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: Objective To assess the efficacy and safety of sildenafil citrate ( Viagra ® , Pfizer Inc. , USA ) in a double‐blind , placebo‐controlled , dose‐escalation study over a period of 26 weeks in men with erectile dysfunction of a broad spectrum of aetiology OBJECTIVE To evaluate the efficacy and safety of tadalafil taken as needed before sexual activity by men with diabetes and erectile dysfunction ( ED ) . RESEARCH DESIGN AND METHODS Men with type 1 or type 2 diabetes and a minimum 3-month history of ED were r and omly allocated to one of three groups : placebo ( n = 71 ) , tadalafil 10 mg ( n = 73 ) , or tadalafil 20 mg ( n = 72 ) taken up to once daily for 12 weeks . Changes from baseline in mean scores on the erectile function domain of the International Index of Erectile Function ( IIEF ) and changes from baseline in the proportion of " yes " responses to question 2 , " Were you able to penetrate ? , " and 3 , " Were you able to complete intercourse ? , " of the Sexual Encounter Profile were co primary outcome measures . RESULTS A total of 191 ( 88 % ) of 216 patients completed the study . Treatment with tadalafil significantly improved all primary efficacy variables , regardless of baseline HbA(1c ) level . Therapy with tadalafil also significantly improved a number of secondary outcome measures , including changes in other IIEF domains , individual IIEF questions , and percentage of positive responses to a global assessment question measuring erection improvement . Treatment with tadalafil did not alter mean HbA(1c ) levels . Tadalafil was well tolerated , with headache and dyspepsia being the most frequent adverse events with active treatment . CONCLUSIONS Tadalafil therapy significantly enhanced erectile function and was well tolerated by men with diabetes and ED Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size BACKGROUND In fixed-dose studies , vardenafil 5 , 10 , and 20 mg improves  erectile function in men with erectile dysfunction ( ED ) . Here , the efficacy and tolerability of vardenafil when used in a flexible-dose regimen was assessed . METHODS In this multicenter trial , 323 patients r and omly received vardenafil 10 mg or placebo .  After 4 weeks , patients could switch to 5 or 20 mg ( or corresponding placebo ) , or remain on 10 mg for an additional 4 weeks ; dose-switching was optional for the last 4 weeks . Efficacy variables included the IIEF-EF domain score , GAQ , and percentage of positive responses to SEP2/SEP3 questions . RESULTS The IIEF-EF domain score significantly improved from a baseline of moderate ED ( 12.6 - 13.1 ) to mild ED in men on  vardenafil  ( 21.0 - 24.2 ) compared with placebo ( 13.7 - 15.6 ) at weeks 4 , 8 , 12 , and last observation carried forward ( LOCF ) ( p<0.005 vs. placebo ) . A significantly greater proportion of men receiving vardenafil at weeks 4 , 8 , 12 , and LOCF reported improved erections ( 80 - 86 % vs. 21 - 36 % for placebo , p<0.005 ) . Successful SEP2 rates increased after vardenafil , reaching 84 % at weeks 8 and 12 vs. 49 - 53 % receiving placebo ( p<0.005 vs. placebo ) . Vardenafil improved successful SEP3 rates ranging from 58 % to 74 % compared to 22 - 34 % for placebo . The most common adverse events , flushing and headache , were generally mild and transient . CONCLUSION In this flexible dose study , vardenafil was well-tolerated , and produced clinical ly relevant improvements in erectile function in men with ED PURPOSE Now that individuals with spina bifida live well into adulthood erectile dysfunction has become a recognized associated medical disorder . To our knowledge no study has dealt specifically with treatment of  erectile dysfunction in men with spina bifida . Therefore , we conducted a prospect i ve , blinded , r and omized , placebo controlled , dose escalation , crossover study to determine the ability to treat erectile dysfunction in men with spina bifida with sildenafil citrate . MATERIAL S AND METHODS Erectile dysfunction was diagnosed in 15 men 19 to 35 years old with spina bifida who were assigned to take 4 sets of tablets , 5 tablets per set , in a r and om order . All patients took 25 and 50 mg . sildenafil and 2 identical looking sets of corresponding placebos 1 hour before planned sexual activity . Efficacy was assessed by the