Comparative efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents in overactive bladder: A systematic literature review and network meta-analysis.

AIMS: To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB). METHODS: Literature searches of MEDLINE, Embase, and the Cochrane Library were undertaken to identify randomized controlled trials in OAB (2000-2015) for antimuscarinic agents. A network meta-analysis (NMA) was performed to estimate efficacy and tolerability outcomes for solifenacin 5 mg/day relative to other antimuscarinics. RESULTS: The NMA included 53 eligible trials (published, n = 48; unpublished on search date, n = 5). Solifenacin 5 mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended-release 10 mg/day, oxybutynin immediate-release (IR) 9-15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation. CONCLUSIONS: This NMA suggests that the efficacy of solifenacin 5 mg/day is at least similar to other common antimuscarinics across the spectrum of OAB symptoms analyzed, and is more effective than tolterodine 4 mg/day in reducing incontinence and UUI episodes. Solifenacin 5 mg/day has a lower risk of dry mouth compared with several agents.

Development of an overactive bladder assessment tool (BAT): A potential improvement to the standard bladder diary.

AIMS: To develop a comprehensive patient-reported bladder assessment tool (BAT) for assessing overactive bladder (OAB) symptoms, bother, impacts, and satisfaction with treatment. METHODS: Subjects were consented and eligibility was confirmed by a recruiting physician; subjects were then scheduled for in-person interviews. For concept elicitation and cognitive interviews, 30 and 20 subjects, respectively, were targeted for recruitment from US sites. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. A draft BAT was created based on the results of the concept elicitation interviews and further revised based on cognitive interviews as well as feedback from an advisory board of clinical and patient-reported outcome (PRO) experts. RESULTS: Nocturia, daytime frequency, and urgency were reported by all subjects (n = 30, 100.0%), and incontinence was reported by most subjects (n = 25, 83.3%). The most frequently reported impacts were waking up to urinate (n = 30, 100.0%), embarrassment/shame (n = 24, 80.0%), stress/anxiety (n = 23, 76.7%), and lack of control (n = 23, 76.7%). Following analysis, item generation, cognitive interviews, and advisory board feedback, the resulting BAT contains four hypothesized domains (symptom frequency, symptom bother, impacts, and satisfaction with treatment) and 17 items with a 7-day recall period. CONCLUSIONS: The BAT has been developed in multiple stages with input from both OAB patients and clinical experts following the recommended processes included in the FDA PRO Guidance for Industry. Once fully validated, we believe it will offer a superior alternative to use of the bladder diary and other PROs for monitoring OAB patients in clinical trials and clinical practice.

Patient-reported outcomes from SYNERGY, a randomized, double-blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients.

AIMS: To evaluate patient-reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial. METHODS: Following a 4-week placebo run-in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2-week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB-q Symptom Bother score, health-related quality of life (HRQOL) Total score, treatment satisfaction-visual analogue scale (TS-VAS), and patient perception of bladder condition (PPBC) questionnaires. RESULTS: Overall, 3527 patients were randomized into the study, with 3494 receiving double-blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB-q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups. CONCLUSIONS: PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB-q Symptom Bother score, HRQOL Total score, and PPBC.

Bladder function after radical hysterectomy for cervical cancer.

AIM: To report the effects of radical hysterectomy and nerve-sparing techniques on lower urinary tract function in women. METHODS: A literature search was performed in Pubmed and Medline using the keywords bladder after radical hysterectomy, nerve sparing radical hysterectomy, and urinary dysfunction following radical hysterectomy. Significant results and citations were reviewed manually by the authors. RESULTS: The sympathetic and parasympathetic systems innervating the lower urinary tract may be disrupted due to resection of uterosacral and rectovaginal ligaments, the dorsal and lateral paracervix, the caudal part of the vesico-uterine ligaments, and the vagina. This supports the neurogenic etiology of early and late bladder dysfunction after radical surgery. Bladder disorders are also related to the extent of radical surgery. The neuropathopysiology of lower urinary tract symptoms after radical hysterectomy is not fully understood. Recent data have highlighted the role of urethral sphincter pressure in the etiology of postoperative incontinence. Various surgical approaches have been developed to preserve autonomic pelvic innervation. CONCLUSIONS: Nerve-sparing techniques appear to improve bladder function without compromising overall survival. Studies comparing the effects of nerve-sparing radical hysterectomy with standard surgery yielded encouraging results in respect of postoperative lower urinary tract function. Clinical trials with a long period of follow-up are required for better comprehension of the complex pathophysiology of bladder dysfunction after radical hysterectomy.

