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 Overactive bladder ( OAB ) syndrome with urinary incontinence ( UI ) is prevalent in the population and impairs health-related quality of life ( HRQOL ) . OBJECTIVE To assess the impact on efficacy , safety , and HRQOL of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) treatment in patients with OAB with UI . DESIGN , SETTING , AND PARTICIPANTS This pivotal , multicentre , double-blind , r and omised , placebo-controlled , phase 3 study enrolled patients with idiopathic OAB with ≥ 3 urgency UI episodes over 3 d and ≥ 8 micturitions per day who were inadequately managed by anticholinergics . INTERVENTION OnabotulinumtoxinA at a 100U dose ( n=277 ) or placebo ( n=271 ) , administered as 20 intradetrusor injections of 0.5 ml . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Co- primary end points were change from baseline in the number of UI episodes per day and proportion of patients reporting positive treatment response on the treatment benefit scale ( TBS ) at week 12 . Additional end points included other OAB symptoms ( episodes of urinary urgency incontinence , micturition , urgency , and nocturia ) and HRQOL ( Incontinence Quality of Life [ I-QOL ] , King 's Health Question naire [ KHQ ] ) . Safety assessment s included adverse events ( AEs ) , postvoid residual ( PVR ) urine volume , and initiation of clean intermittent catheterisation ( CIC ) . RESULTS AND LIMITATIONS OnabotulinumtoxinA significantly decreased UI episodes per day at week 12 ( -2.95 for onabotulinumtoxinA versus -1.03 for placebo ; p<0.001 ) . Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinumtoxinA compared with placebo ( p ≤ 0.01 ) . Patients perceived a significant improvement in their condition , as measured by patients with a positive treatment response on the TBS ( 62.8 % for onabotulinumtoxinA versus 26.8 % for placebo ; p<0.001 ) . Clinical ly meaningful improvements from baseline in all I-QOL and KHQ multi-item domains ( p<0.001 versus placebo ) indicated positive impact on HRQOL . AEs were mainly localised to the urinary tract . Mean PVR was higher in the onabotulinumtoxinA group ( 46.9 ml versus 10.1 ml at week 2 ; p<0.001 ) ; 6.9 % of onabotulinumtoxinA patients versus 0.7 % of placebo patients initiated CIC . CONCLUSIONS OnabotulinumtoxinA 100 U was well tolerated and demonstrated significant and clinical ly relevant improvements in all OAB symptoms , patient-reported benefit , and HRQOL in patients inadequately managed by anticholinergics . TRIAL REGISTRATION Clinical Trials.gov : NCT00910520 PURPOSE We evaluated the use of botulinum toxin-A in treating patients with idiopathic detrusor overactivity refractory to anticholinergics . MATERIAL S AND METHODS This double-blind , placebo controlled trial r and omized participants to intradetrusor injections of 200 U botulinum toxin-A ( 16 patients ) or placebo ( 18 patients ) . The primary outcome measure was change in maximum cystometric capacity . Secondary outcome measures included changes in overactive bladder symptoms , post-void residual , maximum detrusor pressure during filling cystometry and reflex detrusor volume . Quality of life was assessed using the Incontinence Impact Question naire short form 7 and Urogenital Distress Inventory short form 6 . Followup occurred at 4 and 12 weeks after injection , at which point the study was unblinded . Further followup in the botulinum toxin-A group occurred at 24 weeks . RESULTS Significant increases in maximum cystometric capacity were observed at 4 weeks ( difference 144.69 ml , 95 % CI 100.95 to 215.75 , p < 0.0001 ) and 12 weeks ( difference 95.71 ml , 95 % CI 47.47 to 172.45 , p = 0.001 ) in patients treated with botulinum toxin-A compared to placebo . Botulinum toxin-A reduced frequency ( p < 0.001 , p = 0.003 ) and urgency urinary incontinence ( p = 0.03 , p = 0.008 ) episodes at 4 and 12 weeks , respectively . Urgency was reduced at 4 weeks ( p = 0.005 ) in the botulinum toxin-A group . In patients receiving botulinum toxin-A , post-void residual increased at 4 weeks ( p = 0.024 ) but became insignificant by 12 weeks ( p = 0.406 ) . Of these patients 6 required intermittent self-catheterization . Significant improvements in quality of life were observed following botulinum toxin-A. The extension study suggests that the beneficial effects of botulinum toxin-A are maintained for at least 24 weeks . CONCLUSIONS Botulinum toxin-A at 200 U is safe and effective for idiopathic detrusor overactivity and the beneficial effects persist for at least 24 weeks Introduction A prespecified pooled analysis of two placebo-controlled , phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder ( OAB ) patients with urinary incontinence ( UI ) . Methods Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo , sparing the trigone . Change from baseline at week 12 in UI episodes/day , proportion of patients reporting a positive response ( ‘ greatly improved ’ or ‘ improved ’ ) on the treatment benefit scale ( TBS ) , micturition and urgency were evaluated by number of prior anticholinergics ( 1 , 2 or ≥ 3 ) and reason for their discontinuation ( insufficient efficacy or side effects ) . Adverse events ( AE ) were assessed . Results Patients had taken an average of 2.4 anticholinergics before study enrolment . OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo , regardless of the number of prior anticholinergics ( −2.82 vs. −1.52 for one prior anticholinergic ; −2.58 vs. −0.58 for two prior anticholinergics ; and −2.92 vs. −0.73 for three or more prior anticholinergics ; all p < 0.001 ) . The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo ( 69.0 % vs. 37.2 % for one prior anticholinergic ; 58.8 % vs. 24.8 % for two prior anticholinergics and 56.4 % vs. 22.5 % for three or more prior anticholinergics ; all p < 0.001 ) . Similar results were observed regardless of the reason for discontinuation . OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups . AEs were well tolerated , with a comparable incidence in all groups . Conclusion In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics , onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB . Clinical Trials.gov : NCT00910845 , NCT00910520 OBJECTIVE To evaluate the long-term efficacy and safety of repeat onabotulinumtoxinA injections in patients inadequately managed by anticholinergics for urinary incontinence ( UI ) due to neurogenic detrusor overactivity . MATERIAL S AND METHODS Patients who completed either of 2 preceding phase III studies were offered entry into an extension study and received repeat onabotulinumtoxinA 200 U or 300 U. The data were integrated across the phase III and ongoing extension studies . The present interim analysis included all patients who received ≥ 1 onabotulinumtoxinA treatment . The data were analyzed by treatment cycle ( cycles 1 - 5 ) . The primary assessment was the change from baseline in UI episodes/wk at 6 weeks after each treatment . Additional assessment s included ≥ 50 % and 100 % reductions in UI episodes , volume/void , Incontinence Quality of Life responses , and adverse events . RESULTS A total of 387 , 336 , 241 , 113 , and 46 patients received 1 , 2 , 3 , 4 , and 5 onabotulinumtoxinA treatments , respectively . The UI episodes/wk were consistently reduced compared with baseline after repeated onabotulinumtoxinA treatment ( -22.7 , -23.3 , -23.1 , -25.3 , and -31.9 for the 200-U onabotulinumtoxinA group in cycles 1 - 5 ) . The proportion of patients reporting ≥ 50 % and 100 % ( " dry " ) reductions from baseline in UI episodes at week 6 ranged from 73%-94 % and 36%-55 % , respectively . Increases in the mean volume/void ( mean increase > 130 mL ) and improvements in quality of life were also observed after repeat treatment . The most common adverse events were urinary tract infections and urinary retention , with no change in the adverse event profile over time . CONCLUSION The results of our study have shown that repeated onabotulinumtoxinA treatments provide sustained reductions in UI episodes and increases in the volume/void and quality of life in patients with neurogenic detrusor overactivity and UI who were inadequately managed by anticholinergics , with no new safety signals Introduction To evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity ( NDO ) in sub population s of etiology ( multiple sclerosis [ MS ] or spinal cord injury [ SCI ] ) and concomitant anticholinergics ( use/non-use ) . Methods Data were pooled from two double-blind , placebo-controlled , pivotal , phase 3 studies including a total of 691 patients with ≥14 urinary incontinence ( UI ) episodes/week due to MS ( n = 381 ) or SCI ( n = 310 ) . Patients received intradetrusor injections of onabotulinumtoxinA 200U ( n = 227 ) , 300U ( n = 223 ) , or placebo ( n = 241 ) . Change from baseline at week 6 in UI episodes/week ( primary endpoint ) , urodynamics , quality of life ( QOL ) , and adverse events ( AEs ) were assessed . Results Significant and similar reductions in UI episodes were observed regardless of etiology or anticholinergic use : at week 6 , mean weekly decreases of −22.6 and −19.6 were seen in MS and SCI patients , respectively , and −20.3 and −22.5 in anticholinergic users and non-users , respectively , treated with onabotulinumtoxinA 200U . The 300U dose did not add to the clinical efficacy in any sub population . Similar proportions of patients achieved ≥50 % or 100 % reductions in UI episodes in all subgroups . Improvements in maximum cystometric capacity , maximum detrusor pressure during first involuntary detrusor contraction , and QOL were significant in both etiologies and were independent of anticholinergic use . The most common AEs in all groups were urinary tract infection and urinary retention . Conclusion Regardless of concomitant anticholinergic use or etiology , onabotulinumtoxinA significantly improved UI symptoms , urodynamics , and QOL  in patients with UI due to NDO . OnabotulinumtoxinA was well tolerated in all groups PURPOSE We determined the safety and efficacy of each of 2 doses of botulinum toxin type A ( BTX-A ) ( 200 or 300 U BOTOX ) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin . MATERIAL S AND METHODS A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity ( due to spinal cord injury in 53 and multiple sclerosis in 6 ) requiring clean intermittent self-catheterization were r and omized to receive a single dose into the detrusor of BTX-A ( 200 U or 300 U ) or placebo . Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks . Key urodynamic assessment s ( maximum cystometric capacity , reflex 
    Output:
    
agent
These and other outcomes for effectiveness of BTX-A at different dosages in two observation periods indicate that a dose greater than 50 U is significantly more effective for certain symptoms of OAB compared with placebo .
However , there were no significant differences between some dosages .
Compared with placebo , the outcomes of total adverse events for NDO and for IDO show that doses of 300 U and 200 U for NDO are associated with more complications .
Conclusions In consideration that the treatments of BTX-A were with minimal , local , and manageable adverse effects , this meta- analysis demonstrates that BTX-A 200 U is recommended for management of NDO for short-term treatment for there was no significant difference from the larger dose of 300U .
***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 Overactive bladder ( OAB ) syndrome with urinary incontinence ( UI ) is prevalent in the population and impairs health-related quality of life ( HRQOL ) . OBJECTIVE To assess the impact on efficacy , safety , and HRQOL of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) treatment in patients with OAB with UI . DESIGN , SETTING , AND PARTICIPANTS This pivotal , multicentre , double-blind , r and omised , placebo-controlled , phase 3 study enrolled patients with idiopathic OAB with ≥ 3 urgency UI episodes over 3 d and ≥ 8 micturitions per day who were inadequately managed by anticholinergics . INTERVENTION OnabotulinumtoxinA at a 100U dose ( n=277 ) or placebo ( n=271 ) , administered as 20 intradetrusor injections of 0.5 ml . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Co- primary end points were change from baseline in the number of UI episodes per day and proportion of patients reporting positive treatment response on the treatment benefit scale ( TBS ) at week 12 . Additional end points included other OAB symptoms ( episodes of urinary urgency incontinence , micturition , urgency , and nocturia ) and HRQOL ( Incontinence Quality of Life [ I-QOL ] , King 's Health Question naire [ KHQ ] ) . Safety assessment s included adverse events ( AEs ) , postvoid residual ( PVR ) urine volume , and initiation of clean intermittent catheterisation ( CIC ) . RESULTS AND LIMITATIONS OnabotulinumtoxinA significantly decreased UI episodes per day at week 12 ( -2.95 for onabotulinumtoxinA versus -1.03 for placebo ; p<0.001 ) . Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinumtoxinA compared with placebo ( p ≤ 0.01 ) . Patients perceived a significant improvement in their condition , as measured by patients with a positive treatment response on the TBS ( 62.8 % for onabotulinumtoxinA versus 26.8 % for placebo ; p<0.001 ) . Clinical ly meaningful improvements from baseline in all I-QOL and KHQ multi-item domains ( p<0.001 versus placebo ) indicated positive impact on HRQOL . AEs were mainly localised to the urinary tract . Mean PVR was higher in the onabotulinumtoxinA group ( 46.9 ml versus 10.1 ml at week 2 ; p<0.001 ) ; 6.9 % of onabotulinumtoxinA patients versus 0.7 % of placebo patients initiated CIC . CONCLUSIONS OnabotulinumtoxinA 100 U was well tolerated and demonstrated significant and clinical ly relevant improvements in all OAB symptoms , patient-reported benefit , and HRQOL in patients inadequately managed by anticholinergics . TRIAL REGISTRATION Clinical Trials.gov : NCT00910520 PURPOSE We evaluated the use of botulinum toxin-A in treating patients with idiopathic detrusor overactivity refractory to anticholinergics . MATERIAL S AND METHODS This double-blind , placebo controlled trial r and omized participants to intradetrusor injections of 200 U botulinum toxin-A ( 16 patients ) or placebo ( 18 patients ) . The primary outcome measure was change in maximum cystometric capacity . Secondary outcome measures included changes in overactive bladder symptoms , post-void residual , maximum detrusor pressure during filling cystometry and reflex detrusor volume . Quality of life was assessed using the Incontinence Impact Question naire short form 7 and Urogenital Distress Inventory short form 6 . Followup occurred at 4 and 12 weeks after injection , at which point the study was unblinded . Further followup in the botulinum toxin-A group occurred at 24 weeks . RESULTS Significant increases in maximum cystometric capacity were observed at 4 weeks ( difference 144.69 ml , 95 % CI 100.95 to 215.75 , p < 0.0001 ) and 12 weeks ( difference 95.71 ml , 95 % CI 47.47 to 172.45 , p = 0.001 ) in patients treated with botulinum toxin-A compared to placebo . Botulinum toxin-A reduced frequency ( p < 0.001 , p = 0.003 ) and urgency urinary incontinence ( p = 0.03 , p = 0.008 ) episodes at 4 and 12 weeks , respectively . Urgency was reduced at 4 weeks ( p = 0.005 ) in the botulinum toxin-A group . In patients receiving botulinum toxin-A , post-void residual increased at 4 weeks ( p = 0.024 ) but became insignificant by 12 weeks ( p = 0.406 ) . Of these patients 6 required intermittent self-catheterization . Significant improvements in quality of life were observed following botulinum toxin-A. The extension study suggests that the beneficial effects of botulinum toxin-A are maintained for at least 24 weeks . CONCLUSIONS Botulinum toxin-A at 200 U is safe and effective for idiopathic detrusor overactivity and the beneficial effects persist for at least 24 weeks Introduction A prespecified pooled analysis of two placebo-controlled , phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder ( OAB ) patients with urinary incontinence ( UI ) . Methods Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo , sparing the trigone . Change from baseline at week 12 in UI episodes/day , proportion of patients reporting a positive response ( ‘ greatly improved ’ or ‘ improved ’ ) on the treatment benefit scale ( TBS ) , micturition and urgency were evaluated by number of prior anticholinergics ( 1 , 2 or ≥ 3 ) and reason for their discontinuation ( insufficient efficacy or side effects ) . Adverse events ( AE ) were assessed . Results Patients had taken an average of 2.4 anticholinergics before study enrolment . OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo , regardless of the number of prior anticholinergics ( −2.82 vs. −1.52 for one prior anticholinergic ; −2.58 vs. −0.58 for two prior anticholinergics ; and −2.92 vs. −0.73 for three or more prior anticholinergics ; all p < 0.001 ) . The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo ( 69.0 % vs. 37.2 % for one prior anticholinergic ; 58.8 % vs. 24.8 % for two prior anticholinergics and 56.4 % vs. 22.5 % for three or more prior anticholinergics ; all p < 0.001 ) . Similar results were observed regardless of the reason for discontinuation . OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups . AEs were well tolerated , with a comparable incidence in all groups . Conclusion In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics , onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB . Clinical Trials.gov : NCT00910845 , NCT00910520 