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Purpose: To assess efficacy and safety of URO-902, an investigational gene therapy expressing the α subunit of the large-conductance Ca 2+ -activated K + channel, in a phase 2a placebo-controlled trial in women with overactive bladder (OAB)., Materials and Methods: Women, age 40 to 79 years, with OAB and urge urinary incontinence who were refractory to OAB medications were randomized to single-dose URO-902 24 and 48 mg or placebo administered by intradetrusor injection by cystoscopy under local anesthesia. Efficacy end points included change from baseline to week 12 in mean daily micturitions, urgency episodes, urge urinary incontinence episodes, and patient-reported outcomes. Safety assessments included adverse events and postvoid residual urine volume., Results: Of 80 patients randomized (URO-902 24 mg, n = 26; URO-902 48 mg, n = 27; placebo, n = 27), 74 received treatment and 67 reached week 24. At week 12, URO-902 24 and 48 mg were associated with significant improvement vs placebo in daily micturitions (least squares mean change from baseline, -2.3 and -2.4 vs -0.8; least squares mean difference [95% CI], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal P = .017 and P = .009, respectively). URO-902 48 mg was associated with significant improvements vs placebo in urgency episodes (‒3.4 vs ‒1.1; ‒2.2 [‒4.0 to ‒0.4]; nominal P = .016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal P = .026). Among patients receiving URO-902 24 mg, 48 mg, and placebo, 46%, 54%, and 54%, respectively, experienced ≥ 1 treatment-emergent adverse events, most commonly UTI (0%, 15%, 4%) and hematuria (6%, 8%, 8%)., Conclusions: In this phase 2a trial, treatment with URO-902 was associated with improvements vs placebo in efficacy and patient-reported outcomes and was safe and well tolerated.

Introduction: Clinical research can be expensive and time consuming due to high associated costs and/or duration of the study. We hypothesized that urine sample collection using online recruitment and engagement of research participants via social medial has the potential to reach a large population in a small timeframe, at a reasonable cost., Methods: We performed a retrospective cost analysis of a cohort study comparing cost per sample and time per sample for both online and clinically recruited participants for urine sample collection. During this time, cost data were collected based on study associated costs from invoices and budget spreadsheets. The data were subsequently analyzed using descriptive statistics., Results: Each sample collection kit contained 3 urine cups, 1 for the disease sample and 2 for control samples. Out of the 3,576 (1,192 disease + 2,384 control) total sample cups mailed, 1,254 (695 control) samples were returned. Comparatively, the 2 clinical sites collected 305 samples. Although the initial startup cost of online recruitment was higher, cost per sample for online recruited was found to be $81.45 compared to $398.14 for clinic sample., Conclusions: We conducted a nationwide, contactless, urine sample collection through online recruitment in the midst of the COVID-19 pandemic. Results were compared with the samples collected in the clinical setting. Online recruitment can be utilized to collect urine samples rapidly, efficiently, and at a cost per sample that was 20% of an in-person clinic, and without risk of COVID-19 exposure.

Background: Children with hemiparesis are commonly prescribed ankle foot orthoses to help improve gait; however, these orthoses often result in only small and variable changes in gait. Research with adult stroke survivors has suggested that orthoses that extend beyond the ankle using long, passive tendon-like structures (i.e. exotendons) can improve walking., Objectives: The aim of this study was to quantify the impact of an exotendon-based exoskeleton on pediatric gait., Study Design: Repeated-measures study., Methods: Two typically-developing children and two children with hemiparesis completed a gait analysis, walking without and with the exoskeleton. The exotendon was tested at three stiffness levels., Results: All children were able to walk comfortably with the exoskeleton, with minimal changes in step width. Walking speed increased and lower limb joint symmetry improved for the children with hemiparesis with the exoskeleton. Each participant had changes in muscle activity while walking with the exoskeleton, although the impact on specific muscles and response to exotendon stiffness varied., Conclusion: Exotendon-based exoskeletons may provide an alternative solution for optimizing gait in therapy and in the community for children with hemiparesis. Determining the optimal stiffness and configuration for each child is an important area of future research., (Copyright © 2020 International Society for Prosthetics and Orthotics.)

