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.

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.

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.

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.

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 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.

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

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

An evaluation of onobotulinumtoxinA as a therapeutic option for pediatric neurogenic detrusor overactivity.

INTRODUCTION: Neurogenic detrusor overactivity (NDO) results in involuntary detrusor contractions during bladder filling or storage risking transmission of pressure to the upper urinary tracts and/or significant incontinence. The goals of bladder management in children with NDO prioritize the preservation of renal function, prevention of UTIs, and optimizing quality of life. First-line measures include intermittent catheterization and anticholinergic medication. However, when conservative measures fail, surgical intervention may be indicated. Historically, the next step was major reconstructive surgery to create a low-pressure urinary reservoir. The introduction of intravesical botulinum neurotoxin A (BoNT/A) for use in children in 2002 offered a less invasive option for management. However, its exact role is still evolving. AREAS COVERED: This article summarizes the mechanism of action of BoNT/A for management of NDO and evaluates the current literature defining common practice and clinical efficacy in children with NDO. The findings of the recently completed phase III trial for intravesical onabotulinumtoxinA in children are discussed in detail. EXPERT OPINION: As the first BoNT/A approved for use in children with NDO, onabotulinumtoxinA appears to be a safe and less invasive alternative to major reconstructive surgery. However, data defining appropriate patient selection and its role as a long-term treatment option continue to develop.

Manejo exitoso de síndrome de vejiga hiperactiva refractaria con toxina botulínica A / Successful management of refractory overactive bladder syndrome with botulinum toxin A

Introducción: El síndrome de vejiga hiperactiva (VHA) afecta hasta al 43% de las mujeres. La terapia escalonada incluye cambios de hábitos, fármacos y neuromodulación. Hasta el 40% de las pacientes llegan a requerir terapia avanzada alternativa, como toxina botulínica (TB). Objetivo: Reportar los resultados del tratamiento con toxina botulínica en mujeres con VHA refractaria a tratamiento de primera y segunda línea, en un hospital público en Chile. Método: Estudio de cohorte retrospectivo desde una base de datos recolectada prospectivamente del Hospital Sótero del Río entre 2018 y 2022. Se incluyeron 33 pacientes con tratamiento farmacológico y neuromodulación previa, con una edad promedio de 57 años, sometidas a inyección cistoscópica de TB a detrusor, analizando datos demográficos, antecedentes y complicaciones. Se realizó seguimiento con frecuencia miccional, paños/día, escala de gravedad de Sandvik (ISI) y encuesta Patient Global Impression Improvement (PGI-I). Resultados: Los datos comparativos pre/post TB, respectivamente, fueron: frecuencia miccional diurna 11/6 y nocturna 5/1; paños/día 5/3; ISI 8/3. Veinte de 33 mujeres refirieron estar excelente o mucho mejor (PGI-I). Conclusiones: Es posible realizar manejo con TB en mujeres con VHA refractaria a primera y segunda línea, con buenos resultados e impacto significativo en la calidad de vida.

Introduction: Overactive bladder syndrome (OABS) affects up to 43% of women. Staggered therapy includes habit changes, drugs, and peripheral neuromodulation. Up to 40% of patients may require advanced alternative therapy such as botulinum toxin A (BT). Objective: To report the results of treatment with TB in women with OABS refractory to first- and second-line treatment in a public hospital in Chile. Method: Retrospective cohort study from prospectively collected database from Hospital Sótero del Río between 2018 and 2022. Thirty-three patients with previous pharmacological treatment and neuromodulation were included, with an average age of 57 years, undergoing cystoscopic injection of TB to detrusor. Demographic data, history, and complications were analyzed. Follow-up was performed with voiding frequency, cloths/day, Sandvik Severity Scale (ISI) and Patient Global Impression Improvement (PGI-I) survey. Results: Comparative data pre/post TB, respectively showed: daytime voiding frequency 11/6 and nighttime 5/1; cloths/day 5/3; ISI 8/3. 20 of 33 women reported being excellent or much better (PGI-I). Conclusions: TB management in women with OABS refractory to first- and second-line treatment has good results and significant impact on quality of life.

The translational implications of the science behind the overactive bladder and the role of OnabotulinumtoxinA.

