The wet patient: understanding patients with overactive bladder and incontinence

Overactive bladder (OAB) is a constellation of lower urinary tract symptoms, including urinary frequency and urgency,which can occur with or without urinary incontinence. Incontinence is present in over half of female patients with OAB. This condition affects more than 33 million Americans and imposes considerable economic, social, and psychological burdens. Although continued improvements in the pharmacologic management of lower urinary tract disorders have led to the availability of well-tolerated, characteristic features, prevalence and epidemiology, effective treatment options, the symptoms of OAB are generally underreported by patients and under treated by healthcare professionals. Heightened awareness of the multifaceted disease burden imposed by OAB and increased understanding of the characteristics of patients who are likely to be most severely affected, in particular those who suffer from incontinence, may improve the timely identification, diagnosis, and clinical management of the syndrome, enhancing both the health and quality of life of these patients. This review will summarize the clinical consequences, and management of OAB, with particular focus on the incontinent patient.     

曲司氯铵——治疗伴有急迫性尿失禁症状的膀胱过度活动症的新药

曲司氯铵为新近上市的用于治疗伴有急迫性尿失禁症状的膀胱过度活动症的抗胆碱药物,具有抗胆碱能神经末梢M_1,M_2,M_3受体的作用,从而拮抗乙酰胆碱对人膀胱平滑肌的收缩效应。可有效降低膀胱平滑肌的紧张度、解除痉挛状态,显著增加最大膀胱容量、第1次逼尿肌收缩时膀胱容量,提高膀胱顺应性,降低最大逼尿肌压力,有效减轻尿频、尿急以及尿失禁症状。临床效能与奥昔布宁相当,而优于托特罗定。本品起效快、长期疗效优良,此外,本品仅具有抗胆碱药物的外周常见不良反应,如口干、便秘等,但不进入中枢神经系统,没有中枢神经系统毒性。本文对其药理学及临床研究进行综述。     

Clinical outcomes of intravesical injections of botulinum toxin type A in patients with refractory idiopathic overactive bladder

Background

The aim of the study was to estimated the clinical efficacy of intravesical injections of botulinum toxin type A (BTX-A) in refractory idiopathic overactive bladder (OAB) in the aspect of the quality of life. The potential mechanism of BTX-A actions were described.

Effects of tolterodine ER on patient-reported outcomes in sexually active women with overactive bladder and urgency urinary incontinence

ABSTRACT

Objective: To assess the effects of tolterodine extended release (ER) on patient-reported outcomes (PROs) in sexually active women with overactive bladder (OAB) and urgency urinary incontinence (UUI).

Research design and methods: This multicenter, double-blind, placebo controlled trial included 411 women aged?≥18 years reporting OAB symptoms for ≥3 months; ≥8 micturitions per 24 hours (including ≥0.6 UUI episodes and ≥3 OAB micturitions) in 5-day bladder diaries at baseline, and being in a sexually active relationship for ≥6 months. Subjects randomized to placebo or tolterodine ER completed validated OAB- or incontinence-specific questionnaires, including the Patient Perception of Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), Urgency Perception Scale (UPS), and the Incontinence Impact Questionnaire (IIQ) at baseline and week 12, as well as the Perception of Treatment Benefit and Treatment Satisfaction questions at week 12. This study is registered with ClinicalTrials.gov (identifier: NCT00143481)

Results: The mean age of enrolled women was approximately 48 years. Compared with placebo, the tolterodine ER group reported significant baseline to week 12 improvements in PPBC responses (p?=?0.0048); OAB-q Symptom Bother, total Health-Related Quality of Life (HRQL), and HRQL domain scores (all p?<?0.05); IIQ Emotional Health domain scores (p?<?0.05); proportions of subjects reporting treatment benefit (79 vs. 54%; p?<?0.0001) and satisfaction (78 vs. 59%; p?<?0.0001). Improvements on the UPS were not significantly different.

