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Author(s): Jelovsek, J Eric; Chagin, Kevin; Lukacz, Emily S; Nolen, Tracy L; Shepherd, Jonathan P; Barber, Matthew D; Sung, Vivian; Brubaker, Linda; Norton, Peggy A; Rahn, David D; Smith, Ariana L; Ballard, Alicia; Jeppson, Peter; Meikle, Susan F; Kattan, Michael W; NICHD Pelvic Floor Disorders Network | Abstract: ObjectiveTo develop statistical models predicting recurrent pelvic organ prolapse, surgical complications, and change in health status 12 months after apical prolapse surgery.MethodsLogistic regression models were developed using a combined cohort from three randomized trials and two prospective cohort studies from 1,301 participants enrolled in surgical studies conducted by the Pelvic Floor Disorders Network. Composite recurrent prolapse was defined as prolapse beyond the hymen; the presence of bothersome bulge symptoms; or prolapse reoperation or retreatment within 12 months after surgery. Complications were defined as any serious adverse event or Dindo grade III complication within 12 months of surgery. Significant change in health status was defined as a minimum important change of SF-6D utility score (±0.035 points) from baseline. Thirty-two candidate risk factors were considered for each model and model accuracy was measured using concordance indices. All indices were internally validated using 1,000 bootstrap resamples to correct for bias.ResultsThe models accurately predicted composite recurrent prolapse (concordance index=0.72, 95% CI 0.69-0.76), bothersome vaginal bulge (concordance index=0.73, 95% CI 0.68-0.77), prolapse beyond the hymen (concordance index=0.74, 95% CI 0.70-0.77), serious adverse event (concordance index=0.60, 95% CI 0.56-0.64), Dindo grade III or greater complication (concordance index=0.62, 95% CI 0.58-0.66), and health status improvement (concordance index=0.64, 95% CI 0.62-0.67) or worsening (concordance index=0.63, 95% CI 0.60-0.67). Calibration curves demonstrated all models were accurate through clinically useful predicted probabilities.ConclusionThese prediction models are able to provide accurate and discriminating estimates of prolapse recurrence, complications, and health status 12 months after prolapse surgery.

Interstitial cystitis/painful bladder syndrome is a chronic pelvic pain condition of unknown etiology. We hypothesized that related interstitial cystitis/painful bladder syndrome cases were more likely to have a genetic etiology. The purpose of this study was to perform a genetic linkage analysis.We identified interstitial cystitis/painful bladder syndrome cases using diagnostic codes linked to the Utah Population Database genealogy resource and to electronic medical records. For this analysis we used 13 high risk pedigrees, defined as having a statistical excess number of interstitial cystitis/painful bladder syndrome cases among descendants compared to matched hospital population rates. Case status was confirmed in medical records using natural language processing. DNA was obtained from stored, nonneoplastic, formalin fixed, paraffin embedded tissue blocks. Each pedigree had at least 2 cases with DNA available. Parametric linkage analysis was performed.Pedigrees ranged in size from 2 to 12 genotyped cases for a total of 48 cases. Significant genome wide linkage evidence was found under a dominant model on chromosome 3p13-p12.3 (maximum heterogeneity θ logarithm of odds 3.56). Two pedigrees showed at least nominal linkage evidence in this region (logarithm of odds greater than 0.59). The most informative pedigree included 12 interstitial cystitis/painful bladder syndrome cases (pedigree θ logarithm of odds 2.1). Other regions with suggestive linkage evidence included 1p21-q25, 3p21.1-p14.3, 4q12-q13, 9p24-p22 and 14q24-q31, all under a dominant model.While the etiology of interstitial cystitis/painful bladder syndrome is unknown, this study provides evidence that a genetic variant(s) on chromosome 3 and possibly on chromosomes 1, 4, 9 and 14 contribute to an interstitial cystitis/painful bladder syndrome predisposition. Sequence analysis of affected cases in identified pedigrees may provide insight into genes contributing to interstitial cystitis/painful bladder syndrome.

Family history of pelvic organ prolapse among first-degree relatives is an established risk factor for pelvic organ prolapse; however, consideration of the constellation of family history that extends to distant relationships allows for more accurate determination of risk and may improve pelvic organ prolapse risk prediction estimates.The purpose of this study was to assess risk for pelvic organ prolapse treatment based on varying family histories of pelvic organ prolapse and included number and types of affected relatives, ages of relatives at pelvic organ prolapse treatment, and whether the family history is of maternal or paternal origin.This was a retrospective, population-based study that involved the Utah Population Database, which is a population resource that includes extensive genealogy information linked to medical records. The study population included 453,522 total women: 4628 women with a diagnosis of treated (surgical or pessary) pelvic organ prolapse and their 15,530 first-degree relatives; 33,782 second-degree relatives, and 66,469 third-degree relatives. We estimated relative risk of treated pelvic organ prolapse based on specific family history constellations.Relative risk estimates increased with a family history of increasing numbers of treated first-degree relatives with pelvic organ prolapse (first-degree relatives, ≥1 [relative risk, 2.36; 95% confidence interval, 2.15-2.58], first-degree relatives, ≥2 [relative risk, 3.79; 95% confidence interval, 2.65-5.24], and first-degree relatives, ≥3 [relative risk, 6.26; 95% confidence interval, 1.29-18.30]). Having a family history of ≥3 affected third-degree relatives (eg, first cousins) and no affected first- or second-degree relatives was similar in risk to having 1 affected first-degree relative. Relative risk estimates decreased with increasing age of treatment for first-degree family members. Risks in individuals with a positive maternal family history for pelvic organ prolapse were consistently higher than risks in individuals with equivalent paternal family history, but paternal inheritance still played a role. Approximately 4% of the total studied female population was found to have a2-fold risk of being treated for pelvic organ prolapse and is considered high-risk based on their family history.We provide estimates for treated pelvic organ prolapse based on an extensive family history of pelvic organ prolapse using a large population-based sample. Risk for treated pelvic organ prolapse increased with increasing numbers of affected close and distant female relatives, earlier age of pelvic organ prolapse treatment in relatives, and maternal inheritance. These risk estimates may be useful for genetic studies and investigation of risk reduction strategies in those at highest risk for pelvic organ prolapse.

ObjectiveTo longitudinally assess the effect of native tissue vaginal apical prolapse repair with anti-incontinence surgery on quality of life, sexual function, and body image between uterosacral and sacrospinous suspensions.MethodsA planned secondary analysis was performed on 374 women enrolled in a randomized trial of the two types of native tissue repair for apical prolapse. Condition-specific and generic quality of life, sexual function, overall and de novo dyspareunia, and body image were assessed using validated instruments at baseline; 6, 12, and 24 months postoperatively; and changes from baseline were assessed and compared between surgical groups. General linear mixed models were used for comparisons and clinically significant differences were assessed using minimum important differences.ResultsOf the women randomized, 82% had outcomes available at 2 years. Overall, clinically and statistically significant improvements in generic and condition-specific quality of life and sexual function were observed after surgery. Dyspareunia rates decreased from 25% to 16% by 24 months with only 3% of all women undergoing treatment. De novo dyspareunia occurred in 5% and 10% by 12 and 24 months, respectively. Body image scores also significantly improved from baseline. There were no clinically meaningful or statistically significant differences between groups for any of these outcomes (all P>.05).ConclusionNative tissue vaginal prolapse surgery results in statistically and clinically significant improvements in quality of life, sexual function, and body image at 24 months with no significant differences between uterosacral and sacrospinous suspensions. One in 10 women experience de novo dyspareunia but few requested treatment.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT00597935.

