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.

Pilot Study of a Novel Online Comprehensive Pelvic Floor Program for Urinary Incontinence in Women.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is common in women and has a vast impact on quality of life (QOL), financial health, and work disability. Robust evidence demonstrates the efficacy of comprehensive conservative therapy (pelvic floor muscle training [PFMT], and behavioral and dietary modification) in the treatment of UI. However, numerous barriers impede access to this care, including limited specialized therapists, financial barriers, and scheduling obstacles. To address these barriers, we developed a novel comprehensive online pelvic floor program (oPFP). METHODS: We performed a prospective study assessing continence and QOL outcomes in women with stress urinary incontinence (SUI), urge urinary incontinence (UUI), or mixed urinary incontinence (MUI) treated with oPFP between May 2019 and November 2022. Outcomes were assessed at baseline and following completion of the 2-month program using the validated International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms, Urgency Perception Scale (UPS), Incontinence Impact Questionnaire (IIQ-7) questionnaires, and 24-h bladder diary. Data were analyzed using linear, Poisson mixed models, or generalized estimating equations. RESULTS: Twenty-eight women (2 SUI, 3 UUI, 23 MUI) were enrolled and 19 (2 SUI, 2 UUI, 15 MUI) completed the study. Following oPFP, participants showed significantly improved SUI domain scores (3.04 ± 0.19 vs 1.81 ± 0.23, p < 0.001), UPS reason score (2.52 ± 0.18 vs 2.05 ± 0.14, p = 0.003), IIQ-7 sum scores (5.16 ± 0.88 vs 3.07 ± 0.70, p = 0.038), and daily incontinence episodes (2.96 ± 0.60 vs 1.06 ± 0.29, p < 0.001). Mean patient-reported improvement was 5.4 ± 2.5 (ten-point Likert scale). Of respondents, 89% reported program satisfaction, ease of use, and would recommend the program to others. CONCLUSION: The oPFP results in significant improvements to a variety of UI and QOL measures. This program provides an important UI treatment option and gives women greater access to effective conservative therapy.

Management of mixed urinary incontinence: IUGA committee opinion.

INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI) is defined by the International Urogynecology Association (IUGA) and International Continence Society as the complaint of involuntary leakage of urine associated with urgency and also with exertion, effort, sneezing or coughing. It therefore implies the coexistence of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). MUI is a heterogeneous diagnosis that requires an assessment of its individual components of SUI and UUI. Management requires an individualised approach to the symptom components. The aim of this review is to identify the assessment/investigations and management options for MUI. METHODS: A working subcommittee from the IUGA Research & Development (R&D) Committee was created and volunteers invited from the IUGA membership. A literature review was performed to provide guidance focused on the recommended assessment and management of MUI. The document was then evaluated by the entire IUGA R&D Committee and IUGA Board of Directors and revisions made. The final document represents the IUGA R&D Committee Opinion. RESULTS: The R&D Committee MUI opinion paper provides guidance on the assessment and management of women with MUI and summarises the evidence-based recommendations. CONCLUSIONS: Mixed urinary incontinence is a complex problem and successful management requires alleviation of both the stress and urge components. Care should be individualised based on patient preferences. Further research is needed to guide patients in setting goals and to determine which component of MUI to treat first. The evidence for many of the surgical/procedural treatment options for MUI are limited and needs to be explored in more detail.

APP-based treatment of urgency and mixed urinary incontinence in women: factors associated with long-term satisfaction.

