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 Information surrounding the long-term safety of combination inhaled corticosteroid/long-acting β(2)-adrenergic agonist medications in African American asthmatic patients is limited . OBJECTIVE We sought to assess safety and asthma control with a budesonide/formoterol pressurized metered-dose inhaler ( pMDI ) versus budesonide over 1 year in African American patients . METHODS This 52-week , r and omized , double-blind , parallel-group , multicenter , phase 3B safety study ( NCT00419952 ) was conducted in 742 self-reported African American patients 12 years or older with moderate-to-severe asthma previously receiving medium- to high-dose inhaled corticosteroids . After 2 weeks using a 320 μg twice-daily budesonide pMDI , patients were r and omized 1:1 to 320/9 μg twice-daily budesonide/formoterol pMDI or 320 μg twice-daily budesonide pMDI . RESULTS Both treatments were well tolerated . Asthma exacerbation incidence and rate ( per patient-treatment year ) were lower with budesonide/formoterol versus budesonide ( incidence , 7.7 % vs 14.0 % [ P= .006 ] ; rate ratio , 0.615 [ P= .002 ] ) . Time to first asthma exacerbation was longer ( P= .018 ) with budesonide/formoterol versus budesonide . The most common adverse events , regardless of study drug relationship , were headache ( 9.5 % and 7.7 % ) , nasopharyngitis ( 6.9 % and 8.0 % ) , sinusitis ( 4.0 % and 6.3 % ) , and viral upper respiratory tract infection ( 5.8 % and 4.4 % ) for budesonide/formoterol and budesonide , respectively . Serious adverse events occurred in 12 and 15 patients , respectively ; none were considered drug related . No substantial or unexpected patterns of abnormalities were observed in laboratory , electrocardiographic , or Holter monitoring assessment s. Hospitalization caused by asthma exacerbation occurred in 0 and 4 patients in the budesonide/formoterol and budesonide groups , respectively . Pulmonary function and asthma control measures generally favored budesonide/formoterol . CONCLUSIONS In this population budesonide/formoterol pMDI was well tolerated over 12 months , with a safety profile similar to that of budesonide ; the asthma exacerbation rate was reduced by 38.5 % versus budesonide A r and omised , double-blind trial was undertaken to investigate the efficacy and tolerability of formoterol Turbuhaler in children with mild to moderate asthma . After a two-week run-in , 248 children aged 6 - 17 years were r and omised to receive formoterol 4.5 and 9 pmicro b.i.d . or placebo for 12 weeks . Morning PEF ( primary variable ) , was significantly improved versus placebo only in the formoterol 9 pmicro b.i.d . group ( 13 l/min , 95 % CCI 1.9 , 24.2 % ; p = 0 .02 ) . Both formoterol 4.5 and 9 pmicro significantly increased the pre-bronchodilator FEV1 by 5.2 - 6.7 % ( p < 0 .05 ) and reduced use of daytime relief medication versus placebo ( p < 0 .05 ) . Formoterol 9 pmicro significantly reduced night-time reliever use and awakenings due to asthma versus placebo ( p < 0.05 ) . Both doses of formoterol were as well tolerated as placebo . In conclusion , formoterol 4.5 and 9 micro b.i.d . is effective and well tolerated as maintenance therapy in children with mild to moderate asthma BACKGROUND For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid ( ICS ) therapy , the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose . OBJECTIVE To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma . METHODS A r and omized , multicenter , double-blind , active-controlled , parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy . Patients received fluticasone propionate-salmeterol ( 100/50 microg ) or fluticasone propionate ( 100 microg ) alone twice daily for 12 weeks . RESULTS The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone . The overall incidence of adverse events was 59 % for fluticasone propionate-salmeterol and 57 % for fluticasone propionate . Both treatments were well tolerated . Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma . Changes in heart rate , blood pressure , and laboratory variables were infrequent and were similar between treatments . No patients had clinical ly significant abnormal electrocardiographic findings during treatment . Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups ; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment . The incidence of withdrawals due to asthma exacerbations was 2 % in the fluticasone propionate-salmeterol group and 5 % in the fluticasone propionate group . CONCLUSIONS In pediatric patients with persistent asthma , fluticasone propionate-salmeterol twice daily was well tolerated , with a safety profile similar to that of fluticasone propionate used alone Inhalation of on-dem and salbutamol ( ODS ) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma , whereas a long-acting beta2-agonist should be added . This trial aim ed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d . ( Foradil ) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids , in the conditions of real practice . Two hundred and fifty-nine patients were r and omized ( formoterol ; 130 ; ODS : 129 ) in this open , parallel-group trial . The mean increases in morning peak expiratory flow ( PEF primary variable ) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol : + 25.7 and + 24.1 l min(-1 ) , respectively vs. + 4.5 and + 0.5 l min(-1 ) respectively with ODS . The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3 . Formoterol  reduced the use of salbutamol as rescue medication by two-thirds . The percentages of symptom-free days and nights statistically significantly increased with formoterol ( + 20 % and + 33 % respectively ) , but did not significantly change with ODS  .  