Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial.

PURPOSE: To evaluate the efficacy of intermittent percutaneous needle sacral nerve stimulation (IPN-SNS) in women with idiopathic overactive bladder (IOAB) treated with tolterodine. MATERIALS AND METHODS: A total of 240 female patients diagnosed with IOAB were randomized to receive tolterodine only treatment (group 1, n = 120) or tolterodine combined with IPN-SNS (group 2, n = 120). Each group included 120 participants, who were divided into subgroups depending on whether they had dry OAB (urinary frequency and urgency) or wet OAB (urinary frequency and urgency with urgency incontinence). In the treatment group, patients received percutaneous IPN-SNS plus tolterodine (2 mg once daily), while in the control group, only tolterodine (2 mg once daily) was administered for 3 months. The voiding diary and urodynamic parameters were monitored, and patients' psychological depression and anxiety scores were recorded before and after treatment. RESULTS: There were significantly greater improvements in the conditions of first desire to void (FDV), max­imum cystometric capacity (MCC), and daily average volumes, as well as the daily single maximum voided volumes in group 2 (P = .001) than in group 1. In addition, there were significantly greater decreases in self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores in group 2 compared with group 1 (P < .001). CONCLUSION: Combined treatment with tolterodine plus IPN-SNS can not only improve the symptoms of voiding dysfunction but can also reduce the concomitant depression and anxiety in women with IOAB, there­by improving patients' quality of life.

Effect of electroacupuncture combined with tolterodine on treating female mixed urinary incontinence.

PURPOSE: To examine the effectiveness of combination therapy of electroacupuncture and tolterodine in treating female patients with mixed urinary incontinence. MATERIALS AND METHODS: Seventy-one women with mixed urinary incontinence were recruited to receive electroacupuncture therapy or combination therapy with electroacupuncture and tolterodine 2 mg orally twice a day for 8 weeks. In electroacupuncture therapy, the acupoints, including BL32 (Ci Liao), BL35 (Hui Yang), SP6 (San Yin Jiao), and ST36 (Zu San Li), were selected with the stimulation of a low-frequency (20 Hz) disperse-dense wave. The International Consultation on Incontinence Questionnaire score, the number of incontinence episodes, and urine leakage were measured before and after the treatment to evaluate the effect. RESULTS: Response rates were 73.5% and 78.4% in electroacupuncture therapy group and in the combination therapy group respectively. No significant differences were found when group outcomes were compared. The International Consultation on Incontinence Questionnaire score, the number of incontinence episodes, and urine leakage improved significantly (P < .001) after 8 weeks compared with baseline values in both groups. Significantly more patients in the combination therapy group experienced more than 50% reduction in the number of incontinent episodes than in the electroacupuncture group (75.7% vs 58.8%, P < .01). They also had significantly less urine leakage than those in electroacupuncture therapy group (11.2 ± 7.6 g vs 15 ± 9.1 g) (P < .05). CONCLUSIONS: The effect of electroacupuncture for female mixed urinary incontinence may be enhanced by tolterodine.

Combination of foot stimulation and tolterodine treatment eliminates bladder overactivity in cats.

AIMS: To determine whether transcutaneous foot stimulation combined with a lower dose tolterodine would inhibit bladder overactivity more effectively than either treatment alone. METHODS: Cystometrograms were performed on α-chloralose anesthetized cats (N = 6) by infusing 0.25% acetic acid (AA) to induce bladder overactivity. Foot stimulation (5 Hz) was applied at 2 and 4 times the threshold (T) intensity in volts (i.e., 2T or 4T) for inducing toe movement to inhibit bladder overactivity. Cumulative doses of tolterodine (0.003-0.3 mg/kg, i.v.) were also administered to determine the effect of combination treatment. RESULTS: AA irritation of the bladder significantly (P < 0.0001) reduced bladder capacity to 23.6 ± 7.1% of saline control capacity. Foot stimulation alone at 2T and 4T inhibited bladder overactivity and significantly (P < 0.0001) increased bladder capacity to 50.7 ± 6.8% and 79.0 ± 11.6% of saline control, respectively. Tolterodine alone at 0.3 mg/kg significantly (P < 0.05) increased bladder capacity to 65.6 ± 15.5% of saline control. However, when tolterodine at a threshold dose (0.3 mg/kg) was combined with foot stimulation, the bladder capacity was significantly (P < 0.05) increased to 86.2 ± 6.2% and 107.9 ± 10.6% by 2T and 4T stimulation, respectively. Complete inhibition of bladder overactivity could be achieved at a lower tolterodine dose (0.1 mg/kg) when combined with 4T stimulation (97.0 ± 11.2% of saline control). The amplitude of micturition contraction was not changed by tolterodine treatment. CONCLUSIONS: This study suggests a novel, efficacious, non-invasive therapy by combining foot stimulation with a lower dose tolterodine to treat bladder overactivity. It also provides the first objective evidence supporting an additive therapeutic benefit of neuromodulation and antimuscarinic combination treatment.