Conclusions: Tolterodine ER treatment was associated with improvements in multiple OAB- and incontinence-specific PROs in a sexually active, relatively young, and racially diverse population of women. The findings provide clinicians with new insights into the impact of OAB and its treatment on HRQL in this population, which has been underrepresented in previous OAB studies. Study limitations include a potential underestimation of the impact of OAB symptoms resulting from the exclusion of women who may not be sexually active because of their urinary symptoms.

Trial registration: ClinicalTrials.gov identifier: NCT00143481.     

Solifenacin treatment for overactive bladder in black patients: patient-reported symptom bother and health-related quality of life outcomes*

ABSTRACT

Objective: Health-related quality of life (HRQoL) data for black patients receiving overactive bladder (OAB) treatment have not been previously reported. This study presents patient-reported outcomes, measured by symptom bother and HRQoL, in black patients participating in an open-label study of solifenacin succinate. Results are presented, as are those from the full study population.

Methods: In the 12-week, VESIcare Open-Label Trial (VOLT), patients received solifenacin 5?mg or 10?mg once daily according to an individualized, flexible-dosing regimen. A post-hoc analysis assessed solifenacin efficacy and safety in blacks (n = 274). Three patient-derived indices served as study endpoints. The Patient Perception of Bladder Condition (PPBC) scale assessed overall symptom bother, a visual analog scale (VAS) recorded individual symptom bother, the Overactive Bladder Questionnaire (OAB-q) measured OAB-related HRQoL.

Results: Blacks reported significant reductions in bladder-related problems based on PPBC scores (?p < 0.001) and improvements in all OAB-q subscales (symptom severity, coping, concern, sleep, social, and HRQoL; p < 0.001). Based on VAS ratings, significant improvements were reported for urinary urgency, urge incontinence, frequency, and nocturia (?p < 0.001 for change from baseline). Although this study was not placebo-controlled and statistical comparisons were not made, results were similar in the full study population. In total, 46% of black patients experienced adverse events (mostly anticholinergic) and 7.6% discontinued treatment as a result.

Conclusions: Solifenacin treatment was perceived as offering relief from symptom bother and improving HRQoL in the black cohort from VOLT. These results are similar to those in the full VOLT population.     

女性尿失禁对生活质量影响的调查

目的了解尿失禁对生活质量的影响。方法问卷调查福州市某社区女性，回收应用SPSS10．0和SAS6．12统计分析尿失禁患者与非尿失禁人群生活质量的差异，不同程度尿失禁患者生活质量之间的差异以及各类型尿失禁对生活质量影响的不同。结果即使轻度尿失禁也影响患者的日常生活(对压力性、急迫性和混合性尿失禁，P均为0．000)，给患者带来生活的不适且疾病越严重对生活质量的影响越重。尿失禁主要影响患者的行为、心理以及社会的交往。在不同类型的尿失禁中，混合性尿失禁对患者生活质量影响最重。结论尿失禁是一种影响患者生活质量的疾患。     

Characteristics of antimuscarinic responders versus suboptimal responders in a randomized clinical trial of patients with overactive bladder symptoms

Objective: To assess the characteristics of tolterodine extended-release (ER) 4?mg responders and suboptimal responders (≤50% decrease in UUI episodes/24?h) among patients with overactive bladder (OAB), including urgency urinary incontinence (UUI), and identify predictors of a >50% UUI response with fesoterodine 8?mg in tolterodine suboptimal responders.

Methods: Adult patients with OAB symptoms for ≥6 months and ≥8 micturitions, and ≥2 and <15 UUI episodes/24?h at week ?2 received open-label tolterodine ER 4?mg during a 2 week run-in. Suboptimal responders after tolterodine treatment (week 0) were randomized to fesoterodine (4?mg for 1 week, 8?mg for weeks 2–12) or placebo once daily. Post-hoc analyses compared the percentage change from week ?2 to week 0 in UUI episodes/24?h in tolterodine responders versus suboptimal responders and identified significant predictors of a UUI response at week 12 with fesoterodine 8?mg among tolterodine suboptimal responders.

