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.     

The prevalence of chronic constipation and faecal incontinence among men and women with symptoms of overactive bladder

Study Type – Symptom prevalence (non‐consecutive cohort)
Level of Evidence 4 What’s known on the subject? and What does the study add? There have been no previous studies examining the overlap of chronic constipation and overactive bladder in the US population. Limited research to date based on samples of elderly, Asian and pediatric populations suggests that there is substantial overlap. The results of this study suggest that the prevalence of chronic constipation is increased in people with overactive bladder who are ≥40 years and should be considered by healthcare providers treating these patients.

OBJECTIVE

To estimate the prevalence and overlap of overactive bladder (OAB), chronic constipation (CC) and faecal incontinence (FI) among a general population sample of adults in the USA.

PATIENTS AND METHODS

A cross‐sectional internet‐based survey of randomly selected panel members who were ≥40 years of age was conducted. Participants reported how often they experienced symptoms of OAB, CC and FI using Likert scales and modified Rome III criteria. Analyses were conducted to examine the overall prevalence of OAB, CC and FI in men and women separately and to characterize the extent of overlap between these conditions in participants with OAB vs those without OAB, and those participants with continent vs incontinent OAB.

RESULTS

The response rate for the survey was 62.2% and the final sample (N= 2000) included 927 men and 1073 women. The overall prevalence of OAB [defined as a response of ≥‘sometimes’ to urinary urgency (i.e. ‘sometimes’ or more often) or ‘yes’ to urinary urgency incontinence (UUI)] was 26.1% in men and 41.2% in women. The overall prevalence of CC was significantly lower in men than in women (15.3 vs 26.3%), but both men and women with OAB were significantly more likely to report CC (22.3 and 35.9% vs 5.7 and 6.7%, respectively, P < 0.0001). The overall prevalence of FI reported ‘rarely’ or more was 16.7% of men and 21.9% of women. Men and women with OAB were significantly more likely to report FI than those without OAB. FI was also more common in participants with incontinent OAB than in those with continent OAB. Logistic regressions controlling for demographic factors and comorbid conditions suggest that OAB status is a very strong predictor of CC, FI and overlapping CC and FI (odds ratios, range 3.55–7.96).

CONCLUSIONS

Chronic constipation, FI and overlapping CC and faecal incontinence occur more frequently in patients with OAB and should be considered when evaluating and treating patients with OAB. These findings suggest a shared pathophysiology among these conditions. Additional study is needed to determine if successful treatment of one or more of these conditions is accompanied by commensurate improvement in symptoms referable to the other organ system.     

Medical visits among adults with symptoms commonly associated with an overactive bladder

OBJECTIVES: To examine nationally representative data and thus obtain estimates of the use of healthcare providers associated with the overactive bladder (OAB) symptoms, a condition characterized by frequency, urgency and nocturia, with or with no urge incontinence, as although it is ranked among the 10 most common chronic medical conditions in the USA, the level of OAB-associated medical treatment remains largely unknown. METHODS: To estimate the number of annual OAB-associated medical visits among patients aged > or =18 years, three national databases in the USA (year 2000) were examined: the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, and the National Hospital Discharge Survey. Population estimates were constructed using design-based statistical analyses to account for the complex survey designs of data. RESULTS: During 2000, adult Americans made 1.4 million (95% confidence interval 1.1-1.8 million) ambulatory visits to non-Federal office-based physicians with International Classification of Disease (ICD-9) coding indicative of OAB symptoms. Accounting for emergency and outpatient department visits, as well as non-Federal short-stay hospital discharges, the estimated number of medical visits with OAB-associated ICD-9 coding was <1.5 million. CONCLUSION: The prevalence of OAB was estimated to be 34 million adult Americans. When 1.4 million ambulatory visits were compared with this prevalence, as few as 4% of adult Americans with OAB sought medical treatment during the year 2000. The present results therefore suggest a large unmet medical need among the population of adult Americans with OAB.     

