Effectiveness and safety of a novel, collapsible pessary for management of pelvic organ prolapse.

BACKGROUND: Pessaries are an effective treatment for pelvic organ prolapse, yet currently available pessaries can cause discomfort with removal and insertion. An early feasibility trial of an investigational, collapsible pessary previously demonstrated mechanical feasibility during a brief 15-minute office trial. Longer-term, patient-centered safety and efficacy data is needed. OBJECTIVES: To assess the effectiveness and safety of the investigational vaginal pessary for pelvic organ prolapse at three months. STUDY DESIGN: This was a prospective, seven-center, open-label equivalence study with participants serving as their own controls. Subjects were current users of a Gellhorn or ring pessary with ≥ Stage II prolapse. Baseline subjective and objective data were collected for one month using their current pessary, and then data were collected through a three-month treatment phase with use of the study pessary. The primary outcome was change in Pelvic Floor Distress Inventory-20 score. Secondary outcome measures included objective assessment of prolapse support, changes in the Pelvic Floor Impact Questionnaire-7, and pain with insertion and removal measured on a Visual Analog Scale. Subjects fitted with study pessary were analyzed as intention to treat and those who dropped out were assigned scores at the upper limit of the predefined equivalence limits. Secondary per protocol analyses included subjects who completed treatment. The study was powered to 80% with a minimal important change equivalence limit of 18.3 points on the Pelvic Floor Distress Inventory-20 scale. Square root transformations were used for non-parametric data and p-values adjusted for multiple comparisons. RESULTS: Seventy-eight subjects were enrolled, though 16 withdrew prior to study pessary placement. Sixty-two subjects (50 ring and 12 Gellhorn pessary users) were fitted with the study pessary, and 48 (62%) completed the three-month intervention. The change in Pelvic Floor Distress Inventory-20 scores at three months demonstrated equivalence compared to the subjects' baseline scores, (mean difference -3.96 (improvement), 90% confidence interval (CI) [-11.99, 4.08], p=0.002). Per protocol analysis of the Pelvic Floor Distress Inventory-20, equivalence was not demonstrated with scores favoring the study pessary (mean difference -10.45, 90% CI, [-20.35, 0.54] (p=0.095)). Secondary outcomes included: objective measures of support which were similar, mean difference Ba=0.54 cm, Bp=0.04 cm, favoring study pessary; improvement in mean Pelvic Floor Impact Questionnaire-7 scores for those who completed the trial (pre=32.23, post=16.86, p=0.019); and pain with insertion and removal, which was lower with the study pessary compared to subject's own pessary (mean difference Visual Analogue Scale insertion=9.91 mm (p=0.019), removal=11.23 mm (p=0.019)). No serious adverse events related to the pessary were reported. CONCLUSIONS: Equivalence was demonstrated in the study pessary primary outcome compared to current non-collapsible pessaries for change in severity and bother of pelvic floor symptoms. In participants who completed the trial, the Pelvic Floor Impact Questionnaire-7 improved with the study pessary and change in Pelvic Floor Distress Inventory-20 scores were non-equivalent, favoring the study pessary. Subjects reported significantly lower pain scores with both pessary insertion and removal with the novel collapsible pessary compared with their standard pessary.

Utilization of Rectal Examinations Before Magnetic Resonance Defecography Studies.

