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Overactive bladder: prevalence, risk factors and relation to stress incontinence in middle-aged women.

OBJECTIVE: To investigate the prevalence of and factors associated with overactive bladder in middle-aged women. DESIGN: Cross sectional population-based study. SETTING: Southern Sweden and the Women's Health in the Lund Area study (WHILA 1995-2000) where 6917 (64% of the invited) women, 50-59 years old in 1995, participated. POPULATION: From the WHILA study, 1500 women reporting troublesome urinary incontinence (INCONT-1) and 1500 without incontinence (CONT-1) were selected by computerised randomisation and received the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire in January 2001. METHODS: Overactive bladder was defined in two versions using the ICS definition of 2002 as either urgency alone (OAB-1) or urgency combined with frequency more than eight times per day and/or nocturia twice or more per night (OAB-2). Risk factors were analysed by multiple logistic regression analyses. MAIN OUTCOME MEASURES: Prevalence figures and odds ratios with corresponding 95% confidence intervals. RESULTS: The prevalence of OAB-1 was 46.9% in the INCONT-1 and 16.7% in the CONT-1 group, and that of OAB-2 was 21.6% and 8.1%, respectively. Most urgency occurred in combination with stress incontinence (i.e. as mixed incontinence). The overlap between stress and urge symptoms increased with the frequency of stress incontinence episodes (P < 0.001). Metabolic risk factors were body mass index (BMI) >/= 30 for OAB-1, OAB-2 and stress incontinence, positive metabolic screening for OAB-1, family history of diabetes for OAB-2 and elevation of BMI >/= 25% since the age of 25 for stress incontinence. Stress incontinence was associated with the current use of hormonal replacement therapy. CONCLUSIONS: Overactive bladder and stress incontinence are intimately associated with each other. Both OAB and stress incontinence are associated with abnormal metabolic factors, mainly increased BMI.

Body Mass Index↗

Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel.

BK large conductance voltage- and calcium-activated potassium channels respond to elevations in intracellular calcium and membrane potential depolarization, braking excitability of smooth muscle. BK channels are thought to have a particularly prominent role in urinary bladder smooth muscle function and therefore are candidate targets for overactive bladder therapy. To address the role of the BK channel in urinary bladder function, the gene mSlo1 for the pore-forming subunit of the BK channel was deleted. Slo(-/-) mice were viable but exhibited moderate ataxia. Urinary bladder smooth muscle cells of Slo(-/-) mice lacked calcium- and voltage-activated BK currents, whereas local calcium transients ("calcium sparks") and voltage-dependent potassium currents were unaffected. In the absence of BK channels, urinary bladder spontaneous and nerve-evoked contractions were greatly enhanced. Consistent with increased urinary bladder contractility caused by the absence of BK currents, Slo(-/-) mice demonstrate a marked elevation in urination frequency. These results reveal a central role for BK channels in urinary bladder function and indicate that BK channel dysfunction leads to overactive bladder and urinary incontinence.

Alleles↗

Using the circumstances of symptom experience to assess the severity of urgency in the overactive bladder.

PURPOSE: We identified a method for quantifying the symptoms of the overactive bladder that addresses the assessment of urgency. MATERIALS AND METHODS: An observational study of a cohort was used. Data were collected prospectively from 5,423 consultations on 1,797 patients (158 males and 1,639 females) being assessed and treated for the overactive bladder. The study was conducted during 5 years. The reported frequencies and incontinence episodes were recorded. Using ranked ordinal scales (none, mild, moderate, severe) the symptoms of urgency and urge incontinence associated with waking and rising, hearing running water, arriving home ("latchkey"), cold weather and when feeling tired or worried were noted. The experiences of urgency and urge incontinence, without reference to the circumstances in which they were experienced were similarly assessed and if on treatment, they were asked to grade their overall response. RESULTS: Reported urinary frequency and incontinence episodes were strongly associated with patient grading of response to treatment. Therefore, the symptoms assessed on the scale of none, mild, moderate and severe were compared with disease severity by using reported frequency and incontinence episodes. The description of the symptoms with reference to the situations in which they were experienced showed clear associations with frequency and incontinence, falling along a progressive scale. An overall pattern could be detected in that at points on the scale of none, mild, moderate and severe, the least frequency and incontinence tended to be associated with waking, rising and latchkey symptoms. Next followed symptoms precipitated by running water and cold weather. Aggravation by fatigue or worry was associated with the greatest disease severity (ANOVA F = 8.9, p <0.001). This scale covered a wide range from frequencies of 7 to 15 times daily and incontinence episodes through 0 to 4 times daily. CONCLUSIONS: Qualifying the experience of urgency and urge incontinence, according to the circumstances in which these symptoms are experienced, seems to offer a promising new method for assessing the severity of urgency and urge incontinence.

