Search

Background: Effective, well-tolerated novel treatments for overactive bladder (OAB) are lacking. The P2X3 receptor antagonist eliapixant demonstrated potential to reduce OAB symptoms in preclinical studies., Objective: To evaluate the safety, tolerability, and efficacy of eliapixant in patients with OAB with urgency urinary incontinence (UUI)., Design, Setting and Participants: OVADER was a 12-wk, randomised, placebo-controlled, double-blind, parallel-group, multicentre, phase 2a study (NCT04545580) conducted between 2020 and 2022 in private and institutional clinical practices. Eligible patients were aged ≥18 yr with wet OAB symptoms (urgency, urinary frequency, and urinary incontinence) for ≥3 mo before screening., Intervention: Randomisation (1:1 ratio) to oral eliapixant 125 mg or placebo twice daily., Outcome Measurements and Statistical Analysis: The primary endpoint was the mean change from baseline in the mean number of UUI episodes/24 h over weeks 4, 8, and 12 according to an electronic bladder diary, evaluated using a repeated-measurement model in a Bayesian framework., Results and Limitations: Of 202 patients enrolled, 85 were valid for per-protocol analysis. The primary efficacy endpoint was not met. The posterior probability for eliapixant superiority over placebo was 40% (point estimate 0.05, 95% credible interval -∞ to 0.38), which did not meet the predefined criterion of ≥90% probability. Secondary and exploratory endpoints were not met. The incidence of adverse events was similar in the eliapixant (n = 32, 63%) and placebo (n = 27, 56%) groups; most were mild and five led to discontinuation of eliapixant., Conclusions: OVADER did not meet its clinical efficacy endpoints. Potential reasons include the nonspecific OAB symptom complex, the poorly understood pathophysiology, and the coinciding COVID-19 pandemic., Patient Summary: We tested whether a new drug called eliapixant would reduce symptoms of overactive bladder in comparison to placebo. We found that the drug did not work. More knowledge on how overactive bladder occurs is needed to find new drugs to treat this condition., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Robotic assisted radical prostatectomy (RARP) is getting more and more popular becoming the most common radical prostatectomy technique. Unfortunately, a not negligible proportion of patients in whom RARP is performed experience urinary incontinence. We aimed to systematically review the current literature evidence on urinary incontinence conservative treatment after RARP., Edidence Aquisition: A systematic literature review search using PubMed (Medline), Scopus, and Web of Science databases was performed in December 2019. PRISMA guidelines have been adopted. Population consisted of patients with urinary incontinence after RARP (P), conservative intervention was considered of interest (I). No comparator was considered mandatory (C). Outcomes of interest were the recovery of continence and quality of life (O)., Evidedence Synthesis: Six studies were included. Four of them investigated the use of pelvic floor muscle training (PFMT). PFMT improved pelvic muscle strength. Continence recovery was faster when guided PFMT was adopted. Moreover, two studies tested the effect of solifenacin on urinary incontinence. One of them, a randomized clinical trial, failed to show shorter time to continence in solifenacin group compared to placebo., Conclusions: The use of pads is associated with a detrimental effect on quality of life thus active treatments for UI post-RARP are warranted. PFMT has the main advantage to shorten the time for recovery. The use of solifenacin seems to not offer striking advantages in UI following RARP. Future studies should focus on testing the efficacy of these treatments when used after robotic vs. open radical prostatectomy.

Aims: SYNERGY II was a 12-month phase III trial in patients with overactive bladder (OAB) symptoms that investigated the safety and efficacy of the combination of mirabegron and solifenacin in comparison with each monotherapy. This analysis evaluated the trial findings using four age subgroups (<65, ≥65, <75, and ≥75 years)., Methods: Eligible patients were ≥18 years with symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for ≥3 months. Patients were randomized to receive once-daily solifenacin succinate and mirabegron (5 mg/50 mg; combination), solifenacin succinate, or mirabegron (4:1:1). Safety evaluations: treatment-emergent adverse events (TEAEs), vital signs, and electrocardiogram, post-void residual volume, and laboratory assessments. Primary efficacy variables: change from baseline to end of treatment in number of incontinence episodes/24 h and micturitions/24 h., Results: Of 1794 patients (full analysis set), 614 (34.2%) and 168 (9.4%) were ≥65 and ≥75 years old, respectively. Overall, 856 (47.2%) patients experienced ≥1 TEAE. Higher TEAE incidences were typically observed for the combination versus both monotherapies (eg, constipation) and in the older versus younger age groups (eg, urinary tract infection). Increases in mean pulse rate from baseline of >1 bpm were noted in the combination and mirabegron younger age groups only. No clinically significant findings were observed in the other safety parameters. The efficacy variables improved with all treatments and the greatest improvements were typically observed with combination therapy., Conclusions: Mirabegron and solifenacin combination therapy was a well-tolerated and effective treatment for patients with OAB symptoms irrespective of their age., (© 2019 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.)

