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 : Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions . The interpretation of the magnitude of these differences — from trivial to large — can , however , be challenging . We investigated clinicians ’ underst and ing and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses ( st and ardized mean difference , minimal important difference units , mean difference in natural units , ratio of means , relative risk and risk difference ) . Methods : We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate . Paper-based , self-administered question naires presented summary estimates of hypothetical interventions versus placebo for chronic pain . The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes . Questions addressed participants ’ underst and ing of the magnitude of treatment effects and their perception of the usefulness of the presentation format . We r and omly assigned participants 1 of 4 versions of the question naire , each with a different effect size ( large or small ) and presentation order for the 6 formats ( 1 to 6 , or 6 to 1 ) . Results : Overall , 531 ( 87.0 % ) of the clinicians responded . Respondents best understood risk difference , followed by relative risk and ratio of means . Similarly , they perceived the dichotomous presentation of continuous outcomes ( relative risk and risk difference ) to be most useful . Presenting results as a st and ardized mean difference , the longest st and ing and most widely used approach , was poorly understood and perceived as least useful . Interpretation : None of the presentation formats were well understood or perceived as extremely useful . Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful . Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed Sixteen patients were included in the analysis of this double-blind crossover study comparing the effect of sodium cromoglycate , reproterol , sodium cromoglycate plus reproterol , and placebo in exercise-induced asthma . Both the sodium cromoglycate and the reproterol-containing treatment significantly inhibited  exercise-induced asthma .  The best protection is effected by the combination of sodium cromoglycate and reproterol . A synergistic effect of both medications could not be confirmed statistically so that their combined effect is simply additive Background The relative scale has been used for decades in analysing binary data in epidemiology . In contrast , there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute , original measurement , scale . The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations ; however , similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes . The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale . Methods Individual patient data was available for 2 r and omized trials on zinc lozenges for the treatment of the common cold . Mossad ( Ann Intern Med 125:81–8 , 1996 ) found 4.0 days and 43 % reduction , and Petrus ( Curr Ther Res 59:595–607 , 1998 ) found 1.77 days and 25 % reduction , in the duration of colds . In both trials , variance in the placebo group was significantly greater than in the zinc lozenge group . The effect estimates were applied to the common cold distributions of the placebo groups , and the result ing distributions were compared with the actual zinc lozenge group distributions . Results When the absolute effect estimates , 4.0 and 1.77 days , were applied to the placebo group common cold distributions , negative and zero ( i.e. , impossible ) cold duration s were predicted , and the high level variance remained . In contrast , when the relative effect estimates , 43 and 25 % , were applied , impossible common cold duration s were not predicted in the placebo groups , and the cold distributions became similar to those of the zinc lozenge groups . Conclusions For some continuous outcomes , such as the duration of illness and the duration of hospital stay , the relative scale leads to a more informative statistical analysis and more effective communication of the study findings . The transformation of continuous data to the relative scale is simple with a spreadsheet program , after which the relative scale data can be analysed using st and ard meta- analysis software . The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in st and ard meta- analysis programs BACKGROUND Sequential administration of a beta-agonist and cromolyn or nedocromil before exercise is recommended for patients whose symptoms are not controlled by beta-agonists alone ; however , this practice reduces compliance . OBJECTIVE To evaluate the effectiveness of a new pre-combined aerosol formulation ( salbutamol and nedocromil ) in preventing exercise-induced bronchoconstriction and to compare it to salbutamol alone . METHODS Twelve children with asthma were studied in a double-blind , double-dummy , r and omized , crossover , placebo-controlled design to