Deprescribing as a Way to Reduce Inappropriate Use of Drugs for Overactive Bladder in Primary Care (DROP): Protocol for a Cluster Randomized Controlled Trial With an Embedded Explanatory Sequential Mixed Methods Study.

BACKGROUND: Potentially inappropriate medication remains a significant concern in general practices, particularly in the context of overactive bladder (OAB) treatment for individuals aged 65 years and older. This study focuses on the exploration of alternative options for treating OAB and the deprescribing of anticholinergic drugs commonly used in OAB. The research aims to comprehensively evaluate the efficiency of deprescribing through a mixed methods approach, combining quantitative assessment and qualitative exploration of perceptions, experiences, and potential barriers among patients and health care personnel. OBJECTIVE: This study aims to evaluate the efficiency and safety of the intervention in which health care staff in primary care encourage patients to participate in deprescribing their drugs for OAB. In addition, we aim to identify factors contributing to or obstructing the deprescribing process that will drive more informed decisions in the field of deprescribing and support effective and safe treatment of patients. METHODS: The drugs for overactive bladder in primary care (DROP) study uses a rigorous research design, using a randomized controlled trial (RCT) with an embedded sequential explanatory mixed methods approach. All general practices within the North Denmark Region will be paired based on the number of general practitioners (GPs) and urban or rural locations. The matched pairs will be randomized into intervention and control groups. The intervention group will receive an algorithm designed to guide the deprescribing of drugs for OAB, promoting appropriate medication use. Quantitative data will be collected from the RCT including data from Danish registries for prescription analysis. Qualitative data will be obtained through interviews and focus groups with GPs, staff members, and patients. Finally, the quantitative and qualitative findings are merged to understand deprescribing for OAB comprehensively. This integrated approach enhances insights and supports future intervention improvement. RESULTS: The DROP study is currently in progress, with randomization of general practices underway. While they have not been invited to participate yet, they will be. The inclusion of GP practices is scheduled from December 2023 to April 2024. The follow-up period for each patient is 6 months. Results will be analyzed through an intention-to-treat analysis for the RCT and a thematic analysis for the qualitative component. Quantitative outcomes will focus on changes in prescriptions and symptoms, while the qualitative analysis will explore experiences and perceptions. CONCLUSIONS: The DROP study aims to provide an evidence-based intervention in primary care that ensures the deprescription of drugs for OAB when there is an unfavorable risk-benefit profile. The DROP study's contribution lies in generating evidence for deprescribing practices and influencing best practices in health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT06110975; https://clinicaltrials.gov/study/NCT06110975. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56277.

Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.

Efficacy and safety of Vibegron for the treatment of residual overactive bladder symptoms after laser vaporization of the prostate: A single-center prospective randomized controlled trial (VAPOR TRIAL).

OBJECTIVES: This study aimed to evaluate the efficacy and safety of Vibegron for the treatment of residual overactive bladder (OAB) symptoms after laser vaporization of the prostate (photo-selective vaporization of the prostate, contact laser vaporization of the prostate, and thulium laser vaporization). METHODS: This randomized, open-label, parallel-group, single-center superiority trial with a 12-week observation (jRCTs071190040) enrolled male patients with OAB aged 40 years or older who had undergone laser vaporization of the prostate for not less than 12 weeks and not more than 1 year earlier. Patients were allocated to receive Vibegron 50 mg once daily or follow-up without treatment for 12 weeks. RESULTS: Forty-seven patients were enrolled between January 2020 and March 2023. The median age (interquartile range) was 75.5 (72.5-78.5) years for the Vibegron group and 76.5 (71.0-81.0) years for the control group. The intergroup difference in the mean change (95% confidence interval) in the 24-hour urinary frequency at 12 weeks after randomization was -3.66 (-4.99, -2.33), with a significant decrease for the Vibegron group. The Overactive Bladder Symptom Score, International Prostate Symptom Score, IPSS storage score, and Overactive Bladder Questionnaire score significantly improved for the Vibegron group. Voided volume per micturition also increased for the Vibegron group. CONCLUSIONS: The administration of 50 mg of Vibegron once daily for 12 weeks showed significant improvement compared with follow-up without treatment in bladder storage (OAB) symptoms after laser vaporization of the prostate for symptomatic benign prostatic hyperplasia.

