Tolterodine ER reduced increased bladder wall thickness in women with overactive bladder. A randomized,placebo‐controlled,double‐blind,parallel group study

Aims

We evaluated the effect of Tolterodine extended release (TER) versus placebo on bladder wall thickness (BWT) using transvaginal ultrasound in women with overactive bladder (OAB).

Materials and Methods

We recruited 79 women with symptoms of OAB with a mean age of 47 years who had a BWT of at least 5 mm and a post‐micturition volume of less than 50 mL at screening. Subjects received TER 4 mg or placebo once daily for the first 12 weeks of the study. For the subsequent 12 weeks, all subjects received TER 4 mg once daily. BWT was measured at screening, weeks 12 and 24. Subjects recorded number of micturitions, incontinence episodes and urgency episodes, and volume voided per micturition at regular intervals during the study.

Results

Treatment with TER for 12 weeks produced a statistically significant decrease from baseline in BWT (mean [SD] = 0.9 [1.4] mm; P < 0.05) that was not evident following treatment with placebo (0.2 [1.6] mm; P = 0.54). However, the treatment difference did not reach statistical significance (LS Mean = ?0.4; 95%CI: ?1.2, 0.3; P = 0.25). After 12 weeks of treatment, subjects who had taken TER showed an improvement in each bladder diary variable compared to placebo‐treated subjects.

Conclusions

TER may have a direct effect on BWT in women with OAB. Larger studies are warranted to further investigate the effect of behavioral interventions and antimuscarinics, such as TER, on BWT in women with OAB and increased BWT.     

The long‐term natural history of overactive bladder symptoms due to idiopathic detrusor overactivity in women

OBJECTIVES

To assess the long‐term natural history of overactive bladder (OAB) symptoms due to idiopathic detrusor overactivity (IDO) in women.

PATIENTS AND METHODS

Original urodynamic traces were reviewed and women who were referred with OAB symptoms and found to have IDO on investigation in our urodynamic unit ≥10 years previously were invited for a repeat urodynamic and symptomatic assessment.

RESULTS

In all, 174 women were identified and invited to participate; 53 had repeat urodynamics, another 32 attended the unit for symptom assessment and a further 23 completed postal questionnaires. There were no significant symptomatic or urodynamic differences between these groups at baseline. Of the 53 who had repeat urodynamics, 46 (88%) had persistent symptomatic IDO.

CONCLUSIONS

OAB symptoms have a significant effect on the quality of life of those affected. OAB symptoms due to IDO in women are persistent, lasting for ≥10 years in 88% of this study population. This information might affect the treatment choices made by patients and their doctors in the management of this condition.     

Urodynamic effects of solifenacin in untreated female patients with symptomatic overactive bladder

Objectives: To investigate the urodynamic effects of solifenacin in untreated female patients with symptomatic overactive bladder (OAB). Methods: A total of 52 untreated female patients with OAB symptoms were given 5 mg solifenacin once daily for 12 weeks. Before and after treatment, the frequency volume chart, overactive bladder symptom score (OABSS), postvoid residual volume, filling cystometry and adverse events were evaluated. Results: After solifenacin treatment, OAB symptoms were improved, voided volume was increased and voiding number was decreased. Bladder capacities at the first sensation of bladder filling, first desire to void and strong desire to void were significantly increased. Intravesical pressure at the first sensation of bladder filling was significantly decreased. Detrusor overactivity (DO) disappeared in five patients. For 28 patients with persisting DO after treatment, bladder capacity at DO was significantly increased. Both groups with and without DO at baseline had significant improvements of OAB symptoms. Conclusions: Solifenacin urodynamically increases bladder capacity in female patients with symptomatic OAB.     

Ultrasound measurement of detrusor wall thickness in healthy adults

AIMS: Measurements of detrusor wall thickness (DWT) are used to diagnose bladder outlet obstruction (BOO). No values of DWT exist in healthy adults so far. These values, however, are necessary to judge DWT in patients with suspected BOO correctly. The aim of this study was to determine DWT in healthy adults and to investigate if bladder filling, gender, age, or body-mass index (BMI) influences DWT. MATERIALS AND METHODS: In 55 healthy adult volunteers between 15 and 40 years of age, DWT was measured at the anterior bladder wall with a 7.5 MHz ultrasound probe and with a full bladder. In nine of those volunteers, an urodynamic investigation was performed additionally during which DWT was measured in steps of 50 ml until 300 ml and in steps of 100 ml until the maximum bladder volume. RESULTS: DWT decreases rapidly during the first 250 ml of bladder filling but, thereafter, remains almost stable until maximal bladder capacity. No statistical difference was found between DWT at 250 ml and DWT at a higher bladder filling. Men had a greater DWT compared to women (1.4 vs. 1.2 mm, P < 0.001). The age and BMI did not have a significant impact on DWT. CONCLUSIONS: DWT remains stable at a bladder filling of 250 ml. At this state of bladder filling, DWT between different groups are comparable. Men have to be evaluated separately from women.     

萘哌地尔联合舍尼亭治疗女性膀胱过度活动症的疗效观察

目的探讨萘哌地尔联合舍尼亭治疗女性膀胱过度活动症的疗效。方法对31例诊断为女性膀胱过度活动症的患者行萘哌地尔加舍尼亭治疗。以自由尿流率的主要参数如最大尿流率（Qmax）、平均尿流率（Qave）、排尿量（VV）和尿道综合征症状评分（FUSS）、生活质量评分（QOL）为主要疗效指标，来观察治疗效果。砖栗治疗前后的尿流率参数值（Qmax、Qave、VV）、FUSS、QOL相比较，差异显著（P〈0．05），总有效率为83．88％。砖论萘哌地尔加舍尼亭联合应用可作为女性膀胱过度活动症的一种有效治疗手段。     

Voiding urgency and detrusor contractility in women with overactive bladders.