OBJECTIVES Medication adherence with urgency urinary incontinence (UUI) treatment is challenging and the best assessment methodology is uncertain. We sought to describe adherence with anticholinergic (AC) versus placebo (P) by comparing pill counts and MEMSCAP event data and to identify factors associated with adherence. METHODS The randomized controlled AC versus Botox Comparison trial of women with moderate to severe idiopathic UUI included 126 participants initiating AC plus P bladder injection and 121 receiving P pills plus Botox injection. Adherence data on 243 participants (124 AC and 119 P) were calculated by pill count and MEMSCAP data for each 2-month interval during the 6-month study that allowed for dose escalation/drug change. Overall composite adherence estimates were calculated using the average of both methods and weighted by the duration of each 2-month interval. RESULTS Treatment groups had no significant differences in dosing duration (P = 0.76) or mean adherence (AC, 83.3% [16.8] vs. P, 84.8% [13.8]). Only 53% of women met the dichotomous outcome of more than 80% adherence during all intervals. Correlation between adherence by pill counts versus MEMSCAP decreased over time with pill counts demonstrating higher adherence than MEMSCAP (r = 0.53, 0.50, and 0.36 for each 2-month interval). Lower adherence was associated with higher baseline incontinence severity and better UUI quality of life for the AC group and with current smoking status in both groups. CONCLUSIONS Adherence using pill counts and MEMSCAP was reasonably correlated and similar in both the AC and P groups. In the AC group, higher baseline incontinence severity and better UUI Quality of Life were associated with decreased adherence. Smokers were less adherent.

Objective This study aimed to describe the incidence of fecal incontinence (FI) at 6, 12, and 24 weeks postpartum; anal incontinence (AI) and fecal urgency at 24 weeks; and identify predictors of AI in women with obstetric anal sphincter injury (OASI). Methods Primiparous women sustaining OASIs were identified at 8 clinical sites. Third-degree OASIs were characterized using World Health Organization criteria, 3a ( 50%) tear through the sphincter. Fecal incontinence was defined as leakage of liquid/solid stool and/or mucus in the past month; AI was defined as leakage of liquid/solid stool and/or mucus and/or gas in the past month and was assessed at 6, 12, and 24 weeks postpartum using the Fecal Incontinence Severity Index. Logistic regression identified variables associated with AI. Results Three hundred forty-three women participated: 297 subjects sustained a third-degree OASI, 168 type 3a, 98 type 3b and 31 indeterminant; 45 had a fourth-degree OASI. Overall FI incidence at 6, 12, and 24 weeks was 7% [23/326; 95% confidence interval (CI), 4%-10%], 4% (6/145; 95% CI, 2%-9%), and 9% (13/138; 95% CI, 5%-16%), respectively. At 24 weeks, AI incidence was 24% (95% CI, 17%-32%) and fecal urgency 21% (95% CI, 15%-29%). No significant differences in FI and AI rates were noted by third-degree type or between groups with third and fourth OASI. Flatal incontinence was greater in women sustaining a fourth-degree tear (35% vs 16%, P = 0.04). White race (adjusted odds ratio, 4.64; 95% CI, 1.35-16.02) and shorter duration of second stage (adjusted odds ratio, 1.47 per 30 minute decrease; 95% CI, 1.12-1.92) were associated with AI at 24 weeks. Conclusions Overall 24-week incidence of FI is 9% (95% CI, 5%-16%) and AI is 24% (95% CI, 17%-32%). In women with OASI, white race and shorter second-stage labor were associated with postpartum AI. Clinical trial registration NCT01166399 (http://clinicaltrials.gov).

Author(s): Lukacz, ES; Warren, LK; Richter, HE; Brubaker, L; Barber, MD; Norton, P; Weidner, AC; Nguyen, JN; Gantz, MG

Author(s): Zimmern, Philippe E; Gormley, E Ann; Stoddard, Anne M; Lukacz, Emily S; Sirls, Larry; Brubaker, Linda; Norton, Peggy; Oliphant, Sallie S; Wilson, Tracey | Abstract: AimsTo examine treatment options selected for recurrent stress urinary incontinence (rSUI) in follow-up after Burch, autologous fascial and synthetic midurethral sling (MUS) procedures.MethodsWe performed a secondary analysis of the SISTER and ToMUS trials of participants who underwent primary stress urinary incontinence (SUI) treatment (without prior SUI surgery or concomitant procedures). Using Kaplan-Meier analysis, retreatment-free survival rates by initial surgical procedure were compared. Mean MESA (Medical Epidemiologic and Social Aspects of Aging) stress index was also compared between those retreated for rSUI compared to those not retreated.ResultsHalf of the women in the SISTEr trial met inclusion criteria for this analysis (329/655, 174 Burch and 155 fascial sling), as did 444/597 (74%) of subjects in ToMUS (221 transobturator midurethral sling (TMUS), and 223 retropubic midurethral sling (RMUS). Types of surgical retreatment included autologous fascial sling (19), synthetic sling (1), and bulking agent (18). Five-year retreatment free survival rates (and standard errors) were 87% (3%), 96% (2%), 97% (1%), and 99% (0.7%) for Burch, autologous fascial sling, TMUS, and RMUS groups respectively (P l 0.0001). For all index surgery groups, the mean MESA stress index at last visit prior to retreatment for those retreated (n = 23) was significantly higher than mean MESA stress index at last visit for those not retreated (n = 645) (P l 0.0001).ConclusionIn these cohorts, 6% of women after standard anti-incontinence procedures were retreated within 5 years, mostly with injection therapy or autologous fascial sling. Not all women with rSUI chose surgical retreatment.

Aims Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress urinary incontinence (SUI), despite insufficient evidence that it impacts treatment plans or outcomes in patients with uncomplicated SUI. This analysis aimed to calculate the cost incurred when UDS was performed as a supplement to a basic office evaluation and to extrapolate the potential savings of not doing UDS in this patient population on a national basis. Methods This is a secondary analysis from the Value of Urodynamic Evaluation (ValUE) trial, a multicenter non-inferiority randomized trial to determine whether a basic office evaluation (OE) is non-inferior in terms of SUI surgery outcomes to office evaluation with addition of urodynamic studies (UDS). All participants underwent an OE; those patients who randomized to supplementary UDS underwent non-instrumented uroflowmetry, filling cystometry, and a pressure flow study. Costs associated with UDS were calculated using 2014 U.S. Medicare allowable fees. Models using various patient populations and payor mixes were created to obtain a range of potential costs of performing UDS in patients undergoing SUI surgery annually in the United States. Results Six hundred thirty women were randomized to OE or OE plus UDS. There was no difference in surgical outcomes between the two groups. The per patient cost of UDS varied from site to site, and included complex cystometrogram $314–$343 (CPT codes 51728–51729) plus complex uroflowmetry $16 (CPT code 51741). Extrapolating these costs for US women similar to our study population, 13–33 million US dollars could be saved annually by not performing preoperative urodynamics. Conclusion For women with uncomplicated SUI and a confirmatory preoperative basic office evaluation, tens of millions of dollars US could be saved annually by not performing urodynamic testing. In the management of such women, eliminating this preoperative test has a major economic benefit. Neurourol. Urodynam. 35:81–84, 2016. © 2014 Wiley Periodicals, Inc.

Aims The Blaivas–Groutz nomogram defines voiding obstruction in women using Qmax from the NIF and the maximum detrusor pressure (Pdetmax) from the PFS. The aim of this study was to understand the relationship between NIF and PFS maximum flow rates in women with stress incontinence. Methods We analyzed the UDS of 597 women with stress-dominant urinary incontinence. Each subject underwent a NIF and then a PFS. Mixed model was used to test the hypothesis that the relationship between flow rates and voided volume (VV) were similar for NIF and PFS. Results There were 452 subjects with both NIF and PFS studies that met the inclusion criteria and had max flow rate (Qmax) for both NIF and PFS. The mean age was 53. Overall, higher VV were observed during PFS compared to NIF and subjects had higher Qmax with NIF compared to PFS. The relationship between Qmax and VV was significantly different between NIF and PFS (P