IMPORTANCE: More information is needed to guide referring subspecialists on the appropriate patient evaluation before magnetic resonance defecography (MRD). OBJECTIVES: This study aimed to evaluate how often health care providers perform digital rectal examination (DRE) before ordering MRD to investigate causes of bowel and pelvic floor complaints. STUDY DESIGN: We conducted a retrospective cohort review, including MRD performed on female patients at an integrated health care system from 2016 through 2020. The primary outcome was the presence or absence of documented rectal examination in the year before defecography by the referring provider or 6 months prior by a primary care physician or pelvic floor physical therapist. We hypothesized that the overall rate of rectal examination would be high and unaffected by the referring provider's subspecialty. RESULTS: Three hundred-four defecography tests were performed, with 209 patients (68.8%) referred by gastroenterology providers and 95 (31.2%) from other specialties. Gastroenterologists performed DRE in 32.8% of patients, in contrast to 84.4% of patients referred by other specialties ( P < 0.001). When comparing subspecialties that most commonly refer patients for MRD (gastroenterology, colorectal surgery and urogynecology), there was a statistically significant difference between gastroenterologists and colorectal surgeons ( P < 0.001) as well as urogynecologists ( P < 0.001) but no difference in the rate of rectal examination between colorectal surgeons and urogynecologists ( P = 1.00). CONCLUSIONS: At our single integrated health system, the rate of DRE before MRD testing varied significantly by specialty. Our findings highlight the need for better understanding of DRE utility in the algorithms for evaluation of bowel and pelvic floor disorders.

Performance of Perioperative Tasks for Women Undergoing Anti-incontinence Surgery: Developed by the AUGS Quality Improvement and Outcomes Research Network.

OBJECTIVES: Surgery for the correction of stress urinary incontinence is an elective procedure that can have a dramatic and positive impact on quality of life. Anti-incontinence procedures, like inguinal hernia repairs or cholecystectomies, can be classified as high-volume/low-morbidity procedures. The performance of a standard set of perioperative tasks has been suggested as one way to optimize quality of care in elective high-volume/low-morbidity procedures. Our primary objective was to evaluate the performance of 5 perioperative tasks-(1) offering nonsurgical treatment, (2) performance of a standard preoperative prolapse examination, (3) cough stress test, (4) postvoid residual test, and (5) intraoperative cystoscopy for women undergoing surgery for stress urinary incontinence-compared among surgeons with and without board certification in female pelvic medicine and reconstructive surgery (FPMRS). STUDY DESIGN: This study was a retrospective chart review of anti-incontinence surgical procedures performed between 2011 and 2013 at 9 health systems. Cases were reviewed for surgical volume, adverse outcomes, and the performance of 5 perioperative tasks and compared between surgeons with and without FPMRS certification. RESULTS: Non-FPMRS surgeons performed fewer anti-incontinence procedures than FPMRS-certified surgeons. Female pelvic medicine and reconstructive surgery surgeons were more likely to perform all 5 perioperative tasks compared with non-FPMRS surgeons. After propensity matching, FPMRS surgeons had fewer patients readmitted within 30 days of surgery compared with non-FPMRS surgeons. CONCLUSIONS: Female pelvic medicine and reconstructive surgery surgeons performed higher volumes of anti-incontinence procedures, were more likely to document the performance of the 5 perioperative tasks, and were less likely to have their patients readmitted within 30 days.

Minimally Invasive Autologous Fascia Sling at the Midurethra: A Case Series.

STUDY OBJECTIVE: The primary objective was to determine the improvement in stress urinary incontinence symptoms using autologous fascia lata sling placed at the midurethra. The secondary objective was to determine the presence of leg pain after harvest of fascia lata graft. DESIGN: Case series. SETTING: Rural academic tertiary care center. PATIENTS: All women who underwent an autologous fascia midurethral sling over a 1-year period between June 2019 and September 2020. INTERVENTIONS: Autologous fascia lata midurethral sling. MEASUREMENTS: Incontinence severity index, urodynamic distress inventory-6, and Likert pain scale. MAIN RESULTS: Nineteen women received an autologous fascial sling at the midurethra using the described technique-16 fascia lata and 3 rectus fasciae. Mean improvement in incontinence severity index score was 6 points. Mean improvement in urodynamic distress inventory-6 and SUI subscale scores was 14 and 53, respectively, surpassing the minimally important difference for each. Median follow-up time was 9 months (range 2-16). Leg pain at the harvest site was bothersome in 1 patient beyond 6 weeks. Median time to passing voiding trial was 4 days (range 1-13 days). Four patients (21%) had postoperative voiding dysfunction, 3 of which resolved after sling loosening at a mean of 60 days after sling placement. CONCLUSION: Midurethral autologous fascial sling placement significantly improves symptoms of SUI but carries a risk of voiding dysfunction. Harvesting fascia lata using a fascial stripper is associated with minimal postoperative morbidity.

