Multimodal neuroimaging insights into central mechanisms of overactive bladder with an empty bladder: a cross-sectional study.

Overactive bladder (OAB) is a syndrome with symptoms such as urinary frequency, urinary urgency and urge incontinence. The aim of this study is to assess the validity and reliability of the Turkish overactive bladder symptom score (OABSS) and to evaluate the results of mirabegron treatment with OABSS. The study was carried out with 117 patients who applied to the urology outpatient clinic between June 2018-January 2019. OABSS Turkish validation was developed from the English version. Demographic data of the patients were recorded. The OABSS, overactive bladder questionnaire (OAB-v8) and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) were filled out by the patients. The patients were asked to fill in these questionnaires after 2weeks. Patients receiving mirabegon treatment were evaluated with the same questionnaires and bladder diaries after 8weeks. A total of 117 OAB patients, including 82 OAB-wet and 35-OAB dry, were included in the study. The mean age of the patients was 46.79 ± 14.26 (18-78) years, and the mean duration of OAB complaint was 32.28 ± 32.21months. The mean score of the OABSS is 9.9 ± 3.14. The results of the reliability assessment showed that the intraclass correlation coefficient of the total OABSS score was 0.71 (weighted coefficients of individual item points, 0.635-0.831), and the Cronbach α was 0.736. In the validity analysis, the OABSS total score was highly correlated with that belonging to other questionnaire forms (OAB-v8, ICIQ-SF and bladder diary). After the treatment with mirabegron, mean OABSS scores of the patients improved significantly from baseline to the 8th week (p < 0.001). The Turkish version of the OABSS has been approved as a valid and reliable tool for evaluating OAB. Mirabegron used daily improved the symptoms of OAB in patients.

Are patients with the symptoms of overactive bladder and urodynamic detrusor overactivity different from those with overactive bladder but not detrusor overactivity?

Psychometric Validation of the English Version of the Overactive Bladder Symptom Score

To examine the safety and efficacy of mirabegron as 'add-on' therapy to solifenacin in patients with overactive bladder (OAB). This multicentre, open-label, phase IV study enrolled patients aged ≥20 years with OAB, as determined by an OAB symptom score (OABSS) total of ≥3 points and an OABSS Question 3 score of ≥2 points, who were being treated with solifenacin at a stable dose of 2.5 or 5 mg once daily for at least 4 weeks. Study duration was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting eligibility criteria continued to receive solifenacin (2.5 or 5 mg once daily) and additional mirabegron (25 mg once daily) for 16 weeks. After 8 weeks of treatment, the mirabegron dose could be increased to 50 mg if the patient's symptom improvement was not sufficient, if he/she was agreeable to the dose increase, and the investigator judged that there were no safety concerns. Safety assessments included adverse events (AEs), laboratory tests, vital signs, 12-lead electrocardiogram, QT corrected for heart rate using Fridericia's correction (QTcF) interval and post-void residual (PVR) volume. Efficacy endpoints were changes from baseline in OABSS total score, OAB questionnaire short form (OAB-q SF) score (symptom bother and total health-related quality of life [HRQL] score), mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of urinary incontinence (UI) episodes/24 h, mean number of urgency UI episodes/24 h, mean volume voided/micturition, and mean number of nocturia episodes/night. Patients were instructed to complete the OABSS sheets at weeks -2, 0, 8 and 16 (or at discontinuation), OAB-q SF sheets at weeks 0, 8 and 16 (or at discontinuation) and patient voiding diaries at weeks 0, 4, 8, 12 and 16 (or at discontinuation). Overall incidence of drug-related treatment-emergent AEs (TEAEs) was 23.3%. Almost all TEAEs were mild or moderate. The most common TEAE was constipation, with similar incidence in the groups receiving a dose increase to that observed in the groups maintained on the original dose. Changes in PVR volume, QTcF interval, pulse rate and blood pressure were not considered to be clinically significant and there were no reports of urinary retention. Significant improvement was seen for changes in efficacy endpoints from baseline to end of treatment (EOT) in all groups (patients receiving solifenacin 2.5 or 5 mg + mirabegron 25 or 50 mg). Add-on therapy with mirabegron 25 mg once daily for 16 weeks, with an optional dose increase to 50 mg at week 8, was well tolerated in patients with OAB treated with solifenacin 2.5 mg or 5 mg once daily. There were significant improvements from baseline to EOT in OAB symptoms with combination therapy with mirabegron and solifenacin. Add-on therapy with mirabegron and an antimuscarinic agent, such as solifenacin, may provide an attractive therapeutic option.

