Non-neurogenic Overactive Bladder Research Articles

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

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). 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. 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. 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.

Does the setting for intradetrusor onabotulinumtoxinA injection for management of overactive bladder matter?

Intradetrusor onabotulinumtoxinA (Botox) injections, to treat idiopathic overactive bladder (OAB), can be performed in the office setting under local analgesia alone or in the operating room (OR) under local and/or sedation. The objective of this study was to compare the symptomatic improvement in patients with OAB who underwent treatment with intradetrusor onabotulinumtoxinA injections in an in-office versus the OR setting. We performed a multicenter retrospective cohort study of women with the diagnosis of refractory non-neurogenic OAB who elected to undergo treatment with intradetrusor onabotulinumtoxinA injections between January 2015 and December 2020. The electronic medical records were queried for all the demographic and peri-procedural data, including the report of subjective improvement post procedure. Patients were categorized as either "in-office" versus "OR" based on the setting in which they underwent their procedure. Five hundred and thirty-nine patients met the inclusion criteria: 297 (55%) in the in-office group and 242 (45%) in the OR group. A total of 30 (5.6%) patients reported retention after their procedure and it was more common in the in-office group (8.1%) versus the OR group (2.5%), (P = 0.003). The rate of urinary tract infection within 6 months of the procedure was higher in the OR group (26.0% vs. 16.8%, P = 0.009). The overall subjective improvement rate was 77% (95% confidence interval: 73%-80%). Patients in the OR group had a higher reported improvement as compared to the in-office group (81.4% vs. 73.3%, P = 0.03). In this cohort study of patients with OAB undergoing intradetrusor onabotulinumtoxinA injections, post procedural subjective improvement was high regardless of the setting in which the procedure was performed.

Shifts in patient preference of third-line overactive bladder therapy after introduction of the implantable tibial nerve stimulator.

Third-line therapies for overactive bladder (OAB) that are currently recommended include intravesical Onabotulinumtoxin-A injections (BTX-A), percutaneous tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The implantable tibial nerve stimulator (ITNS) is a novel therapy that is now available to patients with OAB. The objective of this study was to analyze shifts in patient preference of third-line therapies for OAB after introducing ITNS as an option amongthe previously established therapies for non-neurogenic OAB. A survey was designed and distributed via SurveyMonkey to the platform's audience of U.S. adults of age 18 and older. Screening questions were asked to include only subjectswho reported symptoms of OAB. Descriptions of current AUA/SUFU guideline-approved third-line therapies (BTX-A, PTNS, and SNM) were provided, and participants were asked to rank these therapies in order of preference (stage A). Subsequently, ITNS was introduced with a description, and participants were then asked to rank their preferences amongst current guideline-approved therapies and ITNS (stage B). Absolute and relative changes in therapy preferences between stage A and stage B were calculated. Associations between ultimate therapy choice in stage B and participant characteristics were analyzed. A total of 485 participants completed the survey (62.5% female). The mean age was 49.1 ± 36.5 years (SD). The most common OAB symptoms reported were urgency urinary incontinence (UUI) (73.0%) and urinary urgency (68.0%). 29.2% of patients had tried medication for OAB in the past, and 8.0%-10.3% of patients were previously treated with a third-line therapy for OAB. In stage A, participants ranked their first choice of third-line therapy as follows: 28% BTX-A, 27% PTNS, and 13.8% SNM. 26.6% of participants chose no therapy, and 4.5% chose all three equally. In stage B, participants ranked their first choice as follows: 27.6% BTX-A, 19.2% PTNS, 7.8% SNM, and 19.2% ITNS. 21.9% of participants chose no therapy and 4.3% chose all four equally as their first choice. There were both absolute and relative declines in proportions of patients interested in BTX-A, SNM, and PTNS as their first choice of third-line therapy with the introduction of ITNS. Patients originally interested in PTNS in stage A had the greatest absolute change after the introduction of ITNS with 7.8% of participants opting for ITNS in stage B. Those interested in SNM in stage A had the largest relative change in interest, with 43.5% of those originally interested in SNM opting for ITNS in stage B. Finally, with the introduction of ITNS, the number of participants initially not interested in any third-line therapy declined by an absolute change of 4.7% and relative change of 17.6%. Participants experiencing concurrent stress urinary incontinence (SUI) symptomswere more likely to choose a current guideline-approved third-line therapy than ITNS or no therapy at all (p = 0.047). Those who had prior experience with third-line therapies were more likely to choose a third-line therapy other than ITNS as their ultimate choice of therapy in stage B. Of those who had chosen a guideline-approvedthird-line therapy in stage B (not ITNS), 13.6% had prior experience with BTX-A, 14.7% with PTNS, and 32 (11.2%) with SNM (p < 0.001, p < 0.001, p = 0.009, respectively). From our study, it appears that ITNS may attract a subset of patients who would not have otherwise pursued current guideline-approved third-line therapies for OAB. When patients are provided with descriptions of third-line OAB therapies including ITNS as an option, ITNS appears to compete with SNM and PTNS. It is possible that ITNS will provide patients with a different phenotype of neuromodulation therapy that can appeal to a niche OAB population. Given that ITNS devices have been introduced relativelyrecently to the market, their application will largely depend on cost and payer coverage, provider bias, and patient comorbidities. Further study is needed to understand how these factors interact with and influence patient preference of advanced OAB therapy to understand which patients will most benefit from this treatment modality.

