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Objectives: To assess urologists' awareness of intraoperative floppy iris syndrome., Materials and Methods: A questionnaire composed of 21 questions was emailed to all of the Urology residency programs in the U.S. and all members of the Western section of the American Urological Association. Responses were collected and analyzed using statistical software., Results: A total of 175 responses were collected from residents, fellows, and attending physicians from a wide range of geographic locations, subspecialties, and practice settings. Thirty percent of the urologists would routinely discuss intraoperative floppy iris syndrome with patients prior to start of benign prostate hyperplasia treatment. Twenty-one percent of the respondents never asked patients about ophthalmologic conditions prior to benign prostate hyperplasia treatment. If patients had concurrent visual complaints, only 37% of the respondents would routinely encourage patients to speak to an ophthalmologist and only 13% would routinely refer patients to an ophthalmologist. A comparison among the subgroups based on training status and practice settings further showed that a significantly higher percentage of residents would not ask about visual complaints or refer patients with visual complaints to an ophthalmologist compared with fellows and attending physicians (P <.01); however, there was no significant difference between urologists in academic and nonacademic settings (P >.05)., Conclusion: Despite continuing effort to educate physicians about intraoperative floppy iris syndrome, there still exists a knowledge gap that may compromise patient care and further education is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To investigate the incidence of benign prostatic hyperplasia (BPH) in Korea and treatment patterns for 3 years after the diagnosis in a nationwide database., Materials and Methods: We created a cohort of patients diagnosed of BPH between 2007 and 2011 from the Health Insurance Review & Assessment database, a nationwide database of reimbursement. The diagnosis of BPH was defined as having the diagnosis of BPH (N40.0 in International Classification of Diseases, 10th revision) as a primary or secondary diagnosis ≥2 times in 2008. The incidence of BPH in 2008 was calculated. Treatment patterns were determined in 3 months interval and traced for 3 years. The incidence and timing of surgery were also determined. For patients taking medications preoperatively, medication-free rate was calculated., Results: The incidence of BPH was 2,105 per 100,000 men (mean age, 59.7±11.4 years), and increased with age. Surgery was performed for 7,955 patients (2.1%), half of the surgery being performed within the first 6 months. Transurethral resection of the prostate was the most commonly performed surgery. The proportion of treatment increased with age until the 7th decade of life. The patients taking medication for >1 year after the initial diagnosis was 21.4%. On average, 82% of patients became medication-free at postoperative 1 year. For patients taking preoperative anticholinergics, 1 year medication-free rate was 73.3%., Conclusions: The incidence of BPH increased with age. Surgery was performed in 2.1% of patients. More than 4/5 patients discontinued medication after surgery, while patients taking preoperative anticholinergics were less likely to., Competing Interests: The authors have nothing to disclose.

Background: At present, there are a lot of research about the effect of Alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention (PCI) in diabetic patients, but the clinical efficacy is not consistent, so we conduct this study and therefore determine the dominant strategy for the treatment of PCI in diabetic patients based on the best evidence currently., Methods: An electronic database search was conducted in MEDLINE, Embase, Cochrane library, CBM, CNKI, VIP, and WanFang to retrieve randomized controlled trial (RCT) comparing Alprostadil versus hydration on preventing CIN for PCI in diabetic patients. Reference lists of relevant articles were also screened manually to retrieve additional ones. Two investigators independently assessed the eligibility of retrieved articles using predefined inclusion and exclusion criteria. All characteristics as well as outcome variables including incidence of CIN, blood urea nitrogen (BUN), cystatin C (CysC), glomerular filtration rate (GFR), serum creatinine (Scr), serum beta 2-microspheres (β2-MG) presented in each included study were extracted. Heterogeneity was thought to be significant when I > 50%. All of the meta-analytic procedures were performed by using Review Manager software, version 5.3., Results: Finally, data from 8 articles including 969 patients were included into this meta-analysis, among them, 487 patients in the experience group, and 482 patients in the control group. Meta analysis showed that the incidence of CIN in the experimental group was significantly lower than that in the control group (OR = 0.28,95%CI[0.18,0.42]). The incidence of adverse reactions in the experimental group was significantly lower than that in the control group (OR = 0.46,95%CI[0.24,0.85]). The BUN of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.77, 95%CI [-1.22, -0.32]; MD = -1.38, 95%CI [-1.83,-0.92]; MD = -2.43, 95%CI [-2.68,-2.19], respectively). The CysC of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.30, 95%CI [-0.40, -0.21]; MD = -0.54, 95%CI [-0.68,-0.41]; MD = -0.49, 95%CI [-0.63, -0.35], respectively). The GFR of 24 hours, 48 hours, and 72 hours in the experimental group were significantly higher than that of control group (MD = 7.86, 95%CI [4.44, 11.29], MD = 18.23, 95%CI [13.76,22.69], MD = 12.81, 95%CI [8.51,17.11], respectively). The Scr of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -9.09, 95%CI [-12.67, -5.51], MD = -19.14, 95%CI [-23.61, -14.66], MD = -6.50, 95%CI [-8.29, -4.71], respectively). The β2-MG of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.12, 95%CI [-0.27, 0.03], MD = -0.55, 95%CI [-0.71, -0.39], MD = -0.50, 95%CI [-0.60, -0.39], respectively)., Conclusion: Our result suggested that comparing with conventional Hydration, Alprostadil can significantly reduce the incidence of CIN, adverse reaction, and protect renal function in PCI in diabetic patients. Due to the limitations of the quality and quantity of the articles, this conclusion still needs further research to confirm., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Overactive Bladder (OAB) is a common problem among men and women. Antimuscarinic drugs are a reference treatment for OAB and act by blocking the muscarinic receptors (M2 and M3 subtypes) in the bladder. Adherence to antimuscarinic treatment is usually low, due to the perceived lack of efficacy and adverse effects. Therefore, new treatments with different mechanisms of action and a more acceptable tolerability profile are needed, and that improve the symptoms of OAB. Mirabegron is a new treatment option for all patients with OAB and could solve an unmet need in patients still not satisfied, or where the antimuscarinic therapy is not indicated, is an alternative option for patients with OAB., (Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Nocturia is an extremely common condition that has major sequelae for affected patients. Through disruption of sleep, nocturia impairs quality of life and worsens health outcomes, and is associated with a variety of morbidities including diabetes, coronary artery disease, obstructive sleep apnoea, obesity, metabolic syndrome, and depression. Unsurprisingly, several studies have also linked nocturia with reduced survival. Nocturia is not simply a consequence of lower urinary tract disease; rather, it is a multifactorial disorder that is often a manifestation of an underlying renal or systemic disease. Through the use of the frequency volume chart, clinicians can accurately quantify nocturia and determine its aetiology. Evaluation of quality of life and sleep using simple measures is essential in order to assess the impact of nocturia on a patient. Numerous treatment options for nocturia exist, but most are associated with minor benefit or lack sufficient evidence supporting their use. By systematically analysing an individual's causes of nocturia, clinicians can design appropriate treatment strategies to most effectively treat this condition.

Despite two decades of clinical use, the effectiveness of medical expulsive therapy (MET) for the noninvasive management of patients with ureteral stones has, in the past year, been called into in question. The primary aim of MET is to expedite stone passage, although it has also shown effectiveness in reducing time to stone passage, thus reducing the incidence of colic episodes, improving stone clearance and improving patients' quality of life. At least 11 systematic reviews and meta-analyses have been published showing clinical benefits of MET; however, the results of these analyses have been challenged by data from two randomized controlled, multicentre trials with large patient cohorts, thus providing higher quality evidence that MET is ineffective in patients with ureteral stones. Results of the various systematic reviews and meta-analyses have suggested that MET is effective, however, such analyses incorporate the biases and limitations of smaller cohort studies, resulting in their conclusions being based upon lower-quality evidence. Evidence for the use of MET for small (<5 mm) distal ureteral stones has weakened based on clinical trial data published in 2015. However, MET might remain effective in the management of larger ureteral stones (>5 mm).

