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Purpose/Objective: The primary objective of this FDA study is to evaluate the safety and efficacy of the ACT device (Adjustable Continence Therapy) in the treatment of female recurrent Stress Urinary Incontinence (SUI). The secondary objective is to evaluate the difficulty of placement and aspects of device adjustability. Materials and Methods: The Adjustable Continence Therapy (ACT) system (Uromedica, Inc., Plymouth, MN) consists of two silicone balloons providing urethral coaption and bladder neck support. Each balloon is attached to a titanium port buried in the labia allowing for post-operative adjustment of volume. Females with recurrent SUI with or without urethral hypermobility were evaluated at baseline and follow-up periods of 6 weeks, 3, 6, 9, 12 months and annually thereafter including urinalysis, a 3-day voiding diary, provocative pad weight test, direct visual stress test, Stamey score and validated questionnaires to assess severity of incontinence, voiding dysfunction, sexual function and quality of life. Results: During a 5 years period (2002-2007), 162 patients were implanted (mean age 67.6, range 31 - 94 years). Of these 162 patients 142, 90, 80, 56 and 31 patients completed the 1, 2, 3, 4 and 5 years follow-up respectively. One hundred and thirty five (83%) had failed at least one surgery for incontinence and 44% had failed 2 or more procedures prior to ACT implantation. Difficulty of ACT placement was rated mild in 62%, moderate in 30% and severe in 9%. Improvement in Stamey score of >1 grade was achieved in 75% (107/142) at 1 year, 76% (68/90) at 2 years, 86% (62/78) at 3 years, 93% (50/54) at 4 years and 83% (25/30) at 5 years. Dry rate (provocative pad weight 2 gms) was 51%, 62% , 76%, 76% and 76% at 1 through 5 years, and >50% improvement was achieved in 83%, 86%, 86%, 90% and 93%,respectively. IQoL improved from 37 at baseline to 71, 71, 75, 77 and 74 during the study, and optimal continence was achieved with a mean of 4 adjustments, and mean balloon volumes of 4.0 ml (1.0 - 11.5 ml). Complications including bladder perforation, erosion, migration, pain and urinary retention were reported in 25% (38/155) at 12 months, and 9% (10/109), 3% (3/91) , 6% (5/79) and 4% (3/69) respectively, and of these, the majority were mild to moderate. At 5 years, 33 patients had undergone permanent explants of both devices, 48 were lost to follow-up and 6 had died of unrelated causes. Conclusions: Five years data suggest that ACT is, a safe and effective, minimally invasive treatment for recurrent SUI, which is easy to place and adjust to optimize urinary control without impairing bladder emptying.

Testosterone deficiency and prostate cancer have an increasing prevalence with age. However, because of the relationship between prostate cancer and androgen receptor activation, testosterone therapy among patients with known prostate cancer has been approached with caution.We identified a cohort of 82 hypogonadal men with prostate cancer who were treated with testosterone therapy. They included 50 men treated with radiation therapy, 22 treated with radical prostatectomy, 8 on active surveillance, 1 treated with cryotherapy and 1 who underwent high intensity focused ultrasound. We monitored prostate specific antigen, testosterone, hemoglobin, biochemical recurrence and prostate specific antigen velocity.Median patient age was 75.5 years and median followup was 41 months. We found an increase in testosterone (p0.001) and prostate specific antigen (p = 0.001) in the entire cohort. Prostate specific antigen increased in patients on active surveillance. However, no patients were upgraded to higher Gleason score on subsequent biopsies and none have yet gone on to definitive treatment. We did not note any biochemical recurrence among patients treated with radical prostatectomy but 3 (6%) treated with radiation therapy experienced biochemical recurrence. It is unclear whether these cases were related to testosterone therapy or reflected the natural biology of the disease. We calculated mean prostate specific antigen velocity as 0.001, 0.12 and 1.1 μg/l per year in the radical prostatectomy, radiation therapy and active surveillance groups, respectively.In the absence of randomized, placebo controlled trials our study supports the hypothesis that testosterone therapy may be oncologically safe in hypogonadal men after definitive treatment or in those on active surveillance for prostate cancer.

Aims OnabotulinumtoxinA significantly reduces urinary incontinence (UI) and improves bladder management in patients with neurogenic detrusor overactivity (NDO). We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes (PROs) in patients with UI due to NDO in a double-blind, placebo-controlled study. Methods Patients with UI due to NDO (from multiple sclerosis or spinal cord injury) were randomized to intradetrusor placebo (n = 92) or onabotulinumtoxinA 200 U (n = 92) or 300 U (n = 91). PROs included Incontinence Quality of Life (I-QOL) Questionnaire to assess health-related quality of life (HRQoL), the 16-item modified Overactive Bladder-Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ) to assess treatment satisfaction, and Patient Global Assessment to assess treatment goal achievement. Results Mean improvement in I-QOL total score at weeks 6 and 12 was significantly greater with both onabotulinumtoxinA 200 U and 300 U versus placebo (Δ12.3 for 200 U and Δ14.9 for 300 U vs. placebo; P