Clinical value of a patient-reported goal-attainment measure: the global development of self-assessment goal achievement (SAGA) questionnaire for patients with lower urinary tract symptoms.

AIMS: To discuss the importance of patients' treatment goals and perceived goal attainment to better address expectations in the treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB). METHODS: The development of the Self-Assessment Goal Achievement (SAGA) questionnaire was driven by measurement principles from the field of qualitative and psychometric research adapted to elicit patients' treatment goals. At baseline, SAGA solicits individualized responses of patient's treatment expectations and goals, and at follow-up SAGA uses a goal-attainment scale (GAS) to document goal achievement. RESULTS: The SAGA questionnaire provides a basis for the patient and physician to discuss realistic treatment expectations and to measure the alignment between patients' expectations and treatment outcomes in terms of improvement in symptoms and impact on function. Therefore, incorporating the SAGA questionnaire into clinical trials may provide an additional dimension of treatment efficacy by incorporating data on treatment satisfaction from the patient's perspective. CONCLUSIONS: The SAGA questionnaire is a useful tool for patient-centered discussions about the treatment and management of LUTS, including OAB, and assisting physicians in tracking progress and managing patient expectations during therapy.

Efficacy of fesoterodine compared with extended-release tolterodine in men and women with overactive bladder.

OBJECTIVE: To assess the efficacy of fesoterodine 8 mg vs extended-release (ER) tolterodine 4 mg for overactive bladder (OAB) symptoms in terms of patient-reported outcomes in women and in men. SUBJECTS AND METHODS: Pooled data from two 12-week, randomized, double-blind, double-dummy studies were analysed. Participants eligible for the studies were ≥18 years old, had self-reported OAB symptoms for ≥3 months in 3-day baseline diaries and had ≥8 micturitions and ≥1 urgency urinary incontinence (UUI) episode per 24 h. Individuals were randomized to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks), ER tolterodine (4 mg), or placebo. Changes from baseline in 3-day bladder diary variables and scores from the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q), were assessed, as was the 'diary-dry' rate (the proportion of subjects with >0 UUI episodes according to baseline diary and no UUI episodes according to post-baseline diary). The primary endpoint was the change from baseline to week 12 in UUI episodes. RESULTS: At week 12, women showed significantly greater improvement with fesoterodine 8 mg (n = 1374) than with ER tolterodine 4 mg (n = 1382) and placebo (n = 679) in UUI episodes (primary endpoint), micturition frequency, urgency episodes, and all other diary endpoints (except nocturnal micturitions versus ER tolterodine), and also in scores on the PPBC, UPS, and all OAB-q scales and domains (all P < 0.005). Diary-dry rates in women were significantly greater with fesoterodine (63%) than with tolterodine (57%; P = 0.002) or placebo (48%; P < 0.0001). In men, there were no significant differences in improvement in UUI episodes between any treatment groups at week 12. Improvements in men were significantly greater with fesoterodine 8 mg (n = 265) than with ER tolterodine (n = 275) for severe urgency and the OAB-q Symptom Bother domain and were also significantly greater with fesoterodine than with placebo (n = 133) for micturition frequency, urgency episodes, severe urgency episodes, PPBC responses and scores on all OAB-q scales and domains at week 12 (all P < 0.04). The most frequently reported treatment-emergent adverse events in both genders were dry mouth (women: fesoterodine, 29%; ER tolterodine, 15%; placebo, 6%; men: fesoterodine, 21%; ER tolterodine, 13%; placebo, 5%) and constipation (women: fesoterodine, 5%; ER tolterodine, 4%; placebo, 2%; men: fesoterodine, 5%; ER tolterodine, 3%; placebo, 1%). Urinary retention rates were low in women (fesoterodine, <1%; ER tolterodine, <1%; placebo, 0%) and men (fesoterodine, 2%; ER tolterodine <1%; placebo, 2%). CONCLUSION: This analysis supports the superiority of fesoterodine 8 mg over ER tolterodine 4 mg on diary endpoints, including UUI, symptom bother and health-related quality of life in women. In men, fesoterodine 8 mg was superior to ER tolterodine 4 mg for improving severe urgency and symptom bother.

