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Expression of neural plasticity related gene in the pontine tegmental area of rats with overactive bladder after cerebral infarction.

PURPOSE: We investigated the expression of the neural plasticity related genes c-fos, zif268, c-jun, brain-derived neurotrophic factor and tissue plasminogen activator in the pontine tegmental area in rats with overactive bladder induced by cerebral infarction. MATERIALS AND METHODS: Cerebral infarction was induced by left middle cerebral artery occlusion in female Sprague-Dawley rats. Bladder activity was monitored by continuous infusion cystometrography in awake rats. Specimens were obtained from the pontine tegmental area 1, 3, 5, 12 and 24 hours after cerebral infarction or sham operation. The effect of 0.1 mg./kg. intravenously of the N-methyl-d-aspartate glutamatergic receptor antagonist MK-801 on bladder activity, and c-fos and zif268 expression after middle cerebral artery occlusion were studied. Real-time reverse transcriptase-polymerase chain reaction was performed with the LightCycler system (Roche Diagnostics, Mannheim, Germany) to evaluate cerebral infarction influences on gene expression in the pontine tegmental area. RESULTS: Bladder capacity in cerebral infarcted rats was significantly reduced 1 to 24 hours after middle cerebral artery occlusion compared with that of sham operated rats (p <0.05 to 0.01). One hour after occlusion mean c-fos messenger (m)RNA expression plus or minus standard error had significantly increased to 18.9 +/- 4.0 in terms of its density relative to the outer control in a sample obtained immediately after occlusion compared with that in sham operated rats (p <0.05). It returned to the control level within 3 hours after occlusion. Mean zif268 mRNA expression significantly increased to a relative density of 3.2 +/- 1.4 3 hours after middle cerebral artery occlusion (p <0.01) and returned to the control level within 5 hours after occlusion. The expressions of c-jun, brain-derived neurotrophic factor and tissue plasminogen activator was not influenced by occlusion. Pretreatment with MK-801 inhibited bladder overactivity and significantly reduced the expression of c-fos and zif268 mRNA in the pontine tegmental area. CONCLUSIONS: These results indicate that the development of bladder overactivity after middle cerebral artery occlusion is mediated by activation of an N-methyl-d-aspartate receptor and accompanied by an increase in c-fos and zif268 mRNA expression in the pontine tegmental area.

Animals↗

[Diagnosis of overactive bladder influenced by methods of clinical assessment--micturition diary vs. urodynamics].

INTRODUCTION: Most characteristic symptom of overactive bladder is urgent, possibly painful, desire to void. This complaint is caused by autonomous bladder contractions. The increased activity of detrusor muscle is not only responsible for the urgency but also is the direct reason for the development of urge urinary incontinence. THE AIM OF THE STUDY: The comparison of the subjective (micturition diary) and objective (urodynamic investigation) mode of diagnosis of overactive bladder. MATERIAL AND METHOD: Twenty one women complaining of symptoms of the overactive bladder were included into the study. The infection of lower urinary tract was ruled out based on the results of urinalysis. Each patient reported urinary symptoms (number of urgency episodes and urge urinary leakages) in micturition diary for seven days. Thereafter, all participants underwent the urodynamic investigation that included uroflowmetry and cystometry. RESULTS: Data obtained from micturition diaries proved that all patients had subjective symptoms of overactive bladder (n = 21). However, only 8 subjects met overactive bladder diagnostic criteria on urodynamic investigation. The data obtained from micturition diaries and urodynamics were compared between group with objectively (urodynamic investigation) and subjectively (micturition diary) diagnosed overactive bladder. CONCLUSIONS: 1. There is marked discrepancy between data obtained from micturition diary and the results of urodynamic investigation. 2. It was shown that the diagnosis of overactive bladder cannot be made solely on the basis of maturation diary. 3. Volume of voided urine measured at uroflowmetry and volume of infused fluid causing strong desire to void are best markers of urodynamically proven diagnosis of overactive bladder.

Diagnosis, Differential↗

Central nervous system safety of anticholinergic drugs for the treatment of overactive bladder in the elderly.

