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1.  An animal study to compare the degree of the suppressive effects on the afferent pathways of micturition between tamsulosin and sildenafil 
Background
Tamsulosin, an α1-adrenoceptor antagonist, and sildenafil, a phosphodiesterase (PDE) inhibitor, are reported to improve lower urinary tract symptoms including overactive bladder (OAB). This study is aimed at investing the effects of tamsulosin and sildenafil and comparing the degree of the suppressive effects on the afferent pathways of micturition between them using an animal model of OAB, the spontaneously hypertensive rat (SHR).
Results
The cystometric parameters, the basal pressure and duration of bladder contraction, were significantly increased in the SHR group as compared with the Wistar-Kyoto (WKY) group. The intercontraction interval also significantly decreased in the SHR group. In the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group, however, the basal pressure and duration were significantly reduced and the intercontraction interval was significantly prolonged. Moreover, the degree of the expression of c-Fos and NGF was significantly higher in the SHR group as compared with the WKY group. But it was significantly reduced in the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group. Furthermore, tamsulosin had a higher degree of effect as compared with sildenafil.
Conclusions
In conclusion, α1-adrenergic receptor antagonists and PDE-5 inhibitors may have an effect in improving the voiding functions through an inhibition of the neuronal activity in the afferent pathways of micturition.
doi:10.1186/1423-0127-20-81
PMCID: PMC3871018  PMID: 24160992
Overactive bladder syndrome; Tamsulosin; Sildenafil; Neuronal activity; Afferent pathways of micturition
2.  The Add-On Effect of Solifenacin for Patients with Remaining Overactive Bladder after Treatment with Tamsulosin for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Obstruction 
Advances in Urology  2010;2010:205251.
Objectives. To investigate the add-on effect of solifenacin for Japanese men with remaining overactive bladder (OAB) symptoms after tamsulosin monotherapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) in real-life clinical practice. Methods. Patients aged ≥ 50 having remaining OAB symptoms (≥ 3 of OAB symptom score (OABSS) with ≥2 of urgency score) after at least 4 weeks treatment by 0.2 mg of tamsulosin for BPO/LUTS received 2.5 or 5.0 mg of solifenacin for 12 weeks. The International Prostate Symptom Score (IPSS), QOL index and OABSS, maximum flow rate (Qmax) and postvoid residual urine volume (PVR) were determined. Results. A total of 48 patients (mean age 72.5 years) completed the study. There were significant improvement in IPSS (15.1 to 11.2) and QOL index (4.2 to 3.0) by add-on of solifenacin. Although the IPSS storage symptom score was significantly improved, there were no changes observed in the IPSS voiding symptom score. The OABSS showed significant improvement (8.0 to 4.8). No changes were observed in Qmax and PVR. Conclusions. Under the supervision of an experienced urologist, the additional administration of solifenacin to patients with BPO/LUTS treated with tamsulosin, is effective in controlling remaining OAB symptoms.
doi:10.1155/2010/205251
PMCID: PMC2964005  PMID: 20981257
3.  Urodynamic Detrusor Overactivity in Patients with Overactive Bladder Symptoms 
Purpose
To evaluate the relationship between urodynamic detrusor overactivity (DO) and overactive bladder (OAB) symptoms in men and women.
Methods
We reviewed the records of adult males and females who attended a tertiary referral center for urodynamic evaluation of OAB syndrome symptoms with the presence or absence of DO. DO was calculated for symptoms alone or in combination.
Results
The overall incidence of DO was 76.1% and 58.7% in male and female OAB patients, respectively. Of men 63% and 61% of women with urgency (OAB dry) had DO, while 93% of men and 69.8% of women with urgency and urgency urinary incontinence (OAB wet) had DO. Of women, 58% who were OAB wet had stress urinary incontinence symptoms with 26.4% having urodynamic stress incontinence. 6% of men and 6.5% of women with OAB symptoms had urodynamic diagnosis of voiding difficulties with postvoid residual greater than 100 mL. Combination of symptoms is more accurate in predicting DO in OAB patients. The multivariate disease model for males included urge urinary incontinence (UUI) and urgency while for females it included UUI and nocturia.
Conclusions
There was a better correlation in results between OAB symptoms and the urodynamic diagnosis of DO in men than in women, more so in OAB wet than in OAB dry. Combination of symptoms of the OAB syndrome seems to have a better correlation with objective parameters from the bladder diary, filling cystometry, and with the occurrence of DO.
doi:10.5213/inj.2011.15.1.48
PMCID: PMC3070227  PMID: 21468287
Overactive bladder; Urodynamic investigation; Urinary incontinence; Detrusor overactivity
4.  Function of the Cold Receptor (TRPM8) Associated with Voiding Dysfunction in Bladder Outlet Obstruction in Rats 
Purpose
Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO.
