Treatment of overactive bladder with modified intravesical oxybutynin chloride

Intravesical oxybutynin chloride has been reported to be effective for overactive bladder, although sometimes the efficacy does not last long enough. To improve this deficiency, we report the effects of intravesical oxybutynin chloride with hydroxypropylcellulose (modified intravesical oxybutynin). Modified intravesical oxybutynin (5 mg/10 mL, twice a day) was administered to six overactive bladder patients for more than 1 year (two men and four women; average age, 56.5 years) who did not respond to oral anticholinergic agents and electric stimulation. Cystometography (CMG) was performed before, 2 hours, and 1 week after the start of modified intravesical oxybutynin. In addition, plasma levels of oxybutynin and its active metabolite, N-desethyl-oxybutynin (DEOB), were measured by high-performance liquid chromatography before, 1, 2, and 4 hours after the initial treatment of modified intravesical oxybutynin. CMG studies revealed that two of the six patients did not demonstrate uninhibited contractions 1 week after the treatment and that cystocapacity of before, 2 hours, and 1 week after the initial modified intravesical oxybutynin was 141.8+/-15.3, 210.0+/-35.5, and 305.0+/-21.3 mL, respectively. Plasma levels of oxybutynin and DEOB before, 1, 2, and 4 hours after the first instillation of modified intravesical oxybutynin were oxybutynin; not detected, 8.8+/-2.5, 6.8+/-1.1, 3.0+/- 1.0 ng/ml, and DEOB; not detected, 4.2+/-1.3, 6.4+/-1.7, 5.1+/- 1.4 ng/ml, respectively. No side effects were observed in any of the patients. Modified intravesical oxybutynin is an effective and safe therapy option for overactive bladder patients who do not respond to other treatments such as oral anticholinergic agents and electric stimulation.     

两种灌注方法治疗女性膀胱过度活动症的比较

目的 探讨膀胱灌注辣椒辣素类似物(Besiniferatoxin,RTX)与异搏定膀胱灌注治疗女性膀胱过度活动症(OAB)的临床效果.方法 将60例OAB患者随机分为实验组与对照组,实验组23例用0.5%利多卡因溶液40mL从导尿管注入膀胱,保留30min后全部排出,予以膀胱灌注辣椒辣素类似物(RTX)治疗;对照组23...     

Diagnostic value of the pediatric lower urinary tract symptom score in children with overactive bladder

Purpose

The aims were (1) to assess the pediatric lower urinary tract symptom score (SS) prior to treatment as a means of determining severity of overactive bladder (OAB) and (2) to investigate relationships between SS results and those of standard diagnostic modalities.

Materials and methods

Symptom scores were recorded pre- and 6 months SS for 294 children with OAB unrelated to neurological disorder. Uroflowmetry–electromyography data, total bladder capacity, and a 2-day bladder diary were also recorded, and upper urinary tract deterioration was investigated as indicated. Overactive bladder was treated with standard approaches. No response to treatment was defined as 0–49 % reduction in OAB-related symptoms based on SS results. Non-responders underwent additional evaluations as indicated.

Results

Two hundred forty-one patients (97 %; mean age 9.8 ± 2.8 years; mean follow-up 11 months; range 6–18 months) completed the study. One hundred thirteen (47 %) required ultrasonography (USG), and those with abnormal USG had a significantly higher pre- and 6 months SS (p = 0.016). All non-responders (n = 38; 16 %) underwent urodynamics evaluation, 34 underwent spinal magnetic resonance imaging (MRI), 34 underwent voiding cystourethrography (VCUG), and 34 underwent dimercaptosuccinic acid scanning (DMSA). Non-responders with terminal detrusor hyperactivity had significantly lower SS after therapy (p = 0.09). Non-responders with abnormal MRI had higher pre- and 6 months SS than those with normal MRI. Thirteen (38 %) of the non-responders who required VCUG had vesicoureteral reflux (VUR), and this subgroup had higher pre-treatment SS (p = 0.030). Seven (21 %) of the non-responders who required DMSA had scarring, and all 7 had VUR. The subgroup with scarring had higher pre-treatment SS (p = 0.030).

Conclusion

Pediatric OAB patients with high 6 months SS have a higher incidence of additional upper urinary tract pathology. Those with low pre-treatment SS require fewer laboratory tests and other assessments. The SS tool can reduce the number of urodynamics evaluations, and other tests required to diagnose renal damage in children with OAB.     

