To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.
This was a 12-week, open-label, flexible-dose study of adults with OAB (≥ 8 micturitions and ≥ 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject’s and physician’s subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed.
Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p< 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement ≥ 2 points. Significant improvements from baseline (p< 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified.
Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.
We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients.
Materials and methods:
The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of ≥ 8 voids per 24 h and episodes of urgency or urgency incontinence ≥ 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King’s Health Questionnaire.
A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively).
Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.
To evaluate the incidence of genitourinary mycoplasmas and the efficacy of antibiotics in women with overactive bladder (OAB) symptoms.
Materials and Methods
Women with OAB symptoms (micturition ≥8/24 hours and urgency ≥1/24 hours) for ≥3 months were screened for Mycoplasma hominis (M. hominis), Ureaplasma urealyticum (U. urealyticum), and Chlamydia trachomatis (C. trachomatis). Specimens from urethral and cervical vaginal swabs were examined for M. hominis and U. urealyticum by using the Mycoplasma IST2 kit and for C. trachomatis by using PCR. Women with positive results were treated with a 1 g dose of azithromycin. Persistent infection was treated with doxycycline. Changes in a 3-day bladder diary, Patient Perception of Bladder Condition (PPBC), and International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) were evaluated 4 weeks after negative conversion. Patient satisfaction was assessed.
Of 84 women screened, 42.8% were positive (U. urealyticum, 40.5%; M. hominis, 7.1%; C. trachomatis, 3.6%; two organisms, 8.3%). After treatment, 82.7% obtained negative conversion, and their median number of micturition episodes decreased from 10.6/24 hours to 8.1/24 hours (p=0.002). PPBC and domain scores of the ICIQ-FLUTS (filling and quality of life) significantly improved. About 87.5% women with negative conversion were satisfied with the treatment.
Considering diagnostic tests and treatment for genitourinary mycoplasmas might be beneficial before invasive workup or treatment in women with OAB symptoms.
Chlamydia trachomatis; Mycoplasma hominis; Overactive urinary bladder; Ureaplasma urealyticum
Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine.
Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models.
The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively.
A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials.
The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).
To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB).
This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8–12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65–74 (n = 1059) and ≥ 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms.
Discontinuation rates were slightly higher among subjects ≥ 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65–74 or ≥ 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment × age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65–74 years, 16%; ≥ 75 years, 15%). The occurrence of all other AEs was ≤ 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts.
The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.
Behavioural interventions are effective treatments for overactive bladder (OAB) and urgency urinary incontinence (UUI). They are in part aimed at improving symptoms with patient education on healthy bladder habits and lifestyle modifications, including the establishment of normal voiding intervals, elimination of bladder irritants from the diet, management of fluid intake, weight control, management of bowel regularity and smoking cessation. Behavioural interventions also include specific training techniques aimed at re-establishing normal voiding intervals and continence. Training techniques include bladder training, which includes a progressive voiding schedule together with relaxation and distraction for urgency suppression, and multicomponent behavioural training, which, in conjunction with pelvic floor muscle (PFM) exercises, includes PFM contraction to control urgency and increase the interval between voids. Guidelines for the conservative treatment of OAB and UUI have been published by several organisations and the physiological basis and evidence for the effectiveness of behavioural interventions, including lifestyle modifications, in the treatment of OAB and UUI have been described. However, many primary care clinicians may have a limited awareness of the evidence supporting the often straight-forward treatment recommendations and guidance for incorporating behavioural interventions into busy primary care practices, because most of this information has appeared in the specialty literature. The purpose of this review is to provide an overview of behavioural interventions for OAB and UUI that can be incorporated with minimal time and effort into the treatment armamentarium of all clinicians that care for patients with bladder problems. Practical supporting materials that will facilitate the use of these interventions in the clinic are included; these can be used to help patients understand lifestyle choices and voiding behaviours that may improve function in patients experiencing OAB symptoms and/or UUI as well as promote healthy bladder behaviours and perhaps even prevent future bladder problems. Interventions for stress urinary incontinence are beyond the scope of this review.
This study assessed the benefit of adding behavioural modification to darifenacin treatment for overactive bladder (OAB).