PURPOSE: App-based treatment of urgency (UUI) and mixed (MUI) urinary incontinence has proved to be effective. To further improve treatment, it will be beneficial to analyze baseline and treatment-related factors that are associated with satisfaction. METHODS: A secondary analysis was conducted of data from a randomized controlled trial (RCT) assessing an app for UUI or MUI treatment, encompassing 98 women for whom there was long-term treatment satisfaction data. All participants completed a short-term (15 weeks) and a long-term (15 months) follow-up questionnaire after being given access to treatment. The outcome was a 3-item question on current treatment satisfaction at the long-term follow-up. Factors potentially associated with the outcome were analyzed using the chi-square test, Student's t test or logistic regression. RESULTS: At the long-term follow-up, 58% of the women were satisfied with the treatment. The most important baseline variable associated with satisfaction was incontinence-related quality of life (International Consultation on Incontinence Questionnaire (ICIQ) - Lower Urinary Tract Symptoms Quality of Life Module) (OR 0.91, 95% CI 0.58-0.97). Short-term follow-up variables associated with long-term treatment satisfaction were improvement in the ability to endure urgency (OR 4.33, 95% CI 1.43-13.12), and confidence in pelvic floor contraction ability (OR 2.67, 95% CI 1.04-6.82). CONCLUSION: App-based treatment for UUI and MUI may be an alternative first-line treatment that is satisfactory to many women over the long-term. Furthermore, short-term treatment that focuses on improving the ability to endure urgency, and confidence in pelvic floor contraction ability, can also be recommended for long-term satisfaction.

Pelvic floor muscle training: Novel versus traditional remote rehabilitation methods. A systematic review and meta-analysis on their effectiveness for women with urinary incontinence.

OBJECTIVE: To investigate the effectiveness of supervised remote rehabilitation programs comprising novel methods of pelvic floor muscle (PFM) training for women with urinary incontinence (UI). DESIGN: A systematic review and meta-analysis including randomized controlled trials (RCTs), involving novel supervised PFM rehabilitation programs as intervention groups (e.g., mobile applications programs, web-based programs, vaginal devices) versus more traditional PFM exercise groups (acting as control); both sets of groups being offered remotely. METHODS: Data have been searched and retrieved from the electronic databases of Medline, PUBMED, and PEDro using relevant key words and MeSH terms. All included study data were handled as reported in the Cochrane Handbook for Systematic Reviews of Interventions and the evaluation of their quality was undertaken utilizing the Cochrane risk-of-bias tool 2 (RoB2) for RCTs. The included RCTs, involved adult women with stress UI (SUI) or mixed urinary incontinence, where SUI were the most predominant symptoms. Exclusion criteria involved pregnant women or up to 6-month postpartum, systemic diseases and malignancies, major gynecological surgeries or gynecological problems, neurological dysfunction or mental impairments. The searched outcomes included subjective and objective improvements of SUI and exercise adherence in PFM exercises. Meta-analysis was conducted and included studies pulled by the same outcome measure. RESULTS: The systematic review included 8 RCTs with 977 participants. Novel rehabilitation programs included mobile applications (1 study), web-based programs (1 study) and vaginal devices (6 studies) versus more traditional remote PFM training, involving home-based PFM exercise programs (8 studies). Estimated quality with Cochrane's RoB2, presented the 80% of the included studies as "some concerns" and the 20% as "high risk." Meta-analysis included 3 studies with no heterogeneity (I2 = 0) across them. Weak-evidenced results presented home PFM training equally effective with novel PFM training methods (mean difference: 0.13, 95% confidence interval: -0.47, 0.73), with small total effect size (0.43). CONCLUSIONS: Novel PFM rehabilitation programs presented as effective (but not superior) to traditional ones in women with SUI, both offered remotely. However, individual parameters of novel remote rehabilitation including supervision by the health professional, remains in question and larger RCTs are required. Connection between devices and applications in combination with real-time synchronous communication between patient and clinician during treatment is challenged for further research across novel rehabilitation programs.

Mixed urinary incontinence: Are there effective treatments?

The aim of this debate article is to discuss whether effective treatments are available for mixed urinary incontinence (MUI). Because patients with MUI have both stress and urgency urinary incontinence (SUI and UUI) episodes and current treatment guidelines currently recommend treating the predominant symptom first, this article presents standard and emerging treatments for both SUI and UUI before discussing how well these treatments meet the medical needs of patients with MUI. Standard treatments presented include noninvasive options such as lifestyle changes and pelvic floor exercises, pharmacological agents, and surgery. Treatment of all three types of urinary incontinence (UI) is usually initiated with noninvasive options, after which treatment options diverge based on UI subtype. Multiple pharmacological agents have been developed for the treatment of UUI and overactive bladder, whereas surgery remains the standard option for SUI and stress-predominant MUI. The divide between UUI and SUI options seems to be propagated in emerging treatments, with most novel pharmacological agents still targeting UUI and even having SUI and stress-predominant MUI as exclusion criteria for participation in clinical trials. Considering that current treatment options focus almost exclusively on treating the predominant symptom of MUI and that emerging pharmacological treatments exclude patients with stress-predominant MUI during the development phase, effective treatments for MUI are lacking both in standard and emerging practice. Ideally, agents with dual mechanisms of action could provide symptom benefit for both the stress and urgency components of MUI.

