Efficacy and safety of solifenacin combined with biofeedback in children with overactive bladder.

BACKGROUND: Overactive bladder is a common chronic urological disorder in children, liable to impact normal social activities, disrupt sleep and even impair self-esteem. We aimed to evaluate the efficacy and safety of solifenacin combined with biofeedback for paediatric overactive bladder. METHOD: Forty-five children with overactive bladder were enrolled and divided into three groups: 15 patients in Group A were treated with solifenacin, 15 cases in Group B with biofeedback, and the other 15 patients in Group C with the combination of solifenacin plus biofeedback. Each group was subdivided into the non-urge incontinence (non-UI) and urge incontinence (UI) groups. The remission rates were compared among the three groups at 2, 4, 8 and 12 weeks from the beginning of treatment. The side effects of solifenacin were recorded and followed up. RESULT: After 2 weeks since initial treatment, the complete response rates were 33.3% (5/15), 20.0% (3/15), and 53.3% (8/15) in the three groups. At 4 weeks, the complete remission rates were 46.7% (7/15), 33.3% (5/15), and 60.0% (9/15) respectively. Moreover, the complete remission rates of the UI groups were higher than the non-UI groups (p < 0.05). At 8 weeks, the complete response rates were 53.3% (8/15), 40.0% (6/15), and 67.7% (10/15). At 12 weeks, the complete response rates were 67.8% (10/15), 60.0% (9/15), and 86.7% (13/15). The complete response rates were higher and urodynamic parameters were improved obviously in group C than the other two groups (p < 0.05) during the follow-ups. The median voiding frequency decreased and median functional bladder capacity increased obviously in Group C after 4 weeks (p < 0.05). Dry mouth was observed in 2 patients (4.4%). 2 patients experienced constipation (4.4%), and neither case was severe. The symptoms of these four patients had relieved by reducing the dose of solifenacin. CONCLUSION: Solifenacin combined with biofeedback had good efficacy and compliance for children experiencing overactive bladder. It took only 2 weeks to achieve the complete response rate over 50%, especially for the improvement of UI symptoms.

Sacral Neuromodulation: Device Improvement and Current Applications in Urology.

Sacral neuromodulation (SNM) offers a therapeutic approach to urological patients suffering from idiopathic overactive bladder (OAB) syndrome, with or without incontinence and non-obstructive urinary retention (NOR), who are not responding to or are not compliant with conservative or medical therapies. The exact mechanism of action of SNM is not fully understood but modulation of the spinal cord reflexes and brain networks by peripheral afferents is regarded as the main pathway. Over the years, surgical techniques improved, leading to the development of the modern two-stage implantation technique. The quadripolar lead is positioned percutaneously under fluoroscopy guidance through the third sacral foramen following the trajectory of S3. The procedure can be performed under local or general anesthesia with the patient in prone position. Current applications of sacral neuromodulation in urology are increasing thanks to the recent improvements of the devices that make this a valuable option not only in conditions such as overactive bladder and non-obstructing urinary retention but also neurogenic lower urinary tract dysfunction.

Medicinal plants and natural products for treating overactive bladder.

BACKGROUND: Overactive bladder (OAB) presents a high prevalence of 16-18% worldwide. The pathophysiology of OAB is still poorly understood while effective therapy or countermeasure are very limited. On the other hand, medicinal plants and herbal remedies have been utilized for treating lower urinary tract symptoms (LUTS) in both Eastern and Western cultures since ancient times. In recent years, accumulating progress has also been made in OAB treatment research by using medicinal plants. METHODS: Relevant literature on the studies of medicinal plants and herbs used to treat OAB was reviewed. The medicinal plants were summarized and categorized into two groups, single-herb medications and herbal formulations. RESULTS: The present review has summarized current understanding of OAB's pathophysiology, its available treatments and new drug targets. Medicinal plants and natural products which have been used or have shown potential for OAB treatment were updated and comprehensively categorized. Studies on a wide variety of medicinal plants showed promising results, although only a few phytochemicals have been isolated and identified. Until now, none of these herbal compounds have been further developed into clinical therapeutics for OAB. CONCLUSIONS: This review provides the basis for discovering and designing new phytopharmaceutical candidates with effective and well-tolerated properties to treat OAB. Increasing evidences indicate new strategies with alternative herbal treatment for OAB have high efficacy and safety, showing great promise for their clinical use. Future studies in a rigorously designed controlled manner will be beneficial to further support the eligibility of herbal treatment as OAB therapeutics.