effect of treatment compared to baseline , that is before treatment , on rating of erections ( scored from 0 to 10 ) , duration of erections , frequency of erections based on response to question 1 ( scored from 0 to 5 ) of the International Index of Erectile Function and confidence to obtain an erection based on response to question 15 ( scored from 1 to 5 ) of the International Index of Erectile Function . RESULTS Improved erectile function was reported while on sildenafil by 12 ( 80 % ) men compared to baseline and placebos . There was a significant dose dependent improvement of erectile function with both 25 and 50 mg . sildenafil compared to baseline ( p < 0.05 ) , as mean erectile score increased by 50 % and 88 % , mean duration of erections increased by 192 % and 266 % , mean frequency of erections increased by 61 % and 96 % , and mean level of confidence increased by 33 % and 63 % , respectively . Furthermore , 50 mg . sildenafil provided greater improvement in all 4 parameters compared to 25 mg . The placebo results were not significantly different compared to baseline for any of the parameters . CONCLUSIONS Erectile dysfunction in patients with spina bifida is a medically treatable condition . Sildenafil is effective in this patient population and improves level of sexual confidence OBJECTIVE To determine whether crossover trials with simple pooling of data over different study periods leads to a different estimate of treatment effect compared with parallel group trials in infertility research using pregnancy as the outcome measure . DESIGN An observational study using nine overviews that included trials with both crossover and parallel group design s. These overviews comprised 17 crossover and 17 parallel group trials . In total , there were 5,291 outcomes including 775 pregnancies . The association between study design and treatment effect estimate was analyzed using multiple logistic regression , controlling for differences in the therapeutic interventions and variations in the method ological quality of the trials . SETTING Infertile patients in an academic research environment . PATIENTS Infertile patients undergoing treatment efficacy evaluation in controlled trials . INTERVENTIONS R and om allocation to a variety of treatments including clomiphene citrate , hCG , IUI , tamoxifen , and bromocriptine . MAIN OUTCOME MEASURE Estimate of bias between study design s , based on the interaction of study design and treatment in the logistic regression model . RESULTS Crossover trials produced a larger average estimate of treatment effect compared with trials with a parallel group design , overestimating the odds ratio by 74 % ( 95 % confidence interval , 2 % to 197 % ) . CONCLUSION The use of a crossover design for evaluating infertility treatments with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinical decisions . Furthermore , the type of study design should be taken into account when assessing the method ological quality of therapy trials in infertility OBJECTIVES To determine the efficacy , safety , and treatment satisfaction of tadalafil 20 mg for erectile dysfunction ( ED ) in patients evaluated at tertiary-care academic centers . METHODS In this r and omized , double-blind , placebo-controlled trial , patients were r and omly allocated to receive fixed-dose tadalafil  20 mg ( n = 146 )  or placebo ( n = 49 ) for 12 weeks . Efficacy was assessed by the International Index of Erectile Function ( IIEF ) , Sexual Encounter Profile ( SEP ) , and Global Assessment Question ( GAQ ) ; patient and partner treatment satisfaction by the Erectile Dysfunction Inventory of Treatment Satisfaction ( EDITS ) and SEP ; and safety by adverse events , laboratory values , and vital signs . RESULTS Mean baseline IIEF erectile function ( EF ) domain was 12.98 . Fifty-one percent of enrolled patients had severe baseline ED , and 82 % had organic ED . Pre-existing , ED-associated comorbid conditions were common . When compared with patients treated with placebo , those receiving tadalafil reported significant improvement from baseline in the IIEF EF domain ( P < 0.001 ) , successful penetration attempts ( SEP question 2 ; P < 0.001 ) , successful intercourse ( SEP question 3 ; P < 0.001 ) , and all secondary efficacy outcomes ( P < 0.001 ) . Patients and their sexual partners were also