Clinical efficacy and safety analysis of type A botulinum toxin in the treatment of adolescents with refractory overactive bladder.

The objective of this study was to assess the clinical effectiveness and safety of type A botulinum toxin in the treatment of refractory overactive bladder in adolescents. We conducted a retrospective analysis of 37 adolescent patients with refractory overactive bladder who were treated at the Urology Department of Hangzhou Third People's Hospital between January 2018 and August 2023. These patients received intravesical injections of type A botulinum toxin at a concentration of 10 U/mL, with an average of 20 injection points. We recorded changes in urination diaries and urodynamic parameters both before and 1 month after treatment. After 1 month of treatment, significant improvements were observed in several parameters, when compared to the pretreatment values. These included daytime frequency of urination (11.13 ±â€…6.45), average single void volume (173.24 ±â€…36.48) mL, nighttime frequency of urination (2.43 ±â€…0.31), urgency episodes (3.12 ±â€…0.27), initial bladder capacity (149.82 ±â€…41.34) mL, and maximum bladder capacity (340.25 ±â€…57.12) mL (all P < .001). After the first treatment, 5 patients had mild hematuria, 4 patients had urinary tract infection, and 1 patient had urinary retention, which was relieved after catheterization. No serious complications or adverse reactions were observed in other patients. The follow-up period ranged from 6 to 18 months, and the duration of efficacy varied from 2 to 8 months. Eight patients who initially had treatment failure achieved symptom relief after reinjection. In adolescents with refractory overactive bladder who do not respond well to conventional drug therapy, type A botulinum toxin can be administered safely and effectively. It significantly improves lower urinary tract symptoms and enhances the quality of life for these patients.

Efficacy and Safety of Mirabegron Add-on Therapy After Failure With Solifenacin in Multiple Sclerosis Patients With Overactive Bladder: A Pilot Study.

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.

Strategies for Safe Transurethral Injections of Botulinum Toxin into the Bladder Wall.

Introduction: Transurethral injections into the bladder wall with botulinum toxin are an established treatment for refractory overactive bladder or detrusor overactivity. With the current injection technique, an average of approx. 18% and up to 40% of botulinum toxin is injected next to the bladder wall, potentially causing reduced efficacy or non-response. The article aims to evaluate the reasons for incorrect injections and propose strategies for complete delivery of the entire botulinum toxin fluid into the bladder wall. Material and Methods: Unstructured literature search and narrative review of the literature. Results: Incorrect injection of botulinum toxin fluid next to the bladder wall is caused by pushing the injection needle too deep and through the bladder wall. Bladder wall thickness decreases with increasing bladder filling and has a thickness of less than 2 mm beyond 100 mL in healthy individuals. Ultrasound imaging of the bladder wall before botulinum toxin injection can verify bladder wall thickness in individual patients. Patient movements during the injection therapy increase the chance of incorrect placement of the needle tip. Conclusions: Based on the literature search, it is helpful and recommended to (1) perform pretreatment ultrasound imaging of the bladder to estimate bladder wall thickness and to adjust the injection depth accordingly, (2) fill the bladder as low as possible, ideally below 100 mL, (3) use short needles, ideally 2 mm, and (4) provide sufficient anesthesia and pain management to avoid patient movements during the injection therapy.

Efficacy of transcutaneous electrical nerve stimulation combined with mirabegron therapy compared with mirabegron monotherapy for overactive bladder: a prospective randomized controlled study.

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).

Concomitant Botulinum Toxin Injections for Neurogenic Detrusor Overactivity and Spasticity-A Retrospective Analysis of Practice and Safety.

As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.

[Botulinum toxin A for idiopathic overactive bladder in women]. / Botulinumtoxin A bei idiopathischer Blasenüberaktivität (iOAB) der Frau.

