Seminal papers in urology: two-year outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for refractory urgency urinary incontinence: a Randomized Trial.

In this critical review, we explore the study design, strengths and limitations of the paper: "Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial." The paper reports 24 month follow-up data of the landmark ROSETTA trial. This multi-centre, open-labelled parallel randomised trial allocated females 1:1 to receive Sacral Neuromodulation (SNM) or OnabotulinumtoxinA(BTX) 200 units (U). The primary outcome was change in mean daily urinary urgency incontinence episodes (UUIE) over 24 months. The study did not demonstrate a difference between treatments (-3.88 vs. -3.50 episodes per day), however women treated with BTX were more satisfied; but reported higher rates of UTI. The two treatments provide comparable third-line treatment options for patients with refractory urgency urinary incontinence.

Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks.

BACKGROUND: Prior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment. OBJECTIVE: This study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging. STUDY DESIGN: A subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks. RESULTS: After treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001). CONCLUSION: Successful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.

Botox rechallenge-An additional tool in the management of an incompletely emptying bladder and inadequate overactive symptom control following sacral neuromodulation.

Two female patients aged 70 and 72 with video-urodynamics-confirmed detrusor overactivity and detrusor underactivity (DO-DU) were treated. Patients were refractory to medical therapies and had previously failed intravesical botulinum toxin type A (BoNT-A) at other centers secondary to urinary retention and difficulty with self-catheterization. Placement of an Interstim II device (Medtronic, Minneapolis, Minnesota) for sacral neuromodulation (SNM) as alternative third-line treatment partially improved overactive bladder (OAB) symptoms while significantly improving voiding symptoms. Postvoid residual (PVR) of patients improved from a median of 118 mL (110-125 mL) to 20 mL (18-26 mL) and 213 mL (195-230 mL) to 70 mL (60-73 mL), respectively. Addition of medical therapies post SNM failed to modify OAB symptoms further and a rechallenge with dose-reduced BoNT-A was undertaken.OAB symptoms were significantly improved by addition of BoNT-A, while urinary retention was avoided (median PVR post BoNT-A 38 mL [34-40 mL] and 185 mL [150-205 mL], respectively). Reduction in incontinence pad use as well as resolution of nighttime incontinence in both patients and daytime incontinence in one patient was achieved. DO-DU patients treated by SNM who have improved bladder emptying (PVR <100 mL) but incomplete resolution of OAB symptoms should be trialed on adjunct medical therapies to improve OAB symptoms. If OAB symptoms are still inadequately controlled, consideration of a rechallenge with BoNT-A, particularly with dose reduction, appears to be efficacious and avoids symptomatic retention in this challenging cohort.

Electroacupuncture for balanced mixed urinary incontinence: secondary analysis of a randomized non-inferiority controlled trial.

INTRODUCTION AND HYPOTHESIS: The aim was to investigate the effectiveness and safety of electroacupuncture (EA) in women with balanced mixed urinary incontinence (MUI) compared with PFMT plus solifenacin. METHODS: This is a secondary analysis of a randomized non-inferiority clinical trial. Seventy-nine patients with balanced MUI were randomly assigned to receive either 12-week EA with 24-week follow-up or 36-week PFMT and solifenacin. Primary outcome was the proportion of participants with ≥50% reduction of mean 24-h incontinence episode frequency (IFE) through weeks 1-12 from baseline. Analysis was performed in an intention-to-treat population using a generalized linear model with a binomial distribution, adjusted for imbalances in baseline variables, and a two-sided p value of less than 0.05 was considered significant. RESULTS: A total of 34 participants in the EA group and 45 participants in the PFMT plus solifenacin group were included in the intention-to-treat analysis of primary outcome. Through weeks 1-12, the proportion of participants with ≥50% reduction of mean 24-h IEF was 32.4% in the EA group, and 37.2% in the PFMT plus solifenacin group, with a mean difference of -2.82% (95%CI: -23.88 to 18.23, p=0.79), revealing non-inferiority. No significant difference held true for all the secondary outcomes. Six adverse events occurred in the EA group and 22 in the PEMT plus solifenacin group. CONCLUSIONS: The effect of EA is similar to PFMT plus solifenacin in relieving the symptoms of both SUI and UUI and increasing participants' quality of life but with better safety. The effects of EA may sustain 24 weeks after treatment.