Methods
Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction.
Results
Cystometry showed that the intercontraction interval (ICI; 428.2±23.4 vs. 880.4±51.2, P<0.001), micturition pressure (MP; 25.7±1.01 vs. 71.80±3.01, P<0.001), and threshold pressure (2.9±0.25 vs. 9.2±1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group.
Conclusions
Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca2+ from the extracellular space or stores. The increase of Ca2+ probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.
doi:10.5213/inj.2012.16.2.69
PMCID: PMC3395802  PMID: 22816047
TRPM8; Menthol; Cold receptor; Bladder outlet obstruction
5.  Associations between subjective overactive bladder symptoms and objective parameters on bladder diary and filling cystometry 
International Urogynecology Journal  2012;23(11):1619-1624.
Introduction and hypothesis
A study was conducted to assess associations between different overactive bladder (OAB) symptoms and their outcomes on bladder diary and filling cystometry parameters.
Methods
We performed a retrospective cohort study in database of 6,876 Urinary Distress Inventories, 3,185 bladder diaries and 2,153 filling cystometries from women referred to our urogynecological center between 2003 and 2009. Women were dichotomized into two groups. Group I: those women without symptoms, and those with symptoms that were not bothersome. Group II: women with bothersome symptoms. Data obtained from bladder diaries were: daytime urinary frequency, nocturnal frequency, minimum voided volume, maximum voided volume, average voided volume, and incontinence episodes. From filling cystometries, volumes at first desire to void, normal desire to void, strong desire to void and maximum cystometric capacity, were extracted. Univariate and multiple linear regression analysis were performed to determine associations between OAB symptoms and bladder diary and filling cystometry measurements.
Results
After multivariate analysis the objective daytime frequency was most strongly associated with the frequency symptom (β 0.27, p < 0.05), night time frequency with the nocturia symptom (β 0.40, p < 0.05) and the number of incontinence episodes with the urge incontinence symptom (β 0.37, p < 0.05). Both frequency and nocturia symptoms were significantly associated with bladder diary and cystometry filling volumes, and their effect size was the same. The urgency symptom proved to be poorly associated with objective parameters.
Conclusions
In contrast to the frequency and nocturia symptom, the urgency symptom is poorly associated with objective parameters on bladder diary and filling cystometry. Therefore, the current practice of using frequency and incontinence episodes in outcome research of OAB trials is justified.
doi:10.1007/s00192-012-1774-3
PMCID: PMC3592260  PMID: 22543547
Bladder diary; Cystometry; Overactive bladder
6.  Effect of Long-term Exercise on Voiding Functions in Obese Elderly Women 
Purpose
An overactive bladder (OAB) may be defined as urgency that is a sudden, compelling, difficult to defer desire to pass urine that is usually accompanied by frequency and nocturia and possibly by incontinence. Obesity and old age are two factors in various causes of OAB. Several epidemiologic studies have identified positive associations among obesity, old age, urinary incontinence, and OAB. However, although exercise has been known to improve obesity and reduce incontinent urine loss, little research has been done in elderly women. Therefore, we investigated the effects of exercise on obesity-related metabolic factors, blood lipid factors, and OAB symptoms in elderly Korean women.
Methods
Twenty-one women aged between 69 and 72 years were recruited from the Seoul senior towers in Korea. All subjects worked out on a motorized treadmill and stationary cycle for 40 minutes, respectively, and performed resistance exercise for 30 minutes once a day for 52 weeks. Body composition, blood pressure, blood lipids, OAB symptom score, and King's health questionnaire were investigated and analyzed.
Results
Before performing physical exercise, all subjects showed increased OAB symptoms in association with enhanced body mass index (BMI), percentage fat, and blood lipid profiles. However, physical exercise for 52 weeks suppressed BMI, percentage fat, and blood lipid profiles and thus improved OAB symptoms.
Conclusions
We suggest that long-term physical exercise can be a valuable tool for remarkable improvement of OAB.
doi:10.5213/inj.2013.17.3.130
PMCID: PMC3797893  PMID: 24143292
Overactive urinary bladder; Obesity; Exercise; Overactive bladder symptom score; King's health questionnaire
7.  Defining and Managing Overactive Bladder: Disagreement among the Experts 
Urology  2013;81(2):257-262.