Trends Among Female Pelvic Medicine and Reconstructive Surgery Fellowships and Graduates.

IMPORTANCE: Understanding differences in female pelvic medicine and reconstructive surgery (FPMRS) urology and gynecology-based fellowships is important because both are accredited by the American Board of Medical Subspecialties. OBJECTIVE: The aim of the study was to characterize urology-based and gynecology-based FPMRS fellowships. MATERIAL AND METHODS: An institutional review board-approved 21-item survey was emailed to Accreditation Council for Graduate Medical Education-accredited FPMRS fellowship program directors from January 8 through March 9, 2021. The survey aimed to characterize fellowships through a series of common and specialty-specific questions. Responses were collected with Qualtrics and analyzed using STATA/MP Version 16.1. RESULTS: The response rate was 75% (52/69). Many programs accept both gynecology- and urology-trained applicants (urology-based fellowships, 45.4%; gynecology-based fellowships, 68.3%) since the Accreditation Council for Graduate Medical Education accreditation in 2012. Within the gynecology-based cohort, there have been 10 urology-trained graduates among 7 programs (n = 1-2). Barriers to accepting urology applicants were limited gynecologic knowledge/experience (n = 14) and length of training (n = 11). Thirty-seven (94.8%) reported their graduates log more than 30 hysterectomies and 8.3% (n = 3) log 3 or more urinary diversions.Within the urology-based cohort, there have been 16 gynecology-trained graduates among 4 programs (n = 2-7). Lack of urologic clinical knowledge (n = 4) and training length (n = 2) were cited as barriers to accepting gynecology-trained applicants. Three (27%) reported that their graduates log more than 30 hysterectomies, while 8 (72.7%) reported that graduates log 3 or more urinary diversions. CONCLUSIONS: Despite many FPMRS programs stating that they accept gynecology or urology-trained applicants, few fellows graduate from outside specialty FPMRS training programs. Several barriers were identified that may prevent trainees acceptance outside of their residency specialty. Procedural training experience differs between urology- and gynecology-based fellowships.

Geographic Variation in Apical Support Procedures for Pelvic Organ Prolapse.

OBJECTIVE: To measure geographic variation in rates of apical support procedures for the treatment of pelvic organ prolapse (POP) among female Medicare beneficiaries. METHODS: We conducted a retrospective, cross-sectional study and used 100% Medicare fee-for-service claims to identify a cohort of women aged 65-99 years who had an apical support procedure, defined by Current Procedural Terminology codes, in 2016-2018. We included all vaginal and abdominal approaches (native tissue and mesh colpopexies) and obliterative procedures. We excluded vaginectomies with a diagnosis of gynecologic cancer that did not have a diagnosis for prolapse. We created rates of apical POP procedures by hospital referral region and computed coefficients of variation to measure the degree of geographic variation. RESULTS: An average of 26,005 apical POP procedures were performed annually from 2016 to 2018. The majority of patients were aged 65-74 years (64.3%), and 28.5% had concomitant hysterectomy. From 2016 to 2018, there was a mean of 1.79 apical POP procedures per 1,000 female beneficiaries performed across hospital referral regions (95% CI 1.74-1.84). Rate estimates ranged between 0.87 (95% CI 0.63-1.11) apical POP procedures per 1,000 female beneficiaries (Alexandria, Louisiana) and 3.33 (95% CI 2.91-3.74) per 1,000 beneficiaries (Akron, Ohio), a nearly fourfold difference in rates. Variation between hospital referral regions for abdominal apical prolapse procedures was the greatest (coefficient of variation 0.52). Vaginal and obliterative approaches demonstrated less variation between hospital referral regions (respectively, coefficient of variation 0.36 and 0.40). CONCLUSION: There is wide geographic variation among hospital referral regions for the treatment of POP. Women may be treated differently based on where they live and seek care, which raises questions about possible overuse in some regions and concerns about underuse and lack of access in other regions.