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., (© 2018 Wiley Periodicals, Inc.)

Introduction: Few population-based data are available evaluating the prevalence of lower urinary tract symptoms (LUTS) in Asia. The objective of our study was to determine LUTS prevalence in China, Taiwan, and South Korea using International Continence Society (ICS) 2002 criteria., Methods: An Internet-based self-administered survey among individuals aged at least 40 years with the ability to use a computer and to read the local language. Survey questions included ICS symptom definitions and the international prostate symptom score (IPSS). Data analysis was based on descriptive statistics and post hoc significance testing., Results: There were 8284 participants, of whom 51% were women and 34% were aged at least 60 years. LUTS prevalence was slightly higher in men than women (62.8% vs. 59.6%; p = 0.004), increasing significantly with age (p = 0.001). All three ICS symptom groups (voiding, storage, and post-micturition) were present in 35% of individuals with LUTS. Symptoms with the highest overall prevalence were nocturia, frequency, incomplete emptying, and terminal dribble. The most bothersome symptoms were terminal dribble, nocturia, and urgency. According to IPSS scores, 87% of participants had at least mild symptoms; 43% of those aged over 60 years had moderate/severe symptoms. The percentage of participants with any LUTS who had visited healthcare professionals because of urinary symptoms was 26%, rising to 45% amongst individuals with all three symptom groups (p = 0.001 vs. other ICS symptom groups)., Conclusions: LUTS are highly prevalent in men and women aged at least 40 years who participated in this study in China, Taiwan, and South Korea and increases with increasing age. A minority of individuals with LUTS seek healthcare and our results suggest an increased patient awareness of LUTS is required., Funding: Astellas Pharma Singapore Pte. Ltd., Trial Registration: ClinicalTrials.gov identifier, NCT02618421.

Background: Incontinence constitutes a major health problem affecting millions of people worldwide. The present study aims to assess cure rates from treating urinary (UI) or fecal incontinence (FI) and the number of people who may remain dependent on containment strategies., Methods: Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and PEDro were searched from January 2005 to June 2015. Supplementary searches included conference abstracts and trials registers (2013-2015). Included studies had patients ≥ 18 years with UI or FI, reported treatment cure or success rates, had ≥ 50 patients treated with any intervention recognized in international guideline algorithms, a follow-up ≥ 3 months, and were published from 2005 onwards. Title and abstract screening, full paper screening, data extraction and risk-of-bias assessment were performed independently by two reviewers. Disagreements were resolved through discussion or referral to a third reviewer where necessary. A narrative summary of included studies is presented., Results: Most evidence was found for UI: Surgical interventions for stress UI showed a median cure rate of 82.3% (interquartile range (IQR), 72-89.5%); people with urgency UI were mostly treated using medications (median cure rate for antimuscarinics = 49%; IQR, 35.6-58%). Pelvic floor muscle training and bulking agents showed lower cure rates for UI. Sacral neuromodulation for FI had a median cure rate of 38.6% (IQR, 35.6-40.6%)., Conclusions: Many individuals were not cured and hence may continue to rely on containment. No studies were found assessing success of containment strategies. There was a lack of data in the disabled and in those with neurological diseases, in the elderly and those with cognitive impairment. Surgical interventions were effective for stress UI. Other interventions for UI and FI showed lower cure rates. Many individuals are likely to be reliant on containment strategies., Prospero Registration: PROSPERO registration number: CRD42015023763 .

Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy., Objective: To evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg., Design, Setting, and Participants: OAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4., Outcome Measurements and Statistical Analysis: The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy., Results and Limitations: A total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001), and incontinence noted in a 3-d diary (p=0.014). Combination was noninferior to solifenacin 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated., Conclusions: Adding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg., Patient Summary: In this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated., Trial Registration: ClinicalTrials.gov NCT01908829., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: A prespecified pooled analysis of two placebo-controlled, phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder (OAB) patients with urinary incontinence (UI)., Methods: Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo, sparing the trigone. Change from baseline at week 12 in UI episodes/day, proportion of patients reporting a positive response ('greatly improved' or 'improved') on the treatment benefit scale (TBS), micturition and urgency were evaluated by number of prior anticholinergics (1, 2 or ≥ 3) and reason for their discontinuation (insufficient efficacy or side effects). Adverse events (AE) were assessed., Results: Patients had taken an average of 2.4 anticholinergics before study enrolment. OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo, regardless of the number of prior anticholinergics (-2.82 vs. -1.52 for one prior anticholinergic; -2.58 vs. -0.58 for two prior anticholinergics; and -2.92 vs. -0.73 for three or more prior anticholinergics; all p < 0.001). The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo (69.0% vs. 37.2% for one prior anticholinergic; 58.8% vs. 24.8% for two prior anticholinergics and 56.4% vs. 22.5% for three or more prior anticholinergics; all p < 0.001). Similar results were observed regardless of the reason for discontinuation. OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups. AEs were well tolerated, with a comparable incidence in all groups., Conclusion: In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics, onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB. ClinicalTrials.gov: NCT00910845, NCT00910520., (© 2014 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