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Phosphodiesterase type-5 (PDE5) inhibitors (tadalafil, vardenafil, and sildenafil) are well-known treatment options for men with erectile dysfunction and should be taken before anticipated sexual activity. Tadalafil is also approved for once daily use in men with erectile dysfunction. Recent 12-week studies in men with benign prostatic hyperplasia (BPH) have shown once daily use of tadalafil significantly reduced their urinary symptoms. This article is the first to report the long-term safety and maintenance of efficacy for once-daily use of tadalafil in men with urinary symptoms secondary to BPH. OBJECTIVE • To evaluate the 1-year safety of 5 mg of tadalafil once daily in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS); efficacy measures were included to evaluate the maintenance of efficacy after an additional year of treatment. PATIENTS AND METHODS • In total, 427 men who completed a 12-week, placebo-controlled, dose- finding study assessing once-daily tadalafil (2.5, 5, 10 or 20 mg) or placebo elected to continue into the open-label extension period. Safety and efficacy parameters were assessed after 1 month and every 3 months. RESULTS • In total, 299 patients (69.9%) completed the 1-year, open-label extension period. Treatment-emergent adverse events (TEAEs) were reported by 57.6% of patients, with most TEAEs being mild (44%) or moderate (45%) in severity; the most common TEAEs (≥2%) were dyspepsia, gastro-oesophageal reflux disease, back pain, headache, sinusitis, hypertension and cough. Twenty-two patients (5.2%) discontinued as a result of AEs. During the open-label extension period, mean prostate-specific antigen increased from 1.6 ± 1.3 ng/mL to 1.8 ± 1.4 ng/mL. • Mean post-void residual volume was 61.1 ± 60.4 mL at study entry and 42.2 ± 64.1 mL after the open-label extension period. Changes in the total International Prostate Symptom Score (IPSS), IPSS irritative and obstructive subscores, IPSS health-related quality of life and BPH Impact Index were maintained after 1 year. In sexually-active patients with erectile dysfunction, improvements in the International Index of Erectile Function–Erectile Function domain were maintained after 1 year. CONCLUSION • In men with BPH-LUTS, 5 mg of tadalafil once daily during 1 year of treatment was well tolerated and efficacy changes were maintained.

Overactive bladder (OAB) is a common condition whose prevalence increases with age. Antimuscarinic agents are the pharmacologic treatment of choice, but adverse events such as dry mouth may lead to early discontinuation. The purpose of this analysis was to compare the incidence and severity of dry mouth and other adverse events with solifenacin 5 mg/day and oxybutynin immediate release (IR) 15 mg/day in patients ≤ 65 years and65 years in the Canadian VECTOR study (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients).VECTOR was a randomized, multicentre, prospective, double-blind, double-dummy study in 132 subjects with ≥ 1 urgency episode per 24 h, with or without urgency incontinence, and ≥ 8 micturitions per 24 h for ≥ 3 months. After a 2-week washout, patients received solifenacin 5 mg once daily or oxybutynin IR 5 mg tid for 8 weeks. For the current post-hoc analysis, adverse events were evaluated in subgroups of patients ≤ 65 years and65 years, using a full logistic regression model, multinomial logit regression model and reduced model.NCT00431041.The incidence and severity of dry mouth and other adverse events with solifenacin were similar between younger and older patients. In both age subgroups, solifenacin 5 mg/day was associated with fewer episodes and lower severity of dry mouth, and a lower discontinuation rate, compared with oxybutynin IR 15 mg/day.Solifenacin 5 mg/day was better tolerated than oxybutynin IR 15 mg/day in younger (≤ 65 years) and older (65 years) subgroups. Solifenacin was equally well tolerated in both age subgroups. Limitations of the analysis were that the study was not preplanned to perform post-hoc subgroup analysis, patients knew that dry mouth was a primary outcome, and the study used fixed doses of each drug.

Although antimuscarinic treatment is indicated for overactive bladder, many patients discontinue it because of dry mouth. Of available antimuscarinics oxybutynin is associated with the highest dry mouth rate. We compared the safety and tolerability of 5 mg solifenacin vs 15 mg oxybutynin immediate release.At 12 Canadian centers a total of 132 patients with overactive bladder symptoms (greater than 1 urgency episode per 24 hours, and 8 or greater micturitions per 24 hours) were randomized to 5 mg solifenacin once daily or 5 mg oxybutynin 3 times daily for 8 weeks. The primary end point was the incidence and severity of dry mouth reported after direct questioning. Efficacy end points (3-day diary documented changes in urgency, frequency, incontinence, nocturia and voided volume), and changes on the Patient Perception of Bladder Condition scale and the Overactive Bladder Questionnaire were evaluated secondarily.Of patients on solifenacin vs oxybutynin immediate release 35% vs 83% reported dry mouth (p0.0001). Of patients reporting dry mouth severity was graded moderate by 13% and 42% of those on solifenacin and oxybutynin immediate release, and severe by 13% and 28%, respectively (p = 0.001). Patients in each group showed improvements in efficacy end points, and Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire scores from baseline to treatment end.Significantly fewer patients on 5 mg solifenacin once daily reported dry mouth vs those receiving 5 mg oxybutynin immediate release 3 times daily. Significantly fewer patients on solifenacin reported moderate/severe dry mouth. Significantly fewer patients on solifenacin withdrew from study due to dry mouth and there were significantly fewer overall adverse events. Solifenacin and oxybutynin immediate release were efficacious in decreasing efficacy end points, and improved Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire results from baseline to treatment end.