Urinary incontinence (UI) is a very common condition that can affect patients of all ages and the commonest cause is an overactive bladder (OAB). Most patients with OAB were treated with pharmacotherapy and major surgery. Over 25 years ago, Dasgupta, Fowler et al. studied the presence and role of C fibres in the human bladder which are highly sensitive to capsaicin, the active ingredient of chillies. When capsaicin was instilled into patients' bladders as a synthetic solution, it was found to be highly effective in some patients. Capsaicin was later replaced by Resiniferatoxin. Both toxins desensitised C-fibres through the capsaicin receptor, TRPV1, without any lasting damage to the bladder itself. The discovery of botulinum toxin and its use in the treatment of OAB represents a major breakthrough, in the treatment of OAB. Another key innovation was the development of technique to administer the drug under local anaesthesia which allowed numerous patients to benefit from treatment who would otherwise have been precluded because of the need for injection under general anaesthetic. After extensive trials over many years Botox (OnabotulinumtoxinA) is now licensed for use in OAB. Compared to other treatments for overactive bladder, OnabotulinumtoxinA is more cost-effective and less invasive. It is thought to have changed the quality of life of an estimated 5 million patients worldwide.

Efficacy and Tolerability of Ich Nieu Khang Dietary Supplement for Overactive Bladder.

This study aims to assess the effectiveness and safety of plant-derived food supplement Ich Nieu Khang (INK) as a dietary supplement for overactive bladder (OAB) symptoms. A total of 50 patients 18-80 years of age with the diagnosis and symptoms of the OAB were enrolled in the study and followed up for 30 days. The INK treatment efficacy, in terms of changes in nocturnal and day-time urination frequency, urination incontinence episodes, level of OAB symptoms according to Homma's OABSS scale, sleep quality according to Pittsburg Sleep Quality Index (PSQI), and possible side effects of the INK phytotherapy, was evaluated. INK significantly improved all OAB symptoms scores with a reduction of average nocturia from 4.06 ± 1.53 to 1.14 ± 0.94, the daily average urination urgency from 7.67 ± 5.00 to 5. 82 ± 3.70, the daily average frequency of urination from 9.96 ± 4.04 to 8.00 ± 3.70, weekly average incontinence of urination from 0.92 ± 1.56 to 0.60 ± 1.02, and OABSS Homma's score decreased from 9.31 ± 1.44 to 6.8 ± 2.21. INK phytotherapy also resulted in sleep quality improvement by PSQI score decreasing from 13.11 ± 1.33 to 10.54 ± 2.21. There were no adverse effects and abnormalities in paraclinical parameters with INK therapy. The results of our study suggest that INK dietary supplement is effective and safe phytotherapy for patients with primary OAB symptoms within 30 days of treatment. Larger control clinical trials are warranted to confirm our findings and promote wider use of INK for OAB and possible other age-related urination disorders.

Efficacy of acupoint application in patients with overactive bladder: A randomized, placebo-controlled pilot trial.

OBJECTIVE: Conventional treatments for alleviating the symptoms of Overactive bladder (OAB) have been reported to have limited efficacy and a high rate of side effects. Traditional Chinese medicine (TCM) has been used in Asia countries because of its low side effects and being easy to operate. To confirm the efficacy of acupoint application treatment for alleviating OAB symptoms, a randomized and placebo-controlled pilot trial was conducted in this study. METHODS: All participants were randomly allocated into a treatment group or control group, receiving either a "Dinggui" acupoint application or placebo treatment for 4 weeks. The outcome measures were OAB symptom scores (OABSS), OAB questionnaire (OAB-q) scores, and TCM syndrome scores. Urine nerve growth factor (NGF) level, NGF normalized to urine creatinine (NGF/Cr), and maximum flow rate (Qmax) were also measured to evaluate the OAB symptoms. RESULTS: In total, 69 participants were included with 34 in the treatment group and 35 in the placebo-treated group. Treatment with "Dinggui" acupoint application showed a statistically significant decrease in OABSS scores (8.10±1.54 to 3.67±1.77), OAB-q scores (61.43±13.93 to 38.13±15.42), and TCM syndrome scores (15.60±5.98 to 9.20±4.82). The NGF and NGF/Cr were also observed meaningful changes in a decrease from 379.68 to 136.17 pg/ml and from 0.30 to 0.16 pg/mg, respectively. The Qmax value showed a significant increase from 14.40 to 24.05 ml/s. CONCLUSIONS: Treatment with "Dinggui" acupoint application could be considered an effective and alternative therapy for OAB management. Further studies with larger sample sizes and longer treatment periods are needed to investigate.

