The POP-Q system: two decades of progress and debate.

I appreciate the opportunity to provide my reflections on the POP-Q, now more than 20 years since it was first conceived and 17 years since its publication in the American Journal of Obstetrics and Gynecology. The invitation led me to dig into old files and recall--through a series of insightful emails, faxes, meeting summaries and draft documents--a document made possible by the combined efforts of an extraordinary group of individuals.

Use of preoperative prolapse reduction stress testing and the risk of a second surgery for urinary symptoms following laparoscopic sacral colpoperineopexy.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to determine the reoperation rate for sling placement or revision in patients who had primary continence procedures based on prolapse reduction stress testing (RST) prior to laparoscopic sacral colpoperineopexy (LSCP). METHODS: This was a retrospective cohort study of women who had RST prior to LSCP for symptomatic pelvic organ prolapse. Patients with positive test (Pos RST) had a concomitant midurethral sling procedure and those with negative test (Neg RST) did not. Variables were compared with either Student's t test or Fisher's exact test. RESULTS: In Neg RST group (n = 70), the rate of surgery for de novo urodynamic stress incontinence was 18.6%. In Pos RST group (n = 82), the rate of sling revision for bladder outlet obstruction was 7.3%. Overall, 88% of patients did not require a second surgery. CONCLUSIONS: The use of RST to recommend concomitant continence procedures during LSCP results in a single surgery for the majority of our patients.

De novo stress urinary incontinence after negative prolapse reduction stress testing for total vaginal mesh procedures: incidence and risk factors.

OBJECTIVE: The primary objective was to estimate the incidence of de novo stress urinary incontinence after total vaginal mesh procedures in women with negative preoperative urodynamics with prolapse reduction. Secondary objective was to identify associated risk factors. STUDY DESIGN: A retrospective cohort study with a nested case-control study of women who underwent total vaginal mesh procedures without midurethral sling after a negative preoperative urodynamics. RESULT: Sixty patients were included in the final analysis. Fifteen (25%) patients were diagnosed with de novo stress urinary incontinence. Although no significant associated risk factors were identified, there was a trend for higher gravidity and better anterior wall support among women who had stress urinary incontinence develop. CONCLUSION: The incidence of de novo stress urinary incontinence after total vaginal mesh procedures in this cohort was 25%. Patients should be appropriately counseled regarding the same.

Reductions in stress urinary incontinence episodes: what is clinically important for women?

AIM: To expand our understanding of the clinical importance to patients with stress urinary incontinence (SUI) of reductions in incontinence episode frequency (IEF) that fall short of a complete cure. METHODS: We used an integrated database that included data from 1,913 women with SUI who were enrolled in four randomized, placebo-controlled pharmaceutical clinical trials and examined the relationship between various levels of reduction in IEF and minimally clinical important difference (MCID) levels established for the validated Incontinence Quality of Life (I-QOL) questionnaire. The first decile of IEF reduction to exceed the within-group MCID was considered to be the point at which the reduction in IEF first became clinically important. The between-group MCID was then used to determine when further reductions in incontinence represented clinically relevant incremental improvements for patients. RESULTS: Improvements in condition-specific quality of life were not clinically important until the fifth decile of IEF reduction, representing a reduction in IEF >40% to 70% to 90% to

Tobacco use is a risk factor for mesh erosion after abdominal sacral colpoperineopexy.

OBJECTIVE: The purpose of this study was to evaluate the association between smoking and vaginal mesh erosion after abdominal sacral colpoperineopexy with the use of type 1 polypropylene mesh. STUDY DESIGN: All cases of mesh erosion (n = 27) that were diagnosed between October 2003 and June 2006 were identified and compared with matched control cases (n = 81). Control cases were matched for age, diabetes mellitus status, hypoestrogenic state (menopausal status, chronic steroid use, use of hormone therapy), abdominal-vaginal rectocele repair, culdoplasty, and concomitant hysterectomy. Demographic data, surgical characteristics, and postoperative complications were also compared between groups. Continuous data were compared using 2-sample Student t tests. Categoric data were compared with the use of Pearson Chi-square tests. RESULTS: The odds of experiencing mesh erosion was significantly greater in smokers than in nonsmokers (odds ratio, 4.4; 95% CI, 1.3, 14.4; P = .010) when potential confounders were similar between groups. CONCLUSION: Tobacco use is a risk factor for vaginal mesh erosion after abdominal sacral colpoperineopexy with the use of type 1 polypropylene mesh.