We determined the efficacy, safety, adjustability and technical feasibility of the adjustable continence therapy device (Uromedica, Plymouth, Minnesota) for the treatment of recurrent female stress urinary incontinence.Female patients with recurrent stress urinary incontinence were enrolled in the study and a defined set of exclusionary criteria were followed. Baseline and regular followup tests to determine eligibility, and to measure subjective and objective improvement were performed. A trocar was passed fluoroscopically and with digital vaginal guidance to the urethrovesical junction through small incisions between the labia majora and minora. The adjustable continence therapy device was delivered and the balloons were filled with isotonic contrast. The injection ports for balloon inflation were placed in a subcutaneous pocket in each labia majora. Device adjustments were performed percutaneously in the clinic postoperatively. An approved investigational device exemption Food and Drug Administration protocol was followed to record all adverse events.A total of 162 subjects underwent implantation with 1 year of data available on 140. Mean Stamey score improved by 1 grade or more in 76.4% (107 of 140) of subjects. Improvement in the mean incontinence quality of life questionnaire score was noted at 36.5 to 70.7 (p0.001). Reductions in mean Urogenital Distress Inventory (60.3 to 33.4) and Incontinence Impact Questionnaire (54.4 to 23.4) scores also occurred (p0.001). Mean provocative pad weight decreased from 49.6 to 11.2 gm (p0.001). Of the patients 52% (67 of 130) were dry at 1 year (less than 2 gm on provocative pad weight testing) and 80% (102 of 126) were improved (greater than 50% reduction on provocative pad weight testing). Complications occurred in 24.4% (38 of 156) of patients. Explantation was required in 18.3% (28 of 153) of the patients during 1 year. In terms of the complications 96.0% were considered to be mild or moderate.The Uromedica adjustable continence therapy device is an effective, simple, safe and minimally invasive treatment for recurrent female stress urinary incontinence. It can be easily adjusted percutaneously to enhance efficacy and complications are usually easily manageable. Explantation does not preclude later repeat implantation.

To report pre-specified and exploratory results on the effect of different surgical approaches on erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) obtained from the multicentre, randomised, double-blind, double-dummy REACTT trial of tadalafil (once a day [OaD] or on-demand [pro-re-nata, PRN]) vs placebo.Patients aged68 years with normal preoperative EF who underwent nsRP for localised prostate cancer (Gleason ≤7, prostate-specific antigen [PSA]10 ng/mL) were randomised after nsRP 1:1:1 to 9-month double-blind treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN, or placebo, followed by 6-week drug-free washout, and 3-month open-label OaD treatment (all patients). Recovery of EF was defined as an International Index of Erectile Function (IIEF)-EF domain score of ≥22 and normal orgasmic function was defined based on IIEF Question 10. Both parameters were analysed at the end of washout using logistic regression including terms for treatment, country, visit, visit-by-treatment interaction, age group, nerve-sparing score (perfect = 2, non-perfect2), and surgical approach (open surgery, robot-assisted laparoscopy, conventional laparoscopy, other). Time to EF recovery was analysed post hoc with a Cox proportional-hazards model including terms for treatment, age-group, country, surgical approach and surgery-by-treatment interaction.Of 422 patients treated, 189 underwent open surgery, 115 robot-assisted laparoscopy, 88 conventional laparoscopy and 30 surgery classified as 'other'. The odds of achieving EF recovery at the end of drug-free washout were about twice as high for the robot-assisted laparoscopy group compared with the open surgery group (odds ratio 2.42; 95% confidence interval [CI] 1.24, 4.72; P = 0.029). Patients who underwent robot-assisted laparoscopy were significantly more likely to recover during double-blind treatment compared with patients who underwent open surgery (hazard ratio 1.92; 95% CI 1.17, 3.15; P = 0.010). No favourable effect of conventional laparoscopy compared with open surgery could be seen.These results may provide further insights into the role of surgery on EF recovery after nsRP. However, the trial was not designed for these analyses and further prospective studies are needed.

