Reply to Satoshi Funada, Takashi Yoshioka, and Yan Luo's Letter to the Editor re: Cosimo De Nunzio, Benjamin Brucker, Thomas Bschleipfer, et al. Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men. Eur Urol 2021;79:492-504 [Letter]
Estimation of urinary frequency: does question phrasing matter?
PURPOSE/OBJECTIVE:To evaluate if question phrasing and patient numeracy impact estimation of urinary frequency. MATERIALS AND METHODS/METHODS:We conducted a prospective study looking at reliability of a patient interview in assessing urinary frequency. Prior to completing a voiding diary, patients estimated daytime and nighttime frequency in 3 ways: 1) how many times they urinated 2) how many hours they waited in between urinations 3) how many times they urinated over the course of 4 hours. Numeracy was assessed using the Lipkus Numeracy Scale. RESULTS:Seventy-one patients completed the study. Correlation of estimates from questions 1, 2 and 3 to the diary were not statistically different. Prediction of nighttime frequency was better than daytime for all questions (correlation coefficients 0.751, 0.754 and 0.670 vs 0.596, 0.575, and 0.460). When compared to the diary, Question 1 underestimated (8.5 vs 9.7, p=0.014) while Question 2 overestimated (11.8 vs 9.7, p=0.027) recorded voids on a diary. All questions overpredicted nighttime frequency with 2.6, 2.9 and 3.9 predicted vs 1.6 recorded voids (p <0.001). Although not statistically significant, for each question, the predicted frequency of numerate patients was more correlated to the diary than those of innumerate patients. CONCLUSIONS:When compared to a voiding diary for daytime urinary frequency, asking patients how many times they urinated underestimated, and asking patients how many hours they waited between urinations overestimated the number recorded voids. Regardless of phrasing, patients overestimated nighttime urination. Patients in our functional urology population have limited numeracy, which may impact accuracy of urinary frequency estimation.
Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men
CONTEXT/BACKGROUND:The role of overactive bladder (OAB) treatment in women beyond antimuscarinics has been evaluated extensively. Beta-3 agonists, botulinum toxin-A (BTX-A), and nerve stimulation are indicated in these patients. However, data on male patients in this clinical scenario are scarce. OBJECTIVE:The aim of this systematic review was to evaluate the evidence on treatment options beyond antimuscarinics in men with OAB. EVIDENCE ACQUISITION/METHODS:A search of PubMed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases was performed for relevant articles published between January 2000 and October 2020, using the following Medical Subject Headings: "male/man," "LUTS," "overactive bladder," "storage symptoms," "urgency," "nocturia," "incontinence," "beta-3 agonist," "PDE-5 inhibitors," "botulinum toxin," "sacral nerve stimulation/neurostimulation," "percutaneous/transcutaneous tibial nerve stimulation," "PTENS," and "combination therapy." Evidence acquisition was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PROSPERO registration number is CRD42020201223. EVIDENCE SYNTHESIS/RESULTS:-blocker tamsulosin improved the mean number of micturitions per day (-0.27, 95% CI: -0.46 to -0.09, pâ€‰<â€‰ 0.05), urgency episodes (-0.50, 95% CI: -0.77 to -0.22, pâ€‰<â€‰ 0.05), total OAB symptom score (-0.66, 95% CI: -1.00 to -0.38, pâ€‰<â€‰ 0.05), and mean volume voided (+10.76 ml, 95% CI: 4.87-16.64, pâ€‰<â€‰ 0.05). MIRA treatment is well tolerated in men. Other pharmacological treatment options, such as phosphodiesterase-5 (PDE-5) inhibitors, should be considered investigational. BTX-A seems to be effective as third-line treatment in male OAB patients. A higher rate of intermittent self-catheterization (5-42%) is observed in male than in female patients. Data on nerve stimulation are scarce. CONCLUSIONS:MIRA has the most robust data in terms of safety and efficacy in this patient population. Preliminary data in men suggest that BTX-A is indicated as an interventional treatment. Evidence for PDE-5 inhibitors and nerve stimulation is too limited to provide recommendations. Future studies in this population should aim to better define the best treatment sequence and to identify predictors for treatment response and failure, to determine a therapeutic approach tailored to patients' characteristics. PATIENT SUMMARY/UNASSIGNED:Overactive bladder is highly prevalent in men. Mirabegron 50â€‰mg is the treatment option supported by the highest level of evidence when antimuscarinics failed. Botulinum toxin A injections seems to be an effective treatment as interventional option. Roles of nerve stimulation and phosphodiesterase inhibitors in male OAB patients are still to be defined.
