Urinary bladder organ hypertrophy is partially regulated by Akt1-mediated protein synthesis pathway.

AIMS: The present study aims to investigate the role of Akt in the regulation of urinary bladder organ hypertrophy caused by partial bladder outlet obstruction (pBOO). MAIN METHODS: Male rats were surgically induced for pBOO. Real-time PCR and western blot were used to examine the levels of mRNA and protein. A phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to inhibit the activity of endogenous Akt. KEY FINDINGS: The urinary bladder developed hypertrophy at 2 weeks of pBOO. The protein but not mRNA levels of type I collagen and α-smooth muscle actin (αSMA) were increased in pBOO bladder when compared to sham control. The phosphorylation (activation) levels of Akt1 (p-Ser473), mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and 4E-BP1 were also increased in pBOO bladder. LY294002 treatment reduced the phosphorylation levels of Akt1 and 4E-BP1, and the protein levels of type I collagen and αSMA in pBOO bladder. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) were increased in pBOO bladder, and PCNA up-regulation occurred in urothelial not muscular layer. LY294002 treatment had no effect on the mRNA and protein levels of PCNA in pBOO bladder. LY294002 treatment partially reduced the bladder weight caused by pBOO. SIGNIFICANCE: pBOO-induced urinary bladder hypertrophy is attributable to fibrosis, smooth muscle cellular hypertrophy, and urothelium cell hyper-proliferation. Akt1-mediated protein synthesis in pBOO bladder contributes to type I collagen and αSMA but not PCNA up-regulation. Target of Akt1 is necessary but not sufficient in treatment of urinary bladder hypertrophy following pBOO.

Spontaneous voiding by mice reveals strain-specific lower urinary tract function to be a quantitative genetic trait.

Lower urinary tract (LUT) symptoms become prevalent with aging and affect millions; however, therapy is often ineffective because the etiology is unknown. Existing assays of LUT function in animal models are often invasive; however, a noninvasive assay is required to study symptom progression and determine genetic correlates. Here, we present a spontaneous voiding assay that is simple, reproducible, quantitative, and noninvasive. Young female mice from eight inbred mouse strains (129S1/SvImJ, A/J, C57BL/6J, NOD/ShiLtJ, NZO/H1LtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were tested for urination patterns on filter paper. Repeat testing at different times of the day showed minimal within-individual and within-strain variations, but all parameters (spot number, total volume, percent area in primary void, corner voiding, and center voiding) exhibited significant variations between strains. Calculation of the intraclass correlation coefficient, an estimate of broad-sense heritability, for each time of day and for each voiding parameter revealed highly significant heritability [spot number: 61%, percent urine in primary void: 90%, and total volume: 94% (afternoon data)]. Cystometrograms confirmed strong strain-specific urodynamic characteristics. Behavior-voiding correlation analysis showed no correlation with anxiety phenotypes. Diagnostically, the assay revealed LUT symptoms in several systems, including a demonstration of voiding abnormalities in older C57BL/6J mice (18-24 mo), in a model of protamine sulfate-induced urothelial damage and in a model of sucrose-induced diuresis. This assay may be used to derive pathophysiological LUT readouts from mouse models. Voiding characteristics are heritable traits, opening the way for genetic studies of LUT symptoms using outbred mouse populations.

Lower urinary tract symptom improvement after radical prostatectomy correlates with degree of prostatic inflammation.

OBJECTIVE: To determine if prostatic inflammation at the time of radical prostatectomy (RP) was associated with the International Prostate Symptom Score (IPSS). METHODS: We performed a proof of principle analytic case control study of patients who underwent RP between January 2005 and August 2008 for lower urinary tract symptoms (LUTS). We reviewed pathology slides of those who had a change of 4 points or greater, as measured by the IPSS and correlated inflammation with change in IPSS. Multivariate linear regression analyses were performed to determine the association of IPSS with degree of inflammation based on the number of inflammatory cells. RESULTS: Of 249 patients, 136 had complete data and 47 (18.8%) underwent pathologic review. The median change in IPSS for the study cohort was -7.0 points compared to +1.0 point for the control cohort. On univariate analysis, the average improvement in IPSS in patients with severe inflammation was (r = -6.02, 95% confidence interval [CI] -11.0 to -1.1, P = .018) after RP. On multivariate analysis, adjusting for age, body mass index (BMI), year of surgery, history of prostatitis, Gleason score, prostate-specific antigen (PSA), prostate weight, and nerve sparing status, only patients with severe prostatic inflammation had significant improvement in their IPSS (r = -5.93, 95% CI -10.81 to -1.04, P = .004). CONCLUSION: Prostatic inflammation measured in prostatectomy specimens is associated with worse baseline IPSS than matched cohorts. Specifically, severe inflammation is an independent predictor of IPSS improvement at 1 year after RP.