Activities of Daily Living↗

Efficacy and tolerability of tolterodine extended-release in men with overactive bladder and urgency urinary incontinence.

UNLABELLED: A group of authors from the USA evaluated the efficacy and tolerability of tolterodine extended-release on objective and subjective endpoints in men with an overactive bladder. They found that it significantly reduced incontinent episodes and improved patient perception of treatment benefit in men with an overactive bladder OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine extended-release (ER) on objective and subjective endpoints in men with overactive bladder (OAB) and urgency urinary incontinence (UI). PATIENTS AND METHODS This was a post hoc analysis of data collected from men with OAB enrolled in a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily; tolterodine ER registration trial) and included men with urinary frequency (> or =8 micturitions/24 h) and urgency UI (> or =5 episodes/week). UI episodes were assessed using 7-day bladder diaries. Patient perception of treatment benefit was evaluated after 12 weeks. Adverse events (AEs) were recorded throughout the study. RESULTS: In all, 163 men with OAB (placebo, 86; tolterodine ER, 77; mean age 65 years) were evaluated. Baseline demographics and clinical characteristics were similar for the two treatment groups. Compared with placebo, tolterodine ER significantly reduced weekly UI episodes (median % change, -71% vs - 40%, P < 0.05; mean numeric change, - 11.9 vs -5.9, P = 0.02). Men receiving tolterodine ER had fewer micturitions/24 h, but this was not a significant difference from placebo (median % change, -12% vs - 4%, P = 0.22). Significantly more men treated with tolterodine-ER (63%) than placebo-treated men (46%) reported a benefit of treatment after 12 weeks (P = 0.04). The most commonly reported AEs associated with tolterodine-ER vs placebo were dry mouth (16% vs 7%), constipation (4% vs 9%), dyspepsia (4% vs 1%), dizziness (5% vs 1%), and somnolence (3% vs 1%). One of the men receiving tolterodine ER had symptoms suggestive of urinary retention that led to his withdrawal from the study. None of the men had acute urinary retention requiring catheterization. CONCLUSION: In men with OAB and urgency UI, tolterodine ER was well tolerated and significantly reduced episodes of urgency UI, and improved patient perception of treatment benefit.

Adolescent↗

[Prevalence of overactive bladder in Spain: a population-based study].

OBJECTIVES: The aim of this study was to assess the prevalence of the urinary symptoms suggestive of overactive bladder (OAB) in Spain based on the International Continence Society (ICS) 2002 consensus criteria as urinary urgency, with or without urge incontinence, usually with frequency and nocturia. METHODS: 1,669 real telephone interviews were conducted to adults aged > or = 40 years. The sample size estimation was made according to the prevalence for OAB described in the Milsom paper stratified by age and gender due to the high variability observed between ranges. Appearance and prevalence of main OAB symptoms, medical diagnostic and therapy due to these symptoms data were collected. RESULTS: the sample population was 1669 aged > or = 40 years, 50.6% women and 49.4% men. The overall prevalence of symptoms suggestive of OAB according to the OAB definition from ICS report 2002 was 21.5%, significantly higher in women (25.6%) than men (17.4%)(p<0.05). Adjusting these data to Spanish National Census of year 2000, the prevalence was 19.9%, being higher as well in women (23.6%) than men (115.4%). Urge urinary incontinence and stress urinary incontinence were superior in women (16.7% vs 10.4% and 33.1% vs 7.9% respectively)(p<0.01). Urinary frequency > 8 voids/day was referred by 9.8% of women and 7.9% of men interviewed. 62% of men and 52.4% of women reported they get up at night to void. A total of 52.1% of patients with urinary symptoms suggestive of overactive bladder reported they had consulted a doctor anytime before the interview due to urinary disorders and 16.7% was currently receiving treatment for some of these symptoms. CONCLUSIONS: Prevalence of urinary symptoms suggestive of Overactive Bladder is high in this study, in accordance with data from international studies. Urinary urgency, symptom which defines the pathology, is more prevalent in Spanish women than men. Further studies are needed to better assess OAB impact in the Spanish general population.

Adult↗

[Anticholinergics for overactive bladder: does subtype selectivity play a role?].