Evaluating the Practicality of Causal Inference From Non-randomized Observational Data in Small-Scale Clinical Settings: A Study on the Effects of Ninjin'yoeito.

Objective The primary goal of this study was to demonstrate the practical application of causal inference using non-randomized observational data, adapting this approach to smaller populations, such as those in hospitals or community healthcare. This adaptation seeks a more effective and practical research method than randomized controlled trials (RCTs), with the goal of revealing novel insights unexplored by traditional research and enhancing understanding within the realm of causal inference. Methods This study evaluated the effects of Ninjin'yoeito (NYT), a traditional Japanese Kampo medicine, on Overactive Bladder Symptom Score (OABSS) and the frailty scores. Employing new statistical methods, this study sought to illustrate the efficacy of estimating causal relationships from non-randomized data in a clinical setting. The database included 985 women aged 65-90 years who visited a clinic between November 2016 and November 2022. By utilizing various statistical techniques, including regression analysis, inverse probability of treatment weighting (IPTW), instrumental variable (IV), and difference-in-differences (DiD) analysis, this study aimed to provide insights beyond traditional methods, attempting to bridge the gap between theory and practice in causal inference. Results After applying propensity score matching, the NYT treatment group (220 participants) and non-treatment group (182 participants) were each adjusted to two groups of 159 individuals. NYT significantly improved OABSS and frailty scores. IPTW analysis highlighted that on average, the NYT treatment group showed an improvement of 0.8671 points in OABSS and 0.1339 points in the frailty scores, surpassing the non-treatment group (p<0.05). IV analysis indicated that NYT treatment is predicted to increase ΔOABSS by an average of approximately 4.86 points, highlighting its significant positive impact on OABSS improvement. The DiD analysis showed that the NYT treatment group demonstrated an average improvement of 0.5457 points in OABSS, which was significantly higher than that of the control group. The adjusted R² value for the model is 0.025. Conclusion This study successfully implemented a practical application of causal inference using non-randomized observational data in a relatively small population. NYT showed a significant improvement in OABSS and vulnerability, and this result was confirmed using a new statistical method. The relatively low adjusted R² of the model suggests the existence of other unmeasured variables that influence OABSS and vulnerability improvement. In particular, the use of diverse statistical techniques, including IPTW, IV, and DiD analysis, is an important step toward revealing the effectiveness of inferring causal relationships from non-randomized data and narrowing the gap between theory and practice. This study provides a valid and practical alternative to RCTs and reveals new insights that have not been explored in traditional research.

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

INTRODUCTION: 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. OBJECTIVE: The objective of this study was to analyze shifts in patient preference of third-line therapies for OAB after introducing ITNS as an option among the previously established therapies for non-neurogenic OAB. METHODS: 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 subjects who 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. RESULTS: 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) symptoms were 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-approved third-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). CONCLUSION: 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 relatively recently 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.

Who Progresses to Third-Line Therapies for Overactive Bladder? Trends From the AQUA Registry.

INTRODUCTION: Overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (percutaneous tibial nerve stimulation, sacral neuromodulation, onabotulinumtoxinA bladder injection [BTX-A]). We aimed to determine which clinical factors affect progression from second- to third-line OAB therapy. METHODS: Between 2014 and 2020, the AUA Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. RESULTS: A total of 641,122 patients met inclusion criteria and were included in analysis. Of these, only 7487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, history of dual anticholinergic and ß3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% sacral neuromodulation, 28% percutaneous tibial nerve stimulation). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9, 32.4). Patients < 50 years old and women progressed fastest to third-line therapy. CONCLUSIONS: Very few patients received third-line therapies, and the time to progression from second- to third-line therapies is > 1 year. The study findings highlight a potential need to improve third-line therapy implementation.

Does choice of anesthesia during stage 1 sacral neuromodulation testing influence outcomes?

