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BOTULINUM TOXIN A (BOTOX®) DEMONSTRATES DOSE-DEPENDENT IMPROVEMENTS IN HEALTH-RELATED QUALITY-OF-LIFE MEASURES IN IDIOPATHIC OVERACTIVE BLADDER
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THE JOURNAL OF UROLOGY®
LBA8 BOTULINUM TOXIN A (BOTOX®) DEMONSTRATES DOSEDEPENDENT IMPROVEMENTS IN HEALTH-RELATED QUALITYOF-LIFE MEASURES IN IDIOPATHIC OVERACTIVE BLADDER Clare Fowler, London, United Kingdom; Stephen Auerbach, Newport Beach, CA; David Ginsberg*, Los Angeles, CA; Douglass Hale, Indianapolis, IN; Piotr Radziszewski, Warsaw, Poland; Tomasz Rechberger, Lublin, Poland; Jonathan Kowalski, Jihao Zhou, Irvine, CA INTRODUCTION AND OBJECTIVES: Symptoms of overactive bladder (OAB), especially urgency urinary incontinence (UUI), can have a substantial negative impact on health-related quality of life (HRQOL). The objective of this dose-ranging study was to assess the effects of BOTOX® treatment for patients with idiopathic OAB (IOAB) and UUI inadequately managed with anticholinergics. METHODS: In a Phase 2 multicenter, randomized, double-blind study, 313 patients with IOAB and UUI received intradetrusor BOTOX 50U (N=57), 100U (N=54), 150U (N=49), 200U (N=53), 300U (N=56), or placebo (N=44). At baseline, patients were required to have q8 UUI episodes/week and q8 micturitions/day. Patients were followed for 36 weeks post-treatment. Assessments included the Incontinence QOL (I-QOL) Instrument, 4 individual Patient Global Assessment (PGA) scales, and a Patient Satisfaction with Treatment Questionnaire (PSTQ). RESULTS: Mean age was 58.8 years; 92% female. Significantly greater improvements from baseline vs. placebo in I-QOL mean total score and for the 3 domain scores (avoidance and limiting behavior, psychosocial impacts, and social embarrassment) were observed in BOTOX dose groups q100U as early as Week 2 and continuing for subsequent post-treatment timepoints to Week 36. A dose-response was apparent. Each individual PGA scale (Symptoms, QOL, Activity Limitations, and Overall Emotions) demonstrated statistically significant improvement for the majority of BOTOX dose groups vs. placebo at visits through Week 12. No BOTOX dose groups demonstrated statistical superiority on the PGA scales beyond 24 weeks. On the PSTQ overall satisfaction question, mean changes from baseline for placebo indicated a negative effect on satisfaction with treatment, while the 100U, 150U, and 300U doses of BOTOX significantly improved satisfaction with treatment at Week 12. On the PSTQ side effects question, 150U, 100U, and 50U BOTOX dose groups were not significantly different from placebo at Week 12. Moreover, none of the BOTOX dose groups were significantly different from placebo beyond Week 12, suggesting that patient ratings of side effects were similar across treatment groups. CONCLUSIONS: BOTOX treatment resulted in positive, durable, and meaningful benefit relative to placebo in HRQOL, symptom severity, satisfaction with treatment, and patient global ratings for patients with IOAB and UUI refractory to anticholinergics. Dose-response was observed across multiple patient-reported measures. Source of Funding: This study was funded by Allergan Inc., Irvine, CA
Vol. 181, No. 4, Supplement, Tuesday, April 28, 2009
Urodynamics/Incontinence/Female Urology: Female Urology (II) Moderated Poster 51 Tuesday, April 28, 2009
1:00 pm - 3:00 pm
1554 DUAL INJURY ANIMAL MODEL OF MATERNAL CHILDBIRTH INJURIES Hui Q Pan, Dan Li Lin, David Sypert, James Steward, Paul Zaszczurynski, Robert S Butler, Cleveland, OH; Christopher R Hoover, James M Kerns, Chicago, IL; Margot S Damaser*, Cleveland, OH INTRODUCTION AND OBJECTIVES: Animal models of the maternal injuries in childbirth that can lead to pelvic floor dysfunction have focused on either vaginal distension (VD) or pudendal nerve crush (PNC). The objective of this project was to investigate urethral function, urethral anatomy, and expression of neurotrophins after a dual injury model of PNC and VD. METHODS: Rats (n=140) were divided into 4 groups and underwent a bilateral PNC, VD, both injuries (PNC+VD), or neither (C). One day after injury, expression of neurotrophins including brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and nerve growth factor (NGF), and tyrosine-specific protein kinase B (Trk-B, a receptor of BDNF and NT-4) in the external urethral