Anticholinergics act in the treatment of overactive bladder by blocking muscarinic receptors of which five subtypes exist. Their desired effects occur via M(3) receptors, but a role for M(2) receptors is being discussed. Adverse effects such as dry mouth and constipation occur also via M(3) receptors, but M(2) and M(1) receptors can mediate side effects in the heart or on cognitive function, respectively. Therefore, an M(3)-selective drug such as darifenacin could theoretically be less effective but also have fewer cardiac or central nervous side effects. However, the limited available clinical data do not support a smaller efficacy or better general tolerability. The lack of adverse effects on cognitive function is well documented for darifenacin, but it cannot yet be determined definitively whether this discriminates it from other modern anticholinergics.

Benzofurans↗

Nocturnal polyuria and nocturia relief in patients treated with solifenacin for overactive bladder symptoms.

The objectives of this study are to determine whether patients with overactive bladder (OAB) and nocturia achieved relief of their nighttime voiding symptoms when treated with solifenacin and whether having nocturnal polyuria (NP) affected that response. The patients pooled from four phase III clinical trials were evaluated for reductions in nocturia episodes after treatment with solifenacin (5 or 10 mg) or placebo. A second analysis was performed in patients with and without NP. The patients treated with solifenacin experienced statistically significant reductions in nocturia episodes; median reductions were -35.5% for 5 mg of solifenacin and -36.4% for 10 mg of solifenacin compared with -25.0% for placebo, and significantly more patients treated with solifenacin vs placebo achieved a mean nocturic frequency of <or=1 episode/night. Solifenacin significantly reduced nocturia episodes only in patients without NP (mean change was -0.61 episodes/night for both doses compared with -0.43 episodes for placebo). Solifenacin significantly improved nocturia symptoms only in OAB patients without NP.

Female↗

Epidemiology, pathophysiology, and evaluation of urinary incontinence and overactive bladder.

OBJECTIVES: To present an overview of current knowledge regarding the epidemiology, pathophysiology, and evaluation of urinary incontinence (UI) with a focus on the problem of the overactive bladder. METHODS: The most recent data on the epidemiology of UI are presented. The literature on the pathophysiology of urinary urge incontinence (UUI) is reviewed, and key concepts related to patient evaluation are summarized. RESULTS: The prevalence of UI depends on the population being surveyed. The overactive bladder constitutes a substantial percentage of the overall problem, ranging from > 50% of incontinent men to only 10% to 15% of incontinent younger women. Few data are available on the incidence of the disorder or on racial/ethnic trends. Overactive bladder or urge incontinence is called detrusor hyperreflexia when a neurologic cause is known and detrusor instability when there is no neurologic abnormality. Although the pathophysiology of idiopathic instability is not well understood, some evidence suggests that this condition may result from subclinical neurologic disease or primary smooth muscle disease. Most patients with UUI can be adequately evaluated with a history, physical examination, determination of postvoid residual volume, and urinalysis. When neurologic disease or other complicating factors are present, or if initial treatment fails, sophisticated urodynamic testing is appropriate. CONCLUSIONS: Urinary incontinence is prevalent in all strata of the population, although it affects women and the elderly disproportionately. With the exception of cases in which a neurologic lesion can be demonstrated, the etiology of UUI remains elusive. A thorough history, physical examination, determination of postvoid residual, and urinalysis will be adequate to classify and treat the majority of patients.

Female↗

Patients with overactive bladders deserve better.

Tolterodine is an effective agent used to treat symptoms of overactive bladder. It is well tolerated and its selectivity for the bladder results in less side effects overall compared to many other agents. Many patients in New Zealand with symptoms of overactive bladder do not have access to tolterodine due to restrictions on its funding by PHARMAC. Alternative treatments are not as well tolerated and are less clinically useful. This leaves many patients vulnerable to significant compromise of their quality of life.

Benzhydryl Compounds↗

The epidemiology of overactive bladder among females in Asia: a questionnaire survey.

A questionnaire-based survey was performed in 5502 females from 11 countries in Asia to establish the prevalence overactive bladder (OAB) and identify the factors related to the occurrence of the condition. The overall prevalence of OAB was 53.1%. The most common presenting symptom was urgency (65.4%). Twenty-one per cent of the OAB population presented with incontinence, giving an overall prevalence of 11.4% for urge incontinence among Asian females. The majority (75.4%) were not significantly bothered by the condition. Only 21.1% sought treatment. Older age, multiparity, a positive family history, residence in a rural area and the use of a sitting type of toilet were found to be associated with a greater occurrence of OAB. The study has shown that overactive bladder in Asian females is significant and warrants closer attention. It has also highlighted the low treatment-seeking rate among its sufferers. This is the first report on the epidemiology of overactive bladder among Asians in the medical literature.