Long-term efficacy of duloxetine in women with stress urinary incontinence.

OBJECTIVE: To assess the maintenance of efficacy of duloxetine beyond 3 months, using data from several long-term, open-label studies, as the efficacy of duloxetine 40-mg twice daily for treating women with stress urinary incontinence (SUI) for up to 3 months has been established in several randomized, placebo-controlled clinical trials. PATIENTS AND METHODS: Data from 1424 patients (Cohort A) enrolled in three 12-week, placebo-controlled clinical trials and their uncontrolled, open-label extensions, and in one uncontrolled, open-label study, were used to assess long-term continuation rates and continued efficacy based on responses to the validated Patient Global Impression of Improvement (PGI-I) scale for up to 30 months. Data from another 2758 patients (Cohort B) enrolled in an additional placebo-controlled study and its open-label extension were used to assess PGI-I ratings, reductions in incontinence episode frequency (IEF) recorded on urinary diaries, and the relationship between PGI-I ratings and reductions in IEF for up to 72 weeks. RESULTS: In Cohort A, the duloxetine continuation rate at 1 year was 42.5%. At 12, 24 and 30 months, most (83%, 83% and 88%, respectively) patients in Cohort A who continued treatment rated their incontinence in one of the three 'better since starting treatment' PGI-I categories. Both the median IEF reductions (50-77%) and the PGI-I 'better' ratings (70-88% of patients) remained fairly consistent over 72 weeks in Cohort B. Finally, IEF reductions increased with increasing PGI-I ratings (approximately 46% for 'a little better', 75% for 'much better' and 95% for 'very much better') over the first year of treatment. CONCLUSION: The benefits of duloxetine were maintained in patients who continued treatment for up to 30 months. However, these favourable results need to be interpreted cautiously, as many patients discontinued treatment and those with better responses are more likely to continue taking medication.

Duloxetine compared with placebo for the treatment of women with mixed urinary incontinence.

AIMS: Evaluate duloxetine in the treatment of women with mixed urinary incontinence (MUI). MATERIALS AND METHODS: 588 women, 19-85 years old with >or=4 incontinence episodes/week were randomly assigned to duloxetine 80 mg/day (N = 300) or placebo (N = 288). Patients were classified into three symptom subgroups: stress or urge predominant MUI (SPMUI or UPMUI) or balanced MUI (BMUI) based on their responses to the validated Stress/Urge Incontinence Questionnaire. Half the population was randomly assigned to have urodynamics; SPMUI, UPMUI, and BMUI condition diagnoses were based on signs, symptoms, and urodynamic observations. The primary outcome measure was the change in incontinence episode frequency (IEF). Secondary outcome measures included the Incontinence Quality of Life (I-QOL) scores, the ICI Quality of Life (ICIQ-SF) score, and the Patient Global Impression of Improvement (PGI-I) rating. RESULTS: At baseline, women with SPMUI averaged 15.9 IEF/week (61% stress), those with UPMUI averaged 13.2 (70% urge), and those with BMUI averaged 16.5 (52% urge). Overall IEF decreases were significantly greater with duloxetine than placebo (median percent reduction 60% vs. 47%, P < 0.001); both UUI and SUI episodes were significantly decreased with duloxetine (median SUI IEF reduction 59% vs. 43%, P = 0.001; UUI IEF reduction 58% vs. 40%, P < 0.001). Duloxetine IEF decreases were significantly greater for patients with SPMUI conditions and symptoms and for those with UPMUI conditions but not symptoms. Significant benefits were also demonstrated with duloxetine for improvements in I-QOL total score (11.5 points vs. 8.1 points, P = 0.002), all three I-QOL subscale scores, and for the ICIQ-SF score (-2.6 vs. -1.7, P = 0.002) as well as for PGI-I ratings (much/very much better 44.2% vs. 27.3%, P = 0.001). CONCLUSION: Duloxetine demonstrated significant efficacy in this population of women with MUI.

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.

Effect of dose escalation on the tolerability and efficacy of duloxetine in the treatment of women with stress urinary incontinence.

