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Introduction: Overactive bladder (OAB) affects approximately 500 million people worldwide, with a higher prevalence in women than in men, significantly impacting the quality of life of female patients. Treatment options for OAB are currently limited. Previous research has proposed that electroacupuncture could be a viable treatment for OAB in women, but there is a lack of high-quality clinical evidence. This study aims to evaluate the effectiveness of electroacupuncture as a safe and efficient non-pharmacological treatment for female OAB by comparing it with solifenacin succinate., Methods and Analysis: This study is a multicentre, single-blind, double-dummy randomised controlled non-inferiority clinical trial involving 204 eligible female participants with OAB. Participants will be randomly assigned in a 1:1 ratio to either the electroacupuncture group (receiving electroacupuncture and placebo) or the solifenacin succinate group (receiving sham electroacupuncture and solifenacin succinate). Each participant will undergo 12 sessions of electroacupuncture (or sham electroacupuncture) treatment and solifenacin succinate (or placebo) treatment over a 4-week period. The primary outcome measure will be the percentage change in the number of micturition episodes every 24 hours at week 4 compared with baseline. Secondary outcomes will include a percentage reduction in the number of micturition episodes every 24 hours at 2th, 8th and 16th weeks of the trial, Overactive Bladder Symptom Score, number of urinary incontinence and urgency episodes every 24 hours based on a 3-day voiding diary, OAB Questionnaire, Generalised Anxiety Disorder Scale-7, King's Health Questionnaire and Participant Self-evaluation of Therapeutic Effects. Adverse events will be monitored throughout the study. Efficacy analyses will be conducted on both the intention-to-treat population and the per-protocol set population., Ethics and Dissemination: Ethical approval has been obtained from the Medical Ethics Committee of Longhua Hospital Shanghai University of Traditional Chinese Medicine (approval number: 2022LCSY097). Each participant will sign a written informed consent before randomisation. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER : NCT05798403., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aims to prospectively analyze the effects of anticholinergic therapy using imidafenacin on detrusor overactivity occurring after robot-assisted radical prostatectomy (RARP)., Materials and Methods: Patients were followed-up at outpatient visits 2-4 weeks post-surgery (visit 2) to confirm the presence of urinary incontinence. Those confirmed with urinary incontinence were randomly assigned in a 1:1 ratio to the anticholinergic medication group (imidafenacin 0.1 mg twice daily) or the control group. Patients were followed-up at 1, 3, and 6 months post-surgery for observational assessments, including the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS)., Results: A total of 49 patients (25 in the treatment group and 24 in the control group) were randomized for the study. There were no differences observed between the groups in terms of age, comorbidities, prostate size, or pathological staging. According to the IPSS questionnaire results, there was no statistically significant difference between the medication and control groups (p=0.161). However, when comparing storage and voiding symptoms separately, there was a statistically significant improvement in storage symptom scores (p=0.012). OABSS also revealed statistically significant improvement in symptoms from 3 months post-surgery (p=0.005), which persisted until 6 months post-surgery (IPSS storage: p=0.023, OABSS: p=0.013)., Conclusions: In the case of urinary incontinence that occurs after RARP, even if the function of the intrinsic sphincter is sufficiently preserved, if urinary incontinence persists due to changes in the bladder, pharmacological therapy using imidafenacin can be beneficial in managing urinary incontinence., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Introduction: Vibegron is a selective β 3 -adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics., Materials and Methods: This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up., Results: The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001)., Conclusion: In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Unsupervised clustering revealed molecular subgroups characterized by expression changes in a large set of genes associated with resistance to finasteride, a 5α-reductase inhibitor. Pathway analyses within this gene cluster found finasteride administration induced changes in fatty acid metabolism, amino acid metabolism, immune response, steroid hormone metabolism, and kinase activity within the transitional zone. We found that patients without this transcriptional response were highly likely to develop clinical progression, which is expected in 13.2% of finasteride-treated patients. Importantly, a patient's transcriptional response to finasteride was associated with their pre-treatment kinase expression. Further, we identified novel expression signatures of finasteride resistance among the transcriptionally responded patients. These patients showed different gene expression profiles at baseline and increased prostate transitional zone volume compared to the patients who responded to the treatment. Our work suggests molecular mechanisms of clinical resistance to finasteride treatment that could be potentially helpful for personalized BPH treatment as well as new drug development to increase patient drug response., (© 2024. The Author(s).)

Introduction: Clinicians frequently rely on patients to accurately tell them what prescription medications and doses they are taking in outpatient visits. This information is essential to monitor the efficacy of a medication and to determine any adverse interactions. This study aimed to assess urologist and urology trainee's visual recognition of common urology medications., Methods: An online survey was distributed to urologists and urology trainees in Ireland. Images of 11 commonly prescribed urological medications were presented with free text options for answering. Information was gathered on respondent's role and experience. Data was analysed using STATA version 17., Results: The survey had a 90% response rate from 50 distributions. Respondents' roles were consultant (31.1%), specialist registrar (33.3%), registrar (22.2%), senior house officer (11.1%) and intern (2.2%). Forty six percent had more than six years urology experience. Average rate of correct responses was 39.4% ± 23.9. The most accurate group were consultants (46.1% ± 22.1), followed by specialist registrars (41.2% ± 24.9), registrars (39.1% ± 26.8), senior house officers (21.8% ± 10.4) and interns (9.1% ± 0). The most and least recognised medications were sildenafil (Viagra © ) (84.4%) and fesoterodine (Toviaz © ) (11.1%), respectively. Just 28.9% of respondents had previously handled any of the medications listed., Conclusion: Patients often do not reliably know their own medications other than to describe them or show an unpackaged tablet. Prescribing safety is paramount to ensuring patient safety and reducing the risk of adverse drug reactions. This study shows that even experienced clinicians do not recognise the medications they regularly prescribe, and decisions should not be made without accurate medication reconciliation., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cm H 2 O ± 26.12 standard deviation (SD) to 21.07 cm H 2 O ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative progressive disease of central nervous system that mostly affects young adults. (1) Because of involvement of spinal cord and brain, lower urinary dysfunction symptoms are commonly encountered. MS patients mostly show overactive bladder symptoms like urgency, frequent daytime urination, and urgency incontinence. Among MS patients, antimuscarinic therapy is the first-line treatment with overactive bladder symptoms as well as in general population yet 30% of the patients show insufficient improvement or intolerance to the treatment (2). In our study, our aim is to evaluate the efficacy and safety of mirabegron add-on treatment in MS patients after inadequate response to antimuscarinic monotherapy., Methods: University of Kyrenia and Dr Burhan Nalbantoglu State hospital's databases were screened for the study. Seventy patients who were residents diagnosed with MS according to McDonald criteria were questioned. Among these patients, a total of 22 of them were included in the study. Inclusion criteria was at least 3 years of MS diagnosis, score of <6 at Expanded Disability Status Scale, and a score of ≥3 at Overactive Bladder Symptom Score Scale., Results: Among selected patients, 10 mg solifenacin treatment was daily started and followed for 4 weeks. Mirabegron add-on treatment was initiated to the 11 patient who had inadequate improvement in overactive bladder symptom score. After mirabegron add-on treatment among 11 patient, there was a sufficient improvement in overactive bladder symptom score ( P < 0.008)., Conclusions: In our study, we have found that antimuscarinic and mirabegron combination causes improved efficacy for overactive bladder in MS population., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB)., Methods: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment., Results: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation., Conclusions: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB., Trial Registration Number: ChiCTR2400080528 (31.01.2024, retrospectively registered)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Overactive bladder syndrome is a common chronic condition with a significant impact on quality of life and economic burden. Persistence with pharmacologic therapy has been limited by efficacy and side effects. A greater understanding of the pathophysiology of overactive bladder has led to the initial evaluation of several drugs affecting ion channels, the autonomic nervous system, and enzymes which may provide useful alternatives for the management of overactive bladder., Areas Covered: A comprehensive review was performed using PubMed and Cochrane databases as well as reviewing clinical trials in the United States. The current standard of care for overactive bladder will be discussed, but this paper focuses on investigational drugs currently in preclinical studies and phase I and II clinical trials., Expert Opinion: Current therapies for overactive bladder have limitations in efficacy and side effects. A greater understanding of the pathophysiology of overactive bladder has identified the role(s) of other pathways in the overactive bladder syndrome. Targeting alternative pathways including ion channels and enzymes may provide alternative therapies of overactive bladder and a more tailored approach to the management of overactive bladder.