Comparing Vitamin D Supplementation Versus Placebo for Urgency Urinary Incontinence: A Pilot Study.

OBJECTIVES: To estimate the efficacy of vitamin D supplementation to reduce urgency urinary incontinence (UUI) episodes. DESIGN: Pilot, two-arm, randomized trial conducted from 2013 to 2017. Interventions were 12 weeks of weekly oral 50,000 IU vitamin D3 or placebo. SETTING: Academic, university-based outpatient clinic. PARTICIPANTS: Community-dwelling postmenopausal women, 50 years or older, with at least three UUI episodes on 7-day bladder diary and serum vitamin 25-hydroxyvitamin D (25[OH]D) of 30 ng/mL or less. MEASUREMENTS: The primary efficacy estimate was the percentage change in UUI episodes. Secondary estimates included changes in other lower urinary tract symptoms, along with exploratory subgroup analysis by race/ethnicity and obesity. RESULTS: We randomized 56 women (aged 50-84 years; mean = 60.5 ± 8.2 years), 28 to vitamin D and 28 to placebo; 51 completed treatments. Mean serum 25(OH)D at baseline (21.2 ± 5.2 and 18.2 ± 5.6, P = .30) improved to 57.9 ± 16.3 ng/mL with vitamin D3 and 21.9 ± 8.2 ng/mL with placebo (P < .001). UUI episodes per 24-hour day decreased by 43.0% with vitamin D3 compared to 27.6% with placebo (P = .22). Among black women (n = 33), UUI episodes decreased by 63.2% with vitamin D3 compared to 22.9% with placebo (P = .03). Among obese women, UUI episodes decreased by 54.1% with vitamin D compared to 32.7% with placebo (P = .29). For all women, changes in voiding frequency (P = .40), nocturia (P = .40), urgency (P = .90), incontinence severity (P = .81), and overactive bladder symptom severity (P = .47) were not different between arms. CONCLUSIONS: Postmenopausal women with UUI and vitamin D insufficiency demonstrated a greater than 40% decrease in UUI episodes, which did not reach statistical significance compared to placebo, except in the subset of black women. The results of this pilot study support further investigation of vitamin D3 alone or in combination with other treatments for UUI, particularly for women in higher-risk subgroups. J Am Geriatr Soc 67:570-575, 2019.

Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial.

BACKGROUND: Urgency urinary incontinence (UUI) is a chronic condition for which sacral neuromodulation (SNM) (InterStim/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/Allergan) are utilized. These therapies have not been compared over extended time. OBJECTIVE: To compare UUI episodes (UUIE) over 24 mo following SNM or BTX. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized, extension trial (February 2012-July 2016) at nine US medical centers involving 386 women with ≥6 UUIE over 3 d inadequately managed by medications. Participants were clinical responders to treatment: ≥50% reduction in UUIEs after SNM placement or 1 mo post BTX. INTERVENTION: SNM (n=194) versus 200 U BTX (n=192). SNM reprogrammings occurred throughout the 24 mo. After 6 mo, two additional BTX injections were allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome: change in mean daily UUIE over 24 mo. SECONDARY OUTCOMES: no UUIE, ≥75% and ≥50% UUIE reduction; Overactive Bladder Questionnaire Short Form; Urinary Distress Inventory short form; Incontinence Impact Questionnaire; Patient Global Impression of Improvement; Overactive Bladder Satisfaction of Treatment Questionnaire; and adverse events (AEs). Primary analysis used a linear mixed model. RESULTS AND LIMITATIONS: Outcome data were available for 260/298 (87%) clinical responders. No difference in decreased mean UUIE was found over 24 mo (-3.88 vs -3.50 episodes/d,95% confidence interval [CI]=-0.14-0.89; p=0.15), with no differences in UUI resolution, ≥75% or ≥50% UUIE reduction. BTX group maintained higher satisfaction (mean difference=-9.14, 95% CI=-14.38--3.90; p<0.001), treatment endorsement (mean difference=-12.16, 95% CI=-17.7--6.63; p<0.001) through 24 mo. Other secondary measures did not differ. Recurrent urinary tract infections (UTIs) were higher after BTX (24% vs 10%; p<0.01), 6% required intermittent catheterization post second injection. SNM revision and removals occurred in 3% and 9% patients, respectively. CONCLUSIONS: Both treatments offered sustainable UUI improvement, and higher BTX dosing had low clean intermittent catheterization rates, but with UTI risk. SNM revision/removal rates were low due to standardized lead placement with strict treatment response definitions. PATIENT SUMMARY: We compared a large group of US women with severe urgency urinary incontinence (UUI) who received sacral neuromodulation (InterStim) or onabotulinumtoxinA (Botox A) therapy during a 2-yr period. We found that both therapies had similar success in reducing UUI symptoms, and adverse events were low. However, women in the BotoxA group had higher satisfaction and endorsement with their treatment, but with a higher chance of a urinary tract infection. We conclude that both therapies offer sustained reduction in daily incontinence over 2 yr.