Importance Uterosacral ligament suspension (ULS) and sacrospinous ligament fixation (SSLF) are commonly performed pelvic organ prolapse procedures despite a lack of long-term efficacy data. Objective To compare outcomes in women randomized to (1) ULS or SSLF and (2) usual care or perioperative behavioral therapy and pelvic floor muscle training (BPMT) for vaginal apical prolapse. Design, Setting, and Participants This 2 × 2 factorial randomized clinical trial was conducted at 9 US medical centers. Eligible participants who completed the Operations and Pelvic Muscle Training in the Management of Apical Support Loss Trial enrolled between January 2008 and March 2011 and were followed up 5 years after their index surgery from April 2011 through June 2016. Interventions Two randomizations: (1) BPMT (n = 186) or usual care (n = 188) and (2) surgical intervention (ULS: n = 188 or SSLF: n = 186). Main Outcomes and Measures The primary surgical outcome was time to surgical failure. Surgical failure was defined as (1) apical descent greater than one-third of total vaginal length or anterior or posterior vaginal wall beyond the hymen or retreatment for prolapse (anatomic failure), or (2) bothersome bulge symptoms. The primary behavioral outcomes were time to anatomic failure and Pelvic Organ Prolapse Distress Inventory scores (range, 0-300). Results The original study randomized 374 patients, of whom 309 were eligible for this extended trial. For this study, 285 enrolled (mean age, 57.2 years), of whom 244 (86%) completed the extended trial. By year 5, the estimated surgical failure rate was 61.5% in the ULS group and 70.3% in the SSLF group (adjusted difference, −8.8% [95% CI, −24.2 to 6.6]). The estimated anatomic failure rate was 45.6% in the BPMT group and 47.2% in the usual care group (adjusted difference, −1.6% [95% CI, −21.2 to 17.9]). Improvements in Pelvic Organ Prolapse Distress Inventory scores were −59.4 in the BPMT group and −61.8 in the usual care group (adjusted mean difference, 2.4 [95% CI, −13.7 to 18.4]). Conclusions and Relevance Among women who had undergone vaginal surgery for apical pelvic organ vaginal prolapse, there was no significant difference between ULS and SSLF in rates of surgical failure and no significant difference between perioperative behavioral muscle training and usual care on rates of anatomic success and symptom scores at 5 years. Compared with outcomes at 2 years, rates of surgical failure increased during the follow-up period, although prolapse symptom scores remained improved. Trial Registration clinicaltrials.gov Identifier:NCT01166373

Objective To describe the prevalence and risk factors for incomplete bladder emptying after midurethral slings (MUS) in a large multicenter trial. Methods Five hundred ninety-seven women were randomized to retropubic (RMUS) or transobturator midurethral slings as part of the Trial of MidUrethral Slings study. Demographic data and voiding symptoms were obtained preoperatively along with urodynamics. Patients underwent a standardized voiding trial at discharge after continence surgery. Incomplete bladder emptying was defined as a postvoid residual of >150 mL. Results Three-quarters of patients (454 of 597) were self-voiding at discharge, whereas 114 of 597 (19%) were managed with an indwelling urethral catheter and 29 of 597 (5%) with intermittent catheterization. At 2 weeks, only 38 of 586 (6%) reported any catheter use, and by 6 weeks, only 9 of 587 (2%) reported any catheter use. Women with incomplete bladder emptying at discharge were more likely to have had a RMUS (odds ratio 1.79; 95% confidence interval 1.22-2.62) and to report preoperative voiding accommodations such as straining to void (odds ratio 1.75; 95% confidence interval 1.04-2.96). Urodynamic and clinicodemographic parameters were not predictive of incomplete bladder emptying. Conclusion Incomplete bladder emptying at discharge after MUS is common, especially after RMUS, but of short duration. Risk factors include preoperative voiding accommodations such as straining or bending over to void, but other variables including urodynamics did not predict incomplete bladder emptying after MUS.

Aims This study examined the association between the need for a repeat voiding trial after midurethral sling (MUS) surgery and 1-year success rates. Methods We conducted this secondary analysis of the participants in the Urinary Incontinence Treatment Network trial of midurethral sling (TOMUS) study which compared retropubic versus transobturator MUS. A standard voiding trial was attempted on all subjects. The “repeat voiding trial” group included subjects discharged with catheterization. All others were considered “self voiding.” Success rates between the groups at 1-year were compared, followed by multivariate analyses controlling for previously reported clinical predictors of success. Results Most women (76%) were self-voiding, while 24% required a repeat voiding trial. The objective success rate at 1-year was 85.8% in the repeat voiding trial group and 75.3% in the self-voiding group (P = 0.01). Subjective success rate at 1-year was 61.0% in the repeat voiding trial group and 55.1% in the self-voiding group (P = 0.23). Women in the repeat voiding trial group continued to demonstrate greater objective success than the self-voiding group in multivariate analysis that controlled for previous incontinence surgery, pad weight, urethral mobility, urge score, and type of MUS (P = 0.04, OR 1.82, 95% CI 1.03–3.22). Conclusions Women who require a repeat voiding trial following MUS surgery have greater objective success at 1-year postoperatively when compared to those who are self-voiding at the time of discharge. These results may help reassure women who require catheterization after MUS surgery that their outcome is not compromised by this immediate transient post-operative result. Neurourol. Urodynam. 33:1225–1228, 2014. © 2013 Wiley Periodicals, Inc.

UT Southwestern Medical Center, Dallas, TexasAims: To determine if pre-operative urodynamic testing (UDS) affects physicians’ diagnostic confidence and ifphysician confidence affects treatment outcomes at 1 year. Methods: The Value of Urodynamic Evaluation(ValUE) trial randomized 630 women with predominant stress urinary incontinence (SUI) to office evaluation (OE)or OE plus UDS prior to surgery. After OE, physicians completed a checklist of five clinical diagnoses: SUI, overactivebladder (OAB) wet and dry, voiding dysfunction (VD), and intrinsic sphincter deficiency (ISD), and reportedtheir confidence in each. Responses ranged from 1 to 5 with; 1¼‘‘not very confident (

Author(s): Lukacz, ES; Warren, LK; Richter, HE; Brubaker, L; Barber, MD; Norton, P; Weidner, AC; Nguyen, JN; Gantz, MG

Introduction Pelvic floor disorders (PFDs), including pelvic organ prolapse (POP), stress and urgency urinary incontinence, and faecal incontinence, are common and arise from loss of pelvic support. Although severe disease often does not occur until women become older, pregnancy and childbirth are major risk factors for PFDs, especially POP. We understand little about modifiable factors that impact pelvic floor function recovery after vaginal birth. This National Institutes of Health (NIH)-funded Program Project, ‘Bridging physical and cultural determinants of postpartum pelvic floor support and symptoms following vaginal delivery’, uses mixed-methods research to study the influences of intra-abdominal pressure, physical activity, body habitus and muscle fitness on pelvic floor support and symptoms as well as the cultural context in which women experience those changes. Methods and analysis Using quantitative methods, we will evaluate whether pelvic floor support and symptoms 1 year after the first vaginal delivery are affected by biologically plausible factors that may impact muscle, nerve and connective tissue healing during recovery (first 8 weeks postpartum) and strengthening (remainder of the first postpartum year). Using qualitative methods, we will examine cultural aspects of perceptions, explanations of changes in pelvic floor support, and actions taken by Mexican-American and Euro-American primipara, emphasising early changes after childbirth. We will summarise project results in a resource toolkit that will enhance opportunities for dialogue between women, their families and providers, and across lay and medical discourses. We anticipate enrolling up to 1530 nulliparous women into the prospective cohort study during the third trimester, following those who deliver vaginally 1 year postpartum. Participants will be drawn from this cohort to meet the project9s aims. Ethics and dissemination The University of Utah and Intermountain Healthcare Institutional Review Boards approved this study. Data are stored in a secure password-protected database. Papers summarising the primary results and ancillary analyses will be published in peer-reviewed journals.