The Effect of Symptomatic Stress Urinary Incontinence on Catheterization Rates After Intradetrusor OnabotulinumtoxinA Injections
OBJECTIVES/OBJECTIVE:To determine whether catheterization rates after intradetrusor onabotulinumtoxinA injection for nonneurogenic overactive bladder and urgency incontinence differ between women with urgency urinary incontinence only and women with urgency-predominant mixed urinary incontinence. METHODS:This was a retrospective cohort study of patients that underwent intradetrusor onabotulinumtoxinA injection of 100 U for nonneurogenic urgency urinary incontinence. The primary outcome was the difference in catheterization rates between women with urgency urinary incontinence alone compared with women with urgency-predominant mixed urinary incontinence. Descriptive statistics and multivariate logistic regression analysis were performed. RESULTS:Of the 177 women included in the final analysis, 105 had urgency urinary incontinence and 72 had urgency-predominant mixed urinary incontinence. The overall catheterization rate after onabotulinumtoxinA injection was 11.3%, with significantly fewer women with mixed urinary incontinence requiring catheterization when compared with women with urgency urinary incontinence alone (4.2% vs 16.2%; P = 0.03), despite an older population (P = 0.02). Patient-reported improvement (P = 0.37) and decision to continue onabotulinumtoxinA treatments (P = 0.89) were similar between groups. Multivariate logistic regression analysis revealed that women with mixed urinary incontinence had significantly lower odds of requiring catheterization after onabotulinumtoxinA injections than women with urgency urinary incontinence alone (odds ratio, 0.16; 95% confidence interval, 0.04-0.67; P = 0.01). CONCLUSIONS:Findings suggest that the presence of symptomatic stress urinary incontinence is associated with lower rates of catheterization after intradetrusor onabotulinumtoxinA, but does not compromise efficacy of treatment for urgency-predominant mixed urinary incontinence.
The impact of concomitant mid-urethral sling surgery on patients undergoing vaginal prolapse repair
INTRODUCTION AND HYPOTHESIS/OBJECTIVE:The aim of this study was to assess whether mid-urethral sling (MUS) placement at the time of vaginal prolapse repair compared to vaginal prolapse repair alone is associated with an increase in 30-day postoperative complications. METHODS:Using the American College of Surgeons National Surgical Quality Improvement Database, Current Procedural Terminology codes were used to identify cases of vaginal prolapse repair with and without concomitant MUS from 2012 to 2017. Student's t-test and chi-square test were used to compare differences between the groups. RESULTS:A total of 1469 cases of vaginal prolapse repair with sling were compared to 4566 cases without sling. There was no difference between prolapse repair with sling compared to without sling in mean hospital length of stay (LOS) (1.42 versus 1.32Â days, pÂ =â€‰0.65), postoperative urinary tract infection (UTI) (6.1% versus 5.8%, pÂ =â€‰0.670), perioperative blood transfusion (1.1% versus 1.2%, pÂ =â€‰0.673), readmission (2.7% versus 2.6%, pÂ =â€‰0.884) and postoperative wound infection (0.5% versus 0.7%, pÂ =â€‰0.51). There was a higher rate of reoperation (2.2% versus 1.5%, pÂ =â€‰0.049) and venous thromboembolism (VTE) (0.4% versus 0.1%, pÂ =â€‰0.030) in patients undergoing concomitant MUS compared to those undergoing prolapse repair alone. CONCLUSIONS:Compared to prolapse repair alone, the addition of a sling did not increase hospital LOS, UTI, perioperative blood transfusions, readmission or postoperative wound infections. However, concomitant sling was found to be associated with a higher risk of reoperation and VTE.
Persistence in percutaneous tibial nerve stimulation treatment for overactive bladder syndrome is best predicted by patient global impression of improvement rather than symptom-specific improvement
OBJECTIVES/OBJECTIVE:To evaluate whether progression to maintenance percutaneous tibial nerve stimulation (PTNS) was related to perceived global impression of improvement (PGII) rather than symptom-specific improvement in patient with overactive bladder (OAB). We hypothesize that PGII will predict continuation of PTNS long-term. METHODS:This prospective observational study included 90 patients with OAB that initiated PTNS. The PGII and overactive bladder short-form questionnaires (OABq-SF) were used to assess bladder symptom severity and improvement. Those that completed the 12-week induction phase were offered to continue PTNS monthly maintenance or pursue other options. The primary outcome was difference in PGII score between those pursuing maintenance therapy versus other options. Descriptive statistics and mixed effect modeling analysis were employed. RESULTS:Seventy patients (78%) completed 12 weeks of PTNS. The majority of completers pursued monthly maintenance (p<0.01) and had significantly lower median PGII scores compared with those who sought alternatives (p<0.01), while OABq-SF scores did not differ significantly (p=0.65). Patients that pursued monthly PTNS maintenance had lower body mass index than those who chose alternative therapies (p<0.01). Only 19% continued PTNS therapy for at least 1 year. CONCLUSIONS:More patients pursued PTNS monthly maintenance over any other therapy, and this was significantly associated with lower PGII scores. Global improvement, and not symptom-specific response, predicts long-term PTNS maintenance. No symptom-specific predictors were identified in those who pursued maintenance over other options. One-year continuation rates are low.
