Faculty Bibliography

Introduction: Despite the widespread use of synthetic mid urethral slings (MUS) in clinical practice, autologous fascial pubovaginal sling (AFPVS) continues to have an important role in women with stress urinary incontinence (SUI), notably in those who failed previous anti-incontinence procedures. The aim of this study was to assess the prevalence, risk factors and management of persistent SUI following AFPVS in patients who failed previous anti-incontinence procedures.
Method(s): The charts of all female patients who underwent AFPVS for SUI from 2012 to 2017 at a single academic center were retrospectively reviewed. Only patients who had failed at least one previous anti-incontinence procedure were included in the present study. Patients with neurogenic bladder were excluded. The primary endpoint was persistent SUI at 3 months defined as patient reporting the need to wear one pad per day or more. Univariate and multivariate logistic regression analysis was performed to assess predictors of persistent SUI at 3 months.
Result(s): After exclusion of 29 patients with no prior anti-incontinence procedures and 6 patients with neurogenic bladder, 70 patients were included in the present study. The mean patient age was 58.2 years, and the most common prior SUI surgeries were MUS (85.7%), bulking agents (25.7%) and Burch Colposuspension (8.6%). Most patients reported improvement of SUI at 3 months (83.2%), however 24 reported persistent SUI (34.3%), of which 14 reported improvement (22.9%) and 10 unchanged or worsened SUI (16.8%). The median number of pads per day at 3 months in those with persistent SUI was 1 (range: 1-10). After a median follow-up of 14.4 months, 10 patients (14.3%) had retreatment for SUI. Those who failed prior MUS had lower risk of persistent SUI than those who failed prior Burch and/or bulking (32.7% vs. 77.8%; p=0.02). This was the only predictor of persistent SUI in univariate analysis (OR=0.14; p=0.02) and in multivariate analysis adjusting for age, BMI and urethral hypermobility (OR=0.10; p=0.01).
Conclusion(s): AFPVS is an effective treatment option for women who failed previous anti-incontinence procedures. Patients who failed MUS may have a lower risk of persistent SUI when compared to this who failed Burch and/or Bulking agents

Introduction: Nocturia is a highly prevalent and underrecognized condition associated with disrupted sleep, increased risks of falls and fractures and negative effects on quality of life (QOL). Long-term consequences may include depression and risks of cardiovascular diseases. Two nocturic voids per night is the threshold at which the impact of nocturia becomes more problematic. A large online poll was conducted to assess women's awareness of nocturia, engagement with healthcare practitioners, and effects on QOL.
Method(s): This was a self-reported online survey conducted by Harris Poll within the US in August 2018 among adults aged 18 years and older. Propensity weighting matched respondents to the US general adult population. Descriptive statistics were used to summarize the results of the survey.
Result(s): Of 2040 respondents, 1104 were female (1056 on a weighted basis). Mean (SD) age of female respondents was 47.1 (17.45) years. Seventy-one percent of the female respondents had never heard of nocturia. Of the 1056 female respondents, 36% reported waking to urinate on average 2 or more times per night (nocturia). Among the female nocturia sufferers, 65% had never heard of nocturia, and 74% were not aware waking up to urinate at least twice per night is a diagnosable medical condition. Seventy-four percent had not spoken with their doctor about waking up to urinate, and only 39% reported that their doctor had ever asked them about frequency of nighttime urination. Of those who had not spoken with their doctor about this condition, 53% thought it was a normal part of aging, and 26% thought nothing could be done about it. Seventy-three percent of the female nocturia sufferers reported negative effects on quality of life during nighttime, and 63% are negatively affected during daytime. The specific nighttime and daytime effects are detailed in the Figure.
Conclusion(s): In this large national survey, more than one-third of women had symptoms of nocturia. Most were not aware nocturia is a medical condition, had not spoken with their doctors about it, and experienced negative nighttime and daytime effects from the condition

PURPOSE/OBJECTIVE:Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. METHODS:Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 μg and 0.12 μg desmopressin subcutaneous (SC) bolus injection. RESULTS:and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 μg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5-6 h. CONCLUSIONS:AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