碱化利多卡因膀胱灌注治疗储尿期膀胱功能障碍的临床研究

目的 探索储尿期膀胱功能障碍的治疗方法,评估碱化利多卡因膀胱灌注在治疗储尿期膀胱功能障碍的临床疗效与安全性,同时通过测定尿液中神经生长因子(nerve growth factor,NGF)的变化找到该类疾病的生物学标志物,为指导治疗与预后判定提供客观依据.方法 收集60例储尿期膀胱功能障碍病例为研究对象,按病种分4组,每组15例:膀胱过度活动组(A),间质性膀胱炎组(B),氯胺酮相关性膀胱炎组(C),抗癌化学药物灌注引起的相关性膀胱炎组(D).60例均采用麻醉下行膀胱镜检查,术后第1天开始行碱化利多卡因扩张性灌注方法进行治疗,每天3次,疗程5d.评估每组治疗前、后下尿路症状及其相关指标变化(OABSS评分、0'Leary-Sant评分及生活质量评分QOL、尿NGF、尿动力学检查等).结果 60例患者均完成治疗及随访,治疗后1个月每组与其对应组治疗前相比:OABSS评分、0'Leary-Sant评分、生活质量评分(QOL)、尿NGF、尿动力学检查比较差异有统计学意义(P＜0.05).结论 碱化利多卡因膀胱灌注治疗储尿期膀胱功能障碍疗效明显,是一种简单、价廉、有效、安全的治疗方法;尿NGF可以作为储尿期膀胱功能障碍系列疾病的生物学标志物,对指导治疗与预后判定具有巨大、潜在的应用价值.     

Transdermal oxybutynin for overactive bladder

Overactive bladder is commonly treated with oral anticholinergic drugs such as oxybutynin chloride. Although oral anticholinergic agents have been effective in controlling urinary urgency and frequency and in decreasing incontinence episodes, adverse events, particularly dry mouth, often cause patients to discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered transcutaneously, maintaining the efficacy of oral oxybutynin while significantly minimizing the side effects (eg, dry mouth) that may complicate therapy. By avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N-desethyloxybutynin is produced (this compound is deemed responsible for the anticholinergic side effects such as dry mouth). This novel oxybutynin formulation offers patients who have overactive bladder and urge urinary incontinence a well-tolerated option for managing the symptoms of overactive bladder.     

Intravesical therapy for overactive bladder

INTRODUCTION: Despite recent advances in the field of anticholinergic drugs, lack of efficiency and side effects are still the main reasons for discontinuation of treatment. The introduction of botulinum A toxin was a milestone in the treatment of detrusor overactivity. The treatment, however, is invasive, the duration of the treatment effects is limited, and long-term results are not yet available. The following addresses therapeutic alternatives to local treatment of overactive bladder. MATERIALS AND METHODS: A total of 52 patients received intravesical oxybutynin. In 16 patients, capsaicin was instilled in the bladder and 28 patients were treated with EMDA. RESULTS: Intravesical oxybutynin was successful in 86%; the success rate of capsaicin instillation was 47%. EMDA was successful in 78%. Two transient ischemic attacks following EMDA were observed as significant side effects. CONCLUSION: Besides botulinum A toxin, several effective treatment options are available for patients with detrusor overactivity refractory to oral anticholinergic treatment. Therefore, in each individual patient, possible risks and complications of the different treatment options should be considered thoroughly to find the optimal method in each case.     

膀胱过度活动症的治疗新进展

膀胱过度活动症(OAB)在不同年龄人群均常见,尤其是老年人。其对患者生活质量影响明显。由于病因不明,改善OAB症状的传统治疗虽有一定效果,但仍局限于部分人群。近来一些新疗法逐渐进入临床,例如肉毒碱A注射、超强辣素、β3受体激动剂和骶神经调节等。本文对这些治疗方法的新进展进行介绍。     

Tolterodine for treatment of overactive bladder

Tolterodine was developed as an antimuscarinic agent specifically for the treatment of overactive bladder. Initial in vivo studies demonstrated a functional selectivity for the muscarinic receptors in the urinary bladder over the salivary glands, and subsequent clinical trials showed an overall superior tolerability profile compared with other drugs in the same class (ie, oxybutynin). With immediate- and extended-release formulations and sustained clinical efficacy during long-term treatment, tolterodine gas become an important treatment option for the symptoms of overactive bladder.     

The value of synchro-cystourethrometry for evaluating the relationship between urethral instability and overactive bladder

Purpose

To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children.

Methods

We retrospectively investigated 126 children with OAB and 36 children without OAB using synchro-cystourethrometry. The prevalence of detrusor overactivity (DO) and URI, and the diagnostic sensitivity of DO alone and DO combined with URI, was compared. The OAB children with URI voluntarily received transcutaneous electrical pudendal nerve stimulation with anisodamine (stimulation group, SG) or anisodamine alone (non-stimulation group, NSG). The effectiveness of treatment was evaluated. Average voided volume (AVV), maximum voided volume (MVV), and number of voids per day (NV) were collected and analyzed.

