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Obstetrics & Gynecology:
Original Research

Mixed Urinary Incontinence Symptoms: Urodynamic Findings, Incontinence Severity, and Treatment Response

Bump, Richard C. MD; Norton, Peggy A. MD; Zinner, Norman R. MD; Yalcin, Ilker PhD; for the Duloxetine Urinary Incontinence Study Group

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Author Information

Lilly Research Laboratories, Indianapolis, Indiana; Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah; and Doctor's Urology Group, Torrance, California.

Address reprint request to: Richard C. Bump, MD, Eli Lilly and Company Corporate Center, DC 6112, Indianapolis, IN 46285; E-mail: bump_richard@lilly.com.

*See Appendix A.

Financial Disclosure This work was sponsored by Eli Lilly and Company. Dr. Bump and Dr. Yalcin are full-time employees of Eli Lilly and Company and hold stock and stock options in the company. Dr. Norton and Dr. Zinner have served on the advisory boards for and have consulting agreements with Eli Lilly and Company.

Received November 5, 2002. Received in revised form February 3, 2003. Accepted February 19, 2003.

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Abstract

OBJECTIVE: To investigate the relationship between the symptom of mixed urinary incontinence and incontinence severity, urodynamic findings, and treatment response.

METHODS: This is a secondary analysis of data from 553 women randomized into a double-blind, placebo-controlled study evaluating duloxetine (serotonin–norepi-nephrine 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.

RESULTS: 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).

CONCLUSION: 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.

“Mixed urinary incontinence” is a term that can apply both to a combination of incontinence symptoms (stress urinary incontinence and urge urinary incontinence) and to a combination of urodynamic conditions (urodynamic stress incontinence and detrusor overactivity) in the same individual. Previous studies report variable prevalence estimates for mixed urinary incontinence symptoms. In a summary by Sandvik et al1 of eight articles, between 29% and 61% of incontinent women reported mixed urinary incontinence. In contrast, Hampel et al2 reported that 29% of female incontinence symptoms were mixed urinary incontinence, based on the average prevalence from 21 epidemiologic studies. Mixed symptoms tend to be more prevalent in clinical than in population-based epidemiologic studies.1,3

It is well known that incontinence symptoms imprecisely predict the pathophysiologic mechanism (as determined by urodynamic testing) responsible for an individual patient's incontinence. As many as 55% of women with only urodynamic stress incontinence and 38% with only detrusor overactivity report mixed symptoms.4 It is also well recognized that mixed symptoms are much more common than mixed conditions. In a clinical sample of 950 consecutive incontinent women at Duke University, 52% of patients presented with mixed symptoms (stress urinary incontinence plus urge urinary incontinence), whereas only 14% had mixed conditions (urodynamic stress incontinence plus detrusor overactivity) confirmed on urodynamic testing.3 These findings are comparable to those of Sandvik et al,1 who reported on 236 women consecutively referred for specialized evaluation of urinary incontinence. Although 46% of these women (108 of 236) presented with mixed urinary incontinence symptoms, only 44% of these (47 of 108) were given a composite clinical diagnosis of mixed urinary incontinence by a gynecologist who considered information from the history, clinical evaluation, and urodynamic testing. The majority of patients whose diagnosis was changed in both studies went from mixed urinary incontinence to pure urodynamic stress incontinence4 or pure stress urinary incontinence.1

In epidemiological studies, women with mixed urinary incontinence symptoms typically have worse incontinence than do women with only stress urinary incontinence or urge urinary incontinence.1,5 In the Norwegian EPINCONT Study,5 severe incontinence (defined by a validated index based on frequency and amount of leakage) was seen in 38% of women with mixed urinary incontinence, compared with 28% and 17% of those with urge urinary incontinence and stress urinary incontinence, respectively (P < .001). In the same study, significantly more women with mixed urinary incontinence (47%) were bothered by their incontinence, compared with women with urge urinary incontinence (36%) or stress urinary incontinence (24%) (P < .001).