Following a description of the historic evolution of botulinum toxin A detrusor injections for neurogenic and nonneurogenic bladder overactivity, which was mainly driven by German-speaking countries, the terminological revolution of 2002 and the influence on design and outcomes of upcoming approval studies for the indication overactive bladder (OAB) are examined. OnabotulinumtoxinA (100 IU) for second-line treatment of OAB received European approval in 2013. Phase IV observational studies concerning therapeutic persistence and adherence with onabotulinumtoxinA are analyzed and compared with therapeutic alternatives. Predictors of treatment success and complications are identified and compared to the required preinterventional diagnostic effort. Since onabotulinumtoxinA and sacral neuromodulation (SNM) are competing for second-line OAB treatment, both options are compared with regard to differential indications, effectivity, durability and patient adherence. Gender-specific causes of urgency and urge incontinence in women are differentiated from the diagnosis of OAB and require priority treatment. On the basis of diagnostic examination results, an algorithm for invasive second-line treatment of OAB is presented, since overly liberal utilization of onabotulinumtoxinA in therapy-naive OAB patients has not proven superiority over oral antimuscarinergic standard therapy, which can only be explained by improper patient selection.

Intradetrusor Versus Suburothelial Onabotulinum Toxin A in Adults with Neurogenic and Non-neurogenic Overactive Bladder Syndrome: A Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor injection for overactive bladder syndrome (OAB). METHODS: This systematic review is registered with PROSPERO (CRD42021237964). A licensed librarian surveyed Medline, EMBASE, Scopus, and Google Scholar databases to conduct a comprehensive search. Studies comparing suburothelial and intradetrusor techniques of OnabotA injection for OAB were included, along with clinical and urodynamic variables and complications. The studies were assessed for quality on the basis of Cochrane Collaboration guidelines and evaluated using statistical analysis via a random-effect model and I2 statistic. Data extraction and analysis were conducted using Covidence systematic review platform and Review Manager software. RESULTS: Six studies with 299 patients were included in the systematic review, with four reporting that suburothelial injection of OnabotA was as effective as intradetrusor injection and two reporting intradetrusor injection to be more effective. The meta-analysis found no significant difference between the suburothelial and intradetrusor groups for mean daily catheter or voiding frequency (mean difference: 2.12 [95% confidence interval (CI): -1.61, 5.84]) and the mean number of urgency/urge incontinence episodes (mean difference: 0.08 [95% CI: -1.42, 1.57]). However, a significant heterogeneity was found among the studies. Only the mean volume at first detrusor contraction showed a significant difference, being higher for suburothelial injection (mean difference: 33.39 [95% CI: 0.16, 66.63]). No significant difference was noted for mean compliance, mean bladder capacity, and mean maximum detrusor pressure. Urinary tract infections (UTIs) (p = 0.24) and acute urinary retention (p = 0.92) showed no significant difference between the two groups. The risk of bias varied among the studies. CONCLUSIONS: Suburothelial injection of OnabotA is as effective as intradetrusor injection in improving OAB symptoms, and it has similar complication rates. A higher mean volume of the first detrusor contraction was found in a urodynamic study with suburothelial injection.

Emerging therapies for overactive bladder: preclinical, phase I and phase II studies.

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.

Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome.

INTRODUCTION: Overactive Bladder Syndrome (OAB) significantly impacts quality of life, necessitating improved diagnostic tools and treatment monitoring. This study explores the potential of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) as urinary biomarkers in patients with OAB undergoing mirabegron therapy, a ß3-adrenergic agonist. This investigation is aimed at providing insights into the potential of neurotrophins to enhance OAB diagnosis and assess treatment efficacy. MATERIALS AND METHODS: Urinary NGF and BDNF levels were measured in 15 healthy controls and 30 patients with OAB. Patients were treated with mirabegron 50 mg once daily. Urinary NGF and BDNF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cre and BDNF/Cre). The urinary NGF/Cre and BDNF/Cre levels were compared between controls and patients with OAB and subsequently at baseline and 3 months after mirabegron treatment. Treatment efficacy was assessed with the Indevus Urgency Severity Scale (IUSS) questionnaire. RESULTS: Urinary NGF/Cre and BDNF/Cre levels were significantly higher in patients with OAB than in the controls (p < 0.001 and p = 0.03 respectively). Moreover, NGF/Cre and BDNF/Cre levels significantly decreased post-mirabegron treatment (p < 0.001 and p = 0.005 respectively). Patients with improvement of OAB symptoms after treatment showed lower levels of NGF/Cre at the 3-month evaluation than those with no improvement (p = 0.05). CONCLUSION: Although both NGF/Cre and BDNF/Cre levels were significantly decreased after mirabegron treatment, only NGF/Cre levels were associated with treatment response.