Introduction: Bladder storage dysfunction is associated with low quality of life in men and remains a challenging field in pharmacotherapy because of low persistence followed by patient-perceived lack of efficacy and adverse effects. The persistent desire for the development of novel pharmacotherapy is evident, leading to numerous research efforts based on its pathophysiology., Areas Covered: This review describes the pathophysiology, current pharmacotherapeutic strategies, and emerging novel drugs for male bladder storage dysfunction. The section on emerging pharmacotherapy provides an overview of current research, focusing on high-potential target molecules, particularly those being evaluated in ongoing clinical trials., Expert Opinion: As pharmacotherapies targeting alpha-adrenergic, beta-adrenergic, and muscarinic receptors - the current primary targets for treating male bladder storage dysfunction - have demonstrated insufficient efficacy and side effects, researchers are exploring various alternative molecular targets. Numerous targets have been identified as central to regulating bladder afferent nerve activity, and their pharmacological effects and potential have been evaluated in animal-based experiments. However, there is a limited number of clinical trials for these new pharmacotherapies, and they have not demonstrated clear superiority over current treatments. Further research is needed to develop new effective pharmacotherapies for bladder storage dysfunction in men.

Purpose: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients., Methods: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable., Results: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron., Conclusion: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Overactive bladder symptoms (OABSs) affect patients' quality of life (QOL) worldwide. This pooled analysis compared the efficacy and safety of mirabegron add-on tamsulosin with those of tamsulosin add-on placebo in OABS treatment., Methods: PubMed, Embase, MEDLINE, and the Cochrane Controlled Trial Register databases were searched for randomized controlled trials (RCTs) examining the efficacy of mirabegron add-on therapy to tamsulosin in the treatment of OABS. Moreover, references from the selected studies were screened. Review Manager 5.4 was used to analyze data., Results: Four RCTs involving 1,397 patients with OABS were selected. Of the total, 697 patients receiving mirabegron add-on tamsulosin constituted the experimental group, and 700 patients receiving tamsulosin add-on placebo constituted the control group. The efficacy endpoints were as follows: mean number of micturition per day (mean difference [MD] = -0.26, 95% confidence interval [CI] = -0.41 to -0.10, p = 0.0001), urgency episodes per day (MD = -0.67, 95% CI = -1.02 to -0.32, p = 0.0002), urgency urinary incontinence (UUI) episodes per day (MD = -0.42, 95% CI = -0.66 to -0.19, p = 0.0005), mean volume voided/micturition (MD = 10.84, 95% CI = 4.97-16.71, p = 0.0003), total International Prostate Symptom Score (IPSS) (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05), and IPSS QOL index (MD = -0.65, 95% CI = -0.94 to -0.35, p &lt; 0.0001). Mirabegron therapy, an add-on therapy to tamsulosin, was effective in treating patients with OABS. Moreover, mirabegron might reduce the total IPSS (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05). The safety endpoint, treatment-emergent adverse events (odds ratio = 0.94, 95% CI = 0.78-1.13, p = 0.49), suggested that although mirabegron was well-tolerated, it possibly increased the post-void residual urine volume (MD = 10.28, 95% CI = 1.82-18.75, p = 0.02)., Conclusion: Combination therapy using mirabegron and tamsulosin may be effective in treating patients with non-neurogenic OABS in terms of UUI episodes, total IPSS, and IPSS QOL index. However, its effectiveness must be verified by analyzing additional factors for OABS through further RCTs., (© 2024 S. Karger AG, Basel.)

Purpose: Medical expulsive therapy (MET) is recommended for distal ureteral stones from 5 to 10 mm. The best drug for MET is still uncertain. In this review, we aim to compare the effectiveness of tadalafil and tamsulosin for distal ureteral stones from 5 to 10 mm in terms of stone expulsion rate (SER), stone expulsion time (SET) and the side effect profile., Materials and Methods: A comprehensive literature search was conducted on MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science, from inception until April 2023. Only randomized controlled trials were included in the analysis., Results: Eleven publications with 1,330 patients were included. We observed that tadalafil has a higher SER (OR 0.55, CI 95% 0.38;0.80, p=0.02, I2=52%) and the same efficacy in SET (MD 1.07, CI 95% -0.25; 2.39, p=0.11, I2=84%). No differences were found when comparing side effects as headache, backache, dizziness, and orthostatic hypotension., Conclusion: Tadalafil has a higher stone expulsion rate than tamsulosin as a medical expulsive therapy for patients with distal stones from 5 to 10 mm without differences in side effects., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD., Objectives: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD., Methods: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods., Results: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses., Conclusions: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study., Competing Interests: Declaration of competing interest Dr. Abraham received financial compensation from the Parkinson's Foundation. Dr. Pham Nguyen is a member of the 2022–2023 Junior Investigator Intensive Program of the U.S. Deprescribing Research Network, which is funded by the National Institute on Aging [Grant #R24AG064025] and receives support from the National Institutes of Health [Grants #R01NS099129, #R01AG02515215, #R01AG06458903] and Acadia Pharmaceuticals Inc. Dr. Hennessy directs the University of Pennsylvania's Center for Real-world Effectiveness and Safety of Therapeutics (CREST), which receives funds from Pfizer and Sanofi to support pharmacoepidemiology education and has received grants from Pfizer, and Johnson and Johnson during the conduct of the study, consulted for Novo Nordisk, Arbor Pharmaceuticals, the Medullary Thyroid Cancer Consortium (Novo Nordisk, AstraZeneca, GlaxoSmithKline and Eli Lilly), Biogen, Intercept Pharmaceuticals, Provention Bio, bluebird bio, and Amylyx Pharmaceuticals, and is a special government employee of the U.S. Food and Drug Administration. Dr. Leonard is an Executive Committee Member of the University of Pennsylvania's CREST and recently received honoraria from the American College of Clinical Pharmacy Foundation, the Consortium for Medical Marijuana Clinical Outcomes Research, the University of Florida, the University of Massachusetts, and the Scientific and Data Coordinating Center for the NIDDK-funded Chronic Renal Insufficiency Cohort Study; he is a Special Government Employee of the United States (US) Food and Drug Administration and consults for their Reagan-Udall Foundation and receives travel support from John Wiley & Sons. Dr. Leonard consults for TriNetX and Novo Nordisk. Dr. Leonard's spouse is an employee of Merck; neither Dr. Leonard nor his spouse owns stock in the company. Dr. Weintraub receives support from the National Institutes of Health [Grant #R01NS099129] and has also received research funding or support from Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative (ATRI), Alzheimer's Disease Cooperative Study (ADCS), the International Parkinson and Movement Disorder Society (IPMDS); honoraria for consultancy from Acadia Pharmaceuticals Inc., Aptinyx, Biogen, Bracket, CHDI Foundation, Clintrex LLC, Enterin, F. Hoffmann-La Roche Ltd, Ferring, Promentis, Sunovion, and Takeda; and license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS. Dr. Willis receives financial support from National Institutes of Health [Grants #R01NS099129, #K24AG075234, #P30AG059302], the Parkinson's Foundation, Acadia Pharmaceuticals Inc., and the University of Pennsylvania. All other authors declared no competing interests for this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to explore the effect of terazosin hydrochloride combined with interventional embolisation on prostate volume and quality of life (QOL) of elderly patients with prostatic hyperplasia (PH)., Methods: The clinical data of 175 elderly patients with PH admitted to Central Hospital Affiliated to Shandong First Medical University from July 2020 to July 2022 were selected for retrospective analysis. Based on different treatment regimens, 89 patients who received interventional embolisation alone were included in the control group (CG), and 86 patients undergoing interventional embolisation combined with terazosin hydrochloride were included in the study group (SG). The prostate volume, serum indicators, adverse reactions and QOL of the two groups before and after treatment were compared between the two groups., Results: Before treatment, no significant difference in 36-item short-form health survey (SF-36) scores, serum tumour necrosis factor-α (TNF-α) and prostate-specific antigen (PSA) was observed in both groups ( p > 0.05). After treatment, the SF-36 score in the SG was 78.20 ± 6.84 points, which was significantly higher than that in the CG (72.67 ± 5.94 points). In addition, the SG had remarkably lower residual urine volume and prostate volume, higher maximum flow rate and lower TNF-α and PSA levels compared with the CG ( p < 0.05). The adverse reaction rate of the SG was only 4.65%, which was significantly lower than that of the CG (14.61%, p < 0.05)., Conclusions: Terazosin hydrochloride combined with interventional embolisation overtly reduces the prostate volume and improves the clinical symptoms of patients with fewer side effects, which has a certain clinical application value., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Introduction: ureteral stents have common complications like ureteral stent-related symptoms (SRSs). This study investigated the effectiveness of tadalafil compared to mirabegron and solifenacin combination therapy in patients with ureteral SRSs after double-J (DJ) stent insertion., Methods: this double-blind, randomized clinical trial used consecutive random sampling in participants with SRSs after double-J stent insertion. The study was conducted at four different hospitals in Makassar, Indonesia, from July to December 2020. Ureteral stent-related morbidity indices which analyzed include urinary symptoms, pain, general health, quality of work, and sex scores. All of the indices were measured by ureteral symptom score questionnaire for the first, second, third, and fourth weeks after drug consumption, either tadalafil 10 mg/day (group A, n=25) and a combination of mirabegron 25 mg/day and solifenacin 5 mg/day (group B, n=28)., Results: before the treatment procedure, the groups were comparable in age, gender, body mass index, DJ stent procedures, type, and indication. In general, the score in all parameters declined over the follow-up time for both groups. Group A had a lower urinary symptom score than group B at week III and week IV (all p-value < 0.001). In addition, group A had a lower pain score, general condition, work activity, and other complaints than group B at week II, week III, and week IV (all p-value <0.001). The sexual activity score is comparable between the group, except in week I., Conclusion: according to our results, we suggest tadalafil to minimize stent-related urinary symptoms and improve general health in patients with double J stent., Competing Interests: The authors declare no competing interests., (Copyright: Tjia Adynata Ciayadi et al.)

