A Longitudinal Population-based Survey of Urinary Incontinence,Overactive Bladder,and Other Lower Urinary Tract Symptoms in Women

Background

Female urinary incontinence (UI), overactive bladder (OAB), and other lower urinary tract symptoms (LUTS) are highly prevalent conditions with a profound influence on well-being and quality of life. There are a few studies describing progression as well as remission, in the short term, of UI in the general population as well as in selected groups; at present, there are very few population-based studies describing the natural course of other LUTS in the same women, and there are no long-term longitudinal studies.

Objective

To describe the prevalence of UI, OAB, and other LUTS in the same women studied prospectively over time and, thus, to assess possible progression or regression.

Design, setting, and participants

A longitudinal population-based study was performed in one primary health care district in the city of Gothenburg, Sweden. The participants were a sample of women aged ≥20 yr who were randomly selected from the Swedish National Population Register, assessed in 1991 (n = 2911), and available for reassessment in 2007 (n = 1408).

Methods

A self-administered postal questionnaire regarding UI, OAB, and other LUTS was returned by 77% of the contacted women in 1991. The same women who responded in 1991 and who were still alive and available in the Swedish National Population Register 16 yr later were reassessed using a similar self-administered postal questionnaire.

Results and limitations

In 2007, 1081 of the available 1408 women responded to the questionnaire (77%). The overall prevalence of UI, OAB, nocturia, and daytime micturition frequency of eight or more times per day increased by 13%, 9%, 20% (p < 0.001), and 3% (p < 0.05), respectively, from 1991 to 2007. The incidence of UI and OAB were 21% and 20%, respectively, and the corresponding remission rates were 34% and 43%, respectively. Women with OAB symptoms were classified as OAB dry or OAB wet, depending on the presence or absence of concomitant UI. The prevalence of OAB dry did not differ between the two assessment occasions (11% and 10%, respectively), but the prevalence of OAB wet increased from 6% to 16% (p < 0.001).

Conclusions

UI and other LUTS constitute dynamic conditions. In this study, there was a marked overall increase in the prevalence of UI, OAB, and nocturia in the same women from 1991 to 2007. Both incidence and remission of most symptoms were considerable.     

A Cross-Sectional,Population-Based,Multinational Study of the Prevalence of Overactive Bladder and Lower Urinary Tract Symptoms: Results from the EPIC Study

The EPIC study was the first large-scale, multinational, population-based, cross-sectional survey to estimate the prevalence of lower urinary tract symptoms (LUTS) using current (2002) International Continence Society (ICS) definitions, with a focus on LUTS subtypes, overactive bladder (OAB), and urinary incontinence (UI). This study was conducted between April and December 2005 using randomly selected men and women ≥18 yr of age living in Canada, Germany, Italy, Sweden, and the United Kingdom. The results of the EPIC study are fairly consistent with the literature, showing that LUTS are highly prevalent; 64.3% of the 19,165 respondents reported experiencing at least one LUTS. Storage LUTS were considerably more prevalent than were voiding and postmicturition LUTS in both men and women. The prevalence of OAB was comparable in men (10.8%) and women (12.8%) and increased with age in both sexes. Nocturia was the most prevalent symptom in both men (48.6%) and women (54.5%). UI was more prevalent among women (13.1%) than men (5.4%). Among women, stress UI and other UI were the most prevalent types of UI; among men, other UI and urgency UI were most prevalent. Rates of physician-diagnosed depression were significantly higher in respondents with OAB, with or without UI, than in respondents without OAB. Further analyses of EPIC data will be available soon and should yield information about OAB regarding bother and impact on quality of life; risk factors and comorbidities; coping and health care-seeking behaviours; and impact on sexuality, mental health, and work productivity.     

Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men

ContextThe role of overactive bladder (OAB) treatment in women beyond antimuscarinics has been evaluated extensively. Beta-3 agonists, botulinum toxin-A (BTX-A), and nerve stimulation are indicated in these patients. However, data on male patients in this clinical scenario are scarce.ObjectiveThe aim of this systematic review was to evaluate the evidence on treatment options beyond antimuscarinics in men with OAB.Evidence acquisitionA search of PubMed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases was performed for relevant articles published between January 2000 and October 2020, using the following Medical Subject Headings: “male/man,” “LUTS,” “overactive bladder,” “storage symptoms,” “urgency,” “nocturia,” “incontinence,” “beta-3 agonist,” “PDE-5 inhibitors,” “botulinum toxin,” “sacral nerve stimulation/neurostimulation,” “percutaneous/transcutaneous tibial nerve stimulation,” “PTENS,” and “combination therapy.” Evidence acquisition was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PROSPERO registration number is CRD42020201223.Evidence synthesisOverall, 24 studies were retrieved. In male OAB, mirabegron (MIRA) is the most intensively investigated pharmacological option. A pooled analysis of five randomized clinical trials (RCTs), including 1187 patients, concluded that MIRA 50 mg was associated with a greater reduction in frequency versus placebo (–0.37, 95% confidence interval [CI]: –0.74, –0.01, p < 0.05). A pooled analysis of three RCTs, including 1317 male patients, has also shown that the addition of MIRA 50 mg in men receiving the α₁-blocker tamsulosin improved the mean number of micturitions per day (–0.27, 95% CI: –0.46 to –0.09, p < 0.05), urgency episodes (–0.50, 95% CI: –0.77 to –0.22, p < 0.05), total OAB symptom score (–0.66, 95% CI: –1.00 to –0.38, p < 0.05), and mean volume voided (+10.76 ml, 95% CI: 4.87–16.64, p < 0.05). MIRA treatment is well tolerated in men. Other pharmacological treatment options, such as phosphodiesterase-5 (PDE-5) inhibitors, should be considered investigational. BTX-A seems to be effective as third-line treatment in male OAB patients. A higher rate of intermittent self-catheterization (5–42%) is observed in male than in female patients. Data on nerve stimulation are scarce.ConclusionsMIRA has the most robust data in terms of safety and efficacy in this patient population. Preliminary data in men suggest that BTX-A is indicated as an interventional treatment. Evidence for PDE-5 inhibitors and nerve stimulation is too limited to provide recommendations. Future studies in this population should aim to better define the best treatment sequence and to identify predictors for treatment response and failure, to determine a therapeutic approach tailored to patients’ characteristics.Patient summaryOveractive bladder is highly prevalent in men. Mirabegron 50 mg is the treatment option supported by the highest level of evidence when antimuscarinics failed. Botulinum toxin A injections seems to be an effective treatment as interventional option. Roles of nerve stimulation and phosphodiesterase inhibitors in male OAB patients are still to be defined.     

Dynamic Progression of Overactive Bladder and Urinary Incontinence Symptoms: A Systematic Review

Context

Overactive bladder (OAB) and urinary incontinence (UI) are worldwide public health problems. Longitudinal epidemiologic studies that assess the natural history of OAB and UI are valuable in making accurate prognoses, determining causes and consequences, and predicting resource utilization.

Objective

Our aim was to assess whether the severity of OAB and UI symptoms progress dynamically over time, with the secondary aim of assessing factors that may be associated with symptom progression and regression.

Evidence acquisition

A systematic review of English articles published between January 1, 1990, and September 20, 2009, was conducted using PubMed and Embase. Search terms included longitudinal, natural history, overactive bladder, incontinence, progression, remission, and regression. Eligibility was assessed by Dr. Irwin with editorial assistance. Studies were required to be longitudinal and population based; meeting abstracts and conference proceedings were excluded. Results were assessed qualitatively.

