A Multicenter Study Evaluating the FREquency of Use and Efficacy of a Novel Closed-Loop Wearable Tibial Neuromodulation System for Overactive Bladder and Urgency Urinary Incontinence (FREEOAB).

OBJECTIVE: To evaluate the effectiveness and safety of a novel wearable neuromodulation system incorporating embedded electromyographic evaluation, representing the first closed-loop wearable therapy for bladder control. METHODS: This 12-week, multicenter, open-label, single-arm study of subjects with overactive bladder assessed response of bladder diary parameters and quality of life (QOL) metrics. Subjects used the transcutaneous tibial neuromodulation system, either once or three times weekly, with evaluations at weeks 1, 4, 8, and 12. Enrolled subjects (N = 96) were assessed for changes in urinary frequency, urgency, and urgency urinary incontinence episodes, and QOL changes using various questionnaires. RESULTS: In the intent-to-treat population (N = 96, mean age 60.8 ± 13.0years, 88.5% female), significant reductions in 3-day diary parameters were observed for daily voids, incontinence, and urgency episodes at 12weeks. QOL improvements exceeded the minimal clinically important difference for all QOL questionnaires. Long-term results remained robust at 12months. Device-related adverse events were mild and there were no device-related serious adverse events. Mean therapy compliance at 12weeks was 88.5%. High satisfaction rates were reported for the device overall. CONCLUSION: The Avation device demonstrates promising efficacy in treating adults with overactive bladder and urge urinary incontinence. At 12weeks, both diary parameters and QOL indicators showed significant improvement and remained robust at 12months. The device had a favorable safety profile with high compliance and patient satisfaction. This novel, closed-loop wearable tibial neuromodulation system represents a significant advancement in bladder control therapy, offering a noninvasive, patient-centered alternative with improved accessibility and ease of use.

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.

Five-year Results from the Prospective, Multicenter, Observational SOUNDS Study of Patients with Overactive Bladder Treated with the InterStim System for Sacral Neuromodulation.

BACKGROUND: Although sacral neuromodulation (SNM) for overactive bladder (OAB) is an established therapy, there is a lack of high-quality, long-term data on real-life practice. OBJECTIVE: To report on real-life therapeutic effectiveness, quality of life (QoL), disease severity, and safety as well as patient-reported symptom bother after approximately 5 yr of follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 291 OAB patients were enrolled at 25 French sites according to local standard of care. Sacral neuromOdUlation with InterStim therapy for intractable lower uriNary tract DySfunctions (SOUNDS) enrolled both de novo and replacement patients, and a total of 229 patients were permanently implanted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over the course of the study, patients were followed up six times with two follow-ups in the year after implantation and annually thereafter. Of the patients, 154 completed the final follow-up after a mean of 57.7 ± 3.9 mo. RESULTS AND LIMITATIONS: The mean number of daily leaks in urinary urge incontinence (UI) patients was reduced from 4.4 ± 3.3 at baseline to 1.8 ± 2.6 after 5 yr in de novo and from 5.4 ± 4.9 to 2.2 ± 3.0 in replacement patients (both p < 0.001). Likewise, the number of voids in urinary frequency patients was reduced compared with baseline (de novo: reduced from 12.6 ± 4.0 [baseline] to 9.6 ± 4.3 [5 yr]; replacements: reduced from 11.5 ± 4.3 [baseline] to 9.2 ± 3.1 [5 yr]; both p < 0.05). Complete continence rates after 5 yr were 44% (25/57) in de novo and 33% (5/15) in replacement UI patients, and 68% (39/57) and 67% (10/15) of UI patients were categorized as therapy responders by showing a >50% improvement in leaks. Disease severity (Urinary Symptom Profile domain 2), Numeric Rating Scale-based symptom bother, and disease-specific QoL (Ditrovie) improved significantly in both groups at all visits (p < 0.001). Adverse events related to device or procedure occurred in 51% (140/274) of patients, with 66% (152/229) of the events being classified as minor (Clavien-Dindo grade I and II). Surgical revisions were reported in 39% (89/229), which include permanent explants in 15% (34/229) of patients. CONCLUSIONS: SOUNDS demonstrates the sustained effectiveness and QoL improvements of SNM in OAB patients after 5 yr in real-world conditions while maintaining an acceptable safety profile consistent with literature. PATIENT SUMMARY: This study confirmed that French overactive bladder patients had a sustained symptom and bother reduction, and improvements in quality of life up to 5 yr after sacral neuromodulation device implantation.

