Concomitant Use of Sodium-Glucose Cotransporter 2 Inhibitors and Overactive Bladder Drugs and the Risk of Urinary Tract Infection.

Concomitant use of sodium glucose cotransporter-2 inhibitors (SGLT-2i) and overactive bladder (OAB) drugs potentially poses a risk of urinary tract infections (UTIs) due to the urinary retention of highly concentrated glucose in the urine. Thus, this study aimed to investigate the risk of UTIs among patients who initiated SGLT-2i treatment while taking OAB drugs. This population-based cohort study included new-users of SGLT-2i or comparator antidiabetics (dipeptidyl peptidase-4 inhibitor (DPP-4i); glucagon-like peptide-1 receptor agonist (GLP-1RA)) with OAB drugs between 2014 and 2020 using claim data from Korea. Primary outcome was a composite UTI event composite end point comprising pyelonephritis, cystitis, and urethritis, using both inpatient and outpatient diagnoses. Propensity score fine stratification was used to adjust for potential confounding factors. Weighted hazard ratios (HR) were calculated using the Cox proportional hazards model. In the first cohort, 796 and 9,181 new-users of SGLT-2i and DPP-4i with OAB drugs were identified, respectively. This study found a similar risk of UTIs in concomitant users of SGLT-2i and DPP-4i (weighted HR 1.08, 95% confidence interval: 0.88-1.32) with OAB drugs. In the second cohort, 2,387 and 280 new-users of SGLT-2i and GLP-1RA with OAB drugs were identified, respectively. Initiation of SGLT-2i while on OAB treatment was not associated with increased risk of UTI (0.89, 0.50-1.60), compared with initiation of GLP-1RA. These results show that the concomitant use of SGLT-2i with OAB drugs was not associated with an increased risk of UTI compared with the concomitant use of DPP-4i or GLP-1RA with OAB drugs.

Anatomical location and number of injection sites of intravesical OnabotulinumtoxinA for females with refractory idiopathic overactive bladder: A scoping review.

AIMS: The negative impact on quality of life and the economic-related burden to the patient and the health care system associated with idiopathic overactive bladder (iOAB) is well-documented. Intradetrusor OnabotulinumtoxinA (BTN/A) injections are a well-used treatment modality for the management of overactive detrusor refractory to medical management, with well-documented efficacy and safety profiles. There is currently no best practice guideline for the administration of BTN/A for this procedure and historically the trigone of the bladder has been excluded from the injection paradigm given the risk of vesicoureteral reflux (VUR). METHODS: A scoping review methodology was employed to assess available literature to evaluate current techniques used. There is emerging literature that the inclusion of the trigone may increase the efficacy of the procedure, while maintaining a similar adverse effect profile. Similar results could also be obtained by decreasing the number of injection sites. A scoping review was completed with systematic methodology using the Preferred Systematic Reviews and Meta Analyses extension for Scoping Review checklist. The search strategy looked to evaluate BTN/A and number of injection sites and the inclusion of the trigone in female patients with iOAB. Studies with male or neurogenic bladder only were excluded. Mixed studies were included. A specialist research librarian was engaged, with supervision from a functional urologist using a combination of MeSH and natural language terms. Two investigators independently reviewed the titles and abstracts. RESULTS: Twelve articles were included and were published between 2005 and 2021. There was no evidence of VUR in any of the results. All but one study reported similar if not improved efficacy of trigone-inclusion. Lower number of injection sites had similar efficacy profiles to higher numbers of intradetrusor injections. CONCLUSIONS: Further high-quality randomized control trials of trigone inclusion and reduction of injection sites are required. It is hoped that with further exploration of intraoperative methods for BTN/A injections, the development of universally accepted guidelines may optimize management and experiences for patients with iOAB.

Comparison of the efficacy and safety of onabotulinum toxin A and mirabegron for overactive bladder in elderly patients.

