Faculty Bibliography

CONTEXT/BACKGROUND:Pharmacological treatment is a cornerstone in the management of patients with lower urinary tract symptoms (LUTS). OBJECTIVE:To review emerging evidence in the medical treatment of LUTS. EVIDENCE ACQUISITION/METHODS:An Embase/Pubmed-based literature search was conducted in December 2017, screening for randomized controlled trials (RCTs), prospective and retrospective series, animal model studies, and reviews on medical treatment of LUTS. EVIDENCE SYNTHESIS/RESULTS:receptor agonist, has recently completed a large phase 3 trial in male patients with nocturia. Other phase 3 trials are ongoing in bladder pain syndrome (AQX 11-25, a SHIP-1 activator) and in neurogenic detrusor overactivity (mirabegron and abobotulinum toxin A). CONCLUSIONS:Medical treatment of LUTS is a very active research field with recently approved drugs for nocturia (desmopressin acetate nasal spray/orally disintegrated tablet) and numerous emerging drugs currently investigated in OAB, LUTS/benign prostatic hyperplasia, nocturia, bladder pain syndrome, and neurogenic detrusor overactivity. PATIENT SUMMARY/UNASSIGNED:Medical treatment of lower urinary tract symptoms is a very active research field with recently approved drugs for nocturia (desmopressin acetate nasal spray/orally disintegrated tablet) and numerous emerging drugs in overactive bladder, nocturia, neurogenic detrusor overactivity, bladder pain syndrome, or benign prostatic hyperplasia.

The use of botulinum toxin A (BTX-A) has revolutionized the treatment of neurogenic lower urinary tract dysfunction (NLUTD) over the past three decades. Initially, it was used as a sphincteric injection for detrusor sphincter dyssynergia but now is used mostly as intradetrusor injection to treat neurogenic detrusor overactivity (NDO). Its use is supported by high-level-of-evidence studies and it has become the gold-standard treatment for patients with NDO refractory to anticholinergics. Several novelties have emerged in the use of BTX-A in neurourology over the past few years. Although onabotulinumtoxinA (BOTOX^®, Allergan, Inc., Irvine, CA) remains the only BTX-A for which use is supported by large, multicenter, randomized, controlled trials (RCT), and is therefore the only one to be licensed in the United States and Europe, a second BTX-A, abobotulinumtoxinA (Dysport^®, Ipsen Biopharmaceuticals, Basking Ridge, NJ), is also supported by high-level-of-evidence studies. Other innovations in the use of BTX-A in neurourology during the past few years include the BTX switch (from abobotulinumtoxinA to onabotulinumtoxinA or the opposite) as a rescue option for primary or secondary failures of intradetrusor BTX-A injection and refinements in intradetrusor injection techniques (number of injection sites, injection into the trigone). There is also a growing interest in long-term failure of BTX-A for NDO and their management, and a possible new indication for urethral sphincter injections.

Nocturia is a condition that has a tremendous impact on a patient's health and wellbeing. Getting up 2 or more times a night to urinate fragments sleep, preventing deep, restorative stages of the sleep cycle. With safer and more effective therapies, nocturia is a treatable condition that no longer should be overlooked. The simplicity of directly targeting the cause of nocturia, the overproduction of urine (ie, nocturnal polyuria) should be considered. Noctivaâ„¢ (desmopressin acetate) nasal spray (Avadel Pharmaceuticals plc, Chesterfield, MO), a novel FDA-approved microdose desmopressin nasal spray, can reduce nighttime urine production and potentially mitigate the potential harm of nocturia.