Evidence synthesis

Overall, the 7 longitudinal studies of OAB and 14 longitudinal studies of UI reviewed reported an increase in the incidence and remission/regression of both OAB and UI symptoms over time that varied across studies (eg, OAB incidence, 3.7–8.8%; UI incidence, 0.8–19%). The studies provide evidence for a dynamic progression of OAB and UI symptoms (eg, among women with OAB without urge urinary incontinence [UUI], 28% reported OAB with UUI 16 yr later) and also show that although symptom severity progresses dynamically, for many individuals symptoms also persist over long time periods.

Conclusions

The results support the hypothesis that OAB and UI symptom severity progress dynamically and are also sustained over time. However, the variations in symptom definitions and methods used across studies prevent statistical determinations of overall incidence rates. The recognition of OAB and UI as progressive conditions allows for a shift from the current treatment paradigm of symptom control alone to one of symptom management.     

OnabotulinumtoxinA 100 U Significantly Improves All Idiopathic Overactive Bladder Symptoms and Quality of Life in Patients with Overactive Bladder and Urinary Incontinence: A Randomised,Double-Blind,Placebo-Controlled Trial

Background

Overactive bladder (OAB) syndrome with urinary incontinence (UI) is prevalent in the population and impairs health-related quality of life (HRQOL).

Objective

To assess the impact on efficacy, safety, and HRQOL of onabotulinumtoxinA (BOTOX^®, Allergan, Inc.) treatment in patients with OAB with UI.

Design, setting, and participants

This pivotal, multicentre, double-blind, randomised, placebo-controlled, phase 3 study enrolled patients with idiopathic OAB with ≥3 urgency UI episodes over 3 d and ≥8 micturitions per day who were inadequately managed by anticholinergics.

Intervention

OnabotulinumtoxinA at a 100 U dose (n = 277) or placebo (n = 271), administered as 20 intradetrusor injections of 0.5 ml.

Outcome measurements and statistical analysis

Co–primary end points were change from baseline in the number of UI episodes per day and proportion of patients reporting positive treatment response on the treatment benefit scale (TBS) at week 12. Additional end points included other OAB symptoms (episodes of urinary urgency incontinence, micturition, urgency, and nocturia) and HRQOL (Incontinence Quality of Life [I-QOL], King's Health Questionnaire [KHQ]). Safety assessments included adverse events (AEs), postvoid residual (PVR) urine volume, and initiation of clean intermittent catheterisation (CIC).

Results and limitations

OnabotulinumtoxinA significantly decreased UI episodes per day at week 12 (−2.95 for onabotulinumtoxinA versus −1.03 for placebo; p < 0.001). Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinumtoxinA compared with placebo (p ≤ 0.01). Patients perceived a significant improvement in their condition, as measured by patients with a positive treatment response on the TBS (62.8% for onabotulinumtoxinA versus 26.8% for placebo; p < 0.001). Clinically meaningful improvements from baseline in all I-QOL and KHQ multi-item domains (p < 0.001 versus placebo) indicated positive impact on HRQOL. AEs were mainly localised to the urinary tract. Mean PVR was higher in the onabotulinumtoxinA group (46.9 ml versus 10.1 ml at week 2; p < 0.001); 6.9% of onabotulinumtoxinA patients versus 0.7% of placebo patients initiated CIC.

Conclusions

OnabotulinumtoxinA 100 U was well tolerated and demonstrated significant and clinically relevant improvements in all OAB symptoms, patient-reported benefit, and HRQOL in patients inadequately managed by anticholinergics.

Trial registration

ClinicalTrials.gov: NCT00910520.     

A Refocus on the Bladder as the Originator of Storage Lower Urinary Tract Symptoms: A Systematic Review of the Latest Literature

Context

The focus of clinical understanding and management of male storage lower urinary tract symptoms (LUTS) has shifted from the prostate to the bladder. This is mirrored by an increasing body of experimental evidence suggesting that the bladder is the central organ in the pathogenesis of LUTS.