BACKGROUND: Overactive bladder (OAB) is characterized by urgency and increased frequency of micturition, with or without urinary urge incontinence. Anticholinergic agents are important in the treatment of OAB. However, concerns have emerged about their central nervous system (CNS) safety and the associated risk of cognitive impairment. OBJECTIVE: This article describes the CNS adverse effects of anticholinergic drugs used for the treatment of OAB, with particular emphasis on their use in the elderly. Its objective is to help physicians make optimal choices when selecting anticholinergic treatment for OAB. METHODS: : Relevant data from the literature were identified primarily through a MEDLINE search of articles published through December 2003. The search terms included overactive bladder, central nervous system, anticholinergic, and antimuscarinic. This was not intended to be a systematic review, and articles were chosen for inclusion based on their pertinence to the focus on treatment of OAB in the elderly. RESULTS: Several anticholinergic drugs are available for the treatment of OAB, including oxybutymn, tolterodine, trospium chloride, and propiverine (not available in the United States). Among the agents reviewed, penetration of the blood-brain barrier (as predicted by lipophilicity, polarity, and molecular size and structure) is highest for oxybutymn, lower for tolterodine, and lowest for trospium chloride; limited data are available for propiverine. The total anticholinergic drug burden may also be important in determining the potential for CNS adverse effects. The spectrum of anticholinergic CNS adverse effects ranges from drowsiness to hallucinations, severe cognitive impairment, and even coma. The immediate-release (IR) and extended-release (ER) formulations of oxybutynin have been associated with cognitive impairment. In the only published clinical trial that was identified, no significant differences in CNS adverse effects were observed between the IR and ER formulations of tolterodine. There were few clinical data on the use of propiverine in patients with OAB. Trospium chloride has shown favorable CNS tolerability in postmarketing surveillance studies. CONCLUSION: When considering treatment choices for patients with OAB, particularly the elderly, the potential CNS adverse effects of each anticholinergic agent must be weighed against the severity of OAB symptoms.

Aged↗

Pharmacologic options for the overactive bladder.

OBJECTIVES: To review the current pharmacologic options for treatment of the overactive bladder and to describe potential therapies on the horizon. METHODS: The literature on the clinical efficacy and safety of the currently available agents is described. RESULTS: According to the guidelines issued by the Agency for Health Care Policy and Research (AHCPR), anticholinergic agents should be the first-line pharmacologic therapy for patients with detrusor instability. Oxybutynin is the anticholinergic of choice for this indication, whereas propantheline is the second-line therapy. Although calcium antagonists have been investigated, the one such drug introduced for the treatment of overactive bladder (terodiline) was withdrawn from the market because of a risk of cardiac arrhythmia. Studies of potassium channel openers have found either a lack of clinical efficacy or an unacceptable level of side effects. Alpha-adrenergic antagonists may be useful for decreasing bladder overactivity in patients who have autonomous bladders as the result of conditions such as spinal cord injury. Tricyclic antidepressants (particularly imipramine) may be effective in decreasing bladder contractility, although the AHCPR guidelines caution that these drugs should be reserved for use in carefully evaluated patients. Future developments in the treatment of detrusor overactivity are likely to occur in 3 categories: drugs that affect peripheral excitatory mechanisms, drugs that inhibit afferent mechanisms, and drugs that affect more central actions at either the ganglionic, spinal cord, or supraspinal level. CONCLUSIONS: Although pharmacologic management of the overactive bladder has progressed little in the past 10 years, the future may hold the promise of more effective therapies.

Antidepressive Agents, Tricyclic↗

Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial.

