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1.  Sacral Nerve Stimulation For Urinary Urge Incontinence, Urgency-Frequency, Urinary Retention, and Fecal Incontinence 
Executive Summary
Objective
The aim of this review was to assess the effectiveness, safety, and cost of sacral nerve stimulation (SNS) to treat urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence.
Background: Condition and Target Population
Urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence are prevalent, yet rarely discussed, conditions. They are rarely discussed because patients may be uncomfortable disclosing their symptoms to a health professional or may be unaware that there are treatment options for these conditions. Briefly, urge incontinence is an involuntary loss of urine upon a sudden urge. Urgency-frequency is an uncontrollable urge to void, which results in frequent, small-volume voids. People with urgency-frequency may or may not also experience chronic pelvic pain. Urinary retention refers to the inability to void despite having the urge to void. It can be caused by a hypocontractile detrusor (weak or no bladder muscle contraction) or obstruction due to urethral overactivity. Fecal incontinence is a loss of voluntary bowel control.
The prevalence of urge incontinence, urgency-frequency, and urinary retention in the general population is 3.3% to 8.2%, and the prevalence of fecal incontinence is 1.4% to 1.9%. About three-quarters of these people will be successfully treated by behaviour and/or drug therapy. For those who do not respond to these therapies, the options for treatment are management with diapers or pads, or surgery. The surgical procedures are generally quite invasive, permanent, and are associated with complications. Pads and/or diapers are used throughout the course of treatment as different therapies are tried. Patients who respond successfully to treatment may still require pads or diapers, but to a lesser extent.
The Technology Being Reviewed: Sacral Nerve Stimulation
Sacral nerve stimulation is a procedure where a small device attached to an electrode is implanted in the abdomen or buttock to stimulate the sacral nerves in an attempt to manage urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence. The device was originally developed to manage urinary urge incontinence; however, it has also been used in patients with urgency-frequency, urinary retention, and fecal incontinence. SNS is intended for patients who are refractory to behaviour, drug, and/or interventional therapy.
There are 2 phases in the SNS process: first, patients must undergo a test stimulation phase to determine if they respond to sacral nerve stimulation. If there is a 50% or greater improvement in voiding function, then the patient is considered a candidate for the next phase, implantation.
Review Strategy
The standard Medical Advisory Secretariat search strategy was used to locate international health technology assessments and English-language journal articles published from 2000 to November 2004. The Medical Advisory Secretariat also conducted Internet searches of Medscape (1) and the manufacturer’s website (2) to identify product information and recent reports on trials that were unpublished but that were presented at international conferences. In addition, the Web site Current Controlled Trials (3) was searched for ongoing randomized controlled trials (RCTs) investigating the role of sacral nerve stimulation in the management of voiding conditions.
Summary of Findings
Four health technology assessments were found that reviewed SNS in patients with urge incontinence, urgency-frequency, and/or urinary retention. One assessment was found that reviewed SNS in patients with fecal incontinence. The assessments consistently reported that SNS was an effective technology in managing these voiding conditions in patients who did not respond to drug or behaviour therapy. They also reported that there was a substantial complication profile associated with SNS. Complication rates ranged from 33% to 50%. However, none of the assessments reported that they found any incidences of permanent injury or death associated with the device.
The health technology assessments for urge incontinence, urgency-frequency, and urinary retention included (RCTs (level 2) as their primary source of evidence for their conclusions. The assessment of fecal incontinence based its conclusions on evidence from case series (level 4). Because there was level 2 data available for the use of SNS in patients with urinary conditions, the Medical Advisory Secretariat chose to review thoroughly the RCTs included in the assessments and search for publications since the assessments were released. However, for the health technology assessment for fecal incontinence, which contained only level 4 evidence, the Medical Advisory Secretariat searched for studies on SNS and fecal incontinence that were published since that assessment was released.
Urge Incontinence
Two RCTs were identified that compared SNS to no treatment in patients with refractory urge incontinence. Both RCTs reported significant improvements (> 50% improvement in voiding function) in the SNS group for number of incontinence episodes per day, number of pads used per day, and severity of incontinence episodes.
Urgency-Frequency (With or Without Chronic Pelvic Pain)
One RCT was identified that compared SNS to no treatment in patients with refractory urgency-frequency. The RCT reported significant improvements in urgency-frequency symptoms in the SNS group (average volume per void, detrusor pressure). In addition to the RCT, 1 retrospective review and 2 prospective case series were identified that measured pelvic pain associated with urgency-frequency in patients who underwent SNS. All 3 studies reported a significant decrease in pain at median follow-up.
Urinary Retention
One RCT was identified that compared SNS to no treatment in patients with refractory urinary retention. The RCT reported significant improvements in urinary retention in the SNS group compared to the control group for number of catheterizations required and number of voids per day. In addition to this RCT, 1 case series was also identified investigating SNS in women with urinary retention. This study also found that there were significant improvements in urinary retention after the women had received the SNS implants.