The role of botulinum toxin in the management of nonneurogenic overactive bladder in children: Highlights for clinical practice. A systematic review.

Overactive bladder (OAB) is the most common voiding dysfunction in children; however, nonneurogenic or idiopathic OAB remains poorly studied. First-line treatment includes conservative measures; however, as many patients are refractory, have adverse effects, or are contraindicated for anticholinergics, new options must be explored. This review covers the use of intravesical botulinum toxin (BoNT) for idiopathic OAB treatment in children, emphasizing its efficacy, safety, differences between toxins, doses, and injection techniques. Clinical results were promising, with all 8 studies reporting good results. All authors used BoNT type A (BoNT-A), either onabotulinum or abobotulinum toxin A. Response rates were variable, with full-response percentages of 32%-60%. As proven by the full-response rates of 50%, repeated injections are as safe and effective as first injections. Only a few cases of urinary tract infection, transient urinary retention, and hematuria have been reported, with no major local or systemic adverse effects. Despite these limitations, evidence encourages and supports BoNT-A use as a safe and effective treatment modality for refractory idiopathic OAB in pediatric settings, regardless of dosage and target toxin. To the best of our knowledge, this is the first systematic review of the use of intravesical BoNT-A for idiopathic OAB treatment in children.

Urodynamic parameter improvements after mirabegron vs. antimuscarinics agents in non-neurogenic overactive bladder: a systematic review and meta-analysis of treatment effect.

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Efficacy of peripheral electrical nerve stimulation on improvements of urodynamics and voiding diary in patients with neurogenic lower urinary tract dysfunction: a systematic review and meta-analysis.

Peripheral electrical nerve stimulation is a routinely recommended treatment for non-neurogenic overactive bladder but has not been approved for patients with neurogenic lower urinary tract dysfunction (NLUTD). This systematic review and meta-analysis was to elucidate the efficacy and safety of electrostimulation and thus provide firm evidence for treating NLUTD. We systematically performed the literature search through PubMed, Web of Science, and Cochrane Library databases in March 2022. The eligible studies were identified across the inclusion criteria and the data on urodynamic outcomes, voiding diary parameters, and safety was collected to quantitatively synthesize the pooled mean differences (MDs) with 95% CIs. Subgroup analyses and sensitivity analyses were subsequently used to investigate the possible heterogeneity. This report was achieved in accordance with the preferred reporting items for systematic reviews and meta-analyses statement. A total of 10 studies involving 464 subjects and 8 studies with 400 patients were included for systematic review and meta-analysis, respectively. The pooled effect estimates indicated that electrostimulation could significantly improve urodynamic outcomes, including maximum cystometric capacity (MD=55.72, 95% CI 15.73, 95.72), maximum flow rate (MD=4.71, 95% CI 1.78, 7.65), maximal detrusor pressure (MD=-10.59, 95% CI -11.45, -9.73), voided volume (MD=58.14, 95% CI 42.97, 73.31), and post-void residual (MD=-32.46, 95% CI -46.63, -18.29); for voiding diary parameters, patients undergoing electrostimulation showed lower MDs of incontinence episodes per 24h (MD=-2.45, 95% CI -4.69, -0.20) and overactive bladder symptom score (MD=-4.46, 95% CI -6.00, -2.91). In addition to surface redness and swelling, no stimulation-related severe adverse events were reported else. The current evidence demonstrated that peripheral electrical nerve stimulation might be effective and safe for managing NLUTD, whereas more reliable data from large-scale randomized controlled trials are necessary to strengthen this concept.