[Botulinum toxin in male lower urinary tract symptoms (LUTS): What can we expect?] / Botulinumtoxin bei Symptomen des unteren Harntraktes beim Mann ("male LUTS"): Was darf man erwarten?

During the last two decades botulinum toxin has also conquered urology. Botulinum toxin reduces the contractility and sensitivity of the detrusor muscle and relieves pain. It is therefore a promising drug whose use in men also appears promising. The following article highlights the practical relevance of botulinum toxin for male lower urinary tract symptoms (LUTS). But first of all, a distinction must be made between use in male LUTS due to benign prostate syndrome (BPS) and use in cases of overactive bladder (OAB) alone. A differentiated diagnosis and treatment of male LUTS is therefore essential.

[Intravesical oxybutynin treatment for neurogenic detrusor overactivity : Efficacy and safety data from clinical practice with the first intravesical oxybutynin treatment authorized in Germany]. / Intravesikale Oxybutynin-Behandlung der neurogenen Detrusorüberaktivität : Wirksamkeits- und Sicherheitsdaten aus der Praxis der ersten in Deutschland zugelassenen intravesikalen Oxybutynin-Behandlung.

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 H2O ± 26.12 standard deviation (SD) to 21.07 cm H2O ± 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.

Efficacy and Safety of Vibegron for Persistent Symptoms of Overactive Bladder in Men Being Pharmacologically Treated for Benign Prostatic Hyperplasia: Results From the Phase 3 Randomized Controlled COURAGE Trial.

PURPOSE: The efficacy and safety of vibegron, a ß3-adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial. MATERIALS AND METHODS: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs). RESULTS: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%). CONCLUSIONS: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

Effects of oral administration of nonselective Trk inhibitor on bladder overactivity in rodent models of prostatic inflammation.

BACKGROUND: Our research focused on the assessment of the impact of systemic inhibition of Trk receptors, which bind to nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), on bladder hypersensitivity in two distinct rodent models of prostatic inflammation (PI). METHODS: Male Sprague-Dawley rats were divided into three groups (n = 6 each): the control group (no PI, vehicle administration), the untreated group (PI, vehicle administration), and the treated group (PI, nonselective Trk inhibitor, GNF 5837, administration). PI in rats was induced by a intraprostatic injection of 5% formalin. Posttreatment, we carried out conscious cystometry and a range of histological and molecular analyses. Moreover, the study additionally evaluated the effects of a nonselective Trk inhibitor on bladder overactivity in a mouse model of PI, which was induced by prostate epithelium-specific conditional deletion of E-cadherin. RESULTS: The rat model of PI showed upregulations of NGF and BDNF in both bladder and prostate tissues in association with bladder overactivity and inflammation in the ventral lobes of the prostate. GNF 5837 treatment effectively mitigated these PI-induced changes, along with reductions in TrkA, TrkB, TrkC, and TRPV1 mRNA expressions in L6-S1 dorsal root ganglia. Also, in the mouse PI model, GNF 5837 treatment similarly improved bladder overactivity. CONCLUSIONS: The findings of our study suggest that Trk receptor inhibition, which reduced bladder hypersensitivity and inflammatory responses in the prostate, along with a decrease in overexpression of Trk and TRPV1 receptors in sensory pathways, could be an effective treatment strategy for male lower urinary tract symptoms associated with PI and bladder overactivity.

Outcomes of sequential third-line therapies in patients with refractory overactive bladder.