Background: Assessments of human movement are clinically important. However, accurate measurements are often unavailable due to the need for expensive equipment or intensive processing. For orthotists and therapists, shank-to-vertical angle is one critical measure used to assess gait and guide prescriptions. Smartphone-based sensors may provide a widely available platform to expand access to this measurement., Objectives: Assess accuracy and repeatability of smartphone-based measurement of shank-to-vertical angle compared to marker-based 3D motion analysis., Study Design: Repeated-measures., Methods: Four licensed clinicians (two physical therapists and two orthotists) measured shank-to-vertical angle during gait with a smartphone attached to the anterior or lateral shank surface of unimpaired adults. We compared the shank-to-vertical angle calculated from the smartphone's inertial measurement unit to marker-based measurements. Each clinician completed three sessions/day on two days with each participant to assess repeatability., Results: Average absolute differences in shank-to-vertical angle measured with a smartphone versus marker-based 3D motion analysis during gait were 0.67 ± 0.25° and 4.89 ± 0.72°, with anterior or lateral smartphone positions, respectively. The inter- and intra-day repeatability of shank-to-vertical angle were within 2° for both smartphone positions., Conclusions: Smartphone sensors can be used to measure shank-to-vertical angle with high accuracy and repeatability during unimpaired gait, providing a widely available tool for quantitative gait assessments., Clinical Relevance: Smartphone sensors demonstrated high accuracy and repeatability for monitoring shank-to-vertical angle during gait. Measurement of shank-to-vertical angle from the front of the shank was more accurate than the side of the shank. Smartphones may expand access to quantitative assessments of gait.

Purpose: In this 12-week, randomized, double-blind, placebo controlled, multicenter, 3-arm, parallel group, phase 3 trial we assessed the effects of a novel SHIP1 activator on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome., Materials and Methods: Subjects with interstitial cystitis/bladder pain syndrome and a mean pain score of 5 or greater on an 11-point scale despite treatment were randomized to 100 or 200 mg of an oral SHIP1 activator or placebo once daily for 12 weeks. Maximum pain scores and urinary frequency were recorded in an e-diary. The ICSI (O'Leary-Sant Interstitial Cystitis Symptom Index) and BPIC-SS (Bladder Pain Interstitial Cystitis Symptom Score) questionnaires were administered. Safety was monitored through 12 weeks of treatment., Results: A total of 298 female subjects with moderate to severe symptoms of interstitial cystitis/bladder pain syndrome were treated with 100 or 200 mg SHIP1 activator orally once daily for 12 weeks. Treatment demonstrated no difference in maximum daily bladder pain compared to placebo. There was no treatment benefit over that of placebo in the secondary end points of urinary voiding frequency, the BPIC-SS, the ICSI and a global response assessment. Exploratory analysis in 87 male subjects yielded a similar result, that is no difference from placebo. Treatment was generally well tolerated at both doses., Conclusions: SHIP1 activation is a safe but ineffective therapeutic approach to interstitial cystitis/bladder pain syndrome. Although this was a negative trial, the important lessons learned from this study in respect to inflammatory phenotype differentiation, including the potential importance of cystoscopy based classification, will improve current treatment in patients with interstitial cystitis/bladder pain syndrome and allow for better future trial design in those with this difficult urological chronic pain syndrome.