AIMS: To check whether the contractility of overactive bladders would be affected by voiding urgency. METHODS: We urodynamically studied 100 women: 20 normal controls (group 1), 60 patients with idiopathic detrusor overactivity (DO), and 20 with neurogenic DO from intracerebral lesions. The idiopathic DO groups 2A (n = 20), 2B (n = 20), and 3 (n = 20) had moderate, severe, and no voiding urgency, respectively. The neurogenic DO group 4 had severe urgency. The delay time of urgent void at cystometry (2 minutes or more or, respectively, less than 2 minutes) defined moderate or severe urgency. Detrusor contractility was defined by the maximum bladder external voiding power (WF(max)). RESULTS: WF(max) was higher in the idiopathic DO patients than in the controls, had the highest values in group 2B, and did not differ significantly between groups 1-4 and 2A-3. CONCLUSIONS: We inferred from our data that idiopathic DO suggests a facilitation of voiding contractions and that such facilitation might be centrally amplified by severe urgency. This amplifying effect would probably be impaired in cases of neurogenic DO from intracerebral lesions.     

经超声逼尿肌厚度测定在可疑膀胱出口梗阻患者中的应用

目的 分析可疑膀胱出口梗阻患者术前逼尿肌厚度,探讨逼尿肌厚度测定对可疑膀胱出口梗阻患者术后疗效的预测作用.方法 对可疑膀胱出口梗阻并行手术治疗的86例患者在行压力流率测定过程中,当膀胱容量为250 ml或灌注量为膀胱最大容量的50%时,应用7.5 MHz高频线纵超声探头行膀胱前壁逼尿肌厚度测定.术后3个月复查,将患者分为疗效显著组与疗效非显著组,比较2组患者年龄、前列腺体积及逼尿肌厚度.结果 疗效显著组(37例)与疗效非显著组(49例)患者年龄及前列腺体积差异无统计学意义(P＞0.05).逼尿肌厚度差异有统计学意义[(2.5±0.3)和(2.2±0.3)mm,P＜0.01].应用受试者工作特性曲线,当逼尿肌厚度≥2.8 mm时,逼尿肌厚度测定作为预测工作特异性和阳性预测值均为100%,而敏感性为19%,阴性预测值为62%.其曲线下面积为0.84±0.04.结论 逼尿肌测定预测可疑膀胱出口梗阻患者术后疗效可靠,但仍需要多中心、大样本的试验进一步确定临界值.

Abstract：

Objective To estimate the application of ultrasound measurement of detrusor wall thickness (DWT) in the assessment of curative effect after operation. Methods Detrusor thickness was measured by linear ultrasound (7. 5 MHz) either at a filling volume of 50% of cystometric capacity or at 250 ml filling in 86 patients, who were diagnosed equivocal BOO, during a pressure-flow study. All patients accepted transurethral resection of the prostate. At 3 months post-surgery, the patients were divided into two groups according to curative effect after operation. The volume of the prostate, age and DWT were compared between the two groups. Results There was no difference in either age or volume of the prostate between the two groups. DWT was significantly higher (P＜0.01) in the more curative effect group (37 cases, DWT 2. 5±0.3 mm) compared to the less curative effect group (49 cases, 2.2±0. 3 mm). As a predictor of curative effect, DWT of 2. 8 mm or greater had a positive predictive value of 100%, a negative predictive value of 62%, specificity of 100% and sensitivity of 19%. Receiver operating characteristic analysis (ROC) revealed that DWT had a high predictive value for curative effect post-surgery with an AUC of 0. 84±0. 04. Conclusions In patients with equivocal BOO, ultrasonographically assessed detrusor thickness may have a predictive value for curative effect post-surgery. However, this cutoff value needs to be validated in a larger study population.     

The potential role of unregulated autonomous bladder micromotions in urinary storage and voiding dysfunction; overactive bladder and detrusor underactivity

The isolated bladder shows autonomous micromotions, which increase with bladder distension, generate sensory nerve activity, and are altered in models of urinary dysfunction. Intravesical pressure resulting from autonomous activity putatively reflects three key variables; the extent of micromotion initiation, distances over which micromotions propagate, and overall bladder tone. In vivo, these variables are subordinate to the efferent drive of the central nervous system. In the micturition cycle storage phase, efferent inhibition keeps autonomous activity generally at a low level, where it may signal ‘state of fullness’, whilst maintaining compliance. In the voiding phase, mass efferent excitation elicits generalised contraction (global motility initiation). In lower urinary tract dysfunction, efferent control of the bladder can be impaired, for example due to peripheral ‘patchy’ denervation. In this case, loss of efferent inhibition may enable unregulated micromotility, and afferent stimulation, predisposing to urinary urgency. If denervation is relatively slight, the detrimental impact on voiding may be low, as the adjacent innervated areas may be able to initiate micromotility synchronous with the efferent nerve drive, so that even denervated areas can contribute to the voiding contraction. This would become increasingly inefficient the more severe the denervation, such that ability of triggered micromotility to propagate sufficiently to engage the denervated areas in voiding declines, so the voiding contraction increasingly develops the characteristics of underactivity. In summary, reduced peripheral coverage by the dual efferent innervation (inhibitory and excitatory) impairs regulation of micromotility initiation and propagation, potentially allowing emergence of overactive bladder and, with progression, detrusor underactivity.     

Measurement of detrusor wall thickness in women with overactive bladder by transvaginal and transabdominal sonography

Introduction and hypothesis  

Women with overactive bladder (OAB) might have a greater detrusor wall thickness (DWT) suggestive of detrusor overactivity (DO).