Efficacy of Intravesical Botulinum Toxin A Injection in the Treatment of Refractory Overactive Bladder in Children.

This study aimed to evaluate the efficacy of intravesical botulinum toxin A (BoNT-A) injections for the treatment of pediatric overactive bladder (OAB) by exploring the differential treatment outcomes in children with different OAB etiologies and those who received additional intrasphincteric BoNT-A injections. We performed a retrospective review of all pediatric patients who received intravesical BoNT-A injections between January 2002 and December 2021. All patients underwent a urodynamic study at baseline and three months after BoNT-A administration. A Global Response Assessment (GRA) score of ≥2 at three months after BoNT-A injection was defined as successful treatment. Fifteen pediatric patients (median age, 11 years), including six boys and nine girls, were enrolled in the study. A statistically significant decrease in detrusor pressure from baseline to three months postoperatively was observed. Thirteen (86.7%) patients reported successful results (GRA ≥ 2). The cause of OAB and additional intrasphincteric BoNT-A injections did not affect the improvement in urodynamic parameters and treatment success. The study demonstrated that intravesical BoNT-A injection is effective and safe for the treatment of neurogenic and non-neurogenic OAB in children refractory to conventional therapies. Additionally, intrasphincteric BoNT-A injections do not provide additional benefits in the treatment of pediatric OAB.

National Trends in Third-Line Treatment for Overactive Bladder Among Commercially Insured Women, 2010-2019

ObjectiveTo investigate whether the 2010 introduction of percutaneous tibial nerve stimulation and the 2013 introduction of intradetrusor onabotulinumtoxinA were associated with an increase in overall utilization of third-line treatments. MethodsUsing medical claims data from IBM Marketscan database 2010-2019, diagnosis codes were used to identify adult women with overactive bladder. Procedure codes were used to identify third-line treatments. The annual proportion of patients receiving third-line treatments was calculated, as well as the proportion of each treatment received. These were modeled as a function of treatment year using linear regression; a regression coefficient significantly different from 0 was considered evidence of a significant change in utilization over time. ResultsWe identified 3,067,515 unique individuals with a diagnosis of overactive bladder, including 14,652 who initiated third-line treatments. The annual percentage of women with overactive bladder who initiated third-line treatment was 0.18% and did not change significantly over 10 years (P = .82). However, the proportion receiving sacral neuromodulation decreased significantly (P <.001), with a compensatory increase in intradetrusor onabotulinumtoxinA. Within 6 years of its introduction, onabotulinumtoxinA accounted for almost half of third-line treatments initiated. ConclusionOverall, third-line therapies for non-neurogenic overactive bladder are utilized infrequently among privately insured women. Over the past decade, the introduction of new treatment options has led to a shift in the type of treatment initiated, rather than to an increase in the overall utilization of third-line therapies.

Postprocedural Pain Associated With 5 Versus 20 Intradetrusor Injections of OnabotulinumtoxinA for Treatment of Overactive Bladder: A Multicenter Randomized Clinical Trial

(Abstracted from Urogynecology 2022;28:518–525) For treating nonneurogenic overactive bladder, female pelvic medicine and urogenital reconstruction guidelines given by the American Urological Association and Society of Urodynamics recommend that onabotulinumtoxinA (botoxA) may be used as third-line therapy following a failure of both first-line lifestyle and behavioral changes and second-line cholinergic or β-agonist therapy. Wide variations on the acceptable number of injections per treatment episode (as much as 1 injection to 40) have been promulgated for botoxA.