Establishing the subspecialty of female pelvic medicine and reconstructive surgery in the United States of America.

OBJECTIVE: In this review I describe the history leading to the creation of the subspecialty of female pelvic medicine and reconstructive surgery and its fellowships, the process involved in the current requirements for subspecialty certification and fellowship applications, and the implications for urological training. RESULTS AND CONCLUSIONS: The route to subspecialty certification and fellowships for female urology in the USA is a lesson in politics, education, medical rivalries and perseverance, with the goal of improving care for women. This decade-long journey culminated in the recognition of a separate subspecialty by the American Board of Medical Specialties in 2011, accreditation by the American Council for Graduate Medical Education in 2012, and certification to be awarded by the Boards of Obstetrics and Gynecology and Urology in 2013. It remains to be seen whether this effort will improve resident education and patient care, or represent a marketing tool in the competitive USA healthcare environment. While many of the details and regulatory issues are specific to the USA, elements of the curriculum and procedures should be relevant to other countries.

Bladder and urethral function in a mouse model of cavernous nerve injury.

AIMS: To determine whether cavernous nerve injury (CNI) alters lower urinary tract function, we assessed bladder and urethral function over time in a mouse model of CNI. METHODS: Twelve-week-old male C57BL/6 mice were divided into three groups: unoperated (UO; n = 6), sham-operated (SO; n = 18), and bilateral CNI (n = 30) group. At 1, 2, 4, 6, 8, 10 days bladder and urethral function were evaluated in these three groups using cystometry (CMG) and leak point pressure (LPP) recording under anesthesia. RESULTS: There was no significant difference in maximum detrusor pressure between groups at all times. Compared with the UO group, bladder compliance, and capacity in the CNI group were significantly decreased at Days 1, 2, 4 (P < 0.05) and recovered gradually from Day 6 to Day 10. In the SO group, they were decreased at Day 1, however, recovered more rapidly than the CNI group. Non-voiding contractions (NVC) developed in the CNI group at all times. Intercontraction interval were significantly decreased in SO and CNI groups and recovered more rapidly in SO group. In the SO group NVC were observed only at Days 1 and 2. LPP in the CNI group was decreased significantly at Days 1 and 2 (P < 0.05) and rapidly recovered with time compared with the UO and SO groups. CONCLUSION: In a mouse model of CNI, a transient decrease in bladder compliance, capacity, LPP and increased NVC was observed. These changes gradually recovered from Day 6 after CNI. Our findings suggest that CNI may affect bladder and urethral function, but alterations are reversible.

Benign prostatic hyperplasia evaluation and management by urologists and primary care physicians: practice patterns from the observational BPH registry.

PURPOSE: We examined the evaluation of and management for lower urinary tract symptoms/benign prostatic hyperplasia by physician specialty (urologist vs primary care physician). MATERIALS AND METHODS: The BPH Registry and Patient Survey is a longitudinal, observational, disease registry cohort of patients enrolled from January 2004 to February 2005 in the United States. The survey examines patient outcomes and physician practice patterns in the management of lower urinary tract symptoms associated with clinical benign prostatic hyperplasia. It includes 402 urologist and primary care physician practices throughout the United States. Included in this study were 6,924 men with lower urinary tract symptoms/benign prostatic hyperplasia managed by watchful waiting or medical therapy. Data were collected on demographics, clinical characteristics and lower urinary tract symptoms/benign prostatic hyperplasia management using physician and patient completed forms. Multivariate analysis was done by physician specialty. RESULTS: Based on multivariate analysis urologists were more likely than primary care physicians to perform urinalysis (OR 3.9), serum prostate specific antigen (OR 1.2) and post-void residual urine (OR 18.9) measurement, uroflowmetry (OR 17.3), prostate ultrasound (OR 7.7) and biopsy (OR 3.5), renal ultrasound (OR 4.0) and cystoscopy (OR 4.6) but less likely to measure creatinine (OR 0.1). Men seeing urologists were twice as likely as men seeing primary care physicians to be treated with benign prostatic hyperplasia medical therapy vs watchful waiting. Significant differences by physician specialty were also observed for specific benign prostatic hyperplasia medical therapies. CONCLUSIONS: Significant differences in practice patterns were observed between primary care physicians and urologists in the evaluation of and management for lower urinary tract symptoms/benign prostatic hyperplasia. These data establish valuable benchmarks and identify possible interventions that may improve the standard of care.

