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Background: Persistence on-treatment with antimuscarinics in patients with overactive bladder (OAB) is reported to be sub-optimal. This retrospective, longitudinal, observational cohort study assessed treatment persistence with β 3 -adrenoceptor agonists (i.e. mirabegron) and antimuscarinics, both classes of OAB pharmacotherapy, in patients with OAB in Spain., Methods: Adults who received mirabegron or an antimuscarinic in routine clinical practice (1 June-31 October 2014), were identified from anonymised prescription data within the Spanish Cegedim Electronic Medical Records database. The primary endpoint, treatment persistence (time to treatment discontinuation [TTD] and the proportion of patients remaining on-treatment after 12 months), was unadjusted for potential confounders. Multivariate Cox regression models of persistence, adjusted for baseline characteristics, were used to compare differences in treatment groups. Adjusted subgroup analyses (target OAB drug, age, treatment status and sex) and sensitivity analyses (extending the time used to define treatment discontinuation from 30 days [base-case] to 45, 60 or 90 days without prescription renewal) were also performed., Results: Overall, 1798 patients received mirabegron (N = 1169) or an antimuscarinic (N = 629); the mean age was 66.42 years. Median TTD was longer for mirabegron versus antimuscarinics (90 vs 56 days) and a higher proportion of patients who received mirabegron were persistent after 12 months (20.2% vs 10.2%); multivariate analyses indicated significantly greater persistence with mirabegron versus antimuscarinics (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.37-1.70; p < 0.001). Significant differences were also observed in subgroup analyses of mirabegron versus individual antimuscarinics (median TTD: 90 vs [range] 28-60 days; HR range: 1.21-2.17; p ≤ 0.013) and in all other subgroups assessed (p < 0.001). Sensitivity analysis showed that the median TTD for mirabegron increased by up to 31 days, and was significantly longer versus antimuscarinics across all adjusted periods (HR range: 1.43-1.53; all p < 0.001)., Conclusions: Patients with OAB in Spain who received mirabegron experienced longer persistence on-treatment than those who received antimuscarinics and the proportion of patients persistent on-treatment at 12 months with mirabegron was two-times higher versus antimuscarinics. These data may provide strategic insights for clinicians and policy makers involved in the management of OAB.

Aims: To evaluate the therapeutic effect of TAC-302, a cyclohexenoic fatty alcohol derivative, on bladder denervation-related storage and voiding dysfunctions in rats with bladder outlet obstruction (BOO)., Methods: BOO was achieved by partial ligature of the proximal urethra in female rats. Two weeks later, BOO rats were divided into two groups and treated orally with vehicle or 10 mg/kg TAC-302 twice a day for 4 weeks. Urodynamic and immunohistochemical evaluation of the bladder muscle layer was performed. In another study, the BOO rats were treated with intravenous tamsulosin at cystometry. The detrusor contractility in each group was evaluated using the modified Shafer's nomogram., Results: Two weeks after BOO, the rats showed significant increases in non-voiding contraction (NVCs) and residual urine volume (RUV) compared to the sham group. Moreover, 6 weeks after BOO, BOO vehicle rats showed significant increases in NVCs and RUV and decreases in detrusor contractility and in the nerve fiber density in the urinary bladder compared to the sham group. BOO-induced denervation of the urinary bladder was partially improved by oral treatment with TAC-302. Oral treatment with TAC-302 significantly reduced the amplitude and frequency of NVCs (P < 0.05) and increased detrusor contractility and tended to reduce RUV compared with the BOO vehicle group. In contrast, the intravenous administration of tamsulosin significantly reduced the frequency of NVCs, but not RUV., Conclusions: TAC-302 improved storage and voiding dysfunctions by improving bladder denervation and detrusor underactivity even when the treatment was started after storage and voiding dysfunctions had already occurred., (© 2018 Wiley Periodicals, Inc.)

Aims: To assess the efficacy and safety of mirabegron in the treatment of neurogenic detrusor overactivity., Methods: This prospective, multicenter, randomized, double-blind, placebo-controlled study was conducted in three tertiary centers, and included 78 patients suffering from spinal cord injury or multiple sclerosis. Patients were randomized for Mirabegron 50 mg (Group A) or placebo (Group B). Urodynamic parameters, the 24 h pad-weight test, and patient-reported outcomes were assessed. Safety assessments included monitoring the incidence and severity of adverse events. Changes in time and differences between groups were assessed with nonparametric Kruskal-Wallis one-way analysis of variance; P ≤ 0.05 was considered statistically significant., Results: In total, 66 patients were eligible for inclusion in the final analysis. There was a significant increase of volume at the first detrusor contraction (P = 0.00047) and an improvement in bladder compliance (P = 0.0041) in the mirabegron group compared with the placebo-treated group, whereas the increase in cystometric capacity did not reach statistical significance (P = 0.061). There was a clear tendency to reduced urine leakage (P = 0.056) in Group A. There were significant changes in all the patient-reported outcomes, favoring the mirabegron group. The incidence of drug-related adverse events was 3.13%., Conclusions: Mirabegron (50 mg) improved both urodynamic variables and patient-reported outcomes in patients with NDO. The treatment was tolerated well., (© 2018 Wiley Periodicals, Inc.)

Erectile dysfunction (ED) associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase (PK) has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate (cGMP) levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED., Competing Interests: All authors declared no competing interests

Background: Men with inflammatory bowel disease (IBD) may have decreased sexual function due to factors related to the underlying disease, medication, and/or surgery. We aimed to examine the use of erectile dysfunction (ED) medications in men with IBD., Methods: This is a nationwide cohort study based on the Danish registries, comprising all men >18 years old with IBD during 1 January 1995 through December 2016. The cohorts included 31,498 men with IBD and 314,980 age-matched men without IBD. Our main outcome was a first prescription of an ED medication. Cox regression analyses were used to estimate the hazard rate (HR) for use of ED medications, controlled for multiple time-varying covariates., Results: Overall, 21,966 (69.7%) men had ulcerative colitis (UC) while 9532 (30.3%) had Crohn's disease (CD). Men with a first ED prescription numbered 3749 (11.9%) (men with IBD) and 30,635 (9.7%) (men without IBD). Adjusting for central nervous system and intestinal anti-inflammatory medications, systemic corticosteroids and co-morbidities, the HR was 1.19 (95% CI: 1.13-1.26) (IBD and no prior IBD operation), and 1.31 (95% CI: 1.20-1.43) (IBD and prior IBD operation). The adjusted HR for UC was 1.17 (95% CI: 1.10-1.24) (no operation) and 1.43 (95% CI: 1.27-1.61) (prior operation), and for CD 1.26 (95% CI: 1.15-1.38) (no operation) and 1.20 (95% CI: 1.06-1.35) (prior operation)., Discussion: Men with IBD are more likely to fill an ED prescription than men without IBD. This result is significant regardless of a history of IBD surgery.

Aim: The present study assessed the therapeutic efficacy and safety of mirabegron 25 mg in older patients aged ≥80 years with overactive bladder and multiple comorbidities., Methods: Patients with overactive bladder were prospectively treated with 25 mg of mirabegron once daily. The patients were divided into a younger group (aged 40-60 years) and an older group (aged ≥80 years), and their underlying comorbidities were recorded. The primary efficacy end-point was the change in symptom score from baseline to the third month. Safety assessments included adverse events and post-void residual urine volume., Results: A total of 217 patients (younger, n = 62; older, n = 155) were included. The older patients had more comorbidities than the younger patients. Statistically significant improvements in the Quality of Life index and Patient Perception of Bladder Condition were noted in the younger patients from 1 month after treatment, whereas the International Prostate Symptom Score-Voiding subscore, International Prostate Symptom Score-Total, Quality of Life index, post-void residual urine volume and Patient Perception of Bladder Condition were all significantly decreased in the older patients after 3 months of treatment. The mean changes in the International Prostate Symptom Score-Voiding subscore, maximal flow rate, post-void residual urine volume, nocturia and Urgency Severity Score were significantly different between the two groups. The younger patients experienced more minor adverse events than the older patients (41.94% vs 24.62%) during treatment. Nevertheless, the adverse event rate was acceptably low in both groups., Conclusions: Mirabegron 25 mg once daily is a safe and effective treatment for older patients with overactive bladder. Geriatr Gerontol Int 2018; 18: 1330-1333., (© 2018 Japan Geriatrics Society.)