OBJECTIVE: This study aimed to investigate the efficacy and tolerability of mirabegron and onabotulinum toxin A (BoNT/A) injections for overactive bladders. The treatment we provided was to patients over the age of 65 years who were not satisfied with the results of anticholinergic monotherapy. PATIENTS AND METHODS: This multicenter retrospective observational study was conducted between March 2017 and December 2021. Thirty patients who were unable to take anticholinergics or mirabegron due to side effects received a total of 100-unit intravesical injections of BoNT/A. Furthermore, 30 patients receiving 50 mg of mirabegron daily were compared. Micturition frequency, urgency of urinary incontinence, pad usage, and nocturia were all evaluated for efficacy. Patients' health-related quality of life and subjective satisfaction ratings were assessed before and six months after treatment using an incontinence-quality-of-life questionnaire. We documented all adverse events for all subjects. RESULTS: There was a statistically significant decrease in the frequency, daily pad usage, and incontinence episodes of both groups. The median (interquartile range) voiding frequency after onabotulinum toxin A treatment was lower than that after mirabegron treatment [9.4 (6.83-10.0) vs. 10.5 (8.37-11.67); p = 0.01]. Incontinence episodes showed similar differences [1.3 (1.17-3.67) vs. 2.53 (2.0-5.67); p = 0.05]. There was no significant difference in nocturia or maximum urine flow rate between the groups before and after treatment. CONCLUSIONS: We determined that mirabegron led to lower urinary retention, hematuria, infection and post-void residual urine volume rates than BoNT/A in the older patient population. In addition, mirabegron treatment had comparable incontinence-quality-of-life scores at six months post-treatment.

Antibiotic prophylaxis for onabotulinum toxin A injections: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: To our knowledge, there are no evidence-based recommendations regarding the optimal prophylactic antibiotic regimen for intradetrusor onabotulinum toxin type A (BTX) injections. This systematic review and meta-analysis was aimed at investigating the optimal prophylactic antibiotic regimen to decrease urinary tract infection (UTI) in patients undergoing BTX for overactive bladder syndrome (OAB). METHODS: A systematic search of MEDLINE, Embase, CINAHL, and Web of Science was conducted from inception through 30 June 2022. All randomized controlled trials and prospective trials with > 20 subjects undergoing BTX injections for OAB in adults that described prophylactic antibiotic regimens were included. Meta-analysis performed to assess UTI rates in patients with idiopathic OAB using the inverse variance method for pooling. RESULTS: A total of 27 studies (9 randomized controlled trials, 18 prospective) were included, representing 2,100 patients (69% women) with 19 studies of idiopathic OAB patients only, 6 of neurogenic only, and 2 including both. No studies directly compared antibiotic regimens for the prevention of UTI. Included studies favor the use of antibiotics in patients with idiopathic OAB and favor continuing antibiotics for 2-3 days after the procedure for prevention of UTI. Given the heterogeneity of the data, direct comparisons of antibiotic type or duration could not be performed. Meta-analysis found a 10% UTI rate at 4 weeks and 15% at 12 weeks post-injection. CONCLUSIONS: Although there are insufficient data to support the use of a specific antibiotic regimen, available studies favor the use of prophylactic antibiotics for 2-3 days in idiopathic OAB patients undergoing BTX injection. Future trials are needed to determine the optimal regimens to prevent UTI in patients undergoing BTX for OAB.

Pathways and parameters of sacral neuromodulation in rats.