MP27-02 THE ASSOCIATION BETWEEN VASCULAR RISK FACTORS AND OVER ACTIVE BLADDER

Objective To characterize the female urinary microbiome associated to OAB (overactive bladder) and investigate relationships between urinary microbiome and psychological factors. Methods 30 women with OAB and 25 asymptomatic controls were recruited and required to finish the overactive bladder symptom score, self-rating anxiety scale, self-rating depression scale and quality of life questionaires. Urine specimens were collected by transurethral catheterization and processed for 16S rRNA gene sequencing. Sequencing reads were processed using QIIME. Analyses for bacterial genera biomarker was used LEfSe algorithms. Bivariate correlations were assessed using Pearson’s correlation. Results The two cohorts showed no significance difference in their demographic characteristics. OAB patients had significantly higher scores on overactive bladder symptom score, self-rating anxiety scale, self-rating depression scale and quality of life than controls (P<0.001). We found that bacterial diversity (Chao1 index: 1 854.09±1 239.34) and richness (Simpson index: 0.75±0.23) were decreased in OAB samples than those of controls (Chao1 index: 2 866.27±1 795.22; Simpson index: 0.86±0.12; P=0.02). At the family level, Enterobacteriaceae and (17.6% vs.8.1%; P=0.03) Bifidobacteriaceae (14.8% vs.3.6%; P=0.01) were significantly more abundant in the OAB samples than the controls. Compared to controls, 7 genera increased in OAB patients (e.g., Proteus and Aerococcus) and 13 reduced (e.g., Lactobacillus and Prevotella). There are negative correlations between scores on Self-Rating Depression Scale and both Chao1 (r=-0.458, P=0.011) and shannon indexes (r=-0.516, P=0.003) in OAB patients, which indicates that OAB patients with depression have further reductions in bacterial diversity and richness. Conclusions The aberrant urinary microbiome may serve as disease biomarkers and potential therapeutic targets of OAB. A negative correlation between depression scores and both bacterial richness and diversity in OAB patients indicated that there might be a connection between central nervous system and urinary microbiome. Key words: Overactive bladder; Urinary microbiome; Psychology

A Slow Stream Is Pathophysiologically Related to a Poor Response to α1-Adrenoceptor Therapy in the Treatment of Storage Symptoms Associated With Benign Prostatic Hyperplasia

ABSTRACTObjectivesTo evaluate the safety and effectiveness of vibegron, a highly selective β3‐adrenoceptor agonist, in Japanese patients with overactive bladder (OAB) in a real‐world clinical setting.MethodsThis prospective survey was conducted from August 2019 to July 2023 using a central registration method. Patients newly treated with vibegron for OAB were followed for 12 weeks, and those who continued treatment were observed for up to 52 weeks. Adverse drug reactions (ADRs) and the overall improvement level were assessed, and overactive bladder symptom score (OABSS) and International Prostate Symptom Score‐Quality of Life (IPSS QOL) score were collected.ResultsOf the 1848 patients in the safety analysis set, 154 ADRs were reported in 141 patients (7.63%). Common ADRs were increased residual urine volume (1.30%), constipation (1.14%), dysuria and urinary retention (0.97% each), cystitis (0.65%), and dry mouth (0.32%). The incidence of urinary retention‐related adverse events (AEs) was higher in male patients, patients ≥ 65 years old, and patients with benign prostatic hyperplasia. The effectiveness rate was 88.8% among the 1561 patients in the effectiveness analysis set. Significant improvement in both OABSS and IPSS QOL scores was observed at all observation periods. The rate of achieving the minimal clinically important change in OABSS total score at the final evaluation was 75.35%. OABSS scores were also significantly reduced in all subgroup analyses.ConclusionsThis survey found no major concerns regarding the safety and effectiveness of vibegron in Japanese OAB patients, except for urinary retention‐related AEs. Vibegron is considered to represent a useful drug for treating OAB symptoms in a real‐world clinical setting.