Current and future need for academic urologists in the United States.

PURPOSE: We assessed the need for academic urologists in 2010 and for the following 5 years. MATERIALS AND METHODS: An 8-question survey was emailed to the 115 accredited academic urology residency programs recognized by the American Urological Association. Questions were related to the anticipated number of hires during the next 5 years, ideal minimum level of training, areas of expertise needed, current top need and allotted research time. RESULTS: Of 115 chairs or division heads 91 (79%) responded to the survey. Of all chairs 71% (65 of 91) expect to hire 2 to 4 physicians in the next 5 years. In total 91 chairs will be attempting to fill 292 openings. When carried out to 115 chairs, there will be 369 openings in the next 5 years (or 74 per year). The ideal minimum level of training was cited as clinical/research fellowship (37.1%), clinical fellowship (33.6%) and residency (10.5%). Areas of expertise needed most from each respective program include female urology/neurourology (51.7%), oncology (44.8%), and pediatrics and general urology (36.8%). The current top needs for respective programs include pediatrics 23.3%, female urology/neurourology 21.1% and oncology 18.9%. Of the chairs and division heads currently attempting to fill positions 53.5% have been searching for 2 or more years. CONCLUSIONS: There will be a tremendous need for academic urologists in the next 5 years. This need is thought to be due to an increased number of physicians retiring and decreased level of compensation compared to private practice.

Angiogenesis therapy for the treatment of erectile dysfunction.

INTRODUCTION: Over the past 15 years, significant advances have been made in the treatment of erectile dysfunction (ED). The most significant of these advances has been pharmacological treatment of ED with phosphodiesterase type 5 (PDE5) inhibitors. This therapy greatly increased the awareness of ED and has helped stimulate research into the underlying causes of ED. While treatment with PDE5 inhibitors continues to be the current therapy of choice, approximately 40% of men treated with PDE5 inhibitors fail to have significant improvement in erectile function and PDE5 inhibitors do not reverse the vasculopathic processes associated with ED. With this in mind, new therapies must be developed. The treatment with angiogenic growth factors such as vascular endothelial cell growth factor (VEGF) may be one such therapy. AIM: This review will focus on defining key terms in the angiogenic process, angiogenic growth factors, and different delivery methods, and summarize results from angiogenic therapies for the treatment of ED. METHODS: A review of the literature was performed on all angiogenic therapies for the treatment of ED. A brief review on the angiogenic factors was also performed. RESULTS: Angiogenic therapies for the treatment of ED are possible and promising; however, further investigation is needed to advance clinically. CONCLUSIONS: Although numerous studies have now employed angiogenic factors for the possible treatment of ED in several animal models, we are still not at the point to begin human investigations. Future studies need to examine proper dosage of the angiogenic agent, route of delivery, time course for delivery, and combination therapies.

Fiberoptic imaging for urologic surgery.

Laparoscopic and robot-assisted surgery is likely to be improved with the development of real-time, intraoperative imaging for diagnosis, margin determination, and anatomical definition. A significant goal of much of this effort has been focused upon providing better outcomes after radical prostatectomy. The feasibility of fluorescent imaging of labeled cavernosal nerves in the operative field has been demonstrated in vivo in animals. Other applications of the technology and capability will certainly be developed over time. This article reviews and assesses the potential and capabilities of the different imaging modes currently in use or development.