Objective: To report the current clinical features, treatment patterns and outcomes of female patients who were seen at a tertiary referral centre with a primary diagnosis of nocturia, and to assess the predictive factors of therapeutic management failure. Patients and methods: A retrospective chart review of all new female patients seen in a single-centre functional urology practice with the diagnosis of nocturia was performed. Up to three visits within a 12-month period from the time of presenting were reviewed. The primary endpoint was patient-reported improvement assessed at each follow-up visit and the change in the number of nocturia episodes. Results: In all, 239 female patients were included for analysis. The prevalence of nocturnal polyuria, reduced bladder capacity, and global polyuria were 75%, 40.2%, and 18.1%, respectively. Within the first two visits, 72.7% of patients had started a treatment beyond behavioural therapies. Anticholinergics were the most commonly initiated treatment (47.2% of patients). At the latest considered visit, 80 patients reported improvement in nocturia (45.5%) and there was a mean - 0.8 decrease in the number of nocturia episodes from 4 to 3.2, which was statistically significant (P < 0.001). There was no statistically significant association between any of the bladder diary findings and treatment outcomes. A smaller number of nocturia episodes was the only predictive factor of therapeutic management failure in multivariate analysis (odds ratio 0.10; P = 0.01). Conclusions: Whilst the prevalence of nocturnal polyuria in women with nocturia is high, the therapeutic management until 2016 seemed to rely mostly upon overactive bladder medications with a relatively low success rate. Abbreviations: BD: bladder diary; BPS: bladder pain syndrome; ICD(-9)-(10): International Classifications of Disease (ninth revision) (10th revision); NPI: Nocturnal Polyuria Index; OAB: overactive bladder; OR: odd ratio; POP: pelvic organ prolapse.

Introduction & Objectives: To evaluate the efficacy and safety of AV002 by age and gender in patients with nocturia. Material(s) and Method(s): This was a pooled analysis of two double-blind phase 3 trials (NCT01357356, NCT01900704). Studies were approved by an institutional review board. Patients >=50 years with >=2 voids/night were randomized to AV002 1.66 mcg, 0.83 mcg, or placebo and treated for 12 weeks. The co-primary efficacy endpoints (based on patient voiding diaries)were percent of patients with >=50% reduction in mean number of nocturic voids/night (>=50% responders)and mean change in number of nocturic voids/night. Safety endpoints included serum sodium and adverse events (AEs). No fluid restrictions or behavioral modifications were implemented. Data were analyzed by gender and age (< or >=65 years). Result(s): The intent-to-treat (ITT)population (>=3 days of diary data)included 1333 patients: 761 males (302 <65 years; 459 >=65 years)and 572 females (304 <65 years; 268 >=65 years). AV002 1.66 mcg significantly increased percent of responders and decreased number of nocturic voids/night compared with placebo for all age and gender subgroups (Tables 1 and 2). Compared with placebo, AV002 0.83 mcg significantly decreased number of nocturic voids/night for all subgroups and significantly increased percent of responders for patients >=65 years and for males. For patients <65 years and for females, the percent of responders was numerically higher in the AV002 0.83 mcg group compared with placebo; however, the difference was not statistically significant, possibly due to a high response rate in the placebo group. AV002 was well tolerated and there were no differences in AEs between AV002 and placebo. Hyponatremia (serum sodium <=125 mmol/mL)occurred in 5 patients (4 male, 1 female; all >=65 years)receiving 1.66 mcg AV002 (1.1%), 1 patient (1 male >=65 years)receiving placebo (0.2%), and no patients receiving AV002 0.83 mcg. In all, 4 of 5 patients with hyponatremia received steroids within days of the event because of a later-reported protocol deviation; systemic and inhaled glucocorticoids are now contraindicated in the US label. [Table Presented]Conclusions: AV002 1.66 mcg was effective and well tolerated for the treatment of nocturia for all age and gender subgroups. The risk of hyponatremia was low, even without fluid restrictions or behavioral modifications.

