A prospective study to assess the effectiveness and safety of the BlueWind System in the treatment of patients diagnosed with urgency urinary incontinence.

BACKGROUND: Overactive bladder (OAB) affects one in six adults in Europe and the United States and impairs the quality of life of millions of individuals worldwide. When conservative management fails, third-line treatments including tibial neuromodulation (TNM) is often pursued. TNM has traditionally been accomplished percutaneously in clinic. OBJECTIVE: A minimally invasive implantable device activated by a battery-operated external wearable unit has been developed for the treatment of urgency urinary incontinence (UUI), mitigating the burden of frequent clinic visits and more invasive therapies that are currently commercially available. METHODS: A prospective, multicenter, single-arm, open-label, pivotal study evaluated the safety and effectiveness of the device in adult females with UUI (i.e., wet OAB) (BlueWind Implantable Tibial Neuromodulation [iTNM] system; IDE number #G200013; NCT03596671). Results with the device were previously published under the name RENOVA iStim, which has been since renamed as the Revi™ System. Approximately 1-month post-implantation of the device, participants delivered therapy at their convenience and completed a 7-day voiding diary before visits 6- and 12-months post-treatment initiation. The primary efficacy and safety endpoints were the proportion of responders to therapy ( ≥ 50% improvement on average number of urgency-related incontinence episodes) and incidence of adverse events from implantation to 12-month post-activation. RESULTS: A total of 151 participants, mean age 58.8 (SD: 12.5), were implanted; 144 and 140 completed the 6- and 12-month visits, respectively. The participants demonstrated mean baseline of 4.8 UUI/day (SD 2.9) and 10 voids/day (SD 3.3). Six and 12-months post-activation, 76.4% and 78.4% of participants, respectively, were responders to therapy in an intent-to-treat analysis. Of the 139 participants with completed 12-month diaries, 82% were responders, 50% were classified as "dry" (on at least 3 consecutive diary days), and 93.5% of participants reported that their symptoms improved. No implanted participant experienced an SAE related to the procedure or device. CONCLUSIONS: iTNM, delivered and powered by a patient-controlled external wearable communicating with an implant, demonstrated clinically meaningful and statistically significant improvement in UUI symptoms and a high safety profile. This therapy highlights the value of patient-centric therapy for the treatment of UUI.

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

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

Complications of ethylene vinyl alcohol copolymer as an intraurethral bulking agent in men with stress urinary incontinence.

OBJECTIVES: To report the short-term safety and efficacy of ethylene vinyl alcohol (EVA) copolymer (Tegress; C.R. Bard, Inc., Covington, GA) in the off-label treatment of male stress urinary incontinence. METHODS: We reviewed the charts of all adult male patients who received EVA copolymer between 2005 and 2006 for demographics, physical examination findings, urodynamic findings, outcomes, and complications. RESULTS: A total of 17 of 18 men completed follow-up after receiving EVA during this time period. With an average of 1.4 injection sessions, 58.8% of patients experienced a complication related to the procedure, with 41.1% of these complications being urethral erosion of the material and 22% experiencing severe pain on injection. Subjective improvement of at least 50% was reported by 41.1% of patients. The mean follow-up period was 4.2 months. CONCLUSIONS: Intraurethral bulking agents are meant to be a minimally invasive procedure with lower complication rates than alternatives such as the artificial urinary sphincter and male sling. The off-label use of EVA in men in this case series resulted in a significant complication rate. Urethral erosion was the most common complication causing dysuria, precluding further bulking in others, and resulting in loss of benefit with passage of material. In addition, EVA used in men may be less efficacious than the Food and Drug Administration data reported in women, especially with prior injectable therapy. In December 2006, EVA was voluntarily taken off the marketplace by CR Bard owing to reports from clinicians.

Current trends in the evaluation and management of female urinary incontinence.

Despite its common occurrence and often seemingly obvious causes, female urinary incontinence requires a thorough and thoughtful evaluation for its proper diagnosis and treatment. With rare exceptions, urinary incontinence is the result of failure of the sphincter mechanism to resist bladder pressures encountered during daily activities. This may be the result of sphincter failure, overactivity of the bladder detrusor muscle or both. In uncomplicated cases, the diagnosis is usually based on an evaluation in the office. Urodynamic and cystoscopic study may be helpful in complex, resistant and recurring cases of urinary incontinence of any cause. Most cases of incontinence may be classified as stress, urge or mixed urinary incontinence. Treatment of stress urinary incontinence focuses on supplementing the urethral continence mechanisms, particularly the urethral supports and periurethral striated muscle function. The current paradigm for the treatment of urge incontinence centres on pharmacologic therapy, primarily by correcting detrusor overactivity with antimuscarinic drugs. Other therapies aimed at altering sensorimotor function may be used in resistant cases. The treatment of mixed urinary incontinence requires consideration of the contribution of each of its components. With proper diagnosis, effective treatment is possible for most patients.

Bladder outlet obstruction in women: iatrogenic, anatomic, and neurogenic.

This paper outlines the presentation, evaluation, and management of bladder outlet obstruction (BOO) in women as it relates to iatrogenic, anatomic, and neurogenic causes. Attention is given to the different diagnostic criteria used by various authors in their case series and studies. The lack of standardization with regard to the diagnosis of BOO in women emphasizes the fact that BOO is often a clinical diagnosis that is made by taking into account the history, physical examination, imaging of the lower urinary tract, and urodynamic pressure-flow parameters. Individual obstructive conditions including urethral stricture, postsurgical obstruction, primary bladder neck obstruction, pelvic organ prolapse, and neurogenic causes are addressed briefly.

The emergence of new drugs for overactive bladder.

Overactive bladder is a common and distressing problem. Standard therapy is directed towards modifying the detrusor motor sensitivity and response via anticholinergic medication. Currently available medications are reviewed and alternative targets for treatment are presented.

Oxybutynin: an overview of the available formulations.

Overactive bladder (OAB) is a common problem presented to by physicians. Standard treatment with antimuscarinic medication is directed at suppressing involuntary detrusor contractions by blocking the binding of acetylcholine to muscarinic receptors in the bladder. Oxybutynin chloride is the first of several antimuscarinic medications to be marketed for OAB. Although efficacious for treating OAB symptoms, the side effects and suboptimal dosing regimen decrease its utility. To improve patient compliance and tolerability, alternative delivery systems for oxybutynin have subsequently been developed and include a once-daily formulation and a transdermal system. The currently available formulations of oxybutynin are the subject of this review.

Female neurogenic vesicourethral dysfunction: evaluation and management.

This paper outlines the evaluation and management of neurogenic vesicourethral dysfunction (NVUD). The anatomy and neurophysiology involved with lower urinary tract functions are reviewed. Multiple sclerosis, diabetes, lumbar disc prolapse, and Parkinson's disease are specifically addressed. Proper evaluation of patients suspected of having NVUD, which is fundamental to making an accurate diagnosis, is discussed. This is followed by options for initiating individualized management plans that focus on protecting and preserving renal function, in addition to relieving the symptoms of NVUD.