Materials and methods
The ABLE trial was a randomised, open-label, parallel-group, multicentre study of 12 weeks of darifenacin treatment [with voluntary up-titration from 7.5 mg once daily (qd) to 15 mg qd at week 2] alone or in combination with a Behavioural Modification Programme (BMP) for men and women with dry or wet OAB. Efficacy was assessed as the change in the number (per day) of micturitions (primary variable), urge urinary incontinence (UUI) episodes, urgency episodes, pads used and nocturnal voids. Health-related quality of life (HRQoL) was also evaluated. Tolerability and safety assessments included adverse events and the number of discontinuations.
Of 592 patients screened, 395 were randomised, 190 to darifenacin alone and 205 to darifenacin + BMP. At baseline, the majority of subjects were dry (mean 2.8 and three UUI episodes per day in the darifenacin and darifenacin + BMP groups respectively). At study end, darifenacin alone and darifenacin + BMP both produced significant reductions from baseline in median numbers of micturitions, UUI episodes, urgency episodes and nocturnal voids (all p < 0.05), but not in the number of pads used. HRQoL also improved. There were no significant differences between treatment groups in efficacy or HRQoL variables.
Darifenacin treatment provides a degree of normalisation of micturition variables and improvement in HRQoL that cannot be further enhanced by behavioural therapy of the type used in this study. Whether behavioural modification would add benefit over darifenacin treatment in patients with more pronounced incontinence problems remains to be determined.
We compared the effectiveness of the retropubic tension-free vaginal tape (TVT) and the transobturator inside-out tape (TVT-O) in treating symptoms of overactive bladder (OAB) in women with stress urinary incontinence (SUI).
Women with urodynamic SUI and OAB (mean urgency episodes ≥1 and frequency ≥8/24 hours on a 3-day voiding diary) were assigned to the TVT or TVT-O group. Preoperative measures were based on a urodynamic study, 3-day voiding diary, the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTSSF), and the urgency perception scale (UPS). At 12 postoperative months, the 3-day voiding diary, symptoms questionnaire, patient satisfaction, and standing stress test were assessed. The primary endpoint was change in the number of urgency episodes/24 hours from baseline to 12 months.
In this group of 132 women, 42 received TVT and 90 received TVT-O. The mean urgency episodes/24 hours decreased from 6.3±5.5 to 1.6±3.2 in the TVT group and from 5.1±4.4 to 1.8±3.0 in the TVT-O group. The mean percent change was significantly greater after TVT than after TVT-O (73% vs. 60%, P=0.049). All subscales of BFLUTSSF and UPS were significantly improved using either method, with significantly greater improvement seen in the quality of life (QoL) domain after TVT (P=0.002). There were no significant differences in the cure and satisfaction rates between the two groups.
Intervention with the TVT or the TVT-O significantly improved symptoms of OAB in women with SUI and OAB. Urgency and QoL significantly improved after TVT compared with that after TVT-O.
Overactive urinary bladder; Stress urinary incontinence
Overactive bladder (OAB) is a medical syndrome defined by symptoms of urgency, with or without urge urinary incontinence (any involuntary loss of urine), usually with frequency and nocturia. Although anticholinergic agents have been the first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Flavoxate was the first anticholinergic and antispasmodic agent approved by the Food and Drug Administration (FDA) to treat symptoms of OAB but is not routinely used today since newer agents are more effective. The more recent drugs, oxybutynin and tolterodine, have appeared to be equally efficacious in treating the symptoms of OAB in clinical trials; however, tolterodine has proven to be better tolerated with fewer adverse effects. In 2004, the FDA approved the three newest agents for the class: darifenacin, solifenacin, and trospium. Compared with oxybutynin and tolterodine, these agents have a more favorable side effect profile, which can enhance tolerability and patient compliance. Side effects are reduced in part because of the drugs' greater tissue selectivity for inhibiting the bladder muscle contraction over other anticholinergic receptors in the body. In recent clinical trials, darifenacin, solifenacin, and trospium have shown superiority to placebo and efficacy comparable to that of oxybutynin and tolterodine.
Introduction and hypothesis
Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.
Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n = 928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume.
Mirabegron 25, 50, 100, and 200 mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p ≤ 0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p < 0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events.
The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.
β3-adrenoceptor agonist; Mirabegron; Overactive; Urinary bladder
Overactive bladder (OAB) is common in men and may exist concomitantly with benign prostatic hyperplasia (BPH) and obstruction. We present a subanalysis of results from men with OAB in a 6-month, open-label study of treatment with the oxybutynin transdermal system (OXY-TDS). Broad entry criteria were incorporated to yield a clinically representative population.