Effects of drug cessation after flexible-dose fesoterodine in patients with overactive bladder.

OBJECTIVE: To determine the course of overactive bladder (OAB) symptoms after 4 weeks of no treatment following a 12-week study of the efficacy and safety of flexible-dose fesoterodine in patients with OAB who were enrolled in the UK healthcare system. There are limited data available on the natural time course of OAB symptoms after the cessation of treatment. PATIENTS AND METHODS: In the open-label UK Study Assessing Flexible-dose Fesoterodine in Adults trial, patients aged ≥18 years with self-reported OAB symptoms for ≥3 months, a mean of at least eight micturitions per 24 h and three or more urgency episodes per 24 h on a 3-day bladder diary at baseline, and at least moderate bladder-related problems reported on the Patient Perception of Bladder Condition (PPBC) at baseline, were treated with fesoterodine for 12 weeks. All patients received fesoterodine 4 mg once daily for the first 4 weeks, at which time they could choose to increase the dose to 8 mg once daily, based on a discussion of treatment efficacy and tolerability with the investigator, or they could remain on fesoterodine 4 mg for the remaining 8 weeks. The 12-week treatment period was followed by a 4-week follow-up period of no fesoterodine treatment. Patients completed 3-day bladder diaries and the PPBC at baseline, week 4, end of treatment (week 12) and end of the follow-up period (week 16); the King's Health Questionnaire at baseline, end of treatment (week 12) and end of the follow-up period (week 16); and the Benefit, Satisfaction and Willingness to Continue questionnaire at week 12. RESULTS: After 12 weeks of fesoterodine treatment, patients had clinically meaningful improvements in bladder diary variables and King's Health Questionnaire domains; 79% (254/322) of patients reported an improvement on the PPBC. After 4 weeks of no treatment, most patients deteriorated back to week 4 levels or worse on all bladder diary and patient-reported outcomes. Patients who expressed a benefit from fesoterodine treatment, satisfaction with their treatment or a willingness to continue treatment showed greater improvement from baseline to week 12 and greater deterioration from week 12 to week 16 than patients who did not respond positively on the Benefit, Satisfaction and Willingness to Continue questionnaire. Both men and women showed a meaningful deterioration in bladder diary variables and patient-reported outcomes at week 16; baseline symptom severity, age and week 4 dose escalation status did not appear to affect outcome deterioration at week 16. CONCLUSIONS: At 4 weeks after fesoterodine was discontinued, patients showed an increase in the frequency of OAB symptoms, an increase in the severity of bladder-related problems and a reduction in health-related quality of life. Many patients with OAB who respond to antimuscarinics may require treatment for more than 12 weeks because symptoms recur as early as 4 weeks after the cessation of therapy.

European content validation of the Self-Assessment Goal Achievement (SAGA) questionnaire in patients with overactive bladder.

INTRODUCTION AND HYPOTHESIS: The Self-Assessment Goal Achievement (SAGA) questionnaire is a patient-completed instrument designed to assess goal attainment in the behavioral or pharmacologic treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB). The SAGA questionnaire allows patients to identify and rank the importance of treatment goals before treatment is initiated; the follow-up SAGA questionnaire quantifies the achievement of these patient-identified goals. The objective of this qualitative research was to confirm the content validity of the German, Spanish, Swedish, and English (UK) language versions of the SAGA questionnaire in patients with OAB with or without other LUTS. METHODS: The SAGA questionnaire was translated to each language in accordance with a well-established forward and backward harmonization method. Patient interviews were then conducted according to a cognitive debriefing methodology. Qualitative analysis of patients' input allowed assessment of content validity of each linguistically adapted SAGA questionnaire. RESULTS: All patients (n = 29; six to eight per targeted country) found the SAGA questionnaire easy to understand and to complete. Most patients completed the nine prespecified (fixed) treatment goals and were able to add up to five personal goals in the open-ended portion and rate each goal by importance. Differences were identified in how the various languages communicated some of the concepts assessed with the SAGA questionnaire. Rewording of the translated versions of the questionnaire was necessary in some cases. CONCLUSIONS: This linguistic content validation study in four European languages indicates that SAGA is a comprehensive, easy-to-understand, and relevant questionnaire for patient-completed evaluation of LUTS/OAB symptoms and treatment goal attainment.