Objectives
To better understand experts’ perceptions of the definition of overactive bladder (OAB), the evaluation of OAB, and treatment of OAB. OAB is defined by the International Continence Society as “urinary urgency, with or without urge urinary incontinence, usually with frequency and nocturia.” Under the current definition, people with very different clinical conditions fall under the OAB umbrella. With the goal of improving the care for women with OAB, we sought to better understand experts’ perceptions of OAB as it is presently defined.
Methods
Twelve interviews with leading urologic, gynecologic, and geriatric practitioners in urinary incontinence and OAB were performed. Questions were asked about their perception and agreement with the current definition of OAB. Interviews were audiotaped and transcribed verbatim. Grounded theory methodology was used to analyze the data.
Results
Overall, there was a great deal of variability in defining and managing OAB. Four categories of definitions were derived from the qualitative analysis: current definition is adequate, OAB is a constellation of symptoms, should include the fear of leakage, and OAB is a marketing term. While there is some consensus on evaluation, several areas demonstrate disagreement over elements of the evaluation. Experts also felt that OAB is a chronic condition, with variability of symptoms, and it has no cure. Managing patient expectation is essential, as OAB is challenging to treat. A focus was placed on behavioral therapy.
Conclusions
There was disagreement among experts over the definition and work-up of OAB. However, experts agree that OAB is a chronic condition with a low likelihood of cure.
doi:10.1016/j.urology.2012.09.028
PMCID: PMC3890251  PMID: 23374774
overactive bladder; urgency; urge incontinence; diagnosis; evaluation; management; definition
8.  Randomized Controlled Trial to Compare the Safety and Efficacy of Tamsulosin, Solifenacin, and Combination of Both in Treatment of Double-J Stent-Related Lower Urinary Symptoms 
Advances in Urology  2013;2013:752382.
Purpose. We evaluated the effectiveness and safety of tamsulosin, solifenacin, and combination of both in reducing double-J stent-related lower urinary symptoms. Materials and Methods. A total of 338 patients with double-J ureteral stenting were randomly divided, postoperatively, into 4 groups. In group I (n = 84), no treatment was given (control group), group II (n = 85) received tamsulosin 0.4 mg daily, group III (n = 84) received solifenacin 10 mg daily, and group IV (n = 85) received a combination of both medications. Before insertion and 2 weeks after, all patients completed the International Prostate Symptom Score (IPSS), quality of life component of the IPSS (IPSS/Qol), Overactive Bladder Questionnaire (OAB-q), and Visual Analogue Pain Scale (VAPS) questionnaire. Results. The demographics and preoperative questionnaires scores of all groups were comparable. There were statistically significant differences in all scores in favour of groups II, III, and IV as compared to control group (P value < 0.005). Group IV showed statistically significant differences in total IPSS, QoL score, and OAB-q score as compared to groups II and III (P value < 0.001). Conclusions. Combined therapy of tamsulosin and solifenacin significantly alleviated lower urinary symptoms associated with double-J stents as compared to either medication alone.
doi:10.1155/2013/752382
PMCID: PMC3819880  PMID: 24235970
9.  Changes of neuregulin-1(NRG-1) expression in a rat model of overactive bladder induced by partial urethral obstruction: is NRG-1 a new biomarker of overactive bladder? 
BMC Urology  2013;13:54.
Background
To determine whether neuregulin-1(NRG-1) is a potential new biomarker of overactive bladder (OAB) induced by partial urethral obstruction in a rat model of OAB and to evaluate the urothelium as a therapeutic target of OAB.
Methods
Female Sprague–Dawley rats were separated into three 20-animal groups: normal, OAB, and 5-hydroxymethyl tolterodine (5-HMT)-treated OAB. In the OAB and OAB + 5-HMT groups, the urethra of each animal was partially obstructed; the OAB + 5-HMT group received intravenous 5-HMT for 3 weeks. At the conclusion of the 5-HMT dosing, the rats in each group underwent cystometrography, and the bladders were histologically evaluated. The expression of brain derived-neurotrophic factor (BDNF) and NRG-1 were evaluated in the urothelium.
Results
Compared with the control group, the OAB group showed a markedly increased bladder weight and a significant decrease in the micturition interval and volume; rats in the OAB + 5-HMT group showed decreased bladder weights and an improved micturition interval and volume. BDNF and NRG-1 were expressed at significantly higher levels in the OAB group, and were significantly reduced in the OAB + 5-HMT group compared with the control group.
Conclusions
The study suggests that NRG-1 is a potential new biomarker of OAB; the urothelium might be a therapeutic target for OAB treatment.
doi:10.1186/1471-2490-13-54
PMCID: PMC4015862  PMID: 24152577
Neuregulin-1; Overactive bladder; Biomarker
10.  Increased Serum Adipokines Implicate Chronic Inflammation in the Pathogenesis of Overactive Bladder Syndrome Refractory to Antimuscarinic Therapy 
PLoS ONE  2013;8(10):e76706.