Objective: To validate the Bladder Control Self-Assessment Questionnaire (B-SAQ), a short screener to assess lower urinary tract symptoms (LUTS) and overactive bladder (OAB) in men., Patients and Methods: This was a prospective, single-centre study including 211 patients in a urology outpatient setting. All patients completed the B-SAQ and Kings Health Questionnaire (KHQ) before consultation, and the consulting urologist made an independent assessment of LUTS and the need for treatment. The psychometric properties of the B-SAQ were analysed., Results: A total of 98% of respondents completed all items correctly in <5 min. The mean B-SAQ scores were 12 and 3.3, respectively for cases (n = 101) and controls (n = 108) (P < 0.001). Good correlation was evident between the B-SAQ and the KHQ. The agreement percentages between the individual B-SAQ items and the KHQ symptom severity scale were 86, 85, 84 and 79% for frequency, urgency, nocturia and urinary incontinence, respectively. Using a B-SAQ symptom score threshold of ≥4 alone had sensitivity, specificity and positive predictive values for detecting LUTS of 75, 86 and 84%, respectively, with an area under the curve of 0.88; however, in combination with a bother score threshold of ≥1 these values changed to 92, 46 and 86%, respectively., Conclusions: The B-SAQ is an easy and quick valid case-finding tool for LUTS/OAB in men, but appears to be less specific in men than in women. The B-SAQ has the potential to raise awareness of LUTS. Further validation in a community setting is required., (© 2013 The Authors. BJU International © 2013 BJU International.)

The demographic development of society shows a clear increase in the elderly population in the coming decades, which will result in an increasing prevalence of urinary incontinence. Diagnosis and treatment of many patients is not carried out for a myriad of reasons and thus incontinence care is often inadequate. A detailed medical history is the basis of identification of the problem and underpins the effective diagnostic and therapeutic management of the problem. In this context, the algorithms based on the national and international guidelines and age-specific characteristics should be considered. The initial focus should be on conservative management. In a few cases of elderly patients, invasive diagnostics using urodynamics or cystoscopy might be indicated. The increased use of medication in the elderly both from an etiological and therapeutic point of view, especially in terms of drug/drug interactions requires special consideration. In particular cognitive impairment using pharmacological approaches should be avoided. Although incontinence surgery of the patient applies less often with increasing age it still plays a role in the appropriate selection of treatment.

Context: The first European Association of Urology (EAU) guidelines on incontinence were published in 2001. These guidelines were periodically updated in past years., Objective: The aim of this paper is to present a summary of the 2009 update of the EAU guidelines on urinary incontinence (UI)., Evidence Acquisition: The EAU working panel was part of the 4th International Consultation on Incontinence (ICI) and, with permission of the ICI, extracted the relevant data. The methodology of the 4th ICI was a comprehensive literature review by international experts and consensus formation. In addition, level of evidence was rated according to a modified Oxford system and grades of recommendation were given accordingly., Evidence Summary: A full version of the EAU guidelines on urinary incontinence is available as a printed document (extended and short form) and as a CD-ROM from the EAU office or online from the EAU Web site (http://www.uroweb.org/guidelines/online-guidelines/). The extent and invasiveness of assessment of UI depends on severity and/or complexity of symptoms and clinical signs and is different for men, women, frail older persons, children, and patients with neuropathy. At the level of initial management, basic diagnostic tests are applied to exclude an underlying disease or condition such as urinary tract infection. Treatment is mostly conservative (lifestyle interventions, physiotherapy, physical therapy, pharmacotherapy) and is of an empirical nature. At the level of specialised management (when primary therapy failed, diagnosis is unclear, or symptoms and/or signs are complex/severe),more elaborate assessment is generally required, including imaging, endoscopy, and urodynamics. Treatment options include invasive interventions and surgery., Conclusions: Treatment options for UI are rapidly expanding. These EAU guidelines provide ratings of the evidence (guided by evidence-based medicine) and graded recommendations for the appropriate assessment and according treatment options and put them into clinical perspective., (Copyright © 2011 AEU. Published by Elsevier Espana. All rights reserved.)

Guidelines for the management of continence and overactive bladder are generally available across Europe. For a majority of countries, these have been adopted by professional societies in either urology or gynaecology for local use. There has, however, been little monitoring of formal implementation of these guidelines and seldom any attempt to audit their operation. The state of continence care therefore remains largely unknown. This article reviews current guidelines and their status across Europe and examines what might be relevant from other disease areas to promote successful implementation.