Adolescent↗

The overactive bladder: review of current pharmacotherapy in adults. Part 1: pathophysiology and anticholinergic therapy.

Overactive bladder is a syndrome characterised by urinary urgency, with or without urge incontinence, and usually with frequency and nocturia. It affects millions of people of all ages worldwide and causes significant morbidity, especially in terms of health-related quality of life. It poses a huge economic burden on health resources. Managing such patients involves a thorough history, physical examination and the use of pertinent investigations before the initiation of treatment. Therapy consists of lifestyle changes, bladder training, anticholinergics, second-line agents such as resiniferatoxin instillation or botulinum toxin injections into the bladder in refractory cases and, finally, in intractable cases, surgery. In the first part of this review of pharmacotherapy for the treatment of this condition, the focus is on the pathophysiological factors potentially involved in overactive bladder and covers the wide range of currently available first-line anticholinergic agents. Treatment algorithms are suggested on the basis of current literature.

Administration, Cutaneous↗

Effectiveness and tolerability of extended-release oxybutynin vs extended-release tolterodine in women with or without prior anticholinergic treatment for overactive bladder.

The efficacy and the tolerability of extended-release oxybutynin chloride, 10 mg daily, and extended-release tolterodine tartrate, 4 mg daily, in women with or without prior anticholinergic treatment for overactive bladder (OAB) were compared in a post-hoc analysis of data from the Overactive Bladder: Performance of Extended Release Agents (OPERA) trial. The patient population and study methods have been described previously (Diokno et al., for the OPERA Study Group, Mayo Clin Proc 78:687-695, 2003). Among the group with anticholinergic experience, extended-release oxybutynin was significantly more effective than extended-release tolterodine in reducing micturition frequency at last observation (p=0.052). Complete freedom from urge incontinence was reported by significantly more patients taking oxybutynin than tolterodine at last observation (23.6 vs 15.1%, p=0.038). In addition, among patients completing a full 12 weeks of oxybutynin treatment, significantly greater reductions were observed compared with those taking tolterodine on the primary efficacy variable, number of urge incontinence episodes (p=0.049), and the combined total of urge and non-urge episodes (p=0.012), although the differences between treatment groups were not significant at last observation. In the anticholinergic-naïve group, efficacy and tolerability outcomes were similar across treatments, except that oxybutynin was associated with a significantly lower frequency of micturition at last observation (p=0.035). No efficacy differences favoring tolterodine were observed, and tolerability of the treatments was comparable. Dry mouth (mostly mild to moderate in severity) was reported significantly more often among participants taking extended-release oxybutynin than extended-release tolterodine (32.2 vs 19.2%, p=0.004), but only among those with previous anticholinergic experience. Discontinuation rates were comparably low across groups. The results demonstrate the appropriateness of initiating treatment for OAB with extended-release oxybutynin, particularly in women presenting with incontinence.

Adult↗

Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics.

PURPOSE: In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. MATERIALS AND METHODS: A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. RESULTS: Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. CONCLUSIONS: Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.

Adult↗

Potential therapeutic targets for treatment of the overactive bladder.

Muscarinic receptor antagonists remain the main therapy for the treatment of the overactive bladder yet severe adverse effects make them unsuitable for a large number of patients. The development of new drugs with novel mechanisms of action for the treatment of this condition is therefore essential. This article considers some of the targets currently under investigation for the development of such compounds. Beta-adrenoceptor agonists and KATP channel openers inhibit detrusor muscle activity and remain targets for drug development. There is also evidence that alpha-adrenoceptor antagonists may be effective in the overactive bladder, but the mechanism involved in this action is unclear. Finally the role of tachykinins in regulating bladder function through both the sensory and the motor innervation make them a potential target for drug development, but as with the the others, a selective action on the bladder must remain the goal of drug development.

Adrenergic alpha-Agonists↗

Tolterodine extended release improves patient-reported outcomes in overactive bladder: results from the IMPACT trial.

We evaluated the effect of tolterodine extended release (ER) on patient- and clinician-reported outcomes in a primary care setting. Patients had overactive bladder (OAB) symptoms for >or=3 months and were at least moderately bothered by their most bothersome symptom, as indicated on the patient-completed OAB Bother Rating Scale. Patients completed the Overactive Bladder Questionnaire (OAB-q), American Urological Association Symptom Index (AUA-SI), and Patient Perception of Bladder Condition at each visit; investigators completed the Clinical Global Impression-Improvement at week 12. By week 12, there were statistically significant and clinically meaningful decreases on the OAB-q and AUA-SI total and subscale scores (p < 0.0001). Seventy-nine per cent of patients experienced some improvement in their overall bladder condition. Physicians reported that 68% of patients were 'much improved' or 'very much improved'. For symptom-defined conditions, patient-reported outcomes are a valuable means for determining responses to treatment.