The stimulation paradigm for sacral neuromodulation has remained largely unchanged since its inception. We sought to determine, in rats, whether stimulation-induced increases in bladder capacity correlated with the proportion of sensory pudendal (PudS) neurons at each stimulated location (L6, S1). If supported, this finding could guide the choice of stimulation side (left/right) and level (S2, S3, S4) in humans. Unexpectedly, we observed that acute stimulation at clinically relevant (low) amplitudes [1-1.5 × motor threshold (Tm)], did not increase bladder capacity, regardless of stimulus location (L6 or S1). More importantly for the ability to test our hypothesis, there was little anatomic variation, and S1 infrequently contributed nerve fibers to the PudS nerve. During mapping studies we noticed that large increases in PudS nerve activation occurred at amplitudes exceeding 2Tm. Thus, additional cystometric studies were conducted, this time with stimulation of the L6-S1 trunk, to examine further the relationship between stimulation amplitude and cystometric parameters. Stimulation at 1Tm to 6Tm evoked increases in bladder capacity and decreases in voiding efficiency that mirrored those produced by PudS nerve stimulation. Many animal studies involving electrical stimulation of nerves of the lower urinary tract use stimulation amplitudes that exceed those used clinically (∼1Tm). Our results confirm that high amplitudes generate immediate changes in cystometric parameters; however, the relationship to low-amplitude chronic stimulation in humans remains unclear. Additional studies are needed to understand changes that occur with chronic stimulation, how these changes relate to therapeutic outcomes, and the contribution of specific nerve fibers to these changes.NEW & NOTEWORTHY Acute low-amplitude electrical stimulation of sacral nerve (sacral neuromodulation) did not increase bladder capacity in anesthetized CD, obese-prone, or obese-resistant rats. Increasing stimulation amplitude correlated with increases in bladder capacity and pudendal sensory nerve recruitment. It is unclear how the high-amplitude acute stimulation that is commonly used in animal experiments to generate immediate effects compares mechanistically to the chronic low-amplitude stimulation used clinically.

Efficacy of KPR-5714, a selective transient receptor potential melastatin 8 antagonist, on chronic psychological stress-induced bladder overactivity in male rats.

AIMS: Chronic psychological stress aggravates lower urinary tract symptoms. Among others, water avoidance stress is a chronic psychological stressor that plays a causal role in the exacerbation and development of bladder dysfunction in rats. In this report, the effects of KPR-5714, which is a selective transient receptor potential melastatin 8 (TRPM8) antagonist, on bladder overactivity induced by water avoidance stress were examined. METHODS: Male rats were subjected to water avoidance stress for 2 h per day for 10 consecutive days. The effects of water avoidance stress on voiding behavior using metabolic cages and histological bladder changes were investigated in rats. The involvement of bladder C-fiber afferent on voiding frequency in rats exposed to water avoidance stress was assessed using capsaicin. The effects of KPR-5714 on storage dysfunction in rats subjected to water avoidance stress were examined. RESULTS: In voiding behavior measurements, water avoidance stress-induced storage dysfunction, causing a decrease in the mean voided volume and increasing voiding frequency. A comparison of bladders from normal rats and rats exposed to water avoidance stress showed no histological differences. Water avoidance stress-induced bladder overactivity was completely inhibited by pretreatment with capsaicin. KPR-5714 showed a tendency to increase the mean voided volume and significantly decreased the voiding frequency without affecting the total voided volume in these rats. CONCLUSION: The results suggest that KPR-5714 is a promising option for treating chronic psychological stress-induced bladder overactivity.

Mirabegron and Anticholinergics in the Treatment of Overactive Bladder Syndrome: A Meta-analysis.

OBJECTIVE: To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). DATA SOURCE: Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence. DATA COLLECTION: RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence. DATA SYNTHESIS: We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]. CONCLUSION: Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.

OBJETIVO: Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH). FONTE DE DADOS: Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão. COLETA DE DADOS: RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. SíNTESE DOS DADOS: Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,89­0,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,48­0,68); 9.375 pacientes; RR: 0,44 (0,35­0,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,98­1,00)]. CONCLUSãO: Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.

Activation of the adenosine A1 receptor in the lumbosacral spinal cord improves bladder overactivity in rats with cystitis induced by cyclophosphamide.