Development of an implant technique and early experience using a novel implantable pulse generator with a quadripolar electrode array at the tibial nerve for refractory overactive bladder.

OBJECTIVES: Tibial nerve stimulation is an effective treatment for overactive bladder (OAB) and has been utilized as an in-person recurring session treatment option for many years. The primary objective of this study was to evaluate the safety and efficacy of a long-term implantable device and the method of utilizing a retrograde approach to place the device (a percutaneous implantable pulse generator [pIPG] with integrated quadripolar electrodes) at the tibial nerve (Protect PNS; Uro Medical Corp.). METHODS: A novel retrograde implant technique was developed through multiple cadaveric dissections to percutaneously implant a chronic, wireless, minimally invasive pIPG device with integrated quadripolar electrodes (now licensed to Uro Medical) at the tibial nerve. A proof-of-concept pIPG device approved as part of an FDA IDE was designed to gain early experience in subjects with refractory OAB. The pIPG was implanted in the office under local anesthesia using the novel retrograde approach, and stimulation was activated using an external wireless energy source called a transmitter. Initially, a pilot study was designed to compare outcomes in subjects randomized to either percutaneous tibial nerve stimulation (PTNS) or Protect PNS. However, due to the small sample sizes available at this time, it was not possible to compare the two groups. Thus, the purpose of this manuscript is to describe the outcome of subjects who underwent implantation of the Protect PNS system. Twelve-month safety and efficacy were evaluated. RESULTS: Nine subjects were enrolled in the randomized pilot study; 5 to the pIPG group and 4 to PTNS, and all completed the 13-week primary endpoint. Subsequently, two subjects in the PTNS group chose to cross over and have the pIPG implanted after 13 weeks. Outcomes of the seven subjects who underwent implantation of the pIPG are described. No complications related to the office procedure were noted. Two of the older model pIPG devices became nonresponsive at 1 and 4 weeks and were replaced. Six minor adverse events were reported and resolved. Subjects reported improvement in urge urinary incontinence (UUI) episodes, OAB symptoms, and quality of life. Subjects impanted with a pIPG reported a 50% reduction in UUI as early as 1 week. CONCLUSIONS: Results of this pilot study suggest that retrograde percutaneous implantation of a pIPG is a safe, minimally invasive one-stage office procedure for treatment for urge incontinence related OAB symptoms, without significant complications after 12 months follow-up. Future studies will be required to compare outcomes among treatment modalities.

The impact of postinjection urinary tract infection on efficacy of intravesical onabotulinumtoxinA-A secondary analysis.