Urinary Biomarkers in Women with Refractory Urgency Urinary Incontinence Randomized to Sacral Neuromodulation versus OnabotulinumtoxinA Compared to Controls.

PURPOSE: We measured urinary biomarker levels in women with refractory urgency urinary incontinence and controls at baseline and 6 months after treatment with sacral neuromodulation or intradetrusor injection of onabotulinumtoxinA. We also assessed the association of baseline biomarkers with posttreatment urgency urinary incontinence episodes and overactive bladder symptom bother outcomes. MATERIALS AND METHODS: First morning urine samples were collected from consented trial participants and age matched women without urgency urinary incontinence. Biomarkers reflecting general inflammation, neuroinflammation, afferent neurotransmitters and tissue remodeling were measured using standardized enzyme-linked immunosorbent assay and activity assays as appropriate. Symptom bother was assessed by the overactive bladder questionnaire and urgency urinary incontinence episodes were determined by bladder diary. Linear models were used to examine differences in mean biomarker levels and the change in urgency urinary incontinence episodes and symptom bother between baseline and 6 months. Modest evidence of a potential association was represented by p ≤0.01 and p ≤0.004 represented moderate evidence of an association with outcomes. RESULTS: Baseline biomarker levels differed little between cases and controls except tropoelastin (p = 0.001) and N-terminal telopeptide collagen type 1 (p <0.001). Changes in biomarker levels 6 months after intervention included decreases in collagenase (p <0.001) in both treatment groups and increases in interleukin-8 (p = 0.002) and matrix metalloprotease-9 (p <0.001) in the onabotulinumtoxinA group. Higher baseline calcitonin gene-related peptide across both treatments (p = 0.007) and nerve growth factor in the onabotulinumtoxinA arm (p = 0.007) were associated with less reduction in overactive bladder symptom bother. CONCLUSIONS: Refractory urgency urinary incontinence is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiological mechanisms and response to treatment.

Effectiveness on mild stress and mixed urinary incontinence and impact on Quality of Life of a phytotherapic product containing astragalus, thyme, lavender, hop, equisetum, red clover, cypress and agrimonia at titrated concentrations. Results from a monocentric study.