We evaluated the influence of preoperative urodynamic studies on diagnoses, global treatment plans and outcomes in women treated with surgery for uncomplicated stress predominant urinary incontinence.We performed a secondary analysis from a multicenter, randomized trial of the value of preoperative urodynamic studies. Physicians provided diagnoses before and after urodynamic studies and global treatment plans, defined as proceeding with surgery, surgery type, surgical modification and nonoperative therapy. Treatment plan changes and surgical outcomes between office evaluation and office evaluation plus urodynamic studies were compared by the McNemar test.Of 315 subjects randomized to urodynamic studies after office evaluation 294 had evaluable data. Urodynamic studies changed the office evaluation diagnoses in 167 women (56.8%), decreasing the diagnoses of overactive bladder-wet (41.6% to 25.2%, p0.001), overactive bladder-dry (31.4% to 20.8%, p = 0.002) and intrinsic sphincter deficiency (19.4% to 12.6%, p = 0.003) but increasing the diagnosis of voiding dysfunction (2.2% to 11.9%, p0.001). After urodynamic studies physicians canceled surgery in 4 of 294 women (1.4%), changed the incontinence procedure in 13 (4.4%) and planned to modify mid urethral sling tension (more or less obstructive) in 20 women (6.8%). Nonoperative treatment plans changed in 40 of 294 women (14%). Urodynamic study driven treatment plan changes were not associated with treatment success (OR 0.96, 95% CI 0.41, 2.25, p = 0.92) but they were associated with increased postoperative treatment for urge urinary incontinence (OR 3.23, 95% CI 1.46, 7.14, p = 0.004).Urodynamic studies significantly changed clinical diagnoses but infrequently changed the global treatment plan or influenced surgeon decision to cancel, change or modify surgical plans. Global treatment plan changes were associated with increased treatment for postoperative urgency urinary incontinence.

To assess change in overactive bladder (OAB) symptoms up to 5 years after surgery and to identify associated predictors of change from baseline.This is a secondary analysis of data from three multicenter urinary incontinence (UI) surgical trials of women with stress-predominant mixed UI assigned to Burch colposuspension, autologous fascial sling, or retropubic or transobturator midurethral slings. The primary outcome was improvement of 70% or greater from baseline in symptoms measured by the Urinary Distress Inventory-Irritative subscale. Surgical groups were compared within respective trials. Generalized linear models were fit using 1-year and up to 5-year data.Significant improvements in Urinary Distress Inventory-Irritative scores were reported by each surgical group 1 year after surgery (P.001). Most women (50-71%) reported improvement in OAB symptoms. Improvements were similar between midurethral sling groups at 1 year (65.5% compared with 70.7%, P=.32; odds ratio [OR] 0.83, 95% confidence interval [CI] 0.57-1.20 for retropubic compared with transobturator sling) and throughout the 5-year follow-up period. More women reported OAB symptom improvement after Burch compared with pubovaginal sling (67.9% compared with 56.6%, P=.01; OR 1.59, 95% CI 1.10-2.31 for Burch compared with sling); this group difference at 1 year persisted throughout the 5-year follow-up. At 1-year, 50.0-64.3% of patients reported 70% greater improvement in UI. This proportion declined to 36.5-54.1% at 5 years (P.001). Preoperative use of anticholinergics and urodynamic parameters was not predictive of OAB symptom change after surgery.Most women with stress-predominant mixed UI experienced significant improvement in OAB symptoms after incontinence surgery although this initial improvement diminished over time. Obesity blunted symptom improvement.II.

PurposeLonger term comparative efficacy information regarding transobturator and retropubic mid urethral slings is needed. We report 24-month continence rates, complications and symptom outcomes from a randomized equivalence trial.Materials and MethodsPrimary outcomes were objective (negative stress test, negative pad test and no re-treatment for stress urinary incontinence) and subjective (no self-report of stress urinary incontinence symptoms, no leakage episodes on 3-day bladder diary and no re-treatment for stress urinary incontinence) success at 24 months. The predetermined equivalence margin was ±12%.ResultsOf 597 randomized participants 516 (86.4%) were assessed. Objective success rates for retropubic and transobturator mid urethral slings were 77.3% and 72.3%, respectively (95% CI for difference of 5.1% was −2.0, 12.1), and subjective success rates were 55.7% and 48.3%, respectively (CI for difference of 7.4% was −0.7, 15.5). Neither objective nor subjective success rates met the prespecified criteria for equivalence. Patient satisfaction (retropubic 86.3% vs transobturator 88.1%, p = 0.58), frequency of de novo urgency incontinence (retropubic 0% vs transobturator 0.3%, p = 0.99) and occurrence of mesh exposure (retropubic 4.4% vs transobturator 2.7%, p = 0.26) were not significantly different. The retropubic mid urethral sling group had higher rates of voiding dysfunction requiring surgery (3.0% vs 0%, p = 0.002) and urinary tract infections (17.1% vs 10.7%, p = 0.025), whereas the transobturator group had more neurological symptoms (9.7% vs 5.4%, p = 0.045).ConclusionsObjective success rates met the criteria for equivalence at 12 months but no longer met these criteria at 24 months. Subjective success rates remained inconclusive for equivalence. Patient satisfaction remained high and symptom severity remained markedly improved. Continued surveillance is important in women undergoing mid urethral sling surgery.

We examined preoperative and postoperative patient related factors associated with continence status up to 7 years after surgery for stress urinary incontinence.Women randomized to Burch colposuspension or fascial sling surgery and assessed for the primary outcome of urinary continence 2 years after surgery were eligible to enroll in a prospective observational study. Survival analysis was used to investigate baseline and postoperative factors in the subsequent risk of stress urinary incontinence, defined as self-report of stress urinary incontinence symptoms, incontinence episodes on a 3-day diary or surgical re-treatment.Of the women who participated in the randomized trial 74% (482 of 655) were enrolled in the followup study. Urinary continence rates decreased during a period of 2 to 7 years postoperatively from 42% to 13% in the Burch group and from 52% to 27% in the sling group, respectively. Among the baseline factors included in the first multivariable model age (p = 0.03), prior stress urinary incontinence surgery (p = 0.02), menopausal status (0.005), urge index (0.006), assigned surgery (p = 0.01) and recruiting site (p = 0.02) were independently associated with increased risk of incontinence. In the final multivariable model including baseline and postoperative factors, Burch surgery (p = 0.01), baseline variables of prior urinary incontinence surgery (p = 0.04), menopausal status (p = 0.03) and postoperative urge index (p0.001) were each significantly associated with a greater risk of recurrent urinary incontinence.Preoperative and postoperative urgency incontinence symptoms, Burch urethropexy, prior stress urinary incontinence surgery and menopausal status were negatively associated with long-term continence rates. More effective treatment of urgency urinary incontinence in patients who undergo stress urinary incontinence surgery may improve long-term overall continence status.

To identify factors that may predict success and satisfaction in women undergoing nonsurgical therapy for stress urinary incontinence.Baseline demographic and clinical characteristics of women participating in a multicenter randomized trial of pessary, behavioral, or combined therapy for stress urinary incontinence were evaluated for potential predictors of success and satisfaction. Success and satisfaction outcomes were assessed at 3 months and included the Patient Global Impression of Improvement, stress incontinence subscale of the Pelvic Floor Distress Inventory, and Patient Satisfaction Questionnaire. Logistic regression was performed to identify predictors, adjusting for treatment and other important clinical covariates. Adjusted odds ratios (ORs), 95% confidence intervals (CIs), and associated P values are presented.Four hundred forty-six women were randomized. College education or more and no previous urinary incontinence surgery predicted success based on the stress subscale of the Pelvic Floor Distress Inventory (adjusted OR 1.61, 95% CI 1.01-2.55, P=.04 and adjusted OR 3.15, 95% CI 1.04- 9.53, P=.04, respectively). Menopausal status predicted success using the Patient Global Impression of Improvement (adjusted OR 2.52 postmenopausal compared with premenopausal, 95% CI 1.29-4.95; adjusted OR 1.32 unsure menopausal status compared with premenopausal, 95% CI 0.65-2.66; P=.03 across all three groups). Fewer than 14 incontinence episodes per week predicted satisfaction with the Patient Satisfaction Questionnaire (adjusted OR 1.97, 95% CI 1.21-3.19; P=.01). These predictors did not differ across the three treatment groups.Menopause, higher education, no previous urinary incontinence surgery, and lower incontinence frequency were found to be predictors of success and satisfaction with nonsurgical therapy for stress urinary incontinence. This information may help better-align provider and patient expectations with nonsurgical treatment outcomes.