Urodynamic classification of patients with symptoms of overactive bladder

PURPOSE: We describe a new classification of patients with overactive bladder symptoms. MATERIALS AND METHODS: The office records of 132 patients who presented for evaluation of symptoms of urinary frequency, urinary urgency and/or urge incontinence, and who underwent videourodynamics were identified. All patients completed a 24-hour voiding diary and 24-hour pad test. Data collection included age, sex, hormone status, number of voids and incontinence episodes per 24 hours, functional bladder capacity, pad weight and associated genitourinary conditions. Videourodynamics were reviewed and patients were divided into 4 clinical categories, including type 1-no evidence of involuntary detrusor contractions on videourodynamics, type 2-involuntary detrusor contractions present, and patient aware and able to abort them, type 3-contractions present, patient aware and able to contract the sphincter but not abort contractions and type 4-contractions present and patient unaware but unable to contract the sphincter or abort contractions. RESULTS: Average patient age +/- SD was 64 years +/- 13. There were an average of 13 +/- 5 voids and 3 +/- 5 incontinence episodes per 24 hours. Average functional bladder capacity was 306 +/- 146 cc and average pad weight was 94 +/- 165 gm. Associated diagnoses included benign prostatic hypertrophy in 28% of cases, sphincteric incontinence in 17%, idiopathic urge incontinence in 29% and uterovaginal or bladder prolapse in 17%. Another 11% of patients had bladder outlet obstruction, impaired detrusor contractility or neurogenic bladder conditions. Of the cases 72 (55%), 32 (25%), 23 (17%) and 5 (4%) were categorized as classes 1 to 4, respectively. ANOVA revealed no statistically significant differences in the number of voids or incontinence episodes, functional bladder capacity or pad test when individual categories were compared to each other. CONCLUSIONS: This overactive bladder classification stratifies patients according to degrees of awareness, and control of bladder and sphincter function. It may prove useful as a guide for prognosis and therapy. Patients can be stratified into clinical groups based on the presence or absence of involuntary detrusor contractions, the ability to abort contractions and the ability to contract the urinary sphincter in response to contractions. Limiting the definition of overactive bladder to apply only to patients with no proved infection or other pathological condition would have eliminated more than 75% of those in this sample with symptoms of urinary urgency, frequency and/or urge incontinence.     

Impact of self-perceived bothersomeness on health-related quality of life in women with overactive bladder symptoms

INTRODUCTION: The objective of this study was to examine the impact of self-perceived bothersomeness of overactive bladder (OAB) symptoms on the health-related quality of life (QOL). PATIENTS AND METHODS: A total of 92 women with a mean age of 53.3 (range 23-79) years suffering from OAB were included in the study. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and King's Health Questionnaire (KHQ) were used to assess the QOL. The patients were divided into two groups according to the bothersomeness degree of OAB: 'low' and 'moderate' to 'high'. RESULTS: The SF-36 and the KHQ scores of the patients were significantly different from those of the controls (p <0.05), except for three domains of the SF-36. No difference in the results of the frequency-volume charts was observed between the two patient groups. The scores of the SF-36 and the KHQ domains did not correlate with the data of the frequency-volume charts. Significant differences were found between the two patient groups for most domains of the SF-36 (p <0.05). Significant differences were also detected in most domains of the KHQ (p <0.05). CONCLUSIONS: Objective data are not a sensitive tool for measuring the QOL in women with OAB symptoms. Our findings suggest that patient-perceived bothersomeness significantly influences QOL and that strategies for assessing bothersomeness should be developed to evaluate the QOL in these patients.     

Outcome of coexistent overactive bladder symptoms in women with urodynamic urinary incontinence following anti-incontinence surgery

Introduction and hypothesis

The objective was to investigate the outcome of stress urinary incontinence (SUI) and overactive bladder (OAB) symptoms in women with urodynamic stress incontinence (USI) after transobturator sling procedures (TOTs).

Methods

We evaluated 109 consecutive patients with USI, who had undergone TOT in a tertiary hospital between 2012 and 2014. All patients received evaluations, including structured urogynecological questionnaires and pelvic organ prolapse quantification examination before, and 3 and 12 months after surgery. One-hour pad test and urodynamic testing were performed before and 3–6 months postoperatively. Patient demographics, lower urinary tract symptoms, and urodynamic results were analyzed between pure USI and USI with OAB symptoms.