Prolapse surgery and sling surgery both lead to improvement in overactive bladder. However, less is known regarding how slings performed concurrently with less is know about how overactive bladder symptoms change in patients having prolapse surgery with a sling compared to prolapse surgery without a sling. The primary aim was to compare change in postoperative overactive bladder symptoms in patients with preoperative overactive bladder who underwent sling placement versus no sling with prolapse surgery. This was a secondary analysis of a cohort study evaluating overactive bladder in patients undergoing prolapse surgery. Sling procedures were performed concomitantly for treatment or prevention of stress incontinence. Baseline and 3-month follow-up urinary symptoms were assessed with the Overactive Bladder Questionnaire Short Form (OAB-q SF) and Urinary Distress Inventory-6 (UDI-6). Of patients with overactive bladder, 26 (40.0%) underwent midurethral sling (MUS) placement and 39 (60.0%) no sling. Preoperative OAB-q SF bother (score [SD], 46.8 [20.2] vs 40.2 [22.1]; P = 0.23) was similar between groups, but UDI-6 scores (59.2 [28.8] vs 43.8 [29.1]; P = 0.04) were higher in the sling group. At 3 months, the change (improvement) in OABq-SF bother (-16.9 [24.1] vs -22.4 [23.0]; P = 0.36), OABq-SF health-related quality of life (22.8 [28.6] vs 22.9 [23.9]; P = 0.99), and UDI-6 (-38.8 [32.9] vs -34.0 [27.8]; P = 0.53) were similar in the MUS and no MUS groups. Patients with prolapse and overactive bladder undergoing prolapse surgery with a sling had similar improvements in OAB-q SF bother scores compared with those who did not have a sling.

Background Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic condition characterized by pelvic pain and urinary symptoms. Despite its significant impact on patients' quality of life, the heterogeneity of BPS/IC symptoms and the presence of comorbidities such as vulvodynia may not be adequately captured by validated questionnaires. Identifying vulvodynia in BPS/IC patients is crucial for providing appropriate treatment options. This study aimed to identify subtypes of BPS/IC patients using unsupervised machine learning and to investigate the prevalence of vulvodynia in each subtype. Methods We conducted a prospective cross-sectional study of 123 BPS/IC patients and 64 age-matched controls. Hierarchical clustering was performed using data from validated questionnaires, including the Numerical Rating Scale-11, Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency scores, Overactive Bladder Questionnaire Short Form (OABq SF), Overactive Bladder Symptom Score (OABSS), and Pelvic Floor Distress Inventory-20. The optimal number of clusters was determined using the elbow method, and the characteristics of each cluster were analyzed. All participants underwent a vulvodynia swab test to assess vulvodynia symptoms. Results Unsupervised machine learning revealed three distinct clusters of BPS/IC patients. Clusters 0 and 2 differed significantly, with Cluster 2 characterized by significantly higher vulvodynia scores compared to other clusters (P < 0.001). In contrast, Cluster 2 had lower bladder pain scores (ICSI and ICPI) and overactive bladder symptom scores (OABq SF and OABSS) compared to other clusters. Clusters 0 and 1 were characterized by a predominance of bladder pain and urinary frequency symptoms, with Cluster 0 exhibiting more severe symptoms. Conclusions Our study identified distinct subtypes of BPS/IC patients using unsupervised machine learning, with Cluster 2 representing a vulvodynia-predominant subtype. This finding, along with the potential of targeted therapies such as non-ablative erbium YAG laser for vulvodynia, underscores the importance of assessing extravesical symptoms, particularly vulvodynia, for the diagnosis and treatment of BPS/IC. A tailored approach, including laser therapy for vulvodynia-predominant patients, may be necessary for optimal management of BPS/IC. The vulvodynia swab test plays a crucial role in assessing vulvodynia symptoms, underlining the limitations of validated questionnaires in capturing the full spectrum of BPS/IC symptoms. A comprehensive evaluation of patients, including the vulvodynia swab test, is essential for accurate subtyping and management of BPS/IC. Further research with larger sample sizes and investigation of the relationship between identified subtypes and other clinical data is warranted to advance our understanding and management of BPS/IC.

We investigated the satisfaction and efficacy of mirabegron in patients with overactive bladder (OAB) symptoms who were unsatisfied with previous antimuscarinic treatment. This was a 12-week, open-label study of adults with OAB who had been treated with antimuscarinics within 2 years of screening and expressed dissatisfaction over poor efficacy or adverse events of antimuscarinics. All enrolled patients have received mirabegron 50 mg once daily for 12 weeks. The primary outcome was the percentage of patients reporting treatment satisfaction questions (TSQ) at week 12 ("very satisfied"or "somewhat satisfied"). Patients completed voiding diaries, Overactive Bladder Questionnaire short form (OAB-q-SF), Overactive Bladder Symptom Score (OABSS), and the global response assessment (GRA) at baseline, Week 4, and Week 12. At 12-weeks, patients were assessed for willingness to continue treatment. The response rate of treatment satisfaction at 12 weeks was 69.3% (275/397) (95% confidence interval 64.7-73.8). Significant improvements from baseline to weeks 4 and 12 were observed in the frequency, urgency due to urinary incontinence, and urgency episodes per 24 h (all p < .0001). Both OAB-q-SF and OABSS were significantly improved compared to baseline. At 4 and 12 weeks, 27.5% and 41.8% of patients, respectively, responded to the GRA as being moderately or markedly improved. At 12 weeks, 80.8% of patients were willing to continue mirabegron. Mirabegron improved the rates of treatment satisfaction and symptoms in patients with OAB who were unsatisfied with prior antimuscarinic treatment.