Introduction and Objectives: Medical treatments for overactive bladder (OAB) have proven efficacy in controlled trials. However, 1-year treatment persistence is reported to be as low as 25% for anticholinergics and 40% for β3 agonists. Real-world data on treatment continuation and treatment sequence is limited. Therefore, we aimed to study treatment persistence trends in women initiated on OAB medications., Materials and Methods: We used advanced data-mining techniques to query the largest regional provider's medication purchase database, dispensing for patients, for all women initiating OAB pharmacotherapy between 2010 and 2020. Treatment persistence was measured as days in which the patient was in possession of medication and nonpersistence was defined as prescription nonrefilling for 90 days. We employed a Sankey diagram to explore trends in OAB medication acquisition and treatment sequence. We compared treatment persistence using Kaplan-Meier survival curves and pairwise log-rank analysis., Results: Here, 46 079 women made 791 681 unique claims of OAB medications. Only 39% of the patients tried more than one OAB formulation, including dose change. The overall persistence rate for all drugs was 55% in 30 days, 46% in 90 days, and 37% per year. The persistence rate for Mirabegron at 30 days was 54%, 42% at 90 days, and 17% at 1 year. Overall, persistence rates were unchanged when stratifying by the time Mirabegron insurance acceptance into coverage (p > 0.05)., Conclusions: Real-world OAB pharmacotherapy persistence rates are lower than previously reported. The introduction of Mirabegron did not seem to improve these rates or affect the treatment sequence., (© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Background: Enuresis, defined as involuntary nocturnal urination without any underlying organic disorder in a child expected to control urination, poses a common problem. This study evaluated the effectiveness of Tolterodine and Oxybutynin in children presenting with primary desmopressin-resistant enuresis., Materials and Methods: A randomized clinical trial was undertaken involving 68 participants aged between 5 and 16 years, all suffering from primary enuresis. These patients were randomly assigned to one of two treatment groups for a three-month period: Group 1, treated with Oxybutynin and Desmopressin, and Group 2, treated with Tolterodine and Desmopressin. Data on demographics, clinical and laboratory findings, and subjective responses to treatment were gathered. The response was measured based on the frequency of wetting incidents per night and week and compared with pre-treatment data., Results: Patients were divided into two groups (30 patients in Group 1 and 38 patients in Group 2). The mean age of the patients was 88.97±27.09 months. In the first treatment group, 6 out of 30 patients (20%) experienced a complete treatment response, as did 5 out of 38 patients (13.2%) in the second treatment group. This difference between the groups was not statistically significant. Seven patients (23%) in the Oxybutynin group and 13 patients (34%) in the Tolterodine group reported a lack of response to treatment, a difference that also lacked statistical significance., Conclusion: For patients resistant to Desmopressin, the addition of anticholinergic drugs elicited a significant response in over half of the patients. However, no benefit was observed in using either Oxybutynin or Tolterodine in the treatment of Desmopressin-resistant enuresis., (© 2023 Neda E., et al.)

Purpose: To assess the prescribing practices for overactive bladder (OAB) pharmacotherapy based on the prescription trend analysis across different specialties of India., Method: s: IQVIA (Quintiles and IMS Health) secondary sales audit (SSA), as well as a prescription audit for antimuscarinics and beta-3 adrenoceptor agonists (mirabegron) from 2014 to 2021, were analyzed. The data includes SSA data of various antimuscarinics like solifenacin, oxybutynin, tolterodine, darifenacin, trospium and mirabegron change in the prescription trend of antimuscarinics and mirabegron across different specialties; prescribers overlap analysis for solifenacin and mirabegron among Indian urologists were also analyzed., Results: Urologists prescription rates of OAB drugs were 65% in 2016 and 54% in 2021. The rate of OAB medication prescription by non-urologist was highest from the surgeon (11%), followed by gynecologists (9%) and consultant physicians (8%) in 2021. In addition, among OAB medication prescription rates for antimuscarinics were 100% in 2016 and 58% in 2021 whereas for mirabegron, it was 0% in 2016 and 42% in 2021. Solifenacin was most frequently prescribed anticholinergics, followed by oxybutynin, tolterodine, darifenacin, and trospium. The proportion of prescribers of OAB medication among urologists was 38% in 2016 and 33% in 2021. Exclusive prescribers of solifenacin were 748 in 2018 and 739 in 2021 at the urologist, whereas for mirabegron, it was 961 in 2018 and 934 in 2021. The compound annual growth rate for prescription of the last 6 years (from 2016-2021) for solifenacin and mirabegron was -3% and 8% respectively., Conclusions: Urology remained a top prescribing specialty for OAB drugs, although prescription share increased at surgeon and consultant physician. OAB medicines prescriptions by urologists are shifting from leading antimuscarinic solifenacin to beta-agonist mirabegron. Data from this study will ultimately lead to the OAB medication preference by the specialist that could lead to more advanced OAB management.

OBJECTIVE: This review aimed to establish the comparison between mirabegron and antimuscarinic agents through the improvement of the urodynamic study (UDS) parameter among overactive bladder (OAB) populations. MATERIALS AND METHODS: The PRISMA checklist and procedure were utilized to standardize our review of studies from scientific databases published between January 2013 and May 2022 in accordance with the applied eligibility criteria. This study mainly focused on UDS parameter improvement; hence, baseline and follow-up completion were mandatory to be included. The quality of each included study was assessed with the Cochrane risk-of-bias tool in RevMan 5.4.1. RESULTS: We included a total of 5 clinical trials encompassing 430 clinically confirmed OAB individuals. Our meta-analysis demonstrated that the improvement of maximum urinary flow rate (Qmax) was more apparent in the mirabegron arm [mean difference (MD), 1.78 (1.31, 2.26); p<0.05] compared to antimuscarinics arm [MD, 0.02 (-2.53, 2.57); p>0.05) as analyzed in random-effect model (REM) analysis within 95% CI. Similar outcomes were also observed on the other UDS parameters related to the bladder's storage function, e.g., post-void residual (PVR) and detrusor overactivity (DO) cases, with most of the MDs favoring mirabegron. CONCLUSIONS: Mirabegron is superior in improving most of the UDS parameter outcomes compared to the antimuscarinics agents though the current guideline should always refer to symptoms improvement. Emphasizing the role of UDS parameter measurements to objectively confirm a therapeutic effect should be considered in the upcoming studies.