Urinary retention and post-void residual urine in men: separating truth from tradition.

PURPOSE: The definitions of acute and chronic urinary retention remain empirical and subject to wide interpretation. Standardized criteria have not been established and many questions remain unanswered. Moreover, the definition of significant post-void residual urine is unclear. We reviewed several aspects of urinary retention that require clarification with the objective of stimulating discussion among urologists to establish an accurate and coherent definition of urinary retention and significant post-void residual urine, and clarify risk factors. MATERIALS AND METHODS: A MEDLINE search for articles written in English and published before April 2007 was done using a list of terms related to urinary retention. Articles not directly relevant to urinary retention or post-void residual urine were excluded. RESULTS: The term urinary retention lacks precise clinical or urodynamic meaning. Use of this term to describe a symptom, a sign, and a condition further complicates the issue. Many factors can contribute to the development of retention, including bladder outlet obstruction, detrusor underactivity, and neurogenic bladder conditions. Community based studies and clinical trials in patients with benign prostatic enlargement and/or lower urinary tract symptoms yield different estimates of the incidence of retention and only provide information on the epidemiology of acute urinary retention. However, age, previous retention episodes, lower urinary tract symptoms, chronic inflammation, serum prostate specific antigen level, prostate size, and urodynamic variables appear to be predictors of acute urinary retention. Alpha-receptor antagonists and 5alpha-reductase inhibitors may be useful in preventing urinary retention episodes and progressive benign prostatic enlargement. Clinical trials on the short-term use of antimuscarinics have not provided evidence that these agents increase the risk of retention; data on longer term administration are needed. CONCLUSIONS: Clinicians are adopting less invasive approaches (eg pharmacology or catheterization) to treating patients who present with the symptoms, sign, and condition of urinary retention. Faced with an abundance of new data on acute urinary retention, urologists need to reach a consensus about the risks of urinary retention; this may promote movement toward patient centered prevention strategies with tailored treatment options.

Surgical versus nonsurgical treatment of women with pelvic floor dysfunction: patient centered goals at 1 year.

PURPOSE: In women with pelvic floor dysfunction we assessed the degree to which treatment (surgical vs nonsurgical) was associated with achievement of patient centered goals, satisfaction with care and quality of life. MATERIALS AND METHODS: In this prospective cohort study between September 2003 and December 2004 we recruited women during their first referral visit for pelvic floor dysfunction treatment at our outpatient Urogynecology Clinic. At the first visit women enumerated up to 5 personal treatment goals, and anchored each goal by anticipating best and worst possible outcomes. At 12-month followup women were asked to indicate the level of goal attainment (-2 worst outcome, +2 best outcome). At baseline and followup women completed short forms of the Incontinence Impact Questionnaire and Urogenital Distress Inventory (range 0 to 100, high scores indicating greater impact or distress). Patients indicated the level of treatment satisfaction on a 4-level ordinal scale. RESULTS: Of the 127 study participants with complete data 46 (36.2%) were treated surgically and 81 (63.8%) were treated nonsurgically. There were no major demographic differences between the 2 groups in terms of age, race, weight, prior pelvic floor dysfunction surgery and vaginal parity. The surgical group was more likely to have received a baseline diagnosis of pelvic organ prolapse (80% vs 60%, p = 0.0259) and be postmenopausal (89% vs 72%, p = 0.0261). There were no significant differences in the distribution of goal type (symptom relief, activity, self-image, general health) by treatment status (p = 0.1074). Using logistic regression to adjust for age and baseline diagnosis, surgically treated patients at 1 year were significantly more likely to report complete primary goal attainment (OR 4.42, p = 0.0154) and complete treatment satisfaction (OR 6.12, p = 0.0109). For all participants 1-year Incontinence Impact Questionnaire-7 and Urogenital Distress Inventory-6 scores were significantly correlated with primary goal attainment scores. CONCLUSIONS: In this nonrandomized, prospective analysis surgically treated patients with pelvic floor dysfunction had higher 1-year self-described complete goal attainment and satisfaction scores compared with patients treated nonsurgically. Goal attainment scores correlated with disease specific quality of life. Patient centered outcomes should be incorporated in multicenter prospective research trials for pelvic floor disorders and in clinical practice to inform treatment plans.