This study explored the efficacy of vardenafil in men with erectile dysfunction (ED) when taken 8 hours before sexual intercourse.A 10-week, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of vardenafil (5, 10 or 20mg) was conducted in men with ED for6 months who failedor=50% of intercourse attempts during a 4-week treatment-free run-in period. Sexual Encounter Profile Question 3 (SEP3) was the primary efficacy measure; secondary measures included SEP2, International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, Global Assessment Question (GAQ), Global Confidence Question (GCQ) and Erection Quality Scale (EQS). Adverse-event and safety monitoring were conducted throughout.383 patients were randomized to vardenafil (n=194) or placebo (n=189). Patients treated with vardenafil 8 hours before sexual activity achieved clinically meaningful (or=18%) and statistically significantly greater least-squares mean per-patient SEP3 and SEP2 success rates over weeks 2-10, compared with patients receiving placebo (SEP3 69% vs 34%; SEP2 81% vs 51%; both p0.001). SEP3 and SEP2 measures demonstrated the significant superiority of vardenafil over placebo from week 2 onwards (p0.001). Measurements of IIEF-EF domain score, GAQ, GCQ and EQS showed that vardenafil led to significantly greater improvements in erectile function, compared with placebo (all p0.001). Vardenafil was generally well tolerated.The extended duration of efficacy of vardenafil up to 8 hours postdose may provide couples with more flexibility in their sexual life than anticipated.

Introduction There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED). Aim One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners’ sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment. Methods A randomized, double‐blind, placebo‐controlled, multi‐institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED >6 months and untreated woman partner). Co‐primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ‐QOL) (untreated woman partner). Main Outcome Measures Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF‐EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ‐QOL and Female Sexual Function Index (FSFI). Results Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per‐treated male SEP3 success rate, IIEF‐EF, and EQS; and (ii) mSLQQ‐QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment‐related improvement in erectile function as assessed by IIEF‐EF and EQS was correlated reliably with improvement in women partners’ FSFI total and individual domain scores. Conclusions Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners’ sexual function improvements relate significantly and consistently to treatment‐related improvements in men's erectile function. ED management should emphasize both members of the couple. Goldstein I, Fisher WA, Sand M, Rosen RC, Mollen M, Brock G, Karlin G, Pommerville P, Bangerter K, Bandel T‐J, and Derogatis LR for the Vardenafil Study Group. Women's sexual function improves when partners are administered vardenafil for erectile dysfunction: a prospective, randomized, double‐blind, placebo‐controlled trial. J Sex Med 2005;2:819–832.

Introduction Erectile dysfunction (ED) has a dual negative impact on men and their female partners; both are likely to face a drop in sexual quality of life and challenges to their intimate relationship as couples’ sexual activities are curtailed by the loss of erectile function. Aim The primary objective of this study was to compare the efficacy of vardenafil vs. placebo in terms of success of maintenance of erection in men with ED and improvement of their female partner's sexual quality of life. Methods This was a randomized, double‐blind, multicenter, flexible‐dose, parallel‐group comparison of vardenafil vs. placebo for 12 weeks in men (≥18 years) with ED of ≥ 6 months duration, and their female partners. Main Outcome Measures Changes in patient's overall response rate to Sexual Encounter Profile question 3 (SEP3) “Did your erection last long enough for you to have sexual intercourse?” and female partner's response to the quality of life domain of the modified Sexual Life Quality Questionnaire (mSLQQ‐QOL) at last observation carried forward (LOCF) were considered the primary efficacy measures. In addition, patient's response to SEP2 “Were you able to insert your penis into your partner's vagina?,” the erectile function domain of the International Index of Erectile Function (IIEF‐EF) and patient's mSLQQ‐QOL score were also assessed. Results Compared with placebo, vardenafil significantly improved overall least square (LS) mean per‐patient SEP3 success rate (28% vs. 68%; P P P P P Conclusions Vardenafil improved erectile function in men with ED and improved the sexual quality of life of the couple. Fisher WA, Rosen RC, Mollen M, Brock G, Karlin G, Pommerville P, Goldstein I, Bangerter K, Bandel T‐J, Derogatis LR, and Sand M for the Vardenafil Study Group. Improving the sexual quality of life of couples affected by erectile dysfunction: a double‐blind, randomized, placebo‐controlled trial of vardenafil. J Sex Med 2005;2:699–708.

Intravesical instillation of Bacillus Calmette-Guerin (BCG) is the most commonly used immunotherapeutic adjuvant therapy for superficial bladder carcinoma. BCG is a live attenuated vaccine of Mycobacterium bovus which has been shown to decrease tumor recurrence rate, delay tumor progression, and improve overall survival. Intravesical BCG is well tolerated, with a complication rate under 5%. A literature review revealed tuberculous epididymitis to be a rare adverse event following intravesical BCG therapy. We report the case of an 82-year-old male undergoing BCG therapy for superficial transitional cell carcinoma of the bladder who presented with a painless right testicular mass. The patient had no previous history of tuberculosis. He successfully underwent a right orchiectomy and histopathology confirmed M. bovis as the etiological agent.