significantly more satisfied with tadalafil treatment ( P < 0.001 ) , including overall satisfaction ( P < 0.001 ) and length of time the treatment worked ( P < 0.001 ) . Mild or moderate headache , dyspepsia , and myalgia were the most frequent treatment-emergent adverse events reported . CONCLUSIONS Tadalafil significantly improved erectile function and patient and partner satisfaction and was well tolerated . These results were observed in a tertiary-care , academic center population with a high incidence of severe , organic ED , and comorbid medical conditions , factors known to compromise erectile function and treatment outcome OBJECTIVE In the 5 - 10 % of diabetic men with type 1 diabetes , erectile dysfunction ( ED ) may be a particularly common and unwanted complication . This is the first study focusing exclusively on the effects of sildenafil in men with type 1 diabetes and ED . RESEARCH DESIGN AND METHODS A total of 188 patients were entered into a double-blind , placebo-controlled , parallel-group , flexible-dose study and were r and omized to receive sildenafil ( 25 - 100 mg ; n = 95 ) or placebo ( n = 93 ) for 12 weeks . Efficacy was evaluated using questions three ( Q3 ; achieving an erection ) and four ( Q4 ; maintaining an erection ) from the International Index of Erectile Function ( IIEF ) , a global efficacy question ( GEQ ; " Did treatment improve your erections ? " ) , and a patient event log of sexual activity . RESULTS Improvements in mean scores from baseline to end-of-treatment for IIEF Q3 ( 35.7 vs. 19.9 % ) and Q4 ( 68.4 vs. 26.5 % ) were significant in patients receiving sildenafil compared with those receiving placebo ( P = 0.0001 ) . Moreover , the percent of improved erections ( GEQ , 66.6 vs. 28.6 % ) and successful intercourse attempts ( 63 vs. 33 % ) was significantly increased with sildenafil compared with placebo . Improvements in sexual function were seen irrespective of the degree of ED severity . Adverse events were generally mild to moderate in severity , with headache ( 20 vs. 8 % ) , flushing ( 18 vs. 3 % ) , and dyspepsia ( 8 vs. 1 % ) reported more often 
    Output:
    
agent
For common outcomes there was similar efficacy between PDE-5 inhibitors
***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 efficacy and safety of sildenafil citrate ( Viagra ® , Pfizer Inc. , USA ) in a double‐blind , placebo‐controlled , dose‐escalation study over a period of 26 weeks in men with erectile dysfunction of a broad spectrum of aetiology OBJECTIVE To evaluate the efficacy and safety of tadalafil taken as needed before sexual activity by men with diabetes and erectile dysfunction ( ED ) . RESEARCH DESIGN AND METHODS Men with type 1 or type 2 diabetes and a minimum 3-month history of ED were r and omly allocated to one of three groups : placebo ( n = 71 ) , tadalafil 10 mg ( n = 73 ) , or tadalafil 20 mg ( n = 72 ) taken up to once daily for 12 weeks . Changes from baseline in mean scores on the erectile function domain of the International Index of Erectile Function ( IIEF ) and changes from baseline in the proportion of " yes " responses to question 2 , " Were you able to penetrate ? , " and 3 , " Were you able to complete intercourse ? , " of the Sexual Encounter Profile were co primary outcome measures . RESULTS A total of 191 ( 88 % ) of 216 patients completed the study . Treatment with tadalafil significantly improved all primary efficacy variables , regardless of baseline HbA(1c ) level . Therapy with tadalafil also significantly improved a number of secondary outcome measures , including changes in other IIEF domains , individual IIEF questions , and percentage of positive responses to a global assessment question measuring erection improvement . Treatment with tadalafil did not alter mean HbA(1c ) levels . Tadalafil was well tolerated , with headache and dyspepsia being the most frequent adverse events with active treatment . CONCLUSIONS Tadalafil therapy significantly enhanced erectile function and was well tolerated by men with diabetes and ED Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size BACKGROUND In fixed-dose studies , vardenafil 5 , 10 , and 20 mg improves  erectile function in men with erectile dysfunction ( ED ) . Here , the efficacy and tolerability of vardenafil when used in a flexible-dose regimen was assessed . METHODS In this multicenter trial , 323 patients r and omly received vardenafil 10 mg or placebo .  