Background: Mirabegron is an established treatment alternative to antimuscarinic therapy for patients with overactive bladder (OAB), as shown by efficacy and tolerability data from phase III trials., Objective: To assess efficacy and tolerability of mirabegron 50mg versus antimuscarinic monotherapies and combination therapies., Design, Setting, and Participants: Systematic literature review and network meta-analysis of randomised controlled trials (2000-2017) assessing eligible treatments for OAB., Outcome Measurements and Statistical Analysis: Efficacy assessments included micturition frequency, urgency urinary incontinence, dry rate, and 50% reduction in incontinence. Tolerability assessments included dry mouth, constipation, blurred vision, and hypertension., Results and Limitations: A total of 64 studies (n=46 666) were included in the network meta-analysis. Mirabegron 50mg was significantly more efficacious than placebo for all efficacy endpoints. Comparable overall efficacy was observed for mirabegron 50mg versus most active treatments, but solifenacin 10mg monotherapy and solifenacin 5mg plus mirabegron 25 or 50mg in combination were more efficacious for some/all outcomes. Mirabegron 50mg was significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators, respectively; similar overall tolerability was observed between mirabegron 50mg and all treatments (including placebo) for the remaining endpoints. Limitations of the study included between-trial variations in the definition of certain endpoints and heterogeneity of the available data (eg, number of studies and patients assessed) for comparator treatments across different endpoints., Conclusions: The relief of key OAB symptoms produced by mirabegron 50mg is significantly better than placebo, and similar to a range of common antimuscarinics, with the benefit of significantly fewer bothersome anticholinergic side effects such as dry mouth. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg appears to provide an efficacy benefit compared with mirabegron 50mg, with the expected side effects of individual antimuscarinics., Patient Summary: This study assessed the efficacy and tolerability of different drug treatments for OAB. Mirabegron 50mg was as effective as antimuscarinic therapy, with fewer common, bothersome side effects such as dry mouth, constipation, and urinary retention. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg was more effective than mirabegron 50mg alone, but with more anticholinergic side effects., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: The impact of mirabegron on clinical outcome and urodynamic parameters may be important for clinical practice. Thus, the aim of this study was to compare the clinical outcomes and urodynamic effects of mirabegron (Betmiga 50 mg) versus tolterodine (Detrusitol ER 4 mg) treatment for women with overactive bladder syndrome (OAB)., Methods: Women with OAB were randomized to receive 12 weeks of mirabegron 50 mg, tolterodine extended-release 4 mg or placebo treatment. The clinical outcomes and urodynamic effects were compared between the subgroups., Results: Thirty-three women completed 12 weeks of mirabegron (n = 12), tolterodine (n = 12) or placebo (n = 9) treatment. A significant increase in the volumes at strong desire to void and a decrease in the daytime frequency episodes were identified in the mirabegron and tolterodine groups (all P < 0.05). Nonetheless, a decrease in the total voided volume was identified following mirabegron treatment but not tolterodine (P = 0.02)., Conclusions: Mirabegron and tolterodine exhibit similar changes in the urodynamics and bladder diary parameters. However, mirabegron may decrease the total voided volume. These findings may serve as an initial guide or assist in consultations regarding the treatment of OAB patients with mirabegron., (© 2017 John Wiley & Sons Australia, Ltd.)

Silodosin, a recently introduced selective α-blocker, has a much higher selectivity for the α-1A receptor. The efficacy and safety of silodosin compared to tamsulosin in medical expulsive therapy (MET) are controversial. The objective of this study was to assess the efficacy and safety of silodosin compared to tamsulosin for treating ureteral stones <10 mm in diameter. We systematically searched the PubMed, EMBASE, Cochrane library, and Scopus databases from their inception to May 2018. We included randomized controlled studies (RCTs) and observational studies, which investigated stone expulsion rates using silodosin compared to tamsulosin. Data were synthesized using a random-effects model. Sixteen studies with 1824 patients were eligible for inclusion. Silodosin achieved significantly higher expulsion rates than tamsulosin (pooled risk difference (RD): 0.13, 95% confidence interval (CI): 0.09 to 0.18, GRADE: high). A subgroup analyses showed that silodosin has a significantly higher expulsion rate on stone sizes of 5-10 mm than tamsulosin (pooled RD: 0.14, 95% CI: 0.06 to 0.22, I2 = 0%). The superior effect was not observed on stone sizes <5 mm. A multivariate regression showed that the RD was negatively associated with the control expulsion rate after adjusting for age and gender (coefficient -0.658, p = 0.01). A sensitivity analysis showed that our findings were robust. Patients receiving silodosin also probably had a significantly shorter expulsion time (pooled mean difference (MD): -2.55 days, 95% CI: -4.06 to -1.04, I2 = 85%, GRADE: moderate) and may have fewer pain episodes (pooled MD: -0.3, 95% CI: -0.51 to -0.09, GRADE: low) but a higher incidence of retrograde ejaculation by 5% compared to those receiving tamsulosin. In conclusion, compared to tamsulosin, silodosin provided significantly better stone passage for patients with ureteral stones (particularly for sizes of 5~10 mm), shorter expulsion times, and fewer pain episodes but caused a higher incidence of retrograde ejaculation., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the anti-cicatricial and anti-restenosis effect of verapamil on anterior urethral stricture.
 Methods: A total of 32 patients received anterior urethral stricture were enrolled in this study. They were divided into 4 blocks according to the duration of previous urethral operations and dilations. Every block was further randomly divided into an experimental group and a control group. Experimental groups received 2 mL injection of verapamil around the anastomosis site of urethra before and after the surgery (2, 4, 6, 8, and 10 weeks after the surgery), while the control groups only received the anastomosis surgery. After surgery, maximal urinary flow rate (Qmax) was examined for all patients once the catheter was removed. In addition, they were also conducted palpation of urethral scar range. The sum of long transverse diameters of urethral scar was measured, and the narrowest urethral inner diameter was examined. The Qmax was rechecked and the urethral scar range was assessed by penis color Doppler elastography after 12 weeks of surgery. The above 4 indexes were used to evaluate the inhibitory effect of verapamil on urethral scar.
 Results: The length of palpated urethral scar in the Block 1 to 4 of the experimental groups was (22.75±1.03), (21.25±0.25), (20.75±1.03), and (20.0±0.58) mm, respectively; and those in the control groups (26.00±0.82), (24.5±1.04), (25.75±1.65), and (28.25±1.75) mm, respectively. The Qmax rates in the Block 1 to 4 of the experimental groups were (11.85±0.77), (11.33±0.81), (10.23±0.26), and (10.35±0.17) mL/s, respectively; and those in the control groups were (10.85±0.39), (10.50±0.76), (10.53±1.00), (12.60±0.39) mL/s, respectively. The Qmax rates in the Block 1 to 4 of the experimental groups were (11.73±0.87), (10.65±0.25), (10.23±0.19), and (10.35±0.29) mL/s, respectively; and those in the control groups were (8.05±0.28), (7.73±0.68), (7.53±0.92), and (9.60±0.32) mL/s, respectively. The narrowest diameters of urethral in the Block 1 to 4 of the experimental groups were (9.00±0.58), (7.50±2.89), (7.00±0.10), and (7.00±0.41) mm, respectively; and those in the control groups were (5.50±0.29), (5.00±0.41), (4.75±0.48), and (6.75±0.48) mm, respectively. The ultrasound strain ratio in the Block 1 to 4 of the experimental groups were 6.10±0.22, 6.10±0.17, 5.10±0.16, and 6.90±0.19, respectively; and those in the control groups were 8.00±0.25, 10.60±0.29, 11.30±0.16, and 8.90±0.33, respectively. Compared with the control groups, the experimental groups displayed smaller urethral scar range, less severe scarring, improved Qmax rates and wider inner diameters (all P<0.05).
 Conclusion: Urethral regional injection of verapamil intraoperatively or postoperatively can prevent overgrowth of urethral scar tissues after the transperineal anastomosis surgery, and reduce the tendency of postoperative restenosis of anterior urethral stricture.