OBJECTIVE To evaluate the long-term efficacy and safety of repeat onabotulinumtoxinA injections in patients inadequately managed by anticholinergics for urinary incontinence ( UI ) due to neurogenic detrusor overactivity . MATERIAL S AND METHODS Patients who completed either of 2 preceding phase III studies were offered entry into an extension study and received repeat onabotulinumtoxinA 200 U or 300 U. The data were integrated across the phase III and ongoing extension studies . The present interim analysis included all patients who received ≥ 1 onabotulinumtoxinA treatment . The data were analyzed by treatment cycle ( cycles 1 - 5 ) . The primary assessment was the change from baseline in UI episodes/wk at 6 weeks after each treatment . Additional assessment s included ≥ 50 % and 100 % reductions in UI episodes , volume/void , Incontinence Quality of Life responses , and adverse events . RESULTS A total of 387 , 336 , 241 , 113 , and 46 patients received 1 , 2 , 3 , 4 , and 5 onabotulinumtoxinA treatments , respectively . The UI episodes/wk were consistently reduced compared with baseline after repeated onabotulinumtoxinA treatment ( -22.7 , -23.3 , -23.1 , -25.3 , and -31.9 for the 200-U onabotulinumtoxinA group in cycles 1 - 5 ) . The proportion of patients reporting ≥ 50 % and 100 % ( " dry " ) reductions from baseline in UI episodes at week 6 ranged from 73%-94 % and 36%-55 % , respectively . Increases in the mean volume/void ( mean increase > 130 mL ) and improvements in quality of life were also observed after repeat treatment . The most common adverse events were urinary tract infections and urinary retention , with no change in the adverse event profile over time . CONCLUSION The results of our study have shown that repeated onabotulinumtoxinA treatments provide sustained reductions in UI episodes and increases in the volume/void and quality of life in patients with neurogenic detrusor overactivity and UI who were inadequately managed by anticholinergics , with no new safety signals Introduction To evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity ( NDO ) in sub population s of etiology ( multiple sclerosis [ MS ] or spinal cord injury [ SCI ] ) and concomitant anticholinergics ( use/non-use ) . Methods Data were pooled from two double-blind , placebo-controlled , pivotal , phase 3 studies including a total of 691 patients with ≥14 urinary incontinence ( UI ) episodes/week due to MS ( n = 381 ) or SCI ( n = 310 ) . Patients received intradetrusor injections of onabotulinumtoxinA 200U ( n = 227 ) , 300U ( n = 223 ) , or placebo ( n = 241 ) . Change from baseline at week 6 in UI episodes/week ( primary endpoint ) , urodynamics , quality of life ( QOL ) , and adverse events ( AEs ) were assessed . Results Significant and similar reductions in UI episodes were observed regardless of etiology or anticholinergic use : at week 6 , mean weekly decreases of −22.6 and −19.6 were seen in MS and SCI patients , respectively , and −20.3 and −22.5 in anticholinergic users and non-users , respectively , treated with onabotulinumtoxinA 200U . The 300U dose did not add to the clinical efficacy in any sub population . Similar proportions of patients achieved ≥50 % or 100 % reductions in UI episodes in all subgroups . Improvements in maximum cystometric capacity , maximum detrusor pressure during first involuntary detrusor contraction , and QOL were significant in both etiologies and were independent of anticholinergic use . The most common AEs in all groups were urinary tract infection and urinary retention . Conclusion Regardless of concomitant anticholinergic use or etiology , onabotulinumtoxinA significantly improved UI symptoms , urodynamics , and QOL  in patients with UI due to NDO . OnabotulinumtoxinA was well tolerated in all groups PURPOSE We determined the safety and efficacy of each of 2 doses of botulinum toxin type A ( BTX-A ) ( 200 or 300 U BOTOX ) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin . MATERIAL S AND METHODS A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity ( due to spinal cord injury in 53 and multiple sclerosis in 6 ) requiring clean intermittent self-catheterization were r and omized to receive a single dose into the detrusor of BTX-A ( 200 U or 300 U ) or placebo . Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks . Key urodynamic assessment s ( maximum cystometric capacity , reflex 
    Output:
    