The overactive bladder symptom complex (OAB) is the commonest cause of urinary incontinence in older people, and is usually due to underlying detrusor overactivity, and as such is a treatable condition. Older people are a heterogeneous group, which includes fit community-dwelling individuals and those with significant medical comorbidity; thus the requirements of care for this group are many and varied. The International Continence Society definition of the frail elderly, those aged >65 years with continence problems, who by virtue of comorbidity are house-bound or living in an institution, is clearly not applicable to all. However, many conditions begin to appear in later life and practitioners need to be aware of the need to manage these, and their treatment, when dealing with older people. Studies of medication for OAB have included the elderly and there is evidence of an equivalent benefit in younger people. The impact of treatment on the cognitively impaired and those receiving acetylcholinesterase inhibitors is discussed.

1 Bladder smooth muscle sensitivity to muscarinic agonists is increased in the overactive bladder. Treatment of rats with streptozotocin induces a diabetic state in which the bladder muscle is overactive and also supersensitive to muscarinic agonists. This study has examined bladder contraction, muscarinic receptor density and receptor/G-protein coupling in the streptozotocin-induced overactive bladder of the rat. 2 Diabetes was induced by a single intraperitoneal dose of streptozotocin. Seven days later contraction of isolated detrusor muscle strips was assessed in tissue bath experiments, while receptor density was assayed in saturation experiments with [3H]-QNB (quinuclidinyl benzilate, L-[benzilic-4,4'-3H]) and receptor/G-protein coupling was determined in agonist displacement experiments with this radioligand. 3 Isolated detrusor strips from diabetic animals displayed an enhanced degree of spontaneous activity (0.060 +/- 0.016 g mg(-1), compared with 0.015 +/- 0.004 g mg(-1), P < 0.05). Carbachol produced contractile responses in tissues from both control and diabetic rats, but the diabetic tissues were more sensitive to this agonist, the pEC50 being 6.52 +/- 0.17 compared with 5.93 +/- 0.06 in controls (P < 0.001). Maximum responses to carbachol were similar in both groups of animals. The increase in carbachol potency was accompanied by a 40% increase in receptor density from 158 +/- 5 to 221 +/- 22 fmol mg(-1) protein (P < 0.05), but this was not enough to fully account for the change in tissue sensitivity. 4 In the absence of GTP-gamma-S, carbachol displaced [3H]-QNB from two binding sites, the high-affinity site (pKi = 7.06 +/- 0.26) which represents the receptors coupled to G-proteins made up 43.1 +/- 5.9% of the total binding sites in control tissues and this value was similar (41.0 +/- 4.0%) in the diabetic tissues (pKi = 6.64 +/- 0.31). In the presence of GTP-gamma-S, carbachol displaced [3H]-QNB from a single binding site which had a low-affinity, similar to the low-affinity site observed in the absence of GTP-gamma-S. 5 These data demonstrate that detrusor supersensitivity is observed after only 1 week of untreated diabetes in the rat. The overactivity is associated with an enhanced sensitivity to carbachol, which is partly explained by an increase in receptor density, but there appears to be no change in receptor/G-protein coupling.

Aim: To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring (AUM) parameters, safety, and tolerability in patients with overactive bladder., Methods: This was a randomized, double-blind, placebo-controlled, multicentre, crossover study. Patients (n = 77) received two of the following treatments during two 2-week periods: propiverine 20 mg once daily, propiverine 15 mg three times daily, oxybutynin 5 mg three times daily, and placebo. AUM parameters, salivary flow, visual near point, and heart rate were assessed., Results: A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions (IDCs; oxybutynin 15 mg

