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Purpose: Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation modality developed to promote functional restoration in patients with neurological injury or disease. Previous pilot data suggest that lower urinary tract dysfunction (LUTD) due to stroke may be partially alleviated by TSCS. In this study, we examine the mechanism of this effect by evaluating bladder-related brain activity in patients before and after TSCS therapy and comparing it to healthy volunteers., Materials and Methods: Patients who developed storage LUTD after a stroke and healthy volunteers without LUTD were recruited. Patients and healthy volunteers underwent simultaneous urodynamics and functional MRI. Patients then completed 24 biweekly sessions of TSCS and underwent another simultaneous urodynamics-functional MRI study. Clinical outcomes were assessed using validated questionnaires and voiding diary., Results: Fifteen patients and 16 healthy volunteers completed the study. Following TSCS, patients exhibited increased blood-oxygen-level-dependent activity in areas including periaqueductal grey, the insula, the lateral prefrontal cortex, and motor cortex. Prior to TSCS therapy, healthy controls exhibited higher blood-oxygen-level-dependent activity in 17 regions, including multiple regions in the prefrontal cortex and basal ganglia. These differences were attenuated after TSCS with no frontal brain differences remaining between healthy volunteers and stroke participants who completed therapy. Neuroimaging changes were complemented by clinically significant improvements in questionnaire scores and voiding diary parameters., Conclusions: TSCS therapy modulated bladder-related brain activity, reducing differences between healthy volunteers and stroke patients with LUTD. These changes, alongside improved clinical outcomes, suggest TSCS as a promising approach for LUTD management.

Purpose: An ill-defined proportion of patients undergoing urethroplasty fail to experience improvement in lower urinary tract symptoms (LUTS) despite being stricture-free. We aim to identify the incidence, associations and causes of "LUTS failure" after urethroplasty., Materials and Methods: Patients undergoing urethroplasty over a 6-year period were offered enrollment in a prospective study examining urinary function after urethroplasty. Patients were assessed preoperatively and 6 months postoperatively using the International Prostate Symptom Score (IPSS) and cystoscopy. "LUTS failure" was defined as ≤3-point improvement in IPSS despite an anatomically successful urethroplasty. Multivariable logistic regression was utilized to evaluate the association between patient factors and "LUTS failure.", Results: Of 365 patients meeting inclusion criteria, mean postoperative IPSS (20.3 vs. 5.4, p <0.0001) and median urinary quality of life (UQOL; 5 vs. 1; p <0.0001) were significantly improved. Despite being stricture-free, 7.7% of patients reported "LUTS failure" and 10.1% reported UQOL nonresponse. On multivariable logistic regression, increasing age (OR 1.04, 95% CI 1.01-1.06; p=0.006) and hypospadias (OR 18.2, 95% CI 2.1-156.0; p=0.008) were associated with "LUTS failure," while stricture location (p=0.76), length (p=0.14), previous urethroplasty (p=0.96), failed endoscopic treatment (p=0.17), type of urethroplasty (p=0.93) and other etiologies were not. Qualitatively, the most likely causes of "LUTS failure" were detrusor underactivity (39.3%), overactivity (21.4%), pelvic floor dysfunction (21.4%) or benign prostatic hyperplasia (14.3%). Only increasing age was associated with UQOL nonresponse (OR 1.03, 95% CI 1.01-1.07; p=0.02)., Conclusions: While many patients experience improved voiding function after urethroplasty, 7.7% experience "LUTS failure" and 10.1% report UQOL nonresponse. Both occurrences are independently associated with increasing patient age and most commonly related to detrusor underactivity.

Purpose: We evaluated the success of minimally invasive management of lichen sclerosus with topical and intraurethral clobetasol, as defined by improvement in patient reported outcome measures and nonprogression to surgery., Materials and Methods: We conducted a review of our prospective ongoing quality improvement study to determine outcomes of our current standard practice for males with penile and urethral biopsy proven lichen sclerosus. Data were collected between 2011 and 2019, and included patient demographic information, medical and surgical histories, and location and extent of lichen sclerosus related pathology. The primary outcomes for this study were voiding function and voiding related quality of life, and were assessed using the AUASS (American Urological Association Symptom Score) and quality of life bother index, respectively., Results: We identified 42 patients with biopsy proven lichen sclerosus related urethral stricture disease. Of these patients 85.7% were treated with intraurethral steroids alone and did not require surgical intervention. Median AUASS significantly improved from 12 to 8, and median quality of life bother index improved from 4 ("mostly dissatisfied") to 2 ("mostly satisfied"). Average stricture length of those with penile urethral disease and bulbar urethral disease was 4.8 cm (SD 3.0) and 16.2 cm (SD 6.5), respectively. Median followup was 8.4 months (IQR 2.6-26.4)., Conclusions: Lichen sclerosus related urethral stricture disease can be effectively managed with intraurethral steroids. This minimally invasive management strategy improves patient reported voiding symptoms and voiding quality of life.

Purpose: Bladder-bowel questionnaires are an important tool in diagnosing nonneurogenic bladder-bowel dysfunction in children. We report the validity and reliability of a bladder-bowel questionnaire that has been in clinical use at our institution for decades., Materials and Methods: The bladder-bowel questionnaire contains 13 questions, with answers ranging from never (score of 0) to daily (3). The questionnaire was answered by 139 healthy controls and 134 children 3 to 16 years old diagnosed with bladder-bowel dysfunction by a pediatric urologist/urotherapist. A subdiagnosis of overactive bladder or dysfunctional voiding was made in each patient. Bladder-bowel questionnaire scales were developed and evaluated against hypotheses of validity (known groups/convergent/discriminating) and reliability (internal consistency/retest reliability), sensitivity and specificity. Responsiveness was tested in 80 patients who answered the bladder-bowel questionnaire after treatment., Results: A total bladder-bowel dysfunction score scale demonstrated the ability to discriminate between patients with bladder-bowel dysfunction and healthy subjects. It resulted in a ROC curve with AUC of 0.96. The maximized sensitivity was 94% and specificity was 89% for a cutoff score of 7. Two subscales were identified referring to 6 filling phase items and 3 voiding phase items. When tested in patients with overactive bladder and dysfunctional voiding, respectively, multivariable scales performed sufficiently to discriminate between those with and without overactive bladder, and those with and without dysfunctional voiding. All of these scales fulfilled the evaluated requirements for validity and reliability. At 1 year after treatment all scale scores corresponded to patient improvement (p <0.0001), suggesting the bladder-bowel questionnaire can detect clinical change over time., Conclusions: The bladder-bowel questionnaire is valid and reliable for diagnosing bladder-bowel dysfunction in pediatric patients, and overactive bladder and dysfunctional voiding in those with bladder-bowel dysfunction.

Purpose: Most international practice guidelines recommend screening for chronic kidney disease among older men with lower urinary tract symptoms. However, prior studies supporting these guidelines are insufficient due to incomplete assessments of kidney function and inadequate adjustment for confounding factors., Materials and Methods: We conducted a cross-sectional study among 5,530 American men older than 65 years in the multicenter Osteoporotic Fractures in Men Study. Chronic kidney disease was defined per international guidelines as estimated glomerular filtration rate less than 60 ml/minute/1.73 m 2 based on serum creatinine or cystatin C, or urinary albumin-to-creatinine ratio 30 mg/gm or greater. Lower urinary tract symptoms were assessed with the American Urological Association Symptom Index. Associations were estimated using multivariable linear and modified Poisson regression models., Results: Chronic kidney disease prevalence was 16% among 5,530 men with serum creatinine, 24% among 1,504 men with serum cystatin C and 14% among 1,487 men with urinary albumin-to-creatinine measurements. Lower urinary tract symptoms were not associated with lower estimated glomerular filtration rate based on serum creatinine or cystatin C. Although symptom severity was modestly associated with a higher prevalence of chronic kidney disease in age/site adjusted analyses, confidence intervals were wide and associations using all 3 definitions were not statistically significant after adjustment for important confounders, including cardiovascular disease and analgesic use., Conclusions: Lower urinary tract symptoms are not independently associated with multiple measures of kidney dysfunction or prevalence of chronic kidney disease among older community dwelling men. Our results do not support recommendations for kidney function testing among older men with lower urinary tract symptoms.