Aim: The aim of this study was to assess the effect of pentoxifylline on proteinuria and renal function in chronic kidney disease (CKD) treatment., Methods: We systematically searched PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov for randomized and non-randomized controlled trials comparing pentoxifylline to placebo, no treatment or renin-angiotensin system blockade in proteinuric CKD patients. The outcomes concerning proteinuria, renal function, blood pressure and adverse events were extracted., Results: Twelve trials with 613 participants were identified. Pentoxifylline significantly decreased proteinuria [weighted mean difference (WMD) -0.60 g/day (95 % CI -0.84 to -0.36); p < 0.001] compared to placebo or no-treatment groups, but the decrease was not significant [WMD: 0.10 g/day (-0.34 to 0.54); p = 0.66] compared to captopril treatment. The decrease of glomerular filtration rate was significantly less [WMD: 3.67 ml/min (2.71-4.62); p < 0.001] in the pentoxifylline group than in the controls. There was no significant difference in serum creatinine [WMD: -0.03 mg/dl (-0.10 to 0.03); p = 0.28], diastolic blood pressure [WMD: 0.94 mmHg (-0.74 to 2.61); p = 0.27] and adverse events [RR: 0.89 (0.60 to 1.32); p = 0.56]., Conclusions: Pentoxifylline may decrease proteinuria and protect renal function in patients with CKD. Further studies are needed to confirm this result.

Objective: The objective of this study was to evaluate the safety and efficacy of tamsulosin hydrochloride 0.2 mg (TAM) and its combination with solifenacin succinate 5 mg (SOL) after transurethral resection of the prostate (TURP)., Patients and Methods: The patients were randomized into three groups: TURP (group 1), TURP plus TAM (group 2), and TURP plus TAM + SOL (group 3). Patients in group 2 and group 3 received medication for 4 weeks. The primary efficacy end points were the mean change in total International Prostate Symptom Score (IPSS) and IPSS subscores. The secondary end points included quality-of-life score, Overactive Bladder Symptom Score, and short-form voiding and storage score of International Continence Society., Results: In total, 37 men (31.8%) in group 1, 37 men (31.8%) in group 2, and 42 men (36.2%) in group 3 completed the study. In total IPSS, no significant improvement was seen from baseline to the end of treatment in groups 2 and 3 compared with group 1. However, in group 2, the decrement in the IPSS storage score was smaller than group 1 ( P =0.02), and in group 3, the decrement in the IPSS voiding score was smaller than group 1 ( P =0.05). In groups 2 and 3 compared with group 1, improvements in the quality of life score, total score of Overactive Bladder Symptom Score, and short-form voiding score and storage score of International Continence Society were not statistically significant., Conclusion: Treatment with TAM and combination of TAM and SOL did not have significant additional benefits for lower urinary tract symptoms during the early recovery period after TURP.

Aims: Measurement of bladder wall thickness (BWT) by transvaginal ultrasound (TVUS) may be a less invasive method to diagnose overactive bladder (OAB) or detrusor overactivity (DO) and monitor response to therapy. This study assessed whether treatment with solifenacin affects BWT., Methods: This was a double-blind, randomised, placebo-controlled, phase 4 study. Adult women with OAB symptoms received solifenacin 5 or 10 mg or placebo once daily for 12 weeks. The co-primary endpoints were change from baseline to Week 12 in TVUS-measured BWT and urinary nerve growth factor. Only results for BWT are presented here., Results: Overall, 547 patients were randomised, 501 patients had a baseline BWT measurement, and change from baseline could be calculated for 478 patients. Mean BWT at baseline was 5.08 mm (range 2.2-11.1, SD = 1.14) and was normally distributed. A significant reduction in BWT from baseline to 12 weeks versus placebo was observed with solifenacin 5 mg (-0.42 vs. -0.16 mm, P = 0.03), but not with the 10 mg dose or with pooled solifenacin, considered the primary comparison. Both solifenacin doses were associated with improvements in efficacy and patient satisfaction endpoints versus placebo. Solifenacin was well tolerated, with dry mouth being the most common adverse event., Conclusions: There was no consistent effect of solifenacin on BWT in women with OAB/DO, despite improvements in efficacy endpoints. This study suggests that routine clinical assessment of BWT with TVUS for monitoring the effects of OAB/DO treatment is not clinically useful. Neurourol. Urodynam. 35:819-825, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient's anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient's ACB., Objective: To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model., Methods: For this budget impact model, 2 analyses were performed. The primary analysis estimated the budgetary impact of increasing the use of mirabegron in a closed patient cohort treated with oral pharmacological treatments. The secondary analysis modeled the economic impact in an open cohort by allowing untreated patients to begin treatment with mirabegron after potential contraindication, intolerance, or lack of effectiveness of antimuscarinics. The analyses were performed over a 3-year time horizon. The economic impact of increased mirabegron use was quantified using direct medical costs, including prescription costs and health resource utilization (HRU) costs. Costs of comorbidities included pharmacy and medical costs of treating OAB-related urinary tract infections (UTI), skin rashes, and depression. An analysis of a large single-site integrated health network database was commissioned to quantify ACB-related HRU in terms of the increases in yearly outpatient and emergency department visits. Based on this analysis, the model associated each unit increase in ACB score with increased HRU and probability of mild cognitive impairment. Clinical outcomes of increased use of mirabegron were presented as the number of AEs and comorbidity episodes that could be avoided. One-way sensitivity analyses were performed to quantify the expected budget impact over the range of uncertainty for the key input variables., Results: Primary analysis calculated the impact of increasing the use of mirabegron from 4.5% to 5.3%, 7.1%, and 9.4% in years 1, 2, and 3, respectively, among oral pharmacological OAB treatments that included generic and branded antimuscarinics: oxybutynin, tolterodine, trospium, darifenacin, fesoterodine, and solifenacin. For a 1 million-member U.S. commercial payer plan, the total prescription costs increased, and the total medical costs decreased during the 3-year time horizon, yielding increases of $0.005, $0.016, and $0.031 from current per member per month (PMPM) costs and $0.90, $2.92, and $5.53 from current per treated member per month (PTMPM) costs, an average of less than 2% of current OAB treatment costs. For the Medicare Advantage plan, the resulting incremental PMPM costs were $0.010, $0.034, and $0.065, and the incremental PTMPM costs were $0.93, $3.04, and $5.76; all were less than 4% of the current cost. The secondary analysis estimated the budgetary effects of reducing the untreated population by 1% annually by initiating treatment with mirabegron. For a commercial payer, this resulted in PMPM cost increases of $0.156, $0.311, and $0.467 from the current value, while the incremental PTMPM cost increased by $6.17, $11.67, and $16.61. For the Medicare Advantage plan, the incremental increases in PMPM costs were $0.277, $0.553, and $0.830, and in PTMPM costs were $6.42, $12.15, and $17.29. Clinically, treating more OAB patients resulted in fewer OAB-related comorbidities from both health plan perspectives, since most events associated with nontreatment could be avoided. In the Medicare Advantage population of the secondary analysis, the total numbers of avoided events were predicted as 452 UTIs, 2,598 depression diagnoses, and 3,020 skin rashes during the time horizon of the model., Conclusions: Mirabegron addresses an unmet need for therapy for certain OAB patients, for whom antimuscarinics are not recommended because of a risk of cognitive impairment and who are intolerant to the anticholinergic AEs. Using mirabegron involves moderate additional economic cost to a commercial or Medicare Advantage health plan for which medical cost savings can offset a substantial part of increased pharmacy costs., Disclosures: Funding for this study was provided by Astellas. Perk, Wielage, T. Klein, and R. Klein are employed by Medical Decision Modeling, a contract research company that was paid to perform the described outcomes research and build the model contained in this study. Campbell and Perkins are employed by the Regenstrief Institute, which conducted a database analysis for this research. Campbell reports consultancy fees from Astellas, as well as pending grants from Merck, Sharpe, and Dohme Corp. Posta, Yuran, and Ng are employed by Astellas Pharma Global Development, the developer of mirabegron. Study concept and design were contributed by Perk, Wielage, R. Klein, and Ng. Campbell, T. Klein, and Perkins took the lead in data collection, assisted by Perk, Wielage, and Ng. Data interpretation was performed by Posta and Yuran, along with Perk, Wielage, R. Klein, Ng, Campbell, and Perkins. The manuscript was written by Perk and R. Klein, along with Wielage, T. Klein, Posta, Yuran, and Ng, and revised by all the authors.