Results: Of 897 patients, 610 (68%) were UUI suboptimal responders during the run-in period. UUI episodes/24?h at week ?2 were similar in tolterodine responders and suboptimal responders (4.2 vs. 4.3), but responders showed a significantly greater median percentage decrease in UUI episodes/24?h after tolterodine treatment at week 0 (80.0% versus 15.3%; p?p?=?.0027). Fesoterodine (vs. placebo), no previous antimuscarinic use before tolterodine run-in, and less UUI severity at baseline were significant predictors of a UUI response.

Conclusions: For patients with OAB, including UUI, who were treated initially with tolterodine and showed a suboptimal UUI response, nearly 70% demonstrated a UUI response with second-line fesoterodine 8?mg. No antimuscarinic use before tolterodine and fewer baseline UUI episodes were significant predictors of a UUI response with fesoterodine.     

Oxybutynin for treatment of urge urinary incontinence and overactive bladder: an updated review

Urge urinary incontinence (UUI) and overactive bladder are common conditions often associated with profound impairment of the health and quality of life of the patient. Antimuscarinic medications have been the mainstay of treatment for these disorders. Oxybutynin hydrochloride, one of the most widely used antimuscarinic agents, has attracted considerable interest from both clinicians and pharmacologists over the last three decades. Although efficacy of this drug has been proven to be high, its use is limited by antimuscarinic adverse effects, possibly related to its active metabolite N-desethyloxybutynin (N-DEO). The extended-release form of oxybutynin uses a push-pull osmotic release system which has significantly improved its tolerability and safety profile. A transdermal transport system has also been developed, bypassing the first-pass metabolism in the liver and gut. This system is associated with significant reduction in the production of the primary metabolite and additional improvement in the tolerability profile of the drug. Intravesical instillation of oxybutynin has been reported although the efficacy and safety of this delivery system has yet to be determined. This article comprehensively reviews the contemporary literature on the pharmacology, clinical efficacy and adverse reactions of oxybutynin in its various delivery forms, and compares them to other frequently used medications for UUI and overactive bladder.     

托特罗定联合氟哌噻吨美利曲辛治疗膀胱过度活动症临床观察

目的 探讨托特罗定联合氟哌噻吨美利曲辛治疗女性膀胱过度活动症（OAB）的临床疗效及安全性.方法 选择确诊为女性膀胱过度活动症患者84例,采用随机数字表法分为观察组和对照组各42例.观察组42例采用托特罗定联合氟哌噻吨美利曲辛治疗,对照组42例单用托特罗定治疗,4周后记录并比较两组临床疗效.结果 观察组总有效率明显优于对照组（95.24％比76.19％,x2=6.291,P＜0.05）;两组平均24h排尿次数、平均24 h尿失禁次数、初始尿意容量及最大膀胱压容量差异均有统计学意义（均P＜0.05）.结论 托特罗定联合氟哌噻吨美利曲辛治疗女性膀胱过度活动症具有疗程短、疗效高、不良反应少等优点.     

Onset of efficacy of tolterodine extended release in patients with overactive bladder*

ABSTRACT

Objective: To assess the onset of efficacy of tolterodine extended release (ER) in patients with overactive bladder (OAB).

Research design and methods: A post hoc analysis was conducted using 3-day bladder diary data from a 12?week, multicenter, prospective, open-label study of tolterodine ER (4?mg qd) in patients (aged ≥ 18 years) with urinary frequency (≥ 8 micturitions/24?h) and urgency (strong and sudden desire to urinate) with or without urgency urinary incontinence (UUI).

Main outcome measures: Changes in micturition frequency, urgency, and UUI episodes/24?h were evaluated for treatment Days 5, 6, and 7. The percentages of patients who achieved normal micturition frequency (< 8/day) and 50%, 70%, 90%, and 100% reductions in urgency and UUI episodes (i.e., responders) were determined at Days 5, 6, and 7. Week 12 data are presented as a referent for the magnitude of treatment efficacy during Week 1.

Results: This analysis included 698 patients. On Day 5, there were significant reductions in all three diary variables (all p < 0.0001), and improvements continued on Days 6 and 7. More than half of the patients reported ≥ 50% reductions in urgency or UUI episodes on Day 5. Responder rates for all three symptoms increased through Week 12.

