Faculty Bibliography

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.

INTRODUCTION AND HYPOTHESIS/OBJECTIVE:To evaluate whether the studies contributing to the national treatment guidelines on pelvic organ prolapse adequately represent the racial and/or ethnic makeup of the American population. METHODS:This analysis examines the racial and ethnic makeup of all primary study cohorts contributing to the American College of Obstetricians and Gynecologists/American Urogynecologic Society Practice Bulletin No. 214 on pelvic organ prolapse. References were excluded if they lacked a primary patient population or were from outside the US. Mean proportional representation of racial/ethnic groups was compared to the 2018 United States Census data on race/ethnicity. The representation quotient was also calculated to evaluate for relative representation of each group. Descriptive statistics were used. RESULTS:Of the 110 references, 53 primary studies were included in the final analysis with 30 studies reporting on race/ethnicity. On average, 82% (SD = 15%) of study populations were White, while Blacks, Hispanics, and Asians represented 67% (SD = 7%), 4% (SD = 8%), and < 1% (SD = 1%), respectively, differing significantly from the 2018 US Census (p < 0.01.) The representation quotients for White women was 1.36, demonstrating a 36% overrepresentation, while Black, Hispanic, and Asian women were underrepresented among studies of all evidence levels, with representative quotients of 0.50, 0.23, and 0.09, respectively. CONCLUSIONS:Our study demonstrates a significant underrepresentation of non-White populations in primary cohorts of studies contributing to the ACOG/AUGS Practice Bulletin No. 214 on POP. This analysis reinforces that more efforts are required to include and report on racial and ethnically diverse cohorts to better serve all patients.

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.

Objective: To compare the safety and efficacy of a dermal bovine tissue transvaginal graft, XenformTM (TVG), to traditional native tissue repair (NTR) in women surgically treated for anterior and/or apical pelvic organ prolapse (POP) Methods: This was a prospective, non-randomized, parallel cohort, a multicenter trial where subjects received TVG or NTR. The primary endpoint of the study was to achieve non-inferiority (NI) of transvaginal repair with TVG to NTR at 36 months compared to baseline. Treatment success was based on a composite of objective (leading edge of prolapse at or above the hymen; no POP re-treatment) and subjective (no symptoms of vaginal bulging) outcomes measured at 12, 24, and 36 months. The non-inferiority margin was set at 12%. A propensity score stratification method was applied to achieve balance inpatient and surgeon characteristics between treatment groups. A co-primary outcome was the rate of serious device or serious procedurerelated adverse events (SAE) within 36 months. Secondary endpoints included evaluation of graft-and procedure-related complications between baseline and 36 months Results: The primary outcome, treatment success at 36 months, was 83.6% in TVG and 80.5% in NTR, demonstrating NI (0.2%, 90%CI[-5.6%, 5.9%]) (Table 1). Composite and objective success in apical compartment rate minimally declined with time in both groups (Figure1). The overall rate of SAEs was 5.3% (12/228) vs 2.7% (13/485) in the TVG vs NTR groups, respectively, and TVG was NI to NTR at the preset margin of 12% (2.0%, 90% CI[-0.8%, 4.7%]). Overall AE rates were similar between the TVG and NTR arms: 46.5% (106/228) in TVG subjects and 46.4% (225/485) in NTR subjects. The majority of AEs occurred within the first 6 months following surgery, 77.4% (82/106) for TVG subjects and 67.1% (151/225) for NTR subjects with the most frequently reported AE being de novo voiding dysfunction. There were no reports of graft erosion, and graft exposure rates were low (0.9% [2/228]).
Conclusion(s): Biologic TVG for the treatment of anterior and/or apical vaginal prolapse was as effective as NTR and as safe as NTR with respect to the rate of the serious device-and/or serious procedure-related AEs at 36 months

Objectives: Studies indicate variations exist in surgical route and outcomes for treatment of gynecologic conditions among different races. The aim of this study was to investigate the difference in route of pelvic organ prolapse (POP) surgery and subsequent complications among women of different races and ethnicity in the United States.
Material(s) and Method(s): Data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) was used to estimate surgical route and complication rates. A total of 48,712 patients underwent a POP repair between 2014 and 2018, based on CPT codes. Based on the NSQIP database, patients were grouped by race and Hispanic ethnicity, and the route of POP repair was assessed. Primary outcome was the difference in surgical route (vaginal, laparoscopic, and abdominal) between groups. Secondary outcomes were differences in concomitant procedures and post-operative complications between groups. Descriptive statistics were used to analyze the data. All confidence intervals were computed using the normal approximation method. Statistical significance was P < 0.05.
Result(s): While a vaginal approach was the most common route across all groups, there was a significant difference in the route of POP repair among women of different races and ethnicities (P < 0.001; Table 1). Analysis revealed significantly more Black women undergoing laparoscopic procedures (P < 0.001), and more Hispanic women undergoing an abdominal approach (P < 0.001) than other groups. Black, Asian, and Hispanic women were more likely to undergo a hysterectomy than White women at the time of POP repair (P < 0.001). Black women were less likely to receive a concomitant sling than all other groups (P < 0.001). While readmission rates were not statistically different (P = 0.06; Table 2), the occurrence of one or more adverse event was significantly different between races (P < 0.0001), as was reoperation rate (P = 0.04). Black and Hispanic women were transfused 2-fold more often than White women, although the rates of transfusion overlapped with other non-White races (P < 0.001).
Conclusion(s): Surgical approach to and outcomes of POP surgery differed significantly between races and Hispanic ethnicity. While more is needed to assess the impact of pre-existing co-morbidities on routes of surgery, reasons for why differences exist may not be fully elucidated from this dataset. Findings may reflect variations in prevalence of concurrent disorders among racial/ethnic groups, provider biases, patient preferences, and access to subspecialty-trained surgeons. [Formula presented] [Formula presented]
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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, p <  0.05), urgency episodes (-0.50, 95% CI: -0.77 to -0.22, p <  0.05), total OAB symptom score (-0.66, 95% CI: -1.00 to -0.38, p <  0.05), and mean volume voided (+10.76 ml, 95% CI: 4.87-16.64, p <  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 50 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.

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 1.32 days, p = 0.65), postoperative urinary tract infection (UTI) (6.1% versus 5.8%, p = 0.670), perioperative blood transfusion (1.1% versus 1.2%, p = 0.673), readmission (2.7% versus 2.6%, p = 0.884) and postoperative wound infection (0.5% versus 0.7%, p = 0.51). There was a higher rate of reoperation (2.2% versus 1.5%, p = 0.049) and venous thromboembolism (VTE) (0.4% versus 0.1%, p = 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.

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.

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%