INTRODUCTION: Staged sacral neuromodulation (SNM) testing has been shown to have a high rate of progression to permanent implantation for the management of voiding dysfunction. Stage 1 lead placement (SNM-I) can be performed under monitored anesthesia care (MAC) or general anesthesia (GA). MAC allows for interpretation of sensory and motor responses to optimize lead placement while GA only permits for motor assessment. However, patient discomfort and movement can make lead placement challenging during MAC. Herein we evaluate whether the anesthesia type impacts the progression rate to permanent implantation (SNM-II). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent SNM-I in the operating room for wet overactive bladder between 2005 and 2023. Patients were divided into two groups based on the type of anesthesia used, MAC or GA. Clinical variables and progression to SNM-II were compared between cohorts. Progression to SNM-II was based on ≥50% symptomatic improvement during a 1-2 week trial period following SNM-I. RESULTS: Of 121 patients included in the study, 95 (79%) underwent MAC and 26 (21%) GA for SNM-I. No difference in the progression rate to SNM-II was noted between groups (MAC, 68/95 patients, 72%; GA, 19/26, 73%; p = 0.39). We also found no difference when comparing the GA group to the 26 most recent MAC patients (MAC, 20/26 patients, 77%; GA, 19/26, 73%; p = 0.48). CONCLUSION: Types of anesthesia for SNM-I did not affect rate of progression to SNM-II. The result lends support to the reliance on motor responses alone for lead placement during SNM-I.

Effects of Transcutaneous Tibial Nerve Stimulation in Women Refractory to and Never Used Pharmacological Agents for Idiopathic Overactive Bladder.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to compare the effectiveness of transcutaneous tibial nerve stimulation (TTNS) on quality of life (QoL) and clinical parameters related to incontinence in pharmacological agents (PhAs) naive and refractory women with idiopathic overactive bladder (iOAB). METHODS: In this prospective nonrandomized clinical trial, women with resistance to PhAs were included in the first group (n=21), PhA-naive women were included in the second group (n=21). TTNS was performed 2 days a week, a total of 12 sessions for 6 weeks. Every session lasted 30 min. Women were evaluated for the severity of incontinence (Pad test), 3-day voiding diary (voiding frequency, nocturia, incontinence episodes, and number of pads), symptom severity (Overactive Bladder Questionnaire-V8), quality of life (Incontinence Impact Questionnaire-7), treatment satisfaction, positive response, and cure-improvement rates. RESULTS: A statistically significant improvement was found in all parameters for each group at the 6th week compared with the baseline values (p<0.05). It was found that the severity of incontinence, incontinence episodes, symptom severity, treatment satisfaction, and QoL parameters were significantly improved in PhA-naive group compared with the PhA-resistant group at the 6th week (p<0.05). There were no statistically significant differences in the frequency of voiding, nocturia, and number of pads between the two groups (p>0.05). Positive response rates, the primary outcome measure, were statistically significantly higher in the PhA-naive group than in the PhA-resistant group. CONCLUSIONS: Although TTNS is more effective in PhA-naive women with iOAB, it appears to be an effective therapy that can also be used in the management of PhA-resistant women with iOAB.

Brain Response Induced by Peroneal Electrical Transcutaneous Neuromodulation Invented for Overactive Bladder Treatment, as Detected by Functional Magnetic Resonance Imaging.

OBJECTIVES: In this study, we aimed to investigate whether peroneal electrical Transcutaneous Neuromodulation invented for overactive bladder (OAB) treatment elicits activation in brain regions involved in neural regulation of the lower urinary tract. MATERIALS AND METHODS: Among 22 enrolled healthy female volunteers, 13 were eligible for the final analysis. Functional magnetic resonance imaging (fMRI) (Siemens VIDA 3T; Erlangen, Germany) was used to compare the brain region activation elicited by peroneal electrical Transcutaneous Neuromodulation with the activation elicited by sham stimulation. Each subject underwent brain fMRI recording during eight 30-second periods of rest, alternating with 30-second periods of passive feet movement using the sham device, mimicking the motor response to peroneal nerve stimulation. Subsequently, fMRI recording was performed during the analogic "off-on" stimulation paradigm using peroneal electrical transcutaneous neuromodulation. Magnetic resonance imaging data acquired during both paradigms were compared using individual and group statistics. RESULTS: During both peroneal electrical Transcutaneous Neuromodulation and sham feet movements, we observed activation of the primary motor cortex and supplementary motor area, corresponding to the cortical projection of lower limb movement. During peroneal electrical Transcutaneous Neuromodulation, we observed significant activations in the brain stem, cerebellum, cingulate gyrus, putamen, operculum, and anterior insula, which were not observed during the sham feet movement. CONCLUSIONS: Our study provides evidence that peroneal electrical Transcutaneous Neuromodulation elicits activation of brain structures that have been previously implicated in the perception of bladder fullness and that play a role in the ability to cope with urinary urgency. Our data suggest that neuromodulation at the level of supraspinal control of the lower urinary tract may contribute to the treatment effect of peroneal electrical Transcutaneous Neuromodulation in patients with OAB.

