Treatment Of Overactive Bladder Research Articles

Is It Time to Rethink Our Approach to Overactive Bladder Treatment?

Is It Time to Rethink Our Approach to Overactive Bladder Treatment?

The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms

Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I—control, II—rats with rapamycin (RA)-induced OAB, III—rats administered IMP at a dose of 10 mg/kg/day, and IV—rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB.

Multi-omic analysis revealed the therapeutic mechanisms of Alpinia oxyphylla fructus water extract against bladder overactivity in spontaneously hypertensive rats

ObjectiveAlpinia oxyphylla fructus without impurities and shells is called “Yi-Zhi-Ren” (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. MethodsA 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. ResultsYZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFβ1, p-SMAD3, collagen III, Gq and PLCβ1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. ConclusionYZR's mechanisms of action in treating OAB involved the TGFβ1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCβ1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.

The Effects of Age, Gender, and Postvoid Residual Volume on Catheterization Rates After Treatment with OnabotulinumtoxinA for Overactive Bladder

BackgroundTransient increases in postvoid residual urine volume (PVR) requiring clean intermittent catheterization (CIC) have occurred with onabotulinumtoxinA treatment for overactive bladder (OAB). ObjectiveTo evaluate onabotulinumtoxinA safety and the effect of age, gender, and maximum PVR (PVRmax) on CIC initiation in adults with OAB and urinary incontinence (UI). Design, setting, and participantsThis was a pooled post hoc analysis of four placebo-controlled, multicenter randomized trials that included adults with idiopathic OAB after first onabotulinumtoxinA treatment (NCT00910845, NCT00910520, NCT01767519, NCT01945489). Patients had at least three urgency UI episodes over 3 d and at least eight micturitions per day, had inadequate management with at least one anticholinergic agent, and were willing to use CIC. Outcome measurements and statistical analysisWe measured the following outcomes: PVRmax within 12 wk after first treatment; CIC incidence; estimated functional capacity; PVR ratio (PVR/estimated functional capacity). Results and limitationsOf 1504 patients, 87.7% were women and 88.8% were White. The mean age was 60.5 yr across 10-yr age groups, baseline PVR was 13.8–35.0 ml, and estimated functional capacity was 293.5–475.7 ml. Mean baseline PVR was 21.3 ml overall versus 34.0 ml in the group that started CIC. The CIC incidence was 6.2% for women (range 1.1–8.4%) and 10.5% for men (range 0–14.6%). Higher CIC rates were observed for PVRmax >350 ml (women 91.9%, men 84.6%) in comparison to PVRmax of 201–350 ml (women 32.5%, men 17.4%) and PVRmax <200 ml (women 1.2%, men 1.6%). Overall, 2/1504 patients (both women) were unable to void spontaneously. The mean PVR ratio was highest at week 2. Some subgroups had small sample sizes. ConclusionsCIC incidence was low overall, was less frequent for women, was rare with PVRmax ≤200 ml, and did not appear to correlate with baseline PVR. Patient summaryAfter onabotulinumtoxinA treatment for OAB, patients sometimes insert a catheter to help in emptying their bladder after urinating. In this study, few patients needed a catheter, especially when less urine volume remained after urination.

Do patients experience decisional regret after sacral neuromodulation for refractory overactive bladder?

Success following urological procedures is traditionally defined through objective endpoints. This approach may not capture the impact on patient satisfaction. There is a paucity of literature evaluating patient-centered metrics such as satisfaction and decisional regret in the field of urology. This study investigates long-term satisfaction and decisional regret amongst patients who underwent sacral neuromodulation (SNM) for the treatment of refractory overactive bladder (OAB). This study retrospectively reviewed patients who underwent SNM for refractory OAB from 2015 to 2022 at a single institution serving an ethnically diverse and underrepresented community. Demographic data were collected through chart review and surveys conducted via telephone calls. Patient satisfaction and decisional regret was measured with the validated modified SDS-DRS scale (satisfaction with decision scale-decision regret scale). Descriptive statistics, Wilcoxan rank sum, and median regression analyses were performed using STATA 15.0 with p < 0.05 as significant. Out of 191 patients who underwent SNM, 63 were unreachable (wrong number in chart, number not in service, patient did not answer, deceased). Eighty-nine out of 128 patients reached agreed to participate (70% response rate). The mean time since surgery was 37.3 ±25.2 months. The median satisfaction with decision score was 4.0 (IQR: 3.7-4.7) with a score of 1 correlating with low satisfaction and a score of 5 correlating with high satisfaction. The median decisional regret score was 2.0 (IQR: 1.2-2.9)with a score of 1 correlating with low decisional regret and a score of 5 correlating with strong decisional regret. Ten patients reported complications after surgery, which was significantly associated with lower SDS and higher DRS scores (p < 0.01), and persisted after adjusting for age, body mass index, sex, and comorbidities (SDS β coef: -0.84, 95% CI: -1.5 to0.15,p = 0.02;DRS β coef: 1.48, 95% CI:0.55-2.41,p < 0.01). Patients who underwent SNMfor refractory OAB overall had low regret and high satisfaction with their decision at an average 3 years of follow-up. As expected, those who developed postoperativecomplications had worse scores. The inclusion of patient-centric outcomes is imperative when determining the success of a surgical procedure and is useful for shared decision-making when advancing to third-line therapy for OAB. Longer-term follow-up is necessary to assess durability of high satisfaction and low regret over time.