Fecal Incontinence
Three case series were identified that investigated the role of SNS in patients with fecal incontinence. All 3 reported significant improvements in fecal incontinence symptoms (number of incontinent episodes per week) after the patients received the SNS implants.
Long-Term Follow-up
None of the studies identified followed patients until the point of battery failure. Of the 6 studies identified describing the long-term follow-up of patients with SNS, follow-up periods ranged from 1.5 years to over 5 years. None of the long-term follow-up studies included patients with fecal incontinence. All of the studies reported that most of the patients who had SNS had at least a 50% improvement in voiding function (range 58%–77%). These studies also reported the number of patients who had their device explanted in the follow-up period. The rates of explantation ranged from 12% to 21%.
Safety, Complications, and Quality of Life
A 33% surgical revision rate was reported in an analysis of the safety of 3 RCTs comparing SNS to no treatment in patients with urge incontinence, urgency-frequency, or urinary retention. The most commonly reported adverse effects were pain at the implant site and lead migration. Despite the high rate of surgical revision, there were no reports of permanent injury or death in any of the studies or health technology assessments identified. Additionally, patients consistently said that they would recommend the procedure to a friend or family member.
Economic Analysis
One health technology assessment and 1 abstract were found that investigated the costing factors pertinent to SNS. The authors of this assessment did their own “indicative analysis” and found that SNS was not more cost-effective than using incontinence supplies. However, the assessment did not account for quality of life. Conversely, the authors of the abstract found that SNS was more cost-effective than incontinence supplies alone; however, they noted that in the first year after SNS, it is much more expensive than only incontinence supplies. This is owing to the cost of the procedure, and the adjustments required to make the device most effective. They also noted the positive effects that SNS had on quality of life.
Conclusions and Implications
In summary, there is level 2 evidence to support the effectiveness of SNS to treat people with urge incontinence, urgency-frequency, or urinary retention. There is level 4 evidence to support the effectiveness of SNS to treat people with fecal incontinence.
To qualify for SNS, people must meet the following criteria:
Be refractory to behaviour and/or drug therapy
Have had a successful test stimulation before implantation; successful test stimulation is defined by a 50% or greater improvement in voiding function based on the results of a voiding diary. Test stimulation periods range from 3 to 7 days for patients with urinary dysfunctions, and from 2 to 3 weeks for patients with fecal incontinence.
Be able to record voiding diary data, so that clinical results of the implantation can be evaluated.
Patients with stress incontinence, urinary retention due to obstruction and neurogenic conditions (such as diabetes with peripheral nerve involvement) are ineligible for sacral nerve stimulation.
Physicians will need to learn how to use the InterStim System for Urinary Control. Requirements for training include these:
Physicians must be experienced in the diagnosis and treatment of lower urinary tract disorders and should be trained in the implantation and use of the InterStim System for Urinary Control.
Training should include the following:
Participation in a seminar or workshop that includes instructional and laboratory training on SNS. This seminar should include a review of the evidence on SNS with emphasis on techniques to prevent adverse events.
Completion of proctoring by a physician experienced in SNS for the first 2 test stimulations and the first 2 implants
PMCID: PMC3382408  PMID: 23074472
2.  Urodynamic Detrusor Overactivity in Patients with Overactive Bladder Symptoms 
Purpose
To evaluate the relationship between urodynamic detrusor overactivity (DO) and overactive bladder (OAB) symptoms in men and women.
Methods
We reviewed the records of adult males and females who attended a tertiary referral center for urodynamic evaluation of OAB syndrome symptoms with the presence or absence of DO. DO was calculated for symptoms alone or in combination.
Results
The overall incidence of DO was 76.1% and 58.7% in male and female OAB patients, respectively. Of men 63% and 61% of women with urgency (OAB dry) had DO, while 93% of men and 69.8% of women with urgency and urgency urinary incontinence (OAB wet) had DO. Of women, 58% who were OAB wet had stress urinary incontinence symptoms with 26.4% having urodynamic stress incontinence. 6% of men and 6.5% of women with OAB symptoms had urodynamic diagnosis of voiding difficulties with postvoid residual greater than 100 mL. Combination of symptoms is more accurate in predicting DO in OAB patients. The multivariate disease model for males included urge urinary incontinence (UUI) and urgency while for females it included UUI and nocturia.
Conclusions
There was a better correlation in results between OAB symptoms and the urodynamic diagnosis of DO in men than in women, more so in OAB wet than in OAB dry. Combination of symptoms of the OAB syndrome seems to have a better correlation with objective parameters from the bladder diary, filling cystometry, and with the occurrence of DO.