Intravesical Injection of Botulinum Toxin Type A in Men without Bladder Outlet Obstruction and Post-Deobstructive Prostate Surgery.

PURPOSE: A significant proportion of men without bladder outlet obstruction (BOO) have been reported to have overactive bladders (OAB). This article aimed to review the specific group of reports on the use of botulinum toxin type A (BTX-A) injections into the bladder wall. MATERIALS AND METHODS: Original articles reporting men with small prostates without BOO were identified through a literature search using the PubMed and EMBASE databases. Finally, we included 18 articles that reviewed the efficacy and adverse effects of BTX-A injections in men. RESULTS: Of the 18 articles screened, 13 demonstrated the therapeutic efficacy and adverse effects of BTX-A injections in men. Three studies compared BTX-A injection response between patients without prior prostate surgery and those undergoing prior prostate surgery, including transurethral resection of the prostate and radical prostatectomy (RP). Patients with prior RP experienced better efficacy and had a low risk of side effects. Two studies focused on patients who had undergone prior surgery for stress urinary incontinence, including male sling and artificial urethral sphincter surgery. The BTX-A injection was a safe and effective procedure for this specific group. OAB in men was found to have a different pathophysiology mechanism from that in female patients, which may decrease the efficacy of BTX-A injection in men. However, patients with small prostates and low prostate-specific antigen levels demonstrated better efficacy and tolerability after BTX-A injection. CONCLUSIONS: Although intravesical injection of BTX-A was a good option for controlling refractory OAB in men, the evidence-based guidelines are still limited. Further research is necessary to better understand the role of BTX-A injections on various aspects and histories. Therefore, treating patients using strategies tailored to their individual conditions is important.

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.

Prospective, Randomized, Multicenter Trial of Peroneal Electrical Transcutaneous Neuromodulation vs Solifenacin in Treatment-naïve Patients With Overactive Bladder.

PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home-based setting in comparison with standard treatment using solifenacin in treatment-naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary-derived variables; Overactive Bladder-Validated 8-question Screener, and European Quality of Life-5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy-one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment-related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment-related adverse events compared to solifenacin and a considerably better benefit-risk profile.

Determining patient preferences in the treatment of medication-refractory overactive bladder.

INTRODUCTION: Overactive bladder (OAB) is often suboptimally addressed by behavioral or pharmacological treatments. Less than 15% of patients choose to pursue advanced OAB therapy (sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], and bladder onabotulinum toxin type-A [BTX-A]). We seek to better understand which factors are most important to patients when choosing a third-line therapy. METHODS/MATERIALS: We developed a conjoint analysis survey that included five attributes of the third-line options for OAB (SNS, PTNS, and BTX-A). We administered the survey to new patients with urinary incontinence at two institutions. A hierarchical Bayes random effects regression analysis was used to determine the relative importance of the attributes. A choice simulator was used to model which third-line treatment options patients preferred. We followed patients to see if they pursued their predicted treatment. RESULTS: A total of 108 patients completed the study of whom 89% were women. There was representation from all age groups. The most important attributes of decision-making were the frequency of future procedures, the risk of catheterization, and the need for a device. On market simulation, SNS was the preferred treatment option (47%), followed by PTNS (29%) and BTX-A (14%). Only 10% of patients did not find any treatment option acceptable. CONCLUSIONS: Frequent follow-up, risk of catheterization, and the need for a device were the most important attributes when making a decision on third-line OAB therapy. On market simulation, SNS is the preferred treatment for all age groups though the ultimate choice in third-line therapy may be affected by external factors.

Neural networks outperform expert humans in predicting patient impressions of symptomatic improvement following overactive bladder treatment.