Purpose: The relationship between fluid intake and lower urinary tract symptoms in individuals with neurogenic bladder is unknown. We investigated the association between fluid intake and urinary symptoms in patients with multiple sclerosis., Materials and Methods: A prospective cross-sectional study of patients with multiple sclerosis presenting to the neurology office was conducted. Fluid intake and lower urinary tract symptoms were assessed by the questionnaire based voiding diary and the American Urological Association Symptom Score, respectively. The relationship between fluid intake and lower urinary tract symptoms was assessed using univariate and multivariate analyses., Results: Among 200 individuals with multiple sclerosis the mean total daily fluid intake was 2,489 ml (SD 1,883) and did not differ according to severity (ie mild, moderate, severe) of lower urinary tract symptoms (F=0.30, p=0.74). Fluid restricting behavior to control urinary symptoms was reported by 47% of subjects. Subjects who reported fluid restricting were more likely to have worse urinary symptoms (OR 1.95, 95% CI 1.53-2.47, p <0.01). After accounting for fluid restricting behavior on multivariate analysis, there was a minimal relationship between caffeinated fluid intake and lower urinary tract symptom severity (OR 1.00, 95% CI 1.00-1.01, p=0.01), and there was no relationship between total fluid intake and lower urinary tract symptom severity (OR 1.00, 95% CI 1.00-1.00, p=0.07)., Conclusions: Caffeinated fluid intake has a minimal effect on lower urinary tract symptoms in patients with multiple sclerosis. On average, patients with multiple sclerosis do not hydrate excessively and a considerable proportion restrict fluid intake to control urinary symptoms. Fluid intake may not contribute considerably to lower urinary tract symptoms in patients with multiple sclerosis.

Purpose: The UroCuff® Test is a noninvasive pressure flow study used to manage men with lower urinary tract symptoms. UroCuff Tests were performed on men with lower urinary tract symptoms to evaluate voiding characteristics and quantify changes in urodynamic parameters with age., Materials and Methods: This cross-sectional study included all UroCuff Tests performed at 103 urology practices in the U.S. Tests were de-identified prior to collection and analysis. Inclusion criteria required initial pressure flow study with subsequent tests excluded, voided volume 50 ml or greater, at least 1 cuff inflation and patient age greater than 20 years. Pressure, maximum flow rate, flow rate efficiency (maximum flow rate/Pcuff), voided volume and post-void residual were plotted by age and stratified by Newcastle Noninvasive Nomogram category., Results: A total of 50,680 patients 20 to 100 years old (median age 66.0) met inclusion criteria. Median Pcuff was 144.3 cmH 2 O and 60.8% of patients were categorized in the obstructed or high pressure/high flow Newcastle Noninvasive Nomogram quadrants. Median maximum flow rate was 10.9 ml per second and 55.8% had maximum flow rate greater than 10 ml per second. Median voided volume and post-void residual were 219.0 and 75.0 ml, respectively. All measures deteriorated with age (p <0.0001). Pcuff reflects the compensated/decompensated bladder function lifecycle. Values initially increased and reached peak pressure at age 62, then decreased by approximately 0.96 cmH 2 O per year until age 90., Conclusions: This study demonstrates that symptomatic patients enter urological practices at different urodynamic stages of bladder function and outlet obstruction, that Pcuff, maximum flow rate, voided volume, flow rate efficiency and post-void residual deteriorate with age, and that UroCuff is a sensitive evaluation of bladder performance.

Purpose: Sacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence., Materials and Methods: Prospective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves., Results: Two-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p <0.01), persisting through 5 years ($36,550 [95% CI 34,787-38,309] vs $12,020 [95% CI 10,330-13,700], p <0.01). At 2 years there were no differences in mean reduction in urgency urinary incontinence episodes per day (-3.00 [95% CI -3.38 - -2.62] vs -3.12 [95% CI -3.48 - -2.76], p=0.66) or QALYs (1.39 [95% CI 1.34-1.44] vs 1.41 [95% CI 1.36-1.45], p=0.60). The probability that sacral neuromodulation is cost-effective relative to onabotulinumtoxinA is less than 0.025 for all willingness to pay values below $580,000 per QALY at 2 years and $204,000 per QALY at 5 years., Conclusions: Although both treatments were effective, the high cost of sacral neuromodulation is not good value for treating urgency urinary incontinence compared to 200 units onabotulinumtoxinA.

Purpose: Although the association between nocturia and depressive symptoms has been demonstrated, the causal direction remains unclear. We investigated the directional association between nocturia and depressive symptoms using longitudinal data from the general population., Materials and Methods: This longitudinal analysis was conducted as part of the Nagahama Cohort Project, a population based cohort study, with baseline and 5-year followup investigations. Nocturnal voiding frequency and mental health were measured with self-report questionnaires, the International Prostate Symptom Score and the 5-item Mental Health Inventory. Logistic regression analyses and a cross-lagged panel analysis were performed to analyze the bidirectional association between nocturia and depressive symptoms., Results: With 9,764 participants at baseline, data from 8,285 were used in this analysis. Median age at baseline was 57.3 years and the proportion of men was 32.0%. New onset depressive symptoms and nocturia were observed among 369 and 793 participants, respectively. In adjusted logistic regression analyses we observed a clear dose-relationship between baseline nocturnal voiding frequency and new onset depressive symptoms (p for trend <0.001) and a weak association between baseline 5-item Mental Health Inventory and new onset nocturia (p for trend=0.0087). In a cross-lagged panel analysis the path coefficient from nocturnal voiding frequency to 5-item Mental Health Inventory (β=-0.06, p <0.001) was stronger than that from 5-item Mental Health Inventory to nocturnal voiding frequency (β=-0.02, p=0.047)., Conclusions: This longitudinal study demonstrated a bidirectional association between nocturia and depressive symptoms. The cross-lagged path coefficient suggested that nocturia could more likely be a cause than a result of depressive symptoms.

Purpose: Conventional classification of patients with lower urinary tract symptoms into diagnostic categories based on a predefined symptom complex or predominant symptom appears inadequate. This is due to the frequent presentation of patients with multiple urinary symptoms which could not be perfectly categorized into traditional diagnostic groups. We used a novel clustering method to identify subtypes of male patients with lower urinary tract symptoms based on detailed multisymptom information., Materials and Methods: We analyzed baseline data on 503 care seeking men in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms and symptom severity were assessed using the LUTS (Lower Urinary Tract Symptoms) Tool and the AUA SI (American Urological Association Symptom Index), which include a total of 52 questions. We used a resampling based consensus clustering algorithm to identify patient subtypes with distinct symptom signatures., Results: Four distinct symptom clusters were identified. The 166 patients in cluster M1 had predominant symptoms of frequency, nocturia, hesitancy, straining, weak stream, intermittency and incomplete bladder emptying suggestive of bladder outlet obstruction. The 93 patients in cluster M2 mainly endorsed post-micturition symptoms (eg post-void dribbling and post-void leakage) with some weak stream. The 114 patients in cluster M3 reported mostly urinary frequency without incontinence. The 130 patients in cluster M4 reported severe frequency, urgency and urgency incontinence. Most other urinary symptoms statistically differed between cluster pairs. Patient reported outcomes of bowel symptoms, mental health, sleep dysfunction, erectile function and urological pain significantly differed across the clusters., Conclusions: We identified 4 data derived clusters among men seeking care for lower urinary tract symptoms. The clusters differed from traditional diagnostic categories. Further subtype refinement will be done to incorporate clinical data and nonurinary patient reported outcomes.