Purpose: This study aimed to compare the safety and efficacy of tamsulosin and tadalafil as medical expulsive therapy for distal ureteral stones., Materials and Methods: This prospective randomized study was conducted at the Department of Urology of Bir Hospital over a period of 12 months in patients with distal ureteral stones sized 5 to 10 mm. Patients were randomly divided into 2 groups: group A received tamsulosin 0.4 mg and group B received tadalafil 10 mg at bedtime for 2 weeks. Stone expulsion rate, number of ureteric colic episodes and pain score, analgesic requirements, and adverse drug effects were noted in both groups. Statistical analyses were performed by using Student t-test and chi-square test., Results: Altogether 85 patients, 41 in group A and 44 in group B, were enrolled in the study. The patients' average age was 31.72±12.63 years, and the male-to-female ratio was 1.5:1. Demographic profiles, stone size, and baseline investigations were comparable between the 2 groups. The stone expulsion rate was significantly higher in the tadalafil group than in the tamsulosin group (84.1% vs. 61.0%, p=0.017). Although the occurrence of side effects was higher with tadalafil, this difference was not significant (p=0.099). There were no serious adverse effects., Conclusions: Tadalafil has a significantly higher stone expulsion rate than tamsulosin when used as a medical expulsive therapy for distal ureteral stones sized 5-10 mm. Both drugs are safe, effective, and well tolerated with minor side effects., Competing Interests: The authors have nothing to disclose.

Objective: We investigated the clinical value of alprostadil combined with the α-lipoic acid in treating type 2 diabetes mellitus with erectile dysfunction (DMED)., Patients and Methods: We selected a total of 76 cases of patients who were admitted to endocrinology department of our hospital from June 2014 to June 2015 and diagnosed as DMED, and the average age was (46.7 ± 7.2) years old, average course of diabetes mellitus was (6.2 ± 2.8) years and average body mass index was (25.4 ± 1.3) kg/m2. 40 cases were randomly divided in the observation group while 36 cases were divided in the control group. They received blood glucose control therapy. The patients in the observation group received 60 mg alprostadil hydrochloride and 600 mg α-lipoic acid added into 250 mL normal saline, intravenous drip once per day for 2 weeks. The patients in the control group took tadalafil 5 mg orally, once per night for 2 weeks as a course of treatment. There were no cases of loss., Results: The effective rate of treatment in observation group is significantly higher than that in the control group (95.0% vs. 80.5%, p < 0.05). The score of IIEF-5, EHGS and the FMD value of brachial artery of the observation group after the operation were significantly higher than that of the control group (p < 0.05). The adverse reaction rate in the observation group was lower than that in the control group (7.5% vs. 13.9%, p < 0.05)., Conclusions: Alprostadil combined with α-lipoic acid can improve DMED patients' vascular endothelial function and erection hardness to treat erectile dysfunction with less adverse effects and better safety.

Objective: Overactive bladder is a syndrome of urinary frequency and urgency, with or without urge incontinence, in the absence of local pathological factors. Since multiple causes are responsible for OAB, it requires proper diagnosis and comprehensive management. For decades, flavoxate is a globally used and accepted molecule by the urologists and the general physicians for the symptomatic treatment of OAB. In spite of its extensive use in OAB, a meta-analysis of the available publications for efficacy, safety and tolerability of flavoxate has not been conducted. This paper evaluates the strength of evidence of clinical effectiveness of safety and tolerability of flavoxate in the symptomatic treatment of OAB., Methods: Review articles, original studies and case reports on MEDLINE, the Cochrane Library, Google Scholar, Scirus, internal repository, etc. were searched using the keyword "flavoxate". For the primary outcome, the comparative data of flavoxate versus comparator was extracted for following parameters - overall efficacy and its side effect profile. Similarly as for secondary outcome, data were extracted for flavoxate per se for overall efficacy, frequency, urinary incontinence, mixed incontinence, nocturia, unpleasant urination, stranguria and its side effect profile and were analyzed using Comprehensive Meta-Analysis (CMA) software version 2.0., Results: In the current meta-analysis, 43 relevant published studies were considered which clearly demonstrated that flavoxate had improved clinical efficacy than placebo, emepronium, propantheline, and phenazopyridine., Conclusions: Amongst all the interventions studied, flavoxate was effective and well-tolerated, with almost negligible side effects, making it worthy of consideration for the treatment of OAB.