Objective: To compare the efficacy and safety of mirabegron versus vibegron in postmenopausal women with treatment-naïve overactive bladder (OAB)., Methods: We conducted a prospective randomized controlled study of women with treatment-naïve OAB. The patients received mirabegron or vibegron at 50 mg daily for 12 weeks by a stratified randomized method. The OAB symptom score (OABSS) and quality of life (QOL) index were evaluated before and 4 and 12 weeks after the treatment. The patients' 3-day voiding diary and postvoided residual urine volumes were evaluated before and 12 weeks after the treatment., Results: Of 213 patients initially enrolled in this study, 199 patients were randomized to the mirabegron group (n = 97) or vibegron group (n = 102). Twelve weeks after the treatment, OABSS, QOL index, the numbers of micturition, urgency episodes, incontinence episodes, and voided volume per 24 hours were significantly improved compared with the baseline in both groups, and there was no significant difference in the rate of change in both groups. The postvoid residual urine volume was not significantly different in the 2 groups at 12 weeks. Discontinuation because of adverse effects was observed in 6.2% of patients in the mirabegron group and 6.8% in the vibegron group, with no significant difference between 2 groups., Conclusion: Both mirabegron at 50 mg and vibegron at 50 mg improved OAB symptoms and the parameters of voiding diary equally in postmenopausal women with treatment naïve OAB., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB)., Methods: Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value < 0.05 was considered to represent statistical significance., Results: Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39)., Conclusions: Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment., (© 2022. The International Urogynecological Association.)

Objective: To compare the efficacy of Tamsulosin, Silodosin and Tadalafil as a medical expulsive therapy for treatment of distal ureteral calculi., Patients and Methods: Over a period of 6 months (January 2022 to June 2022) this prospective randomized study was conducted on 170 patients with distal ureteric stone ≤ 10 mm. Patients were randomly divided into three groups. Patients in group A received Tamsulosin 0.4mg, in group B received Silodosin, and in group C receive Tadalafil 5 mg. Therapy was given for a maximum of 4 weeks. The rate and time of stone expulsion, the analgesic use, attacks of colic and hospital visits for pain, and adverse effects of drugs were recorded., Results: Among 170 patients who were enrolled in study, 20 were lost to follow-up (7, 8, 5 in group A, B, And C respective-ly). There was a significant higher stone passage rate in group C than group A and B (90% vs. 70% and 76% respectively; p-value = 0.043) and shorter expulsion time in group C (8.7 ± 3.3 days) vs. group A (12.5 ± 5.2 days) and group B (11.3 ± 4.2 days) with (p-value = 0.001)(highly statistically significant with p-value < 0.001) and increased amount of analgesics required in group A (225 ± 115.7 mg) and group B (163 ± 77.5 mg) when compared with group C (120 ± 55.3 mg)., Conclusion: Tadalafil is more effective than Tamsulosin and Silodosin in treatment of patients with distal ureteric stones ≤ 10 mm as regard stone expulsion rate, expulsion time with decreased number of colicky episodes and side effects.

Background: The present study aims to assess the efficacy of mirabegron, a novel beta-3 agonist for ameliorating stent related symptoms (SRSs) as compared to tamsulosin and solifenacin., Methods: Total of 150 patients undergoing ureteral stent placement following ureteroscopic lithotripsy, percutaneous nephrolithotomy, or laparoscopic/robotic pyeloplasty were randomized in 1:1:1 fashion to receive mirabegron 50 mg (group A), solifenacin 5 mg (group B), and tamsulosin 0.4 mg (group C) OD respectively. Patients were followed at POD10 (I visit), 4 weeks (II visit) after surgery, and 2 weeks post-stent removal. Validated vernacular version of ureteric stent symptoms questionnaire (USSQ) was administered to the patients at each visit., Results: Out of 150 patients randomized, 123 patients (A; n  = 41, B; n  = 40, and C; n  = 42) completed the study. The groups were comparable in terms of urinary index score of USSQ at I and II visits ( p  = 0.119 and 0.076, respectively). A lower proportion of patients in group B experiencing bodily pain at II visit ( p  = 0.039), however, pain scores were comparable. Significantly lower general health index scores were observed in group A at I visit and over 4 weeks ( p  = 0.007). No significant differences were observed in other domains of USSQ. Age, sex, and surgical procedure undertaken did not significantly impact the scores in various USSQ domains., Conclusion: Mirabegron demonstrates comparable benefit in alleviating SRSs with better general health indices and may be an effective alternative for SRSs, especially when tamsulosin or solifenacin are contra-indicated or poorly tolerated.

Purpose: The primary aim of this study was to identify high prescribing specialties of overactive bladder (OAB) medications for Medicare Part D beneficiaries, and describe prescribing trends by specialty from 2013 to 2017. The secondary aim was to compare the proportion of medication claims by medication class in each specialty., Methods: We used the Medicare Part D Provider Public Use File to identify the four highest prescribing specialties from 2013 to 2017. We then compared patterns of OAB medication prescription for beneficiaries over 65 years of age between specialties. The number of medication claims, cost, and region were considered. OAB medications were classified as anticholinergic or mirabegron for additional comparison. The primary outcome was the number of OAB medication claims, and the secondary outcome was the proportion of mirabegron claims of all medication claims., Results: Primary care providers (PCPs), urology, obstetrics and gynecology (OB/GYNs), and other specialties prescribed the most OAB medications. Total claims increased from 4.06 million in 2013 to 4.51 million in 2017. Mirabegron increased from 65,520 to 892,996 claims. PCPs prescribed the most OAB medications. Urologists had the highest proportion of mirabegron prescribing (19.6%), with an increased odds of mirabegron prescribing compared to OBGYNs (aOR 1.18, 95% CI 1.16-1.19). Compared to OBGYNs, PCPs, and other specialties demonstrated decreased odds of prescribing mirabegron (aOR 0.92 with 95% CI 0.91-0.93, and aOR 0.90 with 95% CI 0.88-0.91, respectively)., Conclusion: In Medicare Part D beneficiaries, PCPs prescribed the most OAB medications between 2013 and 2017. Urologists were most likely to prescribe mirabegron.

The study aims to elucidate the impact of mirabegron versus solifenacin on autonomic function and peripheral arterial conditions in women with overactive bladder syndrome (OAB). All consecutive women with OAB were randomized to receive 12 weeks of mirabegron 25 mg or solifenacin 5 mg once per day. Heart rate variability, cardio-ankle vascular index, ankle-brachial pressure index, blood pressure, and heart rate were compared between the two groups. There were 87 women (mirabegron, n = 43; and solifenacin, n = 44) who completed 12-week treatment and underwent heart rate variability examination. Systolic blood pressure (median: - 4.5 to - 5.5 mmHg) and diastolic blood pressure (median: - 0.5 to - 3.5 mmHg) decreased after solifenacin treatment, and heart rate (median: + 2 bpm) increased after mirabegron treatment, despite of no between-group difference. In addition, posttreatment heart rate variability, cardio-ankle vascular index, and ankle-brachial pressure index did not differ compared with baseline; and there were no between-group differences. In conclusion, solifenacin might decrease blood pressure, and mirabegron might increase heart rate. Nonetheless, there were no significant impacts of 12-week mirabegron versus solifenacin treatment on autonomic function and arterial stiffness., (© 2022. The Author(s).)

Purpose: We aimed to assess the efficacy and safety of Mirabegron vs. solifenacin to treat LUTS resulting from DJ-stent insertion., Methods: A total of 97 patients who had DJ-stent inserted for urinary stone disease were randomly divided into three groups according to received treatment. Group A took Mirabegron 50 mg daily, group B took solifenacin 5 mg daily from the 4th day after stent placement until the stent was removed, and group C only was hydrated well. All patients were evaluated by USSQ and IPSS at 4th day post-insertion of ureteral stent, follow-up day before removing of stent and post-removal of stent., Results: The USSQ urinary symptom scores at day 4 comparing to day of removal of stent showed significant difference in between study groups (32 ± 6-13 ± 6 vs. 31 ± 6-14 ± 4 in Mirabegron and solifenacin, respectively) and without significant difference in control group. The USSQ body pain score significantly decreased in both Mirabegron and solifenacin groups at day of stent removal comparing to day 4 post-insertion of DJ with insignificant decreasing in the control group. Quality of life scores showed significant improving in Mirabegron and solifenacin group, and there was no difference in control group at 4 and 14 days after treatment. No severe complications were observed in either group., Discussion/conclusion: In our series, we indicate that Mirabegron and solifenacin can be used to improve symptoms caused by the insertion of DJ-stent without significant difference., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and Hypothesis: Mirabegron, a beta-3 agonist, is prescribed for urgency urinary incontinence (UUI). We assessed the correlation of symptom improvement with urobiome characteristics in adult women participants prescribed mirabegron for UUI treatment., Methods: We enrolled participants seeking UUI treatment who selected mirabegron and agreed to participate in this 12-week, open label study conducted at the Female Pelvic Medicine and Reconstructive Surgery Center at Loyola University Medical Center. Following eligibility screening and research consent, participants completed the overactive bladder questionnaire (OAB-Q) and provided a catheterized urine sample at baseline, 4, 8, and 12 weeks. The primary outcome, symptom improvement at 12 weeks, was based on the validated Patient Global Symptom Control questionnaire score to dichotomize symptom response (responder vs nonresponder [PGSC score ≤3]). Urine samples were processed by the Expanded Quantitative Urine Culture (EQUC) protocol., Results: Eighty-three participants (mean age 68 years) completed baseline assessment. Of the 47 participants with primary outcome data and samples analysis, there were 16 responders and 31 nonresponders; responder groups were similar demographically. Living microbes were detected in most participants. There were no significant differences in alpha diversity (within sample) at baseline between groups. However, at the 12-week follow-up, the responder urobiome became significantly richer, with a larger number of genera (p = 0.027) and was significantly more diverse than the nonresponders., Conclusions: Longitudinal urobiome changes are associated with symptom improvement in adult women being treated with mirabegron for UUI. The mechanism for symptoms improvement may relate to the detected changes in the urobiome and warrants further study., (© 2022. The Author(s).)