Results

In OAB children, the prevalence of DO and URI was 51.6 and 32.5%, respectively. The prevalence of URI was 5.6% in controls. The prevalence of URI was significantly higher in OAB children. The diagnostic sensitivity and Youden index of DO combined with URI were higher than DO alone. In SG, 45.7% of children were cured, with a ≥ 50% improvement rate of 82.9%, while no child was cured, with a ≥ 50% improvement rate of 36.8% in NSG. A significant increase in AVV and MVV together, with a decrease in NV, was seen in SG. There was a significant difference in visual analogue scale values between SG and NSG (P < 0.01).

Conclusions

Urethral instability plays an essential role in the pathogenesis and progression of OAB in children. Synchro-cystourethrometry is a useful urodynamic technology to precisely diagnose OAB, and transcutaneous electrical pudendal nerve stimulation may be an effective treatment for OAB children induced by URI.

     

Muscarinic receptor antagonists for overactive bladder

Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency urinary incontinence, usually with frequency and nocturia. OAB symptoms are often associated with detrusor overactivity (DO). Like OAB symptoms, the prevalence of DO increases with age and can have a neurogenic and/or myogenic aetiology. Bladder outlet obstruction can be a contributing factor in DO, possibly through cholinergic denervation of the detrusor and supersensitivity of muscarinic receptors to acetylcholine, although the prevalence of OAB is similar in men and women across age groups. Acetylcholine is the primary contractile neurotransmitter in the human detrusor, and antimuscarinics exert their effects on OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M(2) and M(3) on detrusor smooth muscle cells and other structures within the bladder wall. Worldwide, there are six antimuscarinic drugs currently marketed for the treatment of OAB: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin. Each has demonstrated efficacy for the treatment of OAB symptoms, but their pharmacokinetic and adverse event profiles differ somewhat due to structural differences (tertiary vs quaternary amines), muscarinic receptor subtype selectivities, and organ selectivities. Antimuscarinics are generally well tolerated, even in special populations (e.g. men with bladder outlet obstruction, elderly patients, children). The most frequently reported adverse events in clinical studies of antimuscarinics are dry mouth, constipation, headache, and blurred vision; few patients withdraw from clinical trials because of adverse events. Development of an antimuscarinic with functional selectivity for the bladder would reduce the occurrence of antimuscarinic adverse events. The therapeutic potential of several other agents, such as alpha(3)-adrenoceptor agonists, purinergic receptor antagonists, phosphodiesterase inhibitors, neurokinin-1 receptor antagonists, opioids, and Rho-kinase inhibitors, is also under investigation for the treatment of OAB.     

The role of intravesical prostatic protrusion in the evaluation of overactive bladder in male patients with LUTS

Purpose

To evaluate the association of intravesical prostatic protrusion (IPP) and overactive bladder (OAB) in male patients with lower urinary tract symptoms (LUTS). IPP has been suggested to correlate with storage symptoms in addition to bladder outlet obstruction.

Methods

This was an open-labeled, single-center, prospective study involving 128 men older than 40 years presenting with LUTS. We analyzed the relationship of IPP with age, prostate volume, uroflowmetry, post-void residual urine volume (PVR), International Prostate Symptom Score (IPSS), urgency severity scale (USS), and OAB symptom score (OABSS). The patients with an urgency score of?≥?2 (OABSS question 2) and sum score of?≥?3 were considered to have OAB. IPP was measured in the mid-sagittal section using transrectal ultrasound. The degree of IPP was classified as grade 1 (≤?5 mm), grade 2 (>?5–10 mm), and grade 3 (>?10 mm).

Results

The mean age of the patients was 64.9?±?9.2 years, and 101 patients were diagnosed with OAB (79%). Mean IPPs were 2.4?±?1.4 mm (grade 1, n?=?77), 7.6?±?1.4 mm (grade 2, n?=?27), and 14.8?±?4.4 mm (grade 3, n?=?24). IPP was positively correlated with age, prostate size, PSA, PVR, and OABSS nocturia subscore, but not correlated with the presence or severity of OAB. Areas under the receiver-operating characteristic (ROC) curves for the diagnosis of OAB were 0.807 and 0.604 for IPSS-storage subscore and IPP, respectively.

Conclusion

IPP is not a good predictor of OAB in men presenting with LUTS. However, grade 3 IPP indicates higher frequency of nocturia.

     

Pathophysiology of overactive bladder

Overactive bladder (OAB) is a common disorder that negatively affects the quality of life of our patients and carries a large socioeconomic burden. According to the International Continence Society, it is characterized as urinary urgency, with or without urge incontinence, usually, with frequency and nocturia in the absence of causative infection. The pathophysiology of this disease entity varies between neurogenic, myogenic, or idiopathic factors. This paper provides a review of the contemporary theories behind the pathophysiology of OAB.     