Conclusions: Patients with OAB experienced significant reductions in OAB symptoms as early as Day 5 of treatment with tolterodine ER. These data extend the findings of a previous analysis, in which all 3 days of the bladder diary were pooled, that demonstrated improvements in micturition frequency, urgency episodes, and UUI episodes in patients with OAB after 1 week of treatment with tolterodine ER. Limitations are that efficacy was not assessed before Day 5, this was a post hoc analysis, and the study was not placebo-controlled.     

Overactive bladder in women: symptom impact and treatment expectations

ABSTRACT

Objective: The objectives of this survey were to understand (1) the effects of overactive bladder (OAB) and urinary incontinence (UI) on women's lives and to understand (2) women's needs and expectations of health care providers and treatment related to these disorders.

Methods: Women (N = 1046) with self-reported symptoms of UI completed a survey via electronic mail about the impact of urinary symptoms, health care provider interactions, treatment practices and expectations, and co-morbid conditions.

Results: The majority of women rated urinary symptoms such as frequency (61%), urgency (80%), nocturia (72%), and UI (69%–88% by type of incontinence) as moderately or extremely bothersome. Over half of women with UI (55%) had not sought medical treatment, but instead used a variety of non-medical coping mechanisms for symptom management. More than one third of women (37%) would prefer that their health care provider initiate discussion about urinary symptoms. Approximately half of the women with UI in this survey desired a greater than 70% reduction in incontinence episodes in order to consider treatment effective.

Conclusion: Women are making an effort to cope with disruptive symptoms of OAB. However, a communication gap between health care providers and patients with urinary symptoms may be a barrier to appropriate medical therapy. Health care providers should routinely query patients about urinary symptoms. In addition to choosing a medical treatment that can produce a meaningful reduction in symptoms, health care providers should set expectations for patients and monitor patient satisfaction with the prescribed treatment regimen.     

Effects of tolterodine extended release on patient perception of bladder condition and overactive bladder symptoms

ABSTRACT

Objective: To evaluate the efficacy of tolterodine extended release (ER) versus placebo at 1 and 12 weeks using questionnaires and diary measures.

Research design and methods: Subjects with overactive bladder (OAB) were randomized to receive tolterodine ER (4 mg) or placebo for 12 weeks. This double-blind study is registered with ClinicalTrials.gov (identifier: NCT00143377).

Main outcome measures: Subjects completed the Patient Perception of Bladder Condition (PPBC) and 3-day bladder diaries at baseline and weeks 1 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. PPBC score changes were analyzed using 2-category (improvement, no improvement), 3-category (improvement, no change, deterioration), and 4-category (≥2-point improvement, 1-point improvement, no change, deterioration) stratifications. Categorical change in PPBC scores from baseline to week 12 was the primary endpoint.

Results: A total of 617 subjects were randomized (tolterodine ER, n = 410; placebo, n = 207). At week 1, a significantly higher percentage of subjects receiving tolterodine ER reported improvement on the PPBC compared with placebo (p < 0.05). Subjects receiving tolterodine ER also had a significantly greater reduction in all OAB symptoms versus placebo (all p < 0.05). At week 12, a higher percentage of tolterodine ER subjects reported PPBC improvement versus placebo subjects. This was significant in the 3- and 4-category analyses (both p < 0.05) but not in the 2-category analysis (the prespecified method of analysis; p = 0.098). Compared with the placebo group, the tolterodine ER group reported significantly greater week 12 improvements in all bladder diary variables (all p < 0.01) as well as in OAB-q Symptom Bother, total Health-Related Quality of Life, Coping, and Concern scores (all p ≤ 0.02).

Conclusions: Compared with placebo, subjects receiving tolterodine ER reported significantly greater improvements in nondiary patient-reported outcomes and OAB symptoms at week 12. Improvements in subjects’ perception of their bladder-related problems and in OAB symptoms were observed as early as week 1. Further research is required to assess which aspects of subjects’ bladder-related problems were improved. A large placebo effect may have prevented the prespecified 2-category analysis of PPBC improvement from reaching statistical significance at week 12, which was the primary endpoint.     