doi:10.5213/inj.2011.15.1.48
PMCID: PMC3070227  PMID: 21468287
Overactive bladder; Urodynamic investigation; Urinary incontinence; Detrusor overactivity
3.  Emerging treatments for overactive bladder: clinical potential of botulinum toxins 
Overactive bladder (OAB) is a symptom syndrome including urgency, frequency, and nocturia – with or without incontinence. It is a common manifestation of detrusor overactivity (DO). DO is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. OAB is, therefore, both a motor and sensory disorder. Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum and has been used in medicine for many years. Over the last 10 years, it has been used for the treatment of DO and OAB when standard treatments, such as bladder training and oral anticholinergic medication, have failed to provide symptom relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release from the neurons in the motor end plate and also at sensory synapses, although the clinical effect is not permanent due to the growth of new connections within treated tissues. It is known that botulinum toxin modulates vanillioid, purinergic, capsaicin, and muscarinic receptor expression within the lamina propria, returning them to levels seen in normal bladders. Clinically, the effect of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon the symptom of urgency, and also large effects on frequency, nocturia, leakage episodes, and continence rates. These effects have been seen consistently within eight randomized trials and numerous case series. Botulinum toxin appears safe, with the only common side effect being that of voiding difficulty, occurring in up to 10% of treated patients. Dosing regimens are variable, depending on which preparation is used, but it is clear that dose recommendations have fallen over the last 5 years. There is limited evidence about the efficacy of repeat treatments. Botulinum toxin is an effective and safe second-line treatment for patients with OAB and DO.
doi:10.2147/RRU.S44665
PMCID: PMC4039398  PMID: 24892033
overactive bladder; detrusor overactivity; botulinum toxin; efficacy; side-effects; treatment
4.  Effectiveness of Retropubic Tension-Free Vaginal Tape and Transobturator Inside-Out Tape Procedures in Women With Overactive Bladder and Stress Urinary Incontinence 
Purpose
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).
Methods
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.
Results
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.
Conclusions
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.
doi:10.5213/inj.2013.17.3.145
PMCID: PMC3797895  PMID: 24143294
Overactive urinary bladder; Stress urinary incontinence
5.  Tolterodine extended release in the treatment of male oab/storage luts: a systematic review 
BMC Urology  2014;14(1):84.
Background
Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS.
Methods
A wide Medline search was performed including the combination of following words: “LUTS”, “BPH”, “OAB”, “antimuscarinic”, “tolterodine”, “tolterodine ER”. IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER.
Results
Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of α-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment.
Conclusion
Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.
doi:10.1186/1471-2490-14-84
PMCID: PMC4230346  PMID: 25348235
Lower urinary tract symptoms; Overactive bladder; Storage LUTS; Tolterodine; Urge incontinence; Frequency; Nocturia
6.  Efficacy and tolerability of combined medication of two different antimuscarinics for treatment of adults with idiopathic overactive bladder in whom a single agent antimuscarinic therapy failed 
Objective
Recent studies have investigated a combination of two antimuscarinics for adult neurogenic bladder managed with clean intermittent catheterization or pediatric refractory overactive bladder (OAB). We assessed the efficacy and tolerability of this strategy in adults with idiopathic OAB.
Methods:
We reviewed 49 patients with idiopathic OAB who received combined antimuscarinic medication. Patients had serially received different kinds of antimuscarinics as monotherapy, but wished to take combined medication due to a lack of sufficient subjective improvement in urgency, even with dosage escalation. Efficacy was measured by changes of episodes of urgency, daytime voiding, nocturia and mean voided volume before and after the addition of the second antimuscarinic.
Results:
The mean duration of combined medication was 9.3 months. After adding the second antimuscarinic, urgency per day decreased from 3.8 to 1.9 (p < 0.001) and daytime voiding decreased from 10.4 to 7.4 (p < 0.001). The number of nocturia episodes and the mean voided volume also improved, although there was no statistical significance. Efficacy did not differ between the 29 cases, with non-selective and non-selective drugs and 20 cases with non-selective and M3 selective drugs. Thirty-three (67.3%) patients reported to have benefited from combined medication. Maximal flow rate and post-void residual volume did not change in either of the sexes. Eleven (22.4%) patients discontinued the combination due to continued ineffectiveness and dry mouth.
Conclusion:
This retrospective study suggests that combined medication can help adults with refractory idiopathic OAB. Combined medication was tolerated in most of our patients.
doi:10.5489/cuaj.269
PMCID: PMC3650812  PMID: 23671514
7.  Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders 
BMC Urology  2006;6:31.
Background
The Bladder cooling reflex (BCR) i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO) and painful bladder syndrome (PBS), but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders.
Methods
The BCR, elicited by ice water test (IWT) was performed in patients with painful bladder syndrome (PBS, n = 17), idiopathic detrusor overactivity (IDO, n = 22), neurogenic detrusor overactivity (NDO, n = 4) and stress urinary incontinence (as controls, n = 21). The IWT was performed by intravesical instillation of cold saline (0 – 4°C). A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test.
Results
A positive IWT was observed in IDO (6/22, 27.3%) and NDO (4/4, 100%) patients, but was negative in all control and PBS patients. Thirteen (76.5%) PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002), or equivalent amount of bladder filling (100 mls) with saline at room temperature (P = 0.015). None of the control or overactive (NDO/IDO) patients reported any pain during the IWT.