Purpose: We assess the 12-month safety and potential efficacy of autologous muscle derived cells for urinary sphincter repair (Cook MyoSite Incorporated, Pittsburgh, Pennsylvania) in women with stress urinary incontinence., Materials and Methods: Pooled data from 2 phase I/II studies with identical patient selection criteria and outcome measures were analyzed. Enrolled patients had stress urinary incontinence refractory to prior treatment and no symptom improvement during the last 6 months. Patients received intrasphincter injection of 10 (16), 50 (16), 100 (24) or 200×10(6) (24) autologous muscle derived cells for urinary sphincter repair, derived from biopsies of each patient's quadriceps femoris. The primary outcome measure was safety, determined by incidence and severity of adverse events. Potential efficacy was measured by changes in 3-day voiding diaries, 24-hour pad tests, and UDI-6 and IIQ-7 scores., Results: A total of 80 patients underwent injection of autologous muscle derived cells for urinary sphincter repair, and 72 completed diaries and pad tests at 12-month followup. No adverse events attributed to autologous muscle derived cells for urinary sphincter repair were reported. Higher dose groups tended to have greater percentages of patients with at least a 50% reduction in stress leaks and pad weight at 12-month followup. All dose groups had statistically significant improvement in UDI-6 and IIQ-7 scores at 12-month followup compared to baseline., Conclusions: Autologous muscle derived cells for urinary sphincter repair at doses of 10, 50, 100 and 200×10(6) cells appears safe. Efficacy data suggest a potential dose response with a greater percentage of patients responsive to higher doses., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We report the long-term efficacy and safety of percutaneous tibial nerve stimulation with the Urgent® PC Neuromodulation System for overactive bladder after 3 years of therapy., Materials and Methods: Fifty participants in the randomized, double-blind SUmiT (Sham Effectiveness in Treatment of Overactive Bladder Symptoms) Trial who met the primary effectiveness end point after 12 weekly percutaneous tibial nerve stimulation treatments were enrolled in this prospective study to assess long-term outcomes with percutaneous tibial nerve stimulation. STEP (Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation) Study patients were prescribed a fixed schedule 14-week tapering protocol followed by a personal treatment plan aimed at sustaining overactive bladder symptom improvement. Overactive bladder and quality of life questionnaires were completed every 3 months and 3-day voiding diaries were completed every 6 months., Results: A total of 29 patients completed the 36-month protocol and received a median of 1.1 treatments per month after a 14-week treatment tapering protocol. A Bayesian model estimated that 77% (95% CI 64-90) of patients maintained moderate or marked improvement in overactive bladder symptoms at 3 years. Compared to baseline, median voids per day decreased from 12.0 (IQR 10.3-13.7) to 8.7 (IQR 7.3-11.3), nighttime voids per night decreased from 2.7 (IQR 1.7-3.3) to 1.7 (IQR 1.0-2.7) and urge incontinence episodes per day decreased from 3.3 (IQR 0.7-6.0) to 0.3 (IQR 0.0-1.0) (all p <0.0001). All quality of life parameters remained markedly improved from baseline through 3 years (all p <0.0001). One patient experienced 2 mild treatment related adverse events of bleeding at the needle site during followup., Conclusions: Most STEP participants with an initial positive response to 12 weekly percutaneous tibial nerve stimulation treatments safely sustained overactive bladder symptom improvement to 3 years with an average of 1 treatment per month., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes., Materials and Methods: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods., Results: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03)., Conclusions: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Based on basic research findings an increase in chemokines and cytokines (CXCL-1 and 10, nerve growth factor and interleukin-6) is considered responsible for inflammation and afferent sensitization. In this cross-sectional study we tested the hypothesis that select chemokines are increased in the urine of patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome., Materials and Methods: Midstream urinary specimens were collected from 10 patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome, respectively, and from 10 asymptomatic controls. Urinary levels of 7 cytokines were measured by a human cytokine/chemokine assay. Nerve growth factor was measured by enzyme-linked immunosorbent assay., Results: Urinary levels of most chemokines/cytokines were tenfold to 100-fold lower in asymptomatic controls vs patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome. Univariate comparison of 8 tested proteins in the ulcerative vs nonulcerative groups revealed a significant fivefold to twentyfold increase in CXCL-10 and 1, interleukin-6 and nerve growth factor (ANOVA p<0.001)., Conclusions: Differential expression of chemokines in ulcerative and nonulcerative subtypes of interstitial cystitis/painful bladder syndrome suggests differences in paracrine signaling between the 2 entities., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome., Materials and Methods: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated., Results: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported., Conclusions: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome., Materials and Methods: A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries., Results: Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls., Conclusions: In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Restoring bladder and bowel function in spina bifida by creation of a skin-central nervous system-bladder reflex arc via lumbar to sacral nerve rerouting has a reported success rate of 87% in China. We report 1-year results of the first North American trial on nerve rerouting., Materials and Methods: Nine subjects were enrolled in the study. Intradural lumbar to sacral nerve rerouting was performed. Subjects underwent urodynamic testing with stimulation of the cutaneous dermatome and careful neurological followup. Adverse events were closely monitored along with changes in bowel and bladder function., Results: At 1 year 7 patients (78%) had a reproducible increase in bladder pressure with stimulation of the dermatome. Two patients were able to stop catheterization and all safely stopped antimuscarinics. No patient achieved complete urinary continence. The majority of subjects reported improved bowel function. One patient was continent of stool at baseline and 4 were continent at 1 year. Of the patients 89% had variable weakness of lower extremity muscle groups at 1 month. One child had persistent foot drop and the remainder returned to baseline by 12 months., Conclusions: At 1 year a novel reflex arc with stimulation of the appropriate dermatome was seen in the majority of subjects. Improvements in voiding and bowel function were noted. Lower extremity weakness was mostly self-limited, except in 1 subject with a persistent foot drop. More patients and longer followup are needed to assess the risk/benefit ratio of this novel procedure., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports., Materials and Methods: We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment., Results: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01)., Conclusions: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The Study of Urgent PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT) was a multicenter, double-blind, randomized, controlled trial comparing the efficacy of percutaneous tibial nerve stimulation to sham through 12 weeks of therapy. The improvement in global response assessment, voiding diary parameters, and overactive bladder and quality of life questionnaires was evaluated., Materials and Methods: A total of 220 adults with overactive bladder symptoms were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or sham therapy. Overactive bladder and quality of life questionnaires as well as 3-day voiding diaries were completed at baseline and at 13 weeks. Subject global response assessments were completed at week 13., Results: The 13-week subject global response assessment for overall bladder symptoms demonstrated that percutaneous tibial nerve stimulation subjects achieved statistically significant improvement in bladder symptoms with 54.5% reporting moderately or markedly improved responses compared to 20.9% of sham subjects from baseline (p <0.001). All individual global response assessment subset symptom components demonstrated statistically significant improvement from baseline to 13 weeks for percutaneous tibial nerve stimulation compared to sham. Voiding diary parameters after 12 weeks of therapy showed percutaneous tibial nerve stimulation subjects had statistically significant improvements in frequency, nighttime voids, voids with moderate to severe urgency and urinary urge incontinence episodes compared to sham. No serious device related adverse events or malfunctions were reported., Conclusions: This pivotal multicenter, double-blind, randomized, sham controlled trial provides level I evidence that percutaneous tibial nerve stimulation therapy is safe and effective in treating overactive bladder symptoms. The compelling efficacy of percutaneous tibial nerve stimulation demonstrated in this trial is consistent with other recently published reports and supports the use of peripheral neuromodulation therapy for overactive bladder., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The Overactive Bladder Innovative Therapy Trial during phase 1 was a randomized trial demonstrating comparable effectiveness of percutaneous tibial nerve stimulation and extended-release tolterodine during 12 weeks of therapy for frequency, nocturia, urgency, voided volume and urge incontinence episodes. In this second phase of the Overactive Bladder Innovative Therapy Trial we assessed the sustained therapeutic efficacy of percutaneous tibial nerve stimulation in subjects with overactive bladder during 1 year., Materials and Methods: After 12 weeks subjects randomized to weekly percutaneous tibial nerve stimulation with Urgent((R)) PC were offered an additional 9 months of treatment with assessments at 6 and 12 months from baseline. Outcome measures included voiding diary data, overactive bladder questionnaires, global response assessments and safety assessments., Results: A total of 33 percutaneous tibial nerve stimulation responders continued therapy with 32 and 25 subjects completing 6 and 12 months of therapy, respectively. Subjects received a mean of 12.1 treatments during an average of 263 days, with a mean of 21 days (median 17) between treatments. Subject global response assessments showed sustained improvement from 12 weeks at 6 and 12 months, with 94% and 96% of responders, respectively. At 12 months mean improvements from baseline included a frequency of 2.8 voids daily (p <0.001), urge incontinence of 1.6 episodes daily (p <0.001), nocturia with 0.8 voids (p <0.05) and a voided volume of 39 cc (p <0.05). Overactive bladder questionnaire symptom severity was significantly improved from 12 weeks to 12 months (p <0.01) as well as from 6 to 12 months (p <0.01). No serious adverse events occurred., Conclusions: Statistically significant overactive bladder symptom improvement achieved with 12 weekly percutaneous tibial nerve stimulation treatments demonstrates excellent durability through 12 months. The durability of response demonstrates the effectiveness of percutaneous tibial nerve stimulation as a viable, long-term therapy for overactive bladder.