The unexpected absence of urodynamic stress incontinence (USI) in women planning surgery for stress urinary incontinence (SUI) is a challenge to surgeons. We examined the prevalence and clinical and demographic factors associated at baseline (preoperatively) with the unexpected absence of USI among study participants of two multicenter randomized clinical trials of surgery for treating SUI.Women with SUI symptoms and positive stress tests on physical examination enrolled in two separate clinical trials-one comparing the autologous fascial sling with the Burch colposuspension [Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr), and the other comparing the retropubic mid-urethral sling with the transobturator midurethral sling [Trial of Mid-Urethral Slings (TOMUS)]-were evaluated for USI preoperatively. The association of clinical, demographic, and urodynamic parameters was examined in women without USI in univariate and multivariate analyses.Overall, 144 of 1,233 women (11.7 %) enrolled in the two studies showed no USI. These women had a significantly lower mean volume at maximum cystometric capacity than those with USI (347.5 vs. 395.8 in SISTEr, p = 0.012), (315.2 vs. 358.2 in TOMUS, p = 0.003) and a lower mean number of daily accidents reported on a 3-day diary (2.2 vs 2.7 in SISTEr, p = 0.030) (1.7 vs 2.7 in TOMUS, p0.001). Additionally, those without demonstrable USI were more likely to have Pelvic Organ Prolapse Quantification (POP-Q) stage III/IV (31.7 % vs 14.4 % in SISTEr, p = 0.002), (15.5 % vs 6.9 % in TOMUS, p = 0.025). SUI severity as recorded on the Urogenital Distress Inventory (UDI) correlated strongly with the presence of USI in both studies.We observed that about one of eight women planning surgery for SUI does not show USI. Stage 3/4 POP was strongly associated with the unexpected absence of USI. A diminished urodynamic bladder capacity among women who did not display USI may reflect an inability to reach the limits of capacity during urodynamics, at which these women normally leak.

Purpose: We characterized continence, satisfaction and adverse events in women at least 5 years after Burch urethropexy or fascial sling with longitudinal followup of randomized clinical trial participants.Materials and Methods: Of 655 women who participated in a randomized surgical trial comparing the efficacy of the Burch and sling treatments 482 (73.6%) enrolled in this long-term observational study. Urinary continence status was assessed yearly for a minimum of 5 years postoperatively. Continence was defined as no urinary leakage on a 3-day voiding diary, and no self-reported stress incontinence symptoms and no stress incontinence surgical re-treatment.Results: Incontinent participants were more likely to enroll in the followup study than continent patients (85.5% vs 52.2%) regardless of surgical group (p

The following is a report of the proceedings of the Nocturia Think Tank sessions of the annual International Consultation on Incontinence-Research Society, which took place June 13–15, 2011 in Bristol, UK. The report is organized into sections pertaining to the main topics of discussions having occurred at that meeting, centering on the relationship of nocturnal polyuria (NP) and nocturia but also synthesizing more current evidence advancing our knowledge of the diagnosis and management of nocturia. This article is not meant to be a comprehensive review on the subject of nocturia, a number of which are available in the recent literature. All authors were physically present during, or in a preliminary session just prior to, the meeting in Bristol. Neurourol. Urodynam. 31:330–339, 2012. © 2012 Wiley Periodicals, Inc.

Aims To report the conclusions of the Think Tank on mechanisms of incontinence and surgical cure in female and male SUI: surgical research initiatives during the ICI-RS meeting in 2010. Methods The sub-group considered five areas for future research in stress urinary incontinence (SUI); (i) epidemiology and public health efforts in SUI, (ii) the basic sciences examining the physiology and pathophysiology of the continence mechanism, (iii) diagnostic techniques and clinical assessment of SUI, (iv) the future of treatment and surgical cure, and (v) the separate issue of male SUI. Results Roadblocks to progress were identified for each of the five directions. Conclusions Future research directions are suggested for each of these areas. Neurourol. Urodynam. 30:704–707, 2011. © 2011 Wiley-Liss, Inc.

NIH/NIDDK, Bethesda, MarylandAims: To describe perineal surface patch electromyography (EMG) activity during urodynamics (UDS) and compareactivity between filling and voiding phases and to assess for a relationship between preoperative EMG activity andpostoperative voiding symptoms. Methods: 655 women underwent standardized preoperative UDS that included peri-neal surface EMG prior to undergoing surgery for stress urinary incontinence. Pressure-flow studies were evaluatedfor abdominal straining and interrupted flow. Quantitative EMG values were extracted from 10 predetermined time-points and compared between fill and void. Qualitative EMG activity was assessed for the percent of time EMG wasactive during fill and void and for the average amplitude of EMG during fill compared to void. Postoperative voidingdysfunction was defined as surgical revision or catheterization more than 6 weeks after surgery. Fisher’s exact testwith a 5% two-sided significance level was used to assess differences in EMG activity and postoperative voiding dys-function. Results: 321 UDS had interpretable EMG studies, of which 131 (41%) had EMG values at all 10 predeter-mined and annotated time-points. Quantitative and qualitative EMG signals during flow were usually greater thanduring fill. The prevalence of postoperative voiding dysfunction in subjects with higher preoperative EMG activityduring void was not significantly different. Results were similar in the 42 subjects who had neither abdominal strain-ing during void nor interrupted flow. Conclusions: Perineal surface patch EMG did not measure expected pelvic floorand urethral sphincter relaxation during voiding. Preoperative EMG did not predict patients at risk for postoperativevoiding dysfunction. Neurourol. Urodynam. 2011 Wiley-Liss, Inc.Key words: electromyography; pelvic floor; stress urinary incontinence; urethra; urodynamics; voiding dysfunction

To identify clinical and demographic factors predictive of midurethral sling failure.Overall treatment failure was defined by one or more of the following objective outcomes: a positive stress test, positive 24-hour pad test or retreatment for stress urinary incontinence (SUI); subjective outcomes: self reported SUI by the Medical, Epidemiologic and Social Aspect of Aging questionnaire, incontinent episodes by 3-day diary, or retreatment for SUI, or a combination of these. Logistic regression models adjusting for sling type and clinical site were used to predict odds of overall treatment failure after univariable analysis. Models were also fit to compare factors associated with objective failure and subjective failure only.Previous UI surgery (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.47); maximum Q-tip excursion30° (OR 1.89, 95% CI 1.16-3.05); Medical, Epidemiologic and Social Aspect of Aging questionnaire urge score per 10 points (OR 1.97, 95% CI 1.21-3.21); and pad weight per 10 g (OR 1.06, 95% CI 1.02-1.10) were predictors of overall failure. Having concomitant surgery (OR 0.44, 95% CI 0.22-0.90) was predictive of subjective failure only rather than objective failure. Age per 10 years (OR 1.48, 95% CI 1.14-1.90); Urogenital Distress Inventory score per 10 points (OR 1.09, 95% CI 1.02-1.17); pad weight per 10 g (OR 1.05, 95% CI 1.01-1.10) were predictive of objective failure compared with subjective failure only. Associations of risk factors and failure were similar independent of sling type (retropubic or transobturator).Twelve months after surgery, risk factors for overall and objective treatment failure were similar in women undergoing retropubic and transobturator sling procedures. This information may assist in counseling patients regarding efficacy of sling procedures and in setting expectations for women at increased odds for treatment failure.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00325039.II.

We hypothesized that certain preoperative voiding symptoms would be correlated with poorer post-continence surgery outcomes in women.Preoperative voiding symptoms from 655 women were assessed with questionnaires. Outcomes (overall failures, stress-specific failures, and voiding dysfunction) after Burch or sling surgery were measured. Logistic regression models were used to associate preoperative voiding symptoms with postoperative outcomes.Hesitating urinary stream was associated with voiding dysfunction [OR 2.22, p=0.01], overall [OR 1.57, p=0.03], and stress-specific [OR 1.67, p=0.009] failures. A ten-point increase in preoperative Urogenital Distress Inventory-obstructive (UDI-O) subscore was associated with overall [OR 1.10, p=0.049] and stress-specific [OR 1.21, p0.0001] failures. Even controlling for severity of POPQ stage, significant associations of hesitating urinary stream with voiding dysfunction, overall and stress-specific failures remained.Preoperative hesitating urinary stream and obstructive voiding symptoms were associated with poorer surgical outcomes. Further studies in this area may be fruitful.

Objectives To explore whether instruction in fluid management resulted in changes in fluid intake and incontinence over a 10-week study period in women with urinary urge incontinence (UUI), as fluid management might be critical strategy in treating this condition.