Conclusion
The BCR in DO may reflect loss of central inhibition, which appears necessary to elicit this reflex; the pain elicited in PBS suggests afferent sensitisation, hence sensory symptoms are evoked but not reflex detrusor contractions. The ice water test may be a useful and simple marker for clinical trials in PBS, particularly for novel selective TRPM8 antagonists.
doi:10.1186/1471-2490-6-31
PMCID: PMC1766360  PMID: 17192176
8.  Influence of Type of Nocturia and Lower Urinary Tract Symptoms on Therapeutic Outcome in Women Treated With Desmopressin 
Korean Journal of Urology  2013;54(2):95-99.
Purpose
To investigate the type of nocturia and concomitant voiding dysfunction (VD) and the effect of desmopressin treatment on nocturia in women.
Materials and Methods
We reviewed 84 women who experienced more than 2 nocturia episodes as recorded on a pretreatment frequency volume chart and who were treated with desmopressin. All patients underwent history taking, physical examination, urinalysis, International Prostate Symptom Score assessment, completion of a urinary sensation scale, and completion of a 3 day frequency volume chart. Nocturia was divided into nocturnal polyuria (NP), reduced nocturnal bladder capacity (RNBC), and mixed type. After treatment with desmopressin, a reduction in nocturia of over 50% compared with baseline was regarded as effective.
Results
Among 84 women, the most common concomitant VD was overactive bladder (OAB, 60.7%). NP was observed in 70.2% (59/84) of the women, RNBC in 7.1% (6/84), and mixed type in 22.6% (19/84). After medication with desmopressin, 73 women (86.9%) showed a significantly reduced number of nocturia episodes (1.4±1.5) compared with baseline (3.7±1.3, p<0.05). Eleven women (13.1%) did not show improvement. Of the 73 women who showed improvement, 41 women showed a reduction of more than 50% over baseline, and these women had a lower baseline urgency grade.
Conclusions
In the majority of women, nocturia coexisted with other VD such as OAB. Treatment with desmopressin effectively reduced the nocturia. However, other lower urinary tract symptoms (LUTS) such as urgency may reduce the effect of desmopressin. Therefore, consideration of concomitant LUTS seems to be necessary to increase the treatment effect of desmopressin on nocturia in women.
doi:10.4111/kju.2013.54.2.95
PMCID: PMC3580312  PMID: 23549374
Deamino arginine vasopressin; Lower urinary tract symptoms; Nocturia; Women
9.  Efficacy and safety of solifenacin succinate 10 mg once Daily: A multicenter, phase III, randomized, double-blind, placebo-controlled, parallel-group trial in patients with overactive bladder 
Background: Solifenacin succinate is an antimuscarinic drug with reported efficacy and tolerability at a recommended starting dose of 5 mg QD in patients with overactive bladder (OAB).
Objective: The objective of this trial was to investigate the efficacy, safety, and tolerability of solifenacin 10 mg QD in patients with OAB.
Methods: In this multicenter, Phase III, double-blind, placebo-controlled, parallel-group trial, patients aged ≥18 years with OAB were randomized at a 1:1 ratio to receive solifenacin 10 mg or placebo QD for 12 weeks. The patients were instructed to complete a micturition diary for the 3 days preceding each scheduled visit (weeks 4, 8, and 12). The primary end point was the change from baseline in the mean number of micturitions per 24 hours; secondary end points included the mean change from baseline in the number of episodes per 24 hours of urgency, incontinence, nocturnal voiding, and nocturia and the mean volume voided per micturition. Tolerability was monitored through adverse events (AEs), vital sign measurements, ECGs, laboratory assessments, and physical examination.
Results: A total of 672 patients were randomized and received ≥1 dose of study drug (solifenacin, n = 340; placebo, n = 332). The mean (SE) decrease from baseline to study end in the number of micturitions per 24 hours was significantly greater in the solifenacin group compared with the placebo group (−3.0 [0.2] vs −1.5 [0.2], respectively; P < 0.001). The mean decrease in the number of episodes of incontinence was significantly greater in the solifenacin group compared with the placebo group (−2.0 [0.2] vs −1.1 [0.2]; P < 0.001), as was the mean decrease in the number of episodes of urgency (−4.1 [0.2] vs −2.1 [0.2]; P < 0.001). Of the patients with ≥1 incontinence episode per 24 hours at baseline, significantly more patients in the solifenacin group achieved complete continence at study end than did patients in the placebo group (119/225 [52.9%] vs 80/237 [33.8%]; P < 0.001). The change from baseline to study end in the mean volume voided per micturition increased significantly in the solifenacin group compared with the placebo group (47.2 vs 2.7 mL; P < 0.001). Most AEs were mild or moderate in intensity. The AEs that were most commonly reported in the solifenacin-treated group were anticholinergic in nature: dry mouth (91 [26.8%] vs 13 patients [3.9%] in the placebo group; P < 0.001); constipation (58 [17.1%] vs 11 [3.3%]; P < 0.001); and blurred vision (12 [3.5%] vs 4 [1.2%]; P < 0.05). Serious AEs (SAEs) were reported for 5 patients in the solifenacin group and 3 patients in the placebo group. In the solifenacin group, 2 patients experienced chest pain, 1 had cellulitis, 1 had dehydration, and 1 had colonic obstruction; only 1 SAE (colonic obstruction) was judged to be possibly related to the study drug. In the placebo group, 1 patient had chest pain, 1 had bacterial meningitis, and 1 had hemopericardium.