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

Purpose: We investigated whether the novel EP (prostaglandin E2) receptor agonist ONO-8055 would improve the lower urinary tract dysfunction of neurogenic underactive bladder in a rat lumbar spinal canal stenosis model., Materials and Methods: First, we studied the agonistic effect of ONO-8055 on EP receptors in EP receptor expressing CHO (Chinese hamster ovary) cells using the increase in the intracellular calcium level and intracellular cAMP (cyclic adenosine monophosphate) production as indicators of receptor activation. The effects of ONO-8055 on bladder and urethral strips from normal rats were then investigated. Finally, the effects of ONO-8055 on bladder and urethral function in rats with lumbar spinal canal stenosis were evaluated by awake cystometry and intraurethral perfusion pressure, respectively. The effects of tamsulosin and distigmine on urethral pressure were also evaluated., Results: ONO-8055 is a highly potent and selective agonist for EP2 and EP3 receptors on CHO cells. While this compound contracted bladder strips, it relaxed urethral strips. Awake cystometry showed that ONO-8055 significantly decreased bladder capacity, post-void residual urine and voiding pressure. Compared with vehicle, tamsulosin and ONO-8055 significantly decreased urethral pressure., Conclusions: ONO-8055 decreased post-void residual urine, probably by decreasing bladder capacity. The decrease in voiding pressure probably resulted from the lowered urethral pressure due to relaxation of the urethra. Thus, the novel EP2 and EP3 receptor dual agonist ONO-8055 has the potential to improve neurogenic underactive bladder., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: To determine the association between self-reported adherence to anticholinergic medication and clinical outcomes in women with overactive bladder (OAB)., Methods: A prospective study of women with OAB treated with fesoterodine for 8 weeks. Adherence to medication was measured using the Medication Adherence Self-report Inventory (MASRI). A self reported adherence rate of ≥80% was considered adherent. The association between self-reported adherence and clinical outcomes (Global Index of Improvement, Global impression of Severity, urinary symptom and quality of life scores) was examined. We hypothesized that adherent women would have greater improvement in urinary symptoms and quality of life than non-adherent women., Results: Based on the MASRI, 115 (62.5%) women were adherent and 69 (37.5%) were non-adherent to anticholinergic medication at 8weeks. Adherent women were more likely to report overall improvement in their symptoms compared to non-adherent women (84% vs. 24%, P < 0.001). Significantly more non-adherent women described their bladder symptoms as "moderate" or "severe" at 8 weeks compared to adherent women (74% vs. 44%, P = 0.03). At 8 weeks, adherent women reported significantly greater improvement (change) in urinary symptoms from baseline to 8 weeks than non-adherent women (-13.3 ± 25.8 vs. 2.5 ± 14.4, P = 0.04). Similarly, adherent women reported greater improvement in quality of life scores than non-adherent women (- 7.9 ± 24.0 vs. -1.8 ± 11.9, P = 0.003)., Conclusion: Self-reported non-adherence, as measured by the MASRI, is associated with clinically meaningful outcomes in women with OAB. This further validates the MASRI as a clinically useful tool for measuring adherence to anticholinergic medications in women with OAB. Neurourol. Urodynam. 35:738-742, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Aims: This observational study compared data values, reliability, consistency and compliance collected by electronic and paper diaries of differing durations., Methods: Subjects ≥18 years with overactive bladder (OAB) on stable antimuscarinic treatment for ≥12 weeks were assigned to one of five, 15-week diary schedules in this randomized, parallel-group observational study. Sample size was sufficient to assess reliability and consistency of diary data with adequate precision. Reliability was assessed via intraclass correlation coefficients, variability with ANCOVAs, and consistency using Cronbach's alpha., Results: Demographic characteristics of randomized subjects were representative of OAB trial populations. For mean volume voided, reliability was comparable across diary groups. For incontinence, reliability improved with increasing diary duration. For micturition frequency, electronic 7-day diary results had highest reliability and lowest variability. Lowest overall reliability was observed in the 3-day paper diary. Consistency was highest in the electronic continuous groups; Cont A (daily measurements throughout the study period [fully Continuous]) and Cont B (daily measurements for some but not all endpoints of interest [Partially Continuous]). Compliance was generally high; across groups ≥90% of diaries had at least one entry per day. There was no significant change in average micturition frequency with diary duration, suggesting no diary fatigue. One-third of subjects in the electronic Cont B group also reported micturitions as incontinence when they only needed to report incontinence; they also reported lowest satisfaction with the study. The electronic 7-day and electronic Cont A schedules (who reported incontinence and micturitions throughout the study) had lowest residual errors., Conclusions: For future OAB trials, 7-day or continuous electronic diaries may improve accuracy and reliability of micturition and incontinence frequency data compared with shorter collection periods and paper diaries. Neurourol. Urodynam. 35:743-749, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Aims: To provide a clinical view and interpretation on the methods for analysis of incontinence in patients with overactive bladder., Methods: Results are analyzed using the total number of incontinence episodes in a 3-day diary period, using fixed and random effect Poisson regression models to calculate ratio of event rates and 95% confidence interval (CI) together with P-values and are compared with the analysis of the mean number of incontinence episodes/24 hr using analysis of covariance models to calculate P-values and 95% CI for the difference between treatments., Results: Using random effects Poisson regression models demonstrated that the number of incontinence episodes was reduced by 26% more with mirabegron 50 mg than with placebo. For solifenacin 5 and 10 mg, treatment resulted in a 43% (41%) greater decrease in the number of incontinence episodes compared with placebo., Conclusion: Instead of providing a fixed number of incontinence episodes/24 hr that reflects the mean effect, the estimate using Poisson methodology provides an efficacy estimate that can be interpreted in the context of, and relative to, the patient's baseline (severity). Using the total number of incontinence episodes in the diary period, and expressing this as percent decrease in the number of episodes, may be easier to interpret; for example, because this results in a relative measure of effect that provides an alternative understanding of a patient's improvement at end of treatment compared with the comparator arm. Also, it is based on statistical methods that are more suitable for the analysis of count data. Neurourol. Urodynam. 35:728-732, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objective: To determine risks associated with prescribing mirabegron, the first-in-class β3-adrenoreceptor agonist, to non-selected female patients with overactive bladder., Study Design: Routine female patients seeking treatment for overactive bladder (n=221) in a urology/gynecology outpatient clinic. Data on adverse events, cardiovascular outcomes, condition specific symptoms and drug discontinuation was collected at two months follow-up (FU). Non-parametric statistics was used as appropriate. Odds ratios (ORs) with 95% confidence intervals (CIs) for outcome association analyses using logistic regression., Results: 16 patients (7.2%) discontinued treatment because of side effects. There were no significant associations between cardiovascular adverse events and pre-existing cardiovascular disease (OR 0.3, 95% CI 0.3-2.6), or pre-existing ECG abnormalities (OR 2.3, 95% CI 0.3-16.3). At FU ECGs there were no de novo cases of tachyarrhythmias and no significant difference in mean QTc between baseline (403ms, SD 21.7) and the 2 months follow-up ECG (403ms, SD 20.3) (p=0.75). There was a significant decrease in the mean systolic blood pressure (p=0.03) but no significant change in mean diastolic pressure (p=0.8) or heart rates (p=0.2) from baseline to FU. Overactive bladder specific symptoms and quality of life improved significantly (p<0.001 respectively)., Conclusions: Mirabegron treatment is associated with a satisfactory cardiovascular safety profile, as well as, significant symptomatic improvement also in a heterogeneous population of non-selected women with overactive bladder presenting in everyday clinical practice., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

A short cut review was carried out to see if tadalafil, a phosphodiesterase type-5 (PDE5) inhibitor, was superior to standard α-adrenergic antagonists at promoting spontaneous ureteric calculi excretion. Two relevant papers were found, published by the same research group. The author, date and country of publication, patient group studied, study type, relevant outcomes, results study weaknesses of these papers are tabulated. Tadalafil was not shown to have significant superiority in terms of efficacy or adverse effects compared with standard treatment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To assess the benefit-risk balance of silodosin in a real-life setting of benign prostatic hyperplasia patients with lower urinary tract symptoms., Methods: A phase IV trial including men aged ≥60 years with a clinical diagnosis of benign prostatic hyperplasia with an International Prostate Symptom Score ≥12 was carried out. Patients received silodosin 8 mg for 24 weeks. The primary end-point was a decrease ≥25% in the total International Prostate Symptom Score. Secondary end-points were: changes in total, storage and voiding, and quality of life International Prostate Symptom Scores; changes in the International Continence Society-male questionnaire; changes in the frequency/volume chart; and satisfaction according to the Patient Perception of Study Medication questionnaire. Treatment-emergent adverse events were recorded., Results: Overall, 1036 patients were enrolled. Of these, 766 patients (77.1%) had a decrease ≥25% in the total International Prostate Symptom Score. The mean total International Prostate Symptom Score, and storage and voiding symptoms subscores decreased from 18.9, 8.1 and 10.8 to 10.6, 4.9 and 5.7. Nocturia decreased from 85.7% to 52.4%. The mean International Prostate Symptom Score quality of life score decreased from 4.0 to 2.2. Half of the patients reported an improvement in the frequency and bothersomeness of the most frequent symptoms reported at baseline (all P < 0.001). A reduction in the number of voids was documented by the frequency/volume chart data. The most common treatment-emergent adverse event was ejaculation failure (185 patients; 17.9%), which led to study discontinuation in 2.4% of patients. Overall, 74.2% of patients were satisfied with the medication., Conclusions: Silodosin improved lower urinary tract symptoms in three out of four patients, including diurnal voiding and storage symptoms, nocturia, and quality of life. This treatment showed a favorable safety profile in this setting., (© 2016 The Japanese Urological Association.)

Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy., Objective: To evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg., Design, Setting, and Participants: OAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4., Outcome Measurements and Statistical Analysis: The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy., Results and Limitations: A total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001), and incontinence noted in a 3-d diary (p=0.014). Combination was noninferior to solifenacin 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated., Conclusions: Adding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg., Patient Summary: In this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated., Trial Registration: ClinicalTrials.gov NCT01908829., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: The role of α-blockers after shockwave lithotripsy (SWL) is controversial. The aim of our study was to evaluate the effect of tamsulosin and silodosin after SWL for kidney stones., Methods: From 2012 onward, a consecutive series of patients undergoing SWL were prospectively enrolled and randomized by closed envelopes in three groups receiving tamsulosin 0.4 mg (A), silodosin 8 mg (B), and placebo (C) daily for 21 days after SWL. Anthropometrics, stone size, and location were recorded before SWL. Visual analogue scale (VAS) score was collected at 6, 12, and 24 hours after treatment to evaluate patients' discomfort. Stone-free rate was assessed 1 and 3 weeks postoperatively. Complications and medical treatment-related adverse events (AEs) were recorded. Differences in VAS score, stone-free rate, and complications were compared among the groups., Results: Overall, 60 patients were enrolled. Mean stone sizes were 10.28 ± 2.46 mm, 10.45 ± 1.73 mm, and 9.23 ± 2.04 mm in groups A, B, and C, respectively (p = 0.474). There was no significant difference between the three groups with regard to stone location. Comparable energy was used to treat patients from the three groups. The overall 3-week stone-free rate was 53%: 58% in the tamsulosin group, 47% in the silodosin group, and 55% in the placebo group (p = 0.399). No significant differences were observed in the VAS scores reported by the groups at 6 hours (p = 1.254), 12 hours (p = 0.075), and 24 hours (p = 0.490). Overall, 12 complications were reported: 11 patients (7 in group C and 4 in group B) needed analgesics for colic, and 1 patient (group B) was surgically treated for Steinstrasse. Tamsulosin was superior to placebo (p = 0.008) and silodosin (p = 0.021) in preventing complications; no difference between silodosin and placebo (p = 0.629) was noted., Conclusions: Tamsulosin and silodosin are ineffective in increasing stone-free rate as well as early patients' discomfort after extracorporeal lithotripsy.

Context: Lower urinary tract symptoms (LUTSs) affect 75%-80% of men undergoing radiation therapy (RT) for prostate cancer., Objectives: To determine the safety, maximum tolerated dose (MTD), and preliminary efficacy of Serenoa repens commonly known as saw palmetto (SP) for management of LUTS during RT for prostate cancer., Methods: The dose finding phase used the time-to-event continual reassessment method to evaluate safety of three doses (320, 640, and 960 mg) of SP. Dose-limiting toxicities were assessed for 22 weeks using the Common Terminology Criteria for Adverse Events for nausea, gastritis, and anorexia. The exploratory randomized controlled trial phase assessed preliminary efficacy of the MTD against placebo. The primary outcome of LUTS was measured over 22 weeks using the International Prostate Symptom Score. Additional longitudinal assessments included quality of life measured with the Functional Assessment of Cancer Therapy-Prostate., Results: The dose finding phase was completed by 27 men who reported no dose-limiting toxicities and with 20 participants at the MTD of 960 mg daily. The exploratory randomized controlled trial phase included 21 men, and no statistically significant differences in the International Prostate Symptom Score were observed. The prostate-specific concerns score of the Functional Assessment of Cancer Therapy-Prostate improved in the SP group (P = 0.03). Of 11 men in the placebo group, two received physician-prescribed medications to manage LUTS compared with none of the 10 men in the SP group., Conclusion: SP at 960 mg may be a safe herbal supplement, but its efficacy in managing LUTS during RT needs further investigation., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction and Objective: Indwelling double J ureteral stents are used routinely in the resolution of ureteral obstruction caused by different etiologies. Evaluation of urinary symptoms related to double-J stent, indicate that these affect 73-90% of patients. We conducted a prospective, randomized study, to evaluate the efficacy of tamsulosin, oxybutinin and combination therapy in improving the urinary symptoms., Methods: Patients who underwent ureteral stent placement after ureterolithotripsy (total 51), were randomized into three groups: Group I: Tamsulosin 0.4 mg. Once per day(17 patients), Group II: Oxybutinin 5 mg. once per day (17 patients), Group III: Tamsulosin+ oxybutynin once per day (17 patients). All the groups received the drugs for three weeks and completed a Spanish validated Ureteral Stent Symptom Questionnaire (USSQ) at day 7 and 21., Results: Repeated measures ANOVA showed mean urinary symptom index score was 22.3 vs. 15.5 in group three (p<0.001) at day 7 and 21 respectively. The mean work performance index was 6.6 vs 8.1 (p=0.049) favoring tamsulosin group, the mean sexual score was 0.5 vs 1.5 (p=0.03). Among additional problems the mean was 7.2 vs 6.2 (p=0.03). No significant difference was noted among pain and general health index. No side effects were reported., Conclusions: Combination therapy with tamsulosin and oxybutynin improved irritative symptoms and work performance as well as sexual matters. Combination therapy should be considered for patients who complained of stent related symptoms.

Autophagy is the cell biology process in which cytoplasmic components are degraded in lysosomes to maintain cellular homeostasis and energy production. In the healthy kidney, autophagy plays an important role in the homeostasis and viability of renal cells such as podocytes and tubular epithelial cells and of immune cells. Recently, evidence is mounting that (dys)regulation of autophagy is implicated in the pathogenesis of various renal diseases, and might be an attractive target for new renoprotective therapies. In this review, we provide an overview of the role of autophagy in kidney physiology and kidney diseases.

The objectives of the study were to evaluate changes in ureteral stent-related symptoms and urinary glycosaminoglycan (GAG) excretion after alfuzosin treatment, and to further investigate the relationship between stent-related symptoms and loss of urinary GAGs. Seventy consecutive patients scheduled for unilateral retrograde ureteroscopy with stent placement were recruited. Patients were randomly assigned to treatment with alfuzosin 10 mg/day or placebo for 3 weeks starting on the third postoperative day. The ureteral stent was removed when treatment stopped. International Prostate Symptom Score (IPSS), visual analog scale (VAS) score, and urinary GAG excretion were determined before treatment at 1, 2, and 3 weeks after treatment, and at 3 weeks after stent removal. Fifty-nine patients completed the study. IPSS, VAS score, and urinary GAG excretion were significantly lower in the alfuzosin group, compared with the placebo group, at 1, 2, and 3 weeks after treatment (P < 0.01). In both groups, IPSS, VAS score, and urinary GAG excretion were significantly lower at 3 weeks after stent removal compared with those before stent removal. No significant differences in IPSS, VAS score, or urinary GAG excretion were observed between the two groups at baseline and 3 weeks after stent removal (P > 0.05). Positive correlations were found between urinary GAG excretion (R(2) = 0.65, P < 0.001) and IPSS and between urinary GAG excretion and VAS score (R(2) = 0.33, P < 0.001). Stent placement contributes to loss of urinary GAGs. However, alfuzosin effectively reduces such loss and improves ureteral stent-related symptoms. Loss of urinary GAGs plays a role in these symptoms.