Purpose: While lower urinary tract symptoms and bladder behaviors are known to be associated with certain occupations, little is known about restroom access or environmental factors which may contribute to this relationship. We aimed to characterize reasons that women limit restroom use at work. We also sought to determine whether women who limit use at work report more unhealthy bladder habits and lower urinary tract symptoms., Materials and Methods: We performed a cross-sectional study of full-time working women in the United States. Women completed validated questionnaires recording toileting behaviors, lower urinary tract symptoms and perceptions of the occupational toilet environment. We compared women who limited restroom use at work most or all of the time to those who did not limit or did so occasionally or sometimes., Results: Of the 3,062 women in the final analytical sample 11% reported limiting restroom use at work most or all of the time. This group reported lower satisfaction with restroom cleanliness and privacy in particular. They more frequently identified toilet factors of poor quality, limited accessibility and restricted use by employer. The prevalence of unhealthy bladder habits was significantly higher among women who limited restroom use, as was the prevalence of urgency, monthly urinary incontinence and infrequent voiding., Conclusions: In this cross-sectional study of women working full time those who limited restroom use at work reported a higher prevalence of unhealthy bladder habits and certain urinary disorders. Future studies should determine whether limited restroom use at work is a modifiable risk factor for unhealthy bladder habits and bladder health outcomes.

Purpose: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with lower urinary tract symptoms., Materials and Methods: PubMed®, EMBASE® and Web of Science® were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways., Results: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 time point and were cross-sectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for lower urinary tract symptoms. Compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder syndrome and cell migration/cytoskeleton remodeling pathways that were enriched in female stress incontinence., Conclusions: Major deficiencies in the existing biomarker literature include poor reproducibility of laboratory data, unclear classification of patients with lower urinary tract symptoms and lack of adjustment for clinical covariates. Despite these limitations we identified multiple putative pathways in which panels of biological markers need further research.

Purpose: We evaluated the effects of device guided, slow-paced respiration on urgency associated urinary symptoms, perceived stress and anxiety, and autonomic function in women with overactive bladder syndrome., Materials and Methods: We performed a randomized, parallel group trial of slow-paced respiration to improve perceived stress and autonomic dysfunction as potential contributors to overactive bladder. Ambulatory women who reported at least 3 voiding or incontinence episodes per day associated with moderate to severe urgency were randomized to use a portable biofeedback device to practice daily, slow, guided breathing exercises or a control device which appeared identical and was reprogrammed to play music without guiding breathing. During 12 weeks we evaluated changes in urinary symptoms by voiding diaries, perceived stress and anxiety by validated questionnaires, and autonomic function by heart rate variability and impedance cardiography., Results: In the 161 randomized participants, including 79 randomized to paced respiration and 82 randomized to the control group, the average ± SD baseline frequency of voiding or incontinence associated with moderate to severe urgency was 6.9 ± 3.4 episodes per day. Compared to controls the participants randomized to paced respiration demonstrated greater improvement in perceived stress (average Perceived Stress Scale score decrease 2.8 vs 1.1, p=0.03) but not in autonomic function markers. During 12 weeks the average frequency of voiding or incontinence associated with moderate to severe urgency, which was the study primary outcome, decreased by a mean of 0.9 ± 3.2 episodes per day but no significant between group difference was detected., Conclusions: Among women with overactive bladder slow-paced respiration was associated with a modest improvement in perceived stress during 12 weeks. However, it was not superior to a music listening control for reducing urinary symptoms or changing autonomic function.

Purpose: Neurogenic bladder significantly impacts individuals after spinal cord injury. We hypothesized that there would be differences in bladder related symptoms and quality of life for 4 common bladder management methods., Materials and Methods: In this prospective observational study we measured neurogenic bladder related quality of life after spinal cord injury. Study eligibility included age 18 years or greater and acquired spinal cord injury. Bladder management was grouped as 1) clean intermittent catheterization, 2) an indwelling catheter, 3) surgery (bladder augmentation, a catheterizable channel or urinary diversion) and 4) voiding (a condom catheter, involuntary leaking or volitional voiding). The primary outcomes were the NBSS (Neurogenic Bladder Symptom Score) and the SCI-QoL Difficulties (Spinal Cord Injury Quality of Life Measurement System Bladder Management Difficulties). Secondary outcomes were the NBSS subdomains and satisfaction with urinary function. Multivariable regression was done to establish differences between the groups, separated by level., Results: Of the 1,479 participants enrolled in the study 843 (57%) had paraplegia and 894 (60%) were men. Median age was 44.9 years (IQR 34.4-54.1) and median time from injury was 11 years (IQR 5.1-22.4). Bladder management was clean intermittent catheterization in 754 cases (51%), an indwelling catheter in 271 (18%), surgery in 195 (13%) and voiding in 259 (18%). In regard to primary outcomes, in cases of paraplegia and tetraplegia an indwelling catheter and surgery were associated with fewer urinary symptoms on the NBSS compared to clean intermittent catheterization while voiding was associated with more symptoms. In paraplegia and tetraplegia cases surgery was associated with fewer bladder management difficulties according to the SCI-QoL Difficulties. In regard to secondary outcomes, surgery was associated with improved satisfaction in individuals with paraplegia or tetraplegia., Conclusions: In individuals with spinal cord injury fewer bladder symptoms were associated with an indwelling catheter and surgery, and worse bladder symptoms were noted in voiding individuals compared to those on clean intermittent catheterization. Satisfaction with the urinary system was improved after surgery compared to clean intermittent catheterization.

Purpose: Perineal urethrostomy is a viable option for many complex urethral strictures. However, to our knowledge no comparison with anterior urethroplasty regarding patient reported outcome measures has been published. We compared these groups using a large multi-institution database., Materials and Methods: We performed a retrospective study of anterior urethroplasty in the TURNS (Trauma and Urologic Reconstructive Network of Surgeons) database. The anterior urethroplasty cohort was defined by long strictures greater than 6 cm. We compared demographic, clinical, urinary and sexual characteristics using validated patient reported outcome measures between patients treated with long stricture anterior urethroplasty and those who underwent perineal urethrostomy., Results: Of the 131 patients 92 treated with long stricture anterior urethroplasty and 39 treated with perineal urethrostomy met study inclusion criteria. The cumulative incidence of failure at 2 years was 30.2% (95% CI 18.3-47.3) for long stricture anterior urethroplasty and 14.5% (95% CI 4.8-39.1) for perineal urethrostomy (p = 0.09). Compared to baseline metrics, patients who underwent long stricture anterior urethroplasty and perineal urethrostomy had similar improvements in urinary function and stable sexual function after surgery., Conclusions: Patients reported improvement in urinary function after perineal urethrostomy with no deleterious effect on sexual function. These patient reported outcome measures were comparable to those of long stricture anterior urethroplasty. Perineal urethrostomy failure rates were similar to those of long stricture anterior urethroplasty.