The mechanisms underlying overactive bladder (OAB) and the role of sacral neuromodulation (SNM) in its treatment are not fully understood. In this study, functional near-infrared spectroscopy (fNIRS) was used to identify changes in brain activity during SNM in patients with OAB who responded to therapy. We employed a prospective trial method and idiopathic OAB patients selected for SNM treatment at our center were assigned to the experimental group and healthy adults matched by gender and age constituted the healthy control (HC) group. All participants completed 72-h urination diaries, the Overactive Bladder Symptom Score (OABSS), functional near-infrared spectroscopy (fNIRS) scans in both resting and task states, along with synchronous urodynamic monitoring. OAB patients were re-evaluated for these indicators after the SNM electrode implantation phase I test. The MATLAB toolbox NIRS-KIT was used to analyze and compare the differences in the internal functional connectivity (FC) of the prefrontal cortex (PFC) between the OAB group and the HC group before and after the treatment, in addition to assessing the differences in the PFC cortical activation/inactivation regions of the brain. 1. A total of 10 HCs and 12 patients with OAB were included. After the SNM Phase I test, 10 patients with OAB were successful, while 2 patients failed. The average frequency of 24-h urination, the levels of urgency and incontinence, and OABSS in the OAB group were significantly higher than those in the HC group. After the SNM treatment, the parameters recorded in urination diaries, OABSS, and urodynamic measures in the successful OAB group were significantly improved compared to their levels before treatment. 2. Task fNIRS results: Compared to the HC group, BA9 (left dorsolateral prefrontal lobe) was significantly inactivated in the successful OAB group before SNM treatment. Compared to the HC group, there was no significant difference in brain activation after SNM treatment in the successful OAB group. BA9 (left dorsolateral prefrontal lobe) and BA45 (the triangular part of the left inferior frontal gyrus) were significantly activated after the SNM treatment in the successful OAB group in contrast to their activation levels before treatment. 3. Resting fNIRS results: Compared to the HC group, the FC of the PFC in the successful OAB group was significantly weakened in both the empty and filled bladder states before SNM treatment; however, after SNM treatment, it returned to normal. Compared to the HC group, there was no significant difference in the FC of OAB patients in the empty bladder state after treatment, but the FC was significantly activated during the strong desire to void state. We found abnormal deactivation of the FC in the PFC and left dorsolateral prefrontal lobe (BA9), which might lead to socially inappropriate involuntary urination and could be a central pathogenesis of OAB. SNM restored the functional connectivity in the left dorsolateral frontal lobe, the triangular part of the left inferior frontal gyrus, and the interior of the prefrontal lobe in patients with OAB, which may be one of the central mechanisms of SNM treatment for OAB. Our results may provide valuable insights into the central pathogenesis of OAB and the central mechanism of SNM treatment.

Objective To investigate the clinical efficacy of posterior tibial nerve stimulation (PT-NS) for female patients with overactive bladder.Methods From Nov 2011 to Jan 2014,212 female patients with overactive bladder (OAB) were enrolled in this study,prospectively.They were randomly divided into three groups.In the PTNS group (n =70),patients received posterior tibial nerve stimulation therapy once a week for 12 weeks.In the M receptor blockers group (n =73),patients received M receptor blockers (Tolterodine Tartrate Tablets 2mg 2 times per day) for 12 weeks.In the combined treatment group (n =69),patients received PTNS combined with M receptor blockers therapy mentioned above for 12 weeks.The patients underwent a physiotherapeutic evaluation before and after the treatment that included the overactive bladder symptom score (OABSS),mean daily voiding episodes,mean daily incontinence episodes,et al.The PTNS group received the second 12 weeks' PTNS treatment,and part of the patients with an initial positive response to 24 weekly PTNS treatments continued the third round of PTNS therapy (once a week for 24 weeks and Once every 2 weeks for the next 24 weeks).Results During the first 12 weeks' treatment,the OABSS scores declined significantly after the treatment,compared to those before treatment,in each group (The M receptor blockers group:6.3±1.6 vs.8.7±1.8; The PTNS group:6.5±1.9 vs.8,8±1.7; The combined treatment group:5.8± 1.6 vs.8.9± 1.9,P＜0.05).The mean daily voiding episodes,mean nocturia episodes,mean daily incontinence episodes,daily urgency episodes and mean vloume per voiding declined significantly after treatment in each group (P＜0.05).There was no significantly difference in OABSS scores between PTNS group and M receptor blockers group after the treatment (P＞0.05).All recorded items declined significantly in the combined treatment group compared with the other two groups (P＜0.05).In the PTNS group,the OABSS felt from 6.5±1.9 to 6.1±1.9 (P＜0.05) at the end of the second 12 weeks' PTNS treatment.4 patients lost to follow-up in the first 12 weeks' PTNS treatment,4 patients dropped out the the second 12 weeks' PTNS treatment.After the second round treatment,43 patients showed good response to the PTNS treatment.The overall response rate was 69.4％ (43/62).Among them,22 patients continued the third round of PTNS therapy (once a week for 24 weeks and once every 2 weeks for the next 24 weeks).The OABSS scores were 6.4±2.1,6.5±2.2 after 24 and 48 weeks,respectively.Those results were similar to those in the first round treatment (6.4± 1.6,P ＞ 0.05).Conclusions PTNS provides good therapeutic effect for female primary ovcractive bladder.And the combination therapy provided significantly better outcomes than mono therapy.To those patients with an initial positive response,long-term treatment by using this technique could sustain overactive bladder symptom improvement. Key words: Overactive bladder; Posterior tibial nerve stimulation; M receptor blockers