Objectives
Recent studies have shown that chronic inflammation is involved in overactive bladder (OAB) syndrome. OAB could be a subtype of neurogenic inflammation. This pilot study investigated serum adipokine levels in patients with OAB refractory to antimuscarinic therapy.
Methods
Thirty consecutive patients with OAB-dry (n = 16) or OAB-wet (n = 14) refractory to previous antimuscarinic treatment were prospectively enrolled in this study, a group of 26 normal subjects without lower urinary tract symptoms served as controls. Concentrations of serum C-reactive protein (CRP), nerve growth factor (NGF), and adipokines including interleukins ([IL], IL-1β, IL-6, IL-8), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, insulin, and leptin were quantified using a bead-based human serum adipokine panel B kit. Data were analyzed using the LX 200 platform. Patients were further classified as having dry or wet OAB and having medical diseases or not. The serum CRP, NGF, and adipokine levels were compared between OAB patients and the controls, and between OAB subgroups.
Results
The serum concentrations of CRP, NGF, IL-1β, IL-6, IL-8, and TNF-α in OAB-dry and OAB-wet patients were significantly higher than among the controls. There was no significant difference in adipokine levels between OAB-dry and OAB-wet, or between OAB patients with and without medical diseases. Serum CRP and NGF levels were significantly higher only in OAB-wet or OAB patients with medical diseases than among controls. The MCP-1 levels, on the other hand, were significantly higher in OAB-dry or OAB patients with disease, than the controls.
Conclusions
Both OAB-dry and OAB-wet patients showed increased serum CRP, NGF, and adipokine levels compared with the controls, suggesting chronic inflammation of the bladder involving both peripheral and central mechanisms in all OAB patients refractory to antimuscarinic therapy. The increased serum adipokine levels were not relevant to medical diseases.
doi:10.1371/journal.pone.0076706
PMCID: PMC3788120  PMID: 24098552
11.  Refractory overactive bladder: Beyond oral anticholinergic therapy 
Objectives:
In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments.
Materials and Methods:
A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options.
Results:
In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted.
Conclusion:
The vast majority of OAB patients can be managed successfully by behavioral options with or without anticholinergic medications. When those fail, neuromodulation or intravesical botulinum toxin therapies are successful alternatives for most of the remaining group. We encourage practitioners responsible for the care of OAB patients to gain experience with these options. More research is needed to assess the cost-effectiveness of various OAB treatments
doi:10.4103/0970-1591.32069
PMCID: PMC2721527  PMID: 19675795
Behavioral therapy; botulinum toxin type A; electrical stimulation; overactive bladder; urinary incontinence; urologic surgical procedures
12.  Expression of E-series prostaglandin (EP) receptors and urodynamic effects of an EP4 receptor antagonist on cyclophosphamide-induced overactive bladder in rats 
BJU international  2010;106(11):1782-1787.
OBJECTIVE
To investigate the expression of four subtypes of E-series prostaglandin (EP1–EP4) receptors and the urodynamic effects of an EP4 receptor antagonist (AH23848) in cyclophosphamide (CYP)-induced overactive bladder (OAB) in rats, as intravesical prostaglandin E2 (PGE2) induces OAB via activation of EP receptors and sensitization of afferent nerves.
MATERIALS AND METHODS
Experimental and control rats were injected with CYP (200 mg/kg, intraperitoneally) or saline, respectively. Continuous cystometrograms (CMGs) were performed 48 h after CYP or saline injection under urethane anaesthesia. AH23848 was given intravenously at doses of 0.01 and 0.1 mg/kg. The bladder was then harvested for histology. Some bladders were harvested for analysis of EP receptors expression by Western blotting without a CMG study. CMG variables (baseline pressure; intercontraction interval [ICI], pressure threshold [PT], contraction amplitude) and histological changes were measured.
RESULTS
CYP-induced up-regulation of EP4 receptor (100% increase) accompanied by detrusor overactivity (ICI 70.5% decrease; PT, 67.7% increase). However, CYP down-regulated EP1 receptor expression (51.9% decrease), but had no significant effects on the EP2 and EP3 receptors. AH23848 significantly extended the ICI in CYP-treated rats but it had no effects on other urodynamic variables or in control rats.