Vitamin D levels and the risk of overactive bladder: a systematic review and meta-analysis.

CONTEXT: Overactive bladder is treated mainly with behavioral and drug therapy, and symptoms of urinary frequency and incontinence are challenging to eliminate. There is thus a continuous unmet need for new drugs with a substitution effect mechanism. OBJECTIVE: It not known whether vitamin D deficiency can lead to overactive bladder or urinary incontinence or whether vitamin D supplementation alleviates bladder symptoms. This comprehensive systematic review with meta-analysis was conducted to determine whether overactive bladder is associated with vitamin D deficiency. DATA SOURCES: The PubMed and Cochrane Library databases were searched systematically up to July 3, 2022. DATA EXTRACTION: Initially, 706 articles were identified in the literature search, of which 13 were included in the systematic review: 4 randomized controlled trials, 3 cohort studies, 3 cross-sectional studies, and 3 case-control studies. DATA ANALYSIS: An increased risk of overactive bladder and urinary incontinence was observed with vitamin D deficiency (odds ratio [OR] = 4.46; 95%CI, 1.03-19.33; P = 0.046 and OR = 1.30; 95%CI, 1.01-1.66; P = 0.036, respectively). Vitamin D levels were relatively low in patients with overactive bladder or urinary incontinence (SMD = -0.33; 95%CI, -0.61 to -0.06, P = 0.019). On the basis of existing data, the risk of urinary incontinence was reduced by 66% after vitamin D supplementation (OR = 0.34; 95%CI, 0.18-0.66; P = 0.001). Egger test was conducted to assess publication bias, and the results were tested for robustness using a sensitivity analysis. CONCLUSIONS: Vitamin D deficiency increases the risk of overactive bladder and urinary incontinence, and vitamin D supplementation reduces the risk of urinary incontinence. The development of new strategies to prevent or alleviate bladder symptoms is crucial. Vitamin D supplementation may be gaining recognition as an effective strategy for prevention or alleviation of bladder symptoms such as overactive bladder and incontinence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022351443.

Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder.

AIMS: In studies utilizing a 20-injection-site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10-injection-site paradigm targeting the lower bladder. METHODS: In this phase 4, double-blind, parallel-group study, patients with OAB and urinary incontinence (UI) for ≥6 months with ≥3 episodes of urinary urgency incontinence (no more than 1 UI-free day) and ≥8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder. RESULTS: Of 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double-blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (-2.9) versus placebo (-0.3) (least squares mean difference [LSMD]: -2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75-50.37]), ≥75% (OR: 7.25 [2.00-26.29]), and ≥50% improvement (OR: 4.79 [1.87-12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: -2.24, p < 0.0001), nocturia (LSMD: -0.71, p = 0.0004), and urgency (LSMD: -2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23-52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double-blind period; no females used CIC during the double-blind period. Commonly reported adverse events (≥5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo. CONCLUSION: In patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC.

Long-Term Cost Analysis of Third-Line Treatment Options for Overactive Bladder.

INTRODUCTION: We aimed to analyze the long-term cost of overactive bladder third-line treatments. METHODS: This insurance claims review analyzed the 2015 to 2020 MarketScan (MKS) claims data set subjects age ≥ 18, diagnosis of overactive bladder (OAB) using ICD-9/ICD-10 codes and receipt of treatment for percutaneous tibial nerve stimulation, sacral neuromodulation (SNM), or botulinum A. Age, gender, treatment types, and cost were extracted. Treatment costs were aggregated at the level of patient and treatment type for total payment and patient contribution by combining copay, coinsurance, and deductible. We used the Wilcoxon rank-sum test for continuous and chi-square test for categorical variables. SAS v9.4 was used for analyses. Significance was set at P < .05. RESULTS: We identified 17,755 patients from the commercial claims MKS and 10,912 patients from the Medicare supplemental (MDC) database with mean age 50.7±11.1 and 75.5±7.6 years, respectively, who underwent ≥ 1 third-line OAB treatment. Patients receiving third-line treatment were predominantly female (84.9%, MKS, 74.8%, MDC). Long-term costs over a 15-year period were estimated. Percutaneous tibial nerve stimulation is the most expensive in terms of total net payment ($105,337.50 MKS, $94,102.50 MDC) and patient contribution ($9177.60 MKS, $3921.00 MDC). Total net payment for botulinum A was $67,968 (MSK), $54,261 (MDC), and patient contribution cost was $2850 (MSK), $1110 (MDC). The most cost-effective option was SNM in terms of both total net payment ($5179.10 MKS, $6099.00 MDC) and patient contribution ($59.10 MKS, $60.00 MDC). CONCLUSIONS: SNM was the most cost-effective third-line treatment for OAB looking over a 15-year period in terms of both total net payment and patient contribution.