All participants received OXY-TDS 3.9 mg/day. Effectiveness was assessed by changes in scores on validated questionnaires, which included the single-item Patient Perception of Bladder Condition (PPBC), the King's Health Questionnaire (KHQ) and the Beck Depression Inventory-II (BDI-II).
The proportion of men (n = 369; mean age = 69.6 years) who reported that their bladder condition caused moderate, severe or many severe problems (PPBC ≥ 4) improved from 77.3% at baseline to 38.1–53.6% in subsequent months. Mean KHQ scores decreased significantly (p ≤ 0.0196) from baseline to study end in eight of 10 domains, indicating improved health-related quality of life. The proportion of men with BDI-II score > 12 (associated with a diagnosis of depression) decreased from 23.9% to 17.9% (p = 0.0055). Men with a history of ‘prostate problems’ or use of ‘BPH medication’ (32.2%) had KHQ domain changes that were similar (p ≥ 0.1016) to those of other men. Most men (76.2%) reported no treatment-related adverse events; two men (0.5%) experienced symptoms of mild urinary retention, but neither required catheterisation.
Oxybutynin transdermal system treatment of men with OAB was effective and well tolerated, regardless of history of prostate condition.
What's knownCombined treatment of men with and without BPH is an evolving paradigm.What's newThis article contributes significant safety data, from the largest study to date, in a community use situation, where anticholinergics are commonly used.The study provides significant quality of life benefit data in a large population.The community usage design did not employ inclusion or exclusion criteria that would restrict the primary care physician from administrating the medication in a ‘real life’ setting.
The Patient Perception of Intensity of Urgency Scale (PPIUS) is a patient-reported outcome instrument intended to measure the intensity of urgency associated with each urinary or incontinence episode. The objectives of this study were to assess the content validity, test-retest reliability, and acclimation effect of the PPIUS in overactive bladder (OAB) patients.
Patients undergoing treatment for OAB were recruited to participate in a non-interventional study by completing a three-day micturition diary including the PPIUS for three consecutive weeks. Following completion of the three-week study, participants from two select sites also completed a cognitive interview to assess their comprehension of the PPIUS.
Thirty-nine participants successfully completed the three-week test-retest study; twelve of these participants completed the cognitive interview. Test-retest reliability was high based on intra-class correlation coefficient of 0.95. Among stable patients, the difference between the mean ratings of any two weeks was non-significant. Among the twelve interview participants, nine found it simple to choose a PPIUS rating for each of their micturition episodes and most found the urgency rating definitions consistent with their urgency experiences.
The results demonstrated content validity based on qualitative interviews, and excellent test-retest reliability among stable patients. In addition, no acclimation effect was observed among stable patients. These findings support the use of the PPIUS as a reliable measure of urgency in both clinical trial and real life settings. The validity of PPIUS could be further established with future studies investigating the relationship between discretely graded urgency and incontinence continuum.
Over active bladder; OAB; Urinary urgency; Urge incontinence; Patient perception of intensity of urgency scale; PPIUS
We compared the effects of bladder training and/or tolterodine as first line treatment in female patients with overactive bladder (OAB). One hundred and thirty-nine female patients with OAB were randomized to treatment with bladder training (BT), tolterodine (To, 2 mg twice daily) or both (Co) for 12 weeks. Treatment efficacy was measured by micturition diary, urgency scores and patients' subjective assessment of their bladder condition. Mean frequency and nocturia significantly decreased in all treatment groups, declining 25.9% and 56.1%, respectively, in the BT group; 30.2% and 65.4%, respectively, in the To group; and 33.5% and 66.3%, respectively in the Co group (p<0.05 for each). The decrease in frequency was significantly greater in the Co group than in the BT group (p<0.05). Mean urgency score decreased by 44.8%, 62.2% and 60.2% in the BT, To, and Co groups, respectively, and the improvement was significantly greater in the To and Co groups than in the BT group (p<0.05 for each). Although BT, To and their combination were all effective in controlling OAB symptoms, combination therapy was more effective than either method alone. Tolterodine alone may be instituted as a first-line therapy, but may be more effective when combined with bladder training.
Urinary Incontinence; Overactive Bladder; Bladder Training; tolterodine
To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.
This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate).
Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine.
The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB.