After 4 weeks , patients could switch to 5 or 20 mg ( or corresponding placebo ) , or remain on 10 mg for an additional 4 weeks ; dose-switching was optional for the last 4 weeks . Efficacy variables included the IIEF-EF domain score , GAQ , and percentage of positive responses to SEP2/SEP3 questions . RESULTS The IIEF-EF domain score significantly improved from a baseline of moderate ED ( 12.6 - 13.1 ) to mild ED in men on  vardenafil  ( 21.0 - 24.2 ) compared with placebo ( 13.7 - 15.6 ) at weeks 4 , 8 , 12 , and last observation carried forward ( LOCF ) ( p<0.005 vs. placebo ) . A significantly greater proportion of men receiving vardenafil at weeks 4 , 8 , 12 , and LOCF reported improved erections ( 80 - 86 % vs. 21 - 36 % for placebo , p<0.005 ) . Successful SEP2 rates increased after vardenafil , reaching 84 % at weeks 8 and 12 vs. 49 - 53 % receiving placebo ( p<0.005 vs. placebo ) . Vardenafil improved successful SEP3 rates ranging from 58 % to 74 % compared to 22 - 34 % for placebo . The most common adverse events , flushing and headache , were generally mild and transient . CONCLUSION In this flexible dose study , vardenafil was well-tolerated , and produced clinical ly relevant improvements in erectile function in men with ED PURPOSE Now that individuals with spina bifida live well into adulthood erectile dysfunction has become a recognized associated medical disorder . To our knowledge no study has dealt specifically with treatment of  erectile dysfunction in men with spina bifida . Therefore , we conducted a prospect i ve , blinded , r and omized , placebo controlled , dose escalation , crossover study to determine the ability to treat erectile dysfunction in men with spina bifida with sildenafil citrate . MATERIAL S AND METHODS Erectile dysfunction was diagnosed in 15 men 19 to 35 years old with spina bifida who were assigned to take 4 sets of tablets , 5 tablets per set , in a r and om order . All patients took 25 and 50 mg . sildenafil and 2 identical looking sets of corresponding placebos 1 hour before planned sexual activity . Efficacy was assessed by the effect of treatment compared to baseline , that is before treatment , on rating of erections ( scored from 0 to 10 ) , duration of erections , frequency of erections based on response to question 1 ( scored from 0 to 5 ) of the International Index of Erectile Function and confidence to obtain an erection based on response to question 15 ( scored from 1 to 5 ) of the International Index of Erectile Function . RESULTS Improved erectile function was reported while on sildenafil by 12 ( 80 % ) men compared to baseline and placebos . There was a significant dose dependent improvement of erectile function with both 25 and 50 mg . sildenafil compared to baseline ( p < 0.05 ) , as mean erectile score increased by 50 % and 88 % , mean duration of erections increased by 192 % and 266 % , mean frequency of erections increased by 61 % and 96 % , and mean level of confidence increased by 33 % and 63 % , respectively . Furthermore , 50 mg . sildenafil provided greater improvement in all 4 parameters compared to 25 mg . The placebo results were not significantly different compared to baseline for any of the parameters . CONCLUSIONS Erectile dysfunction in patients with spina bifida is a medically treatable condition . Sildenafil is effective in this patient population and improves level of sexual confidence OBJECTIVE To determine whether crossover trials with simple pooling of data over different study periods leads to a different estimate of treatment effect compared with parallel group trials in infertility research using pregnancy as the outcome measure . DESIGN An observational study using nine overviews that included trials with both crossover and parallel group design s. These overviews comprised 17 crossover and 17 parallel group trials . In total , there were 5,291 outcomes including 775 pregnancies . The association between study design and treatment effect estimate was analyzed using multiple logistic regression , controlling for differences in the therapeutic interventions and variations in the method ological quality of the trials . SETTING Infertile patients in an academic research environment . PATIENTS Infertile patients