ObjectiveThe treatment effects of vibegron have not previously been evaluated in a prospective, non-interventional observational study of elderly Japanese patients, particularly those ≥80 years old. In addition, no reports have referred to residual urine volume in switching cases. We therefore grouped patients by condition and investigated the treatment effects of vibegron on Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and residual urine volume in each group.MethodsThis multicenter, prospective, non-interventional, observational study consecutively enrolled OAB patients with total OABSS score ≥3 and OABSS question 3 score ≥2. Sixty-three patients from six centers were recruited. Vibegron 50 mg once daily was administered for 12 weeks as first-line monotherapy (first-line group), monotherapy switching from antimuscarinics or mirabegron due to failure of prior therapy (no washout period), or combination therapy with antimuscarinics (second-line group). OABSS, OAB-q SF, and residual urine volume were collected after 4 and 12 weeks. Adverse events were also recorded at each visit.ResultsOf the 63 patients registered, 61 were eligible for analysis (first line, n=36; second line, n=25). The OABSS, excluding daytime frequency scores, and OAB-q SF scale showed significant improvement in all conditions. Switching from mirabegron to vibegron significantly reduced residual urine volume. No serious treatment-related adverse events were encountered.ConclusionVibegron 50 mg once daily significantly improved OABSS and OAB-q SF even in patients ≥80 years old. Notably, switching from mirabegron to vibegron resulted in significant improvements to residual urine volume.

Overactive bladder (OAB) is a disease that seriously affects patients' quality of life and mental health. To address this issue, more and more researchers are examining the relationship between OAB treatment and urinary microecology. In this study, we sought to determine whether differences in treatment efficacy were related to microbiome diversity and composition as well as the abundance of specific genera. Machine learning algorithms were used to construct predictive models for urine microbiota-based treatment of OAB. Urine samples were obtained from 64 adult female OAB patients for 16S rRNA gene sequencing. Patients' overactive bladder symptom scores (OABSS) were collected before and after mirabegron treatment and patients were divided into effective and ineffective groups. The relationship between the relative abundance of certain genera and OABSS were analyzed. Three machine learning algorithms, including random forest (RF), supporting vector machine (SVM) and eXtreme gradient boosting (XGBoost) were utilized to predict the therapeutic effect of mirabegron based on the relative abundance of certain genera in OAB patients' urine microbiome. The species composition of the two groups differed. For one, the relative abundance of Lactobacillus was significantly higher in the effective group than in the ineffective group. In addition, the relative abundance of Gardnerella and Prevotella in the effective group was significantly lower than in the ineffective group. Alpha-diversity and beta-diversity differed significantly between the two groups. LEfSe analysis revealed that Lactobacillus abundance increased while Prevotella and Gardnerella abundance decreased in the effective group. The Lactobacillus abundance ROC curve had high predictive accuracy. The OABSS after treatment was negatively correlated with the abundance of Lactobacillus, whereas the relationship between OABSS and Prevotella and Gardnerella showed the opposite trend. In addition, RF, SVM and XGBoost models demonstrated high predictive ability to assess the effect of mirabegron in OAB patients in the test cohort. The results of this study indicate that urinary microbiota might influence the efficacy of mirabegron, and that Lactobacillus might be a potential marker for evaluating the therapeutic efficacy of mirabegron in OAB patients.