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

OBJECTIVE: Success following urological procedures is traditionally defined through objective endpoints. This approach may not capture the impact on patient satisfaction. There is a paucity of literature evaluating patient-centered metrics such as satisfaction and decisional regret in the field of urology. This study investigates long-term satisfaction and decisional regret amongst patients who underwent sacral neuromodulation (SNM) for the treatment of refractory overactive bladder (OAB). MATERIALS AND METHODS: This study retrospectively reviewed patients who underwent SNM for refractory OAB from 2015 to 2022 at a single institution serving an ethnically diverse and underrepresented community. Demographic data were collected through chart review and surveys conducted via telephone calls. Patient satisfaction and decisional regret was measured with the validated modified SDS-DRS scale (satisfaction with decision scale-decision regret scale). Descriptive statistics, Wilcoxan rank sum, and median regression analyses were performed using STATA 15.0 with p < 0.05 as significant. RESULTS: Out of 191 patients who underwent SNM, 63 were unreachable (wrong number in chart, number not in service, patient did not answer, deceased). Eighty-nine out of 128 patients reached agreed to participate (70% response rate). The mean time since surgery was 37.3 ±25.2 months. The median satisfaction with decision score was 4.0 (IQR: 3.7-4.7) with a score of 1 correlating with low satisfaction and a score of 5 correlating with high satisfaction. The median decisional regret score was 2.0 (IQR: 1.2-2.9) with a score of 1 correlating with low decisional regret and a score of 5 correlating with strong decisional regret. Ten patients reported complications after surgery, which was significantly associated with lower SDS and higher DRS scores (p < 0.01), and persisted after adjusting for age, body mass index, sex, and comorbidities (SDS ß coef: -0.84, 95% CI: -1.5 to 0.15, p = 0.02; DRS ß coef: 1.48, 95% CI: 0.55-2.41, p < 0.01). CONCLUSIONS: Patients who underwent SNM for refractory OAB overall had low regret and high satisfaction with their decision at an average 3 years of follow-up. As expected, those who developed postoperative complications had worse scores. The inclusion of patient-centric outcomes is imperative when determining the success of a surgical procedure and is useful for shared decision-making when advancing to third-line therapy for OAB. Longer-term follow-up is necessary to assess durability of high satisfaction and low regret over time.

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

OBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. METHODS: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. RESULTS: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFß1, p-SMAD3, collagen III, Gq and PLCß1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. CONCLUSION: YZR's mechanisms of action in treating OAB involved the TGFß1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCß1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.

Efficacy of Biofeedback in Paediatric Urology Patients: A Single Centre Experience.

AIM OF THE STUDY: Biofeedback assisted pelvic floor muscle training is an underutilised nonpharmacological treatment in paediatric urology. We reviewed all patients who underwent a course of treatment at our centre to evaluate its efficacy. METHODS: All patients who underwent a full cycle of biofeedback in the paediatric urology department from 2016 to 2023 were identified. Demographics and outcomes following treatment were accessed. RESULTS: 42 patients (28 female) were identified who underwent 8 one-hour sessions on a weekly basis constituted a completed cycle of treatment. Patients were identified for treatment as per local lower urinary tract symptom guidelines and following discussion in a fortnightly urology MDT and including diagnoses of overactive bladder, dysfunctional voiding, and giggle incontinence. Outcomes were measured as successful 29% (continence, normal postvoid residuals, clean intermittent catherization discontinued), partially successful 19% (reduced wetting, abnormal post void residuals, ongoing CIC) and unsuccessful 52% (no change for patient). Age at time of treatment affected likelihood of success: <9 years, 0% success; ≥9 years, 57% [p < 0.05]. There was no significant difference in success for 9-11 years [60%] vs >11 years [56%]. CONCLUSIONS: Biofeedback has shown success with improvement in symptoms in 48% of patients (complete or partial), which increases to 57% success in ≥9 years group. We would advocate its use in these difficult to manage patients with LUTS.