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.

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.

Efficacy of various forms of acupuncture for the treatment of urinary incontinence in women: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Evidence regarding the efficacy of various forms of acupuncture for the treatment of urinary incontinence (UI) in women is outdated and inconclusive. This review aims to determine the efficacy of different forms of acupuncture for the treatment of UI in women. METHODS: Multiple databases were searched from inception to June 2020. Randomized controlled trials that compared various forms of acupuncture to control were included. RESULTS: Ten trials were included in this review. The pooled analysis demonstrated that an increased proportion of women with stress UI (SUI) reported fewer UI episodes (1.73 [95% CI 1.46, 2.04]; p < 0.00001) in the electroacupuncture group than in the sham group. The meta-analysis also revealed a significantly increased number of women who reported the complete cure of SUI in the electroacupuncture combined with pelvic floor muscle training group than in the medication group (RR 2.67 [95% CI 1.51, 4.71]; p = 0.0007). Body and laser acupuncture caused significant decreases in the number of urge accidents (-2.70 [95% CI -4.86, -0.54]; p = 0.01) and the occurrence of urgency symptoms (-3.60[95% CI -5.34, -1.86]; p < 0.0001), compared with sham acupuncture. CONCLUSIONS: Based on the findings of this review, electroacupuncture may be able to improve SUI in women in clinical settings. This review also identified evidence supporting the use of body, electro,- and laser acupuncture for the treatment of urge UI; however, these results were obtained from single studies, and further research remains necessary to confirm the effects of these interventions on the treatment of urge UI in women.

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.

Urgent PC Versus a Generic Posterior Tibial Neurostimulator for Overactive Bladder: A Retrospective Noninferiority Study.

OBJECTIVE: The aim of the study was to determine whether a generic posterior tibial neurostimulator was noninferior to Urgent PC in the treatment of nonneurogenic OAB, urgency urinary incontinence, and mixed urinary incontinence. Secondary outcomes include rates of starting and completing 3 months of maintenance therapy, treatment success after 3 months, and adverse events. METHODS: We performed a retrospective cohort analysis of women whose nonneurogenic OAB, urgency urinary incontinence, or mixed urinary incontinence was treated with either Urgent PC or a generic posterior tibial neurostimulator. Previous research shows a 55% treatment success rate for posterior tibial nerve stimulation (PTNS). To demonstrate noninferiority with a limit of 14% and 80% power, our analysis required 157 patients per group. RESULTS: We included 267 Urgent PC and 234 generic patients and excluded 51 patients from analysis. A per-protocol analysis demonstrated treatment success in 55.3% (121 of 219) of the Urgent PC and 48.6% (85 of 175) of the generic cohort (P = 0.187). An intention-to-treat analysis showed treatment success in 45.3% (121 of 267) of the Urgent PC and 36.3% (85 of 234) of the generic cohort (P = 0.690). There were no significant differences in rates of starting (82.2% vs 78.2%, P = 0.409) or completing (79.9% vs 70.9%, P = 0.129) 3 months of maintenance therapy, treatment success after 3 months (78.5% vs 73.8%, P = 0.485), and adverse events (0.37% vs 0.85%, P = 1.000) in the Urgent PC versus generic group, respectively. CONCLUSIONS: In this cohort of women undergoing PTNS for nonneurogenic OAB, urgency urinary incontinence, or mixed urinary incontinence, the generic neurostimulator demonstrated noninferior rates of treatment success compared with Urgent PC.

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.

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.

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.

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.

The new therapeutic option for female stress and stress-predominant mixed urinary incontinence: Periurethral hypertonic saline (10%) injection.