Mixed Urinary Incontinence: Diagnosis and Management

The evaluation and treatment of mixed urinary incontinence receives relatively little attention as compared to other forms of incontinence. Mixed incontinence, however, defined as the combination of stress and urgency incontinence, accounts for the largest proportion of incontinence, with an increased incidence in older women. The condition can be very challenging to manage due to the coexistence of multiple pathologies. Treating either component can worsen the other, which means careful discussion of the risks and benefits, in addition to considerations of multimodal treatment approaches are required. In the older adult population, where this condition confers a significant impact on quality of life, there are many special considerations when evaluating and treating patients. Evaluation requires a careful assessment of the impact on QOL and goals of care and may need to involve caregivers and/or family members in the discussion, in addition to considerations of more advance evaluation on an individual basis prior to invasive treatments. Conservative treatments including behavioral and lifestyle modifications and pelvic floor physical therapy should be the mainstay of first-line treatment for older women with MUI, while taking into careful consideration how cognitive and/or physical limitations may impact treatment. Pharmacologic therapy should include a consideration of vaginal estrogen replacement, however oral medications for urgency and overactive bladder have increased risks in older women, which means more advanced treatments may want to be introduced sooner. There is really limited data on the use of third-line overactive bladder treatments in older women with mixed incontinence, however there may be some demonstrated benefits. Finally, when considering surgical interventions in this population, although the data demonstrate some benefit in mixed incontinence, providers may want to utilize a formalized assessment of frailty due to the increased morbidity associated with frailty in surgeries for incontinence.

Use of Fermented Red Clover Isoflavones in the Treatment of Overactive Bladder in Postmenopausal Women: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Postmenopausal women are at risk of developing an overactive bladder (OAB). Conventional vaginal estrogen has shown promise for symptom relief. Isoflavones have proven effective as an alternative to estrogen treatment against menopause-related symptoms. However, its effect on OAB symptoms has not been studied. This study investigates if fermented red clover isoflavones reduce OAB symptoms in postmenopausal women. In this randomized, double-blinded, placebo-controlled trial, women were administered red clover extract (RCE) or a placebo twice daily for three months. Women filled out the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and Urinary Incontinence Short Form (ICIQ-UI-SF), together with a fluid intake and voiding diary. A total of 33 women (16 in the RCE group and 17 in the placebo group) were included in the analysis. Baseline demographics and OAB characteristics were comparable across groups. Intake of RCE did not lead to significant relief in most urinary bladder symptom measures, although a significant reduction in the bother of urinary urgency (p = 0.033) and a tendency towards a decreased ICIQ-OAB score were observed (p = 0.056). In contrast, the placebo exhibited a significant decrease in the ICIQ-OAB score (p = 0.021) and in some diary outcomes. We found that an intake of isoflavones did not relieve OAB symptoms in postmenopausal women.

Patient and Clinician Challenges with Anticholinergic Step Therapy in the Treatment of Overactive Bladder: A Narrative Review.