compare the protective effect of salbutamol and a new pre-combined salbutamol/nedocromil formulation against exercise-induced bronchoconstriction . The drugs were delivered by a metered-dose inhaler ( salbutamol , 200 microg ; salbutamol/nedocromil , 200 microg/4 mg ; placebo , 2 puffs ) 20 minutes before exercise . RESULTS Both active drugs were significantly more protective than placebo but there was no difference between them . Complete protection was obtained in 12/12 , 10/12 , and 1/12 subjects for the salbutamol/nedocromil combination , salbutamol alone and placebo , respectively . CONCLUSIONS Although inhaled beta-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction , a minority of patients exists for whom a combined treatment with salbutamol and nedocromil is advantageous . This group may represent a sub population of subjects who release more , or different , mediators in response to exercise The effect of inhaled salmeterol xinafoate , a long acting beta 2 agonist , on  exercise induced asthma  was studied in a double blind , crossover , and placebo controlled trial . Thirteen asthmatic children with a fall of at least 15 % in their forced expiratory volume in one second ( FEV1 ) after a st and ard exercise test on a motorised treadmill , on separate days performed the same test 1 , 5 , and 9 hours after a single dose of 50 micrograms salmeterol or placebo .  FEV1 was measured before treatment , and before and for 30 minutes after each exercise test . After placebo the number of children with exercise induced asthma was : 10 at 1 hour , 11 at 5 hours , and 12 at 9 hours . Salmeterol prevented exercise induced asthma in all 13 children studied , at 1 , 5 , and 9 hours . Mean maximum falls in FEV1 after exercise were at 1 hour : salmeterol 2.7 % and placebo 24.6 % , 5 hours : salmeterol 5.3 % and placebo 22.7 % ; and 9 hours : salmeterol 3.4 % and placebo 26.6 % . After salmeterol the mean increase in FEV1 was 17.8 % at 1 hour , 19.6 % at 5 hours , and 19.2 % at 9 hours . Inhaled salmeterol prevents exercise induced asthma and produces significant bronchodilatation for at least 9 hours OBJECTIVES The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma , but tolerance may develop to its bronchoprotective effect . We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily , instead of the usual dose of 50 microg twice daily , in adolescents receiving regular glucocorticoid inhalations . Methods . In a r and omized , double-blind , 2x28-day crossover study , we administered salmeterol ( 50 microg ) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance . Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period . The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise . RESULTS Fourteen subjects with a mean age of 13.1 years completed the study . The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours . After the 28th consecutive daily dose of salmeterol , the bronchoprotective effect was significantly greater than that of placebo at 1 hour , but not at 9 hours . CONCLUSIONS We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours , but that this effect may wane during regular once-daily salmeterol treatment , despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids The duration and magnitude of the effect of inhaled formoterol ( 12 micrograms ) against exercise-induced bronchoconstriction ( EIB ) was compared with that of inhaled salbutamol ( 200 micrograms ) and that of placebo in 15 children with asthma and EIB in a double-blind , double-dummy , within-patient , placebo-controlled study . The treatments were given by metered dose aerosol on three different days . The exercise test was performed at the 3rd and the 12th hour after dosing . The magnitude of the blocking effect was assessed both by evaluating the lowest FEV1 reading obtained within an hour after each exercise test and by considering the percent decrease below the baseline FEV1 measured before drug administration . Comparison of the lowest values obtained during the hour after each exercise test shows that formoterol was significantly better than both salbutamol ( p = 0.022 ) , and placebo ( p = 0.001 ) in limiting exercise-induced bronchoconstriction after the first exercise test ( 3 h after dosing ) , while no difference was observed between salbutamol and placebo ( p = 0.198 ) . After the second exercise test ( 12 h after dosing ) , formoterol again proved to be more effective than both salbutamol ( p = 0.008 ) and placebo ( p = 0.001 ) , and no significant difference was observed between salbutamol and placebo ( p = 0.391 ) . The evaluation of the mean percentage decrease in FEV1 confirmed the results in favor of formoterol in both the exercise tests . No adverse effects were reported in any treatment group . The protection against EIB is significantly more prolonged after formoterol than after salbutamol , and persists for 12 h after dosing The effect of aerosolized