OBJECTIVES: We aimed to evaluate the safety and efficacy of periurethral hypertonic saline (10% NaCl) injection in the treatment of stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (S-MUI) in women. METHODS: This was a prospective study conducted between January 2014 and April 2018 with 64 women (44 SUI and 21 S-MUI). Patients with SUI and S-MUI were evaluated using the Urinary Distress Inventory 6. Quality of life was evaluated with the Incontinence Quality of Life Scale and lower urinary tract symptoms of the women were evaluated with the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules. Incontinence status and treatment success were assessed via the Stamey incontinence grade and pad test. RESULTS: The subjective success rate was 58.5%, and the objective success rate was 81.5%. The rate of reinjection was 21.5%, and the mean duration of reinjection was 8.92 months (3-19 months). Minor adverse effects were observed in 30.4% of the 79 injections. International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules and Incontinence Quality of Life Scale scores improved remarkably starting from the first month. Urinary Distress Inventory 6 scores in the S-MUI group also improved. CONCLUSIONS: The results indicate that hypertonic saline injection is an effective and safe method in the treatment of SUI and S-MUI. Since hypertonic saline is a much cheaper and more accessible substance compared to bulking agents, it seems to be a viable alternative for urinary incontinence treatment in women.

Axonics® system for treatment of overactive bladder syndrome and urinary urgency incontinence.

Introduction: Overactive bladder and urge urinary incontinence affect millions of women and men and results in billions of dollars in health-care expenses. First- and second-line therapy includes behavioral modifications and/or pharmacotherapies however, many patients' symptoms remain or progress on these treatments. There has been concern regarding the detrimental side effects of the most widely prescribed medications for these bladder symptom management.Areas covered: As a result, there has been increased interest in continuous sacral neuromodulation, an FDA approved therapy for refractory urinary urgency and urge urinary incontinence. In this article, we specifically review current research on the efficacy and patient/provider satisfaction and safety profile of the Axonics® System. In addition, we address the current state of sacral neuromodulation and potential future direction and applicability.Expert opinion: The Axonics® system is a safe effective device for the treatment of overactive bladder and urinary urge incontinence. Additionally, it affords patient's the convenience of a rechargeable, compact, MRI safe system. It should be noted that the rechargeable system, while allowing for approximately 15 years of battery and lead life, may have its challenges in terms of charge burden. Furthermore, this system is easily adapted for experienced implanters of sacral neuromodulating devices.

Twelve-month Durability of a Fully-implanted, Nickel-sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence: A Single-Arm, Prospective Study.

OBJECTIVES: To evaluate the safety and efficacy of the eCoin - a nickel-sized, primary battery-powered, neuromodulation device for the treatment of urgency urinary incontinence which is implanted in the lower leg in a 20-minute procedure under local anesthesia. A feasibility clinical trial was conducted and the results after 1 year of treatment with the eCoin are presented. METHODS: A total of 46 participants with refractory urgency urinary incontinence were included in this prospective, single-arm, open-label study. This study was conducted at 7 sites in the United States and New Zealand. Participants in this study were implanted with the eCoin in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 3, 6, and 12 months' post-activation, were compared to baseline values. RESULTS: Responders were defined as those who had a ≥50% reduction in reported episodes of urgency urinary incontinence. At 12 months', 65% of participants were considered responders with 26% of participants achieving complete continence. The median number of urgency urinary incontinence episodes per day decreased from 4.2 at baseline to 1.7 at 12 months'. Seventy percent of participants reported feeling "better", "much better", or "very much better" on the Likert 7-point maximum scale. One participant experienced a related serious adverse event. CONCLUSION: The eCoin is a safe and effective treatment for urgency urinary incontinence associated with overactive bladder syndrome, with significant reduction or complete resolution of symptoms and no significant safety concerns.

Pivotal Study of Leadless Tibial Nerve Stimulation with eCoin® for Urgency Urinary Incontinence: An Open-Label, Single Arm Trial.