Fesoterodine (as one of three drugs: dutasteride, finasteride and fesoterodine) was classified B (beneficial) by LUTS-FORTA 2014, indicating that it is a medicinal product with proven or obvious efficacy in the elderly, with limited side effects and/or safety concerns. A systematic literature review was undertaken in January 2018 using the PubMed and Google Scholar databases with the following individual and combined keywords: "fesoterodine", "pharmacology", "overactive bladder" and "antimuscarinics". The aim of the review was to determine which of fesoterodine's pharmacological properties explains its clinical benefits in general patient populations with OAB and the elderly in particular. The articles in the results were then selected by publication language (English and French only), methodology (off-topic studies, reported cases and literature reviews were excluded), relevance to the subject matter and publication date prior to 31 January 2018. A total of 205 articles was initially obtained, with 115 read and 45 selected. It appears that the association of four pharmacological properties specific to fesoterodine can explain that this drug has a good balance between efficacy and tolerability. These properties are namely the drug's high and nearly equal affinity for both the M2 and M3 muscarinic receptors, poor penetration of the blood-brain barrier, lack of hepatic first-pass activation -fesoterodine being rapidly and extensively converted to its active metabolite, 5-hydroxymethyl tolterodine, by ubiquitous esterases-, and its extended-release formulation. Fesoterodine's pharmacological profile is optimal for the treatment of overactive bladder. It is now recognized as one of the leading first-line treatment for this indication., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The field of urology encompasses all benign and malignant disorders of the urinary tract and the male genital tract. Urological disorders convey a huge economic and patient quality-of-life burden. Hospital acquired urinary tract infections, in particular, are under scrutiny as a measure of hospital quality. Given the prevalence of these pathologies, there is much progress still to be made in available therapeutic options in order to minimize side effects and provide effective care. Current drug delivery mechanisms in urological malignancy and the benign urological conditions of overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and urinary tract infection (UTI) will be reviewed herein. Both systemic and local therapies will be discussed including sustained release formulations, nanocarriers, hydrogels and other reservoir systems, as well as gene and immunotherapy. The primary focus of this review is on agents which have passed the preclinical stages of development.

Objective: To investigate the effect of Kangshuailing Gao (KG) on benign prostatic hyperplasia (BPH) in rats and its action mechanisms., Methods: Fifty BPH model rats were randomized into five groups of equal number, BPH model control, finasteride control, and high-, medium- and low-dose KG, to be treated intragastrically with distilled water, finasteride solution at 0.52 mg/kg, and KG solution at 4.16, 2.08 and 1.04 g/kg respectively once a day for 30 days consecutively. Another 10 normal healthy rats were taken as blank controls. The rats were weighed once a week during the treatment. The wet weight and index of the prostate were obtained after treatment, followed by measurement of the contents of serum estradiol (E2) and dihydrotestosterone (DHT), testosterone (T) and hypoxia-inducible factor-1α (HIF-1α) in the prostatic tissue, and observation of histomorphological changes in the prostate under the light microscope., Results: Compared with the BPH model control group, high- and medium-dose KG significantly reduced the prostate wet weight (［0.84 ± 0.08］ vs ［0.69 ± 0.04］ and ［0.71 ± 0.07］ g, P < 0.01), the prostatic index (［0.28 ± 0.03］% vs ［0.20 ± 0.02］% and ［0.22 ± 0.03］%, P < 0.01), and the levels of T (［4.63 ± 1.25］ vs ［2.44 ± 0.47］ and ［2.91 ± 0.69］ ng/L, P < 0.01) and DHT (［154.44 ± 20.25］ vs ［88.23 ± 13.63］ and ［90.52 ± 16.44］ nmol/L, P < 0.01), but increased the level of E2 (［0.95 ± 0.24］ vs ［1.19 ± 0.14］ and ［1.20 ± 0.22］ nmol/L, P < 0.01) in the serum. High-dose KG remarkably reduced the overexpression of HIF-1α in the prostate tissue of the BPH model rats (P < 0.01) and alleviated such BPH-related symptoms as epithelium thinning, intraglandular secretion reduction, and interstitial substance decrease., Conclusions: Kangshuailing Gao acted effectively on BPH in the model rats by reducing the androgen level, balancing the estrogen/androgen ratio, and downregulating the expression of HIF-1α in the prostate tissue.

The acontractile bladder (AcB) is a urodynamic-based diagnosis wherein the bladder is unable to demonstrate any contraction during a pressure flow study. Although it is often grouped with underactive bladder, it is a unique phenomenon and should be investigated independently. The purpose of the present review was to examine the current literature on AcB regarding its pathology, diagnosis, current management guidelines, and future developments. We performed a review of the PubMed database, classifying the evidence for AcB pathology, diagnosis, treatment, and potential future treatments. Over the 67 years covered in our review period, 42 studies were identified that met our criteria. Studies were largely poor quality and mainly consisted of retrospective review or animal models. The underlying pathology of AcB is variable with both neurological and myogenic aetiologies. Treatment is largely tailored for renal preservation and reduction of infection. Although future developments may allow more functional restorative treatments, current treatments mainly focus on bladder drainage. AcB is a unique and understudied bladder phenomenon. Treatment is largely based on symptoms and presentation. While cellular therapy and neuromodulation may hold promise, further research is needed into the underlying neuro-urological pathophysiology of this disease so that we may better develop future treatments., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Mirabegron, a β3-adrenoceptor agonist, was approved for overactive bladder (OAB), but worsened hypertension was a potential risk based on its mechanism of action. Besides, head to head comparisons were limited between mirabegron and antimuscarinic agents, the prior first-line pharmacotherapy of OAB. In this regard, we performed a systematic review and meta-analysis to compare their efficacy as well as safety, especially in blood pressure changes., Materials and Methods: Literature search was conducted in PubMed, Medline and seven randomized clinical trial (RCT) register databases of WHO, EU, USA, Taiwan, China, Japan and Cochrane. Completed RCTs for OAB with mirabegron and antimuscarinics were identified and the last comprehensive search was run in August 2017. Cochrane risk of bias tool was used to assess the potential bias, and RevMan5 software was performed for meta-analysis., Results: Seven eligible RCTs (four for mirabegron vs. tolterodine and three for mirabegron vs. solifenacin) were included and demonstrated similar efficacy in micturitions, incontinence, and nocturia between mirabegron and antimuscarinics. In hypertension issue, no statistical differences were showed in risk ratio (RR) of hypertension events, change of blood pressure from baseline and change of blood pressure from placebo for all participants. On the other hand, RR of dry mouth was significantly lower in mirabegron users., Conclusions: Mirabegron was not inferior effective in improving OAB symptoms compared with antimuscarinic agents. In addition, mirabegron presented lower incidence of dry mouth and not higher risk for hypertension. Therefore, mirabegron has potential to be an alternative therapeutic option for OAB control.

Purpose of Review: Lower urinary tract symptoms (LUTS) result from age-related changes in detrusor function and prostatic growth that are driven by alterations in the ratio of circulating androgens and estrogens. Alpha-adrenergic receptor blockers are commonly used to treat LUTS because they influence urethral tone and intra-urethral pressure. Molecular cloning studies have identified three α 1 -adrenergic receptor subtypes (α 1A , α 1B , and α 1D ). The α 1A subtype is predominant in the human prostate but is also present in many parts of the brain that direct cognitive function. Tamsulosin is the most widely used α 1 -adrenergic receptor antagonist with 12.6 million prescriptions filled in 2010 alone. When compared to the other common types of α 1 -adrenergic receptor antagonists (i.e., terazosin, doxazosin, and alfuzosin), tamsulosin is 10- to 38-fold more selective for the α 1A versus the α 1B subtype., Recent Findings: Duan et al. have recently shown that men taking tamsulosin have a higher risk of developing dementia when compared to men taking other α-adrenergic antagonists or no α-adrenergic antagonists at all (HR 1.17; 95% CI 1.14-1.21). Based upon this retrospective analysis, we believe that tamsulosin, because of its unique affinity for α 1A -adrenergic receptors, may increase the risk of developing dementia when used for an extended period of time. If these findings are confirmed, they carry significant public health implications for an aging society.