Objectives: To identify and synthesise studies of diagnostic processes of urinary incontinence and to construct an economic model to examine the cost-effectiveness of simple, commonly used primary care tests., Data Sources: The electronic databases MEDLINE (1966--2002), CINAHL (1982--2002) and EMBASE (1980--2002)., Review Methods: Studies were selected and assessed using the Quality Assessment of Diagnostic Studies (QUADAS) tool. Studies that reported the results of applying the same diagnostic procedure using the same threshold value (cut-off) were pooled using a random effects meta-analysis model to produce pooled estimates of sensitivity, specificity and diagnostic odds ratio together with 95% confidence intervals., Results: In total, 6009 papers were identified from the literature search, of which 129 were deemed relevant for inclusion in the review, and these papers compared two or more diagnostic techniques. The gold-standard diagnostic test for urinary incontinence with which each reference test was compared was multichannel urodynamics. In general, reporting in the primary studies was poor; there was a lack of literature in the key clinical areas and minimal literature dealing with diagnosis in men. Only a limited number of studies could be combined or synthesised, providing the following results when compared with multichannel urodynamics. A clinical history for diagnosing urodynamic stress incontinence (USI) in women was found to have a sensitivity of 0.92 and specificity of 0.56 and for detrusor overactivity (DO) a sensitivity of 0.61 and specificity of 0.87. For validated scales, question 3 of the Urogenital Distress Inventory was found to have a sensitivity of 0.88 and specificity of 0.60. Seven studies compared a pad test with multichannel urodynamics; however, four different pad tests were studied and therefore it was difficult to draw any conclusions about diagnostic accuracy. Of the four studies comparing urinary diary with multichannel urodynamics, only one presented data in a format that allowed sensitivity and specificity to be calculated. Their reported values of 0.88 and 0.83 suggest that a urinary diary may be effective in the diagnosis of DO in women. Examination of the incremental cost-effectiveness of three primary care tests used in addition to history found that the diary had the lowest cost-effectiveness ratio of between pound 35 and pound 77 per extra unit of effectiveness (or case diagnosed). Imaging by ultrasound to determine leakage was found to be effective in the diagnosis of USI in women, with a sensitivity of 0.94 and specificity of 0.83., Conclusions: This is the first systematic review of methods for diagnosing urinary incontinence. As reporting of the primary studies was poor, clinical interpretation was often difficult because few studies could be synthesised and conclusions made. The report found that a large proportion of women with USI can be correctly diagnosed in primary care from clinical history alone. On the basis of diagnosis the diary appears to be the most cost-effective of the three primary care tests (diary, pad test and validated scales) used in addition to clinical history. Ultrasound imaging may offer a valuable alternative to urodynamic investigation. The clinical stress test is effective in the diagnosis of USI. Adaptation of such a test so that it could be performed in primary care with a naturally filled bladder may prove clinically useful. If a patient is to undergo an invasive urodynamic procedure, multichannel urodynamics is likely to give the most accurate result in a secondary care setting. There is a dearth of literature on the diagnosis of urinary incontinence in men, with no studies meeting the study criteria for data extraction in the diagnosis of bladder outlet obstruction. There is a need for large-scale, high-quality primary studies evaluating the use of a number of diagnostic methods in a primary care setting to be undertaken so that the results of this systematic review can be verified or not. Such studies should include not only an assessment of clinical effectiveness, in this case diagnostic accuracy, but also an assessment of costs and quality of life/satisfaction to inform future health policy decisions. Studies carried out should be reported to a better standard. The recommendations of the Standards for Reporting Diagnostic Accuracy (STARD) initiative should be followed to ensure the accuracy and completeness of reporting design and results.

Objective: To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome (OAB)., Methods: A prospective, double blind, double-dummy, two-arm, parallel-group, 12-week study was conducted to compare the efficacy and safety of solifenacin 5 or 10 mg and tolterodine extended release (ER) 4 mg once daily in OAB patients. After 4 weeks of treatment patients had the option to request a dose increase but were dummied throughout as approved product labelling only allowed an increase for those on solifenacin., Results: Solifenacin, with a flexible dosing regimen, showed greater efficacy to tolterodine in decreasing urgency episodes, incontinence, urge incontinence and pad usage and increasing the volume voided per micturition. More solifenacin treated patients became continent and reported improvements in perception of bladder condition assessments. The majority of side effects were mild to moderate in nature, and discontinuations were comparable and low in both groups., Conclusions: Solifenacin, with a flexible dosing regimen, was found to be superior to tolterodine ER with respect to the majority of the efficacy variables.

Objectives: To evaluate the tolerability, safety and efficacy of antimuscarinic drugs used to treat overactive bladder and to identify any differences between individual antimuscarinics., Methods: Medline, Embase, CCTR and Cinahl databases were searched for published RCTs including an antimuscarinic agent from 1966 to August 2004. Data from included trials were extracted and meta-analysed where possible., Results: Fifty-six trials were included. The antimuscarinics were found to be safe and efficacious. All antimuscarinics apart from oxybutynin IR were found to be well tolerated. Dry mouth was the most commonly reported adverse event and no drug was associated with an increase in any serious adverse event. There were significant differences between the antimuscarinics in rates of withdrawal and rates and range of adverse events and efficacy outcomes., Conclusions: The antimuscarinics have different tolerability and safety profiles, which are clinically significant.

Objectives: To evaluate the effects of darifenacin, an M3 selective receptor antagonist, compared with oxybutynin, on ambulatory urodynamics, salivary flow, heart rate and visual nearpoint in patients with overactive bladder (OAB)., Methods: A double-blind, randomized, crossover study (n=65) with three treatment cohorts: darifenacin immediate release (IR) 2.5 mg three times a day (t.i.d.) or oxybutynin 2.5 mg t.i.d.; darifenacin controlled release (CR) 15 mg once daily (q.d.) or oxybutynin 5 mg t.i.d.; darifenacin CR 30 mg q.d. or oxybutynin 5 mg t.i.d. Within cohorts, patients received 7 days' treatment with each agent separated by 14 days' washout., Results: All active treatments improved urodynamic parameters. Both darifenacin CR doses had significantly less effect on salivary flow than oxybutynin. Effects on urodynamic parameters, heart rate and visual nearpoint were comparable., Conclusion: Ambulatory urodynamics appears to be an innovative and potentially useful investigative tool in the evaluation of the efficacy of new therapeutic agents. Darifenacin CR is an efficacious therapy for OAB with comparable effects on urodynamic parameters but producing significantly less dry mouth than oxybutynin.