PURPOSE: A novel leadless tibial nerve stimulator provides a primary battery-powered, coin-sized, minimally invasive option to deliver automatic low-duty cycle stimulation for overactive bladder syndrome therapy. A pivotal trial was conducted to evaluate the safety and efficacy of this investigational device, eCoin®, for treating refractory urgency urinary incontinence. MATERIALS AND METHODS: This was a prospective, open-label, single arm trial carried out at 15 U.S. medical centers involving 137 subjects with refractory urgency urinary incontinence. After implantation in the lower leg above the fascia over the tibial nerve, eCoin delivered automated stimulation sessions for the duration of the study. The primary efficacy measure was the proportion of subjects who achieved a 50% or greater reduction from baseline in urgency urinary incontinence episodes after 48 weeks of therapy. The primary safety measure was device-related adverse events at the same time point. RESULTS: Of 137 subjects enrolled, 133 were implanted with eCoin, and 132 were included in the intention-to-treat population. Of those 132 subjects, 98% were female, mean±SD age was 63.9±10.9 years, and baseline daily urgency urinary incontinence episodes were 4.3±3.1. The primary efficacy analysis showed 68% (95% CI: 60%-76%) of subjects experienced at least a 50% reduction in urgency urinary incontinence episodes at 48 weeks post-activation; 16% of implanted subjects experienced device-related events through 52 weeks post-implantation. CONCLUSIONS: eCoin demonstrated clinical benefit for treating overactive bladder syndrome with automatic delivery of an intermittent low-duty cycle and implanted with a minimally invasive, brief procedure.

A prospective, multicenter, international study to explore the effect of three different amplitude settings in female subjects with urinary urge incontinence receiving interstim therapy.

AIMS: The aim of this study is to evaluate the effect of sub-sensory amplitude settings of sacral neuromodulation therapy on overactive bladder symptoms in subjects with urinary urge incontinence. METHODS: Subjects who qualified for a neurostimulator device implant were randomized to one of three amplitude settings (50% of sensory threshold [ST], 80% of ST, and ST). Subjects completed urinary voiding diaries (3-day), International consultation on incontinence modular questionnaire-overactive bladder symptoms quality of life questionnaire, and patient global impression of improvement (PGI-I) to assess change in voiding symptoms and quality of life (QoL) from baseline through 12 weeks. RESULTS: Forty-eight subjects had a successful test stimulation, 46 were implanted with a neurostimulator device and 43 completed the 12-week follow-up visit. The change from baseline to 12 weeks is -3.0 urinary incontinence (UI) episodes/day (95% confidence interval [CI]: -4.4 to -1.7) for the 50% of sensory threshold group, -2.9 UI episodes/day (95% CI: -4.7 to -1.2) for 80% of sensory threshold group, and -3.6 UI episodes/day (95% CI: -5.2 to -1.9) for the sensory threshold group. In each randomized group, improvements were observed in health-related QoL, its subscales, and symptom interference. Subjects across all three randomization groups reported on the PGI-I that their bladder condition was better at 12 weeks compared to before they were treated with InterStim therapy. CONCLUSION: These findings provide insights into possible advancements in the postimplantation phase of therapy with potential for improved patient comfort and increased device longevity.

Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system.

AIMS: Sacral neuromodulation (SNM) is a guideline-recommended treatment with proven therapeutic benefit for urinary urgency incontinence (UUI) patients. The Axonics® System is the first Food and Drug Administration-approved rechargeable SNM system and is designed to deliver therapy for a minimum of 15 years. The ARTISAN-SNM study was designed to evaluate UUI participants treated with the Axonics System. Two-year follow-up results are presented. METHODS: One hundred and twenty-nine UUI participants underwent implantation with the Axonics System. Therapeutic response rate, participant quality of life (QoL), and satisfaction were determined using 3-day voiding diaries, ICIQ-OABqol, and satisfaction questionnaires. Participants were considered responders if they had a 50% or greater reduction in UUI episodes post-treatment. As-treated and Completers analyses are presented. RESULTS: At 2 years, 93% of the participants (n = 121 Completers at 2 years) were therapy responders, of which 82% achieved ≥ 75% reduction in UUI episodes and 37% were dry (100% reduction). Daily UUI episodes reduced from 5.6 ± 0.3 at baseline to 1.0 ± 0.2 at 2 years. Statistically significant improvements in ICIQ-OABqol were reported. All participants were able to recharge their device and 94% of participants reported that the recharging frequency and duration were acceptable. Participant demographics nor condition severity were correlated with clinical outcomes or recharging experience. No unanticipated or serious device-related adverse events occurred. CONCLUSIONS: At 2 years, participants treated with the Axonics System demonstrated sustained safety and efficacy, high levels of satisfaction with therapy and recharging. Participant-related factors were not associated with efficacy or recharging outcomes, indicating the reported results are applicable to a diverse population.