OBJECTIVES: To assess any beneficial effect on quality of life of a daily treatment with a phytotherapic product containing astragalus, thyme, lavender, hop, equisetum, red clover, cypress and agrimonia at titrated concentrations in a cohort of female patients complaining mild stress urinary incontinence (SUI) or mixed urinary incontinence (MUI). MATERIALS AND METHODS: 42 non-consecutive female out-patients with mild SUI or mild MUI were assessed with a clinical evaluation, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and Patients' Perception of Intensity of Urgency Scale (PPIUS) at baseline the start of the study and after two months of therapy with the phytotherapic product. At the end of the therapy the patients also compiled Patient Global Impression of Improvement (PGI-I). RESULTS: After the completion of the study there was a trend towards better results in each item of ICIQ-SF, but without any statistical significance with an average score in ICIQ-SF-1 of 3.12 ± 0.981 versus 3.21 ± 0.914 (p = 0.556), in ICIQ-SF-2 of 3.69 ± 1.422 versus 3.79 ± 1.372 (p = 0.68) and in ICIQ-SF-3 of 5.95 ± 1.618 versus 6.14 ± 1.670 (p = 0.462). The average reduction of PPIUS was of 0.09 (1.26 ± 1.481 versus 1.357 ± 1.509, p = 0.705). There was a reduction of average consumption of pads/die from 1.69 ± 0.636 to 1.54 ± 0.543 (p = 0.101). In relation to the PGI score, 23/42 patients (54.7%) reported no changes after the completion of the therapy, 13/42 (30.9%) reported a slight improvement, 5/42 (11.9%) were much improved and 1/42 (2.3%) was slightly worsened. Only 2/42 (4.7%) patients discontinued the treatment before of the completion of the study. We did not observe any adverse effects during the period of the study. CONCLUSIONS: The phytotherapic product seems to cause a slight improvement of the symptoms in a good rate of patients. Moreover it has a low rate of withdrawal, due to the lack of adverse events.

A randomized, multicenter, controlled study, comparing efficacy and safety of a new complementary and alternative medicine (CAM) versus Solifenacin Succinate in women with overactive bladder syndrome.

INTRODUCTION: To assess efficacy and tolerability of a new complementary and alternative medicine (CAM) consisting of vitamins (C and D), herbal products (cucurbita maxima, capsicum annum, polygonum capsicatum) and amino acid L-Glutammina, in the treatment of female Overactive Bladder syndrome (OAB). MATERIALS AND METHODS: 90 consecutive women with OAB symptoms were enrolled in this prospective, randomized, controlled study. Women were divided randomly into two groups of 45 patients each. In group A, women received Solifenacin Succinate (SS), 5 mg. once a day for 12 weeks. In group B, women received CAM, 930 mg, twice daily for 12 weeks. Women were assessed with 3-day micturition diary, Patient Perception of Intensity of Urgency Scale (PPIUS), Overactive Bladder questionnaire Short Form (OAB-q SF) and Patient Global Impression of Improvement questionnaire (PGI-I). RESULTS: 8 patients in group A and 1 patient in group B dropped out from therapy because of side effects. A reduction in the number of daily micturitions, nocturia and episodes of urge incontinence was present with both SS and CAM with statistically highly significant differences, but CAM was significantly more effective than SS. PPIUS and OAB-q SF showed improvements with both SS and CAM with a more significant efficacy of CAM. PGI-I, demonstrated improvements in the two groups of patients with a greater satisfaction expressed by patients treated with CAM. CONCLUSIONS: the small number of patients does not permit definitive conclusions; however, the results of the research showed the greater effectiveness and tolerability of CAM.

Combined Tolterodine and Vaginal Estradiol Cream for Overactive Bladder Symptoms After Randomized Single-Therapy Treatment.