CONCLUSIONS
Modulation of EP receptors plays a role in CYP-induced OAB. Antagonists to the EP4 receptor may be a new target for treatment of patients with OAB.
doi:10.1111/j.1464-410X.2010.09260.x
PMCID: PMC3102303  PMID: 20346049
EP4 receptor; cyclophosphamide; overactive bladder; rat
13.  How Dry is “OAB-Dry”?: Perspectives from Patients and Physician Experts 
The Journal of urology  2012;188(5):1811-1815.
Purpose
Overactive bladder (OAB) is subtyped into OAB-wet and OAB-dry, based on the presence or absence, respectively, of urgency incontinence. In order to better understand patient and physician perspectives on symptoms among women with OAB-wet and OAB-dry, we conducted patient focus groups and interviews with experts in urinary incontinence.
Materials and Methods
Five focus groups totaling 33 patients with OAB symptoms, including three groups of OAB-wet and 2 groups of OAB-dry patients, were conducted. Topics addressed patients’ perceptions of OAB symptoms, treatments, and outcomes. Twelve expert interviews were then conducted in which experts were asked to describe their views on OAB-wet and OAB-dry. Focus groups and expert interviews were transcribed verbatim. Qualitative data analysis was performed using Grounded Theory methodology, as described by Charmaz.
Results
During the focus groups sessions, women screened as OAB-dry shared the knowledge that they would probably leak if no toilet is available. This knowledge was based on a history of leakage episodes in the past. Those few patients with no history of leakage had a clinical picture more consistent with painful bladder syndrome than OAB. Physician expert interviews revealed the belief that many patients labeled as OAB–dry may actually be mild OAB-wet.
Conclusions
Qualitative data from focus groups and interviews with experts suggest that a spectrum exists between very mild OAB-wet and severe OAB-wet. Scientific investigations are needed to determine if urgency without fear of leakage constitutes a unique clinical entity.
doi:10.1016/j.juro.2012.07.044
PMCID: PMC3571660  PMID: 22999694
focus groups; qualitative research; urge urinary incontinence; grounded theory; overactive bladder
14.  Adipose Derived Stem Cells Ameliorate Hyperlipidemia-associated Detrusor-overactivity in a Rat Model System 
The Journal of urology  2010;183(3):1232-1240.
Purpose
It has been previously demonstrated that adipose tissue-derived stem cell (ADSC) can differentiate into muscle and neuron-like cells in vitro. In this study, we investigate the utility of ADSC in the treatment of overactive bladder (OAB) in obese hyperlipidemic rats (OHR).
Materials and Methods
Hyperlipidemia was induced in healthy rats by administration of a high fat diet. The resulting OHR were then treated with bladder injection of saline or ADSC or tail vein injection of ADSC. Bladder function was assessed by 24-h voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining followed by image analysis.
Results
Serum total cholesterol and low-density lipoprotein levels were significantly higher in OHR than in normal rats (p < 0.01). Micturition intervals were shorter in the saline-treated OHR relative to normal rats, OHR that received ADSC via tail vein, and OHR that received ADSC by bladder injection (143 ± 28.7 vs 407 ± 77.9 vs 281 ± 43.9 vs 368 ± 66.7 seconds respectively, p = 0.0084). Smooth muscle content of the bladder wall was significantly lower in OHR than in normal animals (p = 0.0061) while there was no significant difference between OHR groups. Nerve content and blood vessel density were lower in control than in ADSC-treated OHR.
Conclusions
Hyperlipidemia is associated with increased urinary frequency and diminished bladder blood vessel and nerve density in rats. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for OAB.
doi:10.1016/j.juro.2009.11.012
PMCID: PMC3163606  PMID: 20096880
Adipose tissue-derived stem cells; lower urinary tract symptoms; obese hyperlipidemic rat; overactive bladder
15.  The Prevalence and Therapeutic Effect of Constipation in Pediatric Overactive Bladder 
Purpose
Overactive bladder (OAB) is a manifestation of urgency, regardless of urge incontinence, due to involuntary bladder contraction during the storage period. There is a close association between constipation and OAB, but constipation cannot be readily diagnosed. The aims of this study were to evaluate the prevalence of constipation in OAB and the consequent therapeutic effects according to the diagnostic criteria for constipation.
Methods
We collected clinical data from 40 children (mean age, 71±22 months) with chief complaints of urgency, frequency, and incontinence. A voiding questionnaire and a 2-day voiding diary were collected, and urinalysis, the Bristol stool scale, and plain abdominal radiography were performed. Constipation was defined as conditions satisfying at least one of the following criteria: Rome III diagnostic criteria, Bristol stool scale types I/II, or a Leech score higher than 8 points as determined by plain radiography. Lower urinary tract symptoms, defecation symptoms, and the bladder volume of patients were examined, and the therapeutic outcomes by constipation diagnostic criteria were evaluated.