To estimate 2 year incidence, remission and predictors of urgency urinary incontinence (UUI) in a community based population of women ≥50.
We analyzed 2004–2006 data in the Health and Retirement Study. Subjects were women ≥ 50 with baseline and follow-up UUI information. UUI incidence and remission were calculated. Predictors of UUI progression and improvement were estimated controlling for age, ethnicity, body mass index (BMI), parity, psychiatric illness, medical co-morbidities, functional limitations and stress urinary incontinence (SUI). We evaluated whether baseline UUI status predicted follow-up status and used multivariable logistic regression to identify predictor variables.
8,581 women reported UUI status at baseline and follow-up. Of 7,244 women continent at baseline, 268 affirmed UUI at follow-up for a 2 year incidence of 3.7%. Of 581 women with UUI at baseline, 150 were continent at follow-up for a 2 year remission of 25.8%. Predictors of UUI development included increased age (7th and 10th decade compared to 6th decade; OR 1.5 and 7.2, CI 1.1–2.1 and 4.2–12.5, respectively), obesity (OR 1.6, CI 1.2–2.1), history of psychiatric illness (OR 1.6, CI 1.3–2.0), functional limitations (OR 6.2, CI 4.2–9.2) and SUI (OR 5.0, CI 3.0–8.3). Women who denied UUI at baseline were also likely to deny UUI at follow-up (OR 47.4, CI 22.9–98.1).
In this community based population of women ≥ 50 UUI incidence was low and remission was high. Predictors of UUI included increased age, severe obesity, functional limitations, a positive psychiatric history and incontinence status at baseline.
incidence; urgency; urinary; incontinence
Treatment options for overactive bladder (OAB) with urinary urge incontinence (UUI) refractory to oral antimuscarinics include: botulinum toxin type A (BoNTA), sacral neuromodulation (SNM), and augmentation cystoplasty (AC). A standard treatment success metric that can be used in both clinical and economic evaluations of the above interventions has not emerged. Our objective was to conduct a literature review and synthesis of published measures of treatment success for OAB with UUI interventions and to identify a treatment success outcome.
We performed a literature review of primary studies that used a definition of treatment success in the OAB with UUI population receiving BoNTA, SNM, or AC. The recommended success outcome was compared to generic and disease-specific health-related quality-of-life (HRQoL) measures using data from a BoNTA treatment study of neurogenic incontinent patients.
Across all interventions, success outcomes included: complete continence (n = 23, 44%), ≥ 50% improvement in incontinence episodes (n = 16, 31%), and subjective improvement (n = 13, 25%). We recommend the OAB with UUI treatment success outcome of ≥ 50% improvement in incontinence episodes from baseline. Using data from a neurogenic BoNTA treatment study, the average change in the Incontinence Quality of Life questionnaire was 8.8 (95% CI: -4.7, 22.3) higher for those that succeeded (N = 25) versus those that failed (N = 26). The average change in the SF-6D preference score was 0.07 (95% CI: 0.02, 0.12) higher for those that succeeded versus those that failed.
A treatment success definition that encompasses the many components of underlying OAB with UUI symptoms is currently not practical as a consequence of difficulties in measuring urgency. The treatment success outcome of ≥ 50% improvement in incontinence episodes was associated with a clinically meaningful improvement in disease-specific HRQoL for those with neurogenic OAB with UUI. The recommended success definition is less restrictive than a measure such as complete continence but includes patients who are satisfied with treatment and experience meaningful improvement in symptoms. A standardized measure of treatment success will be useful in clinical and health economic applications.
To explore whether instruction in fluid management resulted in changes in fluid intake and incontinence over a 10-week study period in women with urinary urge incontinence (UUI), as fluid management might be critical strategy in treating this condition.
Patients and Methods
In the Behavior Enhances Drug Reduction of Incontinence trial, women with predominant UUI were randomized to daily treatment with tolterodine or tolterodine combined with behavioral therapies among which were individualized instructions on fluid management. Patients in both groups received general fluid management instructions, while in the drug + behavior arm, those with excessive urine output (>2100ml/day) had additional individualized instruction during each of 4 study visits to learn behavioral strategies. Variables measured at baseline and at 10 weeks were: type of incontinence using the Medical, Epidemiological, and Social Aspects of Aging questionnaire, severity of incontinence by number of incontinence episodes based on a 7 day-diary, number of voids per 24h (F24), urgency rating, 24h fluid intake (I24) and 24 hr volume voided (V24), volume average (Vavg), pad use, bothersomeness of UUI (Urogential Distress Inventory and Overactive Bladder questionnaire), and quality of life (Incontinence Impact Questionnaire-7, Short Form-12).