Objectives: The aim of this study was to evaluate the persistence with solifenacin therapy over a 12-month period in patients with overactive bladder (OAB)., Methods: This is a 52-week long, multicenter, prospective, observational study. The subjects were individuals ≥ 18 years old with OAB symptoms for ≥ 3 months, characterised by a total OAB Symptom Score (OABSS) of ≥ 3 and OABSS urgency item score of ≥ 2. Patients were prescribed 5 mg or 10 mg of solifenacin once daily for OAB symptoms. Drug persistence, reasons for discontinuation and factors related to the persistence were evaluated., Results: A total of 1018 patients (329 men, 689 women) with a mean age of 59 years were included. The 52-week drug persistence rate was 22.1%. The drug persistence rates at 12, 24 and 36 weeks were 72.4%, 45.8% and 31.1% respectively. The three most common reasons for discontinuing therapy included symptom improvement in 30.4%, lack of efficacy in 13.4%, and a switch to another antimuscarinic agent in 10.8%. Older patients (odds ratio = 1.02, 95% CI: 1.01-1.04), and female patients (odds ratio = 1.94, 95% CI: 1.37-2.75) were more likely to continue the medication over the 12-month period than were younger, male patients. The number of nocturia episodes was negatively correlated with drug persistence (odds ratio = 0.83, 95% CI: 0.71-0.97)., Conclusions: There was low persistence (22%) to solifenacin therapy for OAB symptoms over a 12-month period. Older patients, female patients and those with fewer episodes of nocturia were more persistent to therapy than were others., (© 2016 John Wiley & Sons Ltd.)

Ciliopathy nephronophthisis (NPHP), a common cause of end-stage renal disease (ESRD) in children and young adults, is characterized by disintegration of the tubular basement membrane accompanied by irregular thickening and attenuation, interstitial fibrosis and tubular atrophy, and occasionally cortico-medullary cyst formation. Pharmacological approaches that delay the development of ESRD could potentially extend the window of therapeutic opportunity for this group of patients, generating time to find an appropriate donor or even for new treatments to mature. In this review we provide an overview of compounds that have been tested to ameliorate kidney cysts and/or fibrosis. We also revisit paclitaxel as a potential strategy to target fibrosis in NPHP. At low dosage this chemotherapy drug shows promising results in rodent models of renal fibrosis. Possible adverse events and safety of paclitaxel treatment in pediatric patients would need to be investigated, as would the efficacy, optimum dose, and administration schedule for the treatment of renal fibrosis in NPHP patients. Paclitaxel is an approved drug for human use with known pharmacokinetics, which could potentially be used in other ciliopathies through targeting the microtubule skeleton.

A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs., (© 2015 The American Society for Clinical Pharmacology and Therapeutics.)

Background: Sexual dysfunction is common after traumatic brain injury (TBI) but evaluation of treatment interventions have been sparse., Objective: To report on the treatment of sexual dysfunction for two males with severe TBI., Methods and Results: Case one was treated for erectile dysfunction (ED). After a medical examination which found no underlying physiological problems, Sildenafil was prescribed. Scores on the Golombok Rust Inventory of Sexual Satisfaction Impotence subscale found that scores had improved from the dysfunction range at baseline to the functional range at 6 weeks follow-up. There was some reduction in this improvement at 3 months follow-up, maybe associated with a co-morbid deterioration of emotional state. Case two was treated for idiopathic delayed ejaculation (DE). A standard sex therapy intervention was employed that resulted in the resolution of the problem, documented on the Sex Behavior sub-scale of the Derogatis Inventory for Sexual Functioning-Self Report (comparing baseline to post intervention and follow-up scores)., Conclusions: The case reports show promise for the treatment of sexual dysfunction after severe TBI using standard medical and sex therapy treatments. In the future, controlled evaluations are required to demonstrate the efficacy of such interventions.

Objectives: Benign prostatic hyperplasia (BPH) is a common and progressive disease affecting elderly males, often associated with lower urinary tract symptoms (LUTS). α1-blockers are the mainstay in symptomatic therapy of BPH. Because of their greater uroselectivity and minimal hemodynamic effects, alfuzosin, tamsulosin, and silodosin are generally preferred. The aim of this study was to compare the efficacy and tolerability of alfuzosin, tamsulosin, and silodosin in patients with BPH and LUTS., Methods: Ninety subjects with BPH and LUTS were randomized into three groups of thirty in each, to receive alfuzosin sustained release (SR) 10 mg, tamsulosin 0.4 mg, or silodosin 8 mg for 12 weeks. The primary outcome measure was a change in the International Prostate Symptom Score (IPSS), and the secondary outcome measures were changes in individual subjective symptom scores, quality of life score (QLS), and peak flow rate (Qmax) from baseline. The treatment response was monitored at 2, 4, 8, and 12 weeks., Results: IPSS improved by 88.18%, 72.12%, and 82.23% in alfuzosin SR, tamsulosin and silodosin groups (P < 0.001) at 12 weeks. Improvement in QLS was >75% in all the three groups (P < 0.001). A significant improvement in Qmax was seen with alfuzosin and tamsulosin (P = 0.025 and P < 0.001) but not with silodosin (P = 0.153). However, the intergroup differences in IPSS, QLS, and Qmax were not significant. Ejaculatory dysfunction was more common with silodosin and corrected QT (QTc) prolongation occurred only with alfuzosin (two subjects) and tamsulosin (three subjects)., Conclusion: Alfuzosin, tamsulosin, and silodosin showed similar efficacy in improvement of LUTS secondary to BPH, with good tolerability, acceptability, and minimum hemodynamic adverse effects. Alfuzosin, tamsulosin, and silodosin are comparable in efficacy in symptomatic management of BPH. The occurrence of QTc prolongation in three subjects with tamsulosin in the present study is an unexpected adverse event as there are no reports of QTc prolongation with tamsulosin in any of the previous studies.

Introduction: Medical expulsive therapy (MET) is a pharmacologic approach thought to augment the spontaneous passage of ureteral calculi. The usage of MET pharmacologics for presumed ureteral calculi during pregnancy has not been studied and their safety and utility are unknown. We sought to characterize the worldwide usage of MET in the setting of pregnancy with presumed ureteral calculus (P-MET), as well as factors associated with physician use. Experts in stone management were specifically sought., Materials and Methods: A nine-question survey was delivered through society-administered e-mail. Questions gathered physician's worldwide region, degree of specialization in stone disease, practice type, interval since training, and willingness to use both MET and P-MET. We assessed drugs of choice in those using P-MET and reasons for avoidance in non-P-MET users. Finally, we assessed the impact of physician-perceived medicolegal risk on usage of P-MET., Results: Five hundred sixty-five responses were recorded. Sixty-three percent were US-based practitioners and the remaining represented a worldwide distribution. Worldwide usage of MET was 97.6%, and tamsulosin was globally preferred by over 90% of urologists. P-MET was endorsed by only 44.3%. 23.6% of European practitioners used this strategy compared with 51.1% of US physicians. Time from training and practice type did not significantly interact with adoption of P-MET; experts were less likely to use P-MET. Physician nonuse of MET during pregnancy was adverse outcome related: 76.7% reported either the fear of legal risk (52.8%) or concerns about safety (23.9%)., Conclusion: Respondents report impressive worldwide adoption of MET. P-MET is less trusted, and fears of legal risk and safety far outweigh questions about effectiveness. The effectiveness of drugs during pregnancy-induced ureteral dilation is unknown. Still, 44% of global respondents embrace usage of this drug strategy despite a paucity of evidence supporting either safety or effectiveness during pregnancy.