The greater perceived severity of mixed urinary incontinence is commonly attributed to the fact that a woman with mixed urinary incontinence has two conditions (urodynamic stress incontinence and detrusor overactivity) and that the effects of the two conditions are additive and thus more severe and bothersome than is a single condition. However, this explanation is difficult to reconcile with the observation that the majority of women with mixed urinary incontinence symptoms do not have both urodynamic stress incontinence and detrusor overactivity on urodynamic testing. An alternative explanation for the more severe incontinence observed in women with mixed urinary incontinence is that mixed symptoms are a result of more severe incontinence rather than the result of two conditions. The aim of the current study was to investigate the relationships between the symptom of mixed urinary incontinence and incontinence severity, urodynamic findings, and treatment response in women, by performing a secondary analysis of data from a previously reported phase II, randomized, clinical trial that studied the role of duloxetine hydrochloride, a selective serotonin–norepinephrine reuptake inhibitor, in the therapy of predominant stress urinary incontinence.6

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MATERIALS AND METHODS

Women aged 18–65 years with urinary incontinence of at least 3 months' duration (N = 553) were enrolled in this double-blind, placebo-controlled, randomized study, details of which have been previously published.6 The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinent episode frequency of at least four; the lack of predominant symptoms of enuresis or urge urinary incontinence; diurnal and nocturnal frequencies less than eight and less than three, respectively, on screening history; negative funnel infusion cystometry with a first sensation greater than 100 mL and a bladder capacity of at least 400 mL; and a positive fixed volume cough stress test and stress pad test (greater than 2 g). Subjects were excluded if they had prolapse stage II or greater7; had a postvoid residual volume of 50 mL or more; were using any pharmacologic agent or device for urinary incontinence; had adopted or changed behavioral management for urinary incontinence within 3 months; or had a history of prior continence surgery. The study was conducted at 48 study centers in the United States. The institutional review board for each site approved the study, and written, informed consent was obtained from all participants.

After a 2-week, no-drug lead-in period followed by a 2-week, blinded, placebo lead-in period, subjects were randomized under double-blind conditions to 12 weeks of acute treatment with duloxetine 20 mg per day (20 mg once daily), duloxetine 40 mg per day (20 mg twice daily), duloxetine 80 mg per day (40 mg twice daily), or placebo. All subjects received two identical capsules twice daily. Subjects were seen at 4-week intervals throughout the acute treatment period.

The primary severity measure at baseline and during treatment was the incontinent episode frequency, recorded realtime on daily diaries for 1 week before each baseline and treatment visit. Diaries were also used to calculate the number of daily voids, the average voiding interval, and the number of voids associated with a strong urge to urinate. A secondary measure of severity at baseline and during treatment was the Incontinence Quality of Life (I-QOL) questionnaire.8,9 This is a validated, disease-specific, 22-item instrument (Appendix B) that evaluates the effects of urinary incontinence in three domains (avoidance and limiting behavior, social embarrassment, and psychosocial impact). It includes questions that evaluate both the distress and impact of urinary incontinence, with a score of 100 being the best possible and 0 the worst possible quality of life. A secondary baseline severity measure, the Patient Global Impression of Severity (PGI-S, Appendix C) scale, was obtained only before the treatment phase.

Three questions from the I-QOL questionnaire were chosen a priori to define the subset of this predominant stress urinary incontinence population that also had significant urge symptoms. These were question 1 (“I worry about not being able to get to the toilet on time”), question 18 (“I worry about wetting myself”), and question 19 (“I feel like I have no control over my bladder”). Further a priori rules for defining mixed urinary incontinence symptoms in this study required that a subject answer “quite a bit,” or “moderately” to all three questions or “extremely” to any question to be considered to have mixed symptoms. When severity of incontinence was determined from the I-QOL questionnaire, a corrected I-QOL score that was calculated without the three index urge questions is reported (Appendix B).

Multichannel urodynamic studies were performed on a subset of 90 women at eight study sites. Tracings from 86 of these women (16% of the study population) were technically satisfactory for central interpretation by a blinded reader. Vesical pressure was recorded with a transurethral bladder catheter, and abdominal pressure was measured with a rectal catheter during medium fill (50 mL per minute) retrograde infusion cystometry with room temperature saline. Urodynamic stress incontinence and detrusor overactivity were diagnosed according to the standards of the International Continence Society.10

Enrollment into the study was set to end when approximately 500 patients (125 per treatment group) had been assigned to a treatment group at visit 3. The sample size was determined to provide at least 80% power to detect a pairwise treatment difference to placebo of 20% in the mean percentage change in weekly incontinent episode frequency, with an overall type I error of 0.05.