Leak episodes per 24 hours, V24, I24 and average urgency ratings all significantly decreased from baseline to 10 weeks (p < 0.001 for each). Vavg increased (p < 0.001), as did voids/L intake (p = 0.01). None of the changes in diary variable outcomes differed by treatment group after accounting for these changes between baseline and 10 weeks. In a multivariable model, treatment group was not associated with change in V24 from baseline to 10 weeks (p=0.81), but the difference in the number of accidents/diary day, F24, I24 and average voids/day each were positively related with the change in V24 (p<0.001 for each). Patients had a response to fluid management instructions: the decrease in the percentage of women with a V24 >2100 ml between baseline and follow-up was statistically significant (p= 0.01 McNemar’s test).
General fluid instructions can contribute to the reduction in UUI symptoms for women taking anticholinergic medications, but additional individualized instructions along with other behavioral therapies did little to further improve the outcome.
Overactive bladder; fluid management; women; urge; incontinence
An overactive bladder (OAB) may be defined as urgency that is a sudden, compelling, difficult to defer desire to pass urine that is usually accompanied by frequency and nocturia and possibly by incontinence. Obesity and old age are two factors in various causes of OAB. Several epidemiologic studies have identified positive associations among obesity, old age, urinary incontinence, and OAB. However, although exercise has been known to improve obesity and reduce incontinent urine loss, little research has been done in elderly women. Therefore, we investigated the effects of exercise on obesity-related metabolic factors, blood lipid factors, and OAB symptoms in elderly Korean women.
Twenty-one women aged between 69 and 72 years were recruited from the Seoul senior towers in Korea. All subjects worked out on a motorized treadmill and stationary cycle for 40 minutes, respectively, and performed resistance exercise for 30 minutes once a day for 52 weeks. Body composition, blood pressure, blood lipids, OAB symptom score, and King's health questionnaire were investigated and analyzed.
Before performing physical exercise, all subjects showed increased OAB symptoms in association with enhanced body mass index (BMI), percentage fat, and blood lipid profiles. However, physical exercise for 52 weeks suppressed BMI, percentage fat, and blood lipid profiles and thus improved OAB symptoms.
We suggest that long-term physical exercise can be a valuable tool for remarkable improvement of OAB.
Overactive urinary bladder; Obesity; Exercise; Overactive bladder symptom score; King's health questionnaire
Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.
overactive bladder; urinary incontinence; pharmacologic management; antimuscarinic agents; anticholinergics
We determined the effectiveness of cystoscopic administration of botulinum-A toxin compared to placebo for the treatment of urinary incontinence in subjects with idiopathic overactive bladder.
Materials and Methods
Subjects were recruited from the Division of Urogynecology at the University of Rochester. Inclusion criteria were overactive bladder refractory to anticholinergic medications, multiple daily incontinence episodes and a 24hour pad weight of 100 gm or greater. Subjects with low leak point pressures, increased post-void residual volume or neurological etiologies were excluded from study. Subjects were randomized to placebo or to 1 of 2 doses of botulinum-A toxin. The detrusor was injected at 8 to 10 sites above the trigone. Evaluations were performed at baseline, and at 3 and 6 weeks after injection, and included bladder diaries, pad weights, quality of life questionnaires and urodynamic studies.
A total of 22 subjects participated in stage 1 of this 2-stage study. We report on the outcomes of stage 1 of this study. Because stage 2 is still ongoing and investigators remain blind to the doses of botulinum-A toxin, the 2 botulinum-A toxin groups were combined for this report. There were no differences in mean baseline measurements between the 2 groups. Statistically significant improvements in daily incontinence episodes, pads changed per day and quality of life questionnaires were seen in the botulinum-A toxin group with no changes in the placebo group. No change in nocturia, daily voiding frequency, peak flow or detrusor pressure was seen in either group. Of 15 subjects 4 (26%) receiving botulinum-A toxin had a post-void residual volume of 200 cc or greater and 1 subject required intermittent catheterization. Four subjects experienced a urinary tract infection, 2 (13%) in the botulinum-A toxin group and 2 (28%) in the placebo group (not significant).
