma ( mean ( SE ) forced expiratory volume in one second ( FEV1 ) 73.6 (1.4)% predicted , mean morning peak expiratory flow ( PEF ) 328 l/min ) were r and omised to receive either a twice daily dose ( 400 micrograms morning and bedtime ) of inhaled budesonide ( group A ) or a once daily dose of 800 micrograms ( group B ) and were followed for a period of 12 months . Asthma symptom scores ( assessed according to a modified Borg scale ) , inhaled beta 2 agonist consumption , and peak expiratory flow rates were recorded daily . Spirometry and airways responsiveness to methacholine ( PC20 ) were measured at the end of each period of three months of treatment . RESULTS --There was no difference between the two groups at baseline and during the follow up period in the PC20 for methacholine . However , a difference was seen between the two groups in the mean daily number of beta 2 agonist inhalations ( 1.4 ( 0.1 ) puffs/patient/day in group A v 2.3 ( 0.1 ) in group B ) , the PEF variability ( episodes of decrease in PEF of > 20 % ) ( 0.22 ( 0.01 ) episodes/patient/day in group A v 0.40 ( 0.02 ) in group B ) , and for asthma symptom scores ( 0.30 ( 0.04 ) in group A v 0.42 ( 0.06 ) in group B ) for the 12 month period of the study . CONCLUSIONS --Although both regimens provide good clinical control , twice daily doses of 400 micrograms inhaled budesonide are more effective than a single dose of 800 micrograms at bedtime in the long term control of stable moderate asthma The objective of this study was to determine the relationship between prescribed daily dose frequency and  patient medication compliance .  The medication compliance of 105 patients receiving antihypertensive medications  was monitored by analyzing data obtained from special pill containers that electronically record the date and time of medication removal . Inaccurate compliance estimates derived using the simple pill count method were thereby avoided . Compliance was defined as the percent of days during which the prescribed number of doses were removed . Compliance improved from 59.0 % on a three-time daily regimen to 83.6 % on a once-daily regimen . Thus , compliance improves dramatically as prescribed dose frequency decreases . Probably the single most important action that health care providers can take to improve compliance is to select medications that permit the lowest daily prescribed dose frequency There are only a few studies assessing the relationship between adherence rate to ICS , as assessed by electronic monitoring , and the level of asthma control in childhood . The present study was carried out to examine the relationship between adherence to  beclomethasone diproprionate ( BDP ) as well as other factors related to poor asthma control . In this prospect i ve cohort study , 102 steroid naïve r and omly selected subjects with persistent asthma , aged 5 - 14 years were prescribed 500 - 750 μg daily of BDP-CFC and followed during one year . Adherence to BDP  was measured electronically in the 4th , 8th and 12th months of study . The level of asthma control was classified as either controlled or uncontrolled instead of the current three categories recommended by the Global Initiative for Asthma ( GINA ) . Mean adherence rate was higher in patients with controlled asthma during follow-up , but went down from 60.4 % in the 4th month to 49.8 % in the 12th month ( p = 0.038 ) . Conversely , among patients with uncontrolled asthma , the mean adherence rate decreased from 43.8 % to 31.2 % ( p = 0.001 ) . Multivariate analysis showed that the level of asthma control was independently associated to the adherence rate in all follow-up visits ( p-values equal or lower than 0.005 ) . The level of asthma control was directly proportional to adherence rate . Our results suggest that a BDP daily dose by 300 μg seems to be enough to attain control over mild and moderate persistent asthma , including exercise induced asthma 
    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: Application of techniques such as cost-effectiveness analysis ( CEA ) is growing rapidly in health care . There are two general approaches to analysis : deterministic models based upon assumptions and secondary analysis of retrospective data , and prospect i ve stochastic analyses in which the design of a clinical experiment such as r and omised controlled trial is adapted to collect patient-specific data on costs and effects . An important method ological difference between these two approaches is in the quantification and analysis of uncertainty . Whereas the traditional CEA model utilizes sensitivity analysis , the mean-variance data on costs and effects from a prospect i ve trial presents the opportunity to analyze cost-effectiveness using conventional inferential statistical methods . In this study we explored some of the implication s of moving economic appraisal away from deterministic models and toward the experimental paradigm . Our specific focus was on the feasibility and desirability of constructing statistical tests of economic hypotheses and estimation of cost-effectiveness ratios with associated 95 % confidence intervals . We show how relevant variances can be estimated for this task and discuss the implication s