Results

Persistent SUI occurred in 8 patients at 3 months (7.3 %) and 7 patients at 12 months (6.4 %) postoperatively. The most common OAB symptom was frequency (54.1 %), followed by urgency urinary incontinence (52.3 %), urinary urgency (42.2 %), and nocturia (33 %). Most of these OAB symptoms were resolved at the 3-month and 12-month follow-ups both in patients treated with TOT only and in those treated with TOT combined with other pelvic surgeries. There was no significant difference in the preoperative urodynamic changes between patients with pure USI and USI without OAB groups. However, postoperative urodynamic results showed a significant decrease in the maximal urethral closure pressure in the group of patients with USI and OAB symptoms, but no significant urodynamic changes in the group with pure USI.

Conclusions

Coexistent OAB symptoms are common in women who were diagnosed with USI and most of these symptoms may resolve 3 and 12 months after TOT.

     

Structured behavioral treatment research protocol for women with mixed urinary incontinence and overactive bladder symptoms

Aims

The primary aim is to provide detailed rationale and methodology for the development and implementation of a perioperative behavioral/pelvic floor exercise research protocol for women who self‐chose surgical intervention and who may or may not have been offered behavioral treatments initially. This protocol is part of the ESTEEM trial (Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence Trial) which was designed to determine the effect of a combined surgical and perioperative behavioral/pelvic floor exercise intervention versus surgery alone on improving mixed urinary incontinence (MUI) and overactive bladder (OAB) symptoms.

Methods

As part of a multi‐site, prospective, randomized trial of women with MUI electing midurethral sling (MUS) surgical treatment, participants were randomized to a standardized perioperative behavioral/pelvic floor exercise intervention + MUS versus MUS alone. The specific behavioral intervention included: education on voiding habits, pelvic floor muscle training (PFMT), bladder training (BT), strategies to control urgency and reduce/prevent urinary symptoms, and monitoring/promoting adherence to behavioral recommendations. To ensure consistency across all eight research sites in the pelvic floor disorders network (PFDN), selective behavioral treatments sessions were audiotaped and audited for protocol adherence.

Results

The behavioral intervention protocol includes individualization of interventions using an algorithm based on pelvic floor muscle (PFM) assessment, participant symptoms, and findings from the study visits. We present, here, the specific perioperative behavioral/pelvic floor exercise interventions administered by study interventionists.

Conclusions

This paper details a perioperative behavioral/pelvic floor exercise intervention research study protocol developed for women undergoing surgery for MUI.     

Relationships among symptoms, bother, and treatment satisfaction in overactive bladder patients

AIMS: We have studied the association between various symptoms, bother, and patient treatment satisfaction in overactive bladder (OAB). METHODS: Episodes of urgency, incontinence, daytime frequency and nocturia and responses to the patient perception of bladder condition scale, the urgency perception scale, and visual analog scales of limitations in daily life and of treatment satisfaction were evaluated in 3,824 OAB patients at baseline and during 9 months treatment with tolterodine ER (4 mg q.d.) in an open-label, observational study. Relationships amongst number of symptoms/ 24 hr and scales were explored. Treatment satisfaction was correlated with improvements in symptoms and scales. RESULTS: At baseline, the number of episodes of the four OAB symptoms correlated only poorly with each other and with the two bother-related scales, while the two scales assessing bother correlated much stronger with each other. Factor analysis identified four components which described "bother," "incontinence," "urgency/frequency," and "nocturia" and in combination explained 81.9% of the total variance. The component "bother" had the strongest individual effect accounting for 42.1% of the total variance. While improvements of symptoms and bother were seen with tolterodine treatment, patient treatment satisfaction correlated strongest with improvements of the two bother-related scales. CONCLUSIONS: We conclude that the counting of episodes of OAB symptoms only insufficiently describes the afflicted patients. Patient bother is the strongest individual component but only poorly explained by episodes of the four symptoms defining OAB. Alterations of bother may better reflect patient-relevant outcomes in OAB treatment than alterations in the number of symptom episodes.     

Severe depression and anxiety in women with overactive bladder

Aim

Depression and anxiety are prevalent psychiatric conditions and are associated with overactive bladder. The objective of this study was to determine prevalence and severity of anxiety and depression associated with overactive bladder (OAB) in women.

Methods

274 women with clinical diagnosis of OAB were recruited from 2012 to 2015. They were submitted to the International Consultation on Incontinence Questionnaire‐Overactive Bladder (ICIQ‐OAB), the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI).