PURPOSE: To investigate the effect of intrathecal administration of CCPA, an adenosine A1 receptor agonist, on voiding function in rats with cystitis induced by cyclophosphamide (CYP). METHODS: Thirty 8-week-old Sprague Dawley rats were randomly divided into a control group (n = 15) and a cystitis group (n = 15). Cystitis was induced by a single intraperitoneal injection of CYP (200 mg/kg, dissolved in physiological saline) in rats. Control rats were injected intraperitoneally with physiological saline. The PE10 catheter reached the level of L6-S1 spinal cord through L3-4 intervertebral space for intrathecal injection. Forty-eight hours after intraperitoneal injection, urodynamic tests were conducted to observe the effect of intrathecal administration of 10% dimethylsulfoxide (vehicle) and 1 nmol CCPA on micturition parameters, including basal pressure (BP), threshold pressure (TP), maximal voiding pressure (MVP), intercontraction interval (ICI), voided volume (VV), residual volume (RV), bladder capacity (BC), and voiding efficiency (VE). Histological changes of the bladder of cystitis rats were studied through hematoxylin-eosin staining (HE staining). Moreover, Western blot and immunofluorescence were used to study the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord in both groups of rats. RESULTS: HE staining revealed submucosal hemorrhage, edema, and inflammatory cell infiltration in the bladder wall of cystitis rats. The urodynamic test showed significant increase in BP, TP, MVP and RV in cystitis rats, while ICI, VV, BC and VE decreased significantly, indicating bladder overactivity. CCPA inhibited the micturition reflex in both control and cystitis rats, and significantly increased TP, ICI, VV, BC, and VE, but had no significant effect on BP, MVP and RV. Western blot and immunofluorescence showed that there was no significant difference in the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord between the control and cystitis rats. CONCLUSION: The findings of this study suggest that intrathecal administration of the adenosine A1 receptor agonist CCPA alleviates CYP-induced bladder overactivity. Furthermore, our results indicate that the adenosine A1 receptor in the lumbosacral spinal cord may be a promising target for treatment of bladder overactivity.

Analysis of Urinary Retention Caused by Selective ß 3-adrenoceptor Agonists Using the Japanese Adverse Drug Event Report Database (JADER).

Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveß 3-adrenoceptor agonists (sß 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sß 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sß 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sß 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sß 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sß 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

A treatment prediction strategy for overactive bladder using a machine learning algorithm that utilized data from the FAITH study.

AIMS: To use machine learning algorithms to develop a model to accurately predict treatment responses to mirabegron or antimuscarinic agents in patients with overactive bladder (OAB), using real-world data from the FAITH registry (NCT03572231). METHODS: The FAITH registry data included patients who had been diagnosed with OAB symptoms for at least 3 months and were due to initiate monotherapy with mirabegron or any antimuscarinic. For the development of the machine learning model, data from patients were included if they had completed the 183-day study period, had data for all timepoints and had completed the overactive bladder symptom scores (OABSS) at baseline and end of study. The primary outcome of the study was a composite outcome combining efficacy, persistence, and safety outcomes. Treatment was deemed "more effective" if the composite outcome criteria for "successful," "no treatment change," and "safe" were met, otherwise treatment was deemed "less effective." To explore the composite algorithm, a total of 14 clinical risk factors were included in the initial data set and a 10-fold cross-validation procedure was performed. A range of machine learning models were evaluated to determine the most effective algorithm. RESULTS: In total, data from 396 patients were included (266 [67.2%] treated with mirabegron and 130 [32.8%] treated with an antimuscarinic). Of these, 138 (34.8%) were in the "more effective" group and 258 (65.2%) were in the "less effective" group. The groups were comparable in terms of their characteristic distributions across patient age, sex, body mass index, and Charlson Comorbidity Index. Of the six models initially selected and tested, the decision tree (C5.0) model was chosen for further optimization, and the receiver operating characteristic of the final optimized model had an area under the curve result of 0.70 (95% confidence interval: 0.54-0.85) when 15 was used for the min n parameter. CONCLUSIONS: This study successfully created a simple, rapid, and easy-to-use interface that could be further refined to produce a valuable educational or clinical decision-making aid.

The efficacy and safety of medication for treating overactive bladder in patients with Parkinson's disease: a meta-analysis and systematic review of randomized double-blind placebo-controlled trials.