Introduction: Pharmacotherapy of overactive bladder (OAB) typically involves treatment with an antimuscarinic or mirabegron, a β3-adrenoceptor agonist, but real-world evidence on their use, including treatment access, persistence, and switching, is limited. Here, we describe the design of a prospective, multicenter, non-interventional registry of patients beginning a new course of OAB pharmacological therapy in routine clinical practice., Methods: Adults with an OAB diagnosis for at least 3 months who either initiated a new course of mirabegron or antimuscarinic, or who switched therapy were enrolled into PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder). The primary objective was to identify factors associated with improved OAB treatment effectiveness from a patient perspective. Secondary objectives were to compare persistence rates, reasons for discontinuation, and switching patterns between patients taking mirabegron or antimuscarinics. Healthcare centers and sites involving medical specialties who routinely participate in the care and treatment of patients with OAB (e.g., gynecology, urology, and primary care practices) were targeted for recruitment. Patient-reported outcomes (PROs), including quality of life, symptom bother, and treatment satisfaction from OAB-validated scales, were collected at baseline, months 1, 3, 6, and 12, and when patients switched or discontinued their current OAB medication., Conclusions: PERSPECTIVE is the first real-world observational study in the United States and Canada on clinical and patient perspectives in OAB management. Recruitment was reflective of centers where patients are treated for OAB to maximize generalizability to the real-world population., Trial Registration: ClinicalTrials.gov, ID number NCT02386072 (date of registration March 6, 2015)., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate accompanied by an increase in prostatic blood perfusion and vascularization. The most indicated treatment is to perform orchiectomy, however, medical treatment with finasteride can be an option for breeding dogs or elderly animals with a critical health status. In dogs, the influence of medical treatment on prostatic hemodynamics is still unknown. Therefore, this study aimed to evaluate the effects of benign prostatic hyperplasia and finasteride therapy on hemodynamic and vascular features of the canine prostate. For this purpose, twenty dogs of different breeds, body weights (10-30 kg) and ages (5-13 years) were used, assigned for: Healthy-non treated group (n = 5), BPH-non treated group (n = 5), Healthy-finasteride treated group (n = 5) and BPH-finasteride treated group (n = 5). Dogs that presented hematospermia and at least one general clinical sign (tenesmus, hematuria or dysuria) were presumptively diagnosed with BPH. Dogs were evaluated ultrasonographycally by B-mode and Doppler of the prostatic artery in a monthly interval (day 0, 30 and 60) in order to measure prostate volume (PV), expected prostate volume (EPV), prostate vascularization score (scored as minimum, intermediary and maximum) and prostatic artery blood flow parameters with the use of spectral and color Doppler ultrasound. It was possible to observe a decrease in prostate vascularization score between Day 0 (intermediary degree) and 60 (minimum degree) in finasteride treated dogs. Moreover, non-treated dogs had higher score of vascularization at Day 60 compared to animals treated with finasteride, regardless of BPH diagnosis. Healthy-non treated animals presented higher peak systolic:diastolic velocity (S/D) than BPH-non treated dogs. Furthermore, BPH-non treated dogs had lower S/D than BPH-finasteride treated dogs. In 30 and 60 days, no difference on PV was observed between BPH-finasteride treated group and Healthy-non treated group. At day 60, no difference between PV and EPV was observed for the BPH-finasteride treated group. In conclusion, finasteride treatment reduces simultaneously the volume, local vascularization and blood flow of the prostate, thus, being considered an effective and additional choice of therapy for BPH. Moreover, the course of therapy in dogs can be followed by analyzing changes in prostatic artery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Experimental autoimmune prostatitis (EAP) shares important clinical features with clinical chronic prostatitis/chronic pelvic pain. We investigated the effect of tadalafil on pelvic pain and prostatic inflammation in a rat EAP model., Methods: EAP was induced in rats by intradermal injection of rat prostate antigen and complete Freund's adjuvant on days 0 and 28. Rats were treated with tadalafil (2 mg/kg, p.o.; EAP-tadalafil) or vehicle (EAP-vehicle) once daily from day 0, while sham-operated animals were treated with vehicle only (Sham). Tactile allodynia was measured on days 28, 35, and 42 by applying von Frey filaments to the lower abdomen as an index of pelvic pain. On day 42, the plasma immunoglobulin G (IgG) concentration and the testosterone/estradiol ratio were measured and histopathological analysis of the prostate was performed., Results: Tactile allodynia in the pelvic region was observed on days 28, 35, and 42 after EAP induction. The tactile allodynia observed on day 42 was significantly reduced by repeated treatment with tadalafil. Plasma IgG concentrations increased after EAP induction but the increase was not changed by tadalafil treatment. Prostate tissues were characterized by epithelial necrosis, infiltration of neutrophils and/or lymphocytes to acini and stroma, and fibrosis, in addition to a high stroma-to-epithelium ratio. Tadalafil treatment significantly suppressed the severity of the lesions., Conclusions: EAP rats developed pelvic pain, prostatic inflammation and increased plasma IgG concentrations. Tadalafil inhibited the chronic pelvic pain and prostatic inflammation, suggesting that its anti-inflammatory action may contribute to its blocking of pain development in the EAP model., (© 2018 Wiley Periodicals, Inc.)

Objective: To determine the impact of physicians' financial relationships with the pharmaceutical industry on prescribing marketed alpha-blockers and overactive bladder (OAB) medications. We also aim to examine if the number or total value of transactions is influential., Materials and Methods: We linked the Open Payments Program database of industry payments to prescribers with Medicare Part D prescription data. We used binomial logistic regression to identify the association between receipt of industry payment and prescribing of marketed alpha-blockers (silodosin) and OAB medications (fesoterodine, solifenacin, and mirabegron). We also evaluated the impact of increasing total value and number of payments on prescribing of marketed drugs., Results: The receipt of industry payment was associated with increased odds of prescribing the marketed drug for all included drugs: silodosin (odds ratio [OR] 34.1), fesoterodine (OR 5.9), solifenacin (OR 2.7), and mirabegron (OR 6.8) (all P <.001). We also found that increasing value of total payment and increasing frequency of payments were both independently associated with increased odds of prescribing with a dose-response effect., Conclusion: There is a consistent association between receipt of industry payment and prescribing marketed alpha-blockers and OAB medications. Both the total value and number of transactions were associated with prescribing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effect of tadalafil compared with four alpha blockers (alfuzosin, doxazosin, tamsulosin and silodosin) as medical expulsive treatment for ureteral stones in male adults., Materials and Methods: Male adults who were admitted to urology clinic with flank pain and diagnosed with non complicated < 10 mm ureteral stone on non-contrast computed tomography (NCCT) between June 2014-September 2015 were retrospectively evaluated. A total of 273 patients with ureteral stone were divided into five groups. Alfuzosin 10 mg/daily, doxazosin 8 mg/daily, tamsulosin 0.4 mg/daily, silodosin 8 mg/daily and tadalafil 5 mg/daily for 6 weeks were prescribed respectively. Stone localization, diameter, volume and Hounsfield units were noted as NCCT findings. The patients were divided into the two groups based on their stone localization as distal and mid-proximal stones. These two groups were evaluated separately. Expulsion rate were noted at the end of 6 weeks. NCCT and treatment findings were compared between five drug groups in distal and mid-proximal stones separately., Results: Age was higher in tadalafil group in distal stones (p = 0.032). Expulsion rate was found 78.1% for alfuzosin, 75.7% for doxazosin, 76.5% for tamsulosin, 88.6% for silodosin and 90% for tadalafil in distal (p = 0.44) and 21.7%, 30%, 30%, 30% and 54.5% in mid-proximal stones (p = 0.034) respectively., Conclusions: Expulsion rate was higher in silodosin and tadalafil for distal ureteral stones but the difference didn't meet statistical significance. However the expulsion rate was significantly higher in tadalafil than in the other groups for mid-proximal ureteral stones. The result of this study showed that tadalafil may increases ureteric stone expulsion.

Background: Αim of the study was to determine the effect of mirabegron, used for overactive bladder (OAB) treatment, on female sexual function., Methods: Eighty five sexually active women suffering from overactive bladder were prospectively enrolled in this study. Females were divided into two groups. In Group A (control), 48 patients received no treatment and in Group B, 37 patients received mirabegron 50 mg/daily for 3 months. Patients were evaluated with FSFI-Gr at the beginning of the study and again after a period of 3 months., Results: In Group B, there was a significant increase post-treatment compared to baseline (p < 0.001) in total FSFI (20.3 (3.8) to 26.6 (4.2)) and all domains (desire: 3.0 (1.2) to 4.8 (1.2)), arousal: 3.0 (0.8) to 4.8 (0.9), lubrication: 3.9 (1.1) to 4.8 (1.2), orgasm: 3.6 (0.8) to 4.8 (1.0), satisfaction: 3.2 (0.4) to 4.0 (0.8) and pain: 3.2 (0.8) to 4.4 (1.2)). In Group A, there were no statistically significant changes in pre- and post-observation values., Conclusions: This study is one of the few demonstrating that management of OAB with mirabegron improves female sexual function., Trial Registration: TRN ISRCTN17199301 , 20/10/2017, retrospectively registered.

Aims: To examine early trends in the use of overactive bladder (OAB) agents across Canada, with a focus on initial uptake and reimbursement of two newer agents: fesoterodine, an anticholinergic, and mirabegron, a therapeutically novel beta-3 agonist., Methods: We conducted a population-based cross-sectional study of outpatient prescriptions for long-acting oral OAB agents dispensed to individuals in Canada between May 2010 and April 2015 to examine the differences in the uptake of the newer agents and their reimbursement through cash, private, and public payers., Results: The national dispensing rate of OAB agents increased by 60% from May 2010 to April 2015 (from 924 to 1475 units per 10 000). We observed an increase in the dispensing rate of fesoterodine, solifenacin, and mirabegron, but a decrease in that of tolterodine and oxybutynin. Mirabegron was adopted rapidly after Health Canada approval, growing to a rate of 191 units per 10 000 by study completion, with its uptake being primarily funded through private payers (72.2%). Conversely, fesoterodine's uptake was minimal (8.3 units per 10 000) prior to its listing on public plans. This increased to 185 units per 10 000 by study completion, with the majority (65%) paid for by public insurers., Conclusions: The differences in the uptake and reimbursement of two new OAB agents emphasize the impact of therapeutically novel agents on the prescription rates of older OAB agents with significant adverse effects. Further studies are needed to explain changes in the dispensing rates as more provinces list the newer drugs on their formulary., (© 2018 Wiley Periodicals, Inc.)