OBJECTIVES: To compare treatment response in women who did and did not develop a urinary tract infection (UTI) within 14 days after intravesical onabotulinumtoxinA injections for treatment of refractory urgency urinary incontinence (UUI). METHODS: This is a secondary analysis of women who received Onabotulinumtoxin A in the Refractory Overactive Bladder: Sacral Neuromodulation vs Botulinum Toxin Assessment (ROSETTA) Trial. Participants were grouped by presence or absence of UTI within 14 days of injection. UTI was defined as symptomatic with positive urine culture per the primary ROSETTA protocol. Our primary outcome was change from baseline in mean number of UUI episodes based on monthly 3-day bladder diaries averaged over 6 months. We performed t tests and chi-square/Fisher's exact for continuous and categorical variables. A p value of <0.05 was considered statistically significant. RESULTS: Of 187 participants in the onabotulinumtoxinA arm, 10 (5.3%) experienced UTI within 14 days of injection, and 177 (94.7%) did not. At baseline, groups did not differ in demographics, mean UUI episodes per day (no UTI [5.37 ± 2.65] vs. UTI [6.40 ± 3.02], p = 0.24), or other diary parameters. For our primary outcome, groups did not differ in the change in mean daily UUI episodes at 1 month (no UTI [-4.29 ± 2.75] vs. UTI [-3.74 ± 2.01]; mean difference [95% confidence interval, CI] -0.55 [-2.39 to 1.28], p: 0.55) or 6 months (no UTI [-3.63 ± 2.89] vs. UTI [-2.15 ± 3.18]; mean difference [95% CI] -1.48 [-3.44 to 0.48], p: 0.14). CONCLUSIONS: UTI within 14 days after intravesical injection of onabotulinumtoxinA for refractory UUI was not significantly associated with inferior treatment response at 1 or 6 months.

Magnetic stimulation in the treatment of female urgency urinary incontinence: a systematic review.

INTRODUCTION AND HYPOTHESIS: This systematic review analyzes published studies about magnetic stimulation (MS) treatment for UUI and determines whether this treatment is effective and non-invasive. METHODS: A systematic literature search was conducted using PubMed, the Cochrane Library, and Embase. The international standard for reporting results of systematic reviews and meta-analyses (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was used to guide the methodology of this systematic review. The key search terms were as follows: "magnetic stimulation" and "urinary incontinence." We limited the time frame to articles published from 1998, when the FDA approved MS as a conservative treatment option for UI. The last search was performed on 5 August 2022. RESULTS: Two authors independently reviewed 234 article titles and abstracts, of which only 5 fitted the inclusion criteria. All 5 studies included women with UUI, but every study had different diagnostic and entry criteria for patients. They also differed in their treatment regimens and methodological approaches to assessing the efficacy of treating UUI with MS, which made it impossible to compare the results. Nonetheless, all five studies established that MS is an effective and non-invasive way of treating UUI. CONCLUSIONS: The systematic literature review led to the conclusion that MS is an effective and conservative way of treating UUI. Despite this, literature in this area is lacking. Further randomized controlled trials are needed, with standardized entry criteria, UUI diagnostics, MS programs, and standardized protocols to measure the efficacy of MS in UUI treatment, with a longer follow-up period for post-treatment patients.

Treatment outcome of women with urodynamic mixed urinary incontinence: an observational study.

INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI) is a common yet understudied condition. It remains a therapeutic challenge, with the presence of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). There is limited information on the optimal management for women with urodynamic MUI (urodynamic stress incontinence and detrusor overactivity). We assessed the treatment outcome of pelvic floor muscle training (PFMT), medical treatment and surgery for women who were diagnosed with urodynamic MUI. METHODS: A prospective observational study was carried out on women with urodynamic MUI from 2010 to 2018. All women underwent clinical assessment and standardised urodynamic evaluation. All women received PFMT from a specialised continence advisor as initial management. Antimuscarinics and/or continence surgery were considered according to the woman's response and symptoms after PFMT. Subjective outcome after each treatment modality was analysed. RESULTS: A total of 198 women were included for analysis. All women received PFMT, 104 (52.5%) showing improvement in urinary incontinence. Eighty-seven (43.9%) women were offered antimuscarinics, of whom 58 (29.3%) showed subjective improvement in both SUI and UUI, and 10 (5%) reported a reduction in UUI but persistent SUI. A total of 55 (27.7%) women received surgical treatment, with 20 receiving continence procedures. Sixteen out of twenty (80%) of them reported improvement in both SUI and UUI. None reported worsening of urgency or UUI. Overall, across all treatment modalities, 73.8% of women showed improvement in both SUI and UUI. CONCLUSION: Future analyses can help to inform which patients will have a higher success rate after each treatment modality and help focus treatment effort on those with a high risk of persistent symptoms. This will provide relevant data in counselling women, giving reasonable expectations and directing the management of women with urodynamic MUI.