INTRODUCTION AND HYPOTHESIS: The objective was to accurately predict patient-centered subjective outcomes following the overactive bladder (OAB) treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM) using a neural network-based machine-learning approach. In the context of treatments designed to improve quality of life, a patient's perception of improvement should be the gold standard outcome measure. METHODS: Cutting-edge neural network-based algorithms using reproducing kernel techniques were trained to predict patient-reported improvements in urinary leakage and bladder function as assessed by Patient Global Impression of Improvement score using the ROSETTA trial datasets. Blinded expert urologists provided with the same variables also predicted outcomes. Receiver operating characteristic curves and areas under the curve were generated for algorithm and human expert predictions in an out-of-sample holdout dataset. RESULTS: Algorithms demonstrated excellent accuracy in predicting patient subjective improvement in urinary leakage (OBTX-A: AUC 0.75; SNM: 0.80). Similarly, algorithms accurately predicted patient subjective improvement in bladder function (OBTX-A: AUC 0.86; SNM: 0.96). The top-performing algorithms outcompeted human experts across outcome measures. CONCLUSIONS: Novel neural network-based machine-learning algorithms accurately predicted OBTX-A and SNM patient subjective outcomes, and generally outcompeted expert humans. Subtle aspects of the physician-patient interaction remain uncomputable, and thus the machine-learning approach may serve as an aid, rather than as an alternative, to human interaction and clinical judgment.

Efficacy of non-pharmacological interventions in females with overactive bladder: A systematic review and network meta-analysis.

AIMS AND OBJECTIVES: To compare and rank the effectiveness of non-pharmacological interventions for symptoms of Overactive Bladder (OAB) in network meta-analysis. BACKGROUND: Overactive Bladder affects many patients, which often generates bothersome symptoms and debilitates the quality of life. Non-pharmacological therapies have been widely used in OAB. However, due to insufficient evidence, it remains unclear which strategies are most suitable for OAB. METHODS: We integrated randomised controlled trials (RCTs), which were searched up to 1 January 2021, from 8 databases (PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc). Studies that met the eligible criteria were assessed the risk of bias. Then, network meta-analyses were conducted by STATA, R, and OpenBUGS. The review followed PRISMA statement. RESULTS: A total of 24 studies comprising 2347 patients with OAB were included in this review, most of which were low to moderate risk of bias. The results of network meta-analysis implied that electric stimulation (ES) was the most effective intervention to reduce voided frequency and nocturia frequency of OAB. CONCLUSIONS: Electric stimulation ranked the best in the management of OAB, and future studies should pay more attention to ES.

Effect of Vitamin D Supplementation on Overactive Bladder and Urinary Incontinence Symptoms in Older Men: Ancillary Findings From a Randomized Trial.

PURPOSE: Our goal was to evaluate vitamin D supplementation for preventing or treating overactive bladder and urinary incontinence in men. MATERIALS AND METHODS: Ancillary study of men aged ≥55 years in VITAL (VITamin D and OmegA-3 TriaL). Randomized treatments included: vitamin D3 (cholecalciferol), marine omega-3 fatty acids, or matching placebo. Structured urinary incontinence questions measured the prevalence of overactive bladder at year 5 and urinary incontinence at years 2 and 5, along with incidence and progression of urinary incontinence from years 2 to 5. Prespecified subgroup analyses examined men with low baseline serum 25-hydroxyvitamin D (<20 ng/mL). RESULTS: Among the 11,486 men who provided data at year 2 and 10,474 at year 5, mean age was 68 years at year 2, with 23% racial/ethnic minorities. In primary analyses, vitamin D supplementation compared to placebo did not lower odds of overactive bladder at year 5 (OR 0.97, 95% CI 0.87-1.08) or weekly urinary incontinence at year 2 (OR 0.94, 95% CI 0.83-1.05) or year 5 (OR 0.98, 95% CI 0.88-1.09). We found interactions of baseline serum 25-hydroxyvitamin D level with vitamin D supplementation for overactive bladder (P value for interaction = .001), and secondarily, for any urinary incontinence at year 2 (P value for interaction = .05). Men with baseline 25-hydroxyvitamin D <20 ng/mL, who were assigned to vitamin D supplements, had lower odds of overactive bladder (OR 0.51, 95% CI 0.35-0.76) compared to placebo, yet higher odds of any urinary incontinence (OR 1.24, 95% CI 0.93-1.64). CONCLUSIONS: Overall, vitamin D supplementation did not improve overactive bladder or urinary incontinence compared to placebo. However, specific use of vitamin D in men with lower 25-hydroxyvitamin D levels had inconsistent findings.