Purpose: Wolfram syndrome is a neurodegenerative disorder characterized by childhood onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing impairment, and commonly bladder and bowel dysfunction. We hypothesized that there is an association between a smaller pons, which contains the pontine micturition center, and abnormal lower urinary tract function., Materials and Methods: Patients with genetically confirmed Wolfram syndrome attended an annual multidisciplinary research clinic. Subjects underwent noninvasive urodynamic testing and brain magnetic resonance imaging, and completed validated patient reported outcome measures. Bowel and bladder diaries were completed before visits. Age and gender corrected linear and logistic mixed effects models were used to correlate pons volume, corrected for whole brain size, to urodynamic and patient reported outcomes., Results: A total of 36 patients attended 142 visits between 2010 and 2016. Mean age was 16.9 years (range 7 to 30) and 64% of patients were female. Functional bladder capacity was decreased in 31% of the patients, normal in 54% and increased in 14%. Of the patients 44% and 54% had abnormal uroflowmetry and post-void residual, respectively, on at least 1 occasion. There was no increase through time in incidence of lower urinary tract dysfunction. Decreased pons volume was associated with increased post-void residual (p = 0.048) and higher PinQ (Pediatric Incontinence Questionnaire) score (p = 0.011), indicating lower quality of life and higher levels of dysfunction., Conclusions: A significant number of children, adolescents and young adults with Wolfram syndrome have objective evidence of lower urinary tract dysfunction. Decreased pons volume is associated with more abnormal urinary function and lower quality of life in patients with Wolfram syndrome., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: In many individuals with spinal cord injury a return of volitional bladder voiding is considered more important than regaining motor function. Recently a predictive model using only composite bilateral lower extremity motor scores for levels L2-S1 (range 0 to 50) was proposed by the EMSCI (European Multicenter Study about Spinal Cord Injury) group. The model showed exceptional predictive power with an AUC of 0.912. We sought to further validate the EMSCI model in a national spinal cord injury cohort., Materials and Methods: We created models of volitional voiding using the United States NSCID (National Spinal Cord Injury Database) for 2007 to 2016. In addition to testing lower extremity motor scores, we evaluated other patient variables that we hypothesized might affect volitional voiding., Results: Volitional voiding was present in 1,333 of the cohort of 4,327 individuals (30.8%) at 1-year followup. While younger age, female gender, increased sacral sparing, improved AIS (American Spinal Injury Association Impairment Scale) classification and a more caudal sensory level predicted volitional voiding, lower extremity motor scores were most predictive (AUC 0.919). Adding the other patient characteristics did little to improve model performance (full model AUC 0.932). Further analysis of the predictive power of lower extremity motor scores suggested that while the AUC appeared to decrease in persons who were most likely to void volitionally, the performance of the predictive model remained outstanding with a combined AIS C and D AUC of 0.792., Conclusions: Our study verifies the validity of the EMSCI predictive model of volitional voiding after spinal cord injury. The differing performance of lower extremity motor scores in various AIS classifications should be noted., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We explored the relation of cycling to urinary and sexual function in a large multinational sample of men., Materials and Methods: Cyclists were recruited to complete a survey through Facebook® advertisements and outreach to sporting clubs. Swimmers and runners were recruited as a comparison group. Cyclists were categorized into low and high intensity cyclists. Participants were queried using validated questionnaires, including SHIM (Sexual Health Inventory for Men), I-PSS (International Prostate Symptom Score) and NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index), in addition to questions about urinary tract infections, urethral stricture, genital numbness and saddle sores., Results: Of 5,488 complete survey responses 3,932 (72%) were included in our analysis. On multivariate analysis swimmers/runners had a lower mean SHIM score than low and high intensity cyclists (19.5 vs 19.9 and 20.7, p = 0.02 and <0.001, respectively). No significant differences were found in I-PSS or NIH-CPSI scores, or urinary tract infection history. Cyclists had statistically higher odds of urethral stricture compared to swimmers/runners (OR 2.5, p = 0.042). Standing more than 20% of the time while cycling significantly reduced the odds of genital numbness (OR 0.4, p = 0.006). Adjusting the handlebar higher or even with the saddle had lower odds of genital numbness and saddle sores (OR 0.8, p = 0.005 and 0.6, p <0.001, respectively)., Conclusions: Cyclists had no worse sexual or urinary functions than swimmers or runners but cyclists were more prone to urethral stricture. Increased time standing while cycling and a higher handlebar height were associated with lower odds of genital sores and numbness., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the perioperative and long-term functional outcomes of bladder neck and peribulbar cuff placement of an artificial urinary sphincter in a population of adult male patients with spinal dysraphism., Materials and Methods: We retrospectively analyzed the French spina bifida network database. Patients who underwent implantation of an artificial urinary sphincter from January 1985 to November 2015 were selected and stratified into 2 groups according to cuff location, that is bladder neck vs bulbar urethra. Explantation-free and revision-free device survival was estimated by the Kaplan-Meier method and compared with the log rank test. Cox regression models were created to assess prognostic factors of artificial urinary sphincter device failure., Results: A total of 65 patients were included in study. Most patients were not wheelchair bound. The cuff was implanted around the bulbar urethra at 46 procedures (59%) and around the bladder neck in 32 (41%). In the peribulbar and bladder neck groups median revision-free device survival was 11.7 and 14.3 years, respectively (p = 0.73). Median explantation-free device survival was 18.5 and 24.5 years, respectively (p = 0.08). On multivariate analysis clean intermittent catheterization was the only predictor of artificial urinary sphincter device failure. Cuff location had no influence. At the last followup satisfactory continence was similar in the 2 groups (83% vs 75%, p = 0.75)., Conclusions: In male patients with spinal dysraphism morbidity and functional outcomes were similar for bladder neck and bulbar urethra cuff placement but with a trend toward longer survival without explantation in the bladder neck group. Clean intermittent catheterization was the only predictor of shorter device survival on multivariate analysis., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Achieving bladder continence in individuals with spina bifida is a lifetime management goal. We investigated bladder continence status through time and factors associated with this status in patients with spina bifida., Materials and Methods: We used National Spina Bifida Patient Registry data collected from 2009 through 2015 and applied generalized estimating equation models to analyze factors associated with bladder continence status., Results: This analysis included 5,250 participants with spina bifida in a large, multi-institutional patient registry who accounted for 12,740 annual clinic visit records during the study period. At last followup mean age was 16.6 years, 22.4% of participants had undergone bladder continence surgery, 92.6% used some form of bladder management and 45.8% reported bladder continence. In a multivariable regression model the likelihood of bladder continence was significantly greater in those who were older, were female, were nonHispanic white, had a nonmyelomeningocele diagnosis, had a lower level of lesion, had a higher mobility level and had private insurance. Continence surgery history and current management were also associated with continence independent of all other factors (adjusted OR and 95% CI 1.9, 1.7-2.1 and 3.8, 3.2-4.6, respectively). The association between bladder management and continence was stronger for those with a myelomeningocele diagnosis (adjusted OR 4.6) than with nonmyelomeningocele (adjusted OR 2.8)., Conclusions: In addition to demographic, social and clinical factors, surgical intervention and bladder management are significantly and independently associated with bladder continence status in individuals with spina bifida. The association between bladder management and continence is stronger in those with myelomeningocele., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To prevent over diagnosis and overtreatment of vesicoureteral reflux the 2007 NICE (National Institute for Health and Care Excellence) and 2011 AAP (American Academy of Pediatrics) guidelines recommended against routine voiding cystourethrograms in children presenting with first febrile urinary tract infections. The impact of these guidelines on clinical practice is unknown., Materials and Methods: Using an administrative claims database (Clinformatics™ Data Mart) children who underwent voiding cystourethrogram studies or had a diagnosis of vesicoureteral reflux between 2001 and 2015 were identified. The cohort was divided into children age 0 to 2 and 3 to 10 years. Single and multiple group interrupted time series analyses (difference-in-difference) were