CONTEXT: Men with overactive bladder and other lower urinary tract symptoms may not respond to monotherapy with antimuscarinic agents or alpha-receptor antagonists. OBJECTIVE: To evaluate the efficacy and safety of tolterodine extended release (ER), tamsulosin, or both in men who met research criteria for both overactive bladder and benign prostatic hyperplasia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted at 95 urology clinics in the United States involving men 40 years or older who had a total International Prostate Symptom Score of 12 or higher and, an International Prostate Symptom Score quality-of-life (QOL) item score of 3 or higher, a self-rated bladder condition of at least moderate bother, and a bladder diary documenting micturition frequency (>or=8 micturitions per 24 hours) and urgency (>or=3 episodes per 24 hours), with or without urgency urinary incontinence. Patients were recruited between November 2004 and February 2006, and the study was completed May 2006. INTERVENTIONS: Patients were randomly assigned to receive placebo (n = 222), 4 mg of tolterodine ER (n = 217), 0.4 mg of tamsulosin (n = 215), or both tolterodine ER plus tamsulosin (n = 225) for 12 weeks. MAIN OUTCOME MEASURES: Patient perception of treatment benefit, bladder diary variables, International Prostate Symptom Scores, and safety and tolerability were assessed. RESULTS: A total of 172 men (80%) receiving tolterodine ER plus tamsulosin reported treatment benefit by week 12 compared with 132 patients (62%) receiving placebo (P<.001), 146 (71%) receiving tamsulosin (P=.06 vs placebo), or 135 (65%) receiving tolterodine ER (P=.48 vs placebo). Patients receiving tolterodine ER plus tamsulosin compared with placebo experienced significant reductions in urgency urinary incontinence (-0.88 vs -0.31, P=.005), urgency episodes without incontinence (-3.33 vs -2.54, P=.03), micturitions per 24 hours (-2.54 vs -1.41, P<.001), and micturitions per night (-0.59 vs -0.39, P.02). Patients receiving tolterodine ER plus tamsulosin demonstrated significant improvements on the total International Prostate Symptom Score (-8.02 vs placebo, -6.19, P=.003) and QOL item (-1.61 vs -1.17, P=.003). All interventions were well tolerated. The incidence of acute urinary retention requiring catheterization was low (tolterodine ER plus tamsulosin, 0.4%; tolterodine ER, 0.5%; tamsulosin, 0%; and placebo, 0%). CONCLUSIONS: These results suggest that treatment with tolterodine ER plus tamsulosin for 12 weeks provides benefit for men with moderate to severe lower urinary tract symptoms including overactive bladder. Clinical Trials Registration clinicaltrials.gov Identifier: NCT00147654.

Adrenergic alpha-Antagonists↗

Effects of bladder training and/or tolterodine in female patients with overactive bladder syndrome: a prospective, randomized study.

We compared the effects of bladder training and/or tolterodine as first line treatment in female patients with overactive bladder (OAB). One hundred and thirty-nine female patients with OAB were randomized to treatment with bladder training (BT), tolterodine (To, 2 mg twice daily) or both (Co) for 12 weeks. Treatment efficacy was measured by micturition diary, urgency scores and patients' subjective assessment of their bladder condition. Mean frequency and nocturia significantly decreased in all treatment groups, declining 25.9% and 56.1%, respectively, in the BT group; 30.2% and 65.4%, respectively, in the To group; and 33.5% and 66.3%, respectively in the Co group (p<0.05 for each). The decrease in frequency was significantly greater in the Co group than in the BT group (p<0.05). Mean urgency score decreased by 44.8%, 62.2% and 60.2% in the BT, To, and Co groups, respectively, and the improvement was significantly greater in the To and Co groups than in the BT group (p<0.05 for each). Although BT, To and their combination were all effective in controlling OAB symptoms, combination therapy was more effective than either method alone. Tolterodine alone may be instituted as a first-line therapy, but may be more effective when combined with bladder training.

Behavior Therapy↗

[Treatment of overactive bladder with sodium chondroitin sulphate].