Introduction: Testosterone deficiency syndrome (TDS) has been shown to be an independent cardiovascular risk factor and a predisposing factor for metabolic syndrome. As general practitioners and cardiologists primarily care for these patients, we sought to assess their knowledge, beliefs and practice patterns with respect to TDS and cardiac health.Methods: We distributed a questionnaire to all 20 cardiologists and a cohort of 128 family practitioners in Victoria, British Columbia. Of the 13 questions, 10 assessed knowledge and beliefs on TDS and 3 assessed current practice patterns.Results: Most respondents believed that TDS is a medical condition (66.7%) and could negatively affect body composition (62%), buta similar majority was unsure whether it was a cardiac risk factor (66.7%). While most believed that testosterone replacement therapy (TRT) could improve exercise tolerance (62%), most were unsure if it was beneficial in cardiac patients. Cardiologists were significantly less likely to believe that TRT was beneficial in preventing recurrent myocardial infarction and improving myocardial perfusion (p = 0.0133, 0.00186, respectively). The vast majority (88%) did not screen cardiac patients for TDS. If a patient was identified as having TDS, only 10% of those surveyed would refer these patients to a urologist.Conclusion: Despite its prevalence in cardiac patients, TDS is not well-understood by general practitioners and cardiologists; they lack knowledge on its deleterious cardiovascular effects. In their role as men’s health advocates, urologists should educate our colleagues regarding the correlation between TDS and cardiovascular mortality and risk factors. Limitations of this study include small sample size and restricted geographic scope.

Scrotal elephantiasis is a condition rarely encountered in developed nations. It is endemic in tropical regions due to the presence of filariasis (Wucheria bancrofti). We report 2 cases of idiopathic scrotal elephantiasis in Canadian citizens with no history of travel to endemic filariasis regions, malignancy, surgery or radiation. Both patients underwent complete excision of the involved tissue with reconstruction. We found that for advanced cases of scrotal lymphedema, surgery is currently the only solution. In our cases of advanced idiopathic disease, surgical treatment combining the expertise of a plastic surgeon and a urologist provided a successful functional and cosmetic result.

Objectives Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) has clinical and perhaps etiologic characteristics similar to interstitial cystitis. Pentosan polysulfate sodium (PPS), an oral medication indicated for the treatment of interstitial cystitis, has shown moderate benefit in reducing chronic pelvic pain and voiding symptoms in patients with interstitial cystitis. We undertook a prospective open-label, multicenter Phase II pilot study to examine the potential efficacy of PPS in the treatment of CPPS in men, using outcome tools validated for CPPS in men. Methods Patients with a diagnosis consistent with National Institutes of Health (NIH) CPPS category IIIA (inflammatory) were treated with PPS, 100 mg three times daily, for 6 months. The evaluation at baseline, 3 months, and 6 months consisted of the Symptom Severity Index, a Symptom Frequency Questionnaire, the NIH-Chronic Prostatitis Symptom Pain Index (NIH-CPSI), a quality-of-life assessment, and a subjective global assessment. Results Thirty-two patients (mean age 45.5 +/- 11 years; duration of symptoms 9.2 +/- 12 years) were enrolled in five centers; 28 patients were available for evaluation. Seven patients experienced drug-related side effects, including hair loss (n = 2), headache (n = 2), mild nausea (n = 1), mild weight gain (n = 1), and skin flushing (n = 1). The decrease in frequency (Symptom Frequency Questionnaire 28.1 to 17.9), severity (Symptom Severity Index 53.6 to 36.3), and combined location/frequency/severity of pain (NIH-CPSI pain 14.5 to 9.2) symptom scores at 6 months compared with baseline was significant. The decrease was associated with a significant improvement in patients' quality of life (quality-of-life assessment 5.3 to 3.8). Forty-three percent of the patients had a greater than 50% improvement in the Symptom Frequency Questionnaire, Symptom Severity Index, and NIH-CPSI (rated as clinically significant improvement). At 6 months, mild, moderate, and marked improvement was noted (subjective global assessment) by 33%, 19%, and 15% of the patients, respectively. Conclusions PPS is well tolerated and appears to have efficacy in reducing the severity and frequency of general symptoms, reducing specific pain symptoms, and improving the quality of life in many male patients with CPPS. The results of this study justify the initiation of a randomized controlled trial comparing the safety and efficacy of PPS to placebo.

Introduction: We sought to understand the contemporary pharmacologic management of overactive bladder (OAB) in a single-payer system. We examined temporal trends in the use of anticholinergicmedications and assessed whether the likelihood of patients changing their anticholinergic therapy was predicted by their current therapy.Methods: We conducted a retrospective, population-based analysis of prescription records from the PharmaNet database in BC, Canada. We identified patients treated with one or more anticholinergicprescriptions between 2001 and 2009. We characterized temporal trends in the use of anticholinergic medications. We used generalized estimating equations with a logit wing to assess the relationship between the type of anticholinergic medication and the change in prescription.Results: The 114 325 included patients filled 1 140 296 anticholinergic prescriptions. The number of prescriptions each year increased over the study, both in aggregate and for each individual medication. While oxybutynin was the most commonly prescribed medication (68% of all prescriptions), the proportion of newer anticholinergics (solifenacin, darifenacin, and trospium) prescribed increased over time (pConclusions: There are an increasing number of anticholinergic prescriptions being filled annually. Patients taking newer anticholinergics are at least as likely to change therapy as those takingoxybutynin. The reimbursement environment in BC likely affects these results. Restrictions in the available data limit assessment of other relevant predictors.