performed with the guidelines as intervention points. The incidence of vesicoureteral reflux was compared across each period., Results: Of the 51,649 children who underwent voiding cystourethrograms 19,422 (38%) were diagnosed with vesicoureteral reflux. In children 0 to 2 years old voiding cystourethrogram use did not decrease after the 2007 NICE guidelines were announced (-0.37, 95% CI -1.50 to 0.77, p = 0.52) but did decrease significantly after the 2011 AAP guidelines were announced (-2.00, 95% CI -3.35 to -0.65, p = 0.004). Among children 3 to 10 years old voiding cystourethrogram use decreased during the entire study period. There was a decrease in the incidence of vesicoureteral reflux in both groups that mirrored patterns of voiding cystourethrogram use., Conclusions: The 2011 AAP guidelines led to a concurrent decrease in voiding cystourethrogram use and incidence of vesicoureteral reflux among children 0 to 2 years old. Further studies are needed to assess the risks and benefits of reducing the diagnosis of vesicoureteral reflux in young children., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Patient centered data are lacking regarding functional and quality of life improvements after artificial urinary sphincter placement. We analyzed the degree of benefit from artificial urinary sphincter placement using ISI (Incontinence Symptom Index), a validated patient reported outcome measure assessing the severity and bother of urinary incontinence, and IIQ-7 (Incontinence Impact Questionnaire-7), a validated patient reported outcome measure assessing the impact and emotional distress of urinary incontinence., Materials and Methods: We performed a retrospective review at 4 centers participating in TURNS (Trauma and Urologic Reconstruction Network of Surgeons). Data were available on 51 and 45 patients who underwent artificial urinary sphincter placement, and had preoperative and postoperative ISI and IIQ-7 data, respectively., Results: Mean age was 64.8 years. Median time from surgery to followup questionnaires was 8.5 months. On ISI the median preoperative severity and bother scores were 24 (IQR 20-28.5) and 6 (IQR 4-7), and the median postoperative severity and bother scores were 10 (IQR 4.5-17) and 1 (IQR 0-3), respectively. Improvement on each ISI item was statistically significant. On IIQ-7 the median preoperative impact and distress scores were 9 (IQR 6-13) and 4 (IQR 2-6), and the median postoperative impact and distress scores were 3 (IQR 0-7) and 0 (IQR 0-3), respectively. Improvement on each IIQ-7 item was statistically significant., Conclusions: Artificial urinary sphincter implantation significantly reduces the severity and bother of stress urinary incontinence symptoms. Longer followup and development are needed of a patient reported outcome measure targeting male stress urinary incontinence., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the effects of long-term testosterone therapy on urinary and sexual function, and quality of life in hypogonadal men., Materials and Methods: We performed an observational, prospective, cumulative registry study in 656 men with a mean ± SD age of 60.7 ± 7.2 years who had total testosterone 12.1 nmol/l or less and symptoms of hypogonadism. In the testosterone treated group 360 men received parenteral testosterone undecanoate 1,000 mg/12 weeks for up to 10 years. The 296 men who elected against testosterone therapy served as controls. From each group 82 patients were propensity matched by age, waist circumference and body mass index, resulting in 82 matched pairs of 164 men. Data were analyzed and estimated differences between the groups were adjusted for components of metabolic syndrome and quality of life., Results: We found significant decreases in I-PSS (International Prostate Symptom Score) and post-void bladder volume (each p <0.0001) in patients receiving testosterone therapy but not in the untreated group. We recorded a decrease in AMS (Aging Males' Symptoms Scale) in the testosterone treated group but not in the untreated group (p <0.0001). We also recorded significant improvement in the IIEF-EF (International Index of Erectile Function-Erectile Function) domain in the testosterone treated group but not in the untreated group (p <0.0001). The improvement was maintained throughout followup., Conclusions: Long-term testosterone therapy in hypogonadal men resulted in significant improvements in urinary and sexual function, and in quality of life. In untreated hypogonadal men voiding and erectile function deteriorated with continued followup., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Postoperative urinary retention is a common complication across surgical specialties. To our knowledge no literature to date has examined postoperative urinary retention as a predictor of long-term receipt of surgery for bladder outlet obstruction., Materials and Methods: We retrospectively reviewed the records of inpatients who underwent nonurological surgery in California between 2008 and 2010. Postoperative urinary retention during the index admission was identified, as was receipt of a bladder outlet procedure (transurethral prostate resection, prostate photoselective vaporization or suprapubic prostatectomy) at a subsequent encounter. Patients were matched using propensity scoring of demographics, comorbidities and surgery type. Adjusted Kaplan-Meier analysis was performed to determine the cumulative incidence of subsequent bladder outlet procedures by patient group, including group 1-age 60 years or greater and postoperative urinary retention, group 2-age 60 years or greater and no postoperative urinary retention, group 3-age less than 60 years and postoperative urinary retention, and group 4-age less than 60 years and no postoperative urinary retention., Results: Of 769,141 eligible male patients postoperative urinary retention developed in 8,051 (1.1%). Following hospital discharge 1,855 patients (0.24%) underwent a bladder outlet procedure. Those treated with a bladder outlet procedure were significantly more likely to have experienced postoperative urinary retention during the index admission (6.3% vs 1.0%, p <0.001). On matched analysis the bladder outlet procedure rate at 3 years was 7.1%, 2.2%, 0.8% and 0.0% in groups 1, 2, 3 and 4, respectively., Conclusions: In men 60 years old or older postoperative urinary retention identified those with an increased incidence of bladder outlet procedures within 3 years. Men younger than 60 years had a low rate of subsequent bladder outlet procedures regardless of a postoperative urinary retention diagnosis., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Diet, fluid intake and caffeine, alcohol and tobacco use may have effects on lower urinary tract symptoms. Constructive changes in these modifiable nonurological factors are suggested to improve lower urinary tract symptoms. To better understand the relationship between nonurological factors and lower urinary tract symptoms, we performed a systematic literature review to examine, grade and summarize reported associations between lower urinary tract symptoms and diet, fluid intake and caffeine, tobacco and alcohol use., Materials and Methods: We performed PubMed® searches for eligible articles providing evidence on associations between 1 or more nonurological factors and lower urinary tract symptoms. A modified Oxford scale was used to grade the evidence., Results: We reviewed 111 articles addressing diet (28 studies), fluid intake (21) and caffeine (21), alcohol (26) and tobacco use (44). The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3 and 59% level 4). Fluid intake and caffeine use were associated with urinary frequency and urgency in men and women. Modest alcohol use was associated with decreased likelihood of benign prostatic hyperplasia diagnosis and reduced lower urinary tract symptoms in men. Associations between lower urinary tract symptoms and ingestion of certain foods and tobacco were inconsistent., Conclusions: Evidence of associations between lower urinary tract symptoms and diet, fluid intake and caffeine, alcohol and tobacco use is sparse and mostly observational. However, there is evidence of associations between increased fluid and caffeine intake and urinary frequency/urgency, and between modest alcohol intake and decreased benign prostatic hyperplasia diagnosis and lower urinary tract symptoms. Given the importance of these nonurological factors in daily life, and their perceived impact on lower urinary tract symptoms, higher quality evidence is needed., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: A recent study demonstrated improvement in nocturnal urgency in patients with overactive bladder when treated with fesoterodine. In the current study we aimed to determine which bladder diary parameters predict the response to fesoterodine in these patients., Materials and Methods: Patients with nocturnal urgency completed a 2-week, single-blind placebo run-in followed by 1:1 double-blind randomization to 12 weeks of fesoterodine or placebo. We analyzed bladder diary parameter changes from baseline to week 12, including the actual number of night voids (total number of nocturia episodes), maximum voided volume, nocturnal bladder capacity, Nocturnal Bladder Capacity Index (NBCi) (actual number of night voids - nocturnal urine volume/maximum voided volume - 1), nocturnal urine volume, the nocturia index (nocturnal urine volume/maximum voided volume) and the nocturnal polyuria index (nocturnal urine volume/24-hour volume). Additionally, we analyzed OAB-q (Overactive Bladder Questionnaire) changes., Results: There was a linear relationship between the likelihood of being a responder for NBCi and the nocturia index. Responders had a significant decrease in nocturnal urine volume relative to baseline (-181.7 ml, p <0.01). Neither group showed a significant change in maximum voided volume relative to