OBJECTIVE: It is not always possible to clearly differentiate the symptoms of overactive bladder and interstitial cystitis. A prospective randomized study was performed to determine whether instillation of sodium chondroitin sulphate for treatment of interstitial cystitis is also effective in treating overactive bladder. The expected benefit of this therapeutic approach in overactive bladder is based on the assumption that the glycosaminoglycan layer may be damaged in overactive bladder as well. MATERIAL AND METHODS: Patients with chronic overactive bladder were randomized to one of two study groups each including 41 patients. Group A was treated with an anticholinergic agent (tolterodine), group B with sodium chondroitin sulphate (Uropol S). The diagnosis was established on the basis of a gynecologic examination and history, urodynamic testing, introital ultrasound, and cystoscopy. Patients were treated for 12 months. RESULTS: An improvement of symptoms was reported by 15/35 (43 %) of the patients in group A (p = 0.000) as compared with 23/32 (72 %) of the patients in group B. The subjective outcome was corroborated by means of urodynamic testing, number of pads used, voiding frequency, and nycturia (voiding diary). Quality of life increased significantly in both groups in the course of treatment but there was no significant difference between both groups. CONCLUSION: The results of the study presented here suggest that restoring the glycosaminoglycan layer also improves or cures the symptoms in patients with overactive bladder. Patients clearly benefit from instillation of sodium chondroitin sulphate. These results must be confirmed in larger studies before a wider use of this therapeutic option can be recommended.

Cholinergic Antagonists↗

Which anticholinergic drug for overactive bladder symptoms in adults.

BACKGROUND: Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments. OBJECTIVES: To compare the effects of different anticholinergic drugs for overactive bladder symptoms. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised trials register (searched 17 January 2002) and reference lists of relevant articles. A search for full publications of abstracts identified in January 2002 was completed in July 2003. SELECTION CRITERIA: Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook. MAIN RESULTS: Forty nine trials, 39 parallel and 10 cross-over designs were included (11,332 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analysis.Four trials collected quality of life data (the primary outcome measure) using validated measures; none reported useable data. Oxybutynin versus tolterodine: There were no statistically significant differences for patient perceive improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events (RR 0.57, 95% CI 0.43 to 0.75), and less risk of dry mouth (RR 0.60, 95% CI 0.54 to 0.66), with tolterodine. Different doses tolterodine: The usual recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effect of 1 mg, 2 mg and 4 mg doses was similar for leakage episodes and micturitions in 24 hours, with greater risk of dry mouth with 2 and 4 mg doses.Extended versus immediate release preparations of oxybutynin and/or tolterodine: There were no statistically significant differences for cure/improvement, leakage episodes or micturitions in 24 hours, or withdrawals due to adverse events, but there were few data. Overall, extended release preparations had less risk of dry mouth. One extended release preparation versus another: There was less risk of dry mouth with oral extended release tolterodine than oxybutynin (RR 0.75, 95% CI 0.59 to 0.95), but no difference between transdermal oxybutynin and oral extended release tolterodine although some people withdrew due to skin reaction at the trandermal patch site. AUTHORS' CONCLUSIONS: Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth. There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

Adult↗

Prevalence of persistent and de novo overactive bladder symptoms after the tension-free vaginal tape.

OBJECTIVE: The purpose of this study was to assess 1) the proportion of de novo urge incontinence and overactive bladder symptoms after a tension-free vaginal tape (TVT), and 2) the natural history of preoperative urge incontinence and overactive bladder symptoms after a TVT. METHODS: A chart review was performed on all patients who underwent a TVT without concomitant procedures from November 1998 to November 2002. Preoperative and postoperative stress and mixed urinary incontinence symptoms as well as overactive bladder symptoms were assessed subjectively, as was the use of anticholinergics to treat overactive bladder symptoms. Two preoperative and postoperative validated quality-of-life questionnaires, the Incontinence Impact Questionnaire (IIQ-7) and Urinary Distress Inventory (UDI-6), were also compared. RESULTS: Ninety-eight patients were included in the study. Postoperatively, de novo urge incontinence symptoms developed in 9.1%, de novo overactive bladder symptoms developed in 4.3%, and 8.7% started taking anticholinergics for the first time. After a TVT, the urge component resolved in 63.1% of those with preoperative symptoms of mixed incontinence, overactive bladder symptoms resolved in 57.3% of those with preoperative overactive bladder symptoms, and 57.7% of those who used anticholinergics preoperatively no longer needed to do so. There was also a statistically significant improvement in comparing the preoperative and postoperative IIQ-7 and UDI-6 scores. CONCLUSION: The proportion of patients in whom de novo overactive bladder or urge incontinence symptoms developed postoperatively is low, and approximately 57% of patients with preoperative overactive bladder symptoms can expect resolution of these symptoms after a TVT.