for the design and analysis of prospect i ve economic studies Abstract Background and objective : Asthma is a chronic-episodic disease characterised by acute , symptomatic episodes of varying severity . We developed a Markov model that can be used to estimate the cost effectiveness of alternative asthma treatments . Because of the costs they incur , asthma exacerbations ( ‘ attacks ’ ) requiring intervention by a healthcare professional were a central consideration in the development of the model . Methods : Treatment success was assessed as asthma control , a composite measure based on goals defined in world-wide asthma management guidelines and in terms of quality -adjusted life-years ( QALYs ) . The data from which the transition probabilities were derived came from patients with asthma who received either salmeterol/fluticasone propionate combination ( SFC ) 50/100μg or fluticasone propionate ( FP ) 100μg , administered twice daily via an inhaler , in a 12-week , r and omised , double-blind , clinical trial . Costs were estimated from re source profiles defined for each of the model states . A key aspect of the model was the use of probabilistic sensitivity analysis techniques to examine the uncertainty in the cost-effectiveness results . Distributions were fitted to transition probabilities and to cost input parameters and values were sample d at r and om from these distributions using a second order Monte Carlo simulation technique . This produced a distribution for incremental cost effectiveness that was employed to construct 95 % uncertainty intervals and to construct cost effectiveness acceptability curves . Results : In this analysis , the model was run over a 12-week period using transition probabilities derived from the trial data . The results showed that treatment with SFC result ed in a higher proportion of successfully controlled weeks per patient than treatment with FP(66 vs 47 % ) , and higher mean weekly direct asthma management costs ( £ 15.77 vs £ 11.83 ; 2000 values ) . The average incremental cost per successfully controlled week with SFC was £ 20.83.Probabilistic sensitivity analysis showed that the 95 % uncertainty intervals for the incremental cost-effectiveness ratio was −£64.94 to £ 112.66 . In approximately 25 % of cases , SFC was dominant ( more effective and less costly ) , but in the remaining cases , it was both more effective and more costly . It was shown that if decision makers are willing to pay approximately £ 45 for an additional successfully controlled week , SFC will be the more cost-effective strategy in this patient population for 80 % of the time . Conclusions : This is one of the first decision-analytic models of asthma to incorporate probabilistic sensitivity analysis techniques to explore uncertainty . The model ’s flexible yet st and ardised framework permits the cost effectiveness of alternative asthma management strategies in different healthcare setting s to be established BACKGROUND Simplifying dosing regimens could improve both adherence and asthma-related morbidity . However , there is little information on the effectiveness of once-daily budesonide , administered through a metered dose inhaler ( MDI ) plus spacer , on asthma symptoms and pulmonary function in asthmatic children . METHODS The aim of this study was to compare the effect of once-daily versus twice-daily doses of inhaled budesonide on symptoms , lung function and bronchial hyperresponsiveness ( BHR ) in asthmatic children . This study was a r and omized , single-blind , parallel clinical trial . Patients received budesonide from an MDI either 800 microg as a daily dose or fractionated in 400 microg twice a day for 12 weeks . Statistical analysis was performed using tests for independent and paired sample s. RESULTS In both groups , asthma symptoms significantly decreased . However , the improvement in asthma symptoms , decrease in BHR and treatment adherence were significantly greater in the once-daily group than in the twice-daily group ( p < 0.05 ) . No significant differences were found between the two groups in spirometric parameters , morning peak expiratory flow or plasma cortisol values . CONCLUSIONS Once-daily administration of 800 microg of inhaled budesonide administered by MDI plus spacer was more effective in controlling symptoms and improving BHR than fractionating the dose to 400 microg twice daily . The differences observed in this study could have been due to the greater adherence to treatment in patients in the once-daily group This study is an extended follow‐up for 24 months of a 12‐week trial to study the long‐term clinical efficacy of low‐dose inhaled budesonide ( BUD ) once or twice daily in children with mild asthma . A total of 122 children ( mean age 9.7 years , girls/boys ; 42/80 ) with mild asthma ( FEV1 103.7 % of predicted , reversibility in FEV1 3.5 % , and fall in FEV1 afterexercise 12.2 % ) , not previously treated with inhaled steroids , were included in a double‐blind , r and omized , parallel‐group study . The children were treated with inhaled BUD 100 or 200 µg administered via Turbuhaler ® once daily in the morning , 100 µg twice daily , or placebo for 27 months . Exercise and methacholine challenges were performed at 3‐month intervals the first year and at 6‐month intervals the second year , in a total of seven visits . A significant dose‐response effect favoring BUD 200 µg daily ( vs 100 µg daily ) was found when comparing changes in FEV1 , FEF25 % , and FEV50 % ; the fall in FEV1 after an exercise test ; and the effect on blood eosinophils . Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 µg daily compared to placebo . Growth rate was not significantly affected except in children aged 7–11 years at baseline after 12 months of treatment . In conclusion , 100 or 200 µg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise‐induced asthma and achieving nearly normal lung function . Baseline lung function was not significantly affected in this group of children with mild asthma BACKGROUND --Inhaled steroids are widely used in the treatment of mild to moderate asthma . However , long term compliance with inhaled steroids is poor and administration of a single daily dose may improve compliance . METHODS --A double blind , r and omised study was performed to determine whether inhaled steroids given once daily at bedtime are as efficacious as a twice daily regimen in the long term maintenance of moderate asthmatic patients . Forty adults of mean age 37 years with moderate asthma ( mean ( SE ) forced expiratory volume in one second ( FEV1 ) 73.6 (1.4)% predicted , mean morning peak expiratory flow ( PEF ) 328 l/min ) were r and omised to receive either a twice daily dose ( 400 micrograms morning and bedtime ) of inhaled budesonide ( group A ) or a once daily dose of 800 micrograms ( group B ) and were followed for a period of 12 months . Asthma symptom scores ( assessed according to a modified Borg scale ) , inhaled beta 2 agonist consumption , and peak expiratory flow rates were recorded daily . Spirometry and airways responsiveness to methacholine ( PC20 ) were measured at the end of each period of three months of treatment . RESULTS --There was no difference between the two groups at baseline and during the follow up period in the PC20 for methacholine . However , a difference was seen between the two groups in the mean daily number of beta 2 agonist inhalations ( 1.4 ( 0.1 ) puffs/patient/day in group A v 2.3 ( 0.1 ) in group B ) , the PEF variability ( episodes of decrease in PEF of > 20 % ) ( 0.22 ( 0.01 ) episodes/patient/day in group A v 0.40 ( 0.02 ) in group B ) , and for asthma symptom scores ( 0.30 ( 0.04 ) in group A v 0.42 ( 0.06 ) in group B ) for the 12 month period of the study . CONCLUSIONS --Although both regimens provide good clinical control , twice daily doses of 400 micrograms inhaled budesonide are more effective than a single dose of 800 micrograms at bedtime in the long term control of stable moderate asthma The objective of this study was to determine the relationship between prescribed daily dose frequency and  patient medication compliance .  The medication compliance of 105 patients receiving antihypertensive medications  was monitored by analyzing data obtained from special pill containers that electronically record the date and time of medication removal . Inaccurate compliance estimates derived using the simple pill count method were thereby avoided . Compliance was defined as the percent of days during which the prescribed number of doses were removed . Compliance improved from 59.0 % on a three-time daily regimen to 83.6 % on a once-daily regimen . Thus , compliance improves dramatically as prescribed dose frequency decreases . Probably the single most important action that health care providers can take to improve compliance is to select medications that permit the lowest daily prescribed dose frequency There are only a few studies assessing the relationship between adherence rate to ICS , as assessed by electronic monitoring , and the level of asthma control in childhood . The present study was carried out to examine the relationship between adherence to  beclomethasone diproprionate ( BDP ) as well as other factors related to poor asthma control . In this prospect i ve cohort study , 102 steroid naïve r and omly selected subjects with persistent asthma , aged 5 - 14 years were prescribed 500 - 750 μg daily of BDP-CFC and followed during one year . Adherence to BDP  was measured electronically in the 4th , 8th and 12th months of study . The level of asthma control was classified as either controlled or uncontrolled instead of the current three categories recommended by the Global Initiative for Asthma ( GINA ) . Mean adherence rate was higher in patients with controlled asthma during follow-up , but went down from 60.4 % in the 4th month to 49.8 % in the 12th month ( p = 0.038 ) . Conversely , among patients with uncontrolled asthma , the mean adherence rate decreased from 43.8 % to 31.2 % ( p = 0.001 ) . Multivariate analysis showed that the level of asthma control was independently associated to the adherence rate in all follow-up visits ( p-values equal or lower than 0.005 ) . The level of asthma control was directly proportional to adherence rate . Our results suggest that a BDP daily dose by 300 μg seems to be enough to attain control over mild and moderate persistent asthma , including exercise induced asthma 
    Output:
    