New technology assessment and current and upcoming therapies for underactive bladder.

BACKGROUND AND AIMS: Stakeholders from around the world came together to address the unmet needs of underactive bladder (UAB) at the 3rd International Congress for Underactive Bladder. METHODS: The main recommendation from the regulatory working group is a need for a meeting of UAB stakeholders and regulatory agencies including the FDA to discuss guidance for regulatory trial design for devices, drugs, and/or biologics for UAB. RESULTS: The following issues to be discussed and agreed upon for UAB trials: 1) Appropriate inclusion and exclusion criteria. 2) Should residual urine volume be the primary outcome parameter and how often should it be measured? 3) Are there secondary measures that should have a place in UAB trials, such as change in the number of catheterizations, quality of life measures, etc.? 4) Use and format of bladder voiding and catheterization diary for trials. 5) Define role and technique of urodynamics in UAB trials. Are urodynamics required to monitor, and possibly exclude, individuals with high pressure voiding induced by bladder prokinetic therapies? 6) Development and use of UAB questionnaires. DISCUSSION AND CONCLUSION: The UAB regulatory working group recognizes the path forward should include engaging the FDA and other regulatory organizations that may harmonize and formalize guidance for regulatory trial designs for therapeutics for UAB.

A Randomized Controlled Trial to Compare 2 Scalable Interventions for Lower Urinary Tract Symptom Prevention: Main Outcomes of the TULIP Study.

PURPOSE: We compared 2-year urinary incontinence and urgency scores of older women who attended a 2-hour bladder health class vs those who viewed a 20-minute abbreviated class video for the purpose of urinary incontinence prevention. MATERIALS AND METHODS: A randomized, 2-arm, parallel design study was done to test the superiority of the 20-minute video over the 2-hour class. Outcomes at baseline, and 3, 12 and 24 months were the scores on questions 1 to 3 of ICIQ-SF (International Consultation on Incontinence Short Form) as the primary outcome and on IUSS (Indevus Urgency Severity Scale). Intent to treat analysis was done to compare the change from baseline in each intervention group across time and also with each other. Multiple imputation was used for missing data. RESULTS: A total of 647 women participated in the study. Mean age was 63 years and approximately 28% of the participants were African American, primarily from an urban setting. The 2 arms were balanced on body mass index at baseline, age, race/ethnicity, education, employment status, income and marital status. No differences in primary or secondary outcomes were demonstrated between the 2 groups from baseline to the 3, 12 or 24-month visits. CONCLUSIONS: The absence of significant differences in the outcome measures of ICIQ-SF and IUSS between the 2-hour class and the 20-minute video groups demonstrates that the 2 interventions were comparable. As urinary incontinence and urgency tend to rise annually in older women, instruction in bladder health self-care provided through either the 2-hour class or the 20-minute video format is a useful intervention to prevent urinary incontinence in older women.

The role of testosterone in men's health: is it time for a new approach?

PURPOSE: Because of many unanswered questions regarding men's health, a literature review was performed to better understand the role of testosterone and testosterone replacement therapy (TRT) in the management of hypogonadism and aging related prostate gland diseases (ARPGD) including prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). METHODS: The PubMed database was screened for pertinent peer reviewed articles published during the last four decades that culminated in the positions and recommendations in this paper. RESULTS: Hypogonadism seriously impacts men's health, and the diagnosis remains controversial. The incidence of ARPGD is projected to increase worldwide and treatment still has significant limitations. There is compelling evidence that lower, not higher, testosterone levels trigger the development of PCa and BPH through androgen receptor over-expression. TRT was found to be safe and effective in treating hypogonadism including in PCa survivors and those harboring PCa. There is also evidence that TRT might reduce the incidence and prevalence of ARPGD. CONCLUSIONS AND RECOMMENDATIONS: This review synthesizes a wide-ranging compendium of basic science and clinical research that strongly encourages altering the present approach to diagnosing and treating men with hypogonadism and ARPGD. These findings underscore the importance of avoiding significant testosterone decline and support the use of TRT. Ten recommendations are offered as a framework for the way forward. It is now time for clinicians, payers, researchers, funding agencies, professional associations, and patient advocacy groups to embrace this new paradigm to increase longevity and improve the quality of life.