Cost-Effectiveness Analysis Between Sacral Neuromodulation and OnabotulinumtoxinA for the Treatment of Refractory Overactive Bladder in Women: A Systematic Review.

OBJECTIVE: We summarized the evidence evaluating the cost-effectiveness of sacral neuromodulation (SNM) versus onabotulinumtoxinA (BONT/A) in the treatment of refractory overactive bladder (OAB) among women. METHODS: We searched PubMed Medline (1946-2019), EMBASE (1947-2019), Web of Science (1900-2019), Clinical Trials.gov, reviewed references of included studies, and Cochrane subsets of CDSR, DARE, CENTRAL, and NHSEED. We included cost-utility and cost-effectiveness analyses or decision analysis comparing SNM versus BONT/A in women with nonneurogenic refractory OAB. Primary outcomes included incremental cost-effectiveness ratios (ICERs), reported as cost per quality-adjusted life year (QALY), which were abstracted or calculated. RESULTS: Five studies met the inclusion criteria. Three studies were industry supported. Two studies of high quality found BONT/A to be dominant over SNM (ICER range of $415,571/QALY at 5 years and $236,370/QALY at 10 years). This trend was further supported by a third study of high quality that favored BONT/A because SNM was not cost-effective (ICER, $116,427/QALY at 2 years). In contrast, 2 other studies of lower quality found that SNM was cost-effective or dominant in comparison to BONT/A (ICER range, $3,717/QALY to €15,226/QALY at 10 years). In general, models were sensitive to treatment duration, intervention setting, and lacked robust data on long-term outcomes. CONCLUSIONS: OnabotulinumtoxinA is more cost-effective for managing refractory OAB when compared with SNM. However, it remains unclear whether this finding holds true long term for what is considered a lifelong condition.

Autologous Fascia Lata for Combined Sacrocolpopexy and Rectopexy.

ABSTRACT: We present a case series and video of our technique using autologous fascia lata for combined sacrocolpopexy and rectopexy, with or without resection.

Information Priorities for Deciding on Treatment of Pelvic Organ Prolapse.

OBJECTIVE: The objective of this study was to elicit information priorities from women considering treatment for pelvic organ prolapse (POP). STUDY DESIGN: This is a cross-sectional study of women before and after treatment of stage II or higher POP. Women were recruited either at the conclusion of their initial evaluation (before treatment) or at postoperative or pessary maintenance visits (after treatment). Women completed a written survey that used a Likert scale to rank potentially frequently asked questions (FAQs) that could be important information to use in decision making for POP. RESULTS: Among the 100 women surveyed, 32 women wanted to pursue surgical options and 18 women wanted to pursue nonsurgical treatment options in the before treatment group. In the after treatment group, 35 women had undergone surgery and 15 women were using a pessary.Overall, women ranked FAQs about treatment success (overall Likert score, 1.11±0.35), quality of life after treatment (1.18±0.41), and complications and side effects (1.20±0.57) as the most important information when making a decision. Women were least concerned with FAQs regarding cost (2.39±1.48), impact on sexual function (2.21±1.4), and impact on hormones (2.20±1.27). CONCLUSIONS: Women with POP identified the most important FAQs related to treatment success and complications, quality of life, and understanding how the treatment works. This information will be used to develop a comprehensive decision aid for women considering treatment options for POP.