We conducted a safety and efficacy evaluation of intraprostatic injection of PRX302, a modified pore forming protein (proaerolysin) activated by prostate specific antigen, as a highly targeted, localized approach to treat lower urinary tract symptoms due to benign prostatic hyperplasia.A total of 92 patients with I-PSS (International Prostate Symptom Score) 15 or greater, peak urine flow 12 ml or less per second and prostate volume 30 to 100 ml were randomized 2:1 to a single ultrasound guided intraprostatic injection of PRX302 vs vehicle (placebo) in this phase IIb double-blind study. Injection was 20% of prostate volume and 0.6 μg PRX302 per gm prostate. Peak urine flow was determined by a blinded reviewer. Benign prostatic hyperplasia medications were prohibited. The primary data set of efficacy evaluable patients (73) was analyzed using last observation carried forward.PRX302 treatment resulted in an approximate 9-point reduction in I-PSS and 3 ml per second increase in peak urine flow that were statistically significant changes from baseline compared to vehicle. Efficacy was sustained for 12 months. Early withdrawal for other benign prostatic hyperplasia treatment was more common for patients in the vehicle group. Relative to vehicle, PRX302 apparent toxicity was mild, transient, and limited to local discomfort/pain and irritative urinary symptoms occurring in the first few days, with no effect on erectile function.A single administration of PRX302 as a short, outpatient based procedure was well tolerated in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. PRX302 produced clinically meaningful and statistically significant improvement in patient subjective (I-PSS) and quantitative objective (peak urine flow) measures sustained for 12 months. The side effect profile is favorable with most effects attributed to the injection itself and not related to drug toxicity.

OnabotulinumtoxinA significantly reduces urinary incontinence (UI) and improves bladder management in patients with neurogenic detrusor overactivity (NDO). We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes (PROs) in patients with UI due to NDO in a double-blind, placebo-controlled study.Patients with UI due to NDO (from multiple sclerosis or spinal cord injury) were randomized to intradetrusor placebo (n = 92) or onabotulinumtoxinA 200 U (n = 92) or 300 U (n = 91). PROs included Incontinence Quality of Life (I-QOL) Questionnaire to assess health-related quality of life (HRQoL), the 16-item modified Overactive Bladder-Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ) to assess treatment satisfaction, and Patient Global Assessment to assess treatment goal achievement.Mean improvement in I-QOL total score at weeks 6 and 12 was significantly greater with both onabotulinumtoxinA 200 U and 300 U versus placebo (Δ12.3 for 200 U and Δ14.9 for 300 U vs. placebo; P 0.001), and was clinically meaningful. For those patients who completed the OAB-PSTQ, improvement in satisfaction at weeks 6 and 12 was significantly greater for onabotulinumtoxinA versus placebo (P 0.001, all comparisons). At 6 weeks, greater proportions of onabotulinumtoxinA-treated patients than placebo reported being somewhat or very satisfied (200 U, 77.5% and 300 U, 67.8% vs. placebo, 39.5%), and significant progress toward or complete achievement of primary treatment goal (200 U, 62.9% and 300 U, 61.6% vs. placebo, 16.5%).NDO patients treated with onabotulinumtoxinA 200 or 300 U had significantly greater improvement in HRQoL and greater treatment satisfaction compared with placebo-treated patients, with no clinically relevant differences between onabotulinumtoxinA doses.

PRX302 is a prostate specific antigen (PSA)-activated pore-forming protein toxin under development as a targeted approach for improving lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) without affecting sexual function.To evaluate the safety and efficacy of PRX302 in men with moderate to severe BPH.Eligible subjects were refractory, intolerant, or unwilling to undergo medical therapies for BPH and had International Prostate Symptom Score (IPSS) ≥12, a quality of life (QoL) score ≥3, and prostate volumes between 30 and 80 g. Fifteen patients were enrolled in phase 1 studies, and 18 patients entered phase 2 studies.Subjects received intraprostatic injection of PRX302 into the right and left transition zone via a transperineal approach in an office-based setting. Phase 1 subjects received increasing concentrations of PRX302 at a fixed volume; phase 2 subjects received increasing volumes per deposit at a fixed concentration.IPSS, QoL, prostate volume, maximum flow rate (Q(max)), International Index of Erectile Function, serum PSA levels, pharmacokinetics, and adverse events were recorded at 30, 60, 90, 180, 270, and 360 d after treatment with PRX302.Sixty percent of men in the phase 1 study and 64% of men in the phase 2 study treated with PRX302 had ≥30% improvement compared to baseline in IPSS out to day 360. Patients also experienced improvement in QoL and reduction in prostate volume out to day 360. Patients receiving ≥1 ml of PRX302 per deposit had the best response overall. PRX302 had no deleterious effect on erectile function. Adverse events were mild to moderate and transient in nature. The major study limitation was the small sample size.The promising safety profile and evidence of efficacy in the majority of treated subjects in these phase 1 and 2 studies supports further development of PRX302 as a minimally invasive, targeted treatment for BPH.