Purpose: The Overactive Bladder Innovative Therapy trial was a randomized, multicenter, controlled study that compared the effectiveness of percutaneous tibial nerve stimulation to extended-release tolterodine. The reduction in overactive bladder symptoms along with global response assessments was evaluated., Materials and Methods: A total of 100 adults with urinary frequency were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or to 4 mg daily extended-release tolterodine. Voiding diaries and an overactive bladder questionnaire were completed at baseline and at the end of therapy to compare 24-hour voiding frequency, urinary urge incontinence episodes, voids causing waking, volume voided, urgency episodes and quality of life indices. Global response assessments were completed by subjects and investigators after 12 weeks of therapy., Results: The global response assessment demonstrated that subject assessment of overactive bladder symptoms compared to baseline was statistically significant in the percutaneous tibial nerve stimulation arm with 79.5% reporting cure or improvement compared to 54.8% of subjects on tolterodine (p = 0.01). Assessments by investigators were similar but did not reach statistical significance (p = 0.05). After 12 weeks of therapy objective measures improved similarly in both groups for reductions in urinary frequency, urge urinary incontinence episodes, urge severity and nighttime voids, as well as for improvement in voided volume. There were no serious adverse events or device malfunctions., Conclusions: This multicenter, randomized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms, and with objective effectiveness comparable to that of pharmacotherapy. Percutaneous tibial nerve stimulation may be considered a clinically significant alternative therapy for overactive bladder.