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder.

We report on the first regulatory approved clinical trial of a prospective open-label physician-initiated study assessing the safety and efficacy of intradetrusor injected Autologous Muscle Derived Cells (AMDC) treatment for underactive bladder (UAB). 20 non-neurogenic UAB patients were treated. Approximately 50-250 mg of quadriceps femoris muscle was collected using a spirotome 8-gauge needle. The muscle biopsy samples were sent to Cook MyoSite (Pittsburgh, PA) for processing, isolation, and propagation of cells. Research patients received approximately 30 intradetrusor injections of 0.5 mL delivered to the bladder, for a total of 15 mL and 125 million AMDC, performed utilizing a flexible cystoscope under direct vision using topical local anesthesia. Follow-up assessments included adverse events and efficacy via voiding diary and urodynamic testing at 1, 3, 6 and 12 months post-injection. An optional second injection was offered at the end of the 6 months visit. 20 patients received the first injection and all 20 patients requested and received a second injection. Median patient age was 65 years old (range 41-82 years). There were 16 male (80%) and 4 female (20%) patients. Etiology included 7 men (35%) with persistent urinary retention after transurethral resection of the prostate for benign prostatic hyperplasia and 13 patients (65%) with idiopathic chronic urinary retention. At the primary outcome time point of 12 months, 11/19 patients (58%) reported a global response assessment (GRA) ≥ 5, showing slight to marked improvement in their UAB symptoms, compared to 6/20 (30%) patients at 3 months post-injection. No serious procedure or treatment-related adverse events occurred. Noted improvements included: decreased post void residual urine volume, increased voiding efficiency, and decreased catheter use. Intradetrusor-injected AMDC as a treatment for UAB was successfully completed in a 20-patient trial without serious adverse event and with signal of efficacy. Cellular therapy may be a promising novel treatment for catheter-dependent chronic urinary retention. A multicenter controlled trial is needed to further assess the promise of regenerative medicine in the treatment of lower urinary tract dysfunction.

Burch colposuspension versus fascial sling to reduce urinary stress incontinence.

BACKGROUND: Many surgical procedures are available for women with urinary stress incontinence, yet few randomized clinical trials have been conducted to provide a basis for treatment recommendations. METHODS: We performed a multicenter, randomized clinical trial comparing two procedures--the pubovaginal sling, using autologous rectus fascia, and the Burch colposuspension--among women with stress incontinence. Women were eligible for the study if they had predominant symptoms associated with the condition, a positive stress test, and urethral hypermobility. The primary outcomes were success in terms of overall urinary-incontinence measures, which required a negative pad test, no urinary incontinence (as recorded in a 3-day diary), a negative cough and Valsalva stress test, no self-reported symptoms, and no retreatment for the condition, and success in terms of measures of stress incontinence specifically, which required only the latter three criteria. We also assessed postoperative urge incontinence, voiding dysfunction, and adverse events. RESULTS: A total of 655 women were randomly assigned to study groups: 326 to undergo the sling procedure and 329 to undergo the Burch procedure; 520 women (79%) completed the outcome assessment. At 24 months, success rates were higher for women who underwent the sling procedure than for those who underwent the Burch procedure, for both the overall category of success (47% vs. 38%, P=0.01) and the category specific to stress incontinence (66% vs. 49%, P<0.001). However, more women who underwent the sling procedure had urinary tract infections, difficulty voiding, and postoperative urge incontinence. CONCLUSIONS: The autologous fascial sling results in a higher rate of successful treatment of stress incontinence but also greater morbidity than the Burch colposuspension. (ClinicalTrials.gov number, NCT00064662 [ClinicalTrials.gov] .).