Anticholinergics have been used in the treatment of overactive bladder (OAB), but their use is limited by poor tolerability and anticholinergic-related side effects. Increasingly, providers are discontinuing anticholinergic prescribing because of growing evidence of the association of anticholinergic use with increased risk of cognitive decline and other adverse effects. Newer medications for OAB, the β3-adrenergic receptor agonists mirabegron and vibegron, do not have anticholinergic properties and are typically well tolerated; however, many insurance plans have limited patient access to these newer OAB medications by requiring step therapy, meaning less expensive anticholinergic medications must be trialed and/or failed before a β3-agonist will be covered and dispensed. Thus, many patients are unable to easily access these medications. Step therapy and other drug utilization strategies (e.g., prior authorization) are often used to manage the growing costs of pharmaceuticals, but these policies do not always follow treatment guidelines and may harm patients as a result of treatment delays, discontinuations, or related increases in adverse events. Medical professionals have called for reform of drug utilization strategies through partnerships that include clinicians and policymakers. This narrative review discusses prescribing patterns for OAB treatment and the effect of switching between drugs, as well as the costs of step therapy and prior authorization on patients and prescribers.

Effects of a new selective β3 -adrenoceptor agonist, vibegron, on bladder and urethral function in a rat model of Parkinson's disease.

Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel β3 -adrenoceptor agonist approved for the treatment of overactive bladder. However, how β3 -adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease. In a rat model of Parkinson's disease induced by unilateral 6-hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity. Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter-contraction interval (p < .05) and reduced voiding pressure (p < .01). However, no significant effects on urethral function were observed. The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of β3 -adrenoceptor agonists.

Experimental inoculation of the Botox perineurally of facial nerve and followed by histological assessment for its effect on the zygomatic bone of rabbits

Background: Botox, derived from the toxin produced by Clostridium botulinum, is an attenuated toxin employed as a treatment for cervical dystonia, overactive bladder, strabismus, cerebral palsy, and non-surgical cosmetic procedures. This study aimed to explore the impact of injecting Botox around the facial nerve on the left side of rabbits, specifically focusing on the histological changes in the zygomatic bone. Methods: Twenty-five adult rabbits of a local breed, weighing 1500-1800 gm and of both sexes, underwent a 15-day acclimation period prior to the experiment. The rabbits were randomly assigned to four groups (1st, 2nd, 3rd, and 4th). A singular intramuscular injection of Botox at a dose of 3.5 U/kg was administered to the left facial muscles. The rabbits in each group were then sacrificed at distinct time points after injection: day 10, day 15, day 30, and day 45. All rabbits survived until the end of the experiment, at which point they were euthanized with chloroform. Post-euthanasia, the rabbits' facial zygomatic bones were dissected and subjected to histological assessment. Results: The results indicated notable changes in the zygomatic bone, including prominent vacuoles within the bony matrix, cracks with cellular debris, limited osteocytes, and collagen bundles resembling woven bone. Additionally, in the day 30 group (T3), irregular bone borders and atrophied osteogenic cells were observed, while the day 45 group (T4) exhibited necrotic areas and bone fragments within the bone matrix. Conclusion: In conclusion, Botox, derived from Clostridium botulinum, serves various medical purposes. The study focused on injecting Botox around rabbits' facial nerves to assess its impact on zygomatic bones histologically. Following a controlled injection and specific time intervals, the examined bone samples exhibited distinct changes, providing insights into Botox's effects on bone morphology.

Efficient biosynthesis of Vibegron intermediate using a novel carbonyl reductase based on molecular modification of hydrogen bonding network regulation

Vibegron is a novel, potent, highly selective β3-adrenergic receptor agonist for the treatment of overactive bladder with higher therapeutic capacity and lower side effects. Methyl(2S,3R)-2-((tert-butoxycarbonyl)amino)-3-hydroxy-3-phenylpropanoate ((2S,3R)-aminohydroxy ester) is a key chiral intermediate for the synthesis of Vibegron. A novel carbonyl reductase from Exiguobacterium sp. s126 (EaSDR6) was isolated using data mining technology from GenBank database with preferable catalytic activity. Hydrogen bond network regulation was performed using site-directed saturation mutagenesis and combination mutagenesis. The mutant EaSDR6A138L/S193A was obtained with the activity improvement by 4.58 folds compared with the wild type EaSDR6. The Km of EaSDR6A138L/S193A was decreased from 1.57 mM to 0.67 mM, kcat was increased by 2.17 folds, and the overall catalytic efficiency kcat/Km was increased by 5.07 folds. The organic-aqueous biphasic bioreaction system for the asymmetric synthesis of (2S,3R)-aminohydroxy ester was constructed for the first time. Under the substrate concentration of 150 g/L, the yield of (2S,3R)-aminohydroxy ester was > 99.99%, the e.e. was > 99.99%, and the spatiotemporal yield was 1.55 g/(L·h·g DCW) after 12 h reaction. While the substrate concentration was increased to 200 g/L and the reaction lasted for 36 h, the yield of (2S,3R)-aminohydroxy ester was > 99.99%, the e.e. was > 99.99% and the spatiotemporal yield was 1.05 g/(L·h·g DCW). The substrate concentration and spatiotemporal yield were higher than ever reported.