Student t test was used to compare all two-group comparisons of continuous measurements. Pearson χ2 test or Fisher exact test was performed in all between-group comparisons of categoric measures. Efficacy of duloxetine in mixed urinary incontinence and stress urinary incontinence groups was evaluated with an analysis of variance model. The model included the outcome measure (ranked percentage change in incontinent episode frequency and absolute change in corrected I-QOL) as a dependent variable and symptom group (mixed urinary incontinence and stress urinary incontinence), treatment (placebo, duloxetine 20, 40, and 80 mg per day), and treatment × group interaction as independent variables. The interaction was used to test the similarity of improvement in the outcome measure between mixed urinary incontinence and stress urinary incontinence groups. A nonsignificant interaction term (P ≥ .10) suggests that the improvement between the two groups was parallel. A logistic regression model was used to assess the relative importance of urodynamic diagnoses compared with symptoms in determining patient self-perceived urinary incontinence severity. The model included the PGI-S (normal/mild versus moderate/severe) as an outcome variable and urodynamic diagnoses (pure urodynamic stress incontinence versus urodynamic stress incontinence plus detrusor overactivity) and symptom groups (mixed urinary incontinence versus stress urinary incontinence) as explanatory variables. All statistical analysis was performed with SAS 6.09 software (SAS Institute, Cary, NC).

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RESULTS

A total of 553 women entered the trial and were randomized to duloxetine 20 mg per day (n = 138), duloxetine 40 mg/day (n = 137), duloxetine 80 mg per day (n = 140), or placebo (n = 138). Overall, the mean age was 49.6 years (standard deviation 8.4), the median vaginal parity was 2 (range, 0–9), and the mean body mass index was 29.4 kg/m2 (standard deviation 6.8). The majority of subjects (93%) were white. None of these characteristics differed significantly among treatment groups or between the mixed urinary incontinence and stress urinary incontinence symptom groups at baseline.

Mixed urinary incontinence symptoms were reported by 171 of 553 subjects (30.9%) at baseline. Table 1 shows the distribution of responses to the three index questions for both the stress urinary incontinence and mixed urinary incontinence groups at baseline. The proportion of subjects with mixed urinary incontinence symptoms was 27%, 37%, 34%, and 26% in the placebo and duloxetine 20, 40, and 80 mg per day groups, respectively (P = .16). The group labeled as having mixed urinary incontinence symptoms based on responses to the three I-QOL questions also had other independent urge-related characteristics at baseline. Compared with the women with pure stress urinary incontinence symptoms, the mixed urinary incontinence group had a significantly shorter average voiding interval (2.28 versus 2.42 hours, P < .02), were significantly more likely to void nine or more times per day during the blinded, placebo lead-in phase of the study (63% versus 50%, P = .005), and had significantly more voids per week associated with strong urgency (34.0 versus 27.6, P < .001). In the subgroup of women who underwent urodynamic testing, those with mixed urinary incontinence symptoms were significantly more likely to have detrusor overactivity demonstrated than were those with pure stress urinary incontinence symptoms (33% versus 13%, P = .02, Table 2).

Table 1
Table 1
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Table 2
Table 2
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Of the subjects with mixed urinary incontinence symptoms at baseline, 162 had data that allowed treatment assessment. Of these, only 55 (34.0%) had persistent mixed urinary incontinence symptoms at the end of the treatment phase. Overall, 88% and 90% of mixed urinary incontinence subjects were bothered at least moderately by all three symptoms at baseline and during treatment, respectively.

At baseline, women with mixed urinary incontinence symptoms had evidence of significantly worse incontinence than did those with only stress urinary incontinence symptoms based on mean weekly incontinent episode frequency, corrected I-QOL, and PGI-I values (Table 3). These differences between mixed urinary incontinence and stress urinary incontinence subjects were also observed during treatment. When the 55 women with treatment-persistent mixed urinary incontinence symptoms were compared with the 107 women whose mixed urinary incontinence symptoms reverted to pure stress urinary incontinence symptoms with treatment, the persistent mixed urinary incontinence subjects had a significantly greater weekly incontinent episode frequency and significantly lower I-QOL scores (Table 3). Subjects with persistent mixed urinary incontinence with treatment also had significantly less success in increasing their voiding intervals than did those whose mixed urinary incontinence resolved (Table 3).