Major postoperative complications following surgical procedures for pelvic organ prolapse: a secondary database analysis of the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Surgical approaches to the correction of pelvic organ prolapse include abdominal, vaginal, and obliterative approaches. These approaches require vastly different anatomical dissections, surgical techniques, and operative times and are often selected by the patient and surgeon to match preoperative multimorbidity and ability of the patient to tolerate the stress of surgery. OBJECTIVE: We sought to describe the occurrence of postoperative complications occurring after 3 different surgical approaches to treat pelvic organ prolapse: vaginal, abdominal, and obliterative. STUDY DESIGN: We conducted a secondary database analysis of the 2006 through 2014 American College of Surgeons National Surgical Quality Improvement Program participant use data files to analyze patients undergoing procedures for pelvic organ prolapse based on Current Procedural Terminology codes. Women were categorized into 3 surgical approaches to prolapse: vaginal, abdominal, and obliterative. Concomitant hysterectomy and sling were also examined. The primary outcome was a composite of 30-day major postoperative complications. RESULTS: A total of 33,416 women were included in our final analysis: 24,928 vaginal procedures, 6834 abdominal (4461 minimally invasive) procedures, and 1654 obliterative procedures. Concomitant hysterectomies and slings were performed in 17,380 (52.0%) and 10,896 (32.6%) of prolapse procedures. The overall prevalence of composite 30-day major postoperative complications was 3.1% (n/N = 1028/33,416). There were 13 perioperative deaths (0.04%) with no difference in the surgical approaches (P = .55). There were no differences in major postoperative complications between vaginal and abdominal procedures (3.0% vs 3.0%; P = .71). Women undergoing obliterative procedures had an occurrence of major postoperative complications of 5.0% (n/N = 83/1654), P < .001. CONCLUSION: The occurrence of major postoperative complications after prolapse surgery is rare. We did not find a significant difference in major postoperative complications between vaginal and abdominal surgeries for pelvic organ prolapse. In this well-characterized cohort of patients who self-selected surgical approach, women undergoing obliterative surgery had more postoperative complications, likely attributed to increased age and multimorbidity.

Functional disability and compromised mobility among older women with urinary incontinence.

OBJECTIVE: Our objective was to determine the prevalence of functional disability among older women with urinary incontinence (UI). METHODS: We conducted a secondary analysis of the 2005-2006 National Social Life, Health and Aging Project. Daily UI was defined as answering "daily" to the question, "How frequently… have you had difficulty controlling your bladder, including leaking small amounts of urine, leaking when you cough or sneeze, or not being able to make it to the bathroom on time?" We then explored functional status. Women were asked about 7 basic activities of daily living (ADLs). Statistical analyses with percentage estimates and 95% confidence intervals (CIs) were performed. Logistic regression was performed to assess the association between functional status and daily UI. RESULTS: In total, 1412 women were included in our analysis. Daily UI was reported by 177 (12.5%) women. Functional dependence or disability with any activities of daily living was reported in 62.1% (95% CI, 54.2%-70.1%) of women with daily UI. Among women with daily UI, 23.6% (95% CI, 16.8%-30.5%) reported specific difficulty or dependence with using the toilet, signifying functional limitations which may contribute to urine leakage. After adjusting for age category, race/ethnicity, education level, and parity, women with daily UI had 3.31 increased odds of functional difficulty or dependence compared with continent older women. CONCLUSIONS: More than 60% of older women with daily UI reported functional difficulty or dependence and one fourth of women with daily UI specifically reported difficulty or dependence with using the toilet.

Functional disability among older women with fecal incontinence.