Purpose: Overactive bladder (OAB) is a symptom-based disease; therefore, clinical trials to evaluate treatments for OAB employ a range of efficacy endpoints. Since factors that influence efficacy endpoints can affect trial outcomes, their identification could aid in the design of future OAB clinical trials. We investigated factors influencing different efficacy endpoints used in clinical trials with OAB patients and examined their characteristics to determine future clinical trial strategies for new medicinal treatments for OAB., Methods: Data from placebo-controlled double-blind trials in patients with OAB were extracted via a systematic literature review. The integrated differences for efficacy endpoints were calculated. Heterogeneity was assessed using the Q statistic and I 2 statistic. Factors influencing efficacy endpoints were identified through univariate and multivariate meta-regression analyses., Results: Forty-one controlled trials were analyzed. Substantial heterogeneity between studies was observed for each efficacy endpoint (P > 0.001, I 2  > 70%). We found with multivariate meta-regression analysis that period of recording in a bladder diary and year of publication were significantly likely to influence the change from baseline in the mean number of urgency episodes in 24 h, year of publication and gender were significantly likely to influence the change from baseline in the mean number of micturitions in 24 h, and gender was significantly likely to influence the change from baseline in the mean volume voided per micturition. In contrast, there were no factors significantly associated with change from baseline in the mean number of incontinence episodes in 24 h., Conclusions: We identified that change from baseline in the mean number of incontinence episodes in 24 h should serve as a relatively stable endpoint. In contrast, we identified factors influencing other endpoints, and the identified factors should be taken into account when planning and conducting future clinical trials.

The first-in-class β 3 -adrenoceptor agonist mirabegron is indicated in the EU (Betmiga™), Japan (Betanis™) and several other countries for the management of overactive bladder (OAB) syndrome. Evidence for its use in this setting includes several large phase 3 trials. Compared with placebo, oral mirabegron for 12 weeks reduced the frequency of micturition and generally also that of incontinence, with other benefits including reduced urgency, increased void volume and improved health related quality-of-life (HR-QOL). Mirabegron comparisons versus tolterodine are descriptive; however, in a 12-week powered comparison versus solifenacin in patients dissatisfied with antimuscarinic efficacy, mirabegron did not demonstrate noninferiority in reducing micturition frequency or significantly differ in terms of improving other urinary symptoms. Urinary and HR-QOL benefits of mirabegron were sustained over up to 52 weeks of treatment and the drug was generally well tolerated, with a numerically lower incidence of dry mouth than antimuscarinics. Real-world data support the trial findings and indicate possible persistence and adherence benefits for mirabegron over antimuscarinics. Mirabegron use is not generally restricted by patient age, sex or antimuscarinic treatment status, although data in men (from a phase 4 study and phase 3 trial subanalyses) are variable; additional studies in older and male OAB patients are awaited with interest. Although further longer-term efficacy and tolerability data would be beneficial, current clinical evidence indicates that mirabegron provides an alternative to antimuscarinics for the management of OAB in adults, including those for whom antimuscarinics have proven unsuitable.

Introduction and Objectives: Percutaneous nephrolithotomy remains a challenging procedure primarily due to difficulties obtaining access. Indeed, few urologists obtain their own access due to difficulties using a fluoroscopic or ultrasonic based antegrade puncture technique. Herein we report the first experience using holmium laser energy to obtain access in a retrograde fashion., Methods: After a pretreatment week of tamsulosin 0.4 mg/day (one center only) and following a documented sterile urine, a total of ten patients underwent retrograde holmium laser-assisted endoscopic-guided nephrostomy access in a prone split leg position., Results: In nine of ten patients, ureteroscopic guided, holmium laser access via an upper pole posterior calyx was achieved. In one patient, the laser tract could not be safely dilated and antegrade endoscopic and fluoroscopic guided access was performed. The mean operative time was 202 min; the mean fluoroscopy time was 32 s (6/9 cases). The mean pre-operative stone volume was 14,420 mm 3 . CT imaging on post-operative day 1 revealed 6/6 patients had residual stone fragments with total mean volume of 250 mm 3 (96% reduction); there were no residual fragments in three patients who were evaluated with non-CT radiographic imaging (KUB). There was a single complication requiring angioembolization due to a subcapsular hematoma with associated secondary tearing of an inter-polar vessel remote from the nephrostomy site., Conclusions: Holmium laser-assisted endoscopic-guided retrograde access in a prone split-leg position was successfully performed at two institutions. The accuracy of nephrostomy placement and lessening of fluoroscopy time are two potential benefits of this approach.

Vascular calcification (VC) is associated with elevated cardiovascular mortality rates in patients with CKD. Recent clinical studies of patients with advanced CKD have observed an association between low serum magnesium (Mg) levels on one hand and elevated VC and cardiovascular mortality on the other. These findings have stimulated interest in understanding Mg's impact on CKD in general and the associated VC in particular. In vitro and preclinical in vivo data indicate that Mg has the potential to protect vascular smooth muscle cells against calcification via several different molecular mechanisms. Accordingly, data from pilot interventional studies in the clinic suggest that oral Mg supplementation reduces VC in patients with CKD. The present review provides an overview of our current understanding of the impact of Mg on the development of VC in patients with CKD., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

As with other electrolytes, magnesium homeostasis depends on the balance between gastrointestinal absorption and kidney excretion. Certain drugs used commonly in patients with CKD can decrease gastrointestinal ingestion and kidney reclamation, and potentially cause hypomagnesemia. Other magnesium-containing drugs such as laxatives and cathartics can induce hypermagnesemia, particularly in those with impaired glomerular filtration and magnesium excretion. In this review, we will discuss the potential magnesium complications associated with a range of commonly encountered drugs in the care of CKD patients, discuss the potential mechanisms, and provide basic clinical recommendations., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Although alpha-adrenergic antagonists (α-blockers) are effective for relieving voiding lower urinary tract symptoms (LUTS) in men, storage symptoms often persist. The aim of this manuscript is to evaluate the efficacy and safety of combination therapy with α-blockers and muscarinic receptor antagonists (anticholinergics)., Recent Findings: High-quality evidence confirms that the addition of an anticholinergic improves micturition diary parameters, such as daytime and nocturnal frequency and urgency incontinence episodes, as well as total and storage subset scores on the International Prostate Symptom Score. Most studies demonstrate a statistically significant improvement over α-blocker monotherapy. Both, incidence of urinary retention and study withdrawal because of treatment-related adverse events with combination therapy, are low. Urodynamic indices, such as maximum flow rate and postvoid residual volume, are also minimally impacted by combination therapy. Outcomes on validated questionnaires and quality-of-life (QoL) indices also indicate a significant improvement., Summary: The addition of an anticholinergic to an α-blocker in men with storage and voiding LUTS is an effective practice in reducing both categories of symptoms. The addition of anticholinergic is associated with a low rate of urinary retention and the impact on efficient bladder emptying is minimal. Not unexpectedly, QoL is improved.

Objectives: The objective of the present study was to evaluate comparative efficacy and tolerability of antimuscarinics and mirabegron as primary and salvage therapy in patients with overactive bladder (OAB)., Methods: Patients ≥50 years with OAB symptoms were enrolled. Patients were initially treated with antimuscrinics or mirabegron for 8 weeks. When patients were refractory or intolerant to an initial treatment, drugs were switched to the other. The initial and second-line efficacy was assessed at baseline, 4 and 8 weeks after the treatment having the following parameters of the International Prostatic Symptom Score (IPSS), quality of life (QOL) index, Overactive Bladder Symptom Score (OABSS) and post-void residual (PVR) urine volume. Dry mouth and constipation were evaluated using dry mouth scale and constipation assessment scale, respectively., Results: A total of 117 patients were enrolled. As an initial treatment, 60 patients were given antimuscarinics and 57 patients received mirabegron. Similar initial treatment efficacy was observed between the two drugs in the whole patients. However, mirabegron was more efficacious to men with OAB unresponsive to prior α1-blocker. Dry mouth and constipation were less burdensome in patients treated with mirabegron. Such differences in efficacy and tolerability were associated with significantly greater persistence of mirabegron. As a second-line setting, both drugs appear to be equally effective at least to relieve urgency symptoms remaining after an initial therapy., Conclusion: The present study suggests that mirabegron seems to have priority as an initial therapy with a distinct efficacy/tolerability balance. Mirabegron also represents a reasonable alternative to antimuscarinics for patients who had insufficient efficacy and poor tolerability., (© 2016 John Wiley & Sons Australia, Ltd.)