Treatment of recurrent stress incontinence after a failed surgical procedure is more complicated, and repeat surgeries have higher rates of complications and limited efficacy. We determined the technical feasibility, efficacy, adjustability, and safety of adjustable continence therapy device for treatment of moderate to severe recurrent urinary incontinence after failed surgical procedure. Female patients with moderate to severe recurrent stress urinary incontinence who had at least one prior surgical procedure for incontinence were enrolled. All patients underwent percutaneous placement of adjustable continence therapy (ACT) device (Uromedica, Plymouth, Minnesota). Baseline and regular follow-up tests to determine subjective and objective improvement were performed. A total of 89 patients have undergone implantation with 1–3 years of follow-up. Data are available on 77 patients at 1 year. Of the patients, 47% were dry at 1 year and 92% improved after 1-year follow-up. Stamey score improved from 2.25 to 0.94 at 1 year (P

Introduction Studies evaluating the effect of education on treatment success with phosphodiesterase type 5 (PDE5) inhibitor therapy in men with erectile dysfunction (ED) are limited. Additional education of the primary care physician (PCP) and the patient are thought to optimize the treatment of ED. Aim To assess the impact of education of the PCP or of the patient in the treatment of ED with vardenafil relative to usual care. Methods In this 12-week, open-label, multicenter, factorial-designed, cluster-randomized Canadian study, 1,029 patients with ED were enrolled into four different education groups: usual care, patient education, PCP education, and both PCP and patient education. All groups started on vardenafil 10 mg, with the option to titrate at weeks 4 and 8. Main Outcome Measures The primary efficacy measure was the difference at week 4 last observation carried forward (LOCF) in the overall improvement in erectile function (EF) as measured by the Global Assessment Question (GAQ), while on background vardenafil, between those receiving education vs. those who did not. Other secondary assessments included responses to diary questions regarding penetration (sexual encounter profile, SEP2) and erection maintenance (SEP3), and to questionnaires regarding treatment satisfaction (Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS]). Results A total of 956 patients were included in the intent-to-treat population. Mean baseline International Index of Erectile Function-EF domain score was 13. GAQ response rates at week 4 LOCF were high (>80%) for all groups, regardless of the education given. Mean per patient SEP2 and SEP3 rates at week 12 LOCF were 86–89% and 79–83%, respectively. In an exploratory analysis, a positive relationship between GAQ responses and EDITS scores was observed ( P ≤ 0.0007). Vardenafil was generally well tolerated. Conclusions In men with moderate ED, vardenafil led to high success rates and satisfaction regardless of the education given. The benefits of education for PCP and patients in Canada were possibly masked by a ceiling effect in this study population. Brock G, Carrier S, Alarie P, Pommerville P, Casey R, Harris S, and Ward R. The effect of physician and patient education when combined with vardenafil treatment in Canadian males with erectile dysfunction: An open-label, factorial-designed, cluster-randomized clinical trial

Study Design. Multicenter, double-blind, placebo-controlled, parallel-group study. Objective. To assess the effect of the oral phosphodiesterase type-5 inhibitor, vardenafil, on ejaculation rates and self-confidence in men with spinal cord injury (SCI). Summary of Background Data. Spinal command of male sexual functions is often seriously impaired by traumatic spinal cord injury (SCI). A high proportion of men with SCI cannot ejaculate during sexual intercourse. SCI-related ejaculatory disorders are often responsible for male infertility. Sexual dysfunction associated with SCI can also affect men's self-confidence. Methods. In this 12-week study, 418 men aged >= 18 years with erectile dysfunction > 6 months resulting from a traumatic SCI were randomized to vardenafil (n = 207) or placebo (n = 211) 10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8. Assessments included questions of the International Index of Erectile Function (IIEF) about ejaculation success and orgasmic perception; the Global Confidence Question; and quality-of-life scales to measure psychological well-being, self-esteem, depression, and mental health status. Results. Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment (19% vs. 10%; P < 0.001). At last observation carried forward, the IIEF "orgasmic function" score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo. Sixteen percent of men receiving vardenafil and 8% receiving placebo felt orgasm "almost always" or "always" at weeks 8-12, compared with 4% and 6%, respectively, at baseline. Significant improvements in confidence scores were observed with vardenafil compared with placebo ( P < 0.0001). There were no clinically significant differences between vardenafil and placebo in the quality-of-life measures at the study endpoint, but these had been in the normal range at baseline. Conclusion. Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI.