INTRODUCTION AND HYPOTHESIS: The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD). METHODS: Papers containing predefined key terms were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases up to December 2021 to collect randomized double-blind placebo-controlled trials (RCTs). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Two reviewers independently assessed the risk of bias using the modified Jadad scale and Cochrane risk-of-bias tool. The GRADEpro GDT was employed to evaluate the strength of evidence based on the findings of this meta-analysis. RESULTS: We eventually included four RCTs involving 313 patients (163 patients in the medication group and 150 patients in the placebo group). Of these, the therapeutic agent in two RCTs was mirabegron (121 and 106 patients and controls, respectively, representing 3/4 -2/3 of the patients). The results showed that the number of micturition episodes per 24 h (MD -1.33; 95% CI -2.30 to -0.36; p = 0.007), the number of nocturia episodes per 24 h (MD -0.33; 95% CI -0.58 to -0.08; p = 0.009) and the number of urinary incontinence episodes per 24 h (MD -0.72; 95% CI -1.32 to -0.12; p = 0.02) were significantly lower in the medication group than in the placebo group. The OAB symptom score (MD -2.84; 95% CI -4.67 to -1.00; p = 0.002) and quality of life score (MD 15.15; 95% CI 12.33 to 17.96; p < 0.0001) of the medication group were significantly improved compared with those of the placebo group. However, no significant difference in the daily frequency of urinary urgency episodes was identified between the medication group and the placebo group (MD -0.79; 95% CI -1.71 to 0.14; p = 0.09). There were no significant differences between the two groups in terms of drug-related adverse events (OR 1.69; 95% CI 0.41 to 6.99; p = 0.47), especially in PD patients receiving mirabegron therapy. CONCLUSIONS: Medication was effective for OAB symptoms in patients with PD, and patients tolerated adverse events well.

The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.

BACKGROUND: Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy. OBJECTIVE: The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO. METHODS: The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual. RESULTS: A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and ß3-adrenoceptor-agonists possessed good effectiveness and safety. CONCLUSION: OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and ß3-adrenoceptor-agonists have good effectiveness and safety.

Efficacy and safety of vibegron compared with mirabegron for overactive bladder: A systematic review and network meta-analysis.

OBJECTIVES: The aim of this study was to indirectly compare the efficacy and safety of mirabegron and vibegron in patients with overactive bladder. METHODS: A systematic search was performed on Pubmed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases to identify studies from the date of database inception to January 1, 2022. All randomized controlled trials comparing mirabegron or vibegron with tolterodine, imidafenacin, or placebo were eligible. One reviewer extracted data, and a second reviewer checked. Included trials were assessed for similarity, and networks were developed using Stata 16.0 software. Mean differences for continuous variables and odds ratios for dichotomous variables together with their 95% confidence intervals (CIs) were used to rank treatments and compare the differences, respectively. RESULTS: A total of 11 randomized controlled trials and 10 806 patients were included. For each outcome, results for all licensed treatment doses were included. Both vibegron and mirabegron were more efficacious than placebo at reducing the frequency of micturition, incontinence, urgency, urgency incontinence, and nocturia. Vibegron was more efficacious than mirabegron in reducing mean voided volume/micturition (95% CI [5.15, 14.98]). Safety outcomes for vibegron and mirabegron were similar to those in the placebo group, except for mirabegron, which had a higher risk of nasopharyngitis and cardiovascular adverse events than placebo. CONCLUSIONS: Both drugs seem to be comparable and well tolerated, particularly as direct comparisons are not available. However, vibegron may be more effective than mirabegron in reducing mean voided volume.

Patient Perception of Bladder Condition after Treatment with Solifenacin and Tolterodine in Overactive Bladder Patients.