terbutaline in a dose of 32.5 micrograms and its placebo , administered in a double-blind fashion , was studied in 14 children with exercise-induced asthma ( EIA ) before and during a 4-wk treatment period with aerosolized steroid ( budesonide , 400 micrograms/day ) . Effects were assessed from the changes in peak expiratory flow ( PEF ) , forced expiratory volume in one second ( FEV1 ) , and forced expiratory flow ( FEF25 - 75 ) before and after treadmill exercise challenge . Compared with placebo there was a significant improvement in pulmonary function after terbutaline . During budesonide therapy , pulmonary function improved further , but there was no enhancement of the response to terbutaline . Terbutaline alone , budesonide plus placebo , and budesonide plus terbutaline reduced the exercise-induced fall in FEV1 by 30 , 51 , and 84 % , respectively . The effect of budesonide on EIA was delayed during the 4 wk of treatment as compared with the improvement in resting pulmonary function . The present results suggest that 1 to 4 wk of therapy with inhaled corticosteroids decreases the severity of EIA . Further , the combined effect of inhaled corticosteroid and beta-2 agonist on pulmonary function appears to be additive Background . Exercise-induced bronchospasm ( EIB ) affects up to 90 % of all patients with asthma . Objective . This study evaluated the ability of levalbuterol hydrofluoroalkane ( HFA ) 90 μg ( two actuations of 45 μg ) administered via metered dose inhaler ( MDI ) to protect against EIB in mild-to-moderate asthmatics . Methods . This was a r and omized , double-blind , placebo-controlled , two-way cross-over study . Patients with asthma ( n = 15 ) were ≥18 years , had a ≥6-month history of EIB , ≥ 70 % baseline predicted forced expiratory volume in 1 second ( FEV1 ) , and a 20 % to 50 % decrease in FEV1 after treadmill exercise challenge using single-blind  placebo MDI . Levalbuterol or placebo was self-administered 30 minutes before exercise . Treatment sequences were separated by a 3-to 7-day washout period . Spirometry was performed predose , 20 minutes postdose/pre-exercise , and 5 , 10 , 15 , 30 , and 60 minutes post-exercise . The primary endpoint was the maximum percent decrease in FEV1 from baseline ( postdose/pre-exercise ) . The percentage of protected ( ≤ 20 % decrease in post-exercise FEV1 ) patients was also assessed . Results . Levalbuterol had significantly smaller maximum percent post-exerc 
    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 : Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions . The interpretation of the magnitude of these differences — from trivial to large — can , however , be challenging . We investigated clinicians ’ underst and ing and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses ( st and ardized mean difference , minimal important difference units , mean difference in natural units , ratio of means , relative risk and risk difference ) . Methods : We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate . Paper-based , self-administered question naires presented summary estimates of hypothetical interventions versus placebo for chronic pain . The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes . Questions addressed participants ’ underst and ing of the magnitude of treatment effects and their perception of the usefulness of the presentation format . We r and omly assigned participants 1 of 4 versions of the question naire , each with a different effect size ( large or small ) and presentation order for the 6 formats ( 1 to 6 , or 6 to 1 ) . Results : Overall , 531 ( 87.0 % ) of the clinicians responded . Respondents best understood risk difference , followed by relative risk and ratio of means . Similarly , they perceived the dichotomous presentation of continuous outcomes ( relative risk and risk difference ) to be most useful . Presenting results as a st and ardized mean difference , the longest st and ing and most widely used approach , was poorly understood and perceived as least useful . Interpretation : None of the presentation formats were well understood or perceived as extremely useful . Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful . Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed Sixteen patients were included in the analysis of this double-blind crossover study comparing the effect of sodium cromoglycate , reproterol , sodium cromoglycate plus reproterol , and placebo in exercise-induced asthma . Both the sodium cromoglycate and the reproterol-containing treatment significantly inhibited  exercise-induced asthma .  