To assess the impact of duloxetine dose escalation on tolerability and efficacy, 516 women with stress urinary incontinence were randomized to receive placebo or duloxetine in one of three regimens: 40 mg BID for 8 weeks, 40 mg QD for 2 weeks escalating to 40 mg BID for 6 weeks or 20 mg BID for 2 weeks escalating to 40 mg BID for 6 weeks. A non-inferiority analysis confirmed that the 20 mg BID starting dose was significantly better than the other two duloxetine regimens for nausea reduction (16.5% vs 25.2% and 29.4%). There were also significant differences in the discontinuation rates (7.5% vs 11.8% and 16.2%). The efficacy after 4 weeks was significantly better with duloxetine than with placebo. Starting duloxetine at 20 mg BID for 2 weeks before increasing to 40 mg BID significantly improved tolerability but did not impact duloxetine efficacy after all the subjects had been on 40 mg BID for at least 2 weeks.

Minimal clinically important differences in Incontinence Quality-of-Life scores in stress urinary incontinence.

OBJECTIVES: To determine the clinically relevant reference points for the Incontinence Quality of Life (I-QOL) questionnaire scores in women with stress urinary incontinence and compare them with the treatment effects observed with duloxetine and placebo. METHODS: Using data from 1133 women with predominant stress urinary incontinence in two randomized, placebo-controlled duloxetine studies, the within-treatment and between-treatment minimal clinically important differences (MCIDs) were obtained by anchoring the I-QOL scores to the validated Patient Global Impression of Improvement scale (PGI-I). The within-treatment MCID (mean I-QOL for women rating their condition "a little better" with treatment) and between-treatment MCID (difference in scores between the group ratings of "no change" and "a little better") were derived. The treatment effects were compared with these MCIDs. Real-time urinary diaries were completed, along with the I-QOL and PGI-I. RESULTS: The within-treatment and between-treatment MCID for the I-QOL total score was 6.3 and 2.5, respectively. The total and subscale scores had almost identical MCIDs. Duloxetine 80 mg significantly improved the I-QOL total and subscale scores. Treatment differences in the I-QOL scores exceeded the between-treatment MCID and the duloxetine I-QOL treatment effect exceeded the within-treatment MCID. The number of patients needed to treat to gain an additional I-QOL responder was 6.8. CONCLUSIONS: Improvements in I-QOL scores should be greater than the within-treatment MCID, and differences between two treatments should be greater than the between-treatment MCIDs, for statistically significant differences to be considered clinically meaningful. We propose 2.5 points as a reasonable guide for the I-QOL between-treatment MCID and 6.3 points for the within-treatment MCID.

Medication use and control of urination among community-dwelling older adults.

OBJECTIVE: The purpose of this study is to evaluate whether the use of medications with urological activity (UA) is associated with self-reported difficulty in control of urination. METHODS: This is a cross-sectional study using data from the Duke Established Populations for Epidemiologic Studies of the Elderly. RESULTS: Difficulty holding urine was reported by 49.5% of men and 54.0% of the women. Overall, 50.9% of men and 72.7% of the women took one or more medications with UA. Multivariable logistic regression for men revealed that neither use of any medication with UA (Adjusted [Adj.] Odds Ratio [OR] 1.12, 95% confidence interval [CI] 0.84-1.50) nor the number of medications with UA used was associated with urinary difficulties (Adj. OR 1.08, 95% CI 0.97-1.21). For women, there was a significant association (p < .05) between use of any medication with UA and reported urinary difficulty (Adj. OR = 1.31, 95% CI = 1.05-1.62). DISCUSSION: Medications with UA may be related to difficulty in controlling urine among community-dwelling elderly women.

A randomized controlled trial of duloxetine alone, pelvic floor muscle training alone, combined treatment and no active treatment in women with stress urinary incontinence.

PURPOSE: We primarily compared the effectiveness of combined pelvic floor muscle training (PFMT) and duloxetine with imitation PFMT and placebo for 12 weeks in women with stress urinary incontinence (SUI). In addition, we compared the effectiveness of combined treatment with single treatments, single treatments with each other and single treatments with no treatment. MATERIALS AND METHODS: This blinded, doubly controlled, randomized trial enrolled 201 women 18 to 75 years old with SUI at 17 incontinence centers in the Netherlands, United Kingdom and United States. Women averaged 2 or more incontinence episodes daily and were randomized to 1 of 4 combinations of 80 mg duloxetine daily, placebo, PFMT and imitation PFMT, including combined treatment (in 52), no active treatment (in 47), PFMT only (in 50) and duloxetine only (in 52). The primary efficacy measure was incontinence episode frequency. Other efficacy variables included the number of continence pads used and the Incontinence Quality of Life questionnaire score. RESULTS: The intent to treat population incontinence episode frequency analysis demonstrated the superiority of duloxetine with or without PFMT compared with no treatment or with PFMT alone. However, pad and Incontinence Quality of Life analyses suggested greater improvement with combined treatment than single treatment. A completer population analysis demonstrated the efficacy of duloxetine with or without PFMT and suggested combined treatment was more effective than either treatment alone. CONCLUSIONS: The data support significant efficacy of combined PFMT and duloxetine in the treatment of women with SUI. We hypothesize that complementary modes of action of duloxetine and PFMT may result in an additive effect of combined treatment.