Preferences for antimuscarinic therapy for overactive bladder

Study Type – Preference (discrete choice experiment) Level of Evidence 2a What’s known on the subject? and What does the study add? Whilst antimuscarinic treatments are widely used little work has been done to understand how patients consider the relative benefits and costs associated with their use. This study provides data which demonstrates both the perceived value of symptom reduction and burden associated with common antimuscarinic AEs. These findings may prove useful in informing prescribing decisions. OBJECTIVE ? To examine patient preferences and strength of preferences for treatment for the various symptoms of overactive bladder and adverse events associated with the use of antimuscarinic treatments. PATIENTS AND METHODS ? A discrete choice experiment (DCE) survey was developed that detailed treatment choices in terms of attributes relating to their efficacy in reducing symptoms and the likelihood of experiencing typical adverse events. Levels for each attribute were based on a literature review, qualitative interviews and a meta‐analysis of clinical trial data. ? Attributes were combined into choice sets using a fractional orthogonal design that had been folded over. Pairs of choice sets were presented to overactive bladder (OAB) patients (n= 332), who indicated which treatment alternative they preferred. Data were analysed using the conditional logit model. RESULTS ? Participants expressed the strongest preference for the avoidance of urgency incontinence episodes, followed by preference for a reduction in the experience of urinary urgency and the number of micturition episodes. The influence of the likelihood of experiencing an adverse event on treatment preference was also estimated. ? Finally, marginal rates of substitution were calculated to demonstrate the relative value of trade‐offs between the various attributes. ? Treatment preferences were found to be broadly similar across two patient age groups (i.e. under 45 s and 45 and over). CONCLUSION ? The study demonstrates that individuals with OAB place significant emphasis on the prospect of reduction in symptoms. Avoidance of incontinence episodes is particularly valued and equivalent to a much greater reduction in the frequency of micturition or experience of urgency. However, even a modest increase in the likelihood of experiencing an adverse event could easily motivate a change in treatment preference.     

Algorithms for the management of overactive bladder

Overactive bladder (OAB) is a highly prevalent and bothersome condition that hampers quality of life in men and women. Increased awareness of available treatment has led growing numbers of patients to seek medical attention in search of relief. Clinical algorithms for the management of OAB would enable physicians who treat these patients to deliver up-to-date, effective care in an expeditious fashion. An algorithmic approach to OAB should allow most patients to receive therapy without the need for an extended evaluation. Patients who fail initial management or have more complicated clinical scenarios should have treatment directed by specialists who can precisely determine the nature of vesicourethral dysfunction underlying their symptoms. This article presents algorithms for the management of OAB in women, men, and patients with neurologic disease.     

Biomarkers in overactive bladder

A biomarker is an indicator of a particular disease. It is generally used to define the presence (diagnostic biomarker), severity, progression (prognostic biomarker) of a condition and/or its response to a specific treatment (predictive biomarker). Biomarkers can be specific cells, enzymes, hormones, genes or gene products, which can be detected and measured in parts of the body such as blood, urine or tissue. Therefore, biomarkers have been suggested to play an important role in both the clinical assessment and the management of patients, as well as in the research setting. Recently, interest has gathered in urinary biomarkers as a tool to assess overactive bladder (OAB), potentially playing a role in the diagnosis, disease progression and monitoring response to treatment. Urinary biomarkers identified so far include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), prostaglandins, cytokines and C-reactive protein. The aim of this review was to review the published literature on biomarkers in OAB. A literature review using Pub Med, clinicaltrials.gov and the controlled trials online registries was performed from 1970 up to June 2012. The search keywords were: the International Continence Society (ICS) definition of "OAB", “nerve growth fac- tor” (NGF), “brain derived growth factor” (BDNF), “prostaglandins,” “cytokines,” “genetic biomarkers” and “C reactive protein”. The results were limited for fully published English-language articles. The search was then subsequently expanded to include urinary biomarkers in interstitial cystitis and bladder pain where relevant. Each of the studies/articles was reviewed, interpreted and discussed to consider the role of urinary biomarkers in OAB. Using the search criteria, a total of 20 studies (animal and human) that investigated the role of urinary biomarkers in OAB were identified. Full text versions of these articles were obtained and reviewed. Studies on NGF suggested that urinary levels were higher in OAB patients and decreased with antimuscarinic and botulinum toxin treatment. BDNF studies have demonstrated raised levels in OAB and also increased levels in situations of acute bladder inflammation. The role of urinary prostaglandins, cytokines and CRP does not appear to be specific to the OAB disease process according to the current available evidence. Based on the evidence so far NGF and BDNF appear to be the most promising biomarkers in OAB. Although still in their infancy these neurotrophic factors could potentially diagnose OAB, replacing urodynamics and aiding in monitoring disease progression and response to treatment in addition to clinical symptoms.