Background and purpose Urodynamic studies (UDS) are routinely obtained prior to surgery for stress urinary incontinence (SUI) despite a lack of evidence that UDS information has an actual impact on outcome. The primary aim of this non-inferiority randomized clinical trial is to determine whether women with symptomatic, uncomplicated SUI who undergo only a basic office evaluation (BOE) prior to SUI surgery (No UDS arm) have non-inferior treatment outcomes compared to women who have BOE and UDS (UDS arm). Secondary aims are: 1) to determine how often physicians use preoperative UDS results to alter clinical and surgical decision-making, 2)to compare the amount of improvement in incontinence outcomes, and 3) to determine the incremental cost and utility of performing UDS compared with not performing UDS. Methods After an initial basic office evaluation, women planning surgery for uncomplicated SUI who consent to study participation will be randomized to receive preoperative UDS or No UDS. Treatment will be planned and performed by the surgeon utilizing all the data available to them. We will compare results from the basic office evaluation (No UDS) with results from the basic office evaluation and preoperative UDS. Results The primary outcome will be measured at 12 months using responses to the Urogenital Distress Inventory and the Patient Global Index-Improvement. Conclusions Randomized trials comparing the effects of different diagnostic alternatives on treatment outcomes pose study design challenges. A non-inferiority design is appropriate when comparing a less invasive and less expensive alternative with a standard of care approach.

Background Mixed urinary incontinence (MUI) is a common, bothersome condition in women. In MUI, the two subtypes of urinary incontinence that coexist are treated differently; stress urinary incontinence (SUI) is primarily treated surgically while urge urinary incontinence (UUI) is primarily treated medically. There is no evidence to guide the treatment for women with significant bother from both incontinence subtypes. Therefore, investigators of the Urinary Incontinence Treatment Network (UITN) designed and initiated a randomized clinical trial comparing outcomes for two distinct initial treatment approaches for women with mixed urinary incontinence (MUI): therapy initiated with surgery versus therapy initiated with nonsurgical treatment. Purpose The aim of this manuscript is to describe the challenges in planning and implementing this randomized clinical trial. Methods The mixed incontinence: medical or surgical approach (MIMOSA) trial was designed as a practical or pragmatic clinical trial to establish the relative efficacy of two specific treatment approaches. The design presented many challenging decisions including: (1) selection of practical paradigm; (2) refining inclusion/ exclusion criteria to offer equipoise; (3) selection of feasibility sample size; (4) recruitment challenges for two divergent treatment approaches (medical vs. surgical), and (5) resolution of ethical and methodological issues. Results MIMOSA recruitment was planned in two phases, starting with a 5-month pilot and feasibility phase followed by a full trial contingent on the outcome of the first phase. The feasibility portion of the MIMOSA trial started in November 2008. 1198 subjects were screened and approached forstudy enrollment, but only 27 consented to randomization. The feasibility study was halted due to lack of enrollment in March 2009. Limitations The challenges of this trial included a lack of information from subjects who did not enroll, increasing the difficulty of interpreting the feasibility phase. Conclusions Successful recruitment to a randomized trial that compares significantly different treatment approaches poses a challenge. Clinical Trials 2009; 6: 355—364. http://ctj.sagepub.com

Background The primary aims of this trial are to determine whether the use of a concomitant prophylactic anti-incontinence procedure may prevent stress urinary incontinence symptom development in women undergoing vaginal prolapse surgery and to evaluate the cost-effectiveness of this prophylactic approach. Purpose To present the rationale and design of a randomized controlled surgical trial (RCT), the Outcomes following vaginal Prolapse repair and mid Urethral Sling (OPUS) Trial highlighting the challenges in the design and implementation. Methods The challenges of implementing this surgical trial combined with a cost-effectiveness study and patient preference group are discussed including the study design, ethical issues regarding use of sham incision, maintaining the masking of study staff, and pragmatic difficulties encountered in the collection of cost data. The trial is conducted by the NICHD-funded Pelvic Floor Disorders Network. Results The ongoing OPUS trial started enrollment in May 2007 with a planned accrual of 350. The use of sham incision was generally well accepted but the collection of cost data using conventional billing forms was found to potentially unmask key study personnel. This necessitated changes in the study forms and planned timing for collection of cost data. To date, the enrollment to the patient preference group has been lower than the limit established by the protocol suggesting a willingness on the part of women to participate in the randomization. Limitations Given the invasive nature of surgical intervention trials, potential participants may be reluctant to accept random assignment, potentially impacting generalizability. Conclusion Findings from the OPUS trial will provide important information that will help surgeons to better counsel women on the benefits and risks of concomitant prophylactic anti-incontinence procedure at the time of vaginal surgery for prolapse. The implementation of the OPUS trial has necessitated that investigators consider ethical issues up front, remain flexible with regards to data collection and be constantly aware of unanticipated opportunities for unmasking. Future surgical trials should be aware of potential challenges in maintaining masking and collection of cost-related information. Clinical Trials 2009; 6: 162—171. http://ctj.sagepub.com

The primary aims of this trial are: 1) to compare surgical outcomes following sacrospinous ligament fixation to uterosacral vaginal vault suspension in women undergoing vaginal surgery for apical or uterine pelvic organ prolapse and stress urinary incontinence and 2) to examine the effects of a structured perioperative program consisting of behavioral techniques and pelvic floor muscle training compared to usual care. This trial is performed through the Pelvic Floor Disorders Network (PFDN), which is funded by National Institute of Child Health and Human Development. Subjects will be enrolled from hospitals associated with seven PFDN clinical centers across the United States. A centralized biostatistical coordinating center will oversee data collection and analysis. Two approaches will be investigated simultaneously using a 2 × 2 randomized factorial design: a surgical intervention (sacrospinous ligament fixation versus uterosacral vaginal vault suspension) and a perioperative behavioral intervention (behavioral and pelvic floor muscle training versus usual care). Surgeons have standardized essential components of each surgical procedure and have met specific standards of expertise. Providers of the behavioral intervention have undergone standardized training. Anatomic, functional, and health-related quality of life outcomes will be assessed using validated measures by researchers blinded to all randomization assignments. Cost-effectiveness analysis will be performed using prospectively collected data on health care costs and resource utilization. The primary surgical endpoint is a composite outcome defined by anatomic recurrence, recurrence of bothersome vaginal prolapse symptoms and/or retreatment and will be assessed 2 years after the index surgery. Endpoints for the behavioral intervention include both short-term (6-month) improvement in urinary symptoms and long-term (2-year) improvement in anatomic outcomes and prolapse symptoms. This article describes the rationale and design of this randomized trial, focusing on several key design features of potential interest to researchers in the field of female pelvic floor disorders and others conducting randomized surgical trials.

Objective To determine reference urodynamic values for preoperative urodynamic studies in women undergoing surgery for pure or predominant stress urinary incontinence (SUI). Materials and Methods Six hundred fifty-five women with pure or predominant SUI were enrolled in a multicenter surgical trial and were randomized to undergo a Burch or autologous fascia sling procedure as part of the Urinary Incontinence Treatment Network (UITN) Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr). Preoperative free uroflowmetry, filling cystometry, and pressure flow studies were performed in all women using a standardized research protocol and standardized urodynamic interpretation guidelines. We define the normal range of urodynamic values in this population as the values that encompass 95% of the results. Results In 655 women undergoing filling cystometry in the standing position, baseline vesical and abdominal pressures were between 12 and 60 cm H2O. The upper limit of detrusor pressure increase during bladder filling to maximum cystometric capacity was 16 cm H2O. Ten percent of women who qualified for stress incontinence surgery with a positive cough stress test on physical exam did not demonstrate urodynamic stress incontinence (USI) and less than 10% of subjects in this study demonstrated detrusor overactivity. Conclusions Results from a large cohort of women with SUI are now available for quantitative plausibility assessments or as reference values when interpreting urodynamic studies. Neurourol. Urodynam. 26:333–340, 2007. © 2007 Wiley-Liss, Inc.