Longitudinal urinary microbiome characteristics in women with urgency urinary incontinence undergoing sacral neuromodulation.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the stability of the urinary microbiome communities in women undergoing sacral neuromodulation (SNM) for urgency urinary incontinence (UUI). We hypothesized that clinical response to SNM therapy would be associated with changes in the urinary microbiome. METHODS: Women completed the Overactive Bladder Questionnaire Short-Form, the International Consultation on Incontinence Questionnaire Short Form, and the Female Sexual Function Index at baseline and 3 months post-SNM implantation. Transurethral urinary specimens were obtained for microbiome analysis at baseline and 3 months postoperatively. The V4 region of the 16S rRNA gene (515F-806R) was amplified with region-specific primers, and Amplicon Sequence Variants (ASVs) were identified with a closed-reference approach of taxonomic classification. Alpha-diversity was calculated using the phylogenetic (i.e., Faith's phylogenetic diversity) and nonphylogenetic metrics (i.e., Shannon diversity, and Pielou's evenness) using the QIIME2 plugin. Longitudinal paired volatility analysis was performed using the DEICODE and Gemelli plugin to account for host specificity across both time and space. RESULTS: Nineteen women who underwent SNM and provided both baseline and 3-month urine samples were included in this analysis. Women reported improvement in objective (number of UUI episodes) and subjective (symptom severity and health-related quality of life) measures. Ninety percent of the bacteria were classified as Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. No significant differences were observed in each subject's beta-diversity at 3 months compared with their baseline microbiome. CONCLUSIONS: Our descriptive pilot study of a cohort of women who had achieved objective and subjective improvements in UUI following SNM therapy demonstrates that the urinary microbiome remains relatively stable, despite variability amongst the cohort.

Flat Magnetic Stimulation for Urge Urinary Incontinence.

Background and Objectives: Strategies for overactive bladder syndrome (OAB) management involve, among others, strengthening the bladder outlet to suppress urgency and neuromodulating the sacral roots. Magnetic stimulation (MS) is a technology that involves an extracorporeal device that is able to provide an electromagnetic field specifically designed to interact with pelvic floor neuromuscular tissue. The resulting tissue electrical activity induces contraction of the pelvic muscle and neuromodulation of the S2-S4 sacral roots. Flat Magnetic Stimulation (FMS) is a relevant advancement involving homogeneous electromagnetic fields, which are able to optimize the effect on the entire pelvic area. However, the benefits of this new technology for OAB syndrome are poorly known. Consequently, the aim of our study is to analyze the outcomes and quality of life (QoL) impact of FMS with Dr. Arnold (DEKA, Calenzano, Italy) in women suffering from OAB syndrome associated with urinary incontinence. Materials and Methods: This prospective study included patients with OAB, urge urinary incontinence, and no ongoing OAB treatments. At baseline (T0), the Incontinence Impact Questionnaire (IIQ-7), the Female Sexual Function Index (FSFI-19), and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) were collected. Patients underwent 8 FMS sessions of 25 min each in one month. At the termination of the therapy (T1), women repeated the ICIQ-UI SF, FSFI-19, and IIQ-7 tools. Moreover, the Patient Global Impression of Improvement (PGI-I) questionnaire was collected to evaluate the cure rate. Results: Our study enrolled a total of 57 consecutive patients. Most women had at least one second- or third-line treatment before FMS, while the remaining naive patients had contraindications to pharmacological treatments. No women reported adverse effects during the treatment. After the treatment, we observed a decrease in the IIQ-7 (p < 0.001) and ICIQ-UI SF scores (p < 0.001) and an improvement in sexual function (p < 0.001) evaluated with FSFI-19. According to PGI-I scores, 42 (73.7%) women referred to some kind of improvement, scoring ≤ 3 points. Specifically, 8.7% of patients considered themselves very much improved, 29.8% much improved, 35.1% minimally improved, and 26.3% found no changes. FMS was effective in treating OAB symptoms without any adverse effects. The mechanism is supposed to be related to suppressing the initiation of micturition. This makes FMS a promising device for treating naive and refractory urge urinary incontinence. Conclusions: The new FMS represents a promising non-pharmacological option for the treatment of naive and refractory OAB.