Botulinum-A toxin can significantly reduce urge urinary incontinence due to overactive bladder at 6 weeks. However, there is a risk of urinary retention requiring self- catheterization.
botulinum toxins; urinary bladder; overactive; urinary incontinence; urge
Bladder desensitization has been investigated as an alternative treatment for refractory detrusor overactivity. Most open and controlled clinical trials conducted with intravesical RTX showed that desensitization delays the appearance of involuntary detrusor contractions during bladder filling and decreases the number of episodes of urgency incontinence.
Urgency is being recognised as the fundamental symptom of overactive bladder (OAB), a symptomatic complex which recent epidemiological studies have shown to affect more than 10% of the Western population. As anti-muscarinic drugs, the first line treatment for OAB, are far from being able to fully control urgency, the opportunity to test other therapeutic approaches is created. The present work was, therefore, designed as an exploratory investigation to evaluate the effect of bladder desensitization on urinary urgency.
Twenty-three OAB patients with refractory urgency entered, after given informed consent, a 30 days run-in period in which medications influencing the bladder function were interrupted. At the end of this period patients filled a seven-day voiding chart where they scored, using a 0–4 scale, the bladder sensations felt before each voiding. Then, patients were instilled with 100 ml of 10% ethanol in saline (vehicle solution) and 30 days later a second seven-day voiding chart was collected. Finally, patients were instilled with 100 ml of 50 nM RTX in 10% ethanol in saline. At 1 and 3 months additional voiding charts were collected.
At the end of the vehicle and 3 months period patients were asked to give their subjective impression about the outcome of the treatment and about the willingness to repeat the previous instillation.
At the end of the run-in period the mean number of episodes of urgency per week was 71 ± 12 (mean ± SEM). After vehicle instillation, the mean number of episodes of urgency was 56 ± 11, but only 4 patients (17%) considered that their urinary condition had improved enough to repeat the treatment. At 1 and 3 months after RTX the number of episodes of urgency decreased to 39 ± 9 (p = 0.002) and 37 ± 6 (p = 0.02), respectively (p indicates statistical differences against vehicle). The percentage of patients with subjective improvement after RTX and willing to repeat the instillation at a later occasion was 69%.
In OAB patients with refractory urgency bladder desensitization should be further investigated as an alternative to the standard management. Additionally, the specific effect of RTX on TRPV1 receptors suggests that urothelium and sub-urothelial C-fibers play an important role to the generation of urgency sensation.
An overactive bladder (OAB) affects a person's quality of life. Patients who suffer from OAB run to the toilet frequently to prevent incontinence, and this behavior increases their risk of falling and fear of falling. This study evaluated the influence of OAB on falls and concern about falling in females aged 40 and over living in urban and rural communities.
We conducted a population-based cohort study using King's Health Questionnaire (KHQ), the Korean version of Falls Efficacy Scale-International (KFES-I) and a questionnaire regarding falls, in females aged 40 and over in Guri city and Yangpyeong county. The data from 514 responders were analyzed. The definition of OAB was 'moderately' or 'a lot' of urgency, or urge incontinence in KHQ. Falls was defined as experience of falls in the last year. High fear of falling was defined as a score of 24 or over in KFES-I. The factors were analyzed by the exact chi-square test and Student's t-test. The multivariate logistic regression model was adopted in order to examine the effects of OAB on falls and concern about falling.
Of the 514 responders, 98 fitted the criterion of OAB. Eighty-nine (17.3%) of the responders had experienced falls in the last year: twenty-seven (27.5%) in the group with OAB and 62 (14.9%) in the group without OAB. There was a significant association between falls and OAB (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.00 to 3.08; P=0.0485), and between high fear of falling and OAB (OR, 2.72; 95% CI, 1.42 to 5.20; P=0.0024).
Urgency and symptoms of urge incontinence increase the risk of falls in women aged 40 or older in the community. Early diagnosis and proper treatment may prevent falls and improve quality of life in OAB patients.
Urinary bladder; Overactive; Urinary incontinence; Urge; Accidental falls
Overactive bladder (OAB) is subtyped into OAB-wet and OAB-dry, based on the presence or absence, respectively, of urgency incontinence. In order to better understand patient and physician perspectives on symptoms among women with OAB-wet and OAB-dry, we conducted patient focus groups and interviews with experts in urinary incontinence.