Pharmacological treatment of women awaiting surgery for stress urinary incontinence.

OBJECTIVE: Duloxetine, a serotonin/norepinephrine reuptake inhibitor, has been effective in the treatment of mild and moderate stress urinary incontinence. The aim of this trial was to assess its efficacy for women with severe stress urinary incontinence. METHODS: One hundred nine women, aged 33-75 years, enrolled into this double-blind, randomized, placebo-controlled study. Subjects had to have a predominant symptom of stress urinary incontinence with an incontinence episode frequency 14 per week or more, pure urodynamic stress urinary incontinence, and continence surgery already scheduled. Women were randomized to placebo (n = 54) or duloxetine 80 mg/d (n = 55) for 4 weeks, escalated to 120 mg/d for 4 weeks. Assessment variables included incontinence episode frequency, continence pad use, the Incontinence Quality of Life (I-QOL) questionnaire, and the Willingness to Consider Surgery rating. A responder was defined as a subject with an incontinence episode frequency reduction of 50% or more. RESULTS: There were significant improvements with duloxetine compared with placebo in incontinence episode frequency (-60% versus -27%, P <.001), I-QOL score (+10.6 versus +2.4, P =.003), and pad use (-34.5% versus -4.8%, P =.008). At the conclusion of the 8-week study, 10/49 (20%) duloxetine-treated women were no longer interested in surgery, compared with 0/45 placebo-treated women (P =.001). Duloxetine-treated subjects were significantly more likely to be classified as responders (relative risk 4.68, 95% confidence interval 2.27-9.66). The number of subjects-needed-to-treat to gain an additional incontinence episode frequency responder with duloxetine was 2.02. All duloxetine responses were observed within 2 weeks. Side effects and discontinuations because of side effects were significantly more common with duloxetine. CONCLUSION: The data support duloxetine's efficacy in women with severe stress urinary incontinence and suggest that some women responding to duloxetine may reconsider their willingness to undergo surgery.

The effect of previous treatment experience and incontinence severity on the placebo response of stress urinary incontinence.

OBJECTIVE: The placebo response associated with stress urinary incontinence (SUI) is sizeable but poorly understood. The aim of this study was to examine the relationship between previous treatment experience and baseline urinary incontinence severity with placebo response. STUDY DESIGN: Nine hundred twenty-one women ages 24 to 83 years received placebo in 4 12-week randomized trials evaluating duloxetine for SUI in 16 countries in Africa, Australia, Europe, and North and South America. Incontinence episode frequency (IEF) was calculated before and after randomization with entries from subject-completed real-time diaries. At baseline, subjects reported on their experience with previous continence surgery and with current pelvic floor muscle training (PFMT) with standardized questions. Analyses included Pearson correlations and the Wilcoxon two-sample test, and were based on intent-to-treat principles. RESULTS: The placebo group averaged 17 IEF per week at baseline. Fifty-five percent of placebo-treated subjects averaged >or=14 IEF/wk, 11.8% had previous continence surgery, and 16.5% currently performed PFMT. The overall median decrease in IEF with placebo was 33%, but ranged from 11% to 57% for individual countries. The placebo response was lower in women with more severe SUI (29.6% vs 36.4%, P=.07), in those who had previous continence surgery (25.0% vs 33.3%, P=.26), and for those using PFMT (23.6% vs 33.3%, P=.02). There was a significant positive correlation (rho=.44; P <.0001) between the placebo response within a country and that country's use rate for PFMT. CONCLUSION: Treatment naivete and less severe incontinence are associated with an increased placebo response in clinical trials for stress urinary incontinence, although this difference was statistically significant only for PFMT.