Neuroimaging of situational urgency and incontinence provoked by personal urgency cues.

INTRODUCTION: Situational triggers for urinary urgency and incontinence (UUI) such as "latchkey incontinence" and running water are often reported clinically, but no current clinical tools exist to directly address symptoms of UUI provoked by environmental stimuli. Previously we have shown that urgency and leakage can be reproduced during urodynamic studies with exposure to personal urgency-related images. Here we investigate the neural signatures associated with such situational triggers to inform potential therapies for reducing reactivity to these personal urgency-related cues among women with situational UUI. METHOD: We recruited 23 women with situational UUI who took photographs of their personal "urgency trigger" and "safe" situations and were exposed to them in a magnetic resonance imaging (MRI) scanner. We identified brain areas that were more active during urgency versus safe image exposure. RESULTS: We found that, during urgency image exposure, main components of the attention network and decision-related processes, the middle and medial frontal gyri, were more active (p < 0.01). In addition, areas well known to be involved in the continence mechanism, such as the cingulate and parahippocampal areas, were also more active during urgency image exposure. CONCLUSION: Exposure to personal situational urgency images activated different areas of the brain compared with safe environments, highlighting the complex brain mechanisms that provoke real-world urgency. Using brain and behavioral-based therapies which target the attentional areas identified here and extinguish cue reactivity might reduce symptom burden in this subset of UUI sufferers.

Prospective, multicenter study to evaluate performance and safety of a re-engineered temporary lead for InterStim™ therapy evaluation.

AIMS: The basic evaluation or percutaneous nerve evaluation (PNE) is a method to assess pre-implantation therapeutic response in patients considering sacral neuromodulation for the treatment of refractory overactive bladder. A new PNE lead with a more robust design and greater distensibility designed to reduce the possibility of lead migration has recently been introduced to the market. The aim of this prospective, multicenter, global, postmarket study was to evaluate the clinical performance and safety of the new InterStim PNE lead with the foramen needle. METHODS: Patients with overactive bladder were enrolled in this study. The primary objective of this study was to determine the proportion of subjects who demonstrated motor or sensory response(s) during lead placement using the InterStim PNE lead. Additional measures included the Patient Global Impression of Improvement (PGI-I), patient satisfaction at the end of therapy evaluation, and change in bladder symptoms from baseline to the end of therapy evaluation (1-week follow-up visit). RESULTS: One-hundred and ten subjects met the inclusion and exclusion criteria and underwent a lead implant procedure. Of those, 108 had a successful procedure and 107 completed the 1-week follow-up visit. Ninety-nine percent of subjects (109/110) had a motor or sensory response during needle placement (95% confidence interval [CI]: 95%-100%) and 97% of subjects (107/110) had a motor or sensory response during lead placement (95% CI: 92%-99%). The majority of subjects (88%, 95/108) reported their bladder condition was better at the follow-up visit compared to before the PNE implant procedure, as reported in PGI-I. Subjects reported being satisfied with how the therapy impacted their voiding symptoms (82%, 88/108) and that they would recommend this therapy (87%, 94/108) to other patients. Symptom improvement was demonstrated with urinary urge incontinence subjects having an average of 4.2 ± 3.4 urinary incontinence episodes/day at baseline and 2.2 ± 2.5 at follow-up, and urinary frequency subjects having an average of 12.5 ± 4.4 voids/day at baseline and 10.5 ± 4.3 voids/day at follow-up. Lead removal was deemed to be easy and safe by the implanting physician, with a total of three adverse device effects in 3/110 subjects. No event was categorized as serious and all were resolved without sequelae. CONCLUSIONS: The updated InterStim PNE lead with a more robust design and greater distensibility designed to reduce migration was shown to have a high rate of motor or sensory response during lead placement. Furthermore, subjects reported high rates of global improvements and amelioration of symptoms, and the lead was easy to remove with minimal morbidity.

App-based self-management of urgency and mixed urinary incontinence in women: One-year follow-up.