Table 3
Table 3
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When only the subgroup of subjects who underwent urodynamic testing were considered, those subjects with mixed conditions (urodynamic stress incontinence plus detrusor overactivity) did not have evidence of worse incontinence at baseline as measured by weekly incontinent episode frequency, I-QOL, or PGI-S, compared with those with urodynamic stress incontinence alone (Table 4). During treatment, the same findings were observed for weekly incontinent episode frequency and I-QOL, although the group sizes were quite small. In contrast to the observation that subjects with mixed conditions tended to have no more severe incontinence than did those with only urodynamic stress incontinence, subjects in the urodynamic group with mixed symptoms tended to have more severe incontinence by all measures than did those with stress urinary incontinence (Table 5). Although the differences between symptom groups for weekly incontinent episode frequency did not reach statistical significance in this subgroup analysis, the absolute differences (3.5 and 3.9 at baseline and with treatment, respectively, Table 4) were comparable to those observed to be highly significant in the larger complete study population (3.8 and 5.0, Table 3).

Table 4
Table 4
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Table 5
Table 5
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In a logistic regression model with PGI-S (moderate or severe) as the outcome variable and symptoms (stress urinary incontinence and mixed urinary incontinence) and conditions (urodynamic stress incontinence and urodynamic stress incontinence plus detrusor overactivity) as the explanatory variables, mixed symptoms were significantly associated with increased severity (P = .001, odds ratio = 6.4, 95% confidence interval [CI] 2.0, 20.2), whereas mixed conditions were not (P = .80, odds ratio = .87, 95% CI 0.2, 3.2). The tendency for comparable or less severe incontinence in subjects with mixed conditions but for more severe incontinence in subjects with mixed symptoms persisted when data were stratified according to condition and symptom classes (Table 5). Twelve of seventeen women (71%) who had mixed symptoms and pure urodynamic stress incontinence and 6 of 7 (86%) who had mixed symptoms and mixed conditions at baseline reverted to the symptom of pure stress urinary incontinence with treatment. No treatment phase urodynamic studies were performed.

The statistically significant efficacy demonstrated by duloxetine at the 40 and 80 mg per day doses compared with placebo in the overall study population has been reported previously.6 When responses were stratified by symptom type and analyzed with the analysis of variance model on ranked percentage changes, both symptom groups demonstrated significant improvements in incontinence (expressed as the median percentage decrease in pooled weekly incontinent episode frequency) with duloxetine 40 mg per day (stress urinary incontinence: 58%, P < 0.05; mixed urinary incontinence: 62%, P < .004) and with 80 mg per day (stress urinary incontinence: 65%, P < .001; mixed urinary incontinence: 63%, P <.01) compared with placebo (stress urinary incontinence: 44%; mixed urinary incontinence: 33%). The decrease in placebo response in the mixed urinary incontinence group is similar to the decreased placebo response reported with more severely incontinent women in the original report.6 The same analysis of variance model revealed that the significant treatment responses observed were not dependent on the symptom type (interaction P = .47).

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DISCUSSION

The results of this analysis indicate that, for women presenting with predominant stress urinary incontinence symptoms, the major determinant of concurrent urge symptoms is incontinence severity and not the pathophysiologic condition(s) causing the incontinence. A major premise of previous explanations for the increased severity of incontinence symptoms reported by women with mixed incontinence has been that two conditions combine to create two symptoms and that having two conditions results in worse symptoms. In contrast, our findings suggest that, in many cases, it is actually the more severe stress incontinence that leads to mixed symptoms. The data show that women with more severe incontinence are more likely to report mixed symptoms. As the severity of incontinence improves during treatment, mixed symptoms resolve.

One explanation for these observations is probably derived from the fact that more severe incontinence recalled over a long period with a greater number of incontinence episodes tends to compromise a patient's ability to focus on the events related to each episode. As a result, distinctions between symptom types blur. As the number of incontinent episodes and the recall period decrease, the patient is better able to discriminate individual events, and her symptom recall becomes more focused and specific. This scenario is roughly synonymous with the unfocused history offered by a patient with chronic pelvic pain compared with the specific recall of events by a patient with acute pain.