Results
Of the 40 OAB patients, 25 had constipation. Among them, 6 had reduced functional bladder capacity (24%; P>0.05). Regarding treatment, in patients who satisfied only one diagnostic criterion, the symptoms improved in 76.9%, 76.9%, and 69.6% of patients meeting the Rome III criteria, Bristol stool scale, and Leech score, respectively (P<0.05). Among the 8 patients satisfying all three criteria, 75% responded to treatment (P<0.05).
Conclusions
The prevalence of constipation in OAB is high. Constipated patients recruited by use of the Rome III criteria, Bristol scale, and Leech score alone and together showed similar outcomes on OAB improvement after the treatment of constipation, which implies that each criterion has the same strength and can be applied comprehensively and generally.
doi:10.5213/inj.2011.15.4.206
PMCID: PMC3256305  PMID: 22259734
Overactive urinary bladder; Pediatrics; Constipation
16.  Effect of Anticholinergic Use for the Treatment of Overactive Bladder on Cognitive Function in Post-Menopausal Women 
Clinical drug investigation  2012;32(10):697-705.
Background
Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs including cognitive changes.
Objective
To investigate the effect of an anticholinergic medication on cognitive function in postmenopausal women being treated for OAB.
Study Design
Prospective cohort study conducted from January to December 2010, with 12-week follow-up after medication initiation.
Setting
Urogynecology clinic at one academic medical center.
Patients
Women age 55 or older seeking treatment for OAB and opting for anticholinergic therapy were recruited.
Intervention
Baseline cognitive function was assessed via the Hopkins Verbal Learning Test – Revised Form (HVLT-R) (and its 5 subscales), the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality of life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance.
Main Outcome Measure
Change in HVLT-R score at Week 4 after medication initiation, compared to baseline (pre-medication) score.
Results
Of 50 women enrolled, 35 completed the assessment. Average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p=0.037), HVLT-R Delayed Recognition subscale (p=0.011) and HVLT-R Recognition Bias subscale (p=0.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p=0.029). All HVLT-R scores normalized by Week 4. OMC remained stable throughout. The Mini-Cog nadired at a 90.9% pass rate at Week 4. OAB symptoms did not improve until Week 4, based on questionnaire scores (p<0.05).
Conclusion
Cognitive function exhibited early changes after initiation of trospium chloride but normalized within four weeks. Cognitive changes occurred weeks prior to OAB symptom improvement. Surveillance for cognitive changes with anticholinergic use should be part of OAB management.
doi:10.2165/11635010-000000000-00000
PMCID: PMC3572901  PMID: 22873491
Anticholinergic; Cognitive Function; Elderly; Overactive Bladder
17.  A prospective randomized study comparing alfuzosin and tamsulosin in the management of patients suffering from acute urinary retention caused by benign prostatic hyperplasia 
Objective:
Prospective randomized study to compare the efficacy and safety of alfuzosin and tamsulosin in patients suffering from acute urinary retention caused by benign prostatic hyperplasia (BPH).
Methods:
Patients with acute urinary retention (AUR) due to BPH (total 150) were catheterized and randomized into three groups: Group A: alfuzosin 10 mg (50 patients), Group B: tamsulosin 0.4 mg (50 patients), Group C: placebo (50 patients). After three days, catheter was removed, and patients were put on trial without catheter (TWOC). Patients with successful TWOC were followed up for three months, taking into account the prostate symptom score (AUA Score), post-void residual urine volume (PVRV), and peak flow rate (PFR). ANOVA was used for statistical analysis.
Results:
Both group A (alfuzosin) and group B (tamsulosin) had similar results of TWOC (group A – 66%, group B – 70%), which were significantly superior than group C (placebo) – 36%. In follow up, three (9.1%) patients in group A, three (8.6%) patients in group B and eight (44.4%) patients in group C had retention of urine, requiring recatheterization. These patients were withdrawn from the study. After three months, alfuzosin- or tamsulosin-treated patients showed a significant decrease in AUA score and PVRV; and a significant increase in PFR as compared to placebo.
Conclusions:
TWOC was more successful in men treated with either alfuzosin or tamsulosin and the subsequent need for recatheterization was also reduced. Tamsulosin was comparable to alfuzosin in all respects, except a small but significant side effect of retrograde ejaculation.
doi:10.4103/0970-1591.57917
PMCID: PMC2808650  PMID: 19955671
Acute urinary retention; alfuzosin; BPH; trial without catheter; tamsulosin
18.  Efficacy and Tolerability of Tamsulosin 0.4 mg in Patients with Symptomatic Benign Prostatic Hyperplasia 
Korean Journal of Urology  2011;52(7):479-484.