Application of fibrin sealant at the urethrovesical anastomosis in robotic assisted radical prostatectomy: does it enable earlier Foley catheter and Jackson-Pratt drain removal?

Leakage at the urethrovesical anastomosis in the post-operative period can result in morbidity including ileus. We examined the effectiveness of using a fibrin sealant at the anastomosis to limit urine leakage thereby facilitating earlier Jackson-Pratt drain and Foley catheter removal following robotic assisted laparoscopic prostatectomy (RALRP). Forty consecutive patients underwent RALRP by one surgeon at our institution. The first 20 patients underwent standard operation and served as the control group. The subsequent 20 patients underwent the same operation with addition of fibrin sealant following a running absorbable sutured urethrovesical anastomosis. The two groups were compared for age (60.5 vs. 58.2 years), pre-operative PSA (5.23 vs. 4.71), Gleason score (6.3 vs. 6.5), stage at resection, and prostate size at resection (51.7 vs. 47.7 g). Wilcoxon rank sum test determined no statistically significant differences in the groups. Patients in the fibrin sealant group had 1.3 versus 2.1 days with a Jackson-Pratt drain, 9.75 versus 12.1 days with a catheter, and an average of 38.6 versus 63.2 cc of drainage per shift. Catheters were removed when a cystogram demonstrated no extravasation of contrast. Two patients in the control group and no patients in the fibrin sealant group had large-volume leakage and ileus post-operatively. In patients undergoing RALRP, application of fibrin sealant at the urethrovesical anastomosis appears to facilitate sealing, thereby allowing earlier removal of the JP drain, by 0.8 days, and the Foley catheter, by 2.35 days, than in controls. No patients in the fibrin sealant group suffered post-operative ileus. This adjunct may be especially useful early in the learning process to reduce morbidity.

Tadalafil increases Akt and extracellular signal-regulated kinase 1/2 activation, and prevents apoptotic cell death in the penis following denervation.

PURPOSE: Despite techniques to preserve the cavernous nerves during radical prostatectomy erectile dysfunction remains a complication. We determined whether bilateral cavernous nerve resection induces apoptosis in the penis. We also determined whether treatment with the phosphodiesterase-5 inhibitor tadalafil prevents apoptosis as well as the specific mechanisms involved. MATERIALS AND METHODS: Mice were subjected to cavernous nerve resection or sham surgery. Penises were processed for the identification of apoptotic cells, changes in phosphorylation of several protein kinases and immunolocalization of specific kinases. Mice were also placed on tadalafil or vehicle after cavernous nerve resection and the penises were processed as described. Statistical analysis was performed with the Mann-Whitney U test for comparisons among groups or Student's t test. RESULTS: An increase in apoptotic cavernous smooth muscle and endothelial cells was evident by 2 weeks, which further increased 4 and 6 weeks after cavernous nerve resection. Apoptosis coincided with an increase in the phosphorylation of c-jun N-terminal kinase and p38 mitogen activated protein kinase. Phospho-c-jun N-terminal kinase was immunolocalized to endothelial and smooth muscle cells. Treatment with tadalafil decreased the number of apoptotic cells and increased the phosphorylation of the 2 survival associated kinases Akt and extracellular signal-regulated kinase 1/2. CONCLUSIONS: These results provide a rationale for the early use of phosphodiesterase-5 inhibition following radical prostatectomy or extensive pelvic surgery, during which there may be injury to the cavernous nerves, to aid in the return of erectile function.

Pharmacologic management of painful bladder syndrome/interstitial cystitis: a systematic review.