Efficacy and Safety of Eliapixant in Overactive Bladder: The 12-Week, Randomised, Placebo-controlled Phase 2a OVADER Study

BackgroundEffective, well-tolerated novel treatments for overactive bladder (OAB) are lacking. The P2X3 receptor antagonist eliapixant demonstrated potential to reduce OAB symptoms in preclinical studies. ObjectiveTo evaluate the safety, tolerability, and efficacy of eliapixant in patients with OAB with urgency urinary incontinence (UUI). Design, setting and participantsOVADER was a 12-wk, randomised, placebo-controlled, double-blind, parallel-group, multicentre, phase 2a study (NCT04545580) conducted between 2020 and 2022 in private and institutional clinical practices. Eligible patients were aged ≥18 yr with wet OAB symptoms (urgency, urinary frequency, and urinary incontinence) for ≥3 mo before screening. InterventionRandomisation (1:1 ratio) to oral eliapixant 125 mg or placebo twice daily. Outcome measurements and statistical analysisThe primary endpoint was the mean change from baseline in the mean number of UUI episodes/24 h over weeks 4, 8, and 12 according to an electronic bladder diary, evaluated using a repeated-measurement model in a Bayesian framework. Results and limitationsOf 202 patients enrolled, 85 were valid for per-protocol analysis. The primary efficacy endpoint was not met. The posterior probability for eliapixant superiority over placebo was 40% (point estimate 0.05, 95% credible interval −∞ to 0.38), which did not meet the predefined criterion of ≥90% probability. Secondary and exploratory endpoints were not met. The incidence of adverse events was similar in the eliapixant (n = 32, 63%) and placebo (n = 27, 56%) groups; most were mild and five led to discontinuation of eliapixant. ConclusionsOVADER did not meet its clinical efficacy endpoints. Potential reasons include the nonspecific OAB symptom complex, the poorly understood pathophysiology, and the coinciding COVID-19 pandemic. Patient summaryWe tested whether a new drug called eliapixant would reduce symptoms of overactive bladder in comparison to placebo. We found that the drug did not work. More knowledge on how overactive bladder occurs is needed to find new drugs to treat this condition.

Predictive Factors for High Post-void Residual Volume in Older Females After OnabotulinumA Treatment for Severe Overactive Bladder Using a Machine Learning Model.

Introduction Intravesical onabotulinumA injection is actively used for the treatment of overactive bladder (OAB). However, it occasionally results in significant post-void residual urine (PVR) volume, which can lead to complications and can further impair the activities of daily living in older people. Therefore, this study aimed to identify the predictors of a high post-onabotulinumA injection PVR volume in older women with severe OAB. Methods An observational study was conducted on older women who had previously received intravesical onabotulinumA injections to treat OAB between 2020 and 2022. Urodynamic studies and symptom assessments were conducted, and machine learning models, including random forest and support vector machine (SVM) models, were developed using the R code generated by Chat Generative Pre-trained Transformer 4 (ChatGPT, OpenAI, San Francisco, USA). Results Among 128 patients with OAB, 23 (18.0%) had a PVR volume of > 200 mL after receiving onabotulinumA injections. The factors associated with a PVR volume of > 200 mL were investigated using univariate and multivariate analyses. Age, frailty, OAB-wet, daytime frequency, and nocturia were significant predictors. Random forest analysis highlighted daytime frequency, frailty, and voiding efficiency as important factors. An SVM model incorporating daytime frequency, frailty, and voiding efficiency improved PVR volume prediction. Logit(p) estimation yielded an area under the receiver operating characteristic curve of 0.926294. Conclusion The study found daytime frequency, frailty, and voiding inefficiency to be significant factors associated with a PVR volume of > 200 mL, in older women with severe OAB. Utilizing advanced machine learning techniques and following the guidance of ChatGPT, this research emphasizes the relevance of considering multiple intersecting factors for predicting PVR volume. The findings contribute to our understanding of onabotulinumA injection treatment for OAB and support evidence-based decision-making using readily available information.