Purpose: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes., Materials and Methods: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods., Results: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03)., Conclusions: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Purpose: We tested for associations between urine markers, bladder biopsy features and bladder ulcers in interstitial cystitis/painful bladder syndrome., Materials and Methods: Subjects were 72 patients with interstitial cystitis/painful bladder syndrome undergoing bladder distention and biopsy. Urine was collected before the procedure. Urine marker levels were correlated with biopsy and cystoscopic findings. Patients with no previous interstitial cystitis/painful bladder syndrome treatments (47) were analyzed separately from previously treated patients (25)., Results: For untreated patients urine interleukin-6 and cyclic guanosine monophosphate were associated with urothelial epidermal growth factor receptor staining (for interleukin-6 r = 0.29; 95% CI 0.07, 0.51; p = 0.01 and for cyclic guanosine monophosphate r = 0.34; 95% CI 0.13, 0.55; p = 0.002). Urine interleukin-8 was negatively associated with urothelial heparin-binding epidermal growth factor-like growth factor staining (r = -0.34; 95% CI -0.55, -0.12; p = 0.002) and positively associated with lamina propria mast cell count (r = 0.29; 95% CI 0.06, 0.52; p = 0.01). The latter association also was seen in treated patients (r = 0.46; 95% CI 0.20, 0.73; p <0.001). None of the urine markers was significantly different for ulcer vs nonulcer groups. All of the patients with ulcer had extensive inflammation on bladder biopsy including severe mononuclear cell infiltration, moderate or strong interleukin-6 staining in the urothelium and lamina propria, and leukocyte common antigen staining in more than 10% of the lamina propria. However, these features also were seen in 24% to 76% of the patients without ulcer., Conclusions: Overall urine markers did not associate robustly with biopsy findings. The strongest association was a positive association between urine interleukin-8 levels and bladder mast cell count. Patients with ulcer consistently had bladder inflammation but the cystoscopic finding of ulcers was not a sensitive indicator of inflammation on bladder biopsy.

Purpose: We evaluated the longer term response in patients with interstitial cystitis who initially responded to intravesical bacillus Calmette-Guerin or placebo in a randomized clinical trial., Materials and Methods: Patients with interstitial cystitis who responded positively to treatment with bacillus Calmette-Guerin or placebo after 34 weeks of followup in a double-blind clinical trial were followed for an additional 34 weeks in an observational study to assess response durability. Outcomes at 68 weeks included a patient reported global response assessment, 24-hour voiding diary, and pain, urgency and validated interstitial cystitis symptom indexes., Results: Of responders to bacillus Calmette-Guerin or placebo in the clinical trial 38 continued extended followup in the observational study. A total of 12 (75%) responders who received placebo and 19 (86%) who received bacillus Calmette-Guerin considered themselves to remain moderately or markedly improved at week 68. Improved symptom outcomes were also generally maintained during followup in the 2 groups., Conclusions: Most patients who respond to therapy with intravesical bacillus Calmette-Guerin or placebo maintain improved symptoms for up to 68 weeks after the initiation of therapy. However, initial response rates are low and placebo responders demonstrated essentially the same durability of response as bacillus Calmette-Guerin responders. These results argue against the routine use of bacillus Calmette-Guerin in this patient group.