Background: We assessed the efficacy and safety of mirabegron, a β 3 -adrenoceptor agonist, in older adults (≥ 80 years old) with overactive bladder (OAB)., Methods: OAB patients aged ≥ 80 years were enrolled in this prospective, single-arm observational study. OAB was diagnosed based on the OAB symptom score (OABSS); i.e., a total score of ≥ 3 points and an urgency score of ≥ 2 points. Patients who received 50 mg mirabegron once daily were evaluated at the baseline and at 4, 8, and 12 weeks. The changes from the baseline in the OABSS, International Prostate Symptom Score (IPSS), OAB questionnaire (OAB-q) score, and Vulnerable Elders Survey (VES-13) score were determined. Adverse events, laboratory tests, 12-lead electrocardiography, the QT interval according to Fridericia's formula (QTcF), uroflowmetry, the post-void residual urine volume (PVR), and the Mini-Mental State Examination (MMSE) score were used to assess safety., Results: Forty-three patients (median age: 84 years, range: 80-96 years) were examined. They had high rates of comorbidities and polypharmacy. Mirabegron significantly improved in total score of the OABSS, including urgency and urge incontinence. The total IPSS, IPSS quality-of-life (QOL) index, and OAB-q scores also significantly improved. Mirabegron improved in the VES-13 score. There were no significant changes in laboratory test values, uroflowmetry findings, PVR, the QTcF, or MMSE score. Two patients (4.7%) withdrew from the study after experiencing adverse events., Conclusions: Mirabegron was well tolerated and significantly improved in OAB symptoms, and QOL in older patients. Trial registration The present clinical study was approved by University of Yamanashi Institutional Review Board prior to study initiation (ID1447) and was retrospectively registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (UMIN000045996) on Nov 6, 2021., (© 2022. The Author(s).)

Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases., Case Presentation: A 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home., Conclusions: IgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy., (© 2022. The Author(s).)

Background: Several studies described post-operative irritative symptoms after laser enucleation of prostate, sometimes associated with urge incontinence, probably linked to laser-induced prostatic capsule irritation, and potential for lower urinary tract infections We aimed to evaluate the efficacy of a suppository based on Phenolmicin P3 and Bosexil (Mictalase®) in control of irritative symptoms in patients undergoing thulium laser enucleation of prostate (ThuLEP)., Methods: In this single-center, prospective, randomized, open label, phase-III study, patients with indication to ThuLEP were enrolled (Dec2019-Feb2021-Institutional ethics committee STS CE Lazio approval no.1/N-726-ClinicalTrials.gov NCT05130918). The report conformed to CONSORT 2010 guidelines. Eligible patients were 1:1 randomized. Randomization defined Group A: patients who were administered Mictalase® suppositories twice a day for 5 days, then once a day for other 10 days; Group B: patients who did not receive Mictalase® ("controls"). Study endpoints were evaluated at 15 and 30 days postoperation. Primary endpoint included evaluation of effects of the suppository on irritative symptoms by administering IPSS + QoL questionnaire. Secondary endpoint included evaluation of effects on urinary tract infections by performance of urinalysis with urine culture., Results: 111 patients were randomized: 56 in Group A received Mictalase®. Baseline and perioperative data were comparable. At 15-days, no significant differences were found in terms of IPSS + QoL scores and urinalysis parameters. A significant difference in the rate of positive urine cultures favored Group A (p = 0.04). At 30-days follow-up, significant differences were found in median IPSS score (6 [IQR 3-11] versus 10 [5-13], Group A vs B, respectively, p = 0.02). Urinalysis parameters and rate of positive urine cultures were not significantly different., Conclusions: The present randomized trial investigated the efficacy of Mictalase® in control of irritative symptoms and prevention of lower urinary tract infections in patients undergoing ThuLEP. IPSS improvement 30-days postoperation was more pronounced in patients who received Mictalase®. Lower rate of positive urine culture favored Mictalase® group 15-days postoperatively., Trial Registration: The clinical trial has been registered on ClinicalTrials.gov on November 23rd, 2021-Registration number NCT05130918., (© 2022. The Author(s).)

Detrusor underactivity (DU) could be resulted from many different etiologies. Patients with DU might have reduced bladder sensation, low detrusor contractility, and large post-void residual volume. This study analyzed therapeutic outcome of active management for male DU patients, based on clinical and urodynamic characteristics. Male DU patients aged > 18 years old were retrospectively reviewed from the videourodynamic study (VUDS) records in recent 10 years. The patients' demographics, VUDS results, treatment modalities, and treatment outcome were analyzed. The treatment outcomes were compared among patients with different DU subgroups, clinical diagnosis and treatment modalities. Patients with voiding efficiency of > 66.7% were considered having a successful treatment outcome. For comparison, 30 men with normal VUDS finding served as the control arm. Most of the DU patients had reduced bladder sensation. The reduced bladder sensation is closely associated with low detrusor contractility. After active treatment, a successful outcome was achieved in 68.4% of patients after bladder outlet surgery, 59.1% after urethral botulinum toxin A injection, and 57.6% after medical treatment, but only 18.2% after conservative treatment. A successful treatment outcome was achieved in patients with an intact detrusor contractility, either low (69.2%) or normal voiding pressure (81.8%), and in patients with a normal or increased bladder sensation (78.1%). However, patients with detrusor acontractile (41.3%) or absent bladder sensation (17.9%) had less favorable treatment outcome after any kind of urological management. This study revealed that active management can effectively improve voiding efficiency in patients with DU. The normal bladder sensation, presence of adequate detrusor contractility, and bladder outlet narrowing during VUDS provide effective treatment strategy for DU patients. Among all management, BOO surgery provides the best treatment outcome., (© 2022. The Author(s).)

Aims: To descriptively evaluate treatment persistence among adults who received mirabegron or antimuscarinics in South Korea., Methods: This study involved a retrospective analysis of the Health Insurance Review and Assessment (HIRA) database. Patients (≥18 years) who had a new prescription for an overactive bladder (OAB) target medication (mirabegron/antimuscarinic) within an 8-month index period (July 1, 2015-February 29, 2016) were included. The date when the target (index) medication was dispensed was the index date. The 6-month period before the index date was used to assess patient eligibility. A 12-month post-index period was used to assess medication persistence, which was defined as the time to discontinuation. Overall data were analyzed and the results were also stratified by age group (≤65, >65 years), sex, or prior OAB medication experience. Persistence rates were calculated after the 1st, 3rd, 6th, 9th, and 12th months., Results: A data set of 52 722 cases was obtained (mirabegron: 11 424, antimuscarinics: 41 298). The mean age was 60.9 ± 16.1 years and the majority of the patients were female (30 862 [58.5%] patients). Median persistence was longer with mirabegron (51 days) versus antimuscarinics (25 days). The persistence rate with mirabegron was higher throughout the study compared with all the antimuscarinics (12-month data: 13.5% and 4.9%, respectively). Longer treatment persistence was noted in older, male, and treatment-experienced patients., Conclusion: The results from the HIRA database showed that persistence was longer with mirabegron than with antimuscarinics in South Korea. This finding may help inform clinical decision-making within the South Korean healthcare system., (© 2021 Wiley Periodicals LLC.)