Urinary incontinence is common in women, but is under-reported and under-treated. Urine storage and emptying is a complex coordination between the bladder and urethra, and disturbances in the system due to childbirth, aging, or other medical conditions can lead to urinary incontinence. The two main types of incontinence in women, stress urinary incontinence and urge urinary incontinence, can be evaluated by history and simple clinical assessment available to most primary care physicians. There is a wide range of therapeutic options, but the recent proliferation of new drug treatments and surgical devices for urinary incontinence have had mixed results; direct-to-consumer advertising has increased public awareness of the problem of urinary incontinence, but many new products are being introduced without long-term assessment of their safety and efficacy.

An international group of authors present a pooled analysis of data from their phase III multicentre double-blind clinical trials in patients with overactive bladder, which evaluated the efficacy, tolerability and safety of darifenacin. They found the drug, a muscarinic M3 selective receptor antagonist, to be effective in the treatment of this condition, with excellent tolerability and safety. A paper from Denmark compares the efficacy and safety of alfuzosin and tamsulosin in a large randomized, double-blind, placebo-controlled, multicentre study. There were similar improvements in urinary symptoms and maximum urinary flow with the two drugs compared to placebo, but the incidence of sexual function adverse events was higher with tamsulosin than placebo. OBJECTIVE To evaluate the efficacy, tolerability and safety of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), from an analysis of pooled data from three phase III, multicentre, double-blind clinical trials in patients with overactive bladder (OAB). PATIENTS AND METHODS After a 4-week washout/run-in period, 1059 adults (85% women) with symptoms of OAB (frequency and urgency with urge incontinence) for ≥ 6 months were randomized to once-daily oral treatment with darifenacin (7.5 mg, 337; or 15 mg, 334) or matching placebo (388) for 12 weeks. Efficacy was evaluated using electronic patient diaries that recorded incontinence episodes (including those resulting in a change of clothing or pads), frequency and severity of urgency, voiding frequency, and bladder capacity (volume voided). Safety was evaluated by analysis of adverse events (AEs), withdrawal rates and laboratory tests. RESULTS Relative to baseline, 12 weeks of treatment with darifenacin resulted in a significant reduction in the median (% change, interquartile range) number of incontinence episodes per week; 7.5 mg (−8.8, −68.4%, −15.1 to −4.4); 15 mg; (−10.6, −76.8%, −17.3 to −5.8: both P

Objective Our purpose was to determine the long-term results after abdominal sacrocolpopexy. Study design Computer-coded procedure logs identified women who had an abdominal sacrocolpopexy performed from 1985 to 1992. Subjects answered a validated, condition-specific symptom questionnaire, a sexual function questionnaire, and a demographic survey. Failures were defined by reoperation or symptoms. The data were analyzed with use of the Student t test and the Fisher exact test. Results At the time of surgery the subjects (n = 38) had a mean age of 59.2 years (range 40-77 years), parity 4.03 (1-9), BMI 26.5 (18.6-40.2), and stage of prolapse 2.56 (0-4). The mean follow-up interval was 13.7 years (10-17 years). The total number of failures was 10 (26.3%), 4 (10.5%) because of reoperation and 6 (16%) because of symptoms. Symptom distress scores were low and similar between failures and successes. Twelve subjects were available for examination and most defects were noted in the anterior wall. Conclusion This long-term outcome analysis of abdominal sacrocolpopexy found the procedure to be durable with a 74% success rate at a mean follow-up of 13.7 years.

Our objective was to determine the availability and utilization of urodynamic investigations by gynecologists in the preoperative evaluation of women with urinary incontinence. Gynecologists in the UK, USA, Australia, New Zealand and Canada were asked what urodynamic investigations were required for four clinical scenarios. Analysis was restricted to frequent operators. Urodynamic investigations were available to 70% of frequent operators. For uncomplicated stress incontinence, cystometry was utilized by 72% of subspecialists and 44% of generalists ( P

To investigate the relationship between the symptom of mixed urinary incontinence and incontinence severity, urodynamic findings, and treatment response.This is a secondary analysis of data from 553 women randomized into a double-blind, placebo-controlled study evaluating duloxetine (serotonin-norepinephrine reuptake inhibitor) for the treatment of predominant stress urinary incontinence. Assessment variables included incontinent episode frequency, the Incontinence Quality of Life Questionnaire (I-QOL), and the Patient Global Impression of Severity Scale (PGI-S). Urge symptoms were identified with three urge I-QOL questions not included in corrected I-QOL calculations.At baseline, 171 women (31%) had mixed urinary incontinence. They had more severe baseline urinary incontinence than did those with stress urinary incontinence (mean incontinent episode frequency 14.3 versus 10.5; PGI-S normal or mild 26.5% versus 70.4%; mean corrected I-QOL 59.1 versus 79.9; all Ps.001). Baseline urodynamics were performed on a subset of 86 women. Subjects with both urodynamic stress incontinence and detrusor overactivity had less severe incontinence compared with subjects with only urodynamic stress incontinence. Both mixed urinary incontinence and stress urinary incontinence groups had significant decreases in median incontinent episode frequency at a 40 mg per day (62% and 58%, respectively) and 80 mg per day (63% and 65%) duloxetine dose compared with placebo (33% and 44%; all Ps.05). Response was not dependent on the type of symptoms (interaction P =.47).For women presenting with predominant stress urinary incontinence symptoms, the major determinant of concurrent urge symptoms was incontinence severity and not the pathophysiologic condition(s) causing the incontinence; duloxetine demonstrated equal efficacy for women with mixed urinary incontinence and pure stress urinary incontinence.

Aims Given the relative frequency of lower urinary tract dysfunction (LUTD) after major pelvic surgery, the main question for this debate is: “Should we [actively] screen for LUTD after major pelvic surgery,” with the intention to treat and improve patient care. Methods The discussants selected relevant papers from a limited review of the literature [PubMed/Medline database (January 1966 to May 2011)] and prepared the YES versus NO presentations. Results The evidence was presented for the following major pelvic procedures: colorectal surgery, hysterectomy, and surgery for other benign gynecologic conditions, radical prostatectomy, brachytherapy, and primary cryotherapy for prostate cancer. Based on the presentations, the audience voted in favor of screening for LUTD after major pelvic surgery. Conclusions Irreversible treatment should be delayed in case of LUTD after major pelvic surgery. In fact, most symptoms spontaneously subside within 6 months after the surgery. Once the period of 6–12 months of conservative management has been completed and if LUTD persists, a new urodynamic screening should be followed by appropriate treatment. Neurourol. Urodynam. 31:327–329, 2012. © 2012 Wiley Periodicals, Inc.

Re: 5-Year Longitudinal Follow-up after Retropubic andTransobturator Midurethral SlingsKenton K, Stoddard AM, Zyczynski H, et alJ Urol. In press. http://dx.doi.org/10.1016/j.juro.2014.08.089Experts’ summary:The observational study by Kenton et al [1] includes a largepercentage of women enrolled in the TOMUS trial, a random-ized equivalence trial of retropubic and transobturator mid-urethral sling (MUS) approaches, published in 2010. In thisarticle, the authors present the 5-yr outcomes for 404 womenin terms of success, satisfaction, symptom-specific distress,quality of life, and adverse events after MUS. Treatmentsuccess was defined as no retreatment and no self-reportedsymptomsofstressurinaryincontinence.Ananswerof‘‘never’’or ‘‘rarely’’ to all stress-specific questions was considered neg-ative for symptoms. Treatment success declined over-time inboth group, and 5 yr after surgery it was 51.3% and 43.4% afterretropubic and transobturator MUS, respectively. In addition,the proportion of women who stated they were ‘‘very muchbetter’’ or ‘‘much better’’ according to a patient global impres-sion of improvement declined over-time in both groups(p < 0.0001). However, a greater proportion of women in thetransobturator group reported that they were ‘‘very muchbetter’’ or ‘‘much better’’ at 5 yr (88% vs 77%, p = 0.01). Theauthorsconcludedthatlong-termtreatmentsuccessandsatis-faction for both retropubic and transobturator MUS declineover time; nevertheless, women undergoing transobturatorMUSreportedagreaterimprovementinurinarysymptoms[1].Experts’ comments:In the present midurethral sling era, the medium- and long-term outcomes for MUS and comparisons between retropubicand transobturator MUS are the two most debated topics.Several randomized or prospective studies showed veryhigh and long-lasting objective cure rates using MUS[2–4]. A recently published randomized control trialcomparing the retropubic tension-free vaginal tape (TVT)procedure with transobturator TVT (TVT-O) showed thatobjective cure rates remained very high forboth approaches(84.7% and 86.2%, respectively) at 5 yr after surgery.Furthermore,subjectivetreatmentsatisfactionwasexcellent(94.2% in the TVT group and 91.7% in the TVT-O group). Nodifferences in terms of objective or subjective cure ratesbetweenretropubicandtransobturatorMUSwerefound[5].The great merit of the study by Kenton et al [1] is that itfocuses attention on these hot topics. However, data on theefficacyofMUStreatmentat5-yrfollow-uparesignificantlylowerincomparisontothosereportedinthevastmajorityoftheliteratureonthisissue.Theauthorsrepeatedlyunderlinethat in their study, pelvic examinations were performed atannual visits to assess for visual and palpable evidence ofmesh exposure and patient symptoms associated withphysical findings. This is a strength of the study, but it isunusual that no objective methods were used during theseannual examinations to assess the efficacy of MUS position-ing. In the study, success was defined as no retreatment andno self-reported symptoms of stress urinary incontinence.However, using this definition, the success rate of MUSappears to be unusually low (43–51%) at 5-yr follow-up; inaddition, the rate is not in agreement with data reported byother authors on this topic or with findings by the sameauthors in terms of patient satisfaction (79–85%).Therefore, we believe that this study offers interestingdataforphysiciansandpatients,butitisnotveryrealistictoattribute a success rate