A Feasibility Study to Evaluate Changes in Urinary Metabolites after OnabotulinumtoxinA Injection for Refractory Overactive Bladder.

Metabolomics analysis of urine before and after overactive bladder (OAB) treatment may demonstrate a unique molecular profile, allowing predictions of responses to treatment. This feasibility study aimed to correlate changes in urinary metabolome with changes in OAB symptoms after intravesical onabotulinumtoxinA (BTX-A) injections for refractory OAB. Women 18 years or older with non-neurogenic refractory OAB were recruited to complete OAB-V8 questionnaires and submit urine samples before and after 100 units intravesical BTX-A injection. Samples were submitted to CE-TOFMS metabolomics profiling. Data were expressed as percent of change from pre-treatment and were correlated with OAB-V8 score improvement. Urinary metabolite changes in the OAB-V8 groups were compared using the Kruskal–Wallis test, and associations between metabolites and OAB-V8 scores were examined using quantile regression analysis. Of 61 urinary metabolites commonly detected before and after BTX-A, there was a statistically significant decrease in adenosine and an increase in N8-acetylspermidine and guanidinoacetic acid levels associated with OAB score improvement, suggesting that intravesical BTX-A injection modifies the urinary metabolome. These urinary metabolites could provide insight into OAB pathophysiology and help identify patients who would benefit most from chemodenervation.

Urodynamic evaluation of the efficacy of vibegron, a new β3-adrenergic receptor agonist, on lower urinary tract function in children and adolescents with overactive bladder

Idiopathic overactive bladder (OAB) is defined as an urgency symptom with or without urge incontinence, which is not due to known neurological abnormalities. Since children present with variable symptoms, pediatric nonneurogenic idiopathic OAB is a condition that is difficult to diagnose and treat. Although there are few reports on bladder function in pediatric patients compared to adult patients, it can be useful for diagnosis. Antimuscarinic therapy is the pharmacological mainstay of OAB management. However, antimuscarinic use is limited by side effects and Insufficient effects. Vibegron, a new drug with a different mechanism of action (β3-adrenoreceptor agonist), was recently introduced for treating OAB in adults but has not been studied in the pediatric population. This study aimed to determine the efficacy and tolerability of vibegron in children and adolescents with idiopathic OAB. We conducted a retrospective study enrolling pediatric patients with OAB whose symptoms did not improve with behavioral therapy or pharmaceutical therapy. Efficacy and tolerability were assessed via a question, and patients underwent video-urodynamic testing before and during treatment with once-daily 50mg vibegron. Statistical differences were evaluated using Wilcoxon matched-pairs signed-rank tests. Out of the 17 patients that were recruited, full study with two urodynamic studies were confirmed by 11 patients. OAB symptoms improved in 14 (82.4%) patients, and 3 patients discontinued treatment because of ineffectiveness. No patients discontinued treatment because of intolerance to vibegron. The median (IQR) first desire to void (133 [82-185]-161 [123-227] mL), bladder capacity (158 [136-238]-204 [150-257] mL), and bladder compliance (18.1 [9.1-76.7]-34.0 [30.0-82.3] mL/cm H2O) improved significantly post treatment compared to before treatment. Detrusor overactivity disappeared in one of the eight patients with this condition. The parameters of voiding function did not change significantly after the administration of vibegron. Treatment with vibegron significantly improved clinical and urodynamic parameters of pediatric OAB with no adverse effects. Little information is available regarding the feasibility of switching drugs when patients discontinue prior pharmacological therapy because of insufficient efficacy or poor tolerability in children. Vibegron may be a promising OAB treatment option with a better balance of efficacy and tolerability. Vibegron is an alternative agent for pediatric patients with idiopathic OAB for improving both subjective symptoms and lower urinary tract function. Future prospective randomized studies with larger sample sizes must be conducted to validate the results of the present study.

On-demand use of fesoterodine: a new paradigm for extended release antimuscarinics.