Aged↗

RNA synthesis in pons necessary for maintenance of bladder overactivity after cerebral infarction in rat.

PURPOSE: The maintenance of long lasting bladder overactivity caused by cerebral infarction is believed to require transcription in the pontine micturition center. Therefore, we examined the influence of the RNA synthesis inhibitor actinomycin D (Banyu Pharmaceutical Co., Ltd., Tokyo, Japan) on bladder overactivity induced by left middle cerebral artery occlusion. MATERIALS AND METHODS: Rats under halothane anesthesia were injected with actinomycin D or vehicle (mannitol) into the bilateral dorsal pontine tegmentum, followed by middle cerebral artery occlusion. Awake rats were cystometrically examined for 12 hours. The expression of c-fos and zif268 mRNA in the dorsal pontine tegmentum was monitored with real-time polymerase chain reaction. RESULTS: Injection of actinomycin D produced a significant decrease in bladder capacity in sham operated rats but bladder capacity returned to control levels before sham operation within 6 hours. In cerebral infarcted rats pretreated with vehicle bladder capacity was significantly decreased after middle cerebral artery occlusion and it remained consistently below half of pre-occlusion capacity. Actinomycin D blocked the decrease in bladder capacity in cerebral infarcted rats. In actinomycin D treated cerebral infarcted rats bladder capacity gradually recovered and returned to the control level before middle cerebral artery occlusion within 10 hours. Actinomycin D suppressed an increase in c-fos mRNA expression 1 hour after middle cerebral artery occlusion as well as in zif268 3 hours after occlusion. Administering actinomycin D 0.5 or 1 hour after middle cerebral artery occlusion also suppressed bladder overactivity until at least 10 hours after occlusion but injection 3 hours after occlusion did not. CONCLUSIONS: These results indicate that an RNA synthesis inhibitor can prevent a late stage of bladder overactivity. Transcription in the dorsal pontine tegmentum was found to be necessary to maintain the long lasting bladder overactivity caused by cerebral infarction.

Animals↗

Pharmacological management of overactive bladder : a systematic and critical review of published economic evaluations.

Overactive bladder is a common condition, with recent findings estimating the prevalence in adults at about 15%. Symptoms, including urinary urgency, high voiding frequency and urge incontinence, have been shown to decrease patients' quality of life. Given its high prevalence, the economic burden of overactive bladder is also substantial, with a recent estimate placing the annual cost in the US at 9.1 billion US dollars (year 2000 values). The objective of this review is to provide a critical appraisal of published economic evaluations of pharmacological and non-pharmacological treatments for overactive bladder. Published economic evaluations of treatments for overactive bladder have focused entirely on pharmacological treatments -- mainly on the two most commonly used drugs, oxybutynin and tolterodine, each of which is available in immediate- and extended-release formulations. Ten economic evaluations (more than half are cost-effectiveness studies) have been published. Modelling with decision trees or Markov models has been the predominant method. Evaluations comparing drug therapy with no treatment have concluded that drug therapy is cost effective. Analyses comparing the formulations of oxybutynin and tolterodine have produced highly inconsistent results, largely due to the sources of data employed for effectiveness and treatment discontinuation rates. There are no evaluations of drugs relative to non-pharmacological treatment, and there are other significant gaps in the economic evaluations of treatment to date. These include gaps resulting from a lack of reliable data on the performance of these drugs in real-world settings, particularly data on long-term persistence with treatment. A more definitive pharmacoeconomic comparison of oxybutynin and tolterodine formulations, incorporating all available clinical data, and other treatment options would help direct treatment.

Benzhydryl Compounds↗

The validation of the patient perception of bladder condition (PPBC): a single-item global measure for patients with overactive bladder.