Response to tibial and sacral nerve modulation in overactive bladder: Is there any correlation?

OBJECTIVES: To assess the correlation between the response to transcutaneous tibial nerve stimulation (TTNS) and subsequent response to sacral nerve modulation (SNM) to treat overactive bladder (OAB). MATERIALS AND METHODS: All patients who consecutively received TTNS followed by a two-stage SNM between January 2016 and June 2022 to treat OAB in two university hospital centers were included. The response to each therapy was evaluated with success defined by a 50% or greater improvement in one or more bothersome urinary symptoms from baseline. The primary endpoint was the statistical relationship between the response to TTNS and the response to SNM, assessed by logistic regression. Secondary endpoints were the statistical relationship between the response to TTNS and the response to SNM when controlling for gender, age (<57 years vs. >57 years), presence of an underlying neurological disease, and presence of DO, adding the factor and interaction to the previous regression model. RESULTS: Among the 92 patients enrolled in the study, 68 of them were women (73.9%), and the median age was 57.0 [41.0-69.0] years. The success was reported in 22 patients (23.9%) under TTNS and 66 patients (71.7%) during the SNM test phase. There was no statistical correlation between response to TTNS and response to SNM in the overall population (confidence interval: 95% [0.48-4.47], p = 0.51). Similarly, there was no statistical correlation when controlling for age <57 years or ≥57 years, with p = 1.0 and p = 0.69, respectively. No statistical study could be conducted for the other subpopulations due to small sample sizes. CONCLUSION: The response to TTNS does not predict the response to SNM in the treatment of OAB. TTNS and SNM should be considered as separate therapies, and the decision-making process for OAB treatment should take this into account.

Longitudinal Fluctuations in Treatment Response After OnabotulinumToxinA and Sacral Neuromodulation for Refractory Urgency Incontinence.

PURPOSE: We compared fluctuations in treatment response after onabotulinumtoxinA and sacral neuromodulation for urgency incontinence using Markov models. MATERIALS AND METHODS: We fit data from a randomized trial to Markov models to compare transitions of success/failure over 6 months between 200 U onabotulinumtoxinA and sacral neuromodulation. Objective failure was <50% reduction in urgency incontinence episodes from baseline; subjective failure "strongly disagree" to "neutral" to the Patient Global Symptom Control questionnaire. RESULTS: Of the 357 participants (median baseline daily urgency incontinence episodes 4.7 [IQR 3.7-6.0]) 61% vs 51% and 3.2% vs 6.1% reported persistent states of objective success and failure over 6 months after onabotulinumtoxinA vs sacral neuromodulation. Participants receiving onabotulinumtoxinA vs sacral neuromodulation had lower 30-day transition probabilities from objective and subjective success to failure (10% vs 14%, ratio 0.75 [95% CI 0.55-0.95]; 14% vs 21%, ratio 0.70 [95% CI 0.51-0.89]). The 30-day transition probability from objective and subjective failure to success did not differ between onabotulinumtoxinA and sacral neuromodulation (40% vs 36%, ratio 1.11 [95% CI 0.73-1.50]; 18% vs 17%, ratio 1.14 [95% CI 0.65-1.64]). CONCLUSIONS: Over 6 months after treatment, 2 in 5 women's symptoms fluctuate. Within these initial 6 months, women receiving onabotulinumtoxinA transitioned from success to failure over 30 days less often than sacral neuromodulation. For both treatments, there was an almost 20%-40% probability over 30 days that women returned to subjective and objective success after failure. Markov models add important information to longitudinal models on how symptoms fluctuate after urgency incontinence treatment.

Efficacy and Safety of High-Dose Vitamin D Supplementation vs Solifenacin or Standard Urotherapy for Overactive Bladder Dry in Children: A Randomized Clinical Trial.