Impact of urodymamics on diagnosis and treatment plans for the overactive bladder patient [Meeting Abstract]
Introduction: Urodynamics (UDS) is the study of urine transport, storage, and evacuation and is the gold standard in assessment of bladder function. Per AUA guidelines, UDS are not to be used in the initial workup of the uncomplicated patient with OAB, however their role in more complex patients remains uncertain. The primary aim of this study is to assess the impact of UDS on diagnosis and treatment plans of complex patients with OAB.
Method(s): Patients undergoing workup for OAB between 2016 and 2018 were prospectively enrolled and completed a voiding diary and UDS. Physicians first provided a diagnosis and treatment plan based on patient history, clinical data and voiding diary alone. The patients then underwent UDS and the physician provided a diagnosis and treatment plan after reviewing the additional testing. The impact of UDS on diagnosis and treatment plan were analyzed.
Result(s): 26 patients underwent evaluation with voiding diary and UDS with prospective documentation of diagnosis and treatment plan. All patients had previously trialed oral OAB medications10 (38.4%), complained of mixed incontinence 11 (42.3%), or were considering third line therapy 14 (53.8%). After UDS were performed, 13 (50%) had a modification in diagnosis and 11 (42.3%) had a change in treatment plan. The most common change in diagnosis was observation of voiding phase dysfunction in 4 (15.4%). Treatment plans changed for 6 patients with mixed incontinence primarily by elucidating severity of stress vs urgency incontinence when it was difficult to determine from patient report and available clinical data. Plans also changed for 1 patient found to have underactive bladder and 2 with bladder outlet obstruction. 9 (34.6%) patients went on to third line therapy.
Conclusion(s): UDS done for patients with complex OAB symptoms led to modification in patient diagnosis in 50% of patients and change in treatment plan in 42.3%. Change to diagnosis and management plan may reflect the utility of UDS especially in complicated patients (ie mixed incontinence) or who have failed second line therapies
Incomplete bladder emptying and urinary tract infections after onabotulinumtoxina injection for overactive bladder in men and women: Multi-institutional collaboration from the sufu research network [Meeting Abstract]
Introduction: OnabotulinumtoxinA (BTX) is an effective third-line therapy for overactive bladder (OAB), however the potential for adverse events may prevent patients from initiating therapy. The objective of this study is to report rates of incomplete emptying and urinary tract infection (UTI) in men and women undergoing BTX for OAB and to identify potential risk factors for these adverse events.
Method(s): Eleven clinical sites performed an IRBapproved retrospective study of adult women and men undergoing first-time BTX injection (100 units) for nonneurogenic OAB in 2016. Exclusions included: post void residual (PVR) >150ml, prior BTX, pelvic radiation, or catheterization. Clinical data was collected 6 months before the index procedure. Incomplete emptying was defined as the need for clean intermittent catheterization (CIC) or a post-procedure PVR>=300 ml without the need for CIC within 6 months of the BTX. UTI was defined as symptoms combined with either positive culture or urinalysis or empiric treatment up to 6 months after BTX. We compared rates of incomplete emptying and UTI between sex and individually by sex, using univariate and multivariable models.
Result(s): 278 patients (48 men and 230 women) met inclusion criteria. Mean age was 65.5 (range 24-95), 13% had history of prior UTI. Within the 6 months after treatment, 35% of men and 17% of women had incomplete emptying and 17% of men and 24% of women had UTI. Outcomes of CIC, PVR>=300mL, incomplete emptying, and UTI by sex are summarized in Table 1. In multivariable analysis, men were associated with 2.4 (95% CI 1.04-5.49) higher odds of incomplete emptying than women. For UTI, 8 (17%) men and 54 (23.5%) women had >=1 UTI (p=0.30), the majority of which occurred within the first month following injection. The strongest predictor of UTI was history of prior UTI compared to those without (OR 4.2 [95% CI 1.7-10.3]).