We aimed to compare on-demand and continuous use of fesoterodine 4 mg concerning efficacy and adverse effects. A total of 100 patients who were diagnosed with non-neurogenic overactive bladder (OAB) syndrome were included in the study. All patients were evaluated with MMSE, ICIQ-SF, SEAPI quality of health and OAB-V8 questionnaires, at the beginning, 1st month and 4th month. Fesoterodine 4 mg was started for treatment. At the end of the 1st month, patients who obtained benefit from the treatment were 1:1 randomized into two groups. In group 1, fesoterodine 4 mg was given 1 × 1 in a standard manner whereas in group 2 patients took the pills on demand. Both groups were evaluated for efficacy and adverse events at 4 months. Final analyses included 69 patients. At 4-month follow-up, OAB-V8 scores were significantly improved compared to 1 month in both groups. Again at h months, no difference was detected between the two groups for MMSE, ICIQ-SF and SEAPI scores. In continuous usage group, 4th month MMSE scores were significantly lower than 1st month scores. At 4 months, dry mouth and constipation were lower in the on-demand group compared to continuous usage group. Compared to standard continuous usage, on-demand usage of fesoterodine showed similar efficacy with fewer adverse events.

OAB supraspinal control network, transition with age, and effect of treatment: A systematic review.

In light of a better understanding of supraspinal control of nonneurogenic overactive bladder (OAB), the prevalence of which increases with age, functional imaging has gained significant momentum. The objective of this study was to perform a systematic review on the transition of supraspinal control of OAB with age, the effect of therapeutic modalities, and a coordinate-based meta-analysis of all neuroimaging evidence on supraspinal OAB control in response to bladder filling. We performed a systematic literature search of all relevant libraries in November 2021. The coordinates of brain activity were extracted from eligible neuroimaging studies to perform an activation likelihood estimation (ALE)meta-analysis. A total of 16 studies out of 241 were selected for our systematic review. Coordinates were extracted from five experiments involving 70 patients. ALE meta-analysis showed activation of the insula, supplementary motor area, dorsolateral prefrontal cortex, anterior cingulate gyrus, and temporal gyrus with a transition of activation patterns with age, using a threshold of uncorrected p < 0.001. Among young patients, neuroplasticity allows the activation of accessory circuits to maintain continence, as in the cerebellum and temporoparietal lobes. Anticholinergics, pelvic floor muscle training, sacral neuromodulation, and hypnotherapy are correlated with supraspinal changes attributed to adaptability and possibly a substratum of an intrinsic supraspinal component. The latter is better demonstrated by a resting-state functional connectivity analysis, a promising tool to phenotype OAB with recent successful models of predicting severity and response to behavioral treatments. Future neuroimaging studies are necessary to better define an OAB neurosignature to allocate patients to successful treatments.

Intravesical botulinum-A toxin in children with refractory non-neurogenic overactive bladder

Overactive bladder (OAB) with urinary incontinence poses a potentially significant impact on daily activities and quality of life. OAB can be unresponsive to specific urotherapy and antispasmodic medication. Due to its successful outcomes in the treatment of neurogenic bladder, intravesical botulinum-A toxin (BTX-A) became a possible solution for children refractory to treatment. To analyse the outcomes of intravesical BTX-A injections on bladder volume and incontinence in children with refractory OAB. The charts of children diagnosed with refractory non-neurogenic OAB who underwent BTX-A treatment in our centre since 2011 were retrospectively analysed. The functional bladder volume (FBV) is expressed as a percentage of the expected bladder capacity (EBC) for age. Dependent variables were compared using the Wilcoxon Signed Rank test. A multivariate logistic regression was used to identify predictors of the response on urinary incontinence. Fifty children (41 boys) with a median age of 9.9 years were included. In the short term, there was a significant increase in FBV after initial BTX-A treatment from a median of 52.9%-70% (p=0.000). In the short (<6 months) and long term (6-12 months) 72% and 46% showed improvement of continence, respectively. Male gender and small baseline FBV predict a positive outcome on continence in the long term. The most prevalent complications were urinary tract infections occurring in five cases (10%). Although BTX-A injections serve as an effective therapy to increase bladder volume in non-neurogenic OAB children, the outcomes on urinary incontinence are highly variable. This may be a consequence of the multifactorial aspects of this condition. BTX-A will enable children to inhibit their bladder urgency. The effectiveness of post-BTX-A urotherapy training will therefore most probably be higher. We believe that BTX-A injections should be reserved for children refractory to both specific urotherapy and medication. An appropriate population seems to be children with severe OAB symptoms, confirmed detrusor overactivity in urodynamic study and reduced bladder volume. In refractory OAB children, BTX-A injections are safe and effective in enlarging bladder volume and reducing OAB symptoms, particularly in the first six months after injection.