AIMS: To evaluate the long-term effect of the Tät®II app for treatment of urgency (UUI) and mixed urinary incontinence (MUI). METHODS: Long-term follow-up of a randomized controlled trial, including 123 women ≥18 years old with UUI or MUI, without red-flag symptoms, and ≥2 leakages per week. All participants, regardless of group, had received the intervention, a treatment app, at the long-term follow-up. Long-term data were collected through web-based questionnaires 15 months after participants received the intervention. The app included pelvic floor muscle training, bladder training, psychoeducation, lifestyle advice, an exercise log, reminders, reinforcement messages, and tailored advice. The primary outcome was a change in incontinence symptoms (International Consultation on Incontinence Questionnaire [ICIQ]-Urinary Incontinence Short Form [ICIQ-UI SF]), from baseline to follow-up. Other outcomes were urgency symptoms (ICIQ-Overactive Bladder Module (ICIQ-OAB)), quality of life (ICIQ-Lower Urinary Tract Symptoms Quality of Life Module [ICIQ-LUTSqol]), and improvement (Patient's Global Impression of Improvement [PGI-I]). RESULTS: Of the 123 women, 102 (83%) completed the long-term follow-up. The ICIQ-UI SF mean score improved from 11.5 to 7.6 (mean difference 4.0, 95% CI 3.2-4.7). The ICIQ-OAB improved from 6.7 to 5.5 (mean difference 1.3, 95% CI 0.9-1.6) and the ICIQ-LUTSqol improved from 38.0 to 30.9 (mean difference 7.1, 95% CI 5.7-8.5). Of the 102 women, 74 (73%) reported improvement. CONCLUSIONS: Self-management with the Tät®II app for UUI and MUI had a significant effect across all outcome measures also long-term and might serve as an alternative first-line treatment for these conditions.

Machine learning provides an accurate prognostication model for refractory overactive bladder treatment response and is noninferior to human experts.

OBJECTIVE: The increasing wealth of clinical data may become unmanageable for a physician to assimilate into optimal decision-making without assistance. Utilizing a novel machine learning (ML) approach, we sought to develop algorithms to predict patient outcomes following the overactive bladder treatments OnabotulinumtoxinA (OBTX-A) injection and sacral neuromodulation (SNM). MATERIALS AND METHODS: ROSETTA datasets for overactive bladder patients randomized to OBTX-A or SNM were obtained. Novel ML algorithms, using reproducing kernel techniques were developed and tasked to predict outcomes including treatment response and decrease in urge urinary incontinence episodes in both the OBTX-A and SNM cohorts, in validation and test sets. Blinded expert urologists also predicted outcomes. Receiver operating characteristic curves were generated and AUCs calculated for comparison to lines of ignorance and the expert urologists' predictions. RESULTS: Trained algorithms demonstrated outstanding accuracy in predicting treatment response (OBTX-A: AUC 0.95; SNM: 0.88). Algorithms accurately predicted mean decrease in urge urinary incontinence episodes (MSE < 0.15) in OBTX-A and SNM. Algorithms were superior to human experts in response prediction for OBTX-A, and noninferior to human experts in response prediction for SNM. CONCLUSIONS: Novel ML algorithms were accurate, superior to expert urologists in predicting OBTX-A outcomes, and noninferior to expert urologists in predicting SNM outcomes. Some aspects of the physician-patient interaction are subtle and uncomputable, and thus ML may complement, but not supplant, a physician's judgment.

Cognitive-behavioral therapy and urge urinary incontinence in women. A systematic review.