Purpose: We evaluated safety and efficacy outcomes in a case series of subjects who received open label intravesical bacillus Calmette-Guerin after failing to respond to bacillus Calmette-Guerin or intravesical placebo in a randomized clinical trial., Materials and Methods: Subjects who met National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency were initially randomized to 6 weekly intravesical instillations of bacillus Calmette-Guerin or placebo and followed for a total of 34 weeks. At 34 weeks subjects who reported that they had not responded to treatment were offered treatment with open label bacillus Calmette-Guerin, using the same course of treatment and followup. Outcomes included a patient reported global response assessment, a 24-hour voiding diary, pain, urgency, validated interstitial cystitis symptom indexes and adverse events., Results: A total of 156 subjects elected open label bacillus Calmette-Guerin, of whom 18 (12%) withdrew during the open label series. The response rate based on the global response assessment was 18% and it was identical between those initially randomized to placebo (first course of bacillus Calmette-Guerin in the open label series) and those initially randomized to bacillus Calmette-Guerin (second course). Small improvements were observed for most secondary efficacy outcomes. Most participants reported at least 1 adverse event, primarily pain, genitourinary symptoms and gastrointestinal disturbances. However, there was no difference in adverse events between those who received the first course of bacillus Calmette-Guerin in this series compared to those who received 2 courses., Conclusions: The low response rate for bacillus Calmette-Guerin in this open label case series further argues against the routine use of bacillus Calmette-Guerin as treatment for interstitial cystitis.

Purpose: We determined whether abuse is associated with interstitial cystitis by surveying patients with interstitial cystitis and controls. We corroborated this association in a clinic population., Materials and Methods: A survey was mailed to 406 women diagnosed with interstitial cystitis and 5,000 age matched, randomly selected women in the United States. Similar data were collected from our interstitial cystitis clinic population by interviews in person., Results: We evaluated surveys from 464 symptom-free controls, 215 established patients with IC and 121 respondents with a history suggestive of interstitial cystitis. A higher proportion of patients with interstitial cystitis reported a history of abuse than controls (37% vs 22%, p <0.001). Sexual, physical and emotional abuse were also reported by a higher proportion of patients with interstitial cystitis. In our clinic population 76 women diagnosed with interstitial cystitis were evaluated, of whom 49% reported a history of abuse. Of those reporting abuse 92% reported emotional abuse, 78% reported physical abuse, 68% reported sexual abuse and 49% reported domestic violence., Conclusions: Our study demonstrates an association between interstitial cystitis and abuse. Thus, it is important for clinicians to assess for abuse in women with interstitial cystitis or pelvic pain and provide appropriate referral to psychologists or other health care workers to provide comprehensive care for managing their symptoms. Further research is needed to evaluate the role of biopsychosocial therapies, in addition to traditional interstitial cystitis medical therapies for women with a history of abuse and interstitial cystitis.

Purpose: Interstitial cystitis significantly negatively impacts quality of life. The demographic and clinical factors associated with decreased quality of life in these patients have not been well studied., Materials and Methods: Women with moderate/severe interstitial cystitis enrolled in a clinical trial of intravesical bacillus Calmette-Guerin were studied. Demographic data and responses to questionnaires were evaluated at baseline, including the O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index, University of Wisconsin Interstitial Cystitis Inventory, Medical Outcomes Study sexual functioning scale, and the physical composite and mental composite scales of the Medical Outcomes Study Short Form Health Status Survey. Three composite indexes were constructed (from the O'Leary-Sant Interstitial Cystitis Symptom Index, O'Leary-Sant Interstitial Cystitis Problem Index, pain/urgency Likert scales and 24-hour voiding diary) to document the severity, frequency and bother of pain, urinary urgency and frequency (frequency composite index). Linear and multivariate regression models were used to examine predictors of the physical composite and mental composite scales of the Medical Outcomes Study Short Form Health Status Survey. Medical Outcomes Study sexual functioning scale data were available for 163 of the 217 women in the trial., Results: Physical composite scale (median 36) and mental composite scale (median 42) were lower than the standard population value of 50. Multivariate models showed that employment, pain composite index and Medical Outcomes Study sexual functioning scale (all p<0.001) predicted physical composite scale, while only Medical Outcomes Study sexual functioning scale (p<0.001) remained a strong predictor of mental composite scale., Conclusions: Sexual functioning, employment and pain issues predict mental and physical quality of life. In particular, this study identifies sexual functioning as a primary predictor of mental quality of life in women with long-standing interstitial cystitis. It is suggested that sexual functioning may be a salient therapeutic target in the multifaceted treatment of patients with interstitial cystitis.