High costs of urinary incontinence among women electing surgery to treat stress incontinence.

OBJECTIVE: To estimate costs for incontinence management, health-related quality of life, and willingness to pay for incontinence improvement in women electing surgery for stress urinary incontinence. METHODS: A total of 655 incontinent women enrolled in the Stress Incontinence Surgical Treatment Efficacy Trial, a randomized surgical trial. Baseline out-of-pocket costs for incontinence management were calculated by multiplying self-report of resources used (supplies, laundry, dry cleaning) by national resource costs (USD2,006). Health-related quality of life was estimated with the Health Utilities Index Mark 3. Participants estimated willingness to pay for 100% improvement in incontinence. Potential predictors of these outcomes were examined by using multivariable linear regression. RESULTS: Mean age was 52+/-10 years, and mean number of weekly incontinence episodes was 22+/-21. Mean and median (25%, 75% interquartile range) estimated personal costs for incontinence management among all women were USD14+/-USD24 and USD8 (interquartile range USD3, USD18) per week, and 617 (94%) women reported any cost. Costs increased significantly with incontinence frequency and mixed compared with stress incontinence. The mean and median Health Utilities Index Mark 3 scores were 0.73+/-0.25 and 0.84 (interquartile range 0.63, 0.92). Women were willing to pay a mean of USD118+/-USD132 per month for complete resolution of incontinence, and willingness to pay increased significantly with greater expected incontinence improvement, household income, and incontinent episode frequency. CONCLUSION: Urinary incontinence is associated with substantial costs. Women spent nearly USD750 per year out of pocket for incontinence management, had a significant decrement in quality of life, and were willing to pay nearly USD1,400 per year for cure.

Guided imagery for women with interstitial cystitis: results of a prospective, randomized controlled pilot study.

INTRODUCTION: In the United States, more than 1 million women and men are affected with interstitial cystititis (IC), which is a clinical syndrome involving urinary urgency, frequency, and pelvic pain. A review of the literature revealed that there are no studies showing the effect of guided imagery in women with IC. The purpose of this clinical investigation was to explore the effect of guided imagery on pelvic pain and urinary symptoms in women with IC symptoms. METHODOLOGY: Thirty (30) women with diagnosed IC were randomized into 2 equal groups. One group (treatment) listened to a 25-minute guided imagery compact disc (CD), that was created specifically for women with pelvic pain and IC, twice a day for 8 weeks. The control group rested for 25 minutes twice daily for 8 weeks. Because no guided imagery CDs specifically for women with IC were found on the commercial market, the authors created a script and recorded the CD specifically for women with IC and pelvic pain. The focus of this guided imagery CD was on healing the bladder, relaxing the pelvic-floor muscles, and quieting the nerves specifically involved in IC. Baseline and end-of-study assessment questionnaires (Interstitial Cystitis Symptom Index & Problem Index [IC-SIPI], IC Self-Efficacy Scale, a visual analogue [VAS] scale for pain, and a global response assessment [GRA]), 2-day voiding diaries, and 24-hour pain diaries were completed by the subjects and were evaluated using SPSS (Chicago, IL). RESULTS: More than 45% of the treatment group were responders to guided imagery therapy noting a moderate or marked improvement on the GRA. Pain scores and episodes of urgency significantly decreased in the treatment group. Responders had significant reductions in IC-SIPI scores (problem index, p = 0.006; symptom index, p = 0.004). In addition, responders on the GRA had significant (p = 0.039) improvements in mean pain scores from 5.50 to 2.57 at the end of the study in contrast to the nonresponders, whose pain levels remained the same (4.89 to 4.39). CONCLUSIONS: This is the first study providing preliminary data supporting the use of guided imagery as a potential therapy for IC. Guided imagery may be a useful tool to offer women with IC for pain and IC symptom management. It is an intervention without negative side-effects, is readily available, and shows a trend toward improvement of IC symptoms.

Costs and Sustainability of a Behavioral Intervention for Urinary Incontinence Prevention.