BACKGROUND: Solefinacin and Tolterodine are new generation antimuscarinics claimed to have bladder specific action and less adverse effect like dry mouth. The objective of the study was to compare the improvement in urinary symptoms among patients using solefinacin and tolterodine with overactive bladder symptoms. METHODS: A hospital based cross-sectional comparative study was done for one year duration. All patients with overactive bladder symptoms were included and in every alternate patient's solefinacin and tolterodine were given after taking note of baseline OAB symptoms, PPBC score and UPS score. Participants were followed up after one month and noted improvement in endpoint OAB symptoms. Comparison of baseline to end-point symptoms changes among each group of participants were analyzed for statistical significance. RESULTS: Among 101 participants included in the study, 49 participants were in solefinacin group and 52 participants were in tolterodine group. The end-point comparison of urgency symptoms were improved by 20.1±6.76 (mean ± SD) units in solefinacin group and by 17.0 ± 9.18 units in tolterodine group. Urgency perception score improved to 2.1±0.66 for patients under solefinacin and 2±0.73 for tolterodine. Patient perception of bladder condition (PPBC) showed improvement in solefinacin group by 3.2±1.26 units and in tolteradine by 2.8±1.54 units (p = 0.165). Comparing the patient's perception of treatment outcome, massive improvement was reported by 81.6% of those receiving Solefinacinand 65.4% receiving tolterodine, though not statistically significant ( p = 0.131). CONCLUSIONS: Solefinacin and Tolterodine showed improvement in urinary symptoms, UPS and PPBC. Both showed comparable efficacy without significant superiority over one another.

OnabotulinumtoxinA discontinuation in patients with prior nerve stimulation.

PURPOSE: The objective of this study is to describe the characteristics of patients who discontinue onabotulinumtoxinA treatment for overactive bladder (OAB) and to determine the impact of prior sacroneuromodulation or peripheral nerve stimulation on the discontinuation rates of onabotulinumtoxinA. MATERIALS AND METHODS: This is a retrospective cohort study of women with at least two onabotulinumtoxinA (BTX-A) treatments for OAB with a Female Pelvic Medicine and Reconstructive surgeon at a referral center between January 2014 and July 2019. Patients were excluded if they underwent BTX-A treatment in the operating room or utilized clean intermittent catheterization at baseline. Women who continued injections throughout the study period were compared to those who did not. Discontinuation was defined as stopping BTX-A during the study period. Treatment failure was defined as a documented failure in the chart and/or moving to other OAB treatments. Loss to follow-up was defined as no follow-up greater than 12 months after the last injection. Discontinuation-free and failure-free survival were estimated by Kaplan-Meier analysis. RESULTS: A total of 214 women met the inclusion criteria with a mean age of 62.9 ± 14 years. Fifty percent were Black. Eighty-six (40.2%) discontinued onabotulinumtoxinA treatment during the study period. There were no demographic differences between patients who discontinued BTX-A and those who continued with the following exceptions: patients who discontinued had higher rates of prior pelvic reconstructive surgery (19.8% vs. 10.2%, p = 0.04) and were more likely to have the concurrent diagnosis of painful bladder syndrome (9.3% vs. 2.3%, p = 0.03). Patients diagnosed with a urinary tract infection (UTI) after ≥50% of treatments were more likely to discontinue (27.9% vs. 14.1%, p = 0.01). On multivariate logistic regression analysis, patients with recurrent UTIs after treatment were significantly more likely to discontinue than those who do not (odds ratio: 2.61, [1.17, 5.82]). Of the cohort, 54 (25%) patients had previously undergone nerve stimulation. A total of 27.8% of patients with prior nerve stimulation discontinued BTX-A compared to 44.4% of those without prior third line treatment (p = 0.03). Patients with prior nerve stimulation had a higher discontinuation-free survival rate (p = 0.013) but there was no difference in failure-free survival. CONCLUSIONS: Patients who have recurrent UTIs after onabotulinumtoxinA injections are 2.6 times more likely to discontinue treatment than those who do not have infections. Patients with prior exposure to nerve stimulation have a significantly lower onabotulinumtoxinA discontinuation rate, but there is no difference in failure rates.