sphincter (EUS) was tested by immunohistochemistry (IHC). Four, 10 and 21 days after injury, urethral function was assessed by leak point pressure (LPP). The urethra and pudendal nerve (PN) were dissected and used for histology. The number of nerve fascicles (NF), normal NF and abnormal NF near the EUS was quantitatively analyzed using ANOVA (p<0.05). RESULTS: Four days after injury, all 3 injury groups had significantly decreased LPP compared to C rats. Ten days after injury, VD rats had recovered to C values but PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, all injury groups had recovered to C values. Histological evidence of injury was evident in the EUS of the VD and PNC+VD rats 1 day after injury. Four and 10 days after injury all injury rats showed striated muscle disruption and atrophy in the EUS. Three weeks after injury the EUS remained disrupted in the PNC+VD rats. IHC showed low expression of BDNF, NT-4 and Trk-B and relatively higher expression of NGF in the EUS of C rats. BDNF expression in the EUS after VD was reduced compared to C rats, while expression of NT-4 and NGF was not different from C rats. Expression of BDNF, NT-4 and NGF was noticeably upregulated in the EUS after PNC, but only upregulated somewhat after PNC+VD compared to C rats and not to the same extent as after PNC. NGF was upregulated after PNC+VD compared to C rats. Trk-B expression was slightly positive in the EUS of all 4 groups. Ten days after injury, PNC+VD and PNC groups had significantly less number of normal NF than C rats. Twenty-one days after injury all injury groups had 2/3 the number of normal NF in C rats, but without significant differences. CONCLUSIONS: PNC+VD injury causes more severe injury than PNC or VD alone. The number of normal NF near the EUS structurally correlates with urinary functional recovery after simulated childbirth injury. Source of Funding: NIH RO1 HD38679
1555 URETHRAL DIVERTICULAE IN WOMEN: DISCREPANCIES BETWEEN MRI AND SURGICAL FINDINGS. Doreen E Chung*, Jerry G. Blaivas, Rajveer Purohit, Jeff Girshman, New York, NY INTRODUCTION AND OBJECTIVES: MRI is considered the gold standard for the diagnosis of urethral diverticulum (UD) with near 100% accuracy. Our aim was to describe instances that contradict this paradigm and to identify reasons for the discrepancies.
THE JOURNAL OF UROLOGY®
LBA8 BOTULINUM TOXIN A (BOTOX®) DEMONSTRATES DOSEDEPENDENT IMPROVEMENTS IN HEALTH-RELATED QUALITYOF-LIFE MEASURES IN IDIOPATHIC OVERACTIVE BLADDER Clare Fowler, London, United Kingdom; Stephen Auerbach, Newport Beach, CA; David Ginsberg*, Los Angeles, CA; Douglass Hale, Indianapolis, IN; Piotr Radziszewski, Warsaw, Poland; Tomasz Rechberger, Lublin, Poland; Jonathan Kowalski, Jihao Zhou, Irvine, CA INTRODUCTION AND OBJECTIVES: Symptoms of overactive bladder (OAB), especially urgency urinary incontinence (UUI), can have a substantial negative impact on health-related quality of life (HRQOL). The objective of this dose-ranging study was to assess the effects of BOTOX® treatment for patients with idiopathic OAB (IOAB) and UUI inadequately managed with anticholinergics. METHODS: In a Phase 2 multicenter, randomized, double-blind study, 313 patients with IOAB and UUI received intradetrusor BOTOX 50U (N=57), 100U (N=54), 150U (N=49), 200U (N=53), 300U (N=56), or placebo (N=44). At baseline, patients were required to have q8 UUI episodes/week and q8 micturitions/day. Patients were followed for 36 weeks post-treatment. Assessments included the Incontinence QOL (I-QOL) Instrument, 4 individual Patient Global Assessment (PGA) scales, and a Patient Satisfaction with Treatment Questionnaire (PSTQ). RESULTS: Mean age was 58.8 years; 92% female. Significantly greater improvements from baseline vs. placebo in I-QOL mean total score and for the 3 domain scores (avoidance and limiting behavior, psychosocial impacts, and social embarrassment) were observed in BOTOX dose groups q100U as early as Week 2 and continuing for subsequent post-treatment timepoints to Week 36. A dose-response was apparent. Each individual PGA scale (Symptoms, QOL, Activity Limitations, and Overall Emotions) demonstrated statistically significant improvement for the majority of BOTOX dose groups vs. placebo at visits through Week 12. No BOTOX dose groups demonstrated statistical superiority on the PGA scales beyond 24 weeks. On the PSTQ overall satisfaction