Conclusions: This study found that solifenacin 10 mg QD for 12 weeks was associated with significantly reduced symptoms of OAB, including the frequency of micturition, and episodes of urgency and of incontinence. With solifenacin, the volume voided per micturition increased by 47.2 mL, and 53% of patients with ≥1 incontinence episode per 24 hours at baseline achieved complete continence. This efficacy was accompanied by a favorable safety and tolerability profile.
doi:10.1016/j.curtheres.2009.11.001
PMCID: PMC3969973  PMID: 24692834
anticholinergic; incontinence; overactive bladder; solifenacin; urgency
10.  Associations between subjective overactive bladder symptoms and objective parameters on bladder diary and filling cystometry 
International Urogynecology Journal  2012;23(11):1619-1624.
Introduction and hypothesis
A study was conducted to assess associations between different overactive bladder (OAB) symptoms and their outcomes on bladder diary and filling cystometry parameters.
Methods
We performed a retrospective cohort study in database of 6,876 Urinary Distress Inventories, 3,185 bladder diaries and 2,153 filling cystometries from women referred to our urogynecological center between 2003 and 2009. Women were dichotomized into two groups. Group I: those women without symptoms, and those with symptoms that were not bothersome. Group II: women with bothersome symptoms. Data obtained from bladder diaries were: daytime urinary frequency, nocturnal frequency, minimum voided volume, maximum voided volume, average voided volume, and incontinence episodes. From filling cystometries, volumes at first desire to void, normal desire to void, strong desire to void and maximum cystometric capacity, were extracted. Univariate and multiple linear regression analysis were performed to determine associations between OAB symptoms and bladder diary and filling cystometry measurements.
Results
After multivariate analysis the objective daytime frequency was most strongly associated with the frequency symptom (β 0.27, p < 0.05), night time frequency with the nocturia symptom (β 0.40, p < 0.05) and the number of incontinence episodes with the urge incontinence symptom (β 0.37, p < 0.05). Both frequency and nocturia symptoms were significantly associated with bladder diary and cystometry filling volumes, and their effect size was the same. The urgency symptom proved to be poorly associated with objective parameters.
Conclusions
In contrast to the frequency and nocturia symptom, the urgency symptom is poorly associated with objective parameters on bladder diary and filling cystometry. Therefore, the current practice of using frequency and incontinence episodes in outcome research of OAB trials is justified.
doi:10.1007/s00192-012-1774-3
PMCID: PMC3592260  PMID: 22543547
Bladder diary; Cystometry; Overactive bladder
11.  Functional MRI of the Brain in Women with Overactive Bladder: Brain Activation During Urinary Urgency 
Objectives
To identify abnormal function of the limbic cortex (LC) in response to urinary urgency among patients with Overactive Bladder (OAB) using brain functional MRI (fMRI)
Methods
5 OAB subjects and 5 Controls underwent bladder filling and rated urgency sensations while fMRI measured activation in discrete volumes (voxels) within the brain. Changes in brain activation were related to bladder distension and individual subject’s rating of urgency via multiple regression analysis. Beta weights from regression equations were converted into percent signal change (PSC) for each voxel and PSC compared to the null hypothesis using T-tests. Significance threshold of P<.05 was applied along with a cluster size threshold of.32 ml (5 voxels).
Results
OAB patients showed increased brain activation in LC, specifically the insula (IN) and Anterior Cingulate Gyrus (ACG), associated with increased urgency. Urgency sensations during low volumes were associated with bilateral IN activation in OAB subjects (7,621 voxels right IN, 4,453 voxels left IN, mean beta weights .018 +/− .014 and .014 +/− .011) Minimal activation was present in Controls (790 voxels right IN, beta weight =.010 +/− .007). Urgency sensations during high volumes were associated with bilateral ACG activation in OAB subjects (2,304 voxels right IN, 5,005 voxels left IN, mean beta weights of 005 +/− .003 and 004+/−.003) without activation in Controls.
Conclusions
Urinary urgency in patients with OAB is associated with increased activation of the LC. This activation likely represents abnormal processing of sensory input in brain regions associated with emotional response to discomfort.
doi:10.1097/SPV.0b013e3182065507
PMCID: PMC3051367  PMID: 21399722
OAB; fMRI; urinary urgency
12.  Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study 
Purpose:
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.
Results:
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).
Conclusions:
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.
doi:10.1111/j.1742-1241.2008.01898.x
PMCID: PMC2680337  PMID: 19143854
13.  A comparison of the efficacy of darifenacin alone vs. darifenacin plus a Behavioural Modification Programme upon the symptoms of overactive bladder 
Purpose
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.
Results
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.