Adolescent↗

Propiverine hydrochloride immediate and extended release: comparison of efficacy and tolerability in patients with overactive bladder.

INTRODUCTION: This study aims to compare the efficacy of propiverine hydrochloride immediate release (IR), propiverine hydrochloride extended release (ER) and placebo for the treatment of overactive bladder syndrome. The primary outcome measure is incontinence episode frequency, with secondary outcome measures including mean volume per void and quality of life as assessed on King's Health Questionnaire. MATERIAL AND METHODS: The double-blind, double-dummy, randomized study compared IR 15 mg twice daily, ER 30 mg once daily and placebo in 3 parallel groups. After a run-in period of 7 days, the patients were treated for 32 days. Nine hundred and eighty-eight patients were randomized, and 910 patients completed the protocol without major violations. RESULTS: The number of incontinence episodes/24 h decreased by 2.26 in the IR group (p < 0.001 vs. placebo), by 2.46 in the ER group (p < 0.0001 vs. placebo) and by 1.75 in the placebo group. The most frequent adverse event was dry mouth with 22.8% of the patients in the IR group, 21.7% in the ER group and 6.4% in the placebo group. The overall tolerability was rated 'very good' or 'good' by more than 80% of the investigators and patients in all 3 groups. CONCLUSIONS: Propiverine ER 30 mg once daily and propiverine IR 15 mg twice daily significantly reduce the number of incontinence episodes/24 h within a treatment period of 32 days. Both formulations are safe and well tolerated. The extended release formulation of propiverine is a suitable new option for the treatment of the overactive bladder.

Benzilates↗

Definition of overactive bladder and epidemiology of urinary incontinence.

OBJECTIVES: To review the definition of the overactive bladder and to summarize the results of epidemiologic studies on this specific disorder as well as urinary incontinence (UI) in general. METHODS: From a literature search covering the time period from 1954 through 1995, 48 epidemiologic studies and several other publications dealing with the prevalence and natural history of UI were reviewed. A meta-analysis of reported data was performed with respect to incontinence definitions, investigation methods, home country of survey, sex, and age groups. RESULTS: Differences in definitions of incontinence, target populations, and study design in different investigations resulted in inhomogeneity and difficulties of comparing the available data. By grouping the studies with respect to similarities in the above-mentioned criteria and analyzing the results for each group of studies, an attempt was made to understand the great variation of reported results. Differences in prevalence of incontinence were identified for all examined groups of studies and for distinct ethnic populations. Scarce information about incidence, spontaneous remission rates, and risk factors was used to elucidate the natural history of UI in women and men. CONCLUSIONS: Although generally accepted definitions of the overactive bladder specifically and UI in general are highly desirable, they have not yet been established. Such definitions should comprise aspects of severity and demonstrability of the condition, bother factor, and impact on quality of life. Moreover, basic requirements for epidemiologic surveys of incontinence, such as validation of questionnaire results, need to be defined and standardized to create a sensible basis for useful epidemiologic studies in the future.

Age Distribution↗

Quality of life in women with multiple sclerosis and overactive bladder syndrome.

The aim of this study was to evaluate the impact of symptoms of overactive bladder syndrome (OAB) on the quality of life (QoL) in female patients with or without multiple sclerosis (MS) and their correlation with findings from urodynamics (UDS). We enrolled 107 female patients with clinically definite MS and urinary symptoms of OAB. One-hundred female patients with similar OAB symptoms were used as a control group. Data on OAB symptoms, onset and progression, and results of any previous investigation were obtained, and any urinary complications were documented. A complete UDS investigation was performed. Health status assessment was obtained using the Kings Health Questionnaire. Results showed that urinary symptoms had a greater impact on the QoL in patients with MS. Nevertheless, the perception of the severity of these symptoms was minor in the MS group compared to the control group. No significant correlations were found between the dysfunctions as detected by UDS and the OAB symptoms in both groups. Recurrent urinary tract infections represented the main complication in the study population. In conclusion, OAB symptoms have a major impact on the QoL in patients with MS, even if their perception of QoL impairment remains limited. Optimal management in these subjects should include a complete UDS assessment.

Disability Evaluation↗