The best protection is effected by the combination of sodium cromoglycate and reproterol . A synergistic effect of both medications could not be confirmed statistically so that their combined effect is simply additive Background The relative scale has been used for decades in analysing binary data in epidemiology . In contrast , there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute , original measurement , scale . The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations ; however , similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes . The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale . Methods Individual patient data was available for 2 r and omized trials on zinc lozenges for the treatment of the common cold . Mossad ( Ann Intern Med 125:81–8 , 1996 ) found 4.0 days and 43 % reduction , and Petrus ( Curr Ther Res 59:595–607 , 1998 ) found 1.77 days and 25 % reduction , in the duration of colds . In both trials , variance in the placebo group was significantly greater than in the zinc lozenge group . The effect estimates were applied to the common cold distributions of the placebo groups , and the result ing distributions were compared with the actual zinc lozenge group distributions . Results When the absolute effect estimates , 4.0 and 1.77 days , were applied to the placebo group common cold distributions , negative and zero ( i.e. , impossible ) cold duration s were predicted , and the high level variance remained . In contrast , when the relative effect estimates , 43 and 25 % , were applied , impossible common cold duration s were not predicted in the placebo groups , and the cold distributions became similar to those of the zinc lozenge groups . Conclusions For some continuous outcomes , such as the duration of illness and the duration of hospital stay , the relative scale leads to a more informative statistical analysis and more effective communication of the study findings . The transformation of continuous data to the relative scale is simple with a spreadsheet program , after which the relative scale data can be analysed using st and ard meta- analysis software . The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in st and ard meta- analysis programs BACKGROUND Sequential administration of a beta-agonist and cromolyn or nedocromil before exercise is recommended for patients whose symptoms are not controlled by beta-agonists alone ; however , this practice reduces compliance . OBJECTIVE To evaluate the effectiveness of a new pre-combined aerosol formulation ( salbutamol and nedocromil ) in preventing exercise-induced bronchoconstriction and to compare it to salbutamol alone . METHODS Twelve children with asthma were studied in a double-blind , double-dummy , r and omized , crossover , placebo-controlled design to compare the protective effect of salbutamol and a new pre-combined salbutamol/nedocromil formulation against exercise-induced bronchoconstriction . The drugs were delivered by a metered-dose inhaler ( salbutamol , 200 microg ; salbutamol/nedocromil , 200 microg/4 mg ; placebo , 2 puffs ) 20 minutes before exercise . RESULTS Both active drugs were significantly more protective than placebo but there was no difference between them . Complete protection was obtained in 12/12 , 10/12 , and 1/12 subjects for the salbutamol/nedocromil combination , salbutamol alone and placebo , respectively . CONCLUSIONS Although inhaled beta-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction , a minority of patients exists for whom a combined treatment with salbutamol and nedocromil is advantageous . This group may represent a sub population of subjects who release more , or different , mediators in response to exercise The effect of inhaled salmeterol xinafoate , a long acting beta 2 agonist , on  exercise induced asthma  was studied in a double blind , crossover , and placebo controlled trial . Thirteen asthmatic children with a fall of at least 15 % in their forced expiratory volume in one second ( FEV1 ) after a st and ard exercise test on a motorised treadmill , on separate days performed the same test 1 , 5 , and 9 hours after a single dose of 50 micrograms salmeterol or placebo .  FEV1 was measured before treatment , and before and for 30 minutes after each exercise test . After placebo the number of children with exercise induced asthma was : 10 at 1 hour , 11 at 5 hours , and 12 at 9 hours . Salmeterol prevented exercise induced asthma in all 13 children studied , at 1 , 5 , and 9 hours . Mean maximum falls in FEV1 after exercise were at 1 hour : salmeterol 2.7 % and placebo 24.6 % , 5 hours : salmeterol 5.3 % and placebo 22.7 % ; and 9 hours : salmeterol 3.4 % and placebo 26.6 % . After salmeterol the mean increase in FEV1 was 17.8 % at 1 hour , 19.6 % at 5 hours , and 19.2 % at 9 hours . Inhaled salmeterol prevents exercise induced asthma and produces significant bronchodilatation for at least 9 hours OBJECTIVES The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma , but tolerance may develop to its bronchoprotective effect . We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily , instead of the usual dose of 50 microg twice daily , in adolescents receiving regular glucocorticoid inhalations . Methods . In a r and omized , double-blind , 2x28-day crossover study , we administered salmeterol ( 50 microg ) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance . Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period . The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise . RESULTS Fourteen subjects with a mean age of 13.1 years completed the study . The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours . After the 28th consecutive daily dose of salmeterol , the bronchoprotective effect was significantly greater than that of placebo at 1 hour , but not at 9 hours . CONCLUSIONS We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours , but that this effect may wane during regular once-daily salmeterol treatment , despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids The duration and magnitude of the effect of inhaled formoterol ( 12 micrograms ) against exercise-induced bronchoconstriction ( EIB ) was compared with that of inhaled salbutamol ( 200 micrograms ) and that of placebo in 15 children with asthma and EIB in a double-blind , double-dummy , within-patient , placebo-controlled study . The treatments were given by metered dose aerosol on three different days . The exercise test was performed at the 3rd and the 12th hour after dosing . The magnitude of the blocking effect was assessed both by evaluating the lowest FEV1 reading obtained within an hour after each exercise test and by considering the percent decrease below the baseline FEV1 measured before drug administration . Comparison of the lowest values obtained during the hour after each exercise test shows that formoterol was significantly better than both salbutamol ( p = 0.022 ) , and placebo ( p = 0.001 ) in limiting exercise-induced bronchoconstriction after the first exercise test ( 3 h after dosing ) , while no difference was observed between salbutamol and placebo ( p = 0.198 ) . After the second exercise test ( 12 h after dosing ) , formoterol again proved to be more effective than both salbutamol ( p = 0.008 ) and placebo ( p = 0.001 ) , and no significant difference was observed between salbutamol and placebo ( p = 0.391 ) . The evaluation of the mean percentage decrease in FEV1 confirmed the results in favor of formoterol in both the exercise tests . No adverse effects were reported in any treatment group . The protection against EIB is significantly more prolonged after formoterol than after salbutamol , and persists for 12 h after dosing The effect of aerosolized terbutaline in a dose of 32.5 micrograms and its placebo , administered in a double-blind fashion , was studied in 14 children with exercise-induced asthma ( EIA ) before and during a 4-wk treatment period with aerosolized steroid ( budesonide , 400 micrograms/day ) . Effects were assessed from the changes in peak expiratory flow ( PEF ) , forced expiratory volume in one second ( FEV1 ) , and forced expiratory flow ( FEF25 - 75 ) before and after treadmill exercise challenge . Compared with placebo there was a significant improvement in pulmonary function after terbutaline . During budesonide therapy , pulmonary function improved further , but there was no enhancement of the response to terbutaline . Terbutaline alone , budesonide plus placebo , and budesonide plus terbutaline reduced the exercise-induced fall in FEV1 by 30 , 51 , and 84 % , respectively . The effect of budesonide on EIA was delayed during the 4 wk of treatment as compared with the improvement in resting pulmonary function . The present results suggest that 1 to 4 wk of therapy with inhaled corticosteroids decreases the severity of EIA . Further , the combined effect of inhaled corticosteroid and beta-2 agonist on pulmonary function appears to be additive Background . Exercise-induced bronchospasm ( EIB ) affects up to 90 % of all patients with asthma . Objective . This study evaluated the ability of levalbuterol hydrofluoroalkane ( HFA ) 90 μg ( two actuations of 45 μg ) administered via metered dose inhaler ( MDI ) to protect against EIB in mild-to-moderate asthmatics . Methods . This was a r and omized , double-blind , placebo-controlled , two-way cross-over study . Patients with asthma ( n = 15 ) were ≥18 years , had a ≥6-month history of EIB , ≥ 70 % baseline predicted forced expiratory volume in 1 second ( FEV1 ) , and a 20 % to 50 % decrease in FEV1 after treadmill exercise challenge using single-blind  placebo MDI . Levalbuterol or placebo was self-administered 30 minutes before exercise . Treatment sequences were separated by a 3-to 7-day washout period . Spirometry was performed predose , 20 minutes postdose/pre-exercise , and 5 , 10 , 15 , 30 , and 60 minutes post-exercise . The primary endpoint was the maximum percent decrease in FEV1 from baseline ( postdose/pre-exercise ) . The percentage of protected ( ≤ 20 % decrease in post-exercise FEV1 ) patients was also assessed . Results . Levalbuterol had significantly smaller maximum percent post-exerc 
    Output:
    