Conclusions
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.
doi:10.1111/j.1742-1241.2008.01714.x
PMCID: PMC2325270  PMID: 18324952
14.  Role of botulinum toxin-A in management of refractory idiopathic detrusor overactive bladder: Single center experience 
Background
Overactive bladder (OAB) is a bothersome condition affecting the quality of life, financial constraint on the individual, and community. Anticholinergic drugs cannot be used for long term due to adverse side effects. Botulinum toxin has recently shown promising and encouraging result in management of OAB.
Aim
Aim was to study the safety, efficacy, tolerability, and duration of effect of 200 units of botulinum toxin in refractory idiopathic detrusor overactivity.
Materials and Methods
Thirty-nine female patients (average age of 52 years) clinically and urodynamically diagnosed as idiopathic OAB were injected 200 units of botulinum toxin-A mixed with 20 ml of normal saline, intradetrusally at the rate of 1 mL at each site for 20 such sites sparing the trigone and ureteric orifices. Follow up at 3rd, 6th, 9th, and 12th month with clinical and urodynamical questionnaire was done.
Results
There were 4 dropouts and 35 patients were evaluated, of which 30 patients (85.7%) showed improvement in clinical features like frequency, urgency, nocturia, and incontinence within 1 week of injection, which lasted for mean period of 7 months (varying from 6 to 9 months). Volume at first desire to void improved from median baseline of 104-204 ml and maximum cystometric capacity of bladder increased from mean baseline value of 205-330 ml. The detrusor pressure decreased by 49% from the baseline and postresidual urine volume increased by 30% of maximum cystometric capacity of bladder. There was no adverse effect on our patient.
Conclusion
Intradetrusor injection of Botox-A in management of refractory overactive idiopathic bladder is not only safe and well tolerated, but also very effective with practically no side effects.
PMCID: PMC2684267  PMID: 19468394
Anticholinergic; botulinum toxin; overactive bladder
15.  The Prevalence and Therapeutic Effect of Constipation in Pediatric Overactive Bladder 
Purpose
Overactive bladder (OAB) is a manifestation of urgency, regardless of urge incontinence, due to involuntary bladder contraction during the storage period. There is a close association between constipation and OAB, but constipation cannot be readily diagnosed. The aims of this study were to evaluate the prevalence of constipation in OAB and the consequent therapeutic effects according to the diagnostic criteria for constipation.
Methods
We collected clinical data from 40 children (mean age, 71±22 months) with chief complaints of urgency, frequency, and incontinence. A voiding questionnaire and a 2-day voiding diary were collected, and urinalysis, the Bristol stool scale, and plain abdominal radiography were performed. Constipation was defined as conditions satisfying at least one of the following criteria: Rome III diagnostic criteria, Bristol stool scale types I/II, or a Leech score higher than 8 points as determined by plain radiography. Lower urinary tract symptoms, defecation symptoms, and the bladder volume of patients were examined, and the therapeutic outcomes by constipation diagnostic criteria were evaluated.
Results
Of the 40 OAB patients, 25 had constipation. Among them, 6 had reduced functional bladder capacity (24%; P>0.05). Regarding treatment, in patients who satisfied only one diagnostic criterion, the symptoms improved in 76.9%, 76.9%, and 69.6% of patients meeting the Rome III criteria, Bristol stool scale, and Leech score, respectively (P<0.05). Among the 8 patients satisfying all three criteria, 75% responded to treatment (P<0.05).
Conclusions
The prevalence of constipation in OAB is high. Constipated patients recruited by use of the Rome III criteria, Bristol scale, and Leech score alone and together showed similar outcomes on OAB improvement after the treatment of constipation, which implies that each criterion has the same strength and can be applied comprehensively and generally.
doi:10.5213/inj.2011.15.4.206
PMCID: PMC3256305  PMID: 22259734
Overactive urinary bladder; Pediatrics; Constipation
16.  Effect of caffeine on bladder function in patients with overactive bladder symptoms 
Urology Annals  2011;3(1):14-18.
Objectives:
To evaluate the effect of caffeine at the dose of 4.5 mg/kg on bladder function in overactive bladder (OAB) adults.
Materials and Methods:
Nine women and three men aged 21-40 years with OAB symptoms were included. Each subject drank 8 ml/kg of water with and without caffeine at two separate sessions. Cystometry and uroflowmetry were performed 30 minutes after each drink. The effects of caffeine on urodynamic parameters were compared.
Results:
After caffeine ingestion, the mean volume at bladder filling phase decreased at first desire to void and normal desire to void (P<0.05), compared to the mean volume after taking water (control) drink. The mean volume at strong desire to void, urgency and maximum cystometric capacity also tended to decrease. No change in the detrusor pressure at filling phase was found. At voiding phase, the maximal flow rate, average flow rate and voided volume were increased (P<0.05). The urine flow time and time to maximal flow rate were not changed.