INTRODUCTION: Many women choose behavioral interventions as first line treatment for urinary incontinence. We developed a 20-minute abbreviated video, which proved to be similar to a 2-hour in-person class in a randomized trial. This study examines economic end points for the 20-minute video relative to the 2-hour class. METHODS: We randomized 332 participants to the 2-hour class and 315 to the 20-minute video. We estimated the cost for the 2-hour class, the 20-minute video and followup health care utilization. Participants were followed for 3, 12 and 24 months, and asked about health care utilization, quality of life and lost productivity. To measure perceived value, we queried each participant regarding willingness to pay. Regression analysis was used for statistical comparisons. RESULTS: The estimated per participant cost for a 2-hour class was $38, which was more than the marginal cost of the video ($0). We found no significant differences between the treatment groups at each followup for quality of life, lost productivity or health care utilization. Women were willing to pay $26, $21 and $30 for a copy of the DVD, video on the Web and in-person class, respectively, all of which were less than the average cost of the in-person class ($38). CONCLUSIONS: Poor adherence remains a challenge for many behavioral interventions designed to prevent urinary incontinence. The 20-minute video is less expensive than the 2-hour class and is equally effective. Distributing the video on the Internet will improve access and will be easier to sustain than in-person classes.

Effect of Group-Administered Behavioral Treatment on Urinary Incontinence in Older Women: A Randomized Clinical Trial.

Importance: Urinary incontinence (UI) guidelines recommend behavioral interventions as first-line treatment using individualized approaches. A one-time, group-administered behavioral treatment (GBT) could enhance access to behavioral treatment. Objective: To compare the effectiveness, cost, and cost-effectiveness of GBT with no treatment for UI in older women. Design, Setting, and Participants: Multisite randomized clinical trial (the Group Learning Achieves Decreased Incidents of Lower Urinary Symptoms [GLADIOLUS] study), conducted from July 7, 2014, to December 31, 2016. The setting was outpatient practices at 3 academic medical centers. Community-dwelling women 55 years or older with UI were recruited by mail and screened for eligibility, including a score of 3 or higher on the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), symptoms of at least 3 months' duration, and absence of medical conditions or treatments that could affect continence status. Of 2171 mail respondents, 1125 were invited for clinical screening; 463 were eligible and randomized; 398 completed the 12-month study. Interventions: The GBT group received a one-time 2-hour bladder health class, supported by written materials and an audio CD. Main Outcomes and Measures: Outcomes were measured at in-person visits (at 3 and 12 months) and by mail or telephone (at 6 and 9 months). The primary outcome was the change in the ICIQ-SF score. Secondary outcome measures assessed UI severity, quality of life, perceptions of improvement, pelvic floor muscle strength, and costs. Evaluators were masked to group assignment. Results: Participants (232 in the GBT group and 231 in the control group) were aged 55 to 91 years (mean [SD] age, 64 [7] years), and 46.2% (214 of 463) were African American. In intent-to-treat analyses, the ICIQ-SF scores for GBT were consistently lower than control across all time points but did not achieve the projected 3-point difference. At 3 months, the difference in differences was 0.96 points (95% CI, -1.51 to -0.41 points), which was statistically significant but clinically modest. The mean (SE) treatment effects at 6, 9, and 12 months were 1.36 (0.32), 2.13 (0.33), and 1.77 (0.31), respectively. Significant group differences were found at all time points in favor of GBT on all secondary outcomes except pelvic floor muscle strength. The incremental cost to achieve a treatment success was $723 at 3 months; GBT dominated at 12 months. Conclusions and Relevance: The GLADIOLUS study shows that a novel one-time GBT program is modestly effective and cost-effective for reducing UI frequency, severity, and bother and improving quality of life. Group-administered behavioral treatment is a promising first-line approach to enhancing access to noninvasive behavioral treatment for older women with UI. Trial Registration: ClinicalTrials.gov identifier: NCT02001714.