Background: This study aims to explore the efficacy and safety of mirabegron in treating irritative symptoms induced by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) after transurethral resection of bladder tumors (TURBT)., Methods: A total of 160 patients subjected to TURBT was randomly divided into the mirabegron group and placebo group with 80 patients in each group. Then, the patients were administered 25 mg mirabegron or placebo daily, starting the first day after BCG infusion. The first BCG perfusion was conducted at least 2 weeks after TURBT. The 3-day bladder diaries were completed in all patients, 1 day before BCG perfusion, and on the 1st, 6th, and 13th days after the first BCG perfusion. Overactive bladder symptom scores were completed 1 day before BCG perfusion, and on the 6th and 13th days after the first BCG perfusion., Results: Symptom scores of bladder hyperactivity were significantly different between the two groups (p < 0.001). Also, the frequency of nocturia, pollakiuria, micturition urgency, urinary incontinence and was significantly lower in group 1 than that in group two (p < 0.05)., Conclusion: Our findings demonstrate that mirabegron is a valuable clinical drug for the management of irritative symptoms after TURBT with subsequent intravesical BCG perfusion., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Benign prostatic hyperplasia (BPH) is the hyperproliferation of the stromal and the epithelial cells within the prostatic transition zone. In recent years, phytotherapy have been studied with the concern for increasing quality of life, improving lower urinary tract symptoms (LUTS) as well as reducing prostate volume and the frequency of adverse events was similar to that of placebo. Linh Phu Khang Tue Tinh (LPKTT) capsules are formulated from 4 herbs widely used in traditional Vietnamese medicine - Panax notoginseng (Burkill) F.H.Chen - Tam thất (radix), Crinum asiaticum L. - Náng hoa trắng or giant crinum lily, Polygonum cuspidatum Willd. ex Spreng. (= Reynoutria japonica Houtt) - Cốt củ khí or Japanese knotweed (radix), Oldenlandia herbacea (L.) Roxb. (formerly known as Hedyotis diffusa Spreng.) - Bạch hoa xà thiẹ^t thảo or slender oldenlandia (herb). The preparation has been used in traditional Vietnamese medicine to treat nocturia, weak urine stream, urinary tract infection. According to modern studies, these herbs have anti-inflammation, antitumor, and antioxidant activities., Aims of the Study: Evaluating the effects of LPKTT capsules on the development of BPH using a rat model of BPH induced by testosterone propionate (TP)., Materials and Methods: 60 male Wistar rats, 10-12 weeks of age, weight 200-250 g were separated into six groups: (G1) a normal control group that was taken orally phosphate-buffered saline (p.o.; PBS.) with corn oil (subcutaneous injection- Sc); (G2) a BPH model group that received PBS (p.o) with TP (Sc); (G3) a positive control group that received dutasteride (25 μg/kg BW/24 h, p.o.) with TP (Sc); (G4) a positive control group that received alfuzosin HCl (1.8 mg/kg BW/24 h, p.o.) with TP (s.c.) and (G5 and G6) LPKTT groups that received LPKTT at 289.8 or 869.4 mg/kg(p.o.) respectively, with TP (s.c.). BPH model was induced by Sc of TP, 3 mg/kg for 4 weeks. After that, rats were received NaCl/Dutasteride/Alfuzosin/LPKTT for the next 28 days. On the 56th day, assessed the results were through the indicators: micturition frequency, voided volume, total voided volume, the prostate and body weights, the ratio of prostate weight to body weight, prostate histology., Results: LPKTT reduced micturition frequency and increased the voided volume when compared to the control group (p < 0.01). The results were equivalent to those of the alfuzosin ones (G4). LPKTT lowered prostate weight and the ratio of prostate weight to body weight when compared to the control group (p < 0.01). These reductions were the same in the dutasteride ones. Histomorphology in G5 and G6 also showed that LPKTT inhibited TP induced prostatic hyperplasia. The results were similar to that in the dutasteride group. Microscopic images of prostate in G5 and G6 were almost similar to that of G1., Conclusion: LPKTT capsules work to inhibit prostate proliferation in rats induced BPH by TP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Benign prostatic hyperplasia (BPH) is very common in aging men. We aimed to compare the effects of tamsulosin and pumpkin (Cucurbita pepo) seed oil on BPH symptoms., Methods: This single-blind randomized clinical trial included patients with BPH aged ≥ 50 years referred to the Urology Clinic of Shahid Beheshti Hospital, Hamadan, Iran, from August 23, 2019 to February 19, 2020. Patients were randomized into two groups. One group received 0.4 mg tamsulosin every night at bedtime and the other received 360 mg pumpkin seed oil twice a day. Patients' age, weight, height, and body mass index (BMI) were recorded. The International Prostate Symptom Score (IPSS) was filled out by the patients at baseline and then 1 month and 3 months after the initiation of treatment. The BPH-associated quality of life (QoL), serum prostate-specific antigen, prostate and postvoid residual volume, and maximum urine flow were also assessed at baseline and 3 months later. Drug side effects were also noted., Results: Of the 73 patients included in this study with a mean age of 63.59 ± 7.04 years, 34 were in the tamsulosin group and 39 in the pupkin seed oil group. Patients were comparable with respect to age, weight, height, BMI, and baseline principal variables in both groups. Also, there was no significant difference between groups in terms of principal variables at any time point. However, there was a significant decrease in IPSS and a significant improvement in QoL in both groups. Although the decrease in IPSS from baseline to 1 month and 3 months was significantly higher in the tamsulosin group compared to the pumpkin group (P = 0.048 and P = 0.020, respectively), the decrease in IPSS from 1 to 3 months was similar (P = 0.728). None of the patients in the pumpkin group experienced drug side effects, while dizziness (5.9%), headache (2.9%), retrograde ejaculation (2.9%), and erythema with pruritus occurred in the tamsulosin group., Conclusions: Pumpkin (Cucurbita pepo) seed oil relieved BPH symptoms with no side effects, but was not as effective as tamsulosin. Further studies are required to confirm the role of pumpkin seed oil as an option for the treatment of BPH symptoms. Trial registration Iranian Registry of Clinical Trials, IRCT20120215009014N340. Registered 19.02.2020. Retrospectively registered, https://en.irct.ir/trial/45335 ., (© 2021. The Author(s).)

Purpose: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text])., Materials and Methods: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text])., Results: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices., Conclusions: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.

Background: Combination drug therapy for lower urinary tract symptoms (LUTS) is beneficial to selected patients and recommended by guidelines. Patterns of real-world LUTS drug use, especially combination drug therapy, have not been studied extensively. Moreover, further understanding of the recent landscape is required following the introduction of the beta-3-adrenoceptor agonist mirabegron in the UK in 2013 for overactive bladder (OAB). The objective was to describe mono- and combination drug therapy use for LUTS in patients in UK clinical practice., Methods: This was a retrospective, descriptive, observational database study using UK Clinical Practice Research Datalink GOLD and linked databases. Men and women ≥ 18 years with a first prescription for any LUTS drug from 2014 to 2016 with ≥ 12 months continuous enrollment pre- and post-index date were included. Primary endpoints were mono- or combination drug therapy use for LUTS in male and female cohorts. Secondary endpoints were description of treatment prescribed, treatment persistence and patient demographics. Data were analyzed descriptively. Sub-cohorts were defined by drugs prescribed at index date., Results: 79,472 patients (61.3% male) were included, based on index treatments. Of all men, 82.5% received any benign prostatic obstruction (BPO) drug, 25.4% any OAB drug, and 7.9% any BPO drug plus any OAB drug. As either mono- or combination drug therapy, 77.1% received an alpha-blocker, 18.9% a 5-alpha reductase inhibitor, 23.9% an antimuscarinic agent, and 2.1% mirabegron. Of all women, 94.5% received any OAB drug, 6.0% duloxetine, and 0.5% any OAB drug plus duloxetine. As either mono- or combination drug therapy, 87.7% received an antimuscarinic, and 9.7% mirabegron. In men or women receiving OAB treatment, approximately 2.5% received combination drug therapy with an antimuscarinic agent and mirabegron. For OAB drug monotherapies, mirabegron had the highest persistence in both male and female cohorts., Conclusions: This study provides a better understanding of the recent landscape of LUTS drug use in UK clinical practice. It highlights potential undertreatment of storage symptoms in men with LUTS and the low use of combination OAB treatments., (© 2021. The Author(s).)