OBJECTIVES: To compare the efficacy of onabotulinumtoxinA, mirabegron, and anticholinergics in adults with idiopathic overactive bladder (OAB) using network meta-analysis (NMA). SUBJECTS AND METHODS: Information sources were searched for randomized blinded controlled trials, of at least 2 weeks duration, comparing any dose of onabotulinumtoxinA, eligible oral/transdermal anticholinergics, or mirabegron, with each other or placebo, in adults with OAB. Bayesian random-effects models were used to synthesize the results at week 12: NMA for responder analyses and network meta-regression (NMR) for change from baseline analyses. The NMR was used to adjust for differences in baseline severity between studies. Sensitivity analysis, excluding studies considered to be at a high risk of methodological bias, was conducted. RESULTS: 56 randomized trials were included in the networks. For each outcome, results are reported for all licensed treatment doses. For each NMR, results are based on patients with an average number of episodes of the outcome at baseline. After 12 weeks, all treatments are more efficacious than placebo. Patients who received onabotulinumtoxinA (100U) had, on average, the greatest reductions in urinary incontinence episodes (UIE), urgency, and micturition frequency, and the highest odds of achieving decreases of 100% and >/=50% in the daily number of UIE. When comparing onabotulinumtoxinA with other pharmacotherapies, mean differences favoured onabotulinumtoxinA 100U over all comparators for UIE and urgency (credible intervals excluded zero) and all but two of the comparators for micturition frequency. OnabotulinumtoxinA 100U was also associated with higher odds of achieving a 100% and >/=50% decrease in daily UIE than most other licensed treatments in the network. The exclusion of studies with a high risk of bias had little impact on the conclusions. CONCLUSION: The results indicate that, after 12 weeks, onabotulinumtoxinA 100U provides greater relief of OAB symptoms compared with most other licensed doses of other pharmacotherapies in the network

Purpose: We sought to assess for impact on management trends in new patients presenting to our institution with stress urinary incontinence (SUI) following the release of the FDA Health Notification in July 2011 for vaginal mesh. Materials and methods: Chart analysis was performed on patients assigned a primary International Classification of Diseases (ICD-9) diagnosis code of 625.6 for SUI at initial consultation by two providers at our institution between June 1, 2010 and November 30, 2014. Rates of treatment and types of procedures performed were analyzed: urethral bulking, mesh sling, or pubovaginal sling. Results: A total of 333 new patients were identified with an increasing trend over time. One hundred and twenty-three patients underwent 153 procedures for stress incontinence. The mean proportion that had a procedure per six-month period was 37%, with decreasing proportions over time. Initially all procedures were midurethral mesh slings, with a decline at the time of and after the notification, and a temporary increase in bulking procedures. Subsequently, there was a rise again in sling placement, namely with an increase in pubovaginal slings. Of the 20 pubovaginal slings placed, 13 were placed in patients who had a prior anti-incontinence surgery (eight for sling failure, vaginal mesh, or fixed urethra, and two in patients with mesh extrusion/erosion). Seven were performed in patients who had never had prior surgery (two for very high-grade incontinence, two with urethral diverticulectomy, and three in patients who expressed concern about mesh). Conclusions: Although there were an increasing number of patients seen for management of SUI over time, there was a progressive decrease in the proportion of patients having anti-incontinence procedures after release of the FDA notification. There was an overall decrease in the use of mesh slings and an increase in bulking, and more notably, placement of pubovaginal slings.