Materials and Methods
Five focus groups totaling 33 patients with OAB symptoms, including three groups of OAB-wet and 2 groups of OAB-dry patients, were conducted. Topics addressed patients’ perceptions of OAB symptoms, treatments, and outcomes. Twelve expert interviews were then conducted in which experts were asked to describe their views on OAB-wet and OAB-dry. Focus groups and expert interviews were transcribed verbatim. Qualitative data analysis was performed using Grounded Theory methodology, as described by Charmaz.
During the focus groups sessions, women screened as OAB-dry shared the knowledge that they would probably leak if no toilet is available. This knowledge was based on a history of leakage episodes in the past. Those few patients with no history of leakage had a clinical picture more consistent with painful bladder syndrome than OAB. Physician expert interviews revealed the belief that many patients labeled as OAB–dry may actually be mild OAB-wet.
Qualitative data from focus groups and interviews with experts suggest that a spectrum exists between very mild OAB-wet and severe OAB-wet. Scientific investigations are needed to determine if urgency without fear of leakage constitutes a unique clinical entity.
focus groups; qualitative research; urge urinary incontinence; grounded theory; overactive bladder
Psychometric properties of the overactive bladder questionnaire (OAB-q) were recently examined. However, since the cross-cultural adaptation of a non-English version of the OAB-q has never been demonstrated, we evaluated the psychometric properties of a Korean version of the OAB-q in a Korean population with OAB.
A prospective cohort study involving 116 women with 58 OAB and 58 control subjects was performed and convergent validity was assessed. Total and subscale OAB-q scores of the control and OAB groups were compared to their sensitivity to score changes before and after administering anti-cholinergic medication for 12 weeks. Short form 36 and King's health questionnaire (KHQ) were also used for comparison or correlation.
Assessment of face validity showed that the Korean version of the OAB-q was reasonable with OAB-q subscale scores being significantly different between the control and patient groups. Significant correlation (range, -0.29 to -0.81) was found between the OAB-q scores and KHQ results for the OAB patients. Cronbach's alpha coefficients (range, 0.77 to 0.95) indicated excellent internal consistency and test-retest analysis involving 35 OAB patients showed that each questions as well as subscale scores were reproducible. Each score of OAB-q also showed statistically significant sensitivity to changes following anti-muscarinic treatment for OAB (n=27, P<0.001 except for social, P=0.059).
The Korean version of the OAB-q is a valid and reliable instrument to measure outcomes in Korean patients with OAB.
Overactive urinary bladder; Quality of life; Questionnaires; Psychometrics
Flexible dosing of anticholinergics used for overactive bladder (OAB) treatment is a useful strategy in clinical practice for achieving a maximum effective and maximum tolerated level of therapeutic benefit. In this post hoc analysis we evaluated the efficacy and tolerability of trospium chloride treatment for urinary urge incontinence (UUI) with focus on flexible dosing.
The data came from a 12-week, randomised, double-blind, phase IIIb study in which 1658 patients with urinary frequency plus urge incontinence received trospium chloride 15 mg TID (n = 828) or 2.5 mg oxybutynin hydrochloride TID (n = 830). After four weeks, daily doses were doubled and not readjusted in 29.2% (242/828) of patients in the trospium group, and in 23.3% (193/830) in the oxybuytnin group, until the end of treatment. We assessed the absolute reduction in weekly UUI episodes and the change in intensity of dry mouth, recorded in patients' micturition diaries. Adverse events were also evaluated. Statistics were descriptive.
Dose escalation of either trospium or oxybutynin increased reduction in UUI episodes in the population studied. At study end, there were no relevant differences between the "dose adjustment" subgroups and the respective "no dose adjustment" subgroups (trospium: P = 0.249; oxybutynin: P = 0.349). After dose escalation, worsening of dry mouth was higher in both dose adjusted subgroups compared to the respective "no dose adjustment" subgroups (P < 0.001). Worsening of dry mouth was lower in the trospium groups than in the oxybutynin groups (P < 0.001). Adverse events were increased in the dose adjusted subgroups.
Flexible dosing of trospium was proven to be as effective, but better tolerated as the officially approved adjusted dose of oxybutynin.
Trial registration (parent study)
The study was registered with the German Federal Institute for Drugs and Medical Devices (BfArM, Berlin, Germany), registration number 4022383, as required at the time point of planning this study.