Introduction & Objectives: Nocturia is a highly prevalent medical condition. Approximately 80% of patients with nocturia (average of >=2 nocturnal voids)have nocturnal polyuria (NP), and 21% also have overactive bladder (OAB). These patients report sleep disruption and negative effect on nighttime symptoms. First-line therapies for OAB, have limited efficacy in treating nocturia. Combination therapy with an antimuscarinic and an antidiuretic may provide better relief of nocturia for patients with this multifactorial pathophysiology. AV002 is an emulsified microdose desmopressin nasal spray indicated for the treatment of nocturia due to NP and may be suitable concomitant therapy for these patients. Material(s) and Method(s): Data from a subgroup of OAB patients with concomitant NP enrolled in two double-blind Phase 3 trials of AV002 for treatment of nocturia were pooled. Studies were approved by an institutional review board. Patients with >=2 nocturic voids for >=6 months received AV002 1.66 mcg, AV002 0.83 mcg, or placebo every night for 12 weeks. No fluid restrictions or behavioral modifications were required. Efficacy endpoints, based on patient voiding diaries, included first uninterrupted sleep period (FUSP; elapsed time from bedtime to first nocturic void). Patients in one trial also completed the validated Impact of Nighttime Urination (INTU)questionnaire to assess changes in quality of life (QoL; range, 0-100; 0, no impact; 100, greatest impact). Result(s): Of 1045 randomized NP patients, 275 with OAB were included in the FUSP analysis. Of these, 136 patients from one study were included in the INTU analysis. Baseline and change from baseline for FUSP and INTU are shown in Table 1. After 12 weeks of treatment, FUSP was extended to 4.0 hours and 3.9 hours in the AV002 1.66 mcg and 0.83 mcg groups, respectively (change from baseline, p<0.05 vs. placebo for each AV002 group). INTU overall impact scores were significantly improved in patients receiving AV002 compared with placebo. [Table Presented]Conclusions: AV002 treatment over 12 weeks significantly extended FUSP and improved INTU (QoL)scores compared with placebo in OAB patients with nocturia due to NP. AV002 may be an appropriate treatment for nocturia in patients with OAB and nocturia due to NP.

OBJECTIVE:To evaluate the effect of radiation on male stress urinary incontinence (SUI) and to assess the relative value of preoperative urodynamic (UDS) testing in radiated vs nonradiated men with SUI. METHODS:A retrospective chart review of all male patients with SUI who underwent UDS testing from 2010 to 2016 was performed. The impact of UDS findings on treatment decision making was assessed. UDS parameters and treatment patterns of radiated vs nonradiated patients were compared as well as the fates of storage symptoms in each group. RESULTS:Two hundred seven men were identified that underwent UDS with a clinical diagnosis of SUI. Sixty-five out of 207 (31.4%) were exposed to radiation as a treatment modality for prostate cancer. All patients that underwent UDS testing moved on to surgical correction of SUI, and the UDS findings did not alter plan to treat SUI in any patients. Men who were radiated prior to surgical correction of SUI were more likely to have detrusor overactivity (70% vs 38%, P <.0001) and had lower maximum cystometric capacity (255 vs 307.4 mL, P = .01) when compared to nonradiated on UDS. After artificial urinary sphincter or sling implantation, the proportion of patients requiring overactive bladder medications was higher in radiated vs nonradiated men (44.3% vs 25.3%; P = .01). CONCLUSION/CONCLUSIONS:Radiation therapy appears to increase the likelihood of bladder dysfunction in male patients with SUI. The UDS findings did not alter the plan to treat SUI in any patients in our series, and its role before SUI surgery in male patients, including those receiving radiation, may be limited.