Effects of percutaneous tibial nerve stimulation on adult patients with overactive bladder syndrome: a systematic review.

AIMS: To assess the effectiveness of percutaneous tibial nerve stimulation (PTNS) on adult patients with overactive bladder syndrome, using a systematic review of randomized controlled trials (RCTs), clinical controlled trials (CCTs), and prospective observational cohort studies. METHODS: A computer-aided literature search was performed in: PubMed, EMBASE and CENTRAL (2000 to November 15, 2011) to identify RCTs, CCTs, and prospective observational cohort studies. The study had to investigate the effect of PTNS on overactive bladder syndrome. The methodological quality of each study was assessed and a qualitative analysis was performed to establish the levels of evidence. RESULTS: Four RCTs and six prospective observational cohort studies were identified. There is strong evidence for the efficacy of PTNS versus a sham treatment. There is limited evidence that the use of PTNS and tolterodine ER is equally effective. No additional effect of a combination of Stoller afferent nerve stimulation (SANS) and anticholinergic medication compared to SANS alone. Most cohort studies suggested decreased frequency and improvement of incontinence and nocturia. However, the level of evidence was insufficient to make any firm conclusions. Because the total duration of all included trials varied between 6 and 12 weeks, so far there is little information on treatment periods. CONCLUSIONS: PTNS is efficacious for frequency and urgency urinary incontinence. More high quality studies are needed to improve the level of evidence concerning the efficacy of PTNS with regard to urgency and nocturia, to specify patient selection criteria, optimal treatment modalities and long-term effects as well as the effectiveness in more pragmatic trials.

In vitro and in vivo pharmacokinetic/pharmacodynamic activity of clofoctol.

The aim of the study was to examine the In vitro susceptibility of clinical isolates of respiratory pathogens to clofoctol compared with amoxicillin and erythromycin, and to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationships of clofoctol using a murine pneumonia infection model. Strains clinically isolated from patients between 2005 and 2009 were used to examine susceptibility: penicillin-susceptible Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, Streptococcus pyogenes, methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and Haemophilus influenzae. The In vitro activity of clofoctol against clinical isolates has essentially remained unchanged over recent years. The MIC50 and MIC90 of clofoctol against penicillin-resistant S. pneumoniae are lower than that of amoxicillin and erythromycin. The area under curve/minimum inhibitory concentration (AUC/MIC) ratio is the PK/PD parameter that best correlates with in vivo clofoctol efficacy; the value of AUC/MIC required to achieve the maximum effect in this study was 75.5.

[Overactive bladder after transurethral resection of prostate treated with electroacupuncture therapy and tolterodine].

OBJECTIVE: To evaluate the therapeutic effect of overactive bladder after transurethral resection of prostate (TURP) preventively treated with electroacupuncture and Tolterodine. METHODS: One hundred and twenty cases of benign prostate hyperplasia of TURP were randomly divided into an electroacupuncture and medicine group, an electroacupuncture group, a medicine group and a control group, 30 cases in each group. All the patients were treated with TURP under the continuous epidural anesthesia, and the catheter was retained for 5-7 days. In electroacupuncture group, before the surgery of the same day, Huiyang (BL 35), Ciliao (BL 32), Qugu (CV 2) and Huiyin (CV 1) were acupunctured with electroacupuncture for 30 min, once a day, 5-7 days' treatment was applied. In medicine group, Tolterodine Tartrate tablet was taken for 2 mg in the morning of surgery day, twice a day and treatment was applied for 5-7 days. In electroacupuncture and medicine group, the comprehensive therapies above in both electroacupuncture group and medicine group were applied. In control group, Pethidine of 50 mg was given by intramuscular injection when bladder was overactive, combined with Anisodamine injection of 10 mg according to the symptoms. The frequency and lasting time of bladder overactivity were compared within 72 hours after TURP in each group. RESULTS: After TURP, the frequency of bladder overactivity were 2-4 times a day, and lasted for 5-15 min each time in control group. The frequency and lasting time of bladder overactivity in treatment groups at different time were less than those in control group (P < 0.01, P < 0.001). There was no significant difference in comparison of frequency and lasting time of bladder overactivity between electroacupuncture and medicine group (all P > 0.05). The frequency and lasting time of bladder hyperactivity in electroacupuncture and medicine group were less than those in the electroacupuncture group and the medicine group at 24 hours, 24-48 hours, 48-72 hours after TUPR (P < 0.05, P < 0.01, P < 0.001). CONCLUSION: After TURP, early prevention of combined therapy of electroacupuncture and Tolterodine with oral administration is superior to that of electroacupuncture therapy or Tolterodine for overactive bladder treatment, and it is the safe and effective method to treat overactive bladder.