This change in perspective—that symptoms are driven by incontinence severity rather than by conditions—helps reconcile some apparent contradictions observed with the latter paradigm. It helps explain why mixed urinary incontinence patients report more severe incontinence despite the fact that most such patients do not have both urodynamic stress incontinence and detrusor overactivity. Because severity of incontinence is a major impetus for a patient's seeking care for her incontinence,5 it helps explain why mixed symptoms are more common in clinical populations1,3 than in representative epidemiologic populations.2 Finally, it helps explain why a treatment that is felt to be relatively specific for one of the two major incontinence symptoms (for example, continence surgery for stress urinary incontinence or bladder retraining for urge urinary incontinence) may also prove effective for the other symptom.

One potential criticism of our methods was our use of I-QOL responses to identify subjects with urge symptoms in this secondary analysis. We feel that several facts substantiate the validity of this approach, however. First, the index questions were identified a priori by the first author, based on more than 20 years of clinical experience in the management of urinary incontinence, before any analysis was performed. Second, there were clear differences in the distributions of responses between the two symptom groups. Finally, the fact that subjects in the mixed urinary incontinence group were significantly more likely to have detrusor overactivity, had significantly greater urinary frequency, and had significantly more voids associated with severe urge, further support the validity of assigning an urge component to this patient group. However, the wording of the I-QOL questions does not allow us to determine whether these subjects had stress urinary incontinence plus urge incontinence or stress urinary incontinence plus dry overactive bladder symptoms.

Our findings differ somewhat from those reported by Kreder from a single-blind, multicenter tolterodine study of a population whose recruitment was based on a predominant symptom complex of overactive bladder (Kreder KJ. Tolterodine is equally effective in patients with mixed incontinence. International Continence Society 31st Annual Meeting; Seoul, South Korea; September 18–21, 2001). The symptom of stress urinary incontinence was also reported by 26% of the female study subjects (165 of 629) with overactive bladder symptoms. In contrast to the findings from our population, whose recruitment was based on a predominant symptom of stress urinary incontinence, Kreder's stress urinary incontinence–overactive bladder group had similar measures of baseline disease severity (daily incontinent episode frequency and voiding frequency) compared to his overactive bladder–only group. No urodynamic studies were performed in this overactive bladder study, so it is not possible to know whether most of the subjects with mixed symptoms also had mixed conditions. It is plausible that many of the stress incontinence symptoms actually represented stress-induced detrusor overactivity. Nonetheless, we would conclude that incontinence severity is not so important in determining mixed symptoms when urge symptoms predominate compared with when stress symptoms predominate. In both studies, it was the predominant urinary symptom that seemed to be most responsible for predicting treatment response.

It has been hypothesized previously that women with mixed urinary incontinence symptoms have urodynamic stress incontinence as their primary problem and that the detrusor overactivity results secondarily when the incompetent bladder neck allows urine to be forced into the proximal urethra during physical activity, eliciting urethrodetrusor facilitative reflexes that trigger an involuntary detrusor contraction.11 The potential for the entry of fluid into the urethra to reflexively initiate a bladder contraction has been a matter of controversy for most of the 20th century. There is evidence that this reflex is species-dependent, being observed in anesthetized cats,12–14 dogs,15 and rats11 but not being demonstrated convincingly in humans.16–18 The current study does not provide direct evidence for or against this facilitative reflex. However, the fact that most women in the current study with mixed symptoms did not have mixed conditions would seem to suggest that such facilitative reflexes play a minor role in determining mixed urinary incontinence symptoms.

In summary, in women with a predominant symptom of stress urinary incontinence, incontinence severity seems to be the driver of mixed urinary incontinence symptoms rather than conditions being the driver of symptoms and severity. As incontinence severity improves, mixed symptoms resolve. The majority of women with mixed symptoms do not have mixed conditions, and conservative therapy can be directed toward the predominant symptom based on the events (stress or urge) associated with the majority of incontinent episodes.

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REFERENCES

1. Sandvik H, Hunskaar S, Vanvik A, Bratt H, Seim A, Hermstad R. Diagnostic classification of female urinary incontinence: An epidemiological survey corrected for validity. J Clin Epidemiol 1995;48:339–43.

2. Hampel C, Wienhold D, Benken N, Eggersmann C, Thuroff JW. Definition of overactive bladder and epidemiology of urinary incontinence. Urology 1997:50 Suppl 6A:4–14.