Objective: To evaluate the efficacy, tolerability and safety of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), from an analysis of pooled data from three phase III, multicentre, double-blind clinical trials in patients with overactive bladder (OAB)., Patients and Methods: After a 4-week washout/run-in period, 1059 adults (85% women) with symptoms of OAB (frequency and urgency with urge incontinence) for > or = 6 months were randomized to once-daily oral treatment with darifenacin (7.5 mg, 337; or 15 mg, 334) or matching placebo (388) for 12 weeks. Efficacy was evaluated using electronic patient diaries that recorded incontinence episodes (including those resulting in a change of clothing or pads), frequency and severity of urgency, voiding frequency, and bladder capacity (volume voided). Safety was evaluated by analysis of adverse events (AEs), withdrawal rates and laboratory tests., Results: Relative to baseline, 12 weeks of treatment with darifenacin resulted in a significant reduction in the median (% change, interquartile range) number of incontinence episodes per week; 7.5 mg (-8.8, -68.4%, -15.1 to -4.4); 15 mg; (-10.6, -76.8%, -17.3 to -5.8: both P < 0.01 vs placebo). There was a significant dose-response trend in each study for which darifenacin 7.5 and 15 mg were evaluated (P < 0.01). There were also significant decreases in the frequency and severity of urgency, voiding frequency, and number of significant leaks (incontinence episodes resulting in a change of clothing or pads; both P < or = 0.001 vs placebo), together with an increase in bladder capacity (both P < 0.01 vs placebo). Darifenacin was well tolerated; the most common AEs were dry mouth and constipation, although together these resulted in few discontinuations (darifenacin 7.5 mg 0.6% of patients; 15 mg 2.1%; placebo 0.3%). The incidence of peripheral/central nervous system and cardiovascular AEs were comparable with those on placebo., Conclusions: Darifenacin (7.5 and 15 mg once daily) is effective in the treatment of patients with OAB. As predicted by its M3 selectivity and associated M1/M2-sparing profile, darifenacin was well tolerated with no central nervous system or cardiovascular safety concerns.

Objective: To examine safety and tolerability findings as primary endpoints, and efficacy outcomes as secondary endpoints, of solifenacin treatment over a period of up to 1 year. Long-term efficacy in the treatment of overactive bladder (OAB) syndrome depends in part on the patient's persistence with pharmacologic therapy. Agents with a favourable therapeutic index supporting high levels of patient satisfaction and persistence are needed., Methods: The present study was a 40-week open-label extension of two 12-week, placebo-controlled, double-blind studies of solifenacin treatment in patients with OAB. Patients who completed the 12-week studies were offered participation in the open-label extension study. All patients who entered the open-label extension study initially received solifenacin 5 mg daily for 4 weeks, after which a flexible dosing regimen allowed patients to individualise their treatment (5 mg or 10 mg) at each of the 3 study visits. Safety and tolerability assessments (the primary variable) included adverse event reporting. Efficacy data were collected from micturition diaries completed at weeks 16, 28, 40, and 52., Results: Ninety-one percent (1637/1802) of patients who completed the two 12-week randomised studies chose to participate in the long-term open-label extension study. A total of 81% of patients completed 40 weeks of open-label treatment. Solifenacin treatment was safe and well tolerated, and rates of anticholinergic side effects were relatively low. Only 4.7% of patients discontinued treatment owing to adverse events. Improvements in major symptoms of OAB were noted for all patients for up to 52 weeks of treatment. In patients randomised to solifenacin in the double-blind studies, there were small incremental improvements in all efficacy parameters (reductions in episodes per 24 hours of urgency, reductions in frequency and urge incontinence, and increases in volume voided per micturition) over the course of the extension study. Efficacy was confirmed when outcomes were assessed as a function of total solifenacin exposure. Patient satisfaction with solifenacin tolerability (85%) and efficacy (74%) were high. These results indicate that long-term treatment with solifenacin was well tolerated and associated with improvements in efficacy parameters based on patient diary data recorded over the 12-month treatment period. Moreover, the high level of patient satisfaction reported appeared to correlate well with the quantified improvements in key symptoms demonstrated in this study., Conclusions: Long-term therapy with solifenacin resulted in a favourable tolerability profile, and was associated with improvements in efficacy parameters based on diary data recorded over a 12-month period. This balance of tolerability and efficacy with solifenacin was associated with excellent persistence with therapy. These results suggest that solifenacin may be useful for the long-term treatment of the chronic symptoms associated with OAB.