[Parkinson's disease combined with overactive bladder syndrome treated with acupuncture and medication].

OBJECTIVE: To evaluate the therapeutic effect of Parkinson's disease combined with overactive bladder syndrome (GAB) treated with combined therapy of oral administration of Tolterodine with low dose and electroacuponcture. METHODS: Sixty cases of Parkinson's disease combined with GAB were randomly divided into a combined acupuncture and medication group (group A) and a medication group (group B), 30 cases in each group. In both groups, Madopar basic doses were same, and anticholinergic agents such as Artane were stopped. In group A, Tolterodine was orally taken for 1 mg, twice a day; Baihui (GV 20), Sishengcong (EX-HN 1) and Yintang (EX-HN 3) were punctured with electroacupuncture, once a day. In group B, Tolterodine was orally taken for 2 mg, twice a day. After 6 weeks, the changes of urination and UPDRS III scores were observed, and the adverse reactions were recorded in both groups. RESULTS: After treatment, the frequency of average urination of 24 hours, frequency of incontinence of 24 hours and average urine volume at a time were obviously improved (all P < 0. 01), of which, the above items in group A were superior to those in group B (all P < 0. 05) the UPDRSIII score in group A was superior to that in group B (P < 0.05). The adverse reactions in group A were less than those in group B. CONCLUSION: The therapeutic effect of Parkinson' s disease combined with GAB treated with combined therapy of Tolterodine with low dose and electroacupuncture is superior to that of complete dose of Tolterodine with oral administration, with less adverse reactions. And it also can improve the motor symptom of Parkinson's disease patients.

Cost-effectiveness of percutaneous tibial nerve stimulation versus extended release tolterodine for overactive bladder.

PURPOSE: We assessed the cost-effectiveness of percutaneous tibial nerve stimulation vs extended release tolterodine for the treatment of overactive bladder. MATERIALS AND METHODS: A 1-year time frame cost-effectiveness model from a societal perspective was developed by comparing medical costs and quality of life determined by improved continence and therapy side effects of percutaneous tibial nerve stimulation and tolterodine ER. Percutaneous tibial nerve stimulation therapy consisted of 12 sessions for 3 months followed by maintenance therapy. Significant side effects of both strategies can result in reduced quality of life or therapy termination. Parameter estimates included utilities of improved urinary incontinence (0.92) and continued urinary incontinence (0.73), reduction in quality of life from side effects (5%), cost of percutaneous tibial nerve stimulation per session ($203) and cost of tolterodine ER per month ($150). Our primary outcome was the incremental cost-effectiveness ratio, defined as the marginal cost per quality adjusted life-years gained. Less than $50,000 per quality adjusted life-year gained was considered cost-effective. The uncertainty of input parameters was addressed by 1-way sensitivity analyses and Monte Carlo simulation to assess the robustness of the model. RESULTS: Percutaneous tibial nerve stimulation added significant cost to the management of overactive bladder with modest improvement in quality of life. For every 100 patients treated with percutaneous tibial nerve stimulation the costs increased by $303,480 and resulted in an additional 4.3 quality adjusted life-years gained compared to tolterodine ER. The incremental cost-effectiveness ratio was $70,754 per quality adjusted life-year gained. In the Monte Carlo analysis percutaneous tibial nerve stimulation was cost-effective only 21% of the time. CONCLUSIONS: Percutaneous tibial nerve stimulation was not cost-effective for treating overactive bladder vs tolterodine ER under a wide range of clinical circumstances.

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.

Comparative study of pelvic floor biofeedback training and tolterodine for treatment of detrusor after-contraction in posturination dribbling in children.