Objective

A systematic review of the literature available on pathophysiologic aspects of storage LUTS.

Evidence acquisition

Medline was searched for the period ending December 2008 for studies on human and animal tissue exploring possible functional and structural alterations underlying bladder dysfunction. Further studies were chosen on the basis of manual searches of reference lists and review papers.

Evidence synthesis

Numerous recent publications on LUTS pathophysiology were identified. They were grouped into studies exploring abnormalities on urothelial/suburothelial, muscular, or central levels.

Conclusions

Studies revealed both structural and functional alterations in bladders from patients with LUTS symptoms or animals with experimentally induced bladder dysfunction. In particular, the urothelium and the suburothelial space, containing afferent nerve fibres and interstitial cells, have been found to form a functional unit that is essential in the process of bladder function. Various imbalances within this suburothelial complex have been identified as significant contributors to the generation of storage LUTS, along with potential abnormalities of central function.     

Systematic Review of Combination Drug Therapy for Non-neurogenic Lower Urinary Tract Symptoms

Context

Several drugs are approved and available for the treatment of lower urinary tract symptoms (LUTS) in men and women. However, the vast majority of available data, upon which the approval and recommendation in guidelines are based, considered only the role of the monotherapies and did not evaluate possible combination therapies.

Pilot Study of Liposome-encapsulated OnabotulinumtoxinA for Patients with Overactive Bladder: A Single-center Study

Background

Intradetrusor onabotulinumtoxinA (BoNT-A) injection benefits overactive bladder (OAB) patients, but increased postvoid residual (PVR) urine volume and urinary tract infection (UTI) remain risks. Intravesical instillation of liposomal BoNT-A instead of injection could prevent such adverse events.

Objective

To evaluate instillation of liquid liposomal BoNT-A (Lipotoxin) for the treatment of OAB and to determine its mechanism of action.

Design, setting, and participants

A double-blind randomized parallel controlled pilot trial in 24 OAB patients at a single tertiary center.

Intervention

Patients were randomly assigned to intravesical instillation of Lipotoxin containing 80 mg liposomes and 200 U BoNT-A or normal saline (N/S). Patients were retreated with Lipotoxin 1 mo later if they failed the first treatment.

Outcome measurement and statistical analysis

Voiding diaries, OAB symptom scores, urodynamic studies, and adverse events were monitored. The primary end point was change of total urinary frequency per 3 d at 1 mo after treatment. Immunohistochemistry and Western blotting for synaptic vesicle glycoprotein 2A (SV2A) and synaptosomal-associated protein, 25 kDa (SNAP25) were performed at baseline and 3 mo after treatment. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis.

Results and limitations

At 1 mo after treatment, the change of urinary frequency per 3 d significantly improved in the Lipotoxin group (n = 12; median: −6.50; interquartile range [IQR]: −18.3 to −0.25; p = 0.008) but not in the N/S group. (n = 12.0; IQR: −7.75 to 8.0; p = 0.792). Urgency episodes also showed a significant decrease in the Lipotoxin group (−12.0; IQR: −20.3 to −2.75; p = 0.012) but not in the N/S group (−1.0; IQR: −11.0 to 2.5; p = 0.196). SV2A and SNAP25 were expressed in urothelial cells and suburothelial tissues. However, the protein expression did not significantly differ between responders and nonresponders at 3 mo after treatment.

Conclusions

Intravesical Lipotoxin instillation effectively reduced frequency episodes 1 mo after treatment in OAB patients without any increase in PVR or risk of UTI.

Patient summary

We demonstrated that intravesical Lipotoxin instillation reduced frequency episodes at 1 mo in overactive bladder patients. This procedure is safe, without an increase in postvoid residual or the risk of urinary tract infection.     