We identify genetic variants associated with urgency urinary incontinence in postmenopausal women.A 2-stage genome-wide association analysis was conducted to identify variants associated with urgency urinary incontinence. The WHI GARNET substudy with 4,894 genotyped post-reproductive white women was randomly split into independent discovery and replication cohorts. Genome-wide imputation was performed using IMPUTE2 with the 1000 Genomes ALL Phase I integrated variant set as a reference. Controls reported no urgency urinary incontinence at enrollment or followup. Cases reported monthly or greater urgency urinary incontinence and leaked sufficiently to wet/soak underpants/clothes. Logistic regression models were used to predict urgency urinary incontinence case vs control status based on genotype, assuming additive inheritance. Age, obesity, diabetes and depression were included in the models as covariates.Following quality control, 975,508 single nucleotide polymorphisms in 2,241 cases (discovery 1,102; replication 1,133) and 776 controls (discovery 405, replication 371) remained. Genotype imputation resulted in 9,077,347 single nucleotide polymorphisms and insertions/deletions with minor allele frequency greater than 0.01 available for analysis. Meta-analysis of the discovery and replication samples identified 6 loci on chromosomes 5, 10, 11, 12 and 18 associated with urgency urinary incontinence at p10(-6). Of the loci 3 were within genes, the zinc finger protein 521 (ZFP521) gene on chromosome 18q11, the ADAMTS16 gene on chromosome 5p15 and the CIT gene on chromosome 12q24. The other 3 loci were intergenic.Although environmental factors also likely contribute, this first exploratory genome-wide association study for urgency urinary incontinence suggests that genetic variants in the ZFP521, CIT and ADAMTS16 genes might account for some of the observed heritability of the condition.

Objective We conducted a genomewide linkage analysis to identify pelvic organ prolapse (POP) predisposition genes using a resource of high-risk POP pedigrees. Study Design Cases are defined as women who reported bothersome symptoms of POP based on standardized symptom questions (Pelvic Floor Distress Inventory, moderately or quite bothered), and/or received treatment for POP documented in medical records. Our complete pedigree resource contains 299 familial POP cases in 83 high-risk pedigrees. Genotype data were obtained from Illumina HumanHap550, 610Q, the Human1M-Duo, Human Omni1-Quad, or the Human Omni 2.5 platforms. A set of single nucleotide polymorphism markers common to all platforms was identified and markers in high linkage disequilibrium were removed. We performed a genomewide linkage analysis under general dominant and recessive models using a Markov chain, Monte Carlo linkage analysis method implemented in MCLINK (University of Utah) software. Because 70 individuals in 32 pedigrees were used in a previously published linkage analysis for a phenotype of POP requiring treatment/surgery, we also performed linkage only including the 225 newly recruited and genotyped cases in 61 pedigrees. Results Linkage analysis using our complete pedigree resource for the loosened criteria of bothersome POP showed evidence for significant genomewide linkage on chromosome 10q24-26 (recessive model, maximum heterogeneity logarithm of odds 3.4); suggestive evidence was identified on chromosomes 6 and 17, and an additional region on chromosome 10. In the subset of only the newly recruited familial POP cases, significant evidence for genomewide linkage was observed on chromosome 17q25 (recessive model, maximum heterogeneity logarithm of odds 3.3), and suggestive evidence for linkage was observed on chromosomes 10 and 11. Neither analysis duplicated the previously published linkage evidence for the POP requiring treatment/surgery phenotype observed on chromosome 9. Conclusion While the etiology of this common condition is unknown, this study provides evidence that loci on chromosomes 10q and 17q may contribute to POP etiology.

ObjectiveThe objective of the study was to estimate the effect of Burch and fascial sling surgery on out-of-pocket urinary incontinence (UI) management costs at 24 months postoperatively and identify predictors of change in cost among women enrolled in a randomized trial comparing these procedures.Study designResources used for UI management (supplies, laundry, dry cleaning) were self-reported by 491 women at baseline and 24 months after surgery, and total out-of-pocket costs for UI management (in 2012 US dollars) were estimated. Data from the 2 surgical groups were combined to examine the change in cost for UI management over 24 months. Univariate and bivariate changes in cost were analyzed using the Wilcoxon signed rank test. Predictors of change in cost were examined using multivariate mixed models.ResultsAt baseline mean (±SD) age of participants was 53 ± 10 years, and the frequency of weekly UI episodes was 23 ± 21. Weekly UI episodes decreased by 86% at 24 months (P < .001). The mean weekly cost was $16.60 ± $27.00 (median $9.39) at baseline and $4.57 ± $15.00 (median $0.10) at 24 months (P < .001), a decrease of 72%. In multivariate analyses, cost decreased by $3.38 ± $0.77 per week for each decrease of 1 UI episode per day (P < .001) and was strongly associated with greater improvement in Urogenital Distress Inventory and Incontinence Impact Questionnaire scores (P < .001) and decreased 24-hour pad weight (P < .02).ConclusionFollowing Burch or fascial sling surgery, the UI management cost at 24 months decreased by 72% ($625 per woman per year) and was strongly associated with decreasing UI frequency. Reduced out-of-pocket expenses may be a benefit of these established urinary incontinence procedures.

Understanding the clustering of pelvic floor disorders (PFDs) within families is important because it may suggest underlying risk factors that may be environmental, genetic or both. The objective of this study was to describe clinical characteristics observed in familial cases with PFDs and compare them with strictly defined controls. Women evaluated and treated for PFDs were recruited as part of a larger genetic study. Here, we define familial cases as those with bothersome symptoms or treatment for a PFD (pelvic organ prolapse [POP], stress urinary incontinence [SUI], and overactive bladder [OAB]) and who had a first-degree relative with bothersome symptoms or treatment for the same pelvic floor defect. We assigned clinical characteristics to probands and their relatives using standardized symptom questions (PFDI), examination, and review of treatment records, if any. We identified 126 familial POP cases, 183 familial SUI cases, and 101 familial OAB cases. Familial cases were more likely to have bothersome symptoms for more than one PFD. Among familial POP cases, bothersome SUI (71 %), OAB (54 %), and a combination of all three disorders (48 %) were common. Among familial SUI cases, bothersome OAB (60 %), POP (59 %), and combinations of all disorders (40 %) were common. Among familial OAB cases, bothersome SUI (88 %), POP (66 %), and combinations of all three disorders (59 %) were common. Familial cases of POP, SUI, and OAB are more likely to have more than one pelvic floor defect. It is likely that underlying genetic factors contribute to more than one pelvic floor defect.