OBJECTIVES: The purpose of this study was to evaluate the validity and responsiveness of a global measure for overactive bladder (OAB), the Patient Perception of Bladder Condition (PPBC). METHODS: Post-hoc analyses were conducted on two 12-wk clinical trials for OAB (Study 1: n = 865; Study 2: n = 520). In addition to the PPBC, patients completed two condition-specific health-related quality of life (HRQL) measures, the Overactive Bladder Questionnaire (OAB-q) and King's Health Questionnaire (KHQ), and bladder diaries at baseline and 12 wk. Validity of the PPBC was evaluated through correlations with baseline diaries, OAB-q, and KHQ. The responsiveness of the PPBC was evaluated using correlations and general linear models to assess the degree of association between change in PPBC and change in the diaries, OAB-q, and KHQ. RESULTS: Both samples were primarily women and white with mean ages of 61.0 and 58.8 yr. The majority of patients were incontinent (75.3% and 80.4%) with the greatest proportion of patients indicating that they had "moderate problems" (47.5% and 51.2%) on the PPBC at baseline. Significant correlations were present at baseline and among change scores between the PPBC and the bladder diaries (p < 0.001), OAB-q (p < 0.001), and KHQ (p < 0.01). In both studies, patients with major PPBC improvement had significantly greater reductions in frequency, urgency episodes, incontinence episodes, and Symptom Bother and significantly greater improvements in HRQL than patients with only a minor PPBC improvement. CONCLUSION: The PPBC, a global patient-reported measure of bladder condition, demonstrated good construct validity and responsiveness to change. These findings support the use of the PPBC as a global assessment of bladder condition among patients with OAB.

Female↗

Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.

OBJECTIVES: To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder. PATIENTS AND METHODS: In a multicentre, single-blind study at 51 Scandinavian centres, 505 patients aged >or= 18 years with symptoms of urinary frequency (>or= 8 micturitions/24 h) and urgency, with or without urge incontinence, were randomized to oral treatment with either tolterodine 2 mg twice daily plus simplified BT or tolterodine alone. Changes in voiding diary variables were evaluated after 2, 12 and 24 weeks of treatment. The patients' perceptions of their bladder symptoms and tolerability (adverse events) were also determined. RESULTS: In all, 501 patients (75% women) were evaluable on an intention-to-treat basis (244 on tolterodine + BT and 257 on tolterodine alone). Tolterodine significantly reduced the voiding frequency and increased the volume voided per void at all sample times; these effects were significantly increased by adding BT. At the end of the study the median percentage reduction in voiding frequency was greater with tolterodine + BT than with tolterodine alone (33% vs 25%, P < 0.001), while the median percentage increase in volume voided per void was 31% with tolterodine + BT and 20% with tolterodine alone (P < 0.001). There was a median of 81% fewer incontinence episodes than at baseline with tolterodine alone, which was not significantly different from that with tolterodine + BT (- 87%). The two groups had comparable median percentage reductions in urgency episodes. Some 76% of patients on tolterodine + BT reported an improvement in their bladder symptoms relative to baseline, compared with 71% on tolterodine alone. Tolterodine was well tolerated; the most common adverse event was mild dry mouth. CONCLUSION: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.

Administration, Oral↗

Special considerations of the overactive bladder in children.

The overactive bladder (OAB) in children is defined as both involuntary detrusor contractions and urethral instability. The development of urinary control plays a key role in its incidence and in our understanding of its pathogenesis. It is seen in a number of conditions but by far is most common among patients with dysfunctional voiding. Urinary infection can be both a cause and an effect of OAB. In some instances, vesicoureteral reflux may result from detrusor overactivity because its successful resolution has been shown to depend on abolition of the hyperactivity. Early diagnosis and appropriate treatment can affect upper urinary tract function and drainage and ultimate bladder function. Recognition is noted via a thorough history and careful physical examination. Urodynamic assessment is indicated in neurologically normal children >5 years old and is combined with a voiding cystourethrogram in boys and a radionuclide cystogram in girls who have a history of recurrent urinary infection. Treatment consists of prophylactic use of anticholinergic agents in patients with neurologic dysfunction, as an early adjunctive measure in boys after ablation of posterior urethral valves, and in children with vesicoureteral reflux. The dose must be carefully titrated in children with cerebral palsy to prevent the appearance of elevated residual urine. Behavioral therapy and biofeedback techniques are effective alternatives to anticholinergic agents for children with dysfunctional voiding.

Adolescent↗

Anticholinergic drugs versus placebo for overactive bladder syndrome in adults.