BACKGROUND: More than 180 different types of therapy have been used in the treatment and management of painful bladder syndrome/interstitial cystitis (PBS/IC), yet evidence from clinical trials remains inconclusive. This study aimed to evaluate the efficacy of pharmacologic approaches to PBS/IC, to quantify the effect size from randomized controlled trials, and to begin to inform a clinical consensus of treatment efficacy for PBS/IC. METHODS: We identified randomized controlled trials for the pharmacologic treatment of patients with PBS/IC diagnosed on the basis of National Institute of Diabetes and Digestive and Kidney Diseases or operational criteria. Study limitations include considerable patient heterogeneity as well as variability in the definition of symptoms and in outcome assessment. RESULTS: We included a total of 1470 adult patients from 21 randomized controlled trials. Only trials for pentosan polysulfate sodium had sufficient numbers to allow a pooled analysis of effect. According to a random-effects model, the pooled estimate of the effect of pentosan polysulfate therapy suggested benefit, with a relative risk of 1.78 for patient-reported improvement in symptoms (95% confidence interval, 1.34-2.35). This result was not heterogeneous (P = .47) and was without evidence of publication bias (P = .18). Current evidence also suggests the efficacy of dimethyl sulfoxide and amitryptyline therapy. Hydroxyzine, intravesical bacille Calmette-Guérin, and resiniferatoxin therapy failed to demonstrate efficacy, but evidence was inconclusive owing to methodological limitations. CONCLUSIONS: Pentosan polysulfate may be modestly beneficial for symptoms of PBS/IC. There is insufficient evidence for other pharmacologic treatments. A consensus on standardized outcome measures is urgently needed.

Fiberoptic imaging of cavernous nerves in vivo.

PURPOSE: A critical intraoperative variable for the return of tumescence following radical prostatectomy is preservation of the cavernous nerves. We developed a nontoxic technique that would allow high resolution, in vivo real-time imaging specifically of the cavernous nerves. MATERIALS AND METHODS: The cavernous nerves were labeled by injecting a fluorescent retrograde nerve tracer into the corpus cavernosum of male rats. Nerves were subsequently imaged in vivo using fiberoptic confocal fluorescent microscopy. Initial screening trials were performed to decide on a nerve tracer capable of axonal labeling, optimize injection concentration and characterize retrograde transport time. Toxicity studies included intracavernous pressure monitoring following electrical nerve stimulation, apoptotic staining of injected cavernous tissue and measurement of lipid peroxidation in nerves exposed to laser emissions during imaging. RESULTS: In vivo real-time video sequences of fluorescently labeled cavernous nerves were recorded. The screening trial indicated that the B subunit of cholera toxin conjugated to AlexaFluor 488 (Invitrogen) provided optimal imaging after 9 days of retrograde transport. Toxicity studies showed that maximal intracavernous pressure responses did not differ between labeled and unlabeled nerves (p = 0.9671). Tracer injection did not increase apoptosis in cavernous tissue and laser exposure did not increase lipid peroxidation in nerves. CONCLUSIONS: In vivo real-time imaging of the cavernous nerves is possible with no measurable toxicity, allowing the maintenance of erection. This novel imaging modality may allow urologists to identify cavernous nerves during pelvic surgery.

Duloxetine compared with placebo for treating women with symptoms of overactive bladder.

OBJECTIVE: To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model. PATIENTS AND METHODS: In all, 306 women (aged 21-84 years) were recruited and randomly assigned to placebo (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks; 153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge urinary incontinence (UI) for > or =3 months. Participants were also required to have a mean daytime voiding interval (VI) of < or=2 h and urodynamic observations of either detrusor overactivity (DOA) or urgency which limited bladder capacity to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared the treatment effects on mean change from baseline to endpoint in the mean number of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety was assessed with vital signs, adverse event reporting, routine laboratory testing, electrocardiogram, and the measurement of postvoid residual urine volumes (PVR). RESULTS: Patients randomized to duloxetine had significant improvements over those randomized to placebo for decreases in VE and IE, for increases in the daytime VI, and for improvements in I-QOL scores at both doses of duloxetine. Urodynamic studies showed no significant increases in maximum cystometric capacity or in the volume threshold for DOA. The most common treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%; dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same as those reported by women with SUI and were significantly more common with duloxetine than placebo. Laboratory assessments, vital signs and electrocardiograms were stable relative to baseline, with no relevant differences detected between groups. There was a significant difference in the change in PVR with duloxetine (<5 mL mean increase) but no patient reported hesitancy or retention. CONCLUSION: In this trial, duloxetine was better than placebo for treating women with 'wet' and 'dry' symptoms of OAB associated with DOA or a bladder capacity of <400 mL.