OBJECTIVES: The aims of this study were to compare 12-week outcomes of single-therapy tolterodine (Detrol LA) extended release to intravaginal estrogen (Estrace) for overactive bladder (OAB) symptoms and characterize 24- and 52-week outcomes in women undergoing combined therapy. METHODS: A single-site randomized, open-label trial in women with urinary frequency, urgency, nocturia, and/or urgency urinary incontinence symptoms was performed. Fifty-eight participants were randomized to oral tolterodine extended release daily or intravaginal estradiol cream nightly for 6 weeks then twice per week. The primary outcome was change in Overactive Bladder Questionnaire (OAB-q) symptom bother score at 12 weeks. Secondary outcomes included the Health-Related Quality of Life Questionnaire (HRQL) of the OAB-q and a 3-day bladder diary. At 12 weeks, subjects were offered addition of the alternative therapy with follow-up at 24 and 52 weeks. RESULTS: There was no difference in symptom bother score improvement between the tolterodine and intravaginal estradiol groups baseline to 12 weeks (20.6 ± 21.7, -15.8 ± 23.3, respectively, P = 0.45). There was a significant within-group decrease in symptom bother score from baseline to 12 weeks (tolterodine, P < 0.0001, and intravaginal estradiol, P = 0.002). Secondary outcome improvement within groups was noted in the HRQL total, urinary incontinence episodes, and median voiding frequency (all P ≤ 0.03) in the tolterodine group and in the HRQL total score (P = 0.03) in the intravaginal estradiol group, with no differences between groups. Combined therapy outcomes at 24 and 52 weeks compared with single therapy at 12 weeks revealed significant improvement in symptom bother score in the intravaginal estradiol + tolterodine group at 24 and 52 weeks (20.0 ± 23.9, P = 0.008; -16.7 ± 23.3, P = 0.02, respectively). CONCLUSIONS: Significant within-group improvement in OAB-q symptom bother was noted in both the intravaginal estradiol and tolterodine groups for OAB symptoms, with no difference between groups. Greater improvement from 12-week single therapy to 24 and 52 weeks of combined therapy was noted in the group originally assigned to intravaginal estradiol. The role of combined medical therapy for OAB symptoms needs further investigation.

[Using autonomous electrostimulation device Erektron in treating female overactive bladder].

INTRODUCTION: Overactive bladder (OAB) is one of the most common syndromes of lower urinary tract dysfunction. Besides standard therapy using anticholinergic medications, comprehensive management of overactive bladder includes physiotherapy. AIM: To test the clinical effectiveness and safety of autonomous electrostimulation device "Erektron" in treating OAB in women. MATERIALS AND METHODS: The study was conducted at the Urology and Gynecology Clinic of the Innovative Medical Technology Center between 25.04.2014 and 30.01.2015. It included 20 women with newly diagnosed OAB both with and without urinary urgency incontinence or urinary stress incontinence. The patients were divided into 2 groups. All patients were treated with the first line anticholinergic agent solifenacin 5 mg daily. In patients of group 1, anticholinergic therapy was administered concurrently with intravaginal electrostimulation using "Erektron" device. RESULTS: In both groups, the treatment resulted in positive results, but a more pronounced improvement was found in group 1 patients with mixed incontinence. CONCLUSION: Autonomous electrostimulation device MT-RV "Erektron" can be used in comprehensive management of patients with OAB, including those with stress urinary incontinence.

The effect of angiotensin inhibition on urinary incontinence: data from the National Health and Nutrition Examination Survey (2001-2008).

INTRODUCTION: Local renin-angiotensin systems exist within the genitourinary tract, specifically in the bladder and urethra. Experimental data suggest that angiotensin receptor blockade with either angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) decreases both detrusor overactivity and urethral sphincter tone leading to decreased urge incontinence (UUI) and increased stress urinary incontinence (SUI). This has not been examined in a human population. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) was accessed for the years 2001-2008. Multivariate logistic regression was used for modeling. RESULTS: We studied 8,754 females and 8,886 males who met inclusion criteria. Use of ACE inhibitors or ARBs was not associated with a change in SUI in either men or women. In men, use of an ACE inhibitor or ARB was associated with a statistically significant 25-30% decrease in UUI (monthly or any urge incontinence). A similar, albeit non-significant trend was also seen for daily and weekly UUI. Other antihypertensive medications (diuretics, beta-blockers, calcium-channel blockers) were not associated with a decrease in UUI. In subanalysis, duration of ACE inhibitor or ARB use did not alter the strength of the effect on UUI nor did an elevated prostate specific antigen (PSA) level (used as a surrogate for bladder outlet obstruction due to benign prostatic hypertrophy). ACE inhibitor and ARB use did not affect UUI rates in women, though did show a trend for improvement in nulliparous women without SUI. CONCLUSION: Angiotensin receptor blockade may be a viable treatment approach for the treatment of UUI, especially in men.

Solifenacin succinate versus percutaneous tibial nerve stimulation in women with overactive bladder syndrome: results of a randomized controlled crossover study.