Clinical ly relevant and statistically significant improvement in the mean total score of the St George 's Hospital Respiratory Question naire was observed in the formoterol group . Adverse events were similar in the two groups . The results show that treatment with formoterol has significant advantages over ODS  in patients with moderate persistent asthma Abstract Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone . Design and setting A 52 week , two period , double blind , multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were r and omised to add montelukast or salmeterol .  Participants Patients ( 15 - 72 years ; n = 1490 ) had a clinical history of chronic asthma for ≥ 1 year , a baseline forced expiratory volume in one second ( FEV 1 ) value 50 - 90 % predicted , and a β agonist improvement of ≥ 12 % in FEV 1 . Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation . Results 20.1 % of the patients in the group receiving montelukast and fluticasone  had an asthma exacerbation compared with 19.1 % in the group receiving salmeterol and fluticasone ; the difference was 1 % ( 95 % confidence interval -3.1 % to 5.0 % ) . With a risk ratio ( montelukast-fluticasone/salmeterol-fluticasone ) of 1.05 ( 0.86 to 1.29 ) , treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone . Salmeterol and fluticasone  significantly increased FEV 1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone ( P ≤ 0.001 ) , whereas FEV 1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups . Montelukast and fluticasone significantly ( P = 0.011 ) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone . Both treatments were generally well tolerated . Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol BACKGROUND Diacerein is a drug used in osteoarthritis ( OA ) that elicits an inhibitory effect on interleukin-1 and metalloproteases . Although diacerein has shown modest efficacy and safety in the treatment of knee and hip OA , there have been no placebo-controlled clinical trials for h and OA . OBJECTIVE The aim of the current study was to investigate the efficacy and tolerability of diacerein in patients with h and OA . METHODS Patients fulfilling the American College of Rheumatology criteria for h and OA participated in this r and omized , double-blind , placebo-controlled study . Eligible patients were > 40 years of age , had at least 1 tender joint , and had a joint pain visual analog scale of > 30 mm . Patients received diacerein ( 50 mg ) or placebo BID for 12 weeks . The primary end point was the Australian/Canadian Osteoarthritis H and Index ( AUSCAN ) pain score at 4 weeks . Secondary end points were AUSCAN pain score at 12 weeks and AUSCAN physical function and stiffness score , patient and physician global assessment , functional index of h and OA scores , and multidimensional health assessment question naire results at 4 weeks and 12 weeks . RESULTS Eighty-six Korean patients were enrolled ( 42 diacerein , 44 placebo ) . The intention-to-treat and per- protocol analyses revealed no significant differences between the 2 groups in terms of change in AUSCAN pain score at 4 weeks , except for improvement in physician global assessment at 4 weeks ( per- protocol analysis , P = 0.004 ) . The safety profile of diacerein was comparable to placebo , except for frequent discoloration of the urine ( 88 % vs 20 % ) . CONCLUSION These results suggest that diacerein 50 mg BID may be ineffective in controlling the symptoms of h and OA . Clinical Trials.gov identifier : NCT00685542 BACKGROUND In vitro the long acting β2 agonist salmeterol can , in contrast to formoterol , behave as a partial agonist and become a partial antagonist to other β2 agonists . To study this in vivo , the bronchodilating effect of salbutamol was measured during methacholine induced moderate to severe bronchoconstriction in patients receiving maintenance treatment with high dose long acting β2agonists . METHODS A r and omised double blind crossover study was performed in 19 asthmatic patients with mean forced expiratory volume in one second ( FEV1 ) of 88.4 % predicted and median concentration of methacholine provoking a fall in FEV1 of 20 % or more ( PC20 ) of 0.62 mg/ml at entry . One hour after the last dose of 2 weeks of treatment with formoterol ( 24 μg twice daily by Turbuhaler ) , salmeterol ( 100 μg twice daily by Diskhaler ) , or placebo a methacholine provocation test was performed and continued until there was at least a 30 % decrease in FEV1 . Salbutamol ( 50 μg ) was administered immediately thereafter , followed by ipratropium bromide ( 40 μg ) after a further 30 minutes . Lung function was monitored for 1 hour after provocation . RESULTS There was a significant bronchodilating and bronchoprotective effect after 2 weeks of active treatment . The dose of methacholine needed to provoke a fall in FEV1 of ⩾30 % was higher after pretreatment with formoterol ( 2.48 mg ) than with salmeterol ( 1.58 mg ) or placebo ( 0.74 mg 