Clinical preferences and treatment attitudes among urologists, gynecologists, and geriatricians: An independent online questionnaire survey for comparison of treatment choices in the management of overactive bladder.

OBJECTIVE: Overactive bladder (OAB) is a common clinical problem with associated morbidities both in men and women. Although real-life management strategies have been examined among urologists (URO), treatment choices may differ between different specialties. In the present study, an online survey was conducted to determine and compare the management strategies and clinical preferences of UROs, obstetricians/gynecologists (OB/GYN), and geriatricians (GER) in the treatment of OAB in their daily practices. METHODS: Between December 2020 and February 2021, an online questionnaire was sent to URO, OB/GYN, and GER specialists/residents. Current strategies and attitudes toward treatment of OAB in patients <65 years were compared between URO and OB/GYN, whereas the responses were compared between all three specialties in patients ≥65 years. RESULTS: A total of 733 specialists/physicians (433 URO, 236 OB/GYN, and 64 GER) completed the online survey. Patients with OAB were more likely to present to URO compared to OB/GYN and GER (p = 0.001). A combination of behavioral modification and pharmacotherapy (antimuscarinics and/or beta-3 agonists) were chosen for the initial treatment of patients with OAB in both specialties with a significantly higher proportion by URO than by OB/GYN (51.9% vs. 38.1%; p = 0.001). Antimuscarinics were the most frequently prescribed medications by both the URO and OB/GYN specialties (81.8% vs. 78.4%; p = 0.27). Combination therapy with antimuscarinics was preferred more often by URO (91.5% vs. 77.1%; p = 0.001) when no or an inadequate response after initial treatment occurred. Multiple medication use, comorbidities, and risk of cognitive side effects affected medication preference by all specialists, especially by GER (p = 0.018). CONCLUSIONS: Patients with OAB present to UROs, OB/GYN and GER more frequently compared to other specialities. Although antimuscarinics and beta-3 adrenoceptor agonists are equally recommended as first-line pharmacotherapy for OAB, antimuscarinics were preferred for most patients as the initial molecule by all specialties. Beta-3 agonists are increasingly preferred for elderly patients.

Pharmacokinetics and Safety of Vibegron 75 mg Administered as an Intact or Crushed Tablet in Healthy Adults.

Oral pharmacotherapy for overactive bladder, a condition that increases with age, includes anticholinergics and ß3 -adrenergic receptor agonists. Older adults, including those with dysphagia, may have difficulty swallowing tablets. In this phase 1 study in healthy adults, we assessed the pharmacokinetic profile of the ß3 -adrenergic receptor agonist vibegron administered as a single 75-mg dose as an intact tablet versus crushed and mixed with applesauce. Additional end points included safety (assessed by adverse events), perception of taste (assessed via questionnaire), and stability over 4 hours after crushing and mixing in applesauce (assessed by chromatography). Overall, 30 participants were randomized, and 29 were included in the pharmacokinetic analysis. Crushing a vibegron tablet and mixing with applesauce decreased vibegron maximum observed plasma concentration and area under the plasma concentration-time curve from time 0 to infinity by ≈30% and ≈10%, respectively; however, these decreases were not considered clinically significant. Treatment-emergent adverse events were reported in 16 (53.3%) participants. Approximately half of participants reported the vibegron and applesauce mixture tasted as expected; of those reporting the taste was different than expected, 50% reported the taste as bitter. The mixture was stable for 4 hours in applesauce. The results of this study showed that crushing and administering vibegron with applesauce may be an appropriate option for patients with overactive bladder and swallowing difficulties.

Association of lower urinary tract symptoms and diuretic adherence.