OBJECTIVES: To investigate the prevalence of detrusor after-contraction (DA-C) in children with posturination dribbling, and compare the outcomes of pharmacological treatment and pelvic floor biofeedback training. METHODS: Children with posturination dribbling underwent urodynamic studies. Patients with DA-C were randomly allocated to one of two groups: pelvic floor biofeedback training or 1 mg tolterodine, orally, twice daily. Treatment was continued for 12 weeks. RESULTS: The study included 45 children. DA-C was present in 39 patients (86.6%), 30 (76.9%) of whom also exhibited detrusor overactivity. Pelvic floor biofeedback training resulted in a significantly better response than tolterodine, in terms of reduction in the number of posturination dribbling events in the month after completion of treatment. CONCLUSIONS: DA-C is closely associated with posturination dribbling in children. Pelvic floor biofeedback training should be considered the initial treatment option in these patients.

Electrical stimulation compared with tolterodine for treatment of urge/urge incontinence amongst women--a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: Few randomized controlled trials have compared electrical stimulation treatment with drug therapy. Our hypothesis was that electrical stimulation treatment in women with urgency/urge incontinence would be more efficient compared to drug treatment. METHODS: Women ≥18 years of age with urgency/urge incontinence were randomized to receive either ten electrical stimulation treatments vaginally and transanally over a period of 5-7 weeks or tolterodine 4 mg orally once daily. RESULTS: Sixty-one women completed the study. There was no significant difference between the two treatment groups in micturition rate from baseline to 6 months, mean difference, -0.40 (95% confidence interval (CI), -1.61 to 0.82), but a clearly significant difference within each group for electrical stimulation, -2.8 (95% CI, -3.7 to -1.9), and for tolterodine, -3.2 (95% CI, -4.1 to -2.4). CONCLUSIONS: Both treatments reduced the number of micturitions, but electrical stimulation was not found to be superior to tolterodine.

The outcome of adding peripheral neuromodulation (Stoller afferent neuro-stimulation) to anti-muscarinic therapy in women with severe overactive bladder.

OBJECTIVE: Anti-muscarinic treatment alone and peripheral neuromodulation with concomitant anti-muscarinic treatment were compared in patients with severe overactive bladder. METHODS: In this prospective study, 40 women with severe overactive bladder according to the 7-day voiding diary without any prior treatment completed the Incontinence Impact Questionnaire (IIQ-7) and were randomised into anti-muscarinic-alone and combination treatment groups. Twenty women received daily 4 mgs of tolterodine orally and in 20 women Stoller afferent neuro-stimulation (SANS) therapy was performed concomitantly for 12 weeks to the same anti-muscarinic regimen. After 12 weeks of therapy, two of the patients drop out of the study and remaining patients filled out the IIQ-7 questionnaire and the 7-day voiding diary again. Pretreatment and post-treatment QoL scores and the 7-day voiding diaries were compared. Mann-Whitney U, Wilcoxon and two sided significance tests were used. RESULTS: Thirty-eight women fulfilling the criteria were included in the study. Severity of overactive bladder symptoms decreased significantly in both treatment groups. However, the decrease in combination treatment group was more significant than the anti-muscarinic-alone group. Adverse events were similar between the two groups. CONCLUSION: Combining SANS and anti-muscarinic therapy resulted in significantly better clinical outcomes and IIQ-7 scores as compared with anti-muscarinic treatment alone in patients with severe overactive bladder.

Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial.

PURPOSE: The Overactive Bladder Innovative Therapy trial was a randomized, multicenter, controlled study that compared the effectiveness of percutaneous tibial nerve stimulation to extended-release tolterodine. The reduction in overactive bladder symptoms along with global response assessments was evaluated. MATERIALS AND METHODS: A total of 100 adults with urinary frequency were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or to 4 mg daily extended-release tolterodine. Voiding diaries and an overactive bladder questionnaire were completed at baseline and at the end of therapy to compare 24-hour voiding frequency, urinary urge incontinence episodes, voids causing waking, volume voided, urgency episodes and quality of life indices. Global response assessments were completed by subjects and investigators after 12 weeks of therapy. RESULTS: The global response assessment demonstrated that subject assessment of overactive bladder symptoms compared to baseline was statistically significant in the percutaneous tibial nerve stimulation arm with 79.5% reporting cure or improvement compared to 54.8% of subjects on tolterodine (p = 0.01). Assessments by investigators were similar but did not reach statistical significance (p = 0.05). After 12 weeks of therapy objective measures improved similarly in both groups for reductions in urinary frequency, urge urinary incontinence episodes, urge severity and nighttime voids, as well as for improvement in voided volume. There were no serious adverse events or device malfunctions. CONCLUSIONS: This multicenter, randomized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms, and with objective effectiveness comparable to that of pharmacotherapy. Percutaneous tibial nerve stimulation may be considered a clinically significant alternative therapy for overactive bladder.