The effectiveness of different electrical nerve stimulation protocols for treating adults with non-neurogenic overactive bladder: a systematic review and meta-analysis.

Electrical nerve stimulation is a widely used treatment for overactive bladder but there is no consensus regarding the best placement of electrodes or protocols. We hypothesised that some non-implanted neurostimulation protocols would be more effective compared to others for treating urinary symptoms and improving quality of life among adults diagnosed with non-neurogenic overactive bladder. A systematic review and meta-analyses of randomized clinical trials were performed in five electronic databases: PubMed/MEDLINE, Lilacs, CINAHL, Web of Science, and PEDro. The main outcome was urinary symptoms-frequency, nocturia, and urgency-and the secondary outcome quality of life. Some protocol characteristics were extracted, e.g., frequency, pulse width, intensity, intervention time, and electrode placement. Nine randomized controlled trials were included. Tibial neurostimulation showed better results than sacral neurostimulation for urge incontinence (mean difference = 1.25 episodes, 95% CI, 0.12-2.38, n = 73). On the pooled analysis, the different neurostimulation protocols-intravaginal, percutaneous tibial, and transcutaneous tibial nerve stimulation-demonstrated similar results for urinary frequency, nocturia, and urgency as well as quality of life. In general, effect sizes from meta-analyses were low to moderate. The best reported parameters for percutaneous tibial nerve stimulation were 20-Hz frequency and 200-μs width, once a week. There was evidence that tibial neurostimulation is more effective than sacral neurostimulation for urge incontinence symptoms among patients with non-neurogenic overactive bladder. Overall, there was no superiority of an electrical nerve stimulation electrode placement and protocol over others considering urinary symptoms and quality of life. Further studies with three-arm trials are necessary. This study was registered at PROSPERO: CRD4201810071.

β3-Adrenoceptor Agonist for the Treatment of Bladder Dysfunction in Children: A Systematic Review and Meta-Analysis.

ß3-adrenergic receptor agonists (ß3 agonists) have been used in treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) in adults. However, their use in children has only recently been approved by the U.S. Food and Drug Administration for patients with NDO. As in adults, the role of ß3 agonists in children may include conditions such as OAB. This systematic review and meta-analysis aims to understand the intended use, efficacy and safety of ß3 agonists in the pediatric population. A literature search was performed in February 2021 across MEDLINE®, Embase®, Scopus®, the Cochrane Library and ClinicalTrials.gov. No language restrictions were placed. All records describing the clinical use of ß3 agonists in pediatric patients (<18 years of age) were included, regardless of the methodological design or outcomes assessed. The identified records were screened by 2 independent authors. The reporting was compliant with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Data extraction was performed by 2 independent reviewers, blinded to each other's extractions. The data were pooled using the fixed effects model. Of 367 records identified, 8 studies were included in the review (3 prospective and 5 retrospective). ß3 agonists led to improvements in both urodynamics parameters and self-reported outcomes such as incontinence. Commonly reported side effects were headaches (3%‒5.9%), constipation (3.5%‒5.7%), rhinitis/nasopharyngitis (1.7%‒5.8%) and blurred vision (1.7%‒2.9%). Clinically meaningful changes in safety outcomes (blood pressure, heart rate, electrocardiogram-related changes, liver function) were rare. Before and after ß3 agonist use, pooled effect estimates for maximum cystometric capacity for 171 patients were mean difference of +98.84 ml (95% CI 74.72, 122.96); for complete dryness, assessment of 235 patients showed a Peto odds ratio of 8.68 (95% CI 5.22, 14.45). ß3 agonists appear to be a promising, effective and safe alternative/adjunctive therapy in management of pediatric NDO or OAB, with improvements in both objective urodynamics parameters and subjective patient-reported outcomes following their use.