Ultrasound-assisted intravesical botulinum toxin A delivery attenuates acetic acid-induced bladder hyperactivity in rats.

Background: Intradetrusor injection of botulinum toxin A (BTX-A) is an effective treatment for overactive bladder (OAB). However, the occurrence of adverse events associated with BTX-A injection therapy hinders its acceptance among patients and its clinical promotion. Intravesical instillation of BTX-A offers a promising alternative to injection therapy for treating OAB. Nevertheless, due to the presence of the bladder permeability barrier (BPB) and the high molecular weight of BTX-A, direct instillation is unable to penetrate the bladder urothelium. Purpose: This study aims to investigate the safety and feasibility of ultrasound-assisted intravesical delivery of BTX-A and its potential benefits in a rat model of bladder hyperactivity induced by acetic acid instillation. Methods: Hengli BTX-A and microbubbles (MB) were mixed and prepared as a novel complex. The size distribution and zeta potentials of the complex were measured. On day 1, rats' bladders were instilled with 1mL of saline, BTX-A (20U in 1mL), MB, or MB-BTX-A (20U in 1mL) complex with or without ultrasound (US) exposure (1MHz, 1.5W/cm2, 50% duty cycle, sonication for 10s with a 10-s pause for a total of 10min). The instillations were maintained for 30min. After 7days, cystometry was performed by filling the bladder with saline and 0.3% acetic acid (AA). Bladders were collected, weighed, and processed for immunoblotting, enzyme-linked immunosorbent assay (ELISA), histologic, and immunofluorescence analyses. Expression and distribution of SNAP-25 and SNAP-23 were assessed using Western blot and immunofluorescence. Calcitonin gene-related peptide (CGRP) in the bladder was detected using ELISA. Results: Intercontraction intervals (ICI) decreased by 72.99%, 76.16%, and 73.96% in rats pretreated with saline, BTX-A, and US + MB, respectively. However, rats treated with US + MB + BTX-A showed a significantly reduced response to AA instillation (57.31% decrease in ICI) without affecting amplitude, baseline pressure, or threshold pressure. Rats treated with US + MB + BTX-A exhibited increased cleavage of SNAP-25 and CGRP expression compared to the control group. Conclusion: Ultrasound-assisted intravesical delivery of BTX-A, with the assistance of MB cavitation, led to cleavage of SNAP-25, inhibition of calcitonin gene-related peptide release from afferent nerve terminals, and amelioration of acetic acid-induced bladder hyperactivity. These results support ultrasound-assisted intravesical delivery as an efficient non-injection method for administering BTX-A.

Proximity of percutaneous tibial nerve stimulation needle insertion to surrounding anatomic structures: a cadaveric study

Percutaneous tibial nerve stimulation is a third-line treatment for overactive bladder and urgency urinary incontinence. During the procedure, a needle is inserted cephalad to the medial malleolus and posterior to the tibia. In recent years, permanent implants and leads have been developed for insertion into the medial ankle via a small incision. There are many important structures present in the medial compartment of the ankle, including the great saphenous vein, saphenous nerve, tibial nerve, posterior tibial vessels, and tendons of the posterior compartment leg muscles. The primary objective of this study was to identify the proximity of the percutaneous tibial nerve stimulation needle placed per Food and Drug Administration-approved device instructions to nearby important anatomic structures. The secondary objectives were to identify the proximity of the tibial nerve to the needle site, identify clinically relevant ankle anatomic structures, and confirm the tibial nerve and posterior tibial vasculature by histologic analysis. Detailed medial ankle dissections were performed bilaterally on 10 female lightly embalmed anatomic donors (cadavers) obtained from the Willed Body Program at the University of Louisville. A pin was inserted at the percutaneous tibial nerve stimulation needle site, and the medial ankle was minimally dissected so the surrounding anatomic structures were visible but not disrupted. The shortest distance from the pin to the selected structures of the medial ankle region was measured. On completion of each dissection and set of measurements, tissue was harvested for histologic examination. The distances between the pin and each structure were assessed using means and standard deviations. A paired t test was used to assess the difference in the locations between the left and right ankles. Statistical analysis was performed on left-sided, right-sided, and combined measurements. An 80% prediction interval was found to represent the expected range of values for the measurement of a new cadaver or patient, and the 95% confidence interval of the mean was computed to characterize the average distance across all cadavers or patients. The medial ankle of 10 adult female lightly embalmed cadavers were examined bilaterally. Dissections were completed from October 2021 to July 2022. Of note, 80% prediction intervals for the tibial nerve, the posterior tibial artery or vein, and the flexor digitorum longus tendon had a lower range of 0.0 mm from the pin and extending to 12.1, 9.5, and 13.9 mm, respectively. Moreover, 2 of the structures were found to be asymmetrical between the right and left ankles. The great saphenous vein was further from the pin on the left (20.5 mm [standard deviation of 6.4 mm] on the left vs 18.1 mm [standard deviation of 5.3 mm] on the right; P=.04). The calcaneal (Achilles) tendon was further from the pin on the right side (13.2 mm [standard deviation of 6.8 mm] vs 7.9 mm [standard deviation of 6.7 mm]; P=.04). Tibial neurovascular structures were confirmed with microscopic analysis. The anatomic structures within the medial ankle lie unexpectedly close to the percutaneous tibial nerve stimulation needle site as noted per Food and Drug Administration-approved device instructions. There is a possibility that some medial ankle structures are not symmetrical. It is crucial that practitioners understand medial ankle anatomy when performing percutaneous tibial nerve stimulation or permanent device insertion.