There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED).One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners' sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment.A randomized, double-blind, placebo-controlled, multi-institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED6 months and untreated woman partner). Co-primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman partner).Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ-QOL and Female Sexual Function Index (FSFI).Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS was correlated reliably with improvement in women partners' FSFI total and individual domain scores.Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners' sexual function improvements relate significantly and consistently to treatment-related improvements in men's erectile function. ED management should emphasize both members of the couple.

Objectives To perform a Canadian multicenter randomized placebo-controlled trial to evaluate the safety and efficacy of 6 weeks of levofloxacin therapy compared with placebo in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Uncontrolled studies have supported the use of antibiotics in CP/CPPS. Methods Men with a National Institutes of Health (NIH) diagnosis of CP/CPPS (specifically, no infection localized to the prostate) were randomized to levofloxacin (500 mg/day) or placebo for 6 weeks in 11 Canadian centers. Patients were assessed at baseline and at 3, 6, and 12 weeks with the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and global patient assessments (subjective global assessment and patient assessment questionnaire). Results Eighty men (average age 56.0 years, range 36 to 78; duration of symptoms 6.5 years, range 0.6 to 32) were randomized to receive levofloxacin (n = 45) or placebo (n = 35). All were evaluated in an intent-to-treat analysis. Both groups experienced progressive improvement in symptoms as measured by the NIH-CPSI. However, the difference in response was not statistically or clinically significant at end of treatment (6 weeks) or at the end of the follow-up visits (12 weeks). No patients withdrew because of adverse events. One patient withdrew before the 6-week assessment. Adverse events (all mild) were reported in 20% of the levofloxacin group and 17% of the placebo group. Conclusions This pilot placebo-controlled study showed that 6 weeks of levofloxacin therapy in men diagnosed with CP/CPPS resulted in symptom improvement that was not significantly different from that with placebo at end of treatment or follow-up. The clinical ramifications of these findings need to be addressed.

Sexual function is a central part of a man's identity, helping to define who he is, and how he feels about himself. It is also a key determinant of relationship health. Erectile dysfunction (ED) threatens all of this, and is thus an important topic in male health. Erectile dysfunction is common around the world, especially in older men. Risk factors for ED overlap significantly with those for cardiovascular disease and endothelial dysfunction, especially diabetes.

Since the introduction of sildenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, oral therapy is first-line therapy in the management of erectile dysfunction (ED). Two new PDE-5 inhibitors are under clinical development: vardenafil and tadalafil. These new agents appear to have advantages over sildenafil in the areas of time to onset of action, period of responsiveness, side effect profile, effectiveness in difficult to treat patient populations and interaction with food. A centrally active sublingual agent recently released in Europe is effective in the treatment of mild and moderate ED. Apomorphine is a dopaminergic agonist that acts at the paraventricular nucleus in the hypothalamus. In the present article, the benefits of these emerging therapies are reviewed.

1. Abrami,L, et al(1998) The pore-forming toxin proaerolysin is activated by furin. J Biol Chem. 273, 32656-32661. 2. Williams,SA, et al. (2007) A prostate-specific antigenactivated channel-forming toxin as therapy for prostatic disease. J Natl Cancer Inst. 99, 376-385. 3. Singh,R, et all. (2007) Recombinant prostate-specific antigen proaerolysin shows selective protease sensitivity and cell cytotoxicity. Anticancer Drugs 18, 809-816. References PRX302 produced a sustained ≥ 30% improvement in IPSS in the majority of patients at Day 360. A 30% improvement in IPSS is indicative of clinically relevant response. Most of the patients (11/15) receiving ≥1mL/deposit were responders. Overall patients in each study receiving ≥ 1mL per deposit had improvements in IPSS of 10.9s point at day 90 and 10.3 points at day 360. These studies confirm the importance of volume in the efficacy of PRX302

High-flow priapism is most often seen following perineal andpenile trauma. We report the case of a 32-year-old man whopresented with recurrent idiopathic priapism initially treated aslow-flow priapism on 8 previous emergency department visits.Pelvic angiography revealed an abnormal communication betweenthe left cavernosal artery and the left corpus cavernosum andled to the diagnosis of high-flow priapism. Treatment involvedembolization of the left common penile artery, which resultedin successful resolution of the recurrent priapism. Our patient’scase highlights the importance of an appropriate work-up, includingimaging, to distinguish high- and low-flow priapism and toprovide appropriate care.Le priapisme à haut débit est le plus souvent observé après untraumatisme périnéal et pénien. Nous décrivons le cas d’un hommede 32 ans atteint de priapisme idiopathique récurrent traité audépart comme un priapisme à bas débit lors de 8 visites antérieuresau service des urgences. Une angiographie pelvienne a révéléun passage anormal entre l’artère caverneuse gauche et le corpscaverneux gauche et a mené au diagnostic de priapisme à hautdébit. Un traitement par embolisation de l’artère pénienne gauchea été réalisé, entraînant la disparition complète du priapisme récurrent.Ce cas illustre l’importance d’une analyse approfondie, notammentà l’aide d’épreuves d’imagerie, afin de distinguer les cas àhaut débit des cas à bas débit et de choisir les soins appropriés.