PURPOSE: We investigated the efficacy and safety of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing overactive bladder dry in children. MATERIALS AND METHODS: A 3-arm, randomized clinical trial was performed at an academic center in China between January 2023 and June 2023. Eligible patients (n=303) were randomized to receive 8 weeks of high-dose VDS (vitamin D3 drops encapsulated as soft capsules, 2400 IU/d) plus SU (VDS + SU group; n=100), solifenacin (5-10 mg/d) plus SU (SOL + SU group; n=102), or SU alone (SU group; n=101). Reduction in voiding frequency was the primary outcome. Secondary outcomes encompassed improvement in urgency, nocturia, quality of life score, pediatric lower urinary tract symptom score, and participant satisfaction. Treatment-emergent adverse events were recorded within each group. RESULTS: Participants had a median age of 82.0 months and their baseline mean vitamin D level was 22.64 ng/mL. The VDS + SU group showed greater improvements in voids/d than the SOL + SU group (median difference 3.0; 95% CI, 2.0 to 3.5; P < .001) and the SU group (median difference 4.0; 95% CI, 3.0 to 5.0; P < .001) after intervention. The VDS + SU group also showed the greatest improvement in quality of life and pediatric lower urinary tract symptom scores. Patient satisfaction was similar between the SOL + SU and SU groups. The VDS + SU group did not exhibit a heightened risk of treatment-emergent adverse events compared to the other groups. CONCLUSIONS: High-dose VDS plus SU was effective and well-tolerated in managing overactive bladder dry in children, suggesting its potential as a novel therapeutic option for this population.

Effects of posterior tibial nerve stimulation (PTNS) on lower urinary tract dysfunction: An umbrella review.

BACKGROUND: Lower urinary tract dysfunction (LUTD) is a common, troublesome condition that often negatively affects patients' quality of life. Current literature has long been interested in how posterior tibial nerve stimulation (PTNS) can affect this condition. AIM: To extensively and systematically explore how PTNS affects LUTD based on the most recent systematic reviews. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All the systematic reviews, with or without meta-analysis that assessed the effects of PTNS on LUTD were retrieved. The quality of the included studies was assessed using the Joanna Briggs Institute tool, and analysis was conducted using the Comprehensive Meta-Analysis version 3 tool. RESULTS: From a total of 3077 citations, 20 systematic reviews entered this study, and 13 of them included meta-analysis. The population of studies varied vastly, for instance, some studies included only children or women while other focused on a specific pathology like multiple sclerosis-induced neurogenic LUTD. The majority of included studies reported an overall improvement in LUTD following percutaneous PTNS, although admitting that these results were derived from moderate to low-quality evidence. CONCLUSION: The findings of this thorough umbrella review showed that the positive benefits of PTNS in treating LUTD are currently supported by low-quality evidence, and it is crucial to interpret them with great care.

Real-life after sacral nerve modulation implantation: Rate, reasons, and risk factors for mid-term follow-up discontinuation.

OBJECTIVES: To evaluate follow-up after implantation of a sacral nerve modulation implantable pulse generator (IPG) and to investigate the reasons and risk factors for follow-up discontinuation. MATERIALS AND METHODS: All patients who underwent an IPG implantation to treat lower urinary tract symptoms between 2014-2019 within 6 hospital centers located in the district of "Hauts-de-France" (France) were systematically called during the year 2020 for a standardized (tele)consultation. Patients were divided into 3 distinct profiles according to the regularity of their 5-year postoperative follow-up: "Regular follow-up", "Irregular follow-up" and "Lost to follow-up". The primary outcome was the change in the annual proportion of the 3 follow-up profiles over the 5 years following IPG implantation. As secondary outcomes we described the reasons reported for follow-up discontinuation and looked for risk factors associated with. RESULTS: Overall, 259 patients were included. At the time of data collection, after a mean follow-up of 28.4 (± 19.8) months, 139 patients (53.7%) had a "Regular follow-up", 54 (20.8%) had an "Irregular follow-up" and 66 (25.5%) were "Lost to follow-up". The proportion of patients with a "Regular follow-up" decreased year by year, representing only 46.2% of patients at five-years. 175 patients (67.6%) underwent a standardized (tele)consultation. In multivariate analysis, only "lack of knowledge of the follow-up protocol" was statistically associated with follow-up discontinuation (OR=5.16; 95% CI [2.12-13.57]). CONCLUSION: The proportion of patients followed up after IPG implantation decreased steadily over the years, often related to a lack of therapeutic education.