Overactive bladder (OAB) is a common and chronic condition that impacts patients' daily activities and quality of life. Pharmaco-therapy for OAB is a mainstay of treatment. Antimuscarinics and β3-adrenoceptor agonists are the two major classes of oral pharmacotherapy and have similar efficacy for treating the symptoms of OAB. Owing to the chronic nature of OAB, long-term use of medication is essential for OAB symptom control and positive health outcomes. However, many patients elect to stop their medications during the treatment period. Unmet expectations of treatment and side effects seem to be the major factors for discontinuing OAB pharmacotherapy. Furthermore, the short- and long-term persistence and compliance with medication management are markedly worse in OAB than in other chronic medical conditions. Improvement in persistence and compliance with OAB pharmacotherapy is a hot topic in OAB treatment and should be an important goal in the treatment of OAB. Effective strategies should be identified to improve persistence and compliance. In this review, we outline what is known about persistence and compliance and the factors affecting persistence with pharmacotherapy in patients with OAB.

In the last decade, chronic kidney disease (CKD), defined as reduced renal function (glomerular filtration rate (GFR) < 60 mL/min per 1.73 m(2) ) and/or evidence of kidney damage (typically manifested as albuminuria) for at least 3 months, has become one of the fastest-growing public health concerns worldwide. CKD is characterized by reduced clearance and increased serum accumulation of metabolic waste products (uremic retention solutes). At least 152 uremic retention solutes have been reported. This review focuses on indoxyl sulphate (IS), a protein-bound, tryptophan-derived metabolite that is generated by intestinal micro-organisms (microbiota). Animal studies have demonstrated an association between IS accumulation and increased fibrosis, and oxidative stress. This has been mirrored by in vitro studies, many of which report cytotoxic effects in kidney proximal tubular cells following IS exposure. Clinical studies have associated IS accumulation with deleterious effects, such as kidney functional decline and adverse cardiovascular events, although causality has not been conclusively established. The aims of this review are to: (i) establish factors associated with increased serum accumulation of IS; (ii) report effects of IS accumulation in clinical studies; (iii) critique the reported effects of IS in the kidney, when administered both in vivo and in vitro; and (iv) summarize both established and hypothetical therapeutic options for reducing serum IS or antagonizing its reported downstream effects in the kidney., (© 2015 Asian Pacific Society of Nephrology.)

Context: OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB)., Objective: To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB., Design: Network meta-analysis., Data Sources: A search of 9 electronic databases, review documents, guidelines and websites., Methods: Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR)., Results: No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis., Conclusions: In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: Ureteral stent discomfort is a significant postoperative problem for many patients. Despite the use of narcotics and α-blockers patients often experience bothersome lower urinary tract symptoms and pain, which impair daily activities. We compared combination therapy with an α-blocker and an anticholinergic to monotherapy with an α-blocker., Materials and Methods: A double-blind, randomized, controlled trial was performed from December 2012 to April 2014. A total of 80 patients were randomized, including 44 to the combination group (tamsulosin 0.4 mg and tolterodine early release 4 mg) and 36 to the monotherapy group (tamsulosin 0.4 mg and placebo). Patients with preexisting ureteral stent placement or current anticholinergic therapy were excluded from study. Patients completed USSQ (Urinary Stent Symptom Questionnaire) before stent placement on the day of surgery, the day after stent placement, the morning of stent removal and the day after stent removal. The questionnaire included questions regarding urinary symptoms, general health, body pain, and work and sexual history., Results: A total of 80 patients (40 males and 40 females) were studied. Mean age was 51.5 vs 51.3 years (p = 0.95) and mean body mass index was 33.6 vs 31.9 kg/m(2) (p = 0.44) in monotherapy group 1 vs combination therapy group 2. Between the 2 groups there was no significant difference in urinary symptoms, body pain and activities of daily living from baseline to just before stent removal (p = 0.95, 0.40 and 0.95, respectively). Although there was no difference between the groups, both showed improvement in urinary symptoms from the time of initial stent insertion to just prior to stent removal (difference -0.50 for combination therapy and -0.40 for monotherapy). The mean stent indwelling time of 9.6 and 8.7 days in the combination and monotherapy groups, respectively, did not differ (p = 0.67). On ANOVA it had no significant impact on results (p = 0.64)., Conclusions: Combination therapy with tamsulosin and tolterodine does not appear to improve urinary symptoms, bodily pain or quality of life in patients after ureteral stent placement for nephrolithiasis compared to tamsulosin alone. Both groups experienced worse urinary symptoms, pain and quality of life with a stent, suggesting that further research is necessary to improve stent discomfort., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Puchta P. You're the flight surgeon: erectile dysfunction. Aerosp Med Hum Perform. 2016; 87(2):152-155.

Despite being recommended for ureteral stone expulsion, tamsulosin or nifedipine are no more effective than placebo.

In Germany, too, adverse drug events (ADEs) have been identified as a central problem in the care of geriatric patients. Especially in elderly patients with multimorbidity and increasing frailty, ADEs are among the most frequent and cost-intensive causes of illness in healthcare. In most cases, they are due to drug-related diseases, which necessitate enhanced risk awareness and improved cooperation between physicians, medical specialists, geriatric nurses and pharmacists. In this context, the use of urologic medication for geriatric patients requires particular attention by the consultant., (© Georg Thieme Verlag KG Stuttgart · New York.)

Study Objective: We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter., Methods: This was a randomized, double-blind, placebo-controlled, multicenter trial of adult participants with calculus on computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion., Results: There were 403 patients randomized, 81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95% confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95% confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was no difference in urologic interventions, time to self-reported stone passage, pain, or analgesia requirements. Adverse events were generally mild and did not differ between groups., Conclusion: We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Lower urinary tract symptoms (LUTS) in men are highly prevalent, and include both storage and voiding symptoms in many cases. The effect of benign prostatic obstruction (BPO) relief on storage symptoms remains unclear., Recent Findings: The present review summarizes data about the relation between overactive bladder (OAB), voiding symptoms, and urodynamic characteristics in men with LUTS. Pathomechanisms of OAB in a context of BPO are reviewed. Rates of persistent bladder dysfunction after BPO relief are described along with predictive factors of persisting OAB., Summary: OAB is a common clinical feature in a population of male LUTS, often concomitant with voiding symptoms. Although detrusor overactivity is found in some patients with OAB and BPO, there is no absolute correspondence between clinical symptoms and urodynamic findings. In the context of BPO, OAB pathophysiology implicates nitric oxide pathway, bladder ischemia, ageing of the urinary tract, and calcium-activated potassium channels activity. BPO relief can be followed in the medium term by persistence of OAB symptoms, and preoperative detrusor overactivity has been identified as the main predictive factor. However, preoperative urodynamics remain only indicated in specific cases, when it could directly influence clinical decision-making. Antimuscarinics may be the treatment of choice for persistent symptoms after surgery, but there is no firm recommendation in this clinical setting.