Results

Severe or moderate depression was present in 59.8% of women and severe or moderate anxiety was identified in 62.4%. Higher scores of depression and anxiety were associated with higher scores of ICIQ‐OAB (P = 0.0031 and 0.0049). Women with severe depression had higher nocturia score than those with mild depression (P = 0.0046). Also, women with severe depression had higher urgency incontinence score than those with minimal depression (P = 0.0261). Patients with severe anxiety had higher nocturia score than those with minimal anxiety (P = 0.0118) and women with moderate anxiety had higher urgency incontinence score than with minimal anxiety (P = 0.0300).

Conclusions

Moderate or severe depression and anxiety are prevalent in women with OAB. There is a correlation between intensity of OAB symptoms with depression and anxiety. Anxiety and depression levels are mainly related with urgency incontinence and nocturia.     

Efficacy and safety of fesoterodine treatment for overactive bladder symptoms in elderly women with and without hypertension

Objective

To assess fesoterodine treatment in elderly women with overactive bladder with and without hypertension.

Methods

Data for 2527 elderly women with overactive bladder symptoms, including urgency urinary incontinence, were pooled from 10 double‐blind, placebo‐controlled fesoterodine studies.

Results

A total of 1523 elderly women (60.3%) had a history of hypertension, and 1004 women (39.7%) had no hypertension history. Overactive bladder symptoms, mean bodyweight and mean body mass index at baseline were significantly higher in women with overactive bladder and hypertension versus those without hypertension (P < 0.05). Statistically significant improvements in overactive bladder symptoms at week 12 were observed for fesoterodine treatment versus placebo in women with hypertension and those without (P < 0.05). The diary‐dry rate (no urgency urinary incontinence episodes), the proportion with less than eight micturitions/24 h, overactive bladder symptom bother and health‐related quality of life were also statistically significantly improved by fesoterodine treatment in both populations. Incidence of treatment‐related adverse events with fesoterodine was similar in women with hypertension (39.3%) and without hypertension (44.6%). Dry mouth and constipation were the most common treatment‐related adverse events with fesoterodine in women with hypertension (26.2% and 5.2%, respectively) and without hypertension (30.5% and 8.0%).

Conclusions

A relationship among the severity of overactive bladder symptoms, hypertension and obesity in elderly women is suggested. Fesoterodine provides significantly greater improvements in overactive bladder symptoms and health‐related quality of life versus placebo in women with or without hypertension. Hypertension does not appear to affect the efficacy and safety of fesoterodine in elderly women with overactive bladder symptoms, including urgency urinary incontinence.     

A retrospective comparison of ring pessary and multicomponent behavioral therapy in managing overactive bladder

Introduction and hypothesis

Overactive bladder (OAB) is a physically, psychologically, and socially disabling condition that affects millions of women worldwide and is especially prevalent postmenopause. The objective of our study was to compare the cure rates of ring pessary with those of multicomponent behavioral therapy in managing overactive bladder.

Methods

We performed a comparative retrospective parallel cohort study of all women whose overactive bladder was treated with multicomponent behavioral therapy or ring pessary over a 42-month period. At the end of the 6-month treatment period, cure was defined as the subjective (self-reported) absence of urinary urgency, frequency, nocturia, and urge incontinence in the preceding 30 days; the objective absence of these symptoms in a 7-day voiding diary; and a Patient Global Impression of Improvement response of “much better” or “very much better.”

Results

Ring pessary and multicomponent behavioral therapy had similar cure rates (29 out of 150 [19 %] vs 46 out of 231 [20 %] respectively, P?=?0.889; OR of 1.04, 95 % confidence interval 0.618–1.742, P?=?0.887). They also produced comparable cure rates in premenopausal (4 out of 31 [13 %] vs 14 out of 68 [21 %], P?=?0.358) and postmenopausal subjects (25/ out of 19 [21 %] vs 32 out of 163 [20 %], P?=?0.776), and in women who had undergone previous treatment (21 out of 108 [19 %] vs 31 out of 176 [18 %], P?=?0.699) and those who had not (8 out of 42 [19 %] vs 15 out of 55 [27 %], P?=?0.345). Logistic regression showed that neither treatment outcome is significantly associated with demographic characteristics; Pelvic Organ Prolapse Quantification at the anterior and posterior vaginal walls and at the vaginal cuff; previous treatment; overactive bladder symptoms; pad usage; or any combination thereof.

Conclusions

Ring pessary has a cure rate similar to that of multicomponent behavioral therapy in managing overactive bladder.