Purpose: We evaluated changes in urine markers and symptom scores after bladder distention in patients with interstitial cystitis., Materials and Methods: Study subjects were 33 new patients who had undergone no prior interstitial cystitis treatment. Urine specimens were taken before and 1 month after bladder distention. University of Wisconsin symptom scores were done the same day as the urine specimen collection. Urine marker levels and symptom scores before and after distention were compared. Changes in markers were tested for associations with changes in symptom scores and other markers. Markers and specific symptoms before distention were tested for their association with post-distention symptom improvement., Results: After distention the median total University of Wisconsin score decreased significantly (28.5 before, 20 after, p <0.001). A total of 12 patients (36%) had at least 30% improvement in University of Wisconsin score, and 8 patients (24%) had at least 50% improvement. No pre-distention markers or symptoms predicted which patients would have a good response. There were 2 urine markers that improved significantly after distention: anti-proliferative factor activity (median -96% before, -17% after, p <0.001) and heparin-binding epidermal growth factor-like growth factor levels (median 0.34 ng/mg creatinine before, 4.1 after, p <0.001). None of the changes in urine markers associated with changes in symptom scores., Conclusions: The median symptom score for newly diagnosed patients with interstitial cystitis decreased after distention, but only a minority of patients had at least 30% symptom improvement. Bladder distention altered urine anti-proliferative factor activity and heparin-binding epidermal growth factor-like growth factor levels toward normal, but the mechanism of symptom relief after distention is still unknown.

Purpose: We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC)., Materials and Methods: Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively., Results: A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates., Conclusions: Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive.

Purpose: We compared urine markers, bladder biopsy findings and clinical features of patients with symptoms of interstitial cystitis (IC) who did or did not meet the cystoscopic criteria defined by the National Institute of Diabetes and Digestive and Kidney Diseases., Materials and Methods: Urine markers and symptom questionnaires were measured before and 1 month after bladder distention for IC. Bladder biopsies were taken at the time of distention. At distention patients were defined as meeting or not meeting the National Institute of Diabetes and Digestive and Kidney Diseases established cystoscopic criteria for IC. The 2 patient groups were compared., Results: Urine marker levels were similar for the 2 groups, including antiproliferative factor, epidermal growth factor, heparin binding epidermal growth factor-like growth factor, cyclic guanosine monophosphate, interleukins 6 and 8, and methylhistamine. Bladder biopsy features were similar for the 2 groups. Bladder capacity with the patients under anesthesia was higher in those who did not meet the criteria (median 750 vs 1,000 ml, p = 0.005). Median age at symptom onset was 26 years in both groups. On the University of Wisconsin symptom scale patients who met the criteria had higher scores for daytime frequency (p = 0.002) and nocturia (p = 0.01). Symptom characteristics and symptom response after bladder distention were similar for the 2 groups., Conclusions: Patients who met the cystoscopic criteria had worse daytime frequency and nocturia, and lower bladder capacity under anesthesia. However, the 2 groups had similar urine markers and bladder biopsy findings. The cystoscopic criteria do not appear to identify a distinct pathophysiological subset of patients with IC symptoms.

Purpose: We determined whether urine methylhistamine (MH) is associated with other clinical features and bladder biopsy findings in interstitial cystitis (IC)., Materials and Methods: Urine MH and University of Wisconsin symptom scores were measured before and 1 month after bladder distention for IC. Bladder biopsies were done at the time of distention. In new patients with IC who met cystoscopic criteria urine MH was compared before and after distention, and changes in urine MH were compared with changes in symptom scores. Pre-distention urine MH was tested for associations with the results of a symptom questionnaire, symptom response after distention, cystoscopic findings and bladder biopsy findings., Results: There were no significant associations between urine MH and symptom scores, response to bladder distention, cystoscopic findings or bladder biopsy features, including mast cell count by tryptase staining. Urine MH was similar in new patients with IC who did vs did not meet cystoscopic criteria. Urine MH was similar in new vs chronically treated patients with IC., Conclusions: Urine MH is unlikely to be useful as an objective marker of the response to bladder distention, as a method to predict which patients will respond to bladder distention or as a noninvasive substitute for bladder biopsy and mast cell counts by tryptase staining.