baseline. There was a significant decrease in NBCi and the nocturia index in responders (-0.82 and -0.61, respectively, each p <0.01). Responders demonstrated improvement in the OAB-q concern, coping, sleep, bother and total score metrics., Conclusions: Patients with nocturnal urgency secondary to overactive bladder syndrome and low nocturnal bladder capacity with a mismatch between nocturnal urine production and bladder capacity may benefit from fesoterodine. Symptom improvement appears to be mediated by increases in typical rather than maximum nocturnal voided volumes. Symptom improvement was associated with improved quality of life., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's α = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p <0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols., (Copyright © 1992 American Urological Association, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction., Materials and Methods: We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia., Results: Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively., Conclusions: We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to understand variations in the expression and temporal relation of bladder control episodes among women with mixed urinary incontinence., Materials and Methods: A random sample of women 40 years old or older with mixed urinary incontinence on GLOBE-UI (General Longitudinal Overactive Bladder Evaluation-Urinary Incontinence) was recruited in a digital daily diary study using a smartphone application. When a bladder control event occurred, women were instructed to answer episode specific questions. Episodes were defined as urgency, and urinary incontinence with and urinary incontinence without urgency. Women and episodes were compared by the type of activity preceding each episode. Urinary incontinence episodes were further defined as stress urinary incontinence, urgency urinary incontinence, stress induced urgency urinary incontinence and other. The chi-square and Wilcoxon tests were used for categorical and continuous variables, respectively., Results: Of 40 women with a mean age of 65.5 years 35 provided complete 30-day diary data. Of the 950 bladder control episodes reported 25% were urgency only, 55% were urinary incontinence with urgency and 19% were urinary incontinence without urgency. Of the urinary incontinence episodes without urgency 82% occurred after a stress activity (eg coughing or sneezing). Notably, a stress activity also occurred just before 52.5% of the urgency urinary incontinence episodes (p <0.001). A total of 24 women (69%) reported at least 1 episode of stress induced urgency urinary incontinence, which was the most prevalent urinary incontinence subtype episode, followed by urgency urinary incontinence and stress urinary incontinence (29% vs 27% and 16%, respectively). The mean number of daily episodes was 1 or 2 across all groups., Conclusions: Women with mixed urinary incontinence express a heterogeneous set of bladder control episodes with stress induced urgency urinary incontinence as the dominant type., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Orthotopic bladder substitution has been performed on a regular basis for more than 30 years and yet data on long-term functional outcomes are still lacking., Materials and Methods: We evaluated 181 men and 19 women who underwent radical cystectomy and urinary diversion with ileal orthotopic bladder substitution from 1985 to 2004 and who had 10 years or more of followup., Results: Median age at radical cystectomy was 63 years (IQR 57-69). Median followup was 167 months (IQR 137-206). Daytime and nighttime continence rates peaked 24 months postoperatively and decreased slightly thereafter during almost 2 decades. At 10, 15 and 20 years daytime continence rates were 92%, 90% and 79%, and nighttime continence rates were 70%, 65% and 55%, respectively. During the day and at night fewer than 3% and 10% of patients, respectively, had urine loss 100 ml or greater at any time 10 years or longer after surgery. At 10 and 20 years 11 of 200 patients (6%) and 1 of 29 (3%), respectively, had to perform clean intermittent self-catheterization. After an initial postoperative decrease in the estimated glomerular filtration rate the subsequent decrease was less than 1 ml/minute/1.73 m(2) per year. A total of 81 complications were observed in 42 of the 200 patients (21%) 10 years or longer after radical cystectomy with pyelonephritis as the most frequent cause., Conclusions: Patients who survive up to 20 years after radical cystectomy and diversion with an ileal orthotopic bladder substitution may enjoy satisfactory urinary continence and retain the ability to void spontaneously while experiencing no more than a physiological decrease in renal function., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: In the current study we examined dynamic changes in neural activity of the anterior cingulate cortex and the midbrain periaqueductal gray during the micturition reflex in a Parkinson's disease model as well as the effects of direct stimulation of the anterior cingulate cortex on the micturition reflex., Materials and Methods: Electrodes were inserted in the anterior cingulate cortex or the periaqueductal gray. The effects of intravenous administration of the adenosine A2A receptor antagonist ZM24138 on pelvic nerve evoked field potentials were examined. The effect of electrical stimulation of the anterior cingulate cortex was also examined., Results: Rats with Parkinson's disease showed bladder overactivity as evidenced by a significant decrease in the intercontraction interval compared with sham operated rats. Intravenous administration of ZM24138 increased the intercontraction interval in both groups with the inhibitory effects greater in rats with Parkinson's disease. It dose dependently increased the amplitude of evoked potentials in the anterior cingulate cortex of rats with Parkinson's disease but not in sham operated rats. Intravenous administration of ZM24138 decreased evoked potential amplitude in the periaqueductal gray of both groups with the inhibitory effects greater in Parkinson's disease vs sham operated rats. Electrical stimulation of the anterior cingulate cortex significantly increased the intercontraction interval., Conclusions: These results suggest that anterior cingulate cortex neurons have an inhibitory role in bladder control. Neural activity in the anterior cingulate cortex was significantly increased along with suppression of bladder overactivity after ZM241385 administration in the Parkinson's disease model and the stimulation of the anterior cingulate cortex inhibited the micturition reflex. Understanding the roles of the anterior cingulate cortex in the modulation of micturition could provide further insights into the pathophysiology of overactive bladder., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluate the characteristics of artificial urinary sphincter mechanical failures and compare outcomes based on the surgical revision strategy, replacing only the failed component or the entire device., Materials and Methods: A total of 1,802 male patients with stress urinary incontinence underwent artificial urinary sphincter procedures from 1983 to 2011 at our institution, of which 1,082 were primary placements. Of these patients 125 experienced mechanical device malfunction. Multiple clinical and surgical variables were evaluated for a potential association with device malfunction. In addition, we evaluated for predictors of failure of the revised device, including time from primary artificial urinary sphincter to revision surgery and surgical revision strategy (single component vs entire device), with failure defined as any tertiary surgery., Results: At a median followup of 4.2 years (IQR 0.8, 7.9) 125 patients experienced device malfunction. The urethral cuff was the most common component failure (46.1%), followed by abdominal reservoir (22.6%), tubing (21.7%) and pump (9.6%). There was no association of time from primary surgery to revision for mechanical failure (HR 0.89, p=0.33) or revision strategy (HR 0.47, p=0.15) with the risk of tertiary surgery. Additionally, as there was no significant interaction between these variables (HR 1.11, p=0.39), no cutoff could be identified at which one revision technique produced significantly improved device survival compared to another. However, there was a trend toward improved 3-year device survival after replacement of the entire device vs a single component (76% vs 60%, p=0.11)., Conclusions: No cutoff in time to mechanical failure could be identified to guide decision making in the management of mechanical artificial urinary sphincter failure. Likewise, it is unclear if replacing the entire device, rather than the single malfunctioning component, alters device survival. As such, further studies are needed. However, given the current trend toward improved overall device survival, the limited additional risk and the lack of adequate clinical predictors for tertiary surgery, we would advocate for replacement of the entire device when possible., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined the association of urinary symptoms with fall risk and physical limitations in older community dwelling women with urinary incontinence., Materials and Methods: We performed an in-depth assessment of daytime and nighttime urinary symptoms, fall risk, physical function, physical performance tests and mental function in older community dwelling women with urinary incontinence who had not sought care for urinary symptoms. All assessments were performed in participant homes. We used univariable and multivariable linear regression to examine the relationship of urinary symptoms to fall risk, physical function and physical performance., Results: Of 37 women with a mean ± SD age of 74 ± 8.4 years who had urinary incontinence 48% were