Purpose: We compared ambulatory urodynamics and conventional video cystometry findings in women with symptoms of bladder overactivity., Materials and Methods: In a prospective randomized crossover study 106 women with symptoms of urinary urgency with or without incontinence were comprehensively investigated by video cystometry and ambulatory urodynamics in random order. In addition, all women completed a validated symptoms questionnaire and voiding diary., Results: Involuntary detrusor activity was detected in 32 and 70 cases on video cystometry and ambulatory urodynamics, respectively (p <0.001). Video cystometry done according to International Continence Society standards diagnosed detrusor instability in 4 women with no involuntary detrusor activity on ambulatory urodynamics. Involuntary detrusor activity resulting in incontinence was observed in 39 cases on ambulatory urodynamics, including 20 (51%) with stable video cystometry results. Stress incontinence was diagnosed in 42 cases on video cystometry and in 34 on ambulatory urodynamics (p = 0.629). Increasingly severe urge and stress incontinence reported in the symptoms questionnaire correlated positively with the subsequent detection of detrusor overactivity and stress incontinence, respectively, on the 2 urodynamic tests., Conclusions: In contrast to video cystometry, ambulatory urodynamics provides objective evidence of clinically important bladder overactivity in the majority of women with symptoms suggestive of bladder overactivity. The correlation of symptoms with ambulatory urodynamic findings implies that greater reliance may be placed on symptomatic diagnosis of bladder overactivity. Improved objective assessment of detrusor function provided by ambulatory urodynamics has implications for the definition of bladder overactivity and relevance of conventional cystometry in this context. In women who complain of urgency stable conventional cystometrography findings should be interpreted with caution.

Antimuscarinic agents are the most widely used therapy for urge incontinence, but have side effects such as constipation, tachycardia and dry mouth, resulting from a lack of selectivity for the bladder. M2 receptors are the predominant cholinoceptors present in urinary bladder, but mainly the minor population of M3 receptors mediate its contraction. M2 receptors modulate detrusor contraction by several mechanisms, and may contribute more to contraction of the bladder in pathological states such as bladder denervation or spinal cord injury. Prejunctional inhibitory M2 or M4 receptors and prejunctional facilitatory muscarinic Ml receptors in the bladder have all been reported. In clinical studies, tolterodine, a non-selective muscarinic antagonist, has been reported to be as effective as oxybutynin but inducing less dry mouth. Thus, although it is not certain which antimuscarinic drugs have the better efficacy and tolerability, the non-selective antimuscarinic drugs seem to be better than M3-selective antagonists in their clinical efficacies. However, controlled release, or intravesical, intravaginal, or rectal administrations of oxybutynin have been reported to cause fewer side effects. Darifenacin, a new M3 selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. To verify which antimuscarinic drugs selective for the muscarinic subtypes have the best efficacy and tolerability, comparative clinical trials between M3 selective antagonists and non-selective compounds, such as olterodine, are required in the future.

A wealth of clinical evidence supports the view that muscarinic receptor antagonists are effective in the treatment of overactive bladder. However, treatment-limiting adverse effects such as dry mouth, constipation, and blurred vision have restricted the usefulness of previously available agents, such as oxybutynin. A real need therefore existed for effective and well-tolerated agents for the long-term management of the troublesome symptoms of overactive bladder. This review outlines the various approaches that have been used in attempts to overcome the tolerability problems of oxybutynin. It also describes how advances in our understanding of muscarinic receptors and bladder function has led to the potential development of either tissue- or subtype-selective antimuscarinic agents with improved tolerability. Drugs that have been developed in this way include tolterodine and darifenacin, each of which shows some bladder selectivity in animal models. Unlike darifenacin, however, the bladder selectivity of tolterodine has been confirmed by numerous clinical studies. Tolterodine's improved tolerability compared with oxybutynin, along with its equivalent therapeutic efficacy at recommended dosages, permits patients to experience the beneficial effects of long-term treatment. Tolterodine therefore represents a real alternative for the long-term management of overactive bladder. The results of ongoing clinical studies with darifenacin are awaited before it can be concluded that selective antagonism of M(3) receptors leads to improved tolerability over existing agents in the treatment of overactive bladder. Similarly, the potential improvements in tolerability associated with different dosage formulations of oxybutynin, and the clinical utility of S-oxybutynin, are yet to be conclusively demonstrated.

A series of 24 patients underwent 27 transtrigonal phenol injections for the treatment of bladder instability. Only 2 of 18 patients with detrusor instability and 2 of 6 with detrusor hyperreflexia continued to derive benefit from the procedure 6 months after it was carried out. Serious complications attributable to phenol were seen in 2 patients in this series and in a further 4 patients referred for complications resulting from this therapy in other centres. These results and a review of the literature lead us to suggest that transvesical phenol injection should not be used except in the hyper-reflexic bladder when no alternative treatment is possible. Particular care should be exercised in patients who have undergone extensive prior surgery or radiotherapy.