question, mean changes from baseline for placebo indicated a negative effect on satisfaction with treatment, while the 100U, 150U, and 300U doses of BOTOX significantly improved satisfaction with treatment at Week 12. On the PSTQ side effects question, 150U, 100U, and 50U BOTOX dose groups were not significantly different from placebo at Week 12. Moreover, none of the BOTOX dose groups were significantly different from placebo beyond Week 12, suggesting that patient ratings of side effects were similar across treatment groups. CONCLUSIONS: BOTOX treatment resulted in positive, durable, and meaningful benefit relative to placebo in HRQOL, symptom severity, satisfaction with treatment, and patient global ratings for patients with IOAB and UUI refractory to anticholinergics. Dose-response was observed across multiple patient-reported measures. Source of Funding: This study was funded by Allergan Inc., Irvine, CA
Vol. 181, No. 4, Supplement, Tuesday, April 28, 2009
Urodynamics/Incontinence/Female Urology: Female Urology (II) Moderated Poster 51 Tuesday, April 28, 2009
1:00 pm - 3:00 pm
1554 DUAL INJURY ANIMAL MODEL OF MATERNAL CHILDBIRTH INJURIES Hui Q Pan, Dan Li Lin, David Sypert, James Steward, Paul Zaszczurynski, Robert S Butler, Cleveland, OH; Christopher R Hoover, James M Kerns, Chicago, IL; Margot S Damaser*, Cleveland, OH INTRODUCTION AND OBJECTIVES: Animal models of the maternal injuries in childbirth that can lead to pelvic floor dysfunction have focused on either vaginal distension (VD) or pudendal nerve crush (PNC). The objective of this project was to investigate urethral function, urethral anatomy, and expression of neurotrophins after a dual injury model of PNC and VD. METHODS: Rats (n=140) were divided into 4 groups and underwent a bilateral PNC, VD, both injuries (PNC+VD), or neither (C). One day after injury, expression of neurotrophins including brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and nerve growth factor (NGF), and tyrosine-specific protein kinase B (Trk-B, a receptor of BDNF and NT-4) in the external urethral sphincter (EUS) was tested by immunohistochemistry (IHC). Four, 10 and 21 days after injury, urethral function was assessed by leak point pressure (LPP). The urethra and pudendal nerve (PN) were dissected and used for histology. The number of nerve fascicles (NF), normal NF and abnormal NF near the EUS was quantitatively analyzed using ANOVA (p<0.05). RESULTS: Four days after injury, all 3 injury groups had significantly decreased LPP compared to C rats. Ten days after injury, VD rats had recovered to C values but PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, all injury groups had recovered to C values. Histological evidence of injury was evident in the EUS of the VD and PNC+VD rats 1 day after injury. Four and 10 days after injury all injury rats showed striated muscle disruption and atrophy in the EUS. Three weeks after injury the EUS remained disrupted in the PNC+VD rats. IHC showed low expression of BDNF, NT-4 and Trk-B and relatively higher expression of NGF in the EUS of C rats. BDNF expression in the EUS after VD was reduced compared to C rats, while expression of NT-4 and NGF was not different from C rats. Expression of BDNF, NT-4 and NGF was noticeably upregulated in the EUS after PNC, but only upregulated somewhat after PNC+VD compared to C rats and not to the same extent as after PNC. NGF was upregulated after PNC+VD compared to C rats. Trk-B expression was slightly positive in the EUS of all 4 groups. Ten days after injury, PNC+VD and PNC groups had significantly less number of normal NF than C rats. Twenty-one days after injury all injury groups had 2/3 the number of normal NF in C rats, but without significant differences. CONCLUSIONS: PNC+VD injury causes more severe injury than PNC or VD alone. The number of normal NF near the EUS structurally correlates with urinary functional recovery after simulated childbirth injury. Source of Funding: NIH RO1 HD38679
1555 URETHRAL DIVERTICULAE IN WOMEN: DISCREPANCIES BETWEEN MRI AND SURGICAL FINDINGS. Doreen E Chung*, Jerry G. Blaivas, Rajveer Purohit, Jeff Girshman, New York, NY INTRODUCTION AND OBJECTIVES: MRI is considered the gold standard for the diagnosis of urethral diverticulum (UD) with near 100% accuracy. Our aim was to describe instances that contradict this paradigm and to identify reasons for the discrepancies.