Validation of a clinical algorithm to diagnose stress urinary incontinence for large studies.

PURPOSE: We assessed the accuracy with which a clinical diagnostic algorithm for stress urinary incontinence (SUI) based on symptoms and signs without including urodynamics predicted the observation of urodynamic SUI and the condition of SUI. Such an algorithm would have applicability to ensure that the majority of women entering large SUI clinical trials would have urodynamic SUI and/or the condition of SUI without performing urodynamic testing in all subjects. MATERIALS AND METHODS: A total of 1455 women with urinary incontinence at least 3 months in duration were enrolled in 3 randomized clinical trials (1 phase 2 and 2 phase 3 trials) of duloxetine vs placebo for the treatment of SUI in Europe and North America. Subjects were identified as having SUI based on a clinical algorithm that required a predominant symptom of SUI with a weekly incontinence episode frequency of 4 or greater (phase 2 study), or 7 or greater (phase 3 studies), absent predominant urge symptoms, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress (sign of SUI) and stress pad test. Multichannel urodynamic studies were performed in a subset of 184 women at 23 study sites. Of these urodynamic tracings 173 (94%) were of adequate quality to make an assessment of the filling phase and assign a diagnosis of urodynamic SUI, detrusor overactivity or a normal filling phase. Two-sided 95% exact CIs for the proportions were calculated. RESULTS: The clinical algorithm had a positive predictive value of 90.2% for urodynamic SUI with or without detrusor overactivity and 76.9% for urodynamic SUI only (pure urodynamic SUI). The positive predictive value for the condition of pure SUI was 85.0%, while for the condition of SUI in pure and mixed forms the positive predictive value was 98.3%. Patient age, previous continence surgery or the severity of incontinence did not influence algorithm accuracy. CONCLUSIONS: The algorithm is suitably feasible and sufficiently predictive to be used in large clinical trials designed to evaluate conservative treatment for women with SUI. It ensures that the overwhelming majority of the study population would have urodynamic SUI and the condition of SUI.

Healthcare utilization among women who undergo surgery for stress urinary incontinence.

This study examined patterns of care for women undergoing surgery for stress urinary incontinence (SUI). A retrospective analysis of administrative claims data was performed and we identified 12520 women with a diagnosis of SUI and a subset of 3735 women with a surgical procedure code for SUI. For the main types of surgeries, we examined length of stay, pharmaceutical use, complications, and healthcare utilization related to incontinence greater than 6 months after surgery. Approximately 30% of women with a coded SUI diagnosis underwent surgery. Of the initial procedures, 40% were retropubic suspensions and 25% were sling procedures. Almost 4% of women underwent an additional surgery, and 14.1% had claims related to incontinence 6 or more months after the initial procedure. We examined medical care and pharmaceutical use for women undergoing continence surgery. This information may be important to patients and physicians discussing treatment options.

Medical and self-care practices reported by women with urinary incontinence.

OBJECTIVES: To determine the extent to which women with incontinence have been identified by physicians, the coping and treatment strategies that incontinent women use, and the factors associated with treatment strategy utilization. STUDY DESIGN: A 2-stage, nationwide, cross-sectional survey. METHODS: Survey participants were adult women from representative US households in NFO WorldGroup survey panels. Of 2310 incontinent women who received the second-stage detailed questionnaire, 1970 (85%) responded. Descriptive analyses were performed to determine the impact of incontinence, the proportion of respondents who had talked to a physician about incontinence, the responses of physicians to these incontinent women, and coping strategies used. We conducted logistic regressions to determine factors associated with treatment strategy utilization. RESULTS: Almost half of incontinent women considered their incontinence moderately to extremely bothersome, yet only 56% of the moderately to extremely bothered women had ever talked to a physician about incontinence. In 85% of all cases, the incontinent woman, rather than the physician, raised the issue of incontinence. Coping strategies women reported ever trying included limiting fluid intake (38%) and physical activity (21%). Kegel exercises and prescription medications were used currently by 20% and 6% of this population, respectively. CONCLUSIONS: Among women of all ages, only about half of women bothered by incontinence have ever talked to a physician about it, and many incontinent women rely on strategies to avoid or conceal incontinence. A better understanding of the current use of coping and treatment strategies as well as the interaction between women and physicians regarding incontinence may help to inform efforts to optimize management of incontinence for women bothered by incontinence symptoms.