INTRODUCTION AND HYPOTHESIS: UUI co-exists with numerous health conditions, having a substantial negative impact on health-related quality of life and mental health. Cognitive-behavioral therapy (CBT) could help patients manage these problems by changing the way they think and behave. METHODS: We carried out a systematic review of the literature assessing the modalities and effects of CBT as a stand-alone strategy, without adding PFMT, on symptoms and clinical signs, in women with UUI. Our secondary objective was to report modalities and effects of CBT on health-related quality of life, psychological symptoms and patient-reported satisfaction. The PRISMA methodology was used to carry out this systematic review. A literature search was conducted in PubMed, PEDro, Web of Science and Cochrane Library databases from inception to December 2020. The PICO approach was used to determine the eligibility criteria. RESULTS: Twelve papers were included in the present review which showed beneficial effects on both symptom severity (p < 0.05) and more subjective areas such as quality of life, psychological symptoms or patient satisfaction level (p < 0.05), respectively). However, results on the effectiveness of CBT on clinical signs remains conflicting. CONCLUSION: Based on the available literature, this review suggested a high level of evidence for the effectiveness of CBT on symptom severity and a moderate level of evidence for the effectiveness of CBT on quality of life, psychological symptoms and patient satisfaction. However, we highlighted no evidence for the effects of CBT on clinical signs.

Does electroacupuncture benefit mixed urinary incontinence? A systematic review and meta-analysis with trial sequential analysis.

INTRODUCTIN AND HYPOTHESIS: Mixed urinary incontinence (MUI) comprises a combination of urgency and stress. The efficacy and safety of electroacupuncture (EA) for the treatment of MUI remain unclear. OBJECTIVE: To assess the efficacy and safety of EA in treating MUI. METHODS: We searched PubMed, CENTRAL, Embase, Web of Science, four Chinese databases, clinical research registration platforms, grey literature, and the reference lists of the selected studies. Risk of bias and quality were evaluated using the Revman 5.4 and Jadad scores. Meta-analysis was performed using Stata 15.1 software. Trial sequential analysis (TSA) was used to assess the stability of the results. RESULTS: Eight randomized controlled trials comprising 847 patients were included. The meta-analysis results showed that compared with antimuscarinic drugs plus pelvic floor muscle training, EA resulted in significantly less pad weight on the 1-h pad test and statistically significantly lower severity scores on the International Consultation on Incontinence Questionnaire Short Form. The change in the 72-h incontinence episode frequency difference was not statistically significant, and there was no outcome of overall response rate and quality of life in this meta-analysis. Few adverse events occurred in the EA group. The TSA results suggested that the result of change from baseline in the 1-h pad test was stable and the evidence was conclusive. CONCLUSIONS: EA could be a potential treatment option for MUI and is relatively safe. Nevertheless, because of the limitations of this study, our conclusions should be interpreted with caution, and further studies are needed to confirm the comprehensive clinical efficacy and placebo effect of EA.

A mobile app for the treatment of female mixed and urgency incontinence: a cost-effectiveness analysis in Sweden.

INTRODUCTION AND HYPOTHESIS: A previous randomized controlled trial (RCT) demonstrated that the app Tät II, for self-management of mixed urinary incontinence (MUI) and urgency urinary incontinence (UUI), yielded significant, clinically relevant improvements in symptom severity and quality of life (QoL) compared with a control group. We aimed to assess the cost-effectiveness of Tät II. METHODS: A cost-utility analysis with a 1-year societal perspective was carried out, comparing Tät II with an information app. Data were collected alongside an RCT: 122 community-dwelling women aged ≥18 years with MUI or UUI ≥2 times/week were randomized to 3 months of Tät II treatment focused on pelvic floor muscle training (PFMT) and bladder training (BT; n = 60), or to an information app (n = 62). Self-assessed data from validated questionnaires were collected at baseline and at 3-month and 1-year follow-ups. Costs for assessment, treatment delivery, incontinence aids, laundry, and time for PFMT and BT were included. We calculated quality-adjusted life-years (QALYs) using the International Consultation on Incontinence Modular Questionnaire Lower Urinary Tract Symptoms Quality of Life. The incremental cost-effectiveness ratio (ICER) between the groups was our primary outcome. Sensitivity analyses were performed. RESULTS: The mean age was 58.3 (SD = 9.6) years. Annual overall costs were €738.42 in the treatment group and €605.82 in the control group; annual QALY gains were 0.0152 and 0.0037 respectively. The base case ICER was €11,770.52; ICERs in the sensitivity analyses ranged from €-9,303.78 to €22,307.67. CONCLUSIONS: The app Tät II is a cost-effective treatment method for women with MUI and UUI.

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

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