Purpose of Review: To date it is unclear whether the selectivity of new alpha-blockers to alpha-adrenergic receptor subtypes translates into more clinical benefits and less adverse effects in clinical practice. We performed a systematic review of the two new Abs silodosin and naftopidil. With the availability of numerous alpha-blockers to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia, the findings of this review will be highly relevant to the field of urology., Recent Findings: Silodosin was found to be more effective than placebo in improving International Prostate Symptom Score (IPSS) and quality of life scores and as effective as other alpha-blockers. Although the incidence of cardiovascular adverse events of silodosin was similar compared with placebo and other alpha-blockers (tamsulosin, naftopidil, alfuzosin), the sexual adverse events were more common with silodosin. No placebo-controlled randomized trial exists investigating the effects of naftopidil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Naftopidil had similar efficacy with regards to IPSS and quality of life compared with tamsulosin. The rate of adverse events was similar compared with tamsulosin., Summary: The two new selective alpha-blockers, silodosin, and naftopidil showed similar efficacy in IPSS and quality of life compared with other alpha-blockers. However, silodosin has more sexual adverse events.

Introduction and Hypothesis: The aim of this study was to establish if the management of women with overactive bladder (OAB) and patient-reported outcomes differed based on the findings of urodynamics (UDS)., Methods: A prospective, longitudinal observational study conducted in urogynaecology clinics in 22 UK hospitals participating in the Diagnostic Accuracy of Bladder Ultrasound Study (BUS). A total of 687 women with OAB symptoms or urgency-predominant mixed urinary incontinence were recruited into a diagnostic study that used UDS as the reference standard. Detailed clinical history and International Consultation on Incontinence OAB Short Form (ICIQ-OAB sf) questionnaire responses were obtained before the UDS test was carried out. These questionnaires were subsequently collected at a mean of 7 and 20 months, along with patient global impression of improvement and details on medical and surgical treatments. The relationship between UDS diagnosis and treatment was examined using a multinomial regression model; logistic and repeated measures regressions were used to examine other outcomes., Results: We recruited 687 women and the response rate was 69% at 20 months. Treatment subsequent to UDS was highly associated with diagnosis (p < 0.0001). Women who received treatment concordant with their UDS findings were more likely to report an improvement in bladder symptoms (57% vs 45%; p = 0.02) and ICIQ-OAB sf scores (0.5 points, 95%CI: 0.1 to 0.9; p = 0.02)., Conclusions: Urodynamics influenced treatment decisions made by clinicians in determining treatment pathways in women presenting with OAB. Women treated based on UDS diagnoses appear to have greater reductions in symptoms than those who do not.

The objective of this study is to investigate the efficacy of silodosin in medical expulsive therapy (MET) for ureteral stones. We conducted a systematic review and meta-analysis to determine the efficacy and safety of silodosin in MET for ureteral calculi. We searched PubMed, Embase, Medline, Central (the Cochrane Library, Issue 1,2013), Google Scholar from the inception to March 2015 for randomized controlled trials (RCTs), comparing silodosin with tamsulosin or control on ureteral stone passage. Eight RCTs with a total of 1145 ureteral stone patients (300 patients in the control group, 287 patients in the tamsulosin group, 558 patients in the silodosin group) were included in this meta-analysis. When compared with control, silodosin significantly improved expulsion rate of distal ureteral stones (RR: 1.42; 95% CI, 1.21-1.67; P < 0.0001), while there was no significant difference between silodosin and the control in expulsion rate of proximal (RR: 0.99; 95% CI, 0.69-1.43; P < 0.97) or mid (RR: 1.13; 95% CI, 0.60-2.16; P < 0.0001) ureteral stones. There was no significant difference between silodosin and tamsulosin in terms of expulsion time (WMD: -2.47; 95% CI, -5.32 to 0.39; P = 0.09), analgesic use (WMD: -0.39; 95% CI, -0.91 to 0.13; P  = 0.14) and retrograde ejaculation rate (RR: 1.85; 95% CI, 0.95-3.59; P = 0.07) in MET for distal ureteral stones. However, silodosin provided a significantly higher expulsion rate (RR: 1.25; 95% CI, 1.13-1.37; P < 0.0001) than tamsulosin for distal ureteral stones. Silodosin significantly improved expulsion rate of distal ureteral stones and was clinically superior to tamsulosin. Silodosin was ineffective in MET for proximal and mid ureteral stones. More RCT studies are needed to compare the efficacy of silodosin versus tamsulosin in MET for distal ureteral stones.

Objective: To prospectively assess the impact of the fixed-dose combination (FDC) of the 5α-reductase inhibitor (5ARI), dutasteride 0.5 mg and the α 1 -adrenoceptor antagonist, tamsulosin 0.4 mg (DUT-TAM FDC) therapy on sexual function domain scores in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), using the Men's Sexual Health Questionnaire (MSHQ)., Patients and Methods: This European and Australian double-blind, placebo-controlled, parallel-group study was conducted at 51 centres., Inclusion Criteria: age ≥50 years, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate-specific antigen 1.5-10 ng/mL. Patients were randomised 1:1 to DUT-TAM FDC therapy or placebo for 12 months. The change from baseline to Month 12 on the total MSHQ (primary endpoint) and MSHQ erection, ejaculation and satisfaction domains (secondary outcome) was assessed, using a mixed model repeated measures analysis. Safety was evaluated., Results: The intention-to-treat population included 489 patients (243 DUT-TAM FDC therapy; 246 placebo). A significant decrease (worsening) was observed with DUT-TAM FDC therapy versus placebo on the total MSHQ score (-8.7 vs -0.7; standard error [se]: 0.81, 0.78; P < 0.001), and the ejaculation (-7.5 vs -0.6; se: 0.56, 0.55; P < 0.001) and satisfaction (-0.6 vs +0.3; se: 0.3, 0.29, P = 0.047) domains, but not the erection domain (-1.0 vs -0.5; se: 0.19, 0.19, P = 0.091)., Conclusion: This is the first domain-specific quantitative evaluation of DUT-TAM FDC therapy on sexual function in men with LUTS secondary to BPH. The observed changes in the MSHQ with DUT-TAM FDC therapy were mainly driven by changes in the ejaculation domain. These findings will help give context to erectile and ejaculatory dysfunction AEs reported spontaneously in earlier 5ARI studies., (© 2017 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction: It is common for men to develop erectile dysfunction after radical prostatectomy. The anatomy of the rat allows the cavernous nerve (CN) to be identified, dissected, and injured in a controlled fashion. Therefore, bilateral CN injury (BCNI) in the rat model is routinely used to study post-prostatectomy erectile dysfunction., Aim: To compare and contrast the available literature on pharmacologic intervention after BCNI in the rat., Methods: A literature search was performed on PubMed for cavernous nerve and injury and erectile dysfunction and rat. Only articles with BCNI and pharmacologic intervention that could be grouped into categories of immune modulation, growth factor therapy, receptor kinase inhibition, phosphodiesterase type 5 inhibition, and anti-inflammatory and antifibrotic interventions were included., Main Outcome Measures: To assess outcomes of pharmaceutical intervention on erectile function recovery after BCNI in the rat model. The ratio of maximum intracavernous pressure to mean arterial pressure was the main outcome measure chosen for this analysis., Results: All interventions improved erectile function recovery after BCNI based on the ratio of maximum intracavernous pressure to mean arterial pressure results. Additional end-point analysis examined the corpus cavernosa and/or the major pelvic ganglion and CN. There was extreme heterogeneity within the literature, making accurate comparisons between crush injury and therapeutic interventions difficult., Conclusions: BCNI in the rat is the accepted animal model used to study nerve-sparing post-prostatectomy erectile dysfunction. However, an important limitation is extreme variability. Efforts should be made to decrease this variability and increase the translational utility toward clinical trials in humans. Haney NM, Nguyen HMT, Honda M, et al. Bilateral Cavernous Nerve Crush Injury in the Rat Model: A Comparative Review of Pharmacologic Interventions. Sex Med Rev 2018;6:234-241., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the feasibility of discontinuing treatment with mirabegron once symptoms have subsided in patients with overactive bladder (OAB)., Methods: The present study evaluated a total of 159 female OAB patients (age 62.9 ± 12.36), each of which were prescribed 50 mg/day mirabegron (Time point 1-T1). Data obtained from voiding diaries and patient-reported outcome variables were assessed during follow-up visits at months 1, 3, 6, 12, 18 (T2), and 21 (T4). At the 18-month visit, patients with an Urgency Bother-Visual Analog Scale score of ≤ 50% were advised to stop treatment with mirabegron. Upon re-emergence or worsening of OAB symptoms, patients were allowed to start taking medication again at their discretion (T3). Statistical analysis was performed using a Chi-square test. An ANOVA analysis and a two-sample t test were used to evaluate differences between groups., Results: A total of 56 out of 159 (35.3%) patients took 50 mg of mirabegron daily between T1 and T2. A total of 17 out of 56 patients (30.4%) did not meet the criteria for mirabegron discontinuation (Group A). A total of 24 out of 56 patients (42.9%) stopped taking the medication temporarily, but later returned to treatment (Group B). The average time span between T2 and T3 was 53.9 days. Fifteen of 56 patients (26.8%) ceased treatment with mirabegron without starting it again before T4 (Group C). The average time span between T2 and T4, in Group C, was 124.7 days., Conclusion: A small percentage of OAB patients were able to discontinue mirabegron due to symptom cessation.