Conclusion(s): In this multicenter retrospective study rates of incomplete emptying and UTI were higher than many previously published studies. Men were at particular risk for incomplete emptying. Prior UTI was the primary risk factor for post-procedure UTI. Other clinically significant predictive factors were not identified in this multicenter cohort
Barriers to completion of voiding diary in patient with overactive bladder [Meeting Abstract]
Introduction: Overactive bladder (OAB) affects 10-19% of adults, strongly influencing quality of life. Voiding diaries may provide valuable information on the OAB patient, identifying modifiable behavior factors and the timing and severity of symptoms that can help guide treatment. The primary aim of this prospective cohort study is to report the percent of patients completing a diary, and secondary aim is to assess what factors may predict completion.
Method(s): 93 patients undergoing workup for OAB between 2016 and 2020 were enrolled and asked to complete a three-day voiding diary. They were provided standard written and oral instructions, in addition to urine collection device and a printed diary template. Completed voiding diary, OAB-q questionnaire, and demographic factors were collected and analyzed.
Result(s): Of the 93 patients enrolled, 61 (65.6%) completed at least one day of a voiding diary. Two of these patients (3.3%) returned diaries that could not be interpreted. There was no difference in OAB-q score for those completing diary and those who did not (76.7 vs 79, p=0.86). In addition, no significant differences were seen in age, BMI, ethnicity, gender or prior surgeries between those who did and did not complete the diary.
Conclusion(s): Voiding diaries are used in the workup of OAB to quantify symptoms and determine their cause. We found a completion rate of 65.6% among patients with bothersome OAB. No demographic differences were observed between those who did and did not complete a diary. Further study of barriers to completion could aid in higher capture rates and improved diagnostic evaluation of the OAB patient
Selectivity and maximum response of vibegron and mirabegron for beta3-adrenergic receptors [Meeting Abstract]
Introduction: The introduction of beta3-adrenergic receptor (AR) agonists has improved management of overactive bladder (OAB) by providing efficacious treatment of symptoms while minimizing adverse events associated with anticholinergics. However, beta-ARs are also found outside the bladder (eg, beta1-ARs on cardiomyocytes), which could lead to off-target activity. Results in humans indicate that mirabegron, a beta3-AR agonist approved for the treatment of OAB, stimulates beta1-ARs at a supratherapeutic dose. Further, onset of action of mirabegron 25 mg may take up to 8 weeks, potentially necessitating dose titration upward. Vibegron is a novel, selective beta3-AR agonist with a rapid, 2-week onset of efficacy at a single dose. Here we assessed the potency and maximal effect of vibegron and mirabegron for beta3-ARs and the selectivity for each beta-AR.
Method(s): Functional cellular assays for vibegron and mirabegron activity were performed using Chinese hamster ovary (CHO) cells expressing beta1-or beta2-ARs and human embryonic kidney (HEK) 293 cells expressing beta3-ARs. Cells were incubated with vibegron, mirabegron, or the appropriate control (isoproterenol for beta1 and beta3, procaterol for beta2). Responses were quantified using homogeneous time-resolved fluorescence of cyclic adenosine monophosphate. Half-maximal effective concentration (EC50) and maximum response (Emax) values were determined by nonlinear least-squares regression analysis.
Result(s): Treatment of HEK293 cells with vibegron or mirabegron resulted in concentration-dependent responses at beta3-ARs (Figure). Mean (SEM) EC50 values at the beta3-AR were 2.13 (0.25) nM for vibegron and 10.0 (0.56) nM for mirabegron. At a concentration of 10 muM, beta3-adrenergic activity relative to isoproterenol was 104% for vibegron and 88% for mirabegron. In CHO cells, beta1-adrenergic activity was 0% and 3% for vibegron and mirabegron, respectively, and beta2-adrenergic activity was 2% and 15%. Emax for vibegron and mirabegron at the beta3-AR was estimated to be 99.2% and 80.4%, respectively.
Conclusion(s): Vibegron showed no measurable beta1 and low beta2 activity compared with mirabegron, which showed measurable beta1 and some beta2 activity. Both vibegron and mirabegron showed significant selectivity at beta3-ARs as expected; however, vibegron demonstrated near-exclusive beta3 activity and was approximately 5 times more potent than mirabegron at activating beta3-ARs. Vibegron also showed higher maximum beta3 response, approximating 100%