Conclusion:
Caffeine at 4.5 mg/kg caused diuresis and decreased the threshold of sensation at filling phase, with an increase in flow rate and voided volume. So, caffeine can promote early urgency and frequency of urination. Individuals with lower urinary tract symptom should avoid or be cautious in consuming caffeine containing foodstuffs.
doi:10.4103/0974-7796.75862
PMCID: PMC3036994  PMID: 21346827
Caffeine; overactive bladder; uroflowmetry
17.  Association of Urinary Urgency and Delay Time of Micturition in Women With Overactive Bladder 
Purpose
Accurately measuring urinary urgency is important for diagnosing overactive bladder (OAB) and quantifying improvements in treatment outcome. Various methods have been recommended for evaluating urinary urgency, but these methods assess individual perceptions and preferences. To overcome the subjectivity in measuring urinary urgency, we evaluated the relationship between uroflowmetric parameters and urinary urgency in women with OAB.
Methods
Consecutive female patients with lower urinary tract symptoms (n=110) were prospectively enrolled in this study between April 2011 and September 2012. Individuals with a history of using medications that are known to affect bladder function were excluded. All enrolled patients completed uroflowmetry with a delayed time to voiding (T2V). After urination was completed, patients were asked whether they experienced any urinary hesitancy or urgency at that time.
Results
The mean patient age was 56.1 years; 70 out of 110 patients reported some degree of urinary urgency. T2V decreased with increased urgency. Several uroflowmetric parameters were observed to have a significant correlation with urinary urgency. T2V had a meaningful correlation coefficient for individuals with urgency, regardless of the voided volume. There was no significant correlation between the presence of urinary hesitancy and T2V.
Conclusions
We believe that T2V would be a complementary tool for diagnosing and determining the degree of urinary urgency in women with OAB.
doi:10.5213/inj.2014.18.3.150
PMCID: PMC4180166  PMID: 25279243
Analysis; Women; Overactive urinary bladder; Questionnaire; Urodynamics
18.  Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study 
Aims:
To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.
Methods:
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.
Results:
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.
Conclusion:
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.
doi:10.1111/j.1742-1241.2009.02035.x
PMCID: PMC2705818  PMID: 19348029
19.  A Comparative Study on the Efficacy of Solifenacin Succinate in Patients with Urinary Frequency with or without Urgency 
PLoS ONE  2014;9(11):e112063.
Objectives
Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency.
Materials and Methods
This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire.
Results
Of the 286 enrolled patients, 240 (83.9%) completed the study (without urgency n = 115; with urgency n = 125). Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of −2.49±0.35 (mean ± standard error) and −2.63±0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was −1.14, which is smaller than the −0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well.
Conclusions
It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency.
Trial Registration
ClinicalTrials.gov NCT00979472
doi:10.1371/journal.pone.0112063
PMCID: PMC4234319  PMID: 25401784
20.  Efficacy and safety of fesoterodine 8 mg in subjects with overactive bladder after a suboptimal response to tolterodine ER 
Aims
To assess fesoterodine 8 mg efficacy over time and vs. placebo in subjects with overactive bladder (OAB) who responded suboptimally to tolterodine extended release (ER) 4 mg.
Methods
In a 12-week, double-blind trial, subjects with self-reported OAB symptoms for ≥ 6 months, mean of ≥ 8 micturitions and ≥ 2 to < 15 urgency urinary incontinence (UUI) episodes/24 h, and suboptimal response to tolterodine ER 4 mg (defined as ≤ 50% reduction in UUI episodes during 2-week run-in) were randomised to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks) or placebo once daily. Change from baseline to week 12 in UUI episodes (primary end-point) was analysed in step-wise fashion: first, baseline vs. week 12 for fesoterodine; if significant, then change from baseline to week 12 for fesoterodine vs. placebo.
Results
By week 12, subjects receiving fesoterodine 8 mg had significantly greater improvement from baseline vs. placebo in UUI episodes, urgency episodes and scores on the Patient Perception of Bladder Control, Urgency Perception Scale and OAB Questionnaire Symptom Bother and Health-Related Quality of Life scales and domains (all p < 0.05). 50% and 70% UUI responder rates were also significantly higher with fesoterodine 8 mg vs. placebo at week 12 (p < 0.05). Dry mouth (placebo, 4%, 12/301; fesoterodine, 16.6%, 51/308) and constipation (placebo, 1.3%, 4/301; fesoterodine, 3.9%, 12/308) were the most frequent adverse events.
Conclusions
Subjects who responded suboptimally to tolterodine ER 4 mg showed significant improvements in UUI and other OAB symptoms and patient-reported outcomes, with good tolerability, during treatment with fesoterodine 8 mg vs. placebo.
doi:10.1111/ijcp.12464
PMCID: PMC4265241  PMID: 24898471
21.  Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection on Elderly Patients with Chronic Central Nervous System Lesions and Overactive Bladder 
PLoS ONE  2014;9(8):e105989.