Long-term safety,tolerability, and efficacy of fesoterodine treatment in men and women with overactive bladder symptoms

Abstract

Objective:

To evaluate long-term safety, tolerability, and efficacy of fesoterodine for men and women with overactive bladder (OAB) symptoms.     

罗西维林片联合缩泉胶囊治疗膀胱过度活动症的临床观察

目的 探讨罗西维林片联合缩泉胶囊治疗膀胱过度活动症（OAB）的临床疗效及安全性.方法 收集2011年10月至2013年10月期间OAB患者126例,采用完全随机方法将患者分为4组：A组（34例,缩泉胶囊1.8g,3次/d＋罗西维林片10 mg,3次/d）,B组（32例,罗西维林片10 mg,3次/d）,C组（32例,缩泉胶囊1.8g,3次/d）,D组（28例,仅给予膀胱训练指导）,疗程均为4周.所有患者都给予膀胱训练指导.观察各组治疗前后的主观指标膀胱过度活动症症状评分（OABSS）及客观指标24 h排尿次数、尿急次数、尿失禁次数、夜尿次数、每次排尿量的变化,评估治疗后患者OAB症状的改善情况及安全性.结果 治疗前后OABSS评分、24 h排尿次数、尿急次数、夜尿次数、尿失禁次数、平均每次排尿量A组分别为（9.5±2.1）和（2.4±1.0）分,（13.6±3.8）和（7.2±1.3）次,（7.7±2.7）和（2.4±1.2）次,（4.1±2.1）和（1.0±0.3）次,（3.5±1.4）和（0.8±0.3）次,（124±28）和（280±36） ml;B组分别为（9.7±1.8）和（5.4±1.9）分,（13.9±3.6）和（8.8±1.4）次,（7.6±2.5）和（4.4±1.4）次,（4.2±1.8）和（1.8±0.4）次,（3.6±1.3）和（1.6±0.4）次,（122±29）和（210±38） ml;C组分别为（9.6±2.0）和（5.3±1.8）分,（13.8±3.7）和（8.7±1.2）次,（7.7±2.4）和（4.3±1.3）次,（4.3±2.1）和（1.7±0.5）次,（3.6±1.5）和（2.0±0.2）次,（124±27）和（212±36） ml;D组分别为（9.2±1.9）和（8.4±1.8）分,（13.5±3.4）和（11.2±2.2）分,（7.6±2.6）和（6.4±2.1）分,（4.3±2.0）和（3.3±0.4）分,（3.5±1.3）和（2.8±0.3）次,（125 ±28）和（161±38） ml;4组治疗前后组内对比,主观指标及客观指标差异均有统计学意义（均P＜0.05）.A组、B组、C组治疗后各项指标与D组比较,差异均有统计学意义（均P＜0.05）.A组与B组、C组之间比较,差异均有统计学意义（P＜0.05）.总的不良反应发生率A组为8.8％ （     

Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea

Objectives: The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz) in Korean patients with overactive bladder (OAB) in routine clinical practice. Methods: This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator’s discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy.

Results: A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24?hours decreased by 4.0, 2.4, and 0.8, respectively (all p?<?0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration.

Conclusion: These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.     

膀胱灌注辣椒辣素类似物治疗特发性膀胱过度活动症随机对照临床研究

目的探讨膀胱灌注辣椒辣素类似物（RTX）治疗特发性膀胱过度活动症（IOAB）的临床效果。方法IOAB患者26例随机分为试验A组和对照B组。A组14例，用100nmol／LRTX 100ml灌注膀胱保留30min后排空。B组12例，用1：5000呋喃西林（安慰剂）替代RTX，方法同A组。观察A，B两组用药前、用药后1个月、用药后3个月的临床症状（每日排尿次数、尿急程度）和尿动力学参数（FDV、MCBC、Qmax）。结果治疗前与治疗后1个月、3个月的临床症状和尿动力学参数比较，A组差异有显著意义（P〈0．01），B组差异无显著意义（P〉0．05）。14／26例（54％）有轻度尿道刺激症状或膀胱区不适，均可耐受。结论RTX单剂量膀胱灌注能安全有效地改善IOAB临床症状和尿动力学指标。