Anticholinergic Drugs in Patients with Bladder Outlet Obstruction and Lower Urinary Tract Symptoms: A Systematic Review

Objectives

To review the available evidence concerning the use of anticholinergic drugs, alone or in combination with α-blockers, in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and concomitant overactive bladder syndrome, to assess whether the currently available evidence suggests a role for antimuscarinic drugs in patients with BPH.

Methods

A systematic review of the literature was performed using Embase, MEDLINE, and Web of Science through a complex search strategy including “free text” and “MeSH” protocols. Moreover, the Cochrane database of systematic review was browsed for records regarding BPH and the abstract books of the American Urological Association, European Association of Urology, and International Continence Society annual meetings from 2000 to 2005 were hand-searched for studies concerning the topic of the review.

Results

From the literature search, we identified four randomised controlled trials (RCTs), two prospective case series, and a few congress abstracts. For methodologic issues, the best RCT was based on urodynamic data, but did not provide any clinical insight on the patients’ symptoms. The other papers were affected by significant methodologic or clinical drawbacks.

Conclusion

The available data may be considered promising in terms of safety and efficacy. The evidence of the limited number of RCTs available, considering their methodologic or clinical shortcomings, is not sufficient to support the clinical use of combination therapy with α-blockers and anticholinergic drugs in patients with associated storage and voiding symptoms. Well-designed, large, double-blind, placebo-controlled, long-term RCTs are needed to assess the long-term safety and efficacy of antimuscarinic drugs, alone or in combination with α-blockers, in this category of patients.     

膀胱过度活动症症状评分表对中国OAB患者结果评估的重复信度及与其他症状评分工具间相关性的研究

目的 评估中文版膀胱过度活动症(OAB)症状评分表(OABSS)对中国OAB患者症状评估的重复信度及与其他评分工具间的相关性. 方法 50例OAB患者分别于第0天和第(14±2)天填写2次OABSS、患者感知膀胱症状情况分级量表(PPBC)、国际前列腺症状评分表(IPSS)及3 d排尿日志卡.采用内部相关系数(ICC)评价基线(0 d)和2周后OABSS问卷表总评分间的相关程度,采用加权Kappa系数评估OABSS各问题评分间的相关程度,采用Cronbach's α系数计算OABSS的内部信度;分别计算基线和2周后OABSS问卷表总评分与3 d排尿日志卡中临床变量、IPSS总评分、IPSS QOL评分及PPBC评分之间的Pearson或Spearman相关系数. 结果 OABSS总评分的ICC为0.9172,各项评分的加权Kappa系数为0.5902～0.9274,基线与2周后OABSS的Cronbach's α系数分别为0.3069和0.3285;OABSS与排尿日志卡上的临床变量间(日平均排尿次数除外)Pearson相关系数为0.2643～0.6900;与IPSS总评分的 Pearson相关系数为0.4734和0.4929,Spearman相关系数为0.4133和0.4149;与PPBC的Spearman相关系数为0.4083和0.4127.结论中文版OABSS对中国OAB患者结果评估的重复信度较好,与排尿日志卡上的临床变量、IPSS总评分以及PPBC之间的相关程度较高.     

The Epidemiology of Overactive Bladder among Females in Asia: A Questionnaire Survey

A questionnaire-based survey was performed in 5502 females from 11 countries in Asia to establish the prevalence overactive bladder (OAB) and identify the factors related to the occurrence of the condition. The overall prevalence of OAB was 53.1%. The most common presenting symptom was urgency (65.4%). Twenty-one per cent of the OAB population presented with incontinence, giving an overall prevalence of 11.4% for urge incontinence among Asian females. The majority (75.4%) were not significantly bothered by the condition. Only 21.1% sought treatment. Older age, multiparity, a positive family history, residence in a rural area and the use of a sitting type of toilet were found to be associated with a greater occurrence of OAB. The study has shown that overactive bladder in Asian females is significant and warrants closer attention. It has also highlighted the low treatment-seeking rate among its sufferers. This is the first report on the epidemiology of overactive bladder among Asians in the medical literature.