Objective: To evaluate the effect of a fixed-dose combination (FDC) of solifenacin and an oral-controlled absorption system (OCAS™) formulation of tamsulosin (TOCAS) on health-related quality of life (HRQoL) in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH)., Patients and Methods: Men with moderate-to-severe storage symptoms and voiding symptoms were treated for 12 weeks with a FDC of solifenacin 6 or 9 mg plus TOCAS (0.4 mg), TOCAS monotherapy (0.4 mg) or placebo in a randomised, double-blind study (NEPTUNE). The co-primary endpoints were Total Urgency Frequency Score (TUFS) and total International Prostate Symptom Score (IPSS). HRQoL was assessed by several secondary endpoints: IPSS QoL index, overactive bladder questionnaire (OAB-q), and Patient Global Impression (PGI) scale. The correlation between symptom improvement (TUFS) and HRQoL was assessed by Spearman rank correlation coefficients. Single and double responder analyses, using subjective and objective measures, were also performed., Results: In the responder analyses, men treated with a FDC of solifenacin 6 mg plus TOCAS consistently had significantly improved outcomes compared with placebo (8/8 responder analyses performed) and TOCAS (6/8 responder analyses performed). There was a significant correlation (P < 0.001) between the reduction in TUFS and the improvement in HRQoL defined by IPSS QoL score, OAB-q symptom bother score, PGI overall bladder symptoms and PGI general health., Conclusions: In men with LUTS/BPH who have moderate-to-severe storage symptoms and voiding symptoms, the reduction in symptoms with a once-daily FDC of solifenacin and TOCAS was associated with consistent patient-relevant improvements in HRQoL compared with placebo and TOCAS monotherapy., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Aim: Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are frequent problems in older men worldwide. We evaluated the effect of short- and long-term sildenafil treatment on erectile function in rats with surgically induced partial bladder outlet obstruction (PBOO)., Methods: A total of 60 male Sprague-Dawley rats were randomized in five groups: (1) control (sham-operated); (2) PBOO for 3 weeks; (3) PBOO for 6 weeks; (4) sildenafil (1.5 mg/rat/day) treated PBOO for 3 weeks; and (5) sildenafil treated PBOO for 6 weeks. We assessed erectile function by measuring intracavernous pressures (ICP), mean arterial pressure (MAP) and total ICP after cavernous nerve stimulation. Corpus cavernous smooth muscle (CCSM) strips were isolated and evaluated for relaxation responses using organ-bath preparation. Neuronal nitric oxide synthase (nNOS) expression was determined immunohistochemically., Results: Experimental PBOO at 3 and 6 weeks showed decreased erectile response based on ICP/MAP ratio, total ICP and decreased expression of nNOS, which returned to normal after prolonged daily treatment with sildenafil. CCSM strips from PBOO rats displayed reduced relaxation responses to both electrical field stimulation (EFS) and acetylcholine (ACh) as well as nNOS enzyme intensity when compared to untreated PBOO group, which was reversed by treatment with sildenafil for 6 weeks., Conclusions: Daily sildenafil treatment prevents development of ED in PBOO rats in a time dependent manner. Further studies are needed to explore the effectiveness of sildenafil in patients with BPH/LUTS in association with ED., (© 2014 Wiley Periodicals, Inc.)

Introduction and Hypothesis: The aim of this study was to evaluate the effectiveness of transcutaneous posterior tibial nerve stimulation (T.C. PTNS) versus extended release oxybutynin (E.R.O.) in patients with overactive bladder., Materials and Methods: Seventy female patients were randomized to receive either 10mg E.R.O. daily or T.C. PTNS, using a TENS machine program with the 20Hz, 200 cycles/s, and normal stimulation setting for two 30-min sessions, each week for a 12-week period. Pre-treatment and after the 12-week intervention, each patient completed a 3-day voiding diary and a self-report quality of life questionnaire (OAB-q). Statistical analysis was performed using Stata V12.1., Results: Sixty-four patients completed the treatment protocol. There were no significant differences between study groups in terms of age, body mass index, past hormone replacement therapy, smoking habits, menopause status, and parity. Prior to treatment, there were also no significant differences in the analysis of the 3-day voiding diary or in the OAB-q questionnaire results. Following the 12-week study, there was a statistically significant reduction in frequency of urination, urgency episodes, and urge incontinent episodes compared to pre-treatment values. However, there were no significant differences in these values between intervention groups after 12-weeks of therapy. There was a similar improvement in OAB-q scores in both treatment groups following therapy, and the T.C. PTNS group showed a statistically significant improvement over the E.R.O. in domain 2 of the OAB-q questionnaire. The other two domains showed similar improvement in both study groups., Conclusion: T.C. PTNS and E.R.O. demonstrated similar improvements in subjects with OAB in a 12-week study., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Objectives: To assess the costs of treating overactive bladder (OAB) with fesoterodine compared to no OAB pharmacotherapy among vulnerable elderly from the US payer perspective., Methods: A decision analytic cost model was developed to estimate the 52-week costs of a cohort of vulnerable elderly with OAB initiating treatment with fesoterodine or no OAB pharmacotherapy. Vulnerable elderly OAB patients were defined as those aged ≥65 years with self-reported urge urinary incontinence (UUI) symptoms for ≥3 months, 2-15 UUI episodes/day, and at risk of deteriorating health by a score of ≥3 on the Vulnerable Elders Survey (VES)-13. Patients were evaluated for fesoterodine treatment response (defined as no UUI episodes) and persistence at weeks 12, 26, and 52. The model included a hypothetical health plan with 100,000 elderly members. A total of 7096 vulnerable elderly subjects were identified as the model target population based on the percentage of vulnerable elderly and annual prevalence of OAB among vulnerable elderly. OAB-related costs included fesoterodine drug acquisition costs, healthcare resource use (inpatient hospitalization, outpatient visits, and physician office visits), and OAB-related co-morbidities (falls/fractures, urinary tract infections, depression, and nursing home admissions). All costs were inflated to 2013 US$ using the medical care component of the consumer price index (CPI)., Results: When 7096 vulnerable elderly OAB patients were treated with fesoterodine, US healthcare payers could save $11,463,981 per year, or $1616 per patient vs no OAB pharmacotherapy. Univariate one-way sensitivity analyses supported the robustness of the findings and showed results were most sensitive to changes in fesoterodine efficacy followed by annual costs of inpatient hospitalization., Conclusions: From a US payer perspective, treating vulnerable elderly OAB patients with fesoterodine was cost-saving compared to no OAB pharmacotherapy.

Objective: Conclusive data comparing treatment efficacy of OAB pharmacotherapy in normal weight versus obese patients are not available. Obesity represents a risk factor for OAB/LUTS. We hypothesized that the effect of treatment with mirabegron might be diminished in obese patients., Study Design: One hundred sixty nine women were prescribed mirabegron, 50mg/day. Subjective and objective parameters were compared prior to and following three months of treatment. The study population was stratified into three groups according to a patients' BMI (A-normal weight, B-overweight, C-obese). We compared the change in parameters before and after treatment within each group. Subsequently the differences between groups were correlated. The same analysis was performed separately in patients who failed anticholinergic therapy (n=85). A paired t-test was used to compare the parameters before and after the procedure within groups, and a two-sample t-test was applied to conduct a comparison between groups. A p value of <0.05 was considered statistically significant., Results: Significant improvement (p<0.001) within all groups was observed in all parameters, with an exception in the number of severe urgency episodes per 24h (p=0.291) in Group B. We did not observe any statistically significant difference between groups A, B and C. The same trend has been observed in subgroup of patients, who did not respond previous antimuscarinic treatment., Conclusions: This study provides evidence in support of previously documented data indicating good efficacy of mirabegron in the treatment of OAB. The data obtained do not confirm our hypothesis that the body weight influences the treatment outcome of mirabegron., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)