OBJECTIVE: The prevalence of functional disability for basic activities of daily living (ADLs) in older women with fecal incontinence (FI) is not well characterized. Our objective was to determine the prevalence of functional disability among community-dwelling older women with FI. STUDY DESIGN: We conducted a secondary database analysis of the 2005-2006 National Social Life, Health and Aging Project, a cross-sectional study of community-dwelling older adults that had been conducted by single in-home interviews. FI was defined as an affirmative answer to the question, "Have you lost control of your bowels (stool incontinence or anal incontinence)?" with a frequency of "at least monthly." We then examined functional status. Women were asked about 7 basic ADLs. Statistical analyses with percentage estimates and 95% confidence intervals (CIs) were performed. RESULTS: We included 1412 women in our analysis. FI, at least monthly, was reported by 5.5% of community-dwelling older women (n = 77); 63.2% (95% CI, 50.1-76.4) of the women with FI reported difficulty or dependence with ≥1 ADLs, and 31.2% (95% CI, 18.9-43.6) of the women specifically reported difficulty or dependence with using the toilet. After adjustment for age category, race/ethnicity, education level, women with FI had 2.6 increased odds (95% CI, 1.26-5.35) of difficulty or dependence compared with women with no FI. Other significant risk factors for increased functional difficulty/dependence included obesity (body mass index, ≥30 kg/m(2)) and depressive symptoms. CONCLUSION: Consistent with other large epidemiologic studies, we found monthly FI was reported by 5.5% of older women (n/N = 77/1412). More than 60% of community-dwelling older women with FI report functional difficulty or dependence with ≥1 ADL and specifically; more than 30% of women with FI report difficulty or dependence using/reaching the toilet. Because of the high prevalence of functional disability in older women with FI, we purpose that initial evaluation and treatment of FI may be improved by considering functional status.

Frailty, cognitive impairment, and functional disability in older women with female pelvic floor dysfunction.

INTRODUCTION AND HYPOTHESIS: There is a growing body of evidence demonstrating frailty as an important predictor of surgical outcomes in older adults undergoing major surgeries. The age-related onset of many symptoms of female pelvic floor dysfunction (PFD) in women suggests that many women seeking treatment for PFD may also have a high prevalence of frailty, which could potentially impact the risks and benefits of surgical treatment options. Our primary objective was to determine the prevalence of frailty, cognitive impairment, and functional disability in older women seeking treatment for PFD. METHODS: We conducted a cross-sectional study with prospective recruitment between September 2011 and September 2012. Women, age 65 years and older, were recruited at the conclusion of their new patient consultation for PFD at a tertiary center. A comprehensive geriatric screening including frailty measurements (Fried Frailty Index), cognitive screening (Saint Louis University Mental Status score), and functional status evaluation for activities of daily living (Katz ADL score) was conducted. RESULTS: Sixteen percent (n/N = 25/150) of women were categorized as frail according to the Fried Frailty Index score. After adjusting for education level, 21.3 % of women (n/N = 32/150) screened positive for dementia and 46 (30.7 %) reported functional difficulty or dependence in performing at least one Katz ADL. Sixty-nine women (46.0 %) chose surgical options for treatment of their PFD at the conclusion of their new patient visit with their physician. CONCLUSIONS: Frailty, cognitive impairment, and functional disability are common in older women seeking treatment for PFD.

Anatomic and functional outcomes of sacrocolpopexy with or without posterior colporrhaphy.

INTRODUCTION AND HYPOTHESIS: The optimal surgery for combined apical and posterior vaginal prolapse is not well defined. Our objective was to examine the anatomic and functional outcomes following sacrocolpopexy (SCP) with or without posterior colporrhaphy (PC). METHODS: We retrospectively evaluated 258 women who underwent abdominal (n = 62) or laparoscopic (n = 196) SCP with or without PC. Preoperative anatomic support and standardized bowel symptoms were compared to 6-week and 1-year postoperative values, using Student's t test and Wilcoxon rank sum test, respectively. RESULTS: Six-week follow-up data were available for 235 of 258 (91.1 %) women, while 125 of 258 (48.4 %) women had 1-year anatomic and functional outcomes recorded. While the SCP + PC group had worse posterior descent and bowel function preoperatively, there were no significant differences in postoperative anatomic support or symptoms. Long-term pelvic floor function was similar, as measured by three validated instruments. Reduction in the proportion of women with splinting was greater in the SCP + PC group. CONCLUSIONS: SCP with or without PC is associated with improved posterior support and decreased obstructive and irritative bowel symptoms at 1 year in women with apical and posterior prolapse.