Aims: The injection of botulinum neurotoxin A (BTA) into the prostate represents a minimally invasive treatment in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). We evaluated the effectiveness of BTA in treating patients with BPH unresponsive to combined medical therapy (CMT), using urodynamic investigations., Methods: This is a randomized, placebo-controlled, double blind trial. Twenty consecutive patients were randomly assigned to receive intraprostatic BTA injection (n = 10) or saline solution (SS) (n = 10). Patients in the intervention group (IG) received 200-300 UI of BTA diluted in 6-8 mL of SS and injected into the transitional zone. Patients in the control group (CG) were treated with SS alone. Primary endpoint was International Prostate Symptom Score (IPSS). Secondary endpoints were: maximum flow rate (Qmax), postvoid residual volume (PVR), maximum cystometric capacity (MCC), bladder outlet obstruction index (BOOI), safety, quality of life (QoL) score, and Patient Reported Outcome (PROs)., Results: All patients in the IG reported subjective improvement starting after 1 month. At 3 months of follow-up IPSS, QoL, PVR were reduced by 55,3% (P < 0.01), and 50% (P < 0.01), 80,6%, (P < 0.01), respectively. Qmax was increased by 68% (P < 0.01). MCC increased by 27% (P < 0.01) and BOOI decreased by 54% (P < 0.01). PROs analysis revealed that 90% of patients in the IG reported a subjective symptomatic relief and treatment satisfaction. No local or systemic side effects were observed in any group., Conclusions: These results indicated that intraprostatic BTA is safe and can improve LUTS and QoL in patients with BPH and unsatisfactory response to CMT., (© 2017 Wiley Periodicals, Inc.)

Introduction: Surgery in patients with large prostates due to benign prostatic hyperplasia (BPH) results in severe dysuria manifesting as frequent or urgent need to urinate and urinary incontinence. Traditionally, these conditions are treated with alpha blockers. Recently, alpha-blockers and the anticholinergic combination have been used showing additional advantages. This study aimed to investigate the comparative effectiveness of monotherapy versus combination therapy in the treatment of postoperative dysuria in BPH patients with large prostates undergoing transurethral surgery., Materials and Methods: From September 2016 to March 2017, 94 BPH patients with prostates greater than 100 cc underwent transurethral surgery at the Department of Urology of D.D. Pletnev Clinical Hospital; 22 patients had exclusion criteria. In the postoperative period, 36 patients received 0.4 mg of modified release tamsulosin (Omnik) for a month, and 36 patients were administered controlled release tablets tamsulosin 0.4 mg + solifenacin 6 mg (Vezomni) as fixed-dose combination therapy. At one month postoperatively, patients were asked to rate their symptoms on a visual analogue scale and fill out I-PSS and QoL questionnaires. Preoperative parameters of the groups were: visual analogue scale scores were 5.1 and 5.2, I-PSS scores were 24 and 24.2, QoL scores were 4.5 in both groups. Prostate volumes were 114 and 118 cc; maximum urinary flow rates were 7.7 vs. 7.5 ml/sec, residual urine volumes were 110 vs. 105 ml, respectively., Results: Visual analogue scale scores were 6.5 versus 9.2 points, I-PSS scores were 16.3 versus 12.1. The patients of the second group had greater mean micturition volume (150 versus 240 ml); other variables did not differ statistically significantly between the groups. Adverse reactions were mild, and drugs were not discontinued in any case., Conclusion: In BPH patients with dysuria after transurethral resection of large prostates, Vezomni administration results in a better quality of life due to an improvement in urgency and nocturia.

Objectives: To evaluate the surgical outcomes of stroke patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP) and compare the clinical outcomes between patients with stroke and those without stroke receiving this procedure., Methods: This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan National Health Insurance Research Database. We enrolled 6625 patients who had persistent lower urinary tract symptoms and underwent TURP for BPH. They were categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient characteristics, postoperative clinical outcomes, medication records, and medical expenses were compared., Results: Compared with the stroke group patients, those in the nonstroke group were younger, had fewer comorbidities, and more favorable postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8% during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year postoperatively (p = .05). TURP reduced the overall medical expenses of patients with stroke. Annual patient medical expense during 1 year preoperatively, 1 year postoperatively, 2 years postoperatively, and 3 years postoperatively was NT$659,000, NT$646,000, NT$560,000, and NT$599,000, respectively., Conclusions: In patients with stroke, TURP reduces the risks of UTI and UR and annual total medical expense.

A systematic review and meta-analysis was carried out to evaluate the efficacy and safety of mirabegron 50 mg and 100 mg in the treatment of storage lower urinary tract symptoms/overactive bladder in comparison with a placebo and tolterodine 4 mg. A total of 491 articles were collected and eight randomized studies were identified as eligible for this meta-analysis. Overall, eight trials were included in the meta-analysis evaluating 10 248 patients. Mirabegron at both doses of 50 mg and 100 mg, and and tolterodine 4 mg were significantly associated with the reduction of incontinence episodes per 24 h, reduction of mean number of micturitions per 24 h, increase of voided volume and reduction of urgency episodes per 24 h, compared to a placebo. Both mirabegron 50 mg and mirabegron 100 mg were associated with a significant reduction of nocturia episodes when compared with a placebo. Conversely, tolterodine 4 mg did not prove to be more effective than a placebo in the reduction of nocturia episodes. Furthermore, mirabegron 50 mg showed a slightly, but significantly, better efficacy than tolterodine 4 mg in the improvement of nocturia episodes. Mirabegron 50 mg and mirabegron 100 mg shared the same risk of overall treatment-emergent adverse events rate with the placebo. Otherwise, tolterodine 4 mg was associated with a significantly greater risk than the placebo. However, mirabegron 100 mg showed a slight trend toward an increased risk of hypertension (odds ratio 1.41; P = 0.08) and cardiac arrhythmia (odds ratio 2.18; P = 0.06). Mirabegron is an effective treatment for patients with storage lower urinary tract symptoms/overactive bladder, providing a reduction of incontinence, urgency and frequency; an improvement of voided volume with a slight, but statistically, significant improvement of nocturia; with a good safety profile. These findings should be considered for the treatment planning of patients with storage lower urinary tract symptoms/overactive bladder., (© 2017 The Japanese Urological Association.)

Purpose: The purpose of this study was to compare the efficacy of tolterodine and gabapentin vs placebo in catheter related bladder discomfort (CRBD) following percutaneous nephrolithotomy (PCNL)., Materials and Methods: This study was a double-blind parallel group randomized clinical trial. Patients who were candidates of PCNL were enrolled. Patients were randomized to treatment groups of tolterodine 2 mg orally (PO) (group T, n = 50), gabapentin 600 mg PO (group G, n = 50), and placebo (group P, n = 70) 1 hour before operation using balanced block randomization. The primary endpoint of interest was visual analog pain scale in 1, 3, 12, and 24 hours after the operation. Secondary endpoints included rescue analgesic use (opioid and nonopioid)., Results: The frequency of severe CRBD in 1,12, and 24 hours after the operation was 4%, 4%, and 6% in group T vs 4%, 0%, and 2% in group G vs 47%, 14%, and 6% in the P group (p < 0.001). The number of paracetamol injections for CRBD in the T and G groups was significantly lower than the placebo group (1.8 ± 0.8 vs 1.8 ± 0.7 vs 3.6 ± 0.7, p < 0.001). Likewise the number of pethidine injections in the T and G groups was significantly lower than the placebo group (0.42 ± 0.54 vs 0.68 ± 0.62 vs 2.4 ± 0.64, p < 0.001). In patients with history of Double-J insertion, the severity of CRBD was lower in all treatment groups., Conclusions: Preoperative administration of oral tolterodine or gabapentin reduces postoperative CRBD and the need for rescue analgesics as much as 24 hours after surgery. Patients with history of Double-J insertion experience less CRBD.