OBJECTIVE: To assess whether more severe urinary symptoms and poorer quality of life among patients on diuretic therapy are associated with decreased adherence to the diuretic regimen. METHODS: Participants were recruited via ResearchMatch.org and sent a REDCap survey. The Overactive Bladder Questionnaire-Short Form (OAB-q SF) was used to assess urinary symptom bother and health-related quality of life (HRQL). Participants were asked if they skip diuretic doses due to urinary symptoms with a bivariate (yes or no) outcome. Subgroup analyses of loop vs non-loop diuretic and those taking the diuretic for a cardiovascular indication (hypertension or heart failure) were performed. RESULTS: A total of 4029 surveys were sent, 285 were returned (7.1% response rate), and 279 were included in the study. Fifty-three participants admitted to skipping diuretic doses due to urinary symptoms. Lower HRQL scores were significantly associated with poorer adherence scores among all participants (P < .001), among participants taking a loop diuretic (P < .001), and among participants with hypertension and heart failure (P < .039). Association between symptoms and adherence remained significant after adjustment in the multivariate model for the whole cohort and loop diuretic subgroup but lost significance in the hypertension and heart failure subgroup. CONCLUSIONS: Worsening quality of life due to urinary symptoms may be associated with poorer adherence to diuretics, particularly loop diuretics.

Effects of ß3 Agonists and Anticholinergic Drugs on Defecation in Patients With Overactive Bladder.

BACKGROUND/AIM: In clinical practice, constipation is one of the most frequent adverse events caused by drugs for overactive bladder (OAB). The occurrence of constipation greatly deteriorates the patient's quality of life. The aim of the study was to evaluate and compare the effects of three commonly used ß3 agonists and anticholinergic drugs on the defecation status in patients with OAB. PATIENTS AND METHODS: We retrospectively reviewed the defecation status in patients who received mirabegron, solifenacin, or fesoterodine for OAB. We evaluated changes in the (a) urological parameters using the OAB symptom score (OABSS) and (b) defecation status using the Bristol Stool Form Scale (BSFS) and constipation scoring system (CSS) following 12 weeks of drug administration. RESULTS: We analyzed data from 165 patients (mirabegron=56, fesoterodine=52, and solifenacin=57). The solifenacin group showed a significant decrease in BSFS (from 3.2±1.0 at baseline to 2.3±12 post-treatment) and an increase in hardened stools (p<0.001). Elimination worsened as assessed by almost all items, and the total modified CSS scores worsened significantly from 4.8±2.6 points at baseline to 8.O±4.8 points after 12 weeks of solifenacin treatment (p<0.001). The mirabegron group showed no changes in any of the CSS items. In the fesoterodine group, the CSS scores for "completeness" and "assistance" increased significantly after treatment (p<0.001 and p=0.013, respectively). CONCLUSION: All three drugs were effective for OAB. Mirabegron had almost no effect on constipation; fesoterodine, an anticholinergic drug, also had hardly any effect on defecation.

Oxybutynin nanosuspension gel for enhanced transdermal treatment for overactive bladder syndrome.

Oxybutynin (OXY) is the most common drug to treat overactive bladder (OAB) syndrome. Transdermal administration is a more ideal route replacing oral administration to resolve problems of low bioavailability and severe side effects. However, commercial transdermal products of OXY frequently cause skin irritation and low permeation efficiency arising discontinued medication. Here, oxybutynin nanosuspension (OXY-NS) and its gel preparation (OXY-NG) were constructed to resolve these issues. In vitro permeation test and in vivo pharmacokinetics study confirmed that OXY-NG significantly enhanced the transdermal permeation of OXY, about 4-fold and 3-fold higher than oxybutynin coarse suspension (OXY-CG), respectively, and in vitro retention test certified that OXY-NG increased OXY concentration especially in viable epidermis (VE) and Dermis (about 3 times that of OXY-CG), consequently improving the bioavailability. Skin irritation assay demonstrated that OXY-NG would not trigger skin adverse effects. In addition, selectively blocking hair follicles test evidenced that hair follicles pathway played an important role in OXY-NS transdermal delivery. In general, by virtue of excellent drug loading, low toxicity and ease of scale-up, OXY-NG is a promising strategy to ameliorate skin permeation of insoluble OXY for better transdermal treatment for OAB, hence increasing its bioavailability, reducing adverse effects, and achieving good patient compliance.