Overactive bladder (OAB) affects an estimated 49 million people in Europe, but only a minority receive appropriate treatment. Others are bothered by unacceptable levels of symptoms that severely impair their quality of life and represent a significant financial burden to themselves and to their healthcare providers. Recently updated guidelines from the International Consultation on Incontinence (ICI) and the European Association of Urology (EAU) take account of important new developments in the management of bladder problems in both primary and secondary care. However, local implementation of previous guidance has been variable, with many patients with OAB and other bladder problems failing to gain full benefit from current clinical and scientific understanding of these conditions. The recent expansion of the range of treatments available for OAB and stress urinary incontinence makes it especially important that physicians become aware of the differential diagnosis of these conditions – the questions they need to ask, and the investigations which will help determine the most appropriate course of action. [ABSTRACT FROM AUTHOR]

Overactive bladder syndrome (OAB) is a chronic condition characterised by urgency, with or without associated urge incontinence. Solifenacin succinate is a once daily, bladder selective antimuscarinic available in two doses (5 and 10 mg). The recommended dose is 5 mg once daily and can be increased to 10 mg once daily if 5 mg is well tolerated. This article presents pooled efficacy and safety data from four large, placebo-controlled, multinational phase III trials of solifenacin succinate with a total enrolment of over 2800 patients. Data from these trials show that solifenacin 5 and 10 mg once daily is significantly more effective than placebo at reducing urgency, incontinence, micturition frequency and nocturia and at increasing volume voided per micturition. Adverse events were mainly mild-to-moderate in all treatment groups. The results of these phase III trials support the use of solifenacin in the treatment of OAB. [ABSTRACT FROM AUTHOR]

An international, multicentre, randomized double-blind trial is presented. Patients were randomized to treatment with tolterodine, placebo, and two doses of solifenacin. The authors concluded that the two doses of solifenacin improved urgency and other symptoms of the overactive bladder, with an acceptable level of side-effects. A further phase 3 study into the effect of duloxetine was undertaken to assess whether the previous evidence of efficacy from North America and Europe could be sustained in other parts of the world. In this double-blind placebo-controlled study, the authors found that duloxetine improved continence and quality of life, in keeping with the findings in North America and Europe. A novel temporary prostatic stent has been evaluated; it looks like the proximal 4-6 cm of a Foley catheter, with a similar proximal balloon to prevent displacement. In this early study it was found to be user-friendly, and to improve symptoms in patients with BOO caused by prostatic enlargement. To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB)) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily. The study was an international, multicentre, randomized, double-blind, tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for ≥ 3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void. In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline (−1.41, −32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (−2.85, −51.9%) and 10 mg (−3.07, −54.7%; both P < 0.001), but not with tolterodine (−2.05, −37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine (−1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 (−1.42; P = 0.008) and 10 mg (−1.45; P = 0.0038). Compared with placebo (−1.20, −8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine (−1.88, −15%; P = 0.0145), solifenacin 5 (−2.19, −17%) and 10 mg (−2.61, −20%; both P < 0.001). The mean volume voided/void was also significantly higher with all three active treatments ( P < 0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most common side-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and 21.3% receiving 10 mg solifenacin. Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic OAB. [ABSTRACT FROM AUTHOR]

The normal bladder functions, storage and elimination of urine, are dependent on neural circuits in the brain and spinal cord that coordinate the activity of the detrusor and that of the smooth and striated muscles of the outflow region. Disturbances at different levels may cause the overactive bladder (OAB) syndrome, characterized by urge, frequency and urge incontinence. Knowledge about the mechanisms controlling both normal and abnormal micturition is mandatory for the detection of targets for pharmacological intervention. Such targets may be found in the central nervous system (CNS) or peripherally. Several CNS transmitters can modulate voiding, but few drugs with a defined CNS site of action have been demonstrated to be clinically useful. Traditionally, drugs for treatment of OAB have had a peripheral site of action. Antimuscarinics are still the gold standard, but their wellknown side effects have focused interest on other modalities of treatment. Promising preclinical results have been obtained for some principles, but so far there are few positive clinical proof of concept studies available. [ABSTRACT FROM AUTHOR]

Oxybutynin is a tertiary amine, which undergoes an extensive first-pass metabolism. It has an active metabolite, N-desethyl oxybutynin, and the effect of oral oxybutynin is to a large extent exerted by this metabolite. Oxybutynin has both an antimuscarinic and a direct muscle relaxant effect, and, in addition, local anesthetic actions. Most probably, oral oxybutynin exerts its effects on the overactive bladder (OAB) by an antimuscarinic action. Several studies have shown that oral oxybutynin is effective in controlling OAB. Admininistred intravesically, it can increase bladder capacity and produce clinical improvement both in patients with hypereflexia and in other types of OAB with few side effects. Adverse effects related to the antimuscarinic activity occur frequently and can necessitate treatment discontinuation in up to 25% of patients, depending on the dosage. A controlled-release preparation has recently been introduced. Oxybutynin has a well-documented efficacy in the treatment of detrusor overactivity, and is a drug of first choice in patients with this disorder. [ABSTRACT FROM AUTHOR]

Comments on the article discussing the pressure-flow analysis of female incontinence. Dependence of detrusor pressure with intravesical volume; Flow-controlling zone dictating the relationship between flow rate; Improvement of flow rate by straining.