Sustained improvement in patient-reported outcomes during long-term fesoterodine treatment for overactive bladder symptoms: pooled analysis of two open-label extension studies.

OBJECTIVES: • To evaluate the effects of long-term fesoterodine treatment on health-related quality of life (HRQL) and treatment satisfaction in subjects with overactive bladder (OAB) symptoms. • To determine the impact of gender and age on these effects. PATIENTS AND METHODS: • This is a post hoc analysis of data pooled from identically designed open-label extensions of two randomized, double-blind, 12-week fesoterodine studies. • Initial treatment was once-daily fesoterodine 8 mg; subjects had the opportunity to receive open-label fesoterodine for ≥24 months. • After 1 month, subjects could elect dose reduction to 4 mg and subsequent re-escalation to 8 mg; dose reduction and re-escalation were each allowed once annually. • Changes in scores on the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and a Likert scale evaluating severity of bladder-related problems were assessed at open-label baseline and months 12 and 24; treatment satisfaction was assessed at open-label baseline and at months 4, 12 and 24. RESULTS: • A total of 864 enrolled subjects were included (men, n= 182; women, n= 682; aged <45 years, n= 134; 45-64 years, n= 432; 65-74 years, n= 204; ≥75 years, n= 94); most subjects (77%) who continued treatment maintained the 8-mg dose. • Among subjects in the overall population, there were significant improvements in all KHQ domains, ICIQ-SF scores, and bladder-related problems at open-label baseline vs double-blind baseline (P < 0.05); additional significant improvements were observed at months 12 and 24 vs open-label baseline in all outcomes (P < 0.05) except for the KHQ General Health Perception domain. • When data were stratified by gender or age, significant improvements at open-label baseline vs double-blind baseline were further significantly enhanced or sustained at months 12 and 24 for most KHQ domains, and for ICIQ-SF scores and bladder-related problems for all groups. Women had significantly greater improvements than men in the KHQ Emotion (P= 0.0173) and Severity/Coping (P= 0.0112) domains and ICIQ-SF scores (P= 0.0276) during open-label treatment. Subjects aged <45 years had significantly greater improvement in the Personal Relationships domain compared with those aged 45-64 years (P= 0.0357) and in the Sleep/Energy domain compared with all other groups (all P < 0.02). • Treatment satisfaction was high (≥92%) throughout open-label treatment regardless of gender or age. CONCLUSIONS: • Long-term fesoterodine treatment was associated with sustained improvement in measures of health-related quality of life and bladder-related problems and with high treatment satisfaction in subjects with overactive bladder symptoms. • Effects of gender and age were minimal.

What are the best outcome measures when assessing treatments for LUTD?--achieving the most out of outcome evaluation: ICI-RS 2011.

A think tank was convened at the third ICI-RS meeting held in the UK, June 2011, to consider the best outcome measures when assessing treatments for lower urinary tract dysfunction (LUTD). Given the vast array of measures available a focus on questionnaires was decided upon, which continued to highlight a plethora of available tools. The decision was therefore taken to approach this topic from an alternative perspective and instead ask the audience of gathered experts in this field to consider, "What we need to ask as a minimum in order to capture the most fundamental parameters when evaluating new treatments for LUTD?" Discussions highlighted the need for inclusion of a global measure in all outcome evaluations in order to increase comparability between different treatment evaluations and different populations. More specific categories of evaluation identified were: treatment satisfaction, symptom quantification, health related quality of life and adverse events. Further optional components were identified for inclusion where relevant, such as health economic, goal setting and psychosocial evaluation. A "Minimum Outcome Set for Testing (MOST)" was therefore proposed by selecting a health outcome measure from each category while not being prescriptive about specific outcome measurement selection. The 'MOST' toolkit is therefore proposed to promote standardized evaluation in this field and represents a useful starting point for further consideration of this concept.

Goal attainment scaling in patients with lower urinary tract symptoms: development and pilot testing of the Self-Assessment Goal Achievement (SAGA) questionnaire.

INTRODUCTION AND HYPOTHESIS: The Self-Assessment Goal Achievement (SAGA) questionnaire was developed to identify treatment goals and assess goal-achievement in patients with lower urinary tract symptoms (LUTS). METHODS: This study consisted of (1) gathering information on goal setting/attainment concepts, (2) goal elicitation (n = 41 patients with LUTS), (3) cognitive debriefing of draft questionnaire (n = 11), and (4) pilot testing (n = 104). RESULTS: SAGA consists of baseline (goal-assessment; ranking) and follow-up (goal-achievement) modules. In addition to goals most frequently mentioned, patients can list up to five open goals. Goals most commonly reported as "very important" in pilot testing included reducing urgency (72%), incontinence (65%), and nocturia (64%). Treatment goals spontaneously reported as "very important" were reducing incontinence (45%), nocturia (40%), and frequency (26%). CONCLUSIONS: SAGA may be used to identify treatment goals and assess goal-achievement in patients with LUTS in the clinic and for research (with additional validation). This information may promote patient-physician interaction and help patients establish realistic treatment goals, which may in turn improve treatment adherence and outcomes.

Validation of the Overactive Bladder-Bladder Assessment Tool (OAB-BAT): A Potential Alternative to the Standard Bladder Diary for Monitoring OAB Outcomes.

BACKGROUND: An advisory board concluded that a new, comprehensive overactive bladder (OAB) patient-reported outcome (PRO) measure should be developed in accordance with regulatory guidelines. The OAB-Bladder Assessment Tool (OAB-BAT) was developed with qualitative input from OAB patients and experts to measure symptoms, bother, impacts, and satisfaction with treatment. OBJECTIVE: Psychometric evaluation of the OAB-BAT assessing PRO OAB symptoms, bother, and impacts during a 7-d recall period. DESIGN, SETTING, AND PARTICIPANTS: Psychometric testing was conducted for a 28-d observational study of 170 OAB patients. Eligibility criteria included clinician-confirmed OAB diagnosis with at least eight micturitions per day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Assessments included the OAB-BAT, a 7-d bladder diary, and co-validating OAB PROs. Analysis included classical and modern test theories. A scoring algorithm was developed and psychometric properties were assessed. RESULTS AND LIMITATIONS: The majority of participants were women (72.4%) with moderate OAB symptom severity (53.5%). More than one-third of participants (34.1%) were incontinent. Responses were well balanced across bother and impact items, while symptom frequency items showed sparse responses. Analysis supported an eight-item unidimensional model based on bother and impacts. No items performed differently by gender or continence status. The OAB-BAT showed internal consistency (ω=0.918), retest reliability (two-way random intraclass correlation coefficient=0.81), and convergent validity with the OAB-q (r>0.4). Known groups showed the expected trend. Comparisons between OAB-BAT scores and components of the bladder diary showed a moderate effect size (r>0.4). CONCLUSIONS: The eight-item OAB-BAT with 7-d recall is valid and reliable as an OAB PRO measure. Structural modeling, balanced with content validity considerations, produced robust scores. The OAB-BAT is a useful addition to the clinical assessment of patients, designed to complement the use of bladder diaries for monitoring OAB outcomes, in clinical trial and clinical practice environments. Future studies will need to assess the treatment satisfaction items in a larger sample of patients receiving OAB treatment. PATIENT SUMMARY: We tested a questionnaire designed to assess overactive bladder (OAB) symptoms, bother, satisfaction, and impacts by asking patients to complete it on a weekly basis. We found that the questionnaire accurately captures the symptoms and impacts that are most important to patients with OAB. We conclude that the questionnaire could be a useful instrument and, after further assessment in clinical practice and research, a possible alternative to a bladder diary in measuring OAB outcomes.

Patient reported outcomes: the ICIQ and the state of the art.

INTRODUCTION: Following the first International Consultation on Incontinence (ICI) in 1998, a multidisciplinary committee was established to develop a universally applicable, brief urinary incontinence patient-reported outcome (PRO) questionnaire: the ICIQ-UI Short Form. The project was expanded to recommend and develop high quality, validated questionnaires for all lower pelvic dysfunction related to incontinence. The ICI Modular Questionnaire project (ICIQ) was then established to include a wider spectrum of urinary, bowel and vaginal symptoms and their impact on health related quality of life (HRQL). Three aims underpin the ICIQ project: To recommend high quality, validated PRO questionnaires. To promote wider use of questionnaires to standardize assessment of lower pelvic dysfunction and its impact on HRQL. To facilitate communication in different patient settings and patient groups. CONCLUSION: The authors, both ICIQ committee members, debated the title. If the conceptualization of the ICIQ is correct, the PROs recommended by the ICIQ need to be under constant evolution and improvement to ensure the aims of the ICIQ project. A modular questionnaire design, recognized and implemented internationally, would add greatly to the universal inclusion, interpretation and understanding of PRO data in clinical practice and clinical research. However, in order to achieve the goals of the ICIQ project, we must ensure that the scientific quality of PRO development, documentation and validation meets current scientific standards, as well as societal and governmental regulatory guidelines. These topics are discussed along with recommendations for future areas of research and need for the ICIQ committee to explore these issues.

Overactive bladder: Is there a link to the metabolic syndrome in men?

It is becoming increasingly clear that a variety of metabolic, cardiovascular, and endocrine factors contribute to male pelvic health. In particular, a growing body of evidence suggests a relationship between lower urinary tract symptoms, benign prostatic hyperplasia, overactive bladder, erectile dysfunction, and the metabolic syndrome. This article explores these relationships, focusing on the role of the autonomic nervous system and hyperinsulinemia, together with their implications for urological practice.

The economic impact of overactive bladder syndrome in six Western countries.

OBJECTIVE: To calculate up-to-date estimates of the economic impact of overactive bladder syndrome (OAB) with and without urgency urinary incontinence (UUI) on the health sector of six countries (Canada, Germany, Italy, Spain, Sweden and the UK), as OAB is a significant health concern for adults aged >18 years living in Western countries. MATERIALS AND METHODS: The prevalence data derived from the EPIC study were combined with healthcare resource-use data to derive current direct and indirect 1-year or annual cost of illness estimates for OAB including UUI in Canada, Germany, Italy, Spain, Sweden and the UK. This model estimates the direct healthcare costs attributed to OAB, as well as the impact of work absenteeism. RESULTS: The estimated average annual direct cost of OAB per patient ranged between 262 in Spain and 619 in Sweden. The estimated total direct cost burden for OAB per country ranges between 333 million in Sweden and 1.2 billion in Germany and the total annual direct cost burden of OAB in these six countries is estimated at 3.9 billion. In addition, nursing home costs were estimated at 4.7 billion per year and it was estimated that work absenteeism related to OAB costs 1.1 billion per year. CONCLUSIONS: The cost of illness for OAB is a substantial economic and human burden. This study may under-estimate the true economic burden, as not all costs for sequelae associated with OAB have been included. Cost-effective treatments and management strategies that can reduce the burden of OAB and in particular UUI have the potential to significantly reduce this economic burden.

Bladder sensations during filling cystometry are different according to urodynamic diagnosis.

PURPOSE: To determine the position and character of bladder filling sensations in women undergoing urodynamic investigations. MATERIALS AND METHODS: Women with lower urinary tract symptoms referred to urodynamic clinics of two tertiary referral teaching hospitals were prospectively studied. During filling cystometry the women were asked to describe the bladder sensations at the first sensation of bladder filling, first desire to void, strong desire to void, maximum bladder capacity and if the woman felt urgency. Women were also asked to define the time that the voiding could be delayed and to indicate the position of each sensation on a body map. Women were classified into four groups according to urodynamic diagnosis: detrusor overactivity (DO), urodynamic stress incontinence (USI), co-existing DO and USI (mixed) and inconclusive urodynamics; the latter was excluded from the study. Bladder sensations were compared between these groups using Chi squared and Kruskall-Wallis tests. RESULTS: Eighty-two women were studied. Women with DO and mixed urodynamic diagnosis predominantly described the bladder sensations as being perineal or vaginal in origin, whereas those with USI felt the sensations suprapubically. The character of bladder sensation was not significantly different between the diagnostic groups and the intensity increased with larger bladder volume. The duration that women could delay voiding was significantly different between different urodynamic groups. CONCLUSIONS: Bladder sensations experienced during cystometry are different in position and duration in relation to urodynamic diagnoses. This indicates that uniform descriptions of sensations during filling cystometry might not be appropriate to different urodynamic diagnoses.

Correlations among improvements in urgency urinary incontinence, health-related quality of life, and perception of bladder-related problems in incontinent subjects with overactive bladder treated with tolterodine or placebo.

BACKGROUND: Previous studies demonstrate that tolterodine extended release (ER) significantly improves urgency urinary incontinence (UUI) episodes. Instruments that measure patient-reported outcomes (PROs) provide additional information that is valuable for assessing whether clinical improvements are meaningful to the patient. This study determined the correlation of changes in bladder diary variables and other PROs in subjects with overactive bladder (OAB). METHODS: Subjects with OAB, urinary frequency, and UUI were treated with 4 mg once-daily tolterodine ER or placebo for 12 weeks. Subjects completed 7-day bladder diaries, the Patient Perception of Bladder Condition (PPBC), and the King's Health Questionnaire (KHQ) at baseline and week 12. Only subjects who reported at least some minor bladder-related problems at baseline (PPBC score > or = 3) were included in this analysis. RESULTS: Reductions in UUI episodes per week were significantly greater in the tolterodine ER group (n = 500) compared with the placebo group (n = 487) at week 12 (-71% vs -33%, P < 0.0001). A significantly greater percentage of subjects in the tolterodine ER group reported improvement on the PPBC versus placebo (58% vs 45%, P < 0.0001), and 7 of 10 KHQ domains were significantly improved versus placebo (all P < 0.05). Significant correlations were found for median percentage changes in UUI episodes with changes in PPBC scores (r = 0.35,P < 0.0001) and the 7 improved KHQ domains (r = 0.16-0.32, P < or = 0.0011). Changes in PPBC scores and all KHQ domains were significantly correlated (r = 0.13-0.38, P < or = 0.009) in the tolterodine ER group. Correlations among endpoints in the placebo group were similar to those observed in the tolterodine ER group. CONCLUSION: Improvement in UUI episodes after 12 weeks of treatment with tolterodine ER or placebo was correlated with improvements in patients' perception of their bladder-related problems and health-related quality of life. Correlations were moderate in magnitude but statistically significant, suggesting that PROs are important and relevant measures for evaluating OAB treatment.

Impact of fesoterodine on quality of life: pooled data from two randomized trials.

OBJECTIVE: To evaluate the effect of fesoterodine on health-related quality of life (HRQoL) in patients with overactive bladder (OAB) syndrome. PATIENTS AND METHODS: Pooled data from two randomized placebo-controlled phase III studies were analysed. Eligible patients with frequency and urgency or urgency urinary incontinence were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks; one trial also included tolterodine extended release (tolterodine-ER) 4 mg. HRQoL was assessed using the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), a six-point Likert scale measuring the severity of bladder-related problems, and treatment response. RESULTS: By the end of treatment, all active-treatment groups had significantly improved HRQoL compared with those on placebo, as shown by an improvement in the KHQ and ICIQ-SF scores, treatment response rate, and a major improvement in self-reported bladder-related problems. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. Fesoterodine 4 mg and tolterodine-ER produced statistically significant improvements in seven of nine KHQ domains. Fesoterodine 8 mg gave better results than 4 mg in two domains; Emotions and Symptom Severity (P < 0.05). A major improvement (>or=2 points) in bladder-related problems was reported by 33% of patients on fesoterodine 4 mg, 38% on fesoterodine 8 mg, and 34% on tolterodine-ER, vs 21% on placebo (P < 0.001). CONCLUSIONS: Fesoterodine significantly improved HRQoL in patients with OAB. Both fesoterodine 4 and 8 mg produced significant improvements on most KHQ domains, the ICIQ-SF, treatment response rate, and a Likert scale measuring bladder-related problems.

Clinical relevance of health-related quality of life outcomes with darifenacin.

OBJECTIVE: To determine the clinical relevance of changes in health-related quality of life (HRQoL) in patients with overactive bladder (OAB) treated with darifenacin. PATIENTS AND METHODS: Data were pooled from three randomized, placebo-controlled, parallel-group, fixed-dose, 12-week studies. After 2-week washout, treatment-free or placebo run-in periods, patients with OAB (n = 1059; 85% women; age 19-88 years) were randomized to 12 weeks' treatment with darifenacin controlled-release 7.5 mg (n = 337) or 15 mg once daily (n = 334) or placebo (n = 388). The King's Health Questionnaire (KHQ) was used to assess HRQoL at baseline and Week 12. The clinical significance of changes in KHQ domain scores was assessed using the concept of minimum important difference (MID), using two different methods. RESULTS: Darifenacin treatment was associated with significantly greater improvements than placebo in six primary KHQ domain scores known to be of importance to patients with OAB. In addition, a significantly greater proportion of darifenacin-treated patients met or exceeded reference MID vs placebo in these domains (Incontinence Impact, Severity Measures, Role Limitations, Social Limitations, Emotions and Physical Limitations; P = 0.01). In darifenacin-treated patients, there were significant correlations between the reductions in incontinence episodes per week and improvements in KHQ scores (P < 0.001). The strongest correlations were in the Incontinence Impact, Social Limitations, Role Limitations, Severity Measures and Emotions domains. CONCLUSIONS: Darifenacin treatment was associated with significant, clinically relevant improvements in HRQoL in patients with OAB, shown using the concept of MID to interpret change in KHQ scores.

The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study.

OBJECTIVES: To examine the effect overactive bladder (OAB) and other lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a population sample, as OAB often occurs in conjunction with many other LUTS. SUBJECTS AND METHODS: A nested case-control analysis was performed on men and women with (cases) and without (controls) OAB, from the EPIC study. OAB was assessed using 2002 International Continence Society definitions. Based on their responses to questions about LUTS, cases were classified into five groups; continent OAB, OAB with incontinence, OAB + postmicturition, OAB + voiding, and OAB + postmicturition + voiding. Both cases and controls were asked questions about symptom bother (OAB-q), generic QoL (EQ-5D), work productivity (Work Productivity and Activity Impairment, WPAI), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sexual satisfaction, and erectile dysfunction (men only) using the Massachusetts Male Aging Study. Cases answered additional condition-specific questions HRQoL (OAB-q short form), Patient Perception of Bladder Condition and work productivity related to a specific health problem (WPAI-SHP). General linear models were used to evaluate group differences. RESULTS: Of the EPIC participants, 1434 identified OAB cases were matched by age, gender and country, with 1434 participants designated as controls. Cases and controls were primarily Caucasian (96.2% and 96.7%, respectively), and most (65%) were female; the mean age was 53.8 and 53.7 years, respectively. Comorbid conditions differed significantly by case/control status, with cases reporting significantly greater rates of chronic constipation, asthma, diabetes, high blood pressure, bladder or prostate cancer, neurological conditions and depression. There were significant differences between the cases and controls in all reported LUTS. The OAB + postmicturition + voiding group reported significantly greater symptom bother, worse HRQoL, higher rates of depression and decreased enjoyment of sexual activity, than the other subgroups. CONCLUSION: OAB has a substantial, multidimensional impact on patients; OAB with additional LUTS has a greater impact. The diagnosis and treatment of OAB should be considered in conjunction with other LUTS, to maximize treatment options and optimize patient outcomes.