Systematic review: randomized, controlled trials of nonsurgical treatments for urinary incontinence in women.

BACKGROUND: Urinary incontinence in women is a common problem that adversely affects quality of life. PURPOSE: To synthesize evidence of management of urinary incontinence in women. DATA SOURCES: MEDLINE, CINAHL, and the Cochrane Library. STUDY SELECTION: 96 randomized, controlled trials (RCTs) and 3 systematic reviews published in English from 1990 through May 2007. DATA EXTRACTION: Using standardized protocols, reviewers abstracted cases of continence, improvement of urinary incontinence, and prevalence of urinary incontinence to calculate risk difference. DATA SYNTHESIS: Compared with regular care, pelvic floor muscle training plus bladder training resolved urinary incontinence (pooled risk difference, 0.13 [95% CI, 0.07 to 0.20]). Pelvic floor muscle training alone resolved or improved urinary incontinence compared with regular care, although the effect size was inconsistent across studies. Different injectable bulking agents and medical devices were associated with similar continence and improvement rates. Electrical stimulation failed to resolve urinary incontinence. Oral hormone administration increased rates of urinary incontinence compared with placebo in most RCTs (1243 women). Transdermal or vaginal estrogen resulted in inconsistent improvement of urinary incontinence. Adrenergic drugs did not resolve or improve urinary incontinence. Oxybutynin or tolterodine resolved urinary incontinence compared with placebo (pooled risk difference, 0.18 [CI, 0.13 to 0.22]). Duloxetine compared with placebo improved (pooled risk difference, 0.11 [CI, 0.07 to 0.14]) but did not resolve urinary incontinence, with no significant dose-response association. LIMITATIONS: Inconsistent measurements of outcomes limited the findings. Predictors of better effect have not been identified in RCTs. CONCLUSION: Moderate levels of evidence suggest that pelvic floor muscle training and bladder training resolved urinary incontinence in women. Anticholinergic drugs resolved urinary incontinence, with similar effects from oxybutynin or tolterodine. Duloxetine improved but did not resolve urinary incontinence. The effects of electrostimulation, medical devices, injectable bulking agents, and local estrogen therapy were inconsistent.

An approach to daytime wetting in children.

Daytime wetting is a common problem with various causes that can usually be identified through a careful history, thorough physical examination, and urinalysis. Conservative approaches to therapy have a successful outcome in most children. Invasive diagnostic imaging studies and pharmacologic or surgical intervention are necessary only for carefully selected children.

The emergence of new drugs for overactive bladder.

Overactive bladder is a common and distressing problem. Standard therapy is directed towards modifying the detrusor motor sensitivity and response via anticholinergic medication. Currently available medications are reviewed and alternative targets for treatment are presented.

Benign prostatic hyperplasia in primary care: what you need to know.

PURPOSE: We reviewed recent literature and treatment guidelines regarding the prevalence, pathophysiology, and management of BPO related to BPH; and management of lower urinary tract symptoms secondary to BPH. MATERIALS AND METHODS: Published literature and current treatment concepts were reviewed regarding the diagnosis and treatment options for BPO. RESULTS: BPH is a histological diagnosis that can contribute to medical problems, including enlargement of the prostate and BPO. These conditions should be treated only if the symptoms are troublesome, there is considerable risk of progression, and/or cancer is suspected. Very effective medical and surgical options are available to treat BPO and improve patient quality of life. CONCLUSIONS: BPO is highly treatable, but should be managed in close collaboration with the patient. Pharmacological agents and minimally invasive procedures, when appropriate, are generally preferred to more invasive surgery. Patients with mild or moderate symptoms usually can be treated by a primary care physician; more complicated cases should be referred to a urologist for evaluation and management.

[Management of neuropathic bladder in multiple sclerosis]. / Management della vescica neurologica nella sclerosi multipla.

It is estimated that almost 70% of patients affected by multiple sclerosis (MS) suffer from urinary symptoms, with devastant impact on Quality of Life (QoL). The major aims of management should be to ameliorate the patients quality of life and to prevent the frequent complications of bladder dysfunction such as infention and renal damage. Therapy can usually eliminate or reduce the symptoms of neuropathic bladder. In the following pages is discussed the complex management of urinary symptoms in MS patients.