Sacral electroacupuncture as a treatment for urge urinary incontinence: a prospective case series.

OBJECTIVE: To examine the impact of electroacupuncture (EA) at the 'four sacral points' on urge urinary incontinence (UUI). METHODS: Twenty-five patients diagnosed with UUI or urgency-predominant mixed urinary incontinence (MUI) were treated by EA at the 'four sacral points'. EA was performed in the sacrococcygeal region using disposable sterile 0.40-mm-diameter acupuncture needles that were either 100 or 125 mm in length. Treatments were delivered once every other day. Before and after treatment, a questionnaire measuring symptom severity and quality of life associated with UUI was administered. RESULTS: The median total score (interquartile range) from the severity of symptoms and the quality of life questionnaire (Q-score) of the participants was significantly reduced from 12 (7.5, 15) before treatment to 3 (0, 6) after 6 (6, 12) EA treatments. The Q-score of urgency-predominant MUI and UUI was 8 (5, 14.5) and 12.5 (11, 15), respectively, before treatment; after treatment these were reduced to 2 (0, 7.5) and 4.5 (2, 6), respectively. There was no statistically significant difference in the Q-score between urgency-predominant MUI and UUI before and after treatment. Upon treatment completion, seven patients (28%) were 'cured' (improvement rate 100%). Treatments were considered 'markedly effective' (improvement rate 75% to <100%) in four patients (16%), 'effective' (improvement rate 50% to <75%) in eight patients (32%), 'minimally effective' (improvement rate 25% to <50%) in three patients (12%), and 'ineffective' (improvement rate <25%) in three patients (12%). The overall success rate (comprising 'cured', 'markedly effective' and 'effective' categories) was 76%, and no adverse effects associated with acupuncture treatment were reported. CONCLUSION: EA at the 'four sacral points' was associated with statistically significant improvements in UUI.

Botox rechallenge-An additional tool in the management of an incompletely emptying bladder and inadequate overactive symptom control following sacral neuromodulation.

Two female patients aged 70 and 72 with video-urodynamics-confirmed detrusor overactivity and detrusor underactivity (DO-DU) were treated. Patients were refractory to medical therapies and had previously failed intravesical botulinum toxin type A (BoNT-A) at other centers secondary to urinary retention and difficulty with self-catheterization. Placement of an Interstim II device (Medtronic, Minneapolis, Minnesota) for sacral neuromodulation (SNM) as alternative third-line treatment partially improved overactive bladder (OAB) symptoms while significantly improving voiding symptoms. Postvoid residual (PVR) of patients improved from a median of 118 mL (110-125 mL) to 20 mL (18-26 mL) and 213 mL (195-230 mL) to 70 mL (60-73 mL), respectively. Addition of medical therapies post SNM failed to modify OAB symptoms further and a rechallenge with dose-reduced BoNT-A was undertaken.OAB symptoms were significantly improved by addition of BoNT-A, while urinary retention was avoided (median PVR post BoNT-A 38 mL [34-40 mL] and 185 mL [150-205 mL], respectively). Reduction in incontinence pad use as well as resolution of nighttime incontinence in both patients and daytime incontinence in one patient was achieved. DO-DU patients treated by SNM who have improved bladder emptying (PVR <100 mL) but incomplete resolution of OAB symptoms should be trialed on adjunct medical therapies to improve OAB symptoms. If OAB symptoms are still inadequately controlled, consideration of a rechallenge with BoNT-A, particularly with dose reduction, appears to be efficacious and avoids symptomatic retention in this challenging cohort.