Introduction: The potential need for clean intermittent catheterization (CIC) is known to increase in overactive bladder (OAB) patients after onabotulinumtoxinA treatment. We determined the risk of CIC and assessed the efficacy and quality of life (QoL) outcomes after treatment with onabotulinumtoxinA in different age groups by performing a post-hoc analysis of a large cohort of OAB patients. Methods: Data from two onabotulinumtoxinA randomized, placebo-controlled, phase 3 trials and a post-marketing study were pooled for analysis (N=1177). Patients treated with onabotulinumtoxinA 100U in treatment 1 and placebo patients who received open-label onabotulinumtoxinA in treatment 2 were grouped by age: <40 (n=90), 40-49 (n=156), 50-59 (n=263), 60-69 (n=343), and >=70 (n=325) years. Assessments at week 12 after treatment were: incidence and duration of CIC, mean and percent change from baseline in urinary incontinence (UI) episodes/day, proportions of patients with >=50% UI reduction, a positive response (urinary symptoms 'improved'/'greatly improved') on the treatment benefit scale (TBS), and change from baseline in Kings Health Questionnaire (KHQ) domains of social limitations and role limitations. Adverse events (AEs) were assessed. Results: CIC rates after onabotulinumtoxinA treatment were lowest in the <40 group (1.1%) and increased slightly with age (3.2%, 5.3%, 5.3%, and 7.2% in the 40-49, 50-59, 60-69, and >=70 groups, respectively). Mean CIC duration was three and 44 days in the <40 and 40-49 groups, respectively, and ranged from 78-88 days in the other groups. Mean UI episodes/day at baseline were 3.9, 4.8, 5.2, 5.7, and 6.0 in the <40, 40-49, 50-59, 60-69, and >=70 groups, respectively. A robust treatment response was noted in all groups, including substantial reductions in UI episodes/day (-2.4, -2.6, -3.1, -3.6, and -2.9) and percent change in UI (-60.8%, -50.4%, -62.4%, -64.4%, and -46.8%). High proportions of patients in all groups achieved >=50% UI reduction (range 58.2-71.1%) and had a positive TBS response (range 66.2-73.8%). Improvements from baseline in KHQ domain scores were approximately 3-6 times the minimally important difference. Urinary tract infection was the most common AE in all groups. Conclusions: In this large cohort of onabotulinumtoxinA-treated OAB patients, CIC risk increased slightly with age, but was low in all age groups and accompanied by substantial reductions in UI episodes/day, improvements in QoL, and treatment benefit. The <40 group had the lowest rate of CIC (1.1%), with a duration of three days. OnabotulinumtoxinA was well-tolerated in all age groups

Gynecologic and urologic etiologies are the sources of pelvic pain for many individuals. This article aims to provide a comprehensive review of the various genitourinary sources of pelvic pain. It is important to recognize that although these disorders predominantly affect women, there are various conditions that affect both men and women, and these should be considered in the differential diagnosis of patients presenting with pelvic pain. Providers who encounter patients with pelvic pain should attempt to localize these symptoms and obtain a comprehensive history from the patient to help direct diagnostic evaluation.

Parkinson's disease (PD) and atypical Parkinsonism are the second most common neurodegenerative movement disorders. Lower urinary tract dysfunction is among the most common types of associated autonomic dysfunctions. Differentiating the subtypes of PD is important for symptom management and understanding prognosis, because Lower urinary tract symptoms (LUTS) can evolve differently depending on the primary disease. LUTS are caused by storage and/or voiding dysfunctions. Urodynamics is a key investigative tool. The complex pathophysiology of this bladder dysfunction is not responsive to levodopa, and add-on therapy is necessary. Newer interventions hold promise as therapy to improve bladder dysfunction.

AIM: The Actionable Bladder Symptom and Screening Tool (ABSST) is used to identify multiple sclerosis (MS) patients in possible need of evaluation for urinary symptoms. The primary objective of this study was to identify barriers experienced by MS patients in seeking evaluation for urinary symptoms. We also assessed the utility of ABSST tool in identifying patients that will follow up with urologic evaluation. METHODS: This was a prospective observational study where 100 patients with MS were enrolled from an MS center. Patients completed demographic information, questions to assess barriers to care, a short form of the ABSST, and incontinence questionnaires. An ABSST score >3 met criteria for referral and evaluation. One year after enrollment, follow up calls assessed whether patients had seen a urinary specialist. RESULTS: The most common barriers to seeking care included "Doctor never referred" (16%) and "Doctor never asked" (13%). Thirty-eight percent (n = 8/21) of men stated "Doctor never referred" compared to 10% (n = 8/79) of women (P = 0.002). Twenty-seven patients had an ABSST Score >/=3 and were more interested in seeing a specialist compared to those scoring <3 (88.9%, n = 24/27 vs. 26%, n = 19/73; P = <0.001). After 1 year, 70 patients were reached for follow up. A total of 57.9% (n = 11/19) patients who followed up for evaluation screened positive on the ABSST. CONCLUSIONS: The ABSST is a valuable tool to identify MS patients with urinary symptoms who will likely follow up for genitourinary evaluation. However, other barriers beyond awareness exist and prevent patients from being evaluated.