at high risk for falls. Nocturnal enuresis was reported by 50% of the women. Increased fall risk was associated with increasing frequency of nocturnal enuresis (p = 0.04), worse lower limb function (p <0.001), worse upper limb function (p <0.0001) and worse performance on a composite physical performance test of strength, gait and balance (p = 0.02). Women with nocturnal enuresis had significantly lower physical performance test scores than women without nocturnal enuresis (median 7, range 0 to 11 vs 9, range 1 to 12, p = 0.04). In a multivariable regression model including age, nocturnal enuresis episodes and physical function only physical function was associated with an increased fall risk (p <0.0001)., Conclusions: Nocturnal enuresis is common in older community dwelling women with urinary incontinence. It may serve as a marker of fall risk even in women who do not seek care for urinary symptoms. Interventions targeting upper and lower body physical function could potentially decrease the risk of falls in older women with urinary incontinence., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Previous reports have revealed significantly higher rates of psychosocial difficulties in children and adolescents with voiding dysfunction compared to their healthy peers. However, these findings are based solely on parental reporting and do not include self-reporting of psychosocial problems in older pediatric patients., Materials and Methods: We collected data from 200 consecutive patients 11 to 16 years old during outpatient clinic visits. Patients completed the Pediatric Symptom Checklist-Youth Report, parents completed the parental report of the same measure, and patients and parents collaboratively completed the Dysfunctional Voiding Scoring System., Results: Of the patients 25.5% met the cutoff score for clinically significant levels of psychosocial difficulties. However, only a fourth of those patients met the cutoff on the parent and self-report measures. Additionally patient self-reports of internalizing and externalizing problems were significantly related to severity of voiding dysfunction., Conclusions: Screening for psychosocial problems in older children and adolescents with voiding dysfunction should include reports from the parent and the child. In our sample 37.3% of patients needing a mental health followup would have been missed if only 1 version of the measure had been administered., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Opioids have traditionally been the mainstay of pain management after radical cystectomy for bladder cancer but they have many side effects. The efficacy of opioid sparing analgesics after cystectomy as part of a protocol of enhanced recovery after surgery has yet to be proved. We compared opioid use, pain score and postoperative ileus in consecutive patients on a protocol of enhanced recovery after surgery and those on a traditional protocol after radical cystectomy., Materials and Methods: Using our institutional review board approved bladder cancer database we retrospectively reviewed the records of patients who underwent open radical cystectomy using a traditional protocol or a protocol of enhanced recovery after surgery for pain management. A total of 205 patients were ultimately enrolled in study, including 81 on a traditional protocol and 124 on the enhanced protocol. Opioid use and pain scores were analyzed and compared up to postoperative day 4. All routes of opioid use were recorded and converted to the morphine equivalent dose for comparison. Postoperative pain was recorded using a visual analog scale. Postoperative records were reviewed for the incidence of ileus., Results: Patients on the enhanced recovery after surgery protocol and those on a traditional protocol were similar demographically. When analyzing data up to the median hospital stay on the case group, patients on enhanced recovery used significantly less opioids per day (4.9 mg vs 20.67 mg morphine equivalents, p <0.001) and reported more pain (visual analog scale 3.1 vs 1.14, p <0.001). They also experienced a significantly lesser incidence of postoperative ileus (7.3% vs 22.2%, p = 0.003) and had a significantly shorter median length of hospital stay (4 vs 8 days, p <0.001)., Conclusions: Patients on the protocol of enhanced recovery after surgery used significantly less opioid analgesics, possibly contributing to decreased postoperative ileus and shorter length of hospital stay., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with neurological conditions often experience severe debilitating lower urinary and bowel dysfunction in addition to the physical disabilities. However, only the bladder has received the attention of medical providers with neurogenic bowel being poorly understood and characterized., Materials and Methods: This is a cross-sectional analysis of a prospective institutional neurogenic bladder database from 2010 to 2013., Results: Of the 175 patients 60.6% had traumatic spinal cord injury and 18.3% had multiple sclerosis. Median ± SD FISI (Fecal Incontinence Severity Index) scores were 18.0 ± 1.39 (moderate). The median neurogenic bowel dysfunction score was 11.0 ± 0.63 (moderate). Those scores were worse in those patients with spinal cord injury and spina bifida compared to those with other diseases and in younger patients (each p = 0.020), and those in the spinal cord injury group with higher levels of injury (p = 0.0046). Based on the Bristol stool scale 65% of patients had abnormal stool consistency, mostly constipation. None of the FISI, Bristol or neurogenic bowel dysfunction scores correlated significantly with SF-12® quality of life measures. However, bladder symptom scores on M-ISI (Michigan Incontinence Symptom Index) (p = 0.05) and AUA-SI (American Urological Association symptom index) (p = 0.03) correlated with FISI severity while the neurogenic bowel dysfunction score correlated with M-ISI (ρ = 0.29, p = 0.02). Patients with abnormal stool consistency on the Bristol scale reported more urgency and stress incontinence on M-ISI., Conclusions: Bowel dysfunction is common among patients with neurogenic bladder. Those with worse bladder symptoms also experience worse bowel dysfunction. This highlights the importance of addressing both bowel and bladder dysfunction in this often poorly understood population., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Normal voiding in neurologically intact patients is triggered by the release of tonic inhibition from suprapontine centers, allowing the pontine micturition center to trigger the voiding reflex. Supraspinal mechanisms of voluntary voiding in humans are just beginning to be described via functional neuroimaging. We further elucidated brain activity processes during voiding using functional magnetic resonance imaging in normal females to gain better understanding of normal voiding as well as changes that may occur in voiding dysfunction., Materials and Methods: We screened 13 healthy premenopausal female volunteers using baseline clinic urodynamics to document normal voiding parameters. We then recorded brain activity via functional magnetic resonance imaging and simultaneous urodynamics, including the pressure flow voiding phase. After motion correction of functional magnetic resonance images we performed activation and connectivity analyses in 10 subjects., Results: Group analysis revealed consistent activation areas, including regions for motor control (cerebellum, thalamus, caudate, lentiform nucleus, red nucleus, supplementary motor area and post-central gyrus), emotion (anterior/posterior cingulate gyrus and insula), executive function (left superior frontal gyrus) and a focal region in the pons. Connectivity analysis demonstrated strong interconnectivity of the pontine micturition center with many short-range and long-range cortical clusters., Conclusions: Our study is one of the first reports of brain activation centers associated with micturition initiation in normal healthy females. Results show activation of a brain network consisting of regions for motor control, executive function and emotion processing. Further studies are planned to create and validate a model of brain activity during normal voiding in women., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The rostral pontine reticular formation has a strong inhibitory effect on micturition by facilitating lumbosacral glycinergic neurons. We assessed the influence of the rostral pontine reticular formation on the micturition reflex after noradrenaline injection in the medial frontal lobe. We also examined the relation between the medial frontal lobe and the rostral pontine reticular formation., Materials and Methods: Continuous cystometry was performed in 28 female rats. After the interval between bladder contractions was shortened by noradrenaline injection in the medial frontal lobe we injected glutamate or flavoxate hydrochloride in the rostral pontine reticular formation or intravenously injected flavoxate or propiverine. The change in bladder activity was examined., Results: Noradrenaline injection in the medial frontal lobe shortened the interval between bladder contractions. In contrast to the bladder contraction interval before and after noradrenaline injection in the medial frontal lobe, the interval was prolonged after noradrenaline injection when glutamate or flavoxate was injected in the rostral pontine reticular formation, or flavoxate was injected intravenously. Noradrenaline injection in the medial frontal lobe plus intravenous propiverine injection also prolonged the interval compared to that after noradrenaline injection alone. However, the interval after noradrenaline injection in the medial frontal lobe plus intravenous injection of propiverine was shorter than that before noradrenaline injection only., Conclusions: Medial frontal lobe neurons excited by noradrenaline may facilitate the micturition