BACKGROUND: Around 16% of adults have symptoms of overactive bladder (urgency with frequency and/or urge incontinence). The prevalence increases with age. Anticholinergic drugs are commonly used to treat this condition. OBJECTIVES: To determine the effects of anticholinergic drugs for the treatment of overactive bladder syndrome. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 14 June 2005) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised trials in adults with overactive bladder syndrome that compared an anticholinergic drug with placebo treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewer authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2005). MAIN RESULTS: Sixty -one trials, 42 with parallel-group designs and 19 crossover trials were included (11,956 adults). Most trials were described as double-blind but were variable in other aspects of quality. The crossover trials did not present data in a way that allowed inclusion in the meta-analysis. Nine medications were tested: darifenacin; emepronium bromide or carrageenate; oxybutynin; propiverine; propantheline; tolterodine; trospium chloride; and solifenacin. One trial included the newer, slow release formulation of tolterodine. At the end of the treatment period, cure or improvement (relative risk (RR) 1.39, 95% CI 1.28 to 1.51), difference in leakage episodes in 24 hours (weighted mean difference (WMD) -0.54; 95% CI -0.67 to -0.41) and difference in number of voids in 24 hours (WMD -0.69; 95% CI -0.84 to -0.54) were statistically significant favouring medication. Statistically significant but modest sized improvements in quality of life scores were reported in recently completed trials. There was three times the rate of dry mouth in the medication group (RR 3.00 95% CI 2.70 to 3.34) but no statistically significant difference in withdrawal (RR 1.11, 95% CI 0.91 to 1.36). Sensitivity analysis, while limited by small numbers of trials, showed little likelihood that the effects were modified by age, sex, diagnosis, or choice of drug. AUTHORS' CONCLUSIONS: The use of anticholinergic drugs by people with overactive bladder syndrome results in statistically significant improvements in symptoms. Recent trials suggest that this is associated with modest improvement in quality of life. Dry mouth is a common side effect of therapy but did not seem to have an effect on the numbers of withdrawals. It is not clear whether any benefits are sustained during long-term treatment or after treatment stops.

Adult↗

Overactive bladder: The importance of new guidance.

Overactive bladder (OAB) affects an estimated 49 million people in Europe, but only a minority receive appropriate treatment. Others are bothered by unacceptable levels of symptoms that severely impair their quality of life and represent a significant financial burden to themselves and to their healthcare providers. Recently updated guidelines from the International Consultation on Incontinence (ICI) and the European Association of Urology (EAU) take account of important new developments in the management of bladder problems in both primary and secondary care. However, local implementation of previous guidance has been variable, with many patients with OAB and other bladder problems failing to gain full benefit from current clinical and scientific understanding of these conditions. The recent expansion of the range of treatments available for OAB and stress urinary incontinence makes it especially important that physicians become aware of the differential diagnosis of these conditions - the questions they need to ask, and the investigations which will help determine the most appropriate course of action.

Algorithms↗

Diagnostic value of intravesical lidocaine for overactive bladder.

PURPOSE: To determine the diagnostic use of intravesical lidocaine, we evaluated its effects on the overactive bladder in patients with brain lesions, spinal lesions, benign prostatic hyperplasia (BPH) and idiopathic overactive bladder. MATERIALS AND METHODS: Cystometry was performed before and 15 minutes after intravesical instillation of 20 ml. 4% lidocaine in 57 patients with an overactive detrusor in the storage phase. RESULTS: The percentage increase in bladder capacity for patients with spinal lesions was 136%, compared to 56%, 29% and 41% for patients with brain lesions, BPH and idiopathic bladder overactivity, respectively (significant difference p <0.01 to 0.05). Of the patients with an increase of 50% or more 55% had brain lesions, 80% spinal lesions, 23% BPH and 31% idiopathic bladder overactivity. The incidence of the disappearance of detrusor contractions in patients with spinal lesions was greater than that in the others. CONCLUSIONS: These results suggest that intravesical instillation of 4% lidocaine is useful for identification of overactive bladder attributable to spinal or other lesions.

Administration, Intravesical↗