3. Weidner AC, Myers ER, Visco AG, Cundiff GW, Bump RC. Which women with stress incontinence require urodynamics? Am J Obstet Gynecol 2001;184:20–7.

4. Cardozo LD, Stanton SL. Genuine stress incontinence and detrusor instability: A review of 200 patients. Br J Obstet Gynaecol 1980;87:184–90.

5. Hannestad YS, Rortveit G, Sandvik H, Hunskaar S. A community-based epidemiological survey of female urinary incontinence: The Norwegian EPINCONT study. J Clin Epidemiol 2000;53:1150–7.

6. Norton PA, Zinner NR, Yalcin I, Bump RC. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol 2002;187:40–8.

7. Bump RC, Mattiasson A, Bø K, Brubaker LP, DeLancey JOL, Klarskov P, et al. The standardisation of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996;175:10–17.

8. Wagner TH, Patrick DL, Bavendam TG, Martin ML, Buesching DP. Quality of life of persons with urinary incontinence: Development of a new measure. Urology 1996;47:67–71.

9. Patrick DL, Martin ML, Bushnell DM, Yalcin I, Wagner TH, Buesching DP. Quality of life of women with urinary incontinence: Further development of the incontinence quality of life instrument (I-QOL). Urology 1999;53:71–6.

10. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardization of terminology of lower urinary tract function: Report from the standardization sub-committee of the International Continence Society. Neurourol Urodyn 2002;21:167–78.

11. Jung SY, Fraser MO, Ozawa H, Yokoyama O, Yoshiyama M, de Groat WC, et al. Urethral afferent nerve activity affects the micturition reflex: Implication for the relationship between stress incontinence and detrusor instability. J Urol 1999;162:204–12.

12. Barrington FJF. The nervous mechanism of micturition. Q J Exp Physiol 1914;8:33–71.

13. Barrington FJF. The relation of the hind-brain to micturition. Brain 1921;44:23–53.

14. Barrington FJF. The effect of lesions of the hind- and mid-brain on micturition in the cat. Q J Exp Physiol 1925;15:81–102.

15. Fukaya Y. Studies on urethrodetrusor facilitative reflex: Characteristics of bladder response and neuroreceptor mechanism. Jpn J Urol 1988;79:765–71.

16. Denny-Brown D, Robertson EG. On the physiology of micturition. Brain 1933;56:149–9.

17. Sutherst JR, Brown M. The effect on the bladder pressure of sudden entry of fluid into the posterior urethra. Br J Urol 1978;50:406–9.

18. Bump RC. The urethrodetrusor facilitative reflex in women: Results of urethral perfusion studies. Am J Obstet Gynecol 2000;182:794–804.