Background: Postoperative urinary retention is common after female pelvic reconstructive surgery. Alpha receptor antagonists can improve dysfunctional voiding by relaxing the bladder outlet and may be effective in reducing the risk of postoperative urinary retention., Objective: This study aimed to determine whether tamsulosin is effective in preventing postoperative urinary retention in women undergoing surgery for pelvic organ prolapse., Study Design: This was a multicenter, double-blind, randomized controlled trial between August 2018 and June 2020, including women undergoing surgery for pelvic organ prolapse. Patients were excluded from recruitment if they had elevated preoperative postvoid residual volume, history of postoperative urinary retention, or a contraindication to tamsulosin. Those who experienced cystotomy were excluded from analysis. Participants were randomized to a 10-day perioperative course of tamsulosin 0.4 mg vs placebo, beginning 3 days before surgery. A standardized voiding trial was performed on postoperative day 1. The primary outcome was the development of postoperative urinary retention, as defined by the failure of the voiding trial or subsequent need for catheterization to empty the bladder. Secondary outcomes included the rate of urinary tract infection and the impact on lower urinary tract symptoms as measured by the American Urological Association Symptom Index., Results: Of 119 patients, 57 received tamsulosin and 62 received placebo. Groups were similar in regard to demographics, preoperative prolapse and voiding characteristics, and surgical details. Tamsulosin was associated with a lower rate of postoperative urinary retention than placebo (5 patients [8.8%] vs 16 patients [25.8%]; odds ratio, 0.28; 95% confidence interval, 0.09-81; P=.02). The number needed to treat to prevent 1 case of postoperative urinary retention was 5.9 patients. The rate of urinary tract infection did not differ between groups. American Urological Association Symptom Index scores significantly improved after surgery in both groups (median total score, 14 vs 7; P<.01). Scores related to urinary stream improved more in the tamsulosin group than in placebo (P=.03)., Conclusion: In this placebo-controlled trial, tamsulosin use was associated with a reduced risk of postoperative urinary retention in women undergoing surgery for pelvic organ prolapse., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Alpha1-adrenoceptor antagonists (α1-blockers) are first-line drugs for the treatment of lower urinary tract symptoms associated with benign prostate hyperplasia (BPH). Doxazosin gastrointestinal therapeutic system (GITS) and tamsulosin belong to the 2 most frequently prescribed α1-blockers. This systematic review and meta-analysis was performed to compare the efficacy and tolerability of these 2 α1-blockers., Methods: A systematic review of published randomized controlled trials in English or Chinese language was performed using the PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and Vip databases. After data extraction and quality assessment, the meta-analysis was performed to compare clinical parameters (International Prostate Symptom Score [IPSS] total [IPSS-T], storage [IPSS-S], voiding [IPSS-V], maximum urine flow [Qmax], and postvoid residual) and adverse events (AEs) that changed after first drug intake., Results: After the screening, 8 eligible randomized controlled trials with 1316 patients were identified. Doxazosin-GITS showed a significantly higher efficacy compared with tamsulosin (IPSS-T P < .001, IPSS-S P < .001, and IPSS-V P < .001). There were no significant differences between the 2 drugs for changes in Qmax (P = .477) or postvoid residual (P = .739). The overall AEs were significantly lower in the doxazosin-GITS group (risk ratio: 0.77; 95% CI: 0.54-1.08; P = .036). However, dizziness (P = .387), headache (P = .745), asthenia (P = .693), postural hypotension (P = .114), and retrograde ejaculation (P = .187) were similar between the 2 groups., Conclusions: This meta-analysis indicates that doxazosin-GITS has significantly higher efficacy and lower AEs than tamsulosin in patients with lower urinary tract symptoms/benign prostate hyperplasia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Ureteral injury is a frequent complication of ureteral access sheath deployment. We sought to define the safe threshold of force for the passage of a ureteral access sheath using a novel ureteral access sheath force sensor., Materials and Methods: Ureteral access sheath-force sensor measurements were recorded in 210 renal units. A 16Fr ureteral access sheath was deployed initially based on a prior porcine study. If 6 N was reached, the surgeon was advised to downsize the 16Fr ureteral access sheath. In each case, a post-ureteroscopic lesion scale was recorded. Regression models were used to estimate the impact of adjusted variables on post-ureteroscopic lesion scale grade, 16Fr ureteral access sheath deployment, and peak force., Results: A 16Fr ureteral access sheath was deployed in 127 (61%) renal units with a mean peak force of 5.7 N. Two high-grade ureteral injuries occurred; in both cases >6 N of force was recorded. Post-ureteroscopic lesion scale grade correlated directly with peak insertion force (p <0.01). Bacteriuria within 60 days of the procedure (OR 2.009, p=0.034), combination of preoperative stent plus oral tamsulosin (OR 2.998, p=0.045), and prior ipsilateral stone surgery (OR 2.13, p=0.01) were independent predictors of successful 16Fr ureteral access sheath deployment. Among patients with neither prior ipsilateral stone surgery nor preoperative stent, preoperative tamsulosin facilitated passage of a 16Fr ureteral access sheath (OR 2.750, p=0.034)., Conclusions: Ureteral access sheath associated ureteral injury can be averted by limiting the insertion force to ≤6 N. Prior stone surgery, preoperative indwelling ureteral stent plus oral tamsulosin, and recently treated bacteriuria favored passage of a 16Fr ureteral access sheath. In the naïve, unstented patient, preoperative tamsulosin favored deployment of a 16Fr ureteral access sheath.

Abstract: This study was to evaluate the impact of the symptoms of overactive bladder (OAB) syndrome on female sexual function. Seventy nine patients with OAB (OAB group) and 79 healthy women (control group) underwent physical examination at our center, and had their sexual function evaluated using the female sexual function index (FSFI). In accordance with the presence or absence of urge incontinence, the OAB group was further divided into the wet and dry groups. The sexual function was evaluated again after 3 months of pharmacotherapy. We investigate the difference of sexual function between OAB and control group. The effect of OAB severity and OAB pharmacotherapy on sexual function was also explored. There were no significant differences between OAB group and control group, including age, body mass index (BMI), education, occupation, fertility, parity, childbirth, and menopause. Compared with the control group, the OAB group had significantly lower FSFI scores. The respective mean ± standard error FSFI scores in the control group and the OAB group were 2.98 ± 1.07 and 2.27 ± 0.96 for desire, 3.48 ± 1.16 and 2.32 ± 1.44 for arousal, 4.60 ± 1.13 and 3.10 ± 1.95 for lubrication, 3.37 ± 0.87 and 2.63 ± 1.04 for orgasm, 3.58 ± 1.02 and 2.41 ± 1.35 for sexual satisfaction, 3.58 ± 1.02 and 2.41 ± 1.35 for sexual pain, and 22.24 ± 5.29 and 15.59 ± 7.47 for the total score (P < .05 for all comparisons). The scores for desire, lubrication, orgasm, sexual satisfaction, pain, and total FSFI between the OAB-dry and OAB-wet subgroup were similar while score of arousal in OAB-wet subgroup was significantly increased compared with that of OAB-dry. OABSS score was commonly used in the assessment of OAB severity. The difference of the FSFI scores among mild OAB group, moderate OAB group, and severe OAB group was statistically significant (P < .05). Female FSFI sexual function scores were significantly improved after OAB pharmacotherapy (P < .05). Women with OAB syndrome have poorer sexual function than healthy women. Patients with more serious OAB experience more disturbing sexual dysfunction. Female sexual function scores were significantly improved after OAB pharmacotherapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To compare the efficacy and tolerability of mirabegron and solifenacin in pediatric patients with idiopathic overactive bladder (OAB) and to identify factors affecting OAB symptom improvement after treatment., Materials and Methods: We retrospectively reviewed 103 patients (5-15 years old) who visited our hospital with OAB symptoms between July 2017 and March 2019. All participants had received solifenacin or mirabegron. Those who had secondary OAB or who did not complete the frequency-volume chart either before or after treatment were excluded. The age-adjusted bladder capacity ratio was used to evaluate bladder capacity. Efficacy was assessed on the basis of patient reports and changes in the frequency-volume chart, and ≥90% reduction was regarded as "responding to medication." Tolerability was assessed by obtaining reports from patients about the adverse effects of the drug., Results: After the exclusion of 58 patients, 45 patients (29 in solifenacin-group and 16 in mirabegron-group) were included in the primary analysis. The age-adjusted bladder capacity ratio increased from 0.71 to 0.96 (p<0.001) and from 0.57 to 0.97 (p=0.002) after solifenacin and mirabegron use, respectively. Decreased bladder capacity before medication was associated with responding to medication (odds ratio, 7.41; p=0.044). There was no significant difference in efficacy between the two drugs. Drug-induced adverse effects were reported in only 3 (10.3%) of the solifenacin-treated patients., Conclusions: Mirabegron showed comparable efficacy to solifenacin in pediatric patients with idiopathic OAB. Additionally, only few adverse effects were reported, suggesting that mirabegron can be a safe alternative for the treatment of idiopathic pediatric OAB., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