reflex via activation of inhibitory interneurons, which inhibit descending rostral pontine reticular formation neurons that innervate the lumbosacral glycinergic inhibitory neurons. Therefore, the mechanism of micturition reflex facilitation by the activation of medial frontal lobe neurons involves the rostral pontine reticular formation., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined prevalence rates, and changes in continence and incontinence before and after radical prostatectomy for prostate cancer by comparing different definitions. We also studied the descriptive validity of the grading system of Ellison et al for post-prostatectomy incontinence and baseline predictors of post-prostatectomy incontinence at 12 months., Materials and Methods: This national prospective study included 844 patients treated with radical prostatectomy between 2005 and 2009. Adverse effects, including urinary dysfunction and bother, were reported by 735 patients (88%) using the EPIC-50 and UCLA-PCI validated questionnaires at baseline and 12-month followup. Linear regression analysis was done to examine baseline predictors and the degree of post-prostatectomy incontinence at followup., Results: At 12 months after radical prostatectomy 74% of patients reported post-prostatectomy incontinence, of whom 40% used pads daily, 34% reported occasional dribbling without pads and 26% had total urinary control. When defined as total incontinence/no urinary control, severe post-prostatectomy incontinence was reported by 3% of the men but 25% had severe post-prostatectomy incontinence according to the stratification of Ellison et al. Of patients with preoperative incontinence 14% improved postoperatively. Predictors of post-prostatectomy incontinence were age 65 years or greater, not working, sexual dysfunction and incontinence preoperatively. The latter 2 remained the strongest predictors on multivariate analysis. Prostate cancer related variables were not associated with post-prostatectomy incontinence., Conclusions: The prevalence of post-prostatectomy incontinence varied considerably according to the definition applied. In our opinion incontinence may be reported as any leakage and not only as pad use with grading done on a symptom scale. Preoperative sexual dysfunction and urinary incontinence were the strongest predictors of post-prostatectomy incontinence at 12-month followup., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated age related changes in urodynamic parameters in 2 large cohorts of women planning stress urinary incontinence surgery., Materials and Methods: Using a standardized protocol we obtained urodynamic parameters for participants in SISTEr (Stress Incontinence Surgical Treatment Efficacy Trial) and TOMUS (Trial of Mid-Urethral Slings) undergoing baseline noninvasive flow followed by filling cystometrogram and pressure flow study. The bladder contractility index (defined as detrusor pressure at maximum flow+5×maximum flow) and detrusor hypocontractility (defined as detrusor pressure at maximum flow less than 10 cm H2O) were also characterized. Patients excluded from analysis had undergone prior stress urinary incontinence surgery or had prolapse stage greater than II. Propensity score analysis controlled for the potential bias of combining participants from 2 clinical trials. Linear and logistic regression analysis adjusting for propensity score quintile was done to assess the association of age and an age cutoff (less than 65 vs 65 or greater years) with urodynamic parameters., Results: A total of 945 women (468 in SISTEr and 477 in TOMUS) were included in analysis. Mean age was 50 years in SISTEr (range 27 to 75) and 51 years (range 24 to 82) in TOMUS. Noninvasive maximum urinary flow decreased significantly with age (26.2 vs 22 ml per second, p=0.002). Noninvasive flow voiding time increased 2.7 seconds for each 10-year age increment and detrusor pressure at maximum flow decreased 2.1 cm H2O for each 10-year increase in age (each p=0.003). Hypocontractility was more likely in women 65 years old or older (OR 2.89, 95% CI 1.59, 5.27). The bladder contractility index was inversely related to age, decreasing a mean±SD of 7.68±1.96 cm H2O for each 10-year age increase (p<0.001)., Conclusions: In these 2 cohorts the observed changes in voiding parameters suggest that detrusor contractility and efficiency decrease with age., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Nocturnal voids are regulated by circadian biological rhythms, including decreased urine production and increased bladder storage capacity at night. A previous experimental study suggested that exogenous melatonin decreases urine production and increases bladder capacity in rats. However, little is known about whether melatonin secretion, which is considerably lower than exogenous melatonin, is associated with nocturia in humans. We evaluated the association between melatonin secretion and nocturia., Materials and Methods: In this cross-sectional study we examined 861 community based elderly individuals with a mean age of 72.1 years. We measured nocturnal void frequency and overnight urinary 6-sulfatoxymelatonin excretion as an index of melatonin secretion. Nocturia was defined as 2 or more nocturnal voids., Results: Univariate comparisons between the 261 and 600 study participants with and without nocturia, respectively, showed marginal to significant associations of nocturia with age, gender, body mass index, estimated glomerular filtration rate, calcium channel blockers, benign prostatic hyperplasia, total voided urine volume, urinary 6-sulfatoxymelatonin, duration in bed, day length, and daytime and nighttime physical activity. The multivariate logistic regression model adjusted for the former confounding factors revealed that higher urinary 6-sulfatoxymelatonin was significantly associated with a lower nocturia OR (adjusted OR 0.73, 95% CI 0.56-0.96, p=0.023). After adjustment for age, gender and duration in bed the mean volume of a single voided urine significantly increased with tertiles of increasing urinary 6-sulfatoxymelatonin (p for trend=0.022)., Conclusions: Melatonin secretion is significantly and inversely associated with nocturia in a general elderly population., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined the oncologic and urological outcomes in patients with bladder/prostate rhabdomyosarcoma according to the type and timing of urinary tract surgery, with emphasis on the role of the Padua orthotopic ileal neobladder., Materials and Methods: We retrospectively analyzed oncologic and urological outcomes of 11 consecutive patients treated at our institution between 1998 and 2012., Results: Two patients underwent urethrectomy and placement of a heterotopic catheterizable ileal neobladder. The membranous urethra was preserved in 9 patients, 6 underwent primary Padua ileal neobladder at radical cystectomy, 2 underwent delayed Padua ileal neobladder and 1 underwent bilateral cutaneous ureterostomy. Four of these 9 patients experienced disease recurrence, including local recurrence in 2 despite negative intraoperative biopsies. Survivors undergoing heterotopic catheterizable ileal neobladder or primary Padua ileal neobladder learned to empty the bladder to completion without long-term upper tract deterioration. Both cases managed by delayed Padua ileal neobladder required clean intermittent catheterization eventually. Erections were reported in 5 of 6 surviving males., Conclusions: The Padua ileal neobladder allowed preservation of volitional urethral voiding in all survivors in whom it was placed at radical cystectomy. Nevertheless, local recurrence was noted in 2 of the 9 cases where the membranous urethra was preserved. By comparison, patients undergoing delayed Padua ileal neobladder after attaining disease-free status never achieved voiding per urethra. Therefore, a heterotopic reservoir might be a more reliable choice under these circumstances. Erectile function is preserved in the majority of cases., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Successful treatment of locally confined prostate cancer is defined by postoperative cancer control, continence and potency. The Expanded Prostate Cancer Index Composite (EPIC) is a validated instrument developed specifically for prostate cancer survivors. The EPIC-Sexual Inventory (EPIC-S) and EPIC-Urinary Inventory (EPIC-UIN) assess sexual and urinary function, respectively. We evaluated the usefulness of urinary and sexual function measured by EPIC at baseline and 3-month followup after prostatectomy to predict functional outcomes 1 year postoperatively., Materials and Methods: We retrospectively reviewed a prospectively maintained, institutional review board approved database for patients treated with prostatectomy from 2000 to 2009. EPIC scores were acquired preoperatively, and at 3 and 12-month followups. We calculated the likelihood of sexual and urinary recovery at 12 months based on 3-month EPIC-UIN and EPIC-S scores., Results: Patients were treated with open (226) or robotic (235) surgery. The 437 patients with complete EPIC-UIN questionnaires had worsened (2.7%), improved (47.8%) or stable (49.4%) urinary function, and the 436 with complete EPIC-S questionnaires had worsened (3.9%), improved (36.9%) or stable (59.2%) sexual function at 12 months compared to 3-month scores. Return to baseline was predicted by 3-month EPIC-UIN scores of 50 or greater (OR 7.76) and EPIC-S scores of 45 or greater (OR 3.64, each p <0.0001). The Pearson correlation coefficient of 3 and 12-month EPIC-UIN and EPIC-S scores was 0.65 and 0.73, respectively., Conclusions: Three-month EPIC-UIN and EPIC-S scores were useful for predicting 12-month functional outcomes. Health related quality of life instruments should be applied in the early postoperative period to aid in counseling patients on recovery., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)