Purpose
Intravesical injection of onabotulinumtoxinA is an effective treatment for overactive bladder (OAB). Nonetheless, the treatment outcome is unclear in OAB patients with central nervous system (CNS) lesions. This study evaluated the efficacy and safety of intravesical onabotulinumtoxinA treatment in elderly patients with chronic cerebrovascular accidents (CVAs), Parkinson’s disease (PD) and dementia.
Materials and Methods
Patients with CVA, PD, dementia, and OAB refractory to antimuscarinic therapy were consecutively enrolled in the study group. Age-matched OAB patients without CNS lesions were selected to serve as a control group. OnabotulinumtoxinA (100 U) was injected into the bladder suburothelium at 20 sites. The clinical effects, adverse events, and urodynamic parameters were assessed at baseline and 3 months post-treatment. The Kaplan-Meier method was used to compare long-term success rates between groups.
Results
A total of 40 patients with OAB due to CVA (23), PD (9), dementia (8) and 160 control patients were included in this retrospetive analysis. Improvement of urgency severity scale, increased bladder capacity and increased post-void residual volume were comparable between the groups at 3 months. Patients with CNS lesions did not experience increased risks of acute urinary retention and urinary tract infection; nonetheless, patients with CVA experienced a higher rate of straining to void. Long-term success rates did not differ between the patients with and without CNS lesions.
Conclusion
Intravesical injection of 100 U of onabotulinumtoxinA effectively decreased urgency symptoms in elderly OAB patients with CNS lesions. The adverse events were acceptable, and long-term effects were comparable to OAB patients in general. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization need careful evaluation for this very vulnerable population before choosing intravesical onabotulinumtoxinA treatment.
doi:10.1371/journal.pone.0105989
PMCID: PMC4141863  PMID: 25148378
22.  Effect of Desmopressin with Anticholinergics in Female Patients with Overactive Bladder 
Korean Journal of Urology  2011;52(6):396-400.
Purpose
The aim of this study was to evaluate the effect of desmopressin combined with anticholinergics on daytime frequency and urgency in female patients with overactive bladder (OAB).
Materials and Methods
We included 68 female patients with OAB. Patients were randomly assigned to receive 5 mg of solifenacin (group I) or 5 mg of solifenacin and 0.2 mg of desmopressin (group II) for 2 weeks. A pre/post-treatment 3-day voiding diary and the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) were used to assess changes in voiding symptoms and quality of life (QoL); results were compared between the two groups.
Results
Groups I and II included 31 and 37 patients, respectively. Time to first void was 12 min later in group II (105 min vs. 117 min), but this difference was not statistically significant. However, time to the second and third voids (203 min vs. 255 min, 312 min vs. 368 min) and the first urgency episode (212 min vs. 255 min) were significantly longer in group II. Compared with group I, patients in group II showed significant improvement in QoL scores. When improvement after treatment was defined as increase in time to first void of greater than 10% after 2 weeks of treatment, desmopressin with anticholinergics was more effective in patients over the age of 65 years and with more than 150 ml of voided volume.
Conclusions
Desmopressin combined with anticholinergics was more effective than anticholinergics only in the treatment of female patients with OAB.
doi:10.4111/kju.2011.52.6.396
PMCID: PMC3123815  PMID: 21750750
Anticholinergics; Desmopressin; Overactive bladder
23.  Role of fesoterodine in the treatment of overactive bladder 
Muscarinic receptors have long been the target receptors for treatment of patients with overactive bladder (OAB). These patients experience symptoms of urgency, urinary frequency and nocturia, with or without urge incontinence (the involuntary leakage of urine associated with urge). Fesoterodine, a pro-drug, structurally and functionally related to tolterodine, is the newest agent developed for the treatment of OAB. Fesoterodine is broken down to the active metabolite, 5-hydroxy-methyl-tolterodine (5-HMT) by non-specific esterases. This metabolism results in the complete breakdown of the parent compound and is responsible for dose related improvements in clinical efficacy and health related quality of life. Like other antimuscarinic agents including tolterodine, fesoterodine is associated with improvements in clinical variables related both to bladder filling (decreasing micturition frequency and increasing mean voided volume) and urgency (urgency and urge incontinence episodes). Improvements in health related quality of life following treatment with fesoterodine is indicated by improvements in 7 of the 9 variables measured by the King’s Health Questionnaire. Also like other antimuscarinic agents, fesoterodine use is associated with adverse events including dry mouth. However the incidence of dry mouth is reduced with fesoterodine, compared to oxybutynin, due to the improved bladder selectivity of 5-HMT.
PMCID: PMC3818872  PMID: 24198608
fesoterodine; 5-hydroxymethy1-tolterodine; muscarinic; overactive bladder; urgency; incontinence
24.  Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence 
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.
doi:10.1111/j.1742-1241.2009.02078.x
PMCID: PMC2734927  PMID: 19575724
25.  A phase II dose-ranging study of mirabegron in patients with overactive bladder 
International Urogynecology Journal  2013;24(9):1447-1458.
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1007/s00192-013-2042-x
PMCID: PMC3745617  PMID: 23471546
β3-adrenoceptor agonist; Mirabegron; Overactive; Urinary bladder

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