A Randomized, Double-Blind, Placebo-Controlled, Bridging Study to Evaluate the Efficacy and Safety of Vibegron in Treating Korean Patients With Overactive Bladder.

Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients' quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB.

Predictors for adverse events following intravesical botulinum toxin injections in men.

Intravesical botulinum toxin A (BTX-A) has been long established as treatment for overactive bladder and neurogenic bladder dysfunction. However, most published data are reported amonga female cohort. Adverse events such as intermittent self-catheterization (ISC) and urinary tract infections (UTIs) play a large role in discontinuation of therapy. There is currently limited information regarding predictive factors to appropriately counsel male patients. We retrospectively collected data on male patients undergoing their first intravesical BTX-A therapy from January 2016 to July 2021 in two high-volume centers. Data included demographics, past medical and surgical history, and urodynamic parameters. Patients were excluded if they had a long-term catheter or ISC before initiation of therapy. A total of 69 men were included in the study with a median age of 66 years. There were 18 patients with neurogenic bladder dysfunction. Thirty men had urge incontinence secondary to radical prostatectomy or bladder outflow surgery. Overall rates of ISC were 43.5%. Predictors for ISC included a baseline postvoid residual (PVR) ≥ 50 mL (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.36-13.03, p = 0.01), BTX-A dose >100 units (OR: 4.2, 95% CI: 1.36-13.0, p = 0.01). Stress urinary incontinence was protective against ISC (OR: 0.20, 95% CI: 0.04-1.00, p = 0.049) as well as history of prostatectomy/bladder outflow obstruction (BOO) surgery (OR: 0.16, 95% CI: 0.05-0.47, p < 0.001). A multivariable logistic regression model with these factors yielded a c-statistic of 0.80 (optimism-adjusted = 0.75). An enlarged prostate was the only predictor for UTI amongour male cohort (OR: 8.0, 95% CI: 2.03-31.5, p = 0.003). This is the first study assessing risk factors of adverse events amongmen following BTX-A injection. High PVR and BTX-A dose of >100U were predictors of requiring ISC after BTX-A. Stress incontinence, previous radical prostatectomy, and BOO surgery were all protective against needing ISC post-BTX-A. An enlarged prostate was associated with development of UTI. These factors can be used to assist in counseling male patients regarding their risk of ISC and UTI.