Self-efficacy as a predictor to PFMT adherence in a prevention of urinary incontinence clinical trial.

Past research suggests a positive correlation between self-efficacy (SE) and adherence to behavioral interventions. Less is known about SE and adherence in behavioral programs that are preventive in nature and specific to urinary incontinence (UI). Using treatment-group data from a previously reported randomized controlled trial, the authors assess the role of SE in predicting adherence to pelvic-floor muscle training (PFMT) for UI prevention in a sample of postmenopausal women. Results indicate that at 12 months follow-up, nearly 70% of participants reported medium or high adherence, performing the recommended PFMT regimen 2 to 3 times per week or more. Summary scores of both Task SE, beta = .25, SE (beta) = .08, p < .01, and Regulatory SE, beta = .43, SE (beta) = .06, p < .0001, predict adherence. Also, the authors found a modest decline in self-efficacy scores over time. These findings highlight the importance of SE in sustained behavioral change.

Adherence to a behavioral program to prevent incontinence.

This exploratory study assesses factors predicting adherence to a behavioral intervention to prevent urinary incontinence. Community-dwelling, post-menopausal women (N = 164) were taught pelvic floor muscle training (PFMT) and bladder training (BT) and followed with surveys for 1 year. Content analysis of open-ended responses coded descriptions of approaches participants used to incorporate PFMT into daily life. Exploratory bivariate and logistic regression analyses determined predictors of approach used and adherence. Results indicate women incorporated PFMT into their lives using either a routine or ad hoc approach. Those using a routine approach at 3 months were 12 times more likely to adhere (odds ratio [OR] = 12.4, confidence interval [CI] = 4.0-38.8, p < .001) at a high level at 3 months and significantly more likely to maintain that level 12 months post-intervention (OR = 2.7, CI = 1.2-6.0, p < .014). Practicing BT was related to high adherence.

Prevalence of urinary incontinence in community dwelling men: a cross sectional nationwide epidemiological survey.

PURPOSE: Epidemiological studies on urinary incontinence (UI) in adult men of all ages are scarce. We aim to describe the UI phenomenon among community dwelling adult males in the United States (US). MATERIALS AND METHODS: We analyzed data from male respondents to a 14-item mailed UI symptoms questionnaire to the National Family Opinion (NFO) World Group Panel of 45,000 households matching the US 2000 census population on five key demographic elements. RESULTS: A total of 29,903 households responded, of which 21,590 were male heads of household (mean age 50 +/-15.2 years old). A total of 2,059 men (12.7%) reported symptoms of UI during the last 30 days. Symptoms of urge urinary incontinence (UUI), stress urinary incontinence (SUI), mixed urinary incontinence (MUI) symptoms, and other types of urinary incontinence (OUI) symptoms, were reported by 44.6%, 24.5%, 18.8%, and 12.3%, respectively. Among those with UI symptoms, the proportion of UUI and MUI symptoms increases with age while SUI symptoms decrease as age increases. Of those with UI symptoms, 44% consulted a physician of whom 57% did so within 6 months of the onset of symptoms. Treatments reported included absorbent pads (48%), prescription medication (30%), surgical procedure (18%), and intermittent catheterization (4%). CONCLUSIONS: Almost 1 in 10 males reported symptoms of UI. The UI prevalence rate increases with age and UUI symptoms is the most prevalent type reported. Less than half of men with UI symptoms sought professional help and half of them did so within 6 months of onset of UI symptoms.

Prevalence of self-reported interstitial cystitis (IC) and interstitial-cystitis-like symptoms among adult women in the community.

PURPOSE: Reported estimates of IC prevalence vary widely. The objective of this study is to determine the prevalence of IC among community-dwelling adult women. METHODS: We analyzed survey responses from 215 established IC cases and 823 age-matched community-dwelling controls. Using a history of diagnosis of urinary conditions and presence of pelvic pain within the last six months, we identified those with possible IC among the controls using various operative definitions. RESULTS: The prevalence rates of self-reported IC (SRIC) and IC-like symptoms (ICLS) among controls in the community were 3.7% and 4.4%, respectively. Expanding ICLS by including women who reported pelvic pain only raised the prevalence to 17.3%. CONCLUSIONS: According to our prevalence rates and population estimates in the United States census 2000, the number of adult women who possibly have interstitial cystitis is estimated to be between 422,803 and 21,454,813. Although estimates based on the question of having ever been diagnosed with IC lead to an estimate close to that derived from symptoms, underestimation of IC prevalence might occur in the absence of additional questions and testing to validate and qualify the responses further. There is also a need for clinical studies to verify and validate the diagnoses to enable accurate assessment of the sensitivity and specificity of such history survey questions.

Group session teaching of behavioral modification program for urinary incontinence: establishing the teachers.

In a past study it was determined that a nurse scientist and an urologist were able to prevent incontinence in women through teaching strategies in a group setting. This study determined that the same knowledge could be taught by an experienced nurse practitioner and an experienced urology nurse.

Evaluation of a mass mailing recruitment strategy to obtain a community sample of women for a clinical trial of an incontinence prevention intervention.

OBJECTIVES: Questions exist about using mass mailings to recruit representative samples to participate in clinical trials. The MESA Prevention Study (Medical, Epidemiologic and Social Aspects of Aging), a randomized controlled clinical trial to prevent urinary incontinence (UI), utilized a mass mailing recruitment procedure to recruit a representative sample of women to participate in a behavioral modification program. This paper seeks to expand the literature of mass mailing recruitment strategies for prevention studies by describing the procedures used to recruit healthy, continent, post-menopausal women aged 55-80 years. METHODS: Sociodemographic data collected from recruited subjects is compared with on-line national census data to evaluate the representativeness of the sample recruited from a purchased mailing list. RESULTS: The mass mailing procedure resulted in 3.3% positive response. Of those that returned a positive response, 37.6% were deemed eligible at first screening. Comparisons of study demographic data with state and county census data indicate that the sample obtained was representative of the communities. CONCLUSIONS: The mass mailing strategy was an effective means of recruiting a representative sample of women, aged 55-80. Short falls and recommendations for successful community sample recruitment strategies for clinical trials in older adult women are elaborated upon.

Continence Index: a new screening questionnaire to predict the probability of future incontinence in older women in the community.

PURPOSE: Urinary incontinence (UI) is a chronic, costly condition that impairs quality of life. To identify older women most at risk, the Medical Epidemiologic and Social Aspects of Aging (MESA) datasets were mined to create a set of questions that can reliably predict future UI. METHODS: MESA data were collected during four household interviews at approximately 1 year intervals. Factors associated with becoming incontinent at the second interview (HH2) were identified using logistic regression (construction datasets). Based on p values and odds ratios, eight potential predictive factors with their 256 combinations and corresponding prediction probabilities formed the Continence Index. Its predictive and discriminatory capability was tested against the same cohort's outcome in the fourth survey (HH4 validation datasets). Sensitivity analysis, area under receiver operating characteristic (ROC) curve, predicted probabilities and confidence intervals were used to statistically validate the Continence Index. RESULTS: Body mass index, sneezing, post-partum UI, urinary frequency, mild UI, belief of developing UI in the future, difficulty stopping urinary stream and remembering names emerged as the strongest predictors of UI. The confidence intervals for prediction probabilities strongly agreed between construction and validation datasets. Calculated sensitivity, specificity, false-positive and false-negative values revealed that the areas under the ROCs (0.802 and 0.799) for the construction and validation datasets, respectively, indicated good discriminatory capabilities of the index as a predictor. CONCLUSION: The Continence Index will help identify older women most at risk of UI in order to apply targeted prevention strategies in women that are most likely to benefit.

Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial.

OBJECTIVE: To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder. PATIENTS AND METHODS: The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated. RESULTS: Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events. CONCLUSIONS: Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.