undergoing treatment efficacy evaluation in controlled trials . INTERVENTIONS R and om allocation to a variety of treatments including clomiphene citrate , hCG , IUI , tamoxifen , and bromocriptine . MAIN OUTCOME MEASURE Estimate of bias between study design s , based on the interaction of study design and treatment in the logistic regression model . RESULTS Crossover trials produced a larger average estimate of treatment effect compared with trials with a parallel group design , overestimating the odds ratio by 74 % ( 95 % confidence interval , 2 % to 197 % ) . CONCLUSION The use of a crossover design for evaluating infertility treatments with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinical decisions . Furthermore , the type of study design should be taken into account when assessing the method ological quality of therapy trials in infertility OBJECTIVES To determine the efficacy , safety , and treatment satisfaction of tadalafil 20 mg for erectile dysfunction ( ED ) in patients evaluated at tertiary-care academic centers . METHODS In this r and omized , double-blind , placebo-controlled trial , patients were r and omly allocated to receive fixed-dose tadalafil  20 mg ( n = 146 )  or placebo ( n = 49 ) for 12 weeks . Efficacy was assessed by the International Index of Erectile Function ( IIEF ) , Sexual Encounter Profile ( SEP ) , and Global Assessment Question ( GAQ ) ; patient and partner treatment satisfaction by the Erectile Dysfunction Inventory of Treatment Satisfaction ( EDITS ) and SEP ; and safety by adverse events , laboratory values , and vital signs . RESULTS Mean baseline IIEF erectile function ( EF ) domain was 12.98 . Fifty-one percent of enrolled patients had severe baseline ED , and 82 % had organic ED . Pre-existing , ED-associated comorbid conditions were common . When compared with patients treated with placebo , those receiving tadalafil reported significant improvement from baseline in the IIEF EF domain ( P < 0.001 ) , successful penetration attempts ( SEP question 2 ; P < 0.001 ) , successful intercourse ( SEP question 3 ; P < 0.001 ) , and all secondary efficacy outcomes ( P < 0.001 ) . Patients and their sexual partners were also significantly more satisfied with tadalafil treatment ( P < 0.001 ) , including overall satisfaction ( P < 0.001 ) and length of time the treatment worked ( P < 0.001 ) . Mild or moderate headache , dyspepsia , and myalgia were the most frequent treatment-emergent adverse events reported . CONCLUSIONS Tadalafil significantly improved erectile function and patient and partner satisfaction and was well tolerated . These results were observed in a tertiary-care , academic center population with a high incidence of severe , organic ED , and comorbid medical conditions , factors known to compromise erectile function and treatment outcome OBJECTIVE In the 5 - 10 % of diabetic men with type 1 diabetes , erectile dysfunction ( ED ) may be a particularly common and unwanted complication . This is the first study focusing exclusively on the effects of sildenafil in men with type 1 diabetes and ED . RESEARCH DESIGN AND METHODS A total of 188 patients were entered into a double-blind , placebo-controlled , parallel-group , flexible-dose study and were r and omized to receive sildenafil ( 25 - 100 mg ; n = 95 ) or placebo ( n = 93 ) for 12 weeks . Efficacy was evaluated using questions three ( Q3 ; achieving an erection ) and four ( Q4 ; maintaining an erection ) from the International Index of Erectile Function ( IIEF ) , a global efficacy question ( GEQ ; " Did treatment improve your erections ? " ) , and a patient event log of sexual activity . RESULTS Improvements in mean scores from baseline to end-of-treatment for IIEF Q3 ( 35.7 vs. 19.9 % ) and Q4 ( 68.4 vs. 26.5 % ) were significant in patients receiving sildenafil compared with those receiving placebo ( P = 0.0001 ) . Moreover , the percent of improved erections ( GEQ , 66.6 vs. 28.6 % ) and successful intercourse attempts ( 63 vs. 33 % ) was significantly increased with sildenafil compared with placebo . Improvements in sexual function were seen irrespective of the degree of ED severity . Adverse events were generally mild to moderate in severity , with headache ( 20 vs. 8 % ) , flushing ( 18 vs. 3 % ) , and dyspepsia ( 8 vs. 1 % ) reported more often 
    Output:
    