AIMS: This study compared the effectiveness of solifenacin succinate (SS) versus percutaneous tibial nerve stimulation (PTNS) in women with overactive bladder syndrome (OABS). METHODS: A randomized controlled crossover study of 40 women with OABS was performed. Patients were randomized into two groups. In group A, patients received SS and then PTNS. In group B, patients underwent PTNS and then SS. Voiding diaries, quality of life surveys and patient perception of intensity of urgency questionnaire were performed before and after each treatment. The global impression of improvement questionnaire was performed at the end of the study. RESULTS: A reduction in the number of daily micturitions, episodes of nocturia and urge incontinence were found with both SS and PTNS in all groups, but PTNS showed a greater effectiveness than SS. There was an increase in voided volume in all groups with both SS and PTNS, but patients treated with PTNS had a greater increase. PTNS showed greater effectiveness in patient perception of urgency and quality of life. CONCLUSION: This study demonstrates the effectiveness of SS and PTNS In women with overactive bladder symptoms. However, greater improvements were found with PTNS.

Anticholinergic drugs versus non-drug active therapies for non-neurogenic overactive bladder syndrome in adults.

BACKGROUND: Overactive bladder syndrome is defined as urgency with or without urgency incontinence, usually with frequency and nocturia. Pharmacotherapy with anticholinergic drugs is often the first line medical therapy, either alone or as an adjunct to various non-pharmacological therapies after conservative options such as reducing intake of caffeine drinks have been tried. Non-pharmacologic therapies consist of bladder training, pelvic floor muscle training with or without biofeedback, behavioural modification, electrical stimulation and surgical interventions. OBJECTIVES: To compare the effects of anticholinergic drugs with various non-pharmacologic therapies for non-neurogenic overactive bladder syndrome in adults. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register (searched 4 September 2012), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised, controlled trials of treatment with anticholinergic drugs for overactive bladder syndrome or urgency urinary incontinence in adults in which at least one management arm involved a non-drug therapy. Trials amongst patients with neurogenic bladder dysfunction were excluded. DATA COLLECTION AND ANALYSIS: Two authors evaluated the trials for appropriateness for inclusion and risk of bias. Two authors were involved in the data extraction. Data extraction was based on predetermined criteria. Data analysis was based on standard statistical approaches used in Cochrane reviews. MAIN RESULTS: Twenty three trials were included with a total of 3685 participants, one was a cross-over trial and the other 22 were parallel group trials. The duration of follow up varied from two to 52 weeks. The trials were generally small and of poor methodological quality. During treatment, symptomatic improvement was more common amongst those participants on anticholinergic drugs compared with bladder training in seven small trials (73/174, 42% versus 98/172, 57% not improved: risk ratio 0.74, 95% confidence interval 0.61 to 0.91). Augmentation of bladder training with anticholinergics was also associated with more improvements than bladder training alone in three small trials (23/85, 27% versus 37/79, 47% not improved: risk ratio 0.57, 95% confidence interval 0.38 to 0.88). However, it was less clear whether an anticholinergic combined with bladder training was better than the anticholinergic alone, in three trials (for example 74/296, 25% versus 95/306, 31% not improved: risk ratio 0.80, 95% confidence interval 0.62 to 1.04). The other information on whether combining behavioural modification strategies with an anticholinergic was better than the anticholinergic alone was scanty and inconclusive. Similarly, it was unclear whether these complex strategies alone were better than anticholinergics alone.In this review, seven small trials comparing an anticholinergic to various types of electrical stimulation modalities such as Intravaginal Electrical Stimulation (IES), transcutaneous electrical nerve stimulation (TENS), the Stoller Afferent Nerve Stimulation System (SANS) neuromodulation and percutaneous posterior tibial nerve stimulation (PTNS) were identified. Subjective improvement rates tended to favour the electrical stimulation group in three small trials (54% not improved with the anticholinergic versus 28/86, 33% with electrical stimulation: risk ratio 0.64, 95% confidence interval 1.15 to 2.34). However, this was statistically significant only for one type of stimulation, percutaneous posterior tibial nerve stimulation (risk ratio 2.21, 95% confidence interval 1.13 to 4.33), and was not supported by significant differences in improvement, urinary frequency, urgency, nocturia, incontinence episodes or quality of life.The most commonly reported adverse effect among anticholinergics was dry mouth, although this did not necessarily result in withdrawal from treatment. For all comparisons there were too few data to compare symptoms or side effects after treatment had ended. However, it is unlikely that the effects of anticholinergics persist after stopping treatment.  AUTHORS' CONCLUSIONS: The use of anticholinergic drugs in the management of overactive bladder syndrome is well established when compared to placebo treatment. During initial treatment of overactive bladder syndrome there was more symptomatic improvement when (a) anticholinergics were compared with bladder training alone, and (b) anticholinergics combined with bladder training were compared with bladder training alone. Limited evidence from small trials might suggest electrical stimulation is a better option in patients who are refractory to anticholinergic therapy, but more evidence comparing individual types of electrostimulation to the most effective types of anticholinergics is required to establish this. These results should be viewed with caution in view of the different classes and varying doses of individual anticholinergics used in this review. Anticholinergics had well recognised side effects, such as dry mouth.