PD06-11 CHANGES IN URINE METABOLITES AFTER ONABOTULINUMTOXIN-A INJECTIONS FOR REFRACTORY OVERACTIVE BLADDER

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I (PD06)1 Sep 2021PD06-11 CHANGES IN URINE METABOLITES AFTER ONABOTULINUMTOXIN-A INJECTIONS FOR REFRACTORY OVERACTIVE BLADDER Laura Tellechea, Samantha Freeman, Ilir Agalliu, Melissa Laudano, Sylvia Suadicani, and Nitya Abraham Laura TellecheaLaura Tellechea More articles by this author , Samantha FreemanSamantha Freeman More articles by this author , Ilir AgalliuIlir Agalliu More articles by this author , Melissa LaudanoMelissa Laudano More articles by this author , Sylvia SuadicaniSylvia Suadicani More articles by this author , and Nitya AbrahamNitya Abraham More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001974.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Overactive Bladder (OAB) is diagnosed based on symptoms and often treated based on patient preference. A urine biomarker could phenotype refractory OAB and identify those who would benefit from chemodenervation vs neuromodulation. Metabolomics is the analysis of metabolic profiles. Urine metabolites may be potential biomarkers for OAB yet little is known about the effect of third line treatments like bladder onabotulinumtoxin-A (BTX-A) on the urinary metabolome. Our study objective was to evaluate changes in the urinary metabolome and correlate with OAB-V8 symptom score change after BTX-A injections in women with refractory OAB. METHODS: Women over 18 years with non-neurogenic refractory OAB were recruited from our female urology clinic. OAB-V8 questionnaires and urine samples were collected before and after 100 units BTX-A injection. Samples were aliquoted, frozen on dry ice, and stored in a -80ºC freezer. Urine metabolomic analysis was conducted by Human Metabolome Technology Inc., Tsuruoka, Japan, and data was expressed as percent change from pre-treatment values. These were correlated with improvement in OAB-V8 Scores categorized as: no improvement (<8), mild improvement (8-16), marked improvement (>17). Change in metabolite levels was compared between groups using ANOVA, and correlations between metabolites and OAB-V8 scores evaluated using linear regression. RESULTS: Fifty-four urine samples were collected from 21 women. Mean age was 56 (46-56). 3 patients had diabetes, 10 had chronic pain disorders, 8 had prior pelvic surgery. Of 42 metabolites, Quinic Acid (p=0.01), N-o-Toluoyl-glycine-1-Phenaceturic acid-1 (p=0.02) and Adenosine (p=0.01) levels were significantly lower and N8-Acetylspermidine (p=0.01) levels significantly higher in the marked improvement vs. no improvement group. In linear regression models, N8-acetylspermidine (p=0.02) and Quinic Acid levels (p=0.009) significantly correlated with improvement in OABV-8 scores, Figure 1. CONCLUSIONS: Bladder BTX-A injection changes the urinary metabolome, with corresponding OAB score improvement. Further investigation of urine metabolites could provide objective data and biomarkers to follow OAB treatment response, and ultimately identify a subset of women who would benefit from certain third line therapies. Source of Funding: Urology Department © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e104-e104 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Laura Tellechea More articles by this author Samantha Freeman More articles by this author Ilir Agalliu More articles by this author Melissa Laudano More articles by this author Sylvia Suadicani More articles by this author Nitya Abraham More articles by this author Expand All Advertisement Loading ...

Characteristics of the Urinary Proteome in Women with Overactive Bladder Syndrome: A Case-Control Study.

Despite an estimated prevalence of 13% in women, the exact etiology of non-neurogenic overactive bladder syndrome is unclear. The aim of our study was to gain a better understanding of the pathophysiology of female overactive bladder syndrome by mapping the urinary proteomic profile. We collected urine samples of 20 patients with overactive bladder syndrome and of 20 controls. We used mass spectrometric analysis for label-free quantitation, Swissprot human database for data search, Scaffold for data allocation and the Reactome Knowledgebase for final pathway enrichment analysis. We identified 1897 proteins at a false discovery rate of 1% and significance level p < 0.001. Thirty-seven significant proteins of the case group and 53 of the control group met the criteria for further pathway analysis (p < 0.0003 and Log2 (fold change) >2). Significant proteins of the overactive bladder group were, according to the 25 most relevant pathways, mainly involved in cellular response to stress and apoptosis. In the control group, significant pathways mainly concerned immunological, microbial-protective processes and tissue- elasticity processes. These findings may suggest a loss of protective factors as well as increased cellular response to stress and apoptosis in overactive bladder syndrome.