Purpose
To evaluate the efficacy and tolerability of tamsulosin 0.4 mg once daily in Korean patients with symptomatic benign prostatic hyperplasia (BPH) and investigate whether tamsulosin 0.4 mg can improve symptoms in patients with refractory lower urinary tract symptoms (LUTS) who were previously receiving tamsulosin 0.2 mg once daily.
Materials and Methods
A total of 116 patients from 3 urology centers participated. All study subjects entered a nonblind phase consisting of 8 weeks of tamsulosin 0.2 mg monotherapy followed by an additional 8 weeks of tamsulosin 0.2 mg (0.2 mg group) or 8 weeks of tamsulosin 0.4 mg (0.4 mg group). At week 8, we chose the 0.4 mg group on the basis of International Prostate Symptom Score (IPSS), quality of life (QoL), maximal urinary flow rate (Qmax), and adverse effects. At week 16, we compared the efficacy and tolerability of tamsulosin between the 0.2 and 0.4 mg groups.
Results
A total of 26 patients (22.4%) were escalated to tamsulosin 0.4 mg at week 8. There were significant differences in IPSS, QoL, and Qmax at week 8 in both groups. There were significant differences in improvement in IPSS, QoL, Qmax, and postvoid residual urine volume from baseline to week 16 in both groups. There were no significant differences in efficacy or tolerability between the groups at week 16.
Conclusions
Our trial demonstrated that tamsulosin 0.4 mg has favorable efficacy and tolerability in Korean patients with symptomatic BPH refractory to tamsulosin 0.2 mg. No patients experienced any serious adverse effects when we escalated the dose of tamsulosin to 0.4 mg.
doi:10.4111/kju.2011.52.7.479
PMCID: PMC3151636  PMID: 21860769
Prostatic hyperplasia; Tamsulosin
19.  Emerging treatments for overactive bladder: clinical potential of botulinum toxins 
Overactive bladder (OAB) is a symptom syndrome including urgency, frequency, and nocturia – with or without incontinence. It is a common manifestation of detrusor overactivity (DO). DO is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. OAB is, therefore, both a motor and sensory disorder. Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum and has been used in medicine for many years. Over the last 10 years, it has been used for the treatment of DO and OAB when standard treatments, such as bladder training and oral anticholinergic medication, have failed to provide symptom relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release from the neurons in the motor end plate and also at sensory synapses, although the clinical effect is not permanent due to the growth of new connections within treated tissues. It is known that botulinum toxin modulates vanillioid, purinergic, capsaicin, and muscarinic receptor expression within the lamina propria, returning them to levels seen in normal bladders. Clinically, the effect of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon the symptom of urgency, and also large effects on frequency, nocturia, leakage episodes, and continence rates. These effects have been seen consistently within eight randomized trials and numerous case series. Botulinum toxin appears safe, with the only common side effect being that of voiding difficulty, occurring in up to 10% of treated patients. Dosing regimens are variable, depending on which preparation is used, but it is clear that dose recommendations have fallen over the last 5 years. There is limited evidence about the efficacy of repeat treatments. Botulinum toxin is an effective and safe second-line treatment for patients with OAB and DO.
doi:10.2147/RRU.S44665
PMCID: PMC4039398  PMID: 24892033
overactive bladder; detrusor overactivity; botulinum toxin; efficacy; side-effects; treatment
20.  The Impact of Overactive Bladder on Health-Related Quality of Life, Sexual Life and Psychological Health in Korea 
Purpose
We aimed to estimate the prevalence of overactive bladder (OAB) in Korea, to assess the variation in prevalence by sex and age, and to measure the impact of OAB on quality of life.
Methods
A population-based, cross-sectional telephone survey was conducted between April and June 2010 with a questionnaire regarding the prevalence of OAB, demographics, and the impact of OAB on quality of life. A geographically stratified random sample of men and women aged ≥30 years was selected.
Results
The overall prevalence of OAB was 22.9% (male, 19%; female, 26.8%). Of a total of 458 participants with OAB, 37.6% and 19.9% reported moderate or severe impact on their daily life and sexual life (5.6% and 3.5%, respectively, in participants without OAB). Anxiety and depression were reported by 22.7% and 39.3% of participants with OAB, respectively (9.7% and 22.8%, respectively, in participants without OAB). Only 19.7% of participants with OAB had consulted a doctor for their voiding symptoms, but 50.7% of respondents with OAB were willing to visit a hospital for the management of their OAB symptoms.