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APPENDIX A

The Duloxetine Urinary Incontinence Study Group included the following principal investigators and their staffs: Joseph S. Sanfilippo, MD, Allegheny General Hospital, Pittsburgh, Pennsylvania; Hillary Browne, MD, Alpine Clinical Research Center, Boulder, Colorado; Ronald L. Young, MD, Baylor College of Medicine, Houston, Texas; Harvey E. Armel, MD, Clinical Research Consultants Inc., Trumbull, Connecticut; Guillermo Davila, MD, Colorado Gynecology and Continence Center, Denver, Colorado; Simon Chung, MD, Dominion Urological Associates, Fairfax, Virginia; Jay M. Baker, MD, Eastern Virginia Medical School, Norfolk, Virginia; Mickey M. Karram, MD, Good Samaritan Hospital, Cincinnati, Ohio; Ronald Tutrone, MD, Greater Baltimore Medical Center, Baltimore, Maryland; Edward J. Durbin, MD, PhD, Health Advance Institute, South Bend, Indiana; Warren O. Kessler, MD, Hillcrest Urological Medical Group, San Diego, California; Veronica T. Mallett, MD, Hutzel Hospital, Detroit, Michigan; Christopher Carey, MD, Milton S. Hershey Medical Center, Hershey, Pennsylvania; Lewis F. Russell, Jr, MD, PA, Institute of Clinical Research, San Antonio, Texas; Vincent Lucente, MD, Lehigh Valley Hospital, Allentown, Pennsylvania; Martin Conway, MD, Lovelace Scientific Resources Inc., Albuquerque, New Mexico; Aaron Kirkemo, MD, Metropolitan Urologic Specialists, Detroit, Michigan; James Schoeck, MD, Orlando Clinical Research Center, Orlando, Florida; Alan D. Garely, MD, North Shore University Hospital, Great Neck, New York; Karny Jacoby, MD, Northwest Outpatient Medical Center, Seattle, Washington; Enrique M. deCastro, MD, Northwest Women's Clinic, Portland, Oregon; Roger D. Fincher, MD, PC3 Inc., Spokane, Washington; Brenda Williams, MD, PC3 Inc., Boise, Idaho; John P. Lenihan, Jr, MD, Pacific Coast Clinical Coordinators, Tacoma, Washington; Thomas Melchione, MD, Pacific Coast Clinical Coordinators, Sacramento, California; Stuart A. Sarshik, MD, Pennridge Urological Associates PC, Sellersville, Pennsylvania; David C. Reed, MD, Pacific Coast Clinical Coordinators, Bellevue, Washington; Mark M. Blatter, MD, Primary Physicians Research, Pittsburgh, Pennsylvania; Jaroslava Zoubek, MD, Portland Clinic, Portland, Oregon; Martha C. Storrie, MD, Research Across America, Dallas, Texas; Wulf H. Utian, MD, PhD, Rapid Medical Research, Cleveland, Ohio; David F. Mobley, MD, Research for Health Inc., Houston, Texas; Linda Brubaker, MD, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois; William E. Friedel, MD, San Diego Urology Center, San Diego, California; Kandasamychetty Perumal, MD, Seton Health Incontinence Center, Troy, New York; Don I. Boychuk, MD, Sharp Rees – Stealy Medical Center, San Diego, California; Gamal Ghoniem, MD, Tulane Medical School, New Orleans, Louisiana; David Ellis, MD, URO Rehab, Bryn Mawr, Pennsylvania; Larry I. Gilderman, MD, University Clinical Research Associates Inc., Pembroke Pines, Florida; Sandra Culbertson, MD, University of Chicago Hospital, Chicago, Illinois; Ellen Wells, MD, University of North Carolina Hospitals, Chapel Hill, North Carolina; Peggy A. Norton, MD, University of Utah, Salt Lake City, Utah; Anne L. Viselli, MD, University of Vermont Women's Center, Williston, Vermont; J. Thomas Benson, MD, Urogynecology Associates, Indianapolis, Indiana; John R. Miklos, MD, Urogynecology, P.C., Alpharetta, Georgia; Peter Knapp, MD, Urology of Indiana, Indianapolis, Indiana; Norman R. Zinner, MD, Western Clinical Research Inc., Torrance, California; and Ananias Diokno, MD, William Beaumont Hospital, Royal Oak, Michigan. Cited Here...

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Life Science Journal-Acta Zhengzhou University Overseas Edition
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Current Opinion in Urology
Mixed incontinence: definitions, outcomes, and interventions
Dmochowski, R; Staskin, D
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Obstetrics & Gynecology
Effect of Transobturator Tape on Overactive Bladder Symptoms and Urge Urinary Incontinence in Women With Mixed Urinary Incontinence
Tahseen, S; Reid, P
Obstetrics & Gynecology, 113(3): 617-623.
10.1097/AOG.0b013e31819639e3
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Current Opinion in Obstetrics and Gynecology
Mixed urinary incontinence: continuing to confound?
Hockey, J
Current Opinion in Obstetrics and Gynecology, 19(6): 521-528.
10.1097/GCO.0b013e3282f1daab
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Current Opinion in Urology
Female stress urinary incontinence: how do patient and physician perspectives correlate in assessment of outcomes?
Padmanabhan, P; Nitti, VW
Current Opinion in Urology, 16(4): 212-218.
10.1097/01.mou.0000232038.72556.b1
PDF (140) | CrossRef
Obstetrics & Gynecology
Prevalence of Persistent and De Novo Overactive Bladder Symptoms After the Tension-Free Vaginal Tape
Segal, JL; Vassallo, B; Kleeman, S; Silva, WA; Karram, MM
Obstetrics & Gynecology, 104(6): 1263-1269.
10.1097/01.AOG.0000147596.44421.72
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© 2003 The American College of Obstetricians and Gynecologists

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