(015) STOMP: Sexual function Trial of Overactive bladder: Medication versus PTNS

Abstract Introduction Female sexual dysfunction affects approximately 45% of women, and an even greater percentage of those with overactive bladder (OAB). Sexual function, measured by the Female Sexual Function Index (FSFI), has been shown to improve with treatment of OAB. To date, no study has compared the effects of percutaneous tibial nerve stimulation (PTNS) versus medication (anticholinergics (ACH) or beta-agonists (BAG)) on sexual function. Objectives The objective of this study was to compare the effect of PTNS and medical therapy (MT) with ACH or BAG on female sexual function. Methods This was a prospective multi-center cohort study. Sample sizes of 63 per group were calculated to be necessary to detect a clinically relevant difference in the primary end point, FSFI. Sexually-active women with OAB completed the Overactive Bladder questionnaire (OAB-q), FSFI, Beck Depression Inventory and a visual analog pain scale prior to and after 12 weeks of therapy. Results 175 patients were recruited and 104 completed follow up (58/108 ACH, 31/49 BAG, 13/18 PTNS). The PTNS group had lower overall FSFI (p=0.04), worse pain (p=0.01) and decreased lubrication (p=0.006) compared to the BAG and ACH groups. After treatment there were no significant differences between the groups in overall or sub-domain FSFI scores. There were within-group FSFI differences from pre- to post-treatment, with a worsening of arousal in the ACH group (p=0.046) and an improvement in overall FSFI (p=0.04) and pain (p=0.04) with BAG. After treatment, postmenopausal women in the BAG group had significantly better overall FSFI (p=0.01), desire (p=0.003), arousal (p=0.009) and orgasm (p=0.01). Conclusions While both PTNS and MT improved OAB, ACH resulted in worsening of aspects of sexual function, such as arousal, while BAG improved overall sexual function and pain. Improvement in sexual function with treatment was pronounced in the sub-group of postmenopausal women. While further research in necessary, this study provides additional information about the comparative effects of OAB treatments on female sexual function, which may ultimately lead to better patient selection and outcomes. Disclosure No.

Efficacy and safety of vaginal electrical stimulation as an alternative or adjunct treatment for overactive bladder syndrome in women: a meta-analysis of randomized controlled trials.

The objective was to evaluate the efficacy and safety of vaginal electrical stimulation (VES) as an alternative or adjunct treatment for overactive bladder (OAB) syndrome in women. Five English-language databases and four Chinese-language databases were searched to identify relevant studies. Studies comparing VES (VES alone or VES plus other interventions) with other interventions (medicines, bladder training, or PFMT) were included. Voiding diary, quality of life (QoL), and adverse events were extracted from the included studies for comparison. Seven trials with 601 patients in total were reviewed. The results showed that when compared with other interventions, VES alone significantly improved urgency episodes (p = 0.0008) and voiding frequency (p = 0.01), but did not significantly reduce nocturia (p = 0.85), urinary incontinence episodes (p = 0.90) and number of pads (p = 0.87). When VES plus other interventions was compared with other interventions, the former significantly improved voiding frequency (p < 0.00001), nocturia (p < 0.00001), and number of pads (p = 0.03), but it did not significantly reduce urinary incontinence episodes (p = 0.24). Both VES alone (p < 0.00001) and VES plus other interventions (p = 0.003) showed significant benefit on QoL. This study demonstrated that VES alone decreased urgency episodes and QoL better than other therapies. Although VES alone reduced voiding frequency better and VES plus other therapies decreased nocturia, number of pads, urgency episodes, and QoL better than other therapies, the results should be interpreted with caution for clinical practice because some of the RCTs included were of low quality and because of the small number of studies included.

Sleep Disturbance Among Adults With Overactive Bladder: A Cross-sectional Survey

To examine differences in sleep disturbance, nocturia, and depression among adults with overactive bladder (OAB) by treatment type. A cross-sectional survey of adults with OAB assessed sleep disturbance, nocturia, and depression using patient-reported outcome measures, including the Patient Reported Outcomes Measurement Information System (PROMIS®)-29 Profile v2.1 (Sleep Disturbance and Depression domains), Lower Urinary Tract Dysfunction Research Network Symptom Index-10, and PROMIS® Sleep Disturbance Short Form 8B. Treatment groups included antimuscarinics, β-3 adrenergic agonists, and no treatment. Analysis of covariance (ANCOVA) was used to test for differences in study endpoints; Bonferroni-adjusted pairwise tests (p<0.05/3) were performed to compare differences in least squares means between groups. One hundred participants were included per treatment group. The overall mean (standard deviation) age across all groups was 47.8 (11.8) years. Symptom scores across all PROMIS domains in all three treatment groups were higher than the US general population. There were no statistically significant differences in outcomes across treatment groups. Adults with OAB reported being affected by sleep disturbance and depression, regardless of treatment. The mirabegron group trended toward the lowest symptom impact across all outcomes, however comparisons were not significant. Future research should examine temporal associations between OAB treatment, sleep disturbance, and outcomes.