BACKGROUND:Nocturia is considered to be a very bothersome lower urinary tract disorder. Yet, to date, the economic burden attributable to this poor health condition remains less well known. OBJECTIVE:To compare differences in health care resource utilization (HCRU), health care costs, and work productivity in adult patients with differing frequencies of nocturia episodes (i.e., < 2 vs. ≥ 2 nocturia episodes per night). METHODS:Adult patients with nocturia enrolled in an integrated proprietary database were recruited to complete a survey on their demographics, nocturia characteristics, and work productivity. Using patients' survey data and health care claims from the previous 6 months, those with < 2 (n = 197; 21.9%) versus ≥ 2 (n = 702; 78.1%) nocturia episodes per night were compared for differences in HCRU, health care costs, and work productivity after adjusting for potential confounders. HCRU was reported as the mean number per patient per month (PPPM) for outpatient visits (all types), physician office visits, and prescriptions filled and the proportion of patients with ≥1 hospitalization or emergency department visit in the previous 6 months. Health care costs were reported as mean PPPM. Work productivity was assessed via patient survey and reported as a mean percentage for absenteeism, presenteeism, overall work impairment, and activity impairment during the past week. RESULTS:899 adult patients (mean age = 71.4 years; 57.2% men) were enrolled and analyzed. Compared with patients with <2 nocturia episodes per night, patients with ≥ 2 nocturia episodes had more outpatient health care visits (unadjusted mean visits PPPM: 2.1 vs. 1.6; P < 0.001; adjusted mean visits PPPM: 2.1 vs. 1.6; P = 0.017), office visits (unadjusted and adjusted mean visits PPPM: 0.9 vs. 0.7; P < 0.001), and prescriptions filled (unadjusted mean prescription fills PPPM: 3.1 vs. 2.1; P < 0.001; adjusted mean prescription fills PPPM: 3.2 vs. 2.2; P = 0.027). Patients with ≥ 2 nocturia episodes per night also displayed significantly higher outpatient health care costs (unadjusted mean PPPM costs: $676 vs. $516; P = 0.028; adjusted mean PPPM costs: $678 vs. $506; P = 0.017). In terms of work productivity impairment, patients with ≥ 2 nocturia episodes per night experienced higher rates of unadjusted (20% vs. 10%; P = 0.002) and adjusted presenteeism (20% vs. 10%; P = 0.004) and unadjusted (20% vs. 10%; P = 0.002) and adjusted overall work impairment (20% vs. 10%; P = 0.001). CONCLUSIONS:Study findings demonstrate that nocturia was associated with higher outpatient encounters and related costs in the presence of a greater occurrence of nocturic episodes. DISCLOSURES/UNASSIGNED:This study was funded by Allergan plc, Dublin, Ireland. Neither honoraria nor payments were provided for authorship. Dmochowski is a consultant and speaker for Allergan plc and a consultant for Serenity Pharmaceuticals. Brucker is a consultant and speaker for Allergan plc, a consultant for Watkins-Conti and Avadel, and an investigator for Medtronic and Ipsen. Cole is a consultant for Allergan plc and an employee of Sharp Rees-Stealy Medical Group. Kawahara and Pulicharam are full-time employees of DaVita Medical Group. Burk is a consultant for Allergan plc and a health outcomes consultant. Tung is an employee of Allergan plc. Hale has served as a consultant/advisor to and has received research funding from Allergan plc. The data from this manuscript were previously presented in poster format by Steve Kawahara at the Academy of Managed Care & Specialty Pharmacy Annual Meeting; April 19-22, 2016; San Francisco, CA.

Primary bladder neck obstruction (PBNO) is a functional obstruction caused by abnormal opening of the bladder neck during the voiding phase of micturition. PBNO may present with a variety of symptoms including voiding symptoms (slow urinary stream, intermittent stream, incomplete emptying), storage symptoms (frequency, urgency, urgency incontinence, nocturia), and/or pelvic pain and discomfort. The diagnosis of PBNO can be made with videourodynamic testing, which demonstrates elevated voiding pressures with low flow, and fluoroscopic imaging demonstrating obstruction at the level of the bladder neck. Treatment options include conservative management with watchful waiting, pharmacologic management, and surgical intervention. In this article, we review the etiology, presentation, diagnosis, and treatment of PBNO in men, women, and children.