The 1-year continuation rate and discontinuation factors of vibegron and mirabegron: A retrospective comparative study in a rehabilitation hospital in Japan.

To compare the 1-year continuation rate and discontinuation factors between vibegron and mirabegron in patients with neurogenic and nonneurogenic overactive bladder. Continuation or discontinuation of the target drugs and reasons for discontinuation as well as patients' grounds and adverse effects were evaluated retrospectively from the medical records between September 2018 and December 2020. After selecting patients according to the inclusion and exclusion criteria, 180 cases taking mirabegron and 132 taking vibegron were adjusted for intergroup variability by propensity score matching. We performed Cox proportional hazards regression for the 1-year continuation rate and Fine-Gray proportional hazards regression for the 1-year cumulative incidence of discontinuation events. Subgroup analysis was also performed for the background factors related to the 1-year continuation rate. The 1-year continuation rate was 83.8% for vibegron and 58.2% for mirabegron, and the hazard ratio was 0.32 (95% CI: 0.18-0.57, P < .001) as for an incidence of discontinuation events of vibegron against mirabegron. The incidence of discontinuation due to an inadequate efficacy was 8.7% for vibegron and 29.1% for mirabegron, and similarly the hazard ratio was 0.26 (95% CI: 0.12-0.55, P < .001). The subgroup analysis indicated a similar tendency in each subgroup except for that of catheterization, and there was no significant interaction between the groups. It is suggested that vibegron is superior to mirabegron in the continuity of administration in neurogenic and nonneurogenic overactive bladder populations without catheterization with fewer discontinuations due to inadequate efficacy.

Efficacy and safety of tamsulosin vs its combination with mirabegron in the management of lower urinary tract non-neurogenic overactive bladder symptoms (OABS) because of Benign Prostatic Enlargement (BPE)-An open label randomised controlled clinical study.

The efficacy and safety of βeta-3 agonists (Mirabegron 50mg) have been sparingly assessed in the published English literature. We aim to do an efficacy-safety analysis of Mirabegron-Tamsulosin combination therapy vs tamsulosin-placebo monotherapy in a select subset of medication virgin Benign Prostatic Enlargement (BPE) patients with coexisting predominant non-neurogenic overactive bladder symptoms (OABS). After prior written informed consent and IEC, 80 patients of uncomplicated BPE with coexisting non-neurogenic OABS and IPSS of >7 without contraindications to drug therapy were computer randomised/allocated to receive either[50mg Mirabegron plus Tamsulosin 0.4mg (Intervention arm-I)]or [Tamsulosin 0.4mg plus capsule lactobacillus (Comparator arm-II)] once daily for 8weeks. Efficacy was evaluated using the OABS Score (OABSS), mean change in nocturnal frequency (NF), PVR and IPSS, while safety was assessed by recording treatment emergent adverse events (TEAE). Follow-up visits were performed at second, fourth and eighth week. Patient data in both groups were generally comparable with the exception of NF and IPSS storage sub score (IPSS-ss). Significant improvements were visualised in the eighth week primary endpoint total OABS sub score (OABSS-ss) in the combination group (P<.001).Similar significant improvements were seen with most secondary parameters such as the mean change in NF, IPSS, IPSS-ss, OABS-ss, voided volume, Qmax, and Quality of life index (QOL) (P<.001). No significant increase in PVR was observed in the Mirabegron arm and no patient developed urinary retention. The TEAE were minor, self-limiting and managed symptomatically without drug discontinuity. Mirabegron can be significantly efficacious and safe in ameliorating non-neurogenic OABS induced by BPE vs placebo by initiating combination therapy from the start as opposed to the usual 'add on therapy' protocol. This combination appeared to be superior in terms of overall safety, minimal side effects, better compliance and tolerability vs Tamsulosin monotherapy in select BPE patients with predominant non-neurogenic OABS.