    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 Information surrounding the long-term safety of combination inhaled corticosteroid/long-acting β(2)-adrenergic agonist medications in African American asthmatic patients is limited . OBJECTIVE We sought to assess safety and asthma control with a budesonide/formoterol pressurized metered-dose inhaler ( pMDI ) versus budesonide over 1 year in African American patients . METHODS This 52-week , r and omized , double-blind , parallel-group , multicenter , phase 3B safety study ( NCT00419952 ) was conducted in 742 self-reported African American patients 12 years or older with moderate-to-severe asthma previously receiving medium- to high-dose inhaled corticosteroids . After 2 weeks using a 320 μg twice-daily budesonide pMDI , patients were r and omized 1:1 to 320/9 μg twice-daily budesonide/formoterol pMDI or 320 μg twice-daily budesonide pMDI . RESULTS Both treatments were well tolerated . Asthma exacerbation incidence and rate ( per patient-treatment year ) were lower with budesonide/formoterol versus budesonide ( incidence , 7.7 % vs 14.0 % [ P= .006 ] ; rate ratio , 0.615 [ P= .002 ] ) . Time to first asthma exacerbation was longer ( P= .018 ) with budesonide/formoterol versus budesonide . The most common adverse events , regardless of study drug relationship , were headache ( 9.5 % and 7.7 % ) , nasopharyngitis ( 6.9 % and 8.0 % ) , sinusitis ( 4.0 % and 6.3 % ) , and viral upper respiratory tract infection ( 5.8 % and 4.4 % ) for budesonide/formoterol and budesonide , respectively . Serious adverse events occurred in 12 and 15 patients , respectively ; none were considered drug related . No substantial or unexpected patterns of abnormalities were observed in laboratory , electrocardiographic , or Holter monitoring assessment s. Hospitalization caused by asthma exacerbation occurred in 0 and 4 patients in the budesonide/formoterol and budesonide groups , respectively . Pulmonary function and asthma control measures generally favored budesonide/formoterol . CONCLUSIONS In this population budesonide/formoterol pMDI was well tolerated over 12 months , with a safety profile similar to that of budesonide ; the asthma exacerbation rate was reduced by 38.5 % versus budesonide A r and omised , double-blind trial was undertaken to investigate the efficacy and tolerability of formoterol Turbuhaler in children with mild to moderate asthma . After a two-week run-in , 248 children aged 6 - 17 years were r and omised to receive formoterol 4.5 and 9 pmicro b.i.d . or placebo for 12 weeks . Morning PEF ( primary variable ) , was significantly improved versus placebo only in the formoterol 9 pmicro b.i.d . group ( 13 l/min , 95 % CCI 1.9 , 24.2 % ; p = 0 .02 ) . Both formoterol 4.5 and 9 pmicro significantly increased the pre-bronchodilator FEV1 by 5.2 - 6.7 % ( p < 0 .05 ) and reduced use of daytime relief medication versus placebo ( p < 0 .05 ) . Formoterol 9 pmicro significantly reduced night-time reliever use and awakenings due to asthma versus placebo ( p < 0.05 ) . Both doses of formoterol were as well tolerated as placebo . In conclusion , formoterol 4.5 and 9 micro b.i.d . is effective and well tolerated as maintenance therapy in children with mild to moderate asthma BACKGROUND For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid ( ICS ) therapy , the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose . OBJECTIVE To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma . METHODS A r and omized , multicenter , double-blind , active-controlled , parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy . Patients received fluticasone propionate-salmeterol ( 100/50 microg ) or fluticasone propionate ( 100 microg ) alone twice daily for 12 weeks . RESULTS The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone . The overall incidence of adverse events was 59 % for fluticasone propionate-salmeterol and 57 % for fluticasone propionate . Both treatments were well tolerated . Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma . Changes in heart rate , blood pressure , and laboratory variables were infrequent and were similar between treatments . No patients had clinical ly significant abnormal electrocardiographic findings during treatment . Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups ; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment . The incidence of withdrawals due to asthma exacerbations was 2 % in the fluticasone propionate-salmeterol group and 5 % in the fluticasone propionate group . CONCLUSIONS In pediatric patients with persistent asthma , fluticasone propionate-salmeterol twice daily was well tolerated , with a safety profile similar to that of fluticasone propionate used alone Inhalation of on-dem and salbutamol ( ODS ) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma , whereas a long-acting beta2-agonist should be added . This trial aim ed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d . ( Foradil ) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids , in the conditions of real practice . Two hundred and fifty-nine patients were r and omized ( formoterol ; 130 ; ODS : 129 ) in this open , parallel-group trial . The mean increases in morning peak expiratory flow ( PEF primary variable ) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol : + 25.7 and + 24.1 l min(-1 ) , respectively vs. + 4.5 and + 0.5 l min(-1 ) respectively with ODS . The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3 . Formoterol  reduced the use of salbutamol as rescue medication by two-thirds . The percentages of symptom-free days and nights statistically significantly increased with formoterol ( + 20 % and + 33 % respectively ) , but did not significantly change with ODS  .  