Introduction and Hypothesis: The objective of this study was to assess the tolerability and treatment preference in patients with overactive bladder (OAB) treated with mirabegron or tolterodine., Methods: This was a two-period, 8-week crossover, double-blind, phase IV study (PREFER; NCT02138747) in treatment-naive adults with OAB for 3 months or longer randomized to one of four treatment sequences in a 5:5:1:1 ratio (mirabegron/tolterodine, tolterodine/mirabegron, mirabegron/mirabegron, or tolterodine/tolterodine), separated by a washout period of 2 weeks. The primary endpoint was drug tolerability using the Medication Tolerability scale of the OAB Treatment Satisfaction (OAB-S) questionnaire at end of treatment (EoT). Period-by-treatment interactions were analyzed to determine any effect of drug order. Patient preference, change from baseline in OAB symptoms, and treatment-emergent adverse events (TEAEs) were assessed., Results: A total of 358 randomized patients completed the OAB-S Medication Tolerability scale questionnaire at one or more visits after the baseline evaluation. The mean (95% CI) OAB-S Medication Tolerability scores were significantly higher (better tolerability) for mirabegron (86.29 [83.50, 89.08]) than for tolterodine (83.40 [80.59, 86.20]; p = 0.004). The period-by-treatment interaction was not significant (p = 0.955). Improvements in OAB-S Medication Tolerability scores at EoT were more evident in women, patients aged ≥65 years, and in patients without baseline incontinence, and were greater with mirabegron than with tolterodine extended release. There were no significant differences in patient preference or improvements in OAB symptoms. Significant differences in favor of mirabegron were observed for anticholinergic TEAEs (20.4% vs. 27.4%; p = 0.042) and specifically for gastrointestinal disorders (14.7% vs. 22.5%; p = 0.015)., Conclusions: Tolerability of mirabegron was significantly higher than that of tolterodine, and patient preference and improvements in OAB symptoms were comparable. Both treatments were well tolerated; however, anticholinergic side effects were higher with tolterodine.

Background: Overactive bladder is stated as the occurrence of urinary urgency which will cause negative impacts and decrease patients' health-related quality of life. The aim of this systematic review is to assess the efficiency and safety of acupuncture for adults with overactive bladder (OAB) comparing with sham-acupuncture, drugs, and acupuncture plus drugs., Methods: We independently searched 9 databases from beginning to August 15, 2017. Two writers extracted data at the same time independently. Study outcomes were calculated by standardized mean differences (SMD) with 95% confidence intervals (CIs) and mean difference (MD) with 95% CIs., Results: Ten randomized controlled trials (RCTs) with 794 patients were included in this systematic review. The combined results showed that electroacupuncture (EA) may be more effective than sham electroacupuncture (sham EA) in improving the 24-hour nocturia episodes and EA may enhance tolterodine for relieving voiding symptoms and enhancing patients' quality of life. However, more trials with high quality and larger sample sizes will be needed in the future to provide sufficient evidence. Only 15 of 794 OAB patients from the included studies reported mild adverse reactions related to EA, therefore, acupuncture is safe for treating OAB., Conclusion: Acupuncture might have effect in decreasing the number of micturition episodes, incontinence episodes, and nocturia episodes. However, the evidence is insufficient to show the effect using acupuncture alone or the additional effect to drugs in treating OAB.

Background: Despite several new medications being Food and Drug Administration-approved for overactive bladder (OAB) and new prescription drug payment programs, there are limited population-based data regarding OAB medication use among older adults., Objectives: To examine: (1) impacts of new medications and $4 generic programs on time trends for OAB-related medication dispensing for older adults in the United States; (2) differences by age and sex; and (3) temporal changes in OAB-related medication payments., Methods: Using Truven Health Analytics' Medicare Supplemental Database (2000-2015), we analyzed OAB-related medication claims for 9,477,061 Medigap beneficiaries age 65-104. We estimated dispensing rates (per 1000 person-months), assessed dispensing trends using interrupted time-series methods, compared dispensing rates by age and sex, and summarized payment trends., Results: From 2000 to 2015, 771,609 individuals filled 13,863,998 OAB-related prescriptions. During 2000-2007, 3 new extended-release medications became available (tolterodine, darifenacin, solifenacin), leading to increases in overall OAB-related dispensing rates by 19.1 (99% confidence interval, 17.0-21.2), a 92% increase since 2000; overall rates remained stable during 2008-2015. By 2015, the most common medications were oxybutynin (38%), solifenacin (20%), tolterodine (19%), and mirabegron (12%). Dispensing rates peaked at age 90 (rate, 53.4; 99% confidence interval, 53.1-53.7). Women had higher rates than men at all ages (average ratewomen-ratemen, 22.0). The gap between upper and lower percentiles of medication payments widened between 2008-2015; by 2015, 25% of reimbursed dispensed prescriptions had total payments exceeding $250., Conclusions: Medication-specific dispensing rates for OAB changed when new alternatives became available. Recent changes in utilization and cost of OAB medications have implications for clinical guidelines, pharmacoepidemiologic studies, and payment policies.

Introduction: The obstruction of the urinary tract by calculi at the narrowest anatomical areas leads to impaired drainage and severe pain. The aim of this study was to evaluate a new technology, extracorporeal physical vibrational lithecbole (EPVL) combined with tamsulosin, as a treatment for distal ureteral calculi (DUC)., Materials and Methods: Between July 2013 and July 2014, 672 patients diagnosed with DUC were randomly divided into three groups; a group receiving EPVL plus 0.4 mg oral tamsulosin daily (PO qd) (experimental group, n = 236), a group receiving 0.4 mg tamsulosin PO qd (n = 222), and a group receiving EPVL only (n = 214) (control groups)., Results: There were no significant differences in general characteristics between the three groups. Stone diameters ranged from 0.32 to 1 cm. In the EPVL plus tamsulosin group, 60.1% of patients showed detectable fragment expulsion at 48 hours, and 91.1% were stone free at 7 days. Compared with the two control groups, these rates were significantly higher (EPVL group was 0% and 50.5% and medical expulsive therapy group was 0% and 50.0%, p < 0.05). The stone-free rates were similar in the three groups 2 weeks later (94.5%, 93.6%, and 93.5%; p > 0.05). Patients in the EPVL plus tamsulosin group achieved similar stone-free rates compared with the other two groups, but the speed of the stone expulsion was quicker for both sexes and all age groups (about a week; p < 0.05)., Conclusion: This indicates that EPVL plus tamsulosin could be used as an effective, but faster treatment option for patients with DUC, alleviating the symptoms of DUC in a shorter period of time.

Background: Storage lower urinary tract symptoms (LUTS) including overactive bladder (OAB) and urinary incontinence (UI) affect millions of people worldwide, significantly impacting quality of life. Plant based medicines have been documented both empirically and in emerging scientific research to have varying benefits in reducing bladder symptoms. We assessed the efficacy of Urox®, a proprietary combination of phytomedicine extracts including, Cratevox™ (Crataeva nurvala) stem bark, Equisetem arvense stem and Lindera aggregata root, in reducing symptoms of OAB and UI., Methods: Efficacy of the herbal combination on a variety of bladder symptoms compared to an identical placebo, were documented in a randomised, double-blind, placebo controlled trial conducted at two primary care centres. Data were collected at baseline, 2, 4 and 8 weeks, with the primary outcome being self-reported urinary frequency. Statistical analysis included mixed effects ordered logistic regression with post hoc Holm's test to account for repeated measures, and included an intention-to-treat analysis., Results: One hundred and fifty participants (59% female, aged; mean ± SD; 63.5 ± 13.1 years) took part in the study. At week 8, urinary day frequency was significantly lower (OR 0.01; 95%CI 0.01 to 0.02; p < 0.001) in response to treatment (mean ± SD; 7.69 ± 2.15/day) compared to placebo (10.95 ± 2.47/day). Similarly, episodes of nocturia were significantly fewer (OR 0.03; 95%CI 0.02 to 0.05) after 8 weeks of treatment (2.16 ± 1.49/night) versus placebo (3.14 ± 1.36/night). Symptoms of urgency (OR 0.02; 95%CI 0.01 to 0.03), and total incontinence (OR 0.03; 95% CI 0.01 to 0.06) were also lower (all p < 0.01) in the treatment group. Significant improvements in quality of life were reported after treatment in comparison to placebo. No significant side effects were observed resulting in withdrawal from treatment., Conclusions: The outcome of this study demonstrated both statistical significance and clinical relevance in reducing symptoms of OAB, urinary frequency and/or urgency and incontinence. The demonstrated viability of the herbal combination to serve as an effective treatment, with minimal side-effects, warrants further longer term research and consideration by clinicians., Trial Registration: NCT02396160 (registered on 17 March 2015 - before any statistical analyses commenced).

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies.