Do patients with OAB experience bladder sensations in the same way as healthy volunteers? A focus group investigation.

AIMS: To describe the terminology and pattern of bladder sensations experienced during non-invasive rapid bladder filling in a controlled setting in patients with OAB and to compare these results with a previous study conducted in healthy volunteers. METHODS: Three groups of patients with OAB, in total 10 patients, participated in three consecutive focus group sessions. Before each session a strict water loading protocol was given. During the first two sessions, participants described how they experienced their bladder sensations in daily life and during a non-invasive bladder filling with constant focus on their bladder. The third session focused on verifying the interpretation of the data gathered and describing the pattern of sensations. RESULTS: Patients describe their bladder sensations as a pressure or a tingling sensation and the pattern can be described by terms ranging from no sensation to an absolute need to void. The absolute need to void may develop suddenly or more slowly progressive. The mean development of bladder sensation is significantly different between patients and healthy volunteers as well as their average diuresis. CONCLUSIONS: Patients with OAB describe their bladder sensations as a pressure or a tingling sensation. There appear to be two types of urgency: a sudden absolute need to void and a slowly developing absolute need to void. Furthermore bladder sensation develops significantly different in volunteers than in OAB patients.

What treatment should we use if drugs fail for OAB; and, what really works after drugs?

AIMS: To determine (using structured brain storm sessions), which treatments should be used if drugs fail for OAB and to determine priority research questions in relation to this issue. METHODS: A frame work for discussion was prepared by the chairman of the session; this included a brief summary of the currently existing evidence. Several experts had been asked to prepare a presentation of their personal treatment algorithm and to identify the [lack of] evidence for such an algorithm. These presentations were summarized by the chairman. Next, this summary was discussed with a large group of experts and opinion leaders and audio-recorded. The proceedings of this process are the basis for this manuscript. RESULTS: The structured sessions resulted in detailed statements about: possible reasons for failure of conservative treatment, the evaluation of outcomes of RCT's, the use of botulinum toxin A in refractory OAB patients, the relative place of neuromodulation or sacral nerve stimulation and botulinum toxin A in the treatment of refractory OAB. CONCLUSIONS: A list of 10 unanswered questions and research topics was compiled. Additionally, 5 top priority research topics were identified.

Long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder symptoms.

AIMS: The aim of this study was to assess the long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder (OAB) symptoms. METHODS: This was an open-label extension study of a 12-week, double-blind fesoterodine study. During open-label treatment, all subjects received fesoterodine 8 mg for an initial 4 weeks, after which subjects could elect dose reduction to 4 mg or subsequent reescalation to 8 mg during clinic visits (dose reduction and reescalation each permitted once annually). The maximum allowable duration of open-label fesoterodine treatment ranged from 24 to 32 months across study sites. Safety and tolerability were evaluated via discontinuations, fesoterodine exposure, treatment-emergent adverse events (TEAEs) and subject-reported treatment tolerance. Three-day bladder diaries and other patient-reported outcomes (PROs) were assessed during the first 24 months of open-label treatment. PROs included evaluations of health-related quality of life [HRQL; King's Health Questionnaire (KHQ), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)], severity of bladder-related problems and treatment satisfaction. Subjects completed 3-day diaries before open-label baseline and months 1, 4, 8, 12 and 24; the ICIQ-SF and measures of bladder-related problems and treatment satisfaction at open-label baseline and months 4, 12 and 24; and the KHQ at open-label baseline and months 12 and 24. RESULTS: Of the 417 eligible subjects who enrolled in the open-label extension, 61% continued fesoterodine treatment for > or = 24 months and 71% elected to maintain the fesoterodine 8-mg dose throughout treatment. No unexpected safety signals were observed. Most subjects rated treatment tolerance as at least 'good' throughout the study (> or = 88%). Dry mouth was the most commonly reported TEAE (34%) during open-label treatment, resulting in discontinuation in 2% of subjects (n = 8). Improvements from open-label baseline in OAB symptoms, HRQL and bladder-related problems were statistically significant at the earliest point measured and maintained through month 24. Treatment satisfaction rates were high throughout the study (> or = 84%). CONCLUSIONS: Long-term fesoterodine treatment was well tolerated and associated with sustained improvements in OAB symptoms and HRQL.

The localization of cyclo-oxygenase immuno-reactivity (COX I-IR) to the urothelium and to interstitial cells in the bladder wall.

Localized phasic contractions in the bladder wall (autonomous activity) have been hypothesized to be an integral part of a motor/sensory system contributing to bladder sensation. The sites responsible for generating this activity, the mechanisms involved in its propagation and modulation remain unknown. This phasic motor activity is modulated by exogenous prostaglandins. Therefore, analysis of the sites of prostaglandin production and action within the bladder wall may shed light on the mechanisms of generation and modulation of this phasic activity. In this paper we report the localization of immuno-reactivity indicative of the expression of cyclo-oxygenase enzyme type I (COX I-IR) within the bladder wall. Basically, three types of COX I-IR cell were identified: epithelial cells in the basal and intermediate layers of the urothelium, complex vimentin-positive and COX I-IR cells in the lamina propria and vimentin-negative COX I-IR cells in the lamina propria and on the surface of the inner muscle bundles. These vimentin-negative/COX I-IR cells appear to be in close apposition to a continuous network of vimentin-positive cells, which extends from the lamina propria into the inner muscle layers and subsequently into the outer muscle layers. However, the interstitial cells in this region might form a distinctly different sub-type. First, the interstitial cells in this region differ from those in the inner layer by their responsiveness to NO with a rise in cGMP. Two subtypes have been identified: cells on the surface of the muscle bundles and within the muscle bundles. Second, COX I-IR cells are not associated with the interstitial cells in the outer layers. The physiological significance for these apparent differences in the interstitial cell network is not clear. However, such differences are likely to reflect differences in the processes involved in their activation, modulation and control.

Alterations to network of NO/cGMP-responsive interstitial cells induced by outlet obstruction in guinea-pig bladder.

Interstitial cells (ICs) play a role in regulating normal bladder activity. This study explores the possibility that the sub-urothelial and muscle networks of NO/cGMP-responsive ICs are altered in animals with surgically induced outflow obstruction. In sham-operated animals, the urothelium comprised NO-stimulated cGMP-positive (cGMP(+)) umbrella cells, an intermediate layer and a basal layer that stained for nNOS. cGMP(+) sub-urothelial interstitial cells (su-ICs) were found below the urothelium. cGMP(+) cells were also associated with the outer muscle layers: on the serosal surface, on the surface of the muscle bundles and within the muscle bundles. Several differences were noted in tissues from obstructed animals: (1) the number of cGMP(+) umbrella cells and intensity of staining was reduced; (2) the intermediate layer of the urothelium consisted of multiple cell layers; (3) the su-IC layer was increased, with cells dispersed being throughout the lamina propria; (4) cGMP(+) cells were found within the inner muscle layer forming nodes between the muscle bundles; (5) the number of cells forming the muscle coat (serosa) was increased; (6) an extensive network of cGMP(+) cells penetrated the muscle bundles; (7) cGMP(+) cells surrounded the muscle bundles and nodes of ICs were apparent, these nodes being associated with nerve fibres; (8) nerves were found in the lamina propria but rarely associated with the urothelium. Thus, changes occur in the networks of ICs following bladder outflow obstruction. These changes must have functional consequences, some of which are discussed.

Predictive factors for sacral neuromodulation in chronic lower urinary tract dysfunction.

OBJECTIVES: To investigate data from 211 patients who underwent a trial stimulation (percutaneous nerve evaluation [PNE]) to determine the clinical parameters that can enhance the prediction of PNE success. The advantageous effect of sacral neuromodulation depends on the accurate identification of suitable candidates during the preimplantation PNE. METHODS: A total of 211 patients (161 women and 50 men), with refractory urge incontinence, urgency-frequency syndrome, and urinary retention, underwent a PNE. Patient data (demographics, medical history, urologic investigations, and diagnosis) were collected. The PNE results were evaluated from a voiding diary and patient history. More than 50% improvement of voiding parameters was considered a successful PNE, and those patients were selected for implantation. Logistic regression analysis was performed. The factors tested for predicting the test result were sex, patient age, diagnosis, previous surgery, neurogenic bladder dysfunction, duration of complaints, and previous treatments. RESULTS: The PNEs were positive in 85 patients (40.3%) and negative in 105 patients (49.8%). In 18 patients (8.5%), the test electrode had migrated; 3 more patients were not assessable and were also excluded. Missing data on the variable "duration of complaints" reduced the number of patients in the analyses from 190 to 174 patients. CONCLUSIONS: Intervertebral disk prolapse, duration of complaints, neurogenic bladder dysfunction, and urge incontinence were found to be significant predictive factors. However, a PNE remains necessary to evaluate a patient's chance of implant success objectively.