The selective β 3 -adrenoceptor agonist mirabegron, an established alternative to antimuscarinic therapy for patients with overactive bladder, induces additional effects against receptors, transporters, and hepatic enzymes. The present study aimed to elucidate the effects of mirabegron on muscarinic receptors in the rat bladder using radioligand binding and functional assays. Mirabegron (0.1-100 μM) inhibited specific [ N -methyl- 3 H]scopolamine methyl chloride binding in the bladder and other tissues of rats in a concentration-dependent manner. Binding affinity in the bladder was similar to that in the heart and significantly higher than those in the submaxillary gland and brain. Mirabegron induced the concentration-dependent relaxation of carbachol-induced contractions in the rat isolated bladder. Further analyses using a two-site model revealed that the relative quantities of high- and low-affinity components for mirabegron were 44.5% and 55.5%, respectively. Respective pEC 50 values were 7.06 and 4.97. Based on the receptor binding affinity and pharmacokinetics of mirabegron, muscarinic receptor occupancy in the human bladder for 24 hours after the administration of a single oral dose of 50 mg mirabegron was 37%-76%. The present results demonstrate for the first time that mirabegron may relax the detrusor smooth muscle not only by β 3 -adrenoceptor activation but also muscarinic receptor blockade. SIGNIFICANCE STATEMENT: Mirabegron, the first selective β 3 -adrenoceptor agonist, represents an alternative to antimuscarinic agents for management of overactive bladder (OAB). The present study aimed to clarify whether mirabegron directly binds to muscarinic receptors and affects cholinergic agonist-induced contractions in rat urinary bladder and to predict muscarinic receptor occupancy in human bladder after oral administration of mirabegron. The results demonstrated that mirabegron therapy for patients with OAB may be due not only to β 3 -adrenoceptor activation but also muscarinic receptor blockade., Competing Interests: The authors indicated no conflicts of interest., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Purpose: Williams-Beuren syndrome is a chromosomal disorder caused by a deletion at region 7q11.23. Lower urinary tract symptoms are highly prevalent and significantly affect quality of life. We assessed the long-term outcomes of lower urinary tract symptoms in children with Williams-Beuren syndrome., Materials and Methods: From February 2001 to July 2016, 90 patients with Williams-Beuren syndrome were evaluated in our hospital, of whom 31 (20 boys) had at least 5 years of followup. Baseline evaluation included a history of lower urinary tract symptoms, frequency-volume chart and the impact on quality of life measured on a scale of 0 (delighted) to 6 (terrible). Pharmacological therapy with oxybutynin or doxazosin was offered to symptomatic patients. We present the outcome of lower urinary tract symptoms after 5 and 10 years of followup., Results: At baseline 27 (87.1%) patients were symptomatic. Median duration of followup was 10 (range 6-13) years. Pharmacological therapy was started for 25 (92.6%) symptomatic patients at baseline, including oxybutynin for 19 (76.0%), doxazosin for 1 (4.0%) and a combination of the 2 agents for 5 (20.0%). Medical therapy was still in use by 61.2% after 5 years and 52.9% after 10 years (p=0.043). Median duration of pharmacological treatment was 7 (range 6-11) years. A significant improvement of lower urinary tract symptoms was observed over time, with 35.5% and 29.5% patients considered symptomatic after 5 years and 10 years, respectively (p <0.001). Quality of life was also markedly improved over time (p <0.001)., Conclusions: This long-term study showed significant improvement of lower urinary tract symptoms in children and adolescents with Williams-Beuren syndrome over time. Long-term pharmacological treatment was needed in most patients.

Background: Safety and efficacy of tamsulosin and tadalafil for men with benign prostatic enlargement (BPE) and/or erectile dysfunction (ED) are defined. However, there are only a few pilot studies on combination therapy with these drugs for men with lower urinary tract symptom (LUTS)/BPE and ED. Moreover, preliminary reports are limited to 12 wk, without any information about subsequent therapies., Objective: To evaluate the impact of discontinuation of tamsulosin versus tadalafil 12 wk after combination therapy., Design, Setting, and Participants: Fifty consecutive patients with moderate-to-severe LUTS (International Prostate Symptom Score [IPSS] > 7) and mild-to-severe ED (International Index of Erectile Function-5 [IIEF-5] < 22) were treated with combination therapy (tamsulosin 0.4mg/d plus tadalafil 5mg/d) for 12 wk. After 12 wk, 25 patients discontinued tamsulosin (Group TAD), while 25 patients discontinued tadalafil (Group TAM)., Outcome Measurements and Statistical Analysis: Efficacy variables were IPSS (total, voiding, storage) and IIEF-5. Paired samples t test and analysis of variance were used., Results and Limitations: Groups TAD and TAM presented similar features (age, BMI, metabolic profile) including symptoms scores at baseline. Similar and significant improvements in IPSS (total, voiding, and storage) and IIEF-5 were recorded in both groups after 12 wk of combination therapy (all p< 0.001). Total IPSS was similar between the two groups at the end of the trial. However, we found between-group significant differences from baseline to 24 wk and from 12 to 24 wk in storage-IPSS (Group TAD: -3.32 vs Group TAM: -1.24, p= 0.002; Group TAD: +0.24 vs Group TAM: +1.20, p= 0.040, respectively) and in IIEF-5 (Group TAD: +4.64 vs Group TAM: +0.16, p< 0.001; Group TAD: -1.64 vs Group TAM: -4.40, p= 0.003). No significant treatment-related adverse event was recorded in both groups., Conclusions: After 12 wk of combination therapy, monotherapy with tadalafil for further 12 wk allows to preserve the improvement of storage IPSS and IIEF-5, in addition to total IPSS., Patient Summary: In this report we evaluated the discontinuation of tamsulosin or tadalafil after 12 wk of combination therapy. We found that tadalafil monotherapy, for a further 12 wk, aids in retaining the improvement of storage symptoms and erectile function., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We performed a post hoc analysis of data from phase 3 and 4 studies to evaluate the efficacy of silodosin 8mg in patients with severe lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). The presence of two or more of the following criteria was adopted to define severity: total International Prostate Symptom Score (IPSS) 20-35, quality of life (QoL) score 5-6, maximum urinary flow <5ml/s or postvoid residual volume ≥100ml, and prostate volume ≥50ml. Mean improvements in total (8.1 vs 4.7), storage (3.1 vs 2.0), voiding (5.0 vs 2.7), and QoL (1.3 vs 0.7) IPSS scores were significantly greater for patients receiving silodosin compared to placebo (all p< 0.0001). Mean improvements in total, storage, voiding, and QoL IPSS scores were similar for the severe and not severe LUTS cohorts. In conclusion, silodosin significantly improves symptoms and QoL in all LUTS/BPO patients, including those with severe symptoms. PATIENT SUMMARY: Silodosin improves symptoms and quality of life for patients with severe lower urinary tract symptoms related to benign prostatic obstruction., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The International Prostate Symptom Score (IPSS), the quality of life (QoL) score, and the benign prostatic hyperplasia impact index (BII) are three different scales commonly used to assess the severity of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH-LUTS). Based on a phase II clinical trial including 403 patients with moderate to severe BPH-LUTS, the objectives of this study were to (i) develop traditional pharmacometric and bounded integer (BI) models for the IPSS, QoL score, and BII endpoints, respectively; (ii) compare the power and type I error in detecting drug effects of BI modeling with traditional methods through simulation; and (iii) obtain quantitative translation between scores on the three abovementioned scales using a BI modeling framework. All developed models described the data adequately. Pharmacometric modeling using a continuous variable (CV) approach was overall found to be the most robust in terms of type I error and power to detect a drug effect. In most cases, BI modeling showed similar performance to the CV approach, yet severely inflated type I error was generally observed when inter-individual variability (IIV) was incorporated in the BI variance function (g()). BI modeling without IIV in g() showed greater type I error control compared to the ordered categorical approach. Lastly, a multiple-scale BI model was developed and estimated the relationship between scores on the three BPH-LUTS scales with overall low uncertainty. The current study yields greater understanding of the operating characteristics of the novel BI modeling approach and highlights areas potentially requiring further improvement.