INTRODUCTION: Sacral neuromodulation (SNM) and onabotulinumtoxinA (BoNTA) injection are third-line therapies for overactive bladder (OAB). Although the efficacy of each third-line treatment has been well established in clinical trials, there is far less information about performing one third-line therapy after the other. Our aim is thus to investigate the outcomes of post-SNM BoNTA and post-BoNTA SNM as "second" third-line treatments. METHODS: We retrospectively reviewed all OAB patients who had both SNM and BoNTA between 2013 and 2022. The primary endpoint was the response rates (>50% improvements) of the second third-line treatments. Secondary endpoints were the proportion of the patients who achieved total dry, the duration of treatments of patients who had significant responses, and risk factors that are associated with treatment response or duration of treatments. RESULTS: A total of 172 patients had two third-line therapies. There were 104 patients who had post-SNM BoNTA and 68 patients who had post-BoNTA SNM. In the post-SNM BoNTA group, 62.5% (65/104) had significant responses after BoNTA treatment. In the post-BoNTA SNM group, 61.8% (44/68) had significant responses after SNM treatment. The proportions of patients who became dry were 21.2% and 23.5%, respectively. In the post-SNM BoNTA group, spinal pathology is associated with a lower probability of a significant response (48.9% vs. 73.7%, p-value = 0.0105). CONCLUSIONS: BoNTA or SNM remains a viable option for refractory OAB after patients fail from one another. Spinal pathology is associated with a poorer response of post-SNM BoNTA.

The impact of pharmacotherapy on sexual function in female patients being treated for idiopathic overactive bladder: a systematic review.

BACKGROUND: Overactive bladder (OAB) is a condition defined by urgency with or without incontinence which disproportionately affects female patients and has a negative impact on sexual enjoyment and avoidance behaviour. Pharmacotherapy can be considered one of the main options for treating OAB. This research set out to determine the impact of pharmacotherapy on sexual function in females with OAB. METHODS: This research used the robust methodology of a systematic review. The clinical question was formulated using the PICO (population, intervention, control, and outcomes) format to include females being treated with pharmacotherapy (anticholinergics or beta-3 adrenergic agonists) for idiopathic OAB with the use of a validated questionnaire assessing self-reported sexual function at baseline and post-treatment. The review incorporated the MEDLINE, PubMed and EMBASE databases. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) appraisal tool was used to guide the review process. Two reviewers worked independently in screening abstracts, deciding on the inclusion of full-texts, data extraction and risk of bias assessment. RESULTS: In female patients with OAB, pharmacotherapy does seem to offer at least partial improvement in self-reported sexual function outcomes after 12 weeks of therapy. Still, the value of this finding is limited by an overall poor quality of evidence. Patients with a higher degree of bother at baseline stand to benefit the most from treatment when an improvement within this health-related quality of life domain is sought. CONCLUSION: This research should form the basis for a well-conducted randomized controlled study to accurately assess sexual function improvements in females being treated with pharmacotherapy for OAB.

Protective effect of equol intake on bladder dysfunction in a rat model of bladder outlet obstruction.

OBJECTIVES: This study evaluates the impact of equol, a metabolite of soy isoflavone, on bladder dysfunction in rats with bladder outlet obstruction (BOO). In addition, we investigate its potential as a neuroprotective agent for the obstructed bladder and discuss its applicability in managing overactive bladder (OAB). METHODS: Eighteen male Sprague-Dawley rats were divided into three groups (six rats per group) during the rearing period. The Sham and C-BOO groups received an equol-free diet, while the E-BOO group received equol supplementation (0.25 g/kg). At 8 weeks old, rats underwent BOO surgery, followed by continuous cystometry after 4 weeks of rearing. The urinary oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) were measured, and the bladder histology was analyzed using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining (neurofilament heavy chain for myelinated nerves, peripherin for unmyelinated nerves, and malondialdehyde). RESULTS: Equol reduced BOO-induced smooth muscle layer fibrosis, significantly prolonged the micturition interval (C-BOO: 193 s, E-BOO: 438 s) and increased the micturition volume (C-BOO: 0.54 mL, E-BOO: 1.02 mL) compared to the C-BOO group. Equol inhibited the increase in urinary and bladder tissue malondialdehyde levels. While the C-BOO group exhibited reduced peripherin alone positive nerve fibers within the smooth muscle layer, equol effectively attenuated this decline. CONCLUSIONS: Equol reduces lipid peroxidation and smooth muscle layer fibrosis in the bladder and exhibited neuroprotective effects on bladder nerves (peripheral nerves) and prevented the development of bladder dysfunction associated with BOO in rats. Consumption of equol is promising for the prevention of OAB associated with BOO.