Clinical ly relevant and statistically significant improvement in the mean total score of the St George 's Hospital Respiratory Question naire was observed in the formoterol group . Adverse events were similar in the two groups . The results show that treatment with formoterol has significant advantages over ODS  in patients with moderate persistent asthma Abstract Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone . Design and setting A 52 week , two period , double blind , multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were r and omised to add montelukast or salmeterol .  Participants Patients ( 15 - 72 years ; n = 1490 ) had a clinical history of chronic asthma for ≥ 1 year , a baseline forced expiratory volume in one second ( FEV 1 ) value 50 - 90 % predicted , and a β agonist improvement of ≥ 12 % in FEV 1 . Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation . Results 20.1 % of the patients in the group receiving montelukast and fluticasone  had an asthma exacerbation compared with 19.1 % in the group receiving salmeterol and fluticasone ; the difference was 1 % ( 95 % confidence interval -3.1 % to 5.0 % ) . With a risk ratio ( montelukast-fluticasone/salmeterol-fluticasone ) of 1.05 ( 0.86 to 1.29 ) , treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone . Salmeterol and fluticasone  significantly increased FEV 1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone ( P ≤ 0.001 ) , whereas FEV 1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups . Montelukast and fluticasone significantly ( P = 0.011 ) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone . Both treatments were generally well tolerated . Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol BACKGROUND Diacerein is a drug used in osteoarthritis ( OA ) that elicits an inhibitory effect on interleukin-1 and metalloproteases . Although diacerein has shown modest efficacy and safety in the treatment of knee and hip OA , there have been no placebo-controlled clinical trials for h and OA . OBJECTIVE The aim of the current study was to investigate the efficacy and tolerability of diacerein in patients with h and OA . METHODS Patients fulfilling the American College of Rheumatology criteria for h and OA participated in this r and omized , double-blind , placebo-controlled study . Eligible patients were > 40 years of age , had at least 1 tender joint , and had a joint pain visual analog scale of > 30 mm . Patients received diacerein ( 50 mg ) or placebo BID for 12 weeks . The primary end point was the Australian/Canadian Osteoarthritis H and Index ( AUSCAN ) pain score at 4 weeks . Secondary end points were AUSCAN pain score at 12 weeks and AUSCAN physical function and stiffness score , patient and physician global assessment , functional index of h and OA scores , and multidimensional health assessment question naire results at 4 weeks and 12 weeks . RESULTS Eighty-six Korean patients were enrolled ( 42 diacerein , 44 placebo ) . The intention-to-treat and per- protocol analyses revealed no significant differences between the 2 groups in terms of change in AUSCAN pain score at 4 weeks , except for improvement in physician global assessment at 4 weeks ( per- protocol analysis , P = 0.004 ) . The safety profile of diacerein was comparable to placebo , except for frequent discoloration of the urine ( 88 % vs 20 % ) . CONCLUSION These results suggest that diacerein 50 mg BID may be ineffective in controlling the symptoms of h and OA . Clinical Trials.gov identifier : NCT00685542 BACKGROUND In vitro the long acting β2 agonist salmeterol can , in contrast to formoterol , behave as a partial agonist and become a partial antagonist to other β2 agonists . To study this in vivo , the bronchodilating effect of salbutamol was measured during methacholine induced moderate to severe bronchoconstriction in patients receiving maintenance treatment with high dose long acting β2agonists . METHODS A r and omised double blind crossover study was performed in 19 asthmatic patients with mean forced expiratory volume in one second ( FEV1 ) of 88.4 % predicted and median concentration of methacholine provoking a fall in FEV1 of 20 % or more ( PC20 ) of 0.62 mg/ml at entry . One hour after the last dose of 2 weeks of treatment with formoterol ( 24 μg twice daily by Turbuhaler ) , salmeterol ( 100 μg twice daily by Diskhaler ) , or placebo a methacholine provocation test was performed and continued until there was at least a 30 % decrease in FEV1 . Salbutamol ( 50 μg ) was administered immediately thereafter , followed by ipratropium bromide ( 40 μg ) after a further 30 minutes . Lung function was monitored for 1 hour after provocation . RESULTS There was a significant bronchodilating and bronchoprotective effect after 2 weeks of active treatment . The dose of methacholine needed to provoke a fall in FEV1 of ⩾30 % was higher after pretreatment with formoterol ( 2.48 mg ) than with salmeterol ( 1.58 mg ) or placebo ( 0.74 mg 
    Output:
    