Does pelvic organ prolapse reduction affect abdominal leak point pressures?

OBJECTIVE: To determine if pelvic organ prolapse reduction decreases cystometric leak point pressure. STUDY DESIGN: A retrospective review was performed of women with pelvic organ prolapse points Aa, Ba or C > or = -1 cm that leaked with and without vaginal support (barrier testing) during multichannel urodynamic investigation (N=44). An analysis of the mean and difference between leak point pressure (LPP) (vesicle pressure) with and without prolapse reduction was used to determine significance. RESULTS: Among 460 possible study subjects, 15% (71/460) leaked only with and 4% (17/460) only without prolapse reduction. Among the 44 women who leaked both with and without prolapse reduction, prolapse reduction was associated with a mean decrease in LPP of 16.1 cm H2O (95% CI 7.4-24.7, p = 0.0005). CONCLUSION: Reduction of pelvic organ prolapse is associated with a mean decrease in LPP of 16.1 cm H2O.

Urodynamic leak point pressures weakly correlate with subjective urinary incontinence severity.

OBJECTIVE: To evaluate preoperative abdominal leak point pressures (ALPP) with pre- and postoperative Incontinence Severity Index (ISI) scores. METHODS: A review of women who underwent a midurethral sling procedure between August 2004 and April 2006 was conducted. Eligible women completed preoperative urodynamic testing with ALPP determination and subjective incontinence severity assessment using the ISI before and 6 weeks after surgery. The ISI and ALPP relationship was analyzed using a Spearman rank correlation (Rho). RESULTS: Ninety-nine women met the inclusion criteria. Mean ALPP was 77.7 (25-172 cm H2O). Mean improvement in ISI following surgery was 4 (-8 to 12). ALPP correlated with preoperative ISI (Spearman Rho -0.28, P=0.01), preoperative leakage frequency (ISI question 1) (Spearman Rho -0.32, P=0.001), and the ISI change 6 weeks postoperatively (ISI-delta) (Spearman Rho -0.23, P=0.002). CONCLUSION: ALPP is associated with subjective incontinence severity. Women with the lowest ALPP improved most following a midurethral sling procedure.

Duloxetine compared with placebo for treating women with symptoms of overactive bladder.

OBJECTIVE: To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model. PATIENTS AND METHODS: In all, 306 women (aged 21-84 years) were recruited and randomly assigned to placebo (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks; 153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge urinary incontinence (UI) for > or =3 months. Participants were also required to have a mean daytime voiding interval (VI) of < or=2 h and urodynamic observations of either detrusor overactivity (DOA) or urgency which limited bladder capacity to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared the treatment effects on mean change from baseline to endpoint in the mean number of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety was assessed with vital signs, adverse event reporting, routine laboratory testing, electrocardiogram, and the measurement of postvoid residual urine volumes (PVR). RESULTS: Patients randomized to duloxetine had significant improvements over those randomized to placebo for decreases in VE and IE, for increases in the daytime VI, and for improvements in I-QOL scores at both doses of duloxetine. Urodynamic studies showed no significant increases in maximum cystometric capacity or in the volume threshold for DOA. The most common treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%; dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same as those reported by women with SUI and were significantly more common with duloxetine than placebo. Laboratory assessments, vital signs and electrocardiograms were stable relative to baseline, with no relevant differences detected between groups. There was a significant difference in the change in PVR with duloxetine (<5 mL mean increase) but no patient reported hesitancy or retention. CONCLUSION: In this trial, duloxetine was better than placebo for treating women with 'wet' and 'dry' symptoms of OAB associated with DOA or a bladder capacity of <400 mL.