Purpose: There has been a recent trend to diagnose interstitial cystitis (IC) in a noninvasive way using a potassium sensitivity test, and a pelvic pain, urgency and frequency questionnaire. The concern is that significant pathology causing the bladder symptoms may be missed, such as transitional cell carcinoma. We present our experience with patients "labeled" as having IC who truly had cancer as the cause of irritative symptoms., Materials and Methods: A retrospective review of patient records at our IC center was performed from 1998 to 2002. A total of 600 patients were seen at that time with the diagnosis of interstitial cystitis., Results: Six patients (1%) previously diagnosed as having IC were found to have transitional cell carcinoma as the cause of symptoms, 4 of whom (67%) had no hematuria. Mean time from the diagnosis of IC to diagnosis of transitional cell carcinoma was 29.8 months. Irritative bladder symptoms resolved after identifying and treating the malignancy., Conclusions: Patients with irritative voiding symptoms require a thorough evaluation which may include cystoscopy, cytology and upper tract imaging. Hematuria was not a good predictor of cancer in our series. In the era before widespread use of minimally invasive means to diagnose IC (ie potassium sensitivity test, pelvic pain, urgency and frequency questionnaire) 1% of patients who were considered to have IC actually had transitional cell cancer as the cause of symptoms. One would expect that this number would increase if the criteria to diagnose IC and initiate treatment were oversimplified. Interstitial cystitis remains a diagnosis of exclusion.

Purpose: Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, double-blind, placebo controlled study of the use of intravesical bacillus Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months. Results demonstrated a 60% BCG response rate, compared to a 27% placebo response rate. We now report the long-term followup results of those patients who received intravesical BCG., Materials and Methods: Subjects randomized to receive BCG were followed at routine intervals with questionnaires and voiding diaries identical to those in the blinded study. Adverse events were closely monitored in the treatment and followup phases of the study. Subject baseline values were compared to followup data., Results: Of the BCG responders mean followup was 27 months (range 24 to 33), and 8 of 9 (89%) continue to have an excellent response in all parameters measured. The global interstitial cystitis survey improved 70%, daily voids decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia resolved. Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup, suggesting that BCG does not worsen interstitial cystitis symptoms. No long-term adverse events from BCG were noted., Conclusions: Intravesical Tice BCG is safe, effective and durable in the treatment of interstitial cystitis. Of those patients who received only 6 weekly treatments and responded favorably 89% continue to have an excellent response with followup ranging from 24 to 33 months.

Purpose: A psychometric analysis of the University of Wisconsin Interstitial Cystitis Scale was conducted on 30 females previously enrolled in a phase II double-blind randomized controlled trial evaluating the efficacy of six weekly intravesical instillations of TICE BCG. The analyses were to: (1) evaluate the adequacy of the seven individual IC component items for measuring the range of patient responses; (2) verify the 2-factor (IC versus reference) construct of the scale; (3) evaluate the internal consistency and reliability of the IC items; (4) better define the scale's applicability and limitations; and (5) if possible, make recommendations for improvements in the scale., Materials and Methods: Standard psychometric analyses were used to perform the evaluation, and included descriptive analysis of individual items, computing of item-total correlations and Cronbach's internal consistency measures, and the application of factor and Rasch analyses., Results: The original 7-item IC scale was found to have ceiling effects that could limit its use in detecting small therapeutic differences. It was also found that the Pelvic item originally assigned to the reference set of items of the scale should be included as an IC item when used in a comparable IC population. After including this item into the IC scale Cronbach's alpha was 0.84, compared with 0.82., Conclusions: The UW-IC Scale has psychometric properties similar to other measurement instruments used in clinical research, and appears worthy of further study in well-characterized IC populations. The reference items suggest that IC patients do not indiscriminately report high values for generalized body complaints, but do so on bladder related symptoms as recorded by the IC items of the scale. Although the scale has limitations it appears applicable for use in future IC intervention clinical trials.

Purpose: Traditional teaching in urology has been to avoid electrosurgical devices in penile surgical procedures. In the last several years cutting current has been routinely used on the penis for making skin incisions, degloving, creating Byars flaps and destroying skin bridges. The purpose of this study was to determine the complications and final outcomes of electro-surgery., Materials and Methods: A 5-year retrospective chart review was done to determine the complications and final outcomes of exclusively using electrical current to perform pediatric penile procedures., Results: Electrosurgery was used to perform the entire surgical dissection in 346 patients, including circumcision in 124, repeat circumcision in 68, penoscrotal fusion/chordee repair in 127 and skin bridge procedures in 27. All patients had a satisfactory cosmetic result. After correction of penoscrotal fusion, separation at the scrotal suture line in 2 patients healed secondarily without sequelae. There was no hematoma, tissue necrosis or skin sloughing and all surgery was performed on an outpatient basis., Conclusions: Electrosurgery can be used safely and effectively for routine penile procedures, providing a bloodless operative field and excellent cosmetic results.