Sacral neuromodulation and intravesical botulinum toxin for refractory overactive bladder.

PURPOSE OF REVIEW: To provide an overview of sacral neuromodulation (SNM) and intravesical botulinum toxin (BTX) injections in the treatment of refractory overactive bladder (OAB) and urge urinary incontinence. RECENT FINDINGS: SNM has been a successful treatment option for OAB for over a decade with efficacy rates reported between 50 and 90%. Recently, intravesical BTX has been studied as a less invasive but more transient option with similar efficacy rates. Side-effect profiles differ greatly between the treatments, with elevated postvoid residuals and urinary tract infections most commonly occurring after botulinum injection and pain or device revision or removal occurring with SNM. Recent studies have tried to elucidate the optimal dosing regimen for BTX and patient variables predicting success for both therapies in order to improve outcomes while reducing adverse events. SUMMARY: Both intravesical BTX and SNM have been shown to be effective treatment options for OAB. Further research is needed to determine equivalence or if one therapy is superior and to identify the ideal patient population for each therapy.

Comparative adherence to oxybutynin or tolterodine among older patients.

PURPOSE: To compare persistence of oxybutynin or tolterodine therapy among older patients newly prescribed one of these drugs. METHODS: We conducted a retrospective cohort study of Ontarians aged 66 years and older who were newly prescribed either drug between January 1, 2000 and December 31, 2007. Persistence with treatment was defined on the basis of refills for the drug within a grace period equal to 50% of the prescription duration. RESULTS: We identified 31,996 patients newly treated with oxybutynin and 24,855 newly treated with tolterodine. After 2 years of follow-up, persistence on oxybutynin (9.4%) was significantly lower than that on tolterodine (13.6%, p < 0.0001). The median time to discontinuation of oxybutynin and tolterodine was 68 and 128 days, respectively. CONCLUSIONS: Our findings suggest that the tolerability of these drugs differs substantially.

[Influence of suoquan capsule on detrusor of D-galactose mimetic rats].

OBJECTIVE: To discuss the influence of Suoquan capsule (SQJN) on the detrusor of D-galactose mimetic rats, and to explore the mechanism of reducing urine. METHOD: Investigate the enzymes (ATPase, SDH, SOD, MDA, Na+ -K+ -ATPase, Ca2+ - Mg2+ -ATPase) which influence the production and excretion of urine and the reactivity of urinary detrusor strips to different concentrations of ISO and ATP. RESULT: Compared with the model group, the activity of SOD, Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase and SDH increased significantly in aging rats after administrating SQJN (P < 0.01); the complaisance and elasticity of bladder also increased (P < 0.05). The frequency of spontaneous contraction and the MDA decreased significantly (P < 0.05-0.01). The decreased relaxation response to ISO and increased contractile response to ATP were also changed after administrating SQJN. CONCLUSION: SQJN can regulate the metabolism of fluid through recovering the normal physiologic function of the detrusor of bladder.