Conclusions
This study confirmed that OAB symptoms are highly prevalent in Korea, and many sufferers appear to have actively sought medical help. OAB has severe effects on daily and sexual life as well as psychological health.
doi:10.5213/inj.2011.15.3.143
PMCID: PMC3212588  PMID: 22087423
Overactive urinary bladder; Prevalence; Demography
21.  Effectiveness of Retropubic Tension-Free Vaginal Tape and Transobturator Inside-Out Tape Procedures in Women With Overactive Bladder and Stress Urinary Incontinence 
Purpose
We compared the effectiveness of the retropubic tension-free vaginal tape (TVT) and the transobturator inside-out tape (TVT-O) in treating symptoms of overactive bladder (OAB) in women with stress urinary incontinence (SUI).
Methods
Women with urodynamic SUI and OAB (mean urgency episodes ≥1 and frequency ≥8/24 hours on a 3-day voiding diary) were assigned to the TVT or TVT-O group. Preoperative measures were based on a urodynamic study, 3-day voiding diary, the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTSSF), and the urgency perception scale (UPS). At 12 postoperative months, the 3-day voiding diary, symptoms questionnaire, patient satisfaction, and standing stress test were assessed. The primary endpoint was change in the number of urgency episodes/24 hours from baseline to 12 months.
Results
In this group of 132 women, 42 received TVT and 90 received TVT-O. The mean urgency episodes/24 hours decreased from 6.3±5.5 to 1.6±3.2 in the TVT group and from 5.1±4.4 to 1.8±3.0 in the TVT-O group. The mean percent change was significantly greater after TVT than after TVT-O (73% vs. 60%, P=0.049). All subscales of BFLUTSSF and UPS were significantly improved using either method, with significantly greater improvement seen in the quality of life (QoL) domain after TVT (P=0.002). There were no significant differences in the cure and satisfaction rates between the two groups.
Conclusions
Intervention with the TVT or the TVT-O significantly improved symptoms of OAB in women with SUI and OAB. Urgency and QoL significantly improved after TVT compared with that after TVT-O.
doi:10.5213/inj.2013.17.3.145
PMCID: PMC3797895  PMID: 24143294
Overactive urinary bladder; Stress urinary incontinence
22.  The Changes of Voiding Pattern After Midurethral Sling Between Pure Stress Urinary Incontinence and Stress Urinary Incontinence With Overactive Bladder Group 
Korean Journal of Urology  2014;55(6):400-404.
Purpose
The purpose of this study is to compare changes in voiding pattern after midurethral sling surgery (MUS) between the stress urinary incontinence (SUI) group and the overactive bladder (OAB)+SUI group.
Materials and Methods
From January 2008 to February 2011, a retrospective survey was conducted of 225 female patients who had been diagnosed with SUI and undergone MUS. The subjects were divided into the SUI group and the OAB+SUI group. Changes in the overactive bladder symptom score (OABSS) and American Urological Association-Symptom Index (AUA-SI) before and three months after the MUS were compared.
Results
Of the 225 patients, 165 patients (73.3%) were classified as SUI group, and 60 patients (26.7%) were classified as OAB+SUI group. The mean age of the subjects was 54.7 years (range, 31-80 years), and the mean age of patients was 53.9 years (range, 34-80 years), and 56.8 years (range, 31-78 years) in the SUI group and OAB+SUI group. In SUI group, voiding symptom and storage symptom among the AUA-SI were significantly increased (p<0.05). OABSS were slight increased, but was statistically insignificant (p=0.847). In OAB+SUI group, voiding symptom score and OABSS showed a significant increase (p<0.05), but storage symptom score showed an insignificant increase (p=0.790).
Conclusions
OAB may occur in approximately 18% of SUI patients who undergo MUS surgery, and voiding dysfunctions with deteriorated voiding symptom and storage symptom may also occur. The deteriorated OAB was shown in 45% of SUI patients with OAB after the surgery.
doi:10.4111/kju.2014.55.6.400
PMCID: PMC4064049  PMID: 24955225
Midurethral sling; Overactive bladder; Stress urinary incontinence; Urge incontinence
23.  Bladder sensory desensitization decreases urinary urgency 
BMC Urology  2007;7:9.
Background
Bladder desensitization has been investigated as an alternative treatment for refractory detrusor overactivity. Most open and controlled clinical trials conducted with intravesical RTX showed that desensitization delays the appearance of involuntary detrusor contractions during bladder filling and decreases the number of episodes of urgency incontinence.
Urgency is being recognised as the fundamental symptom of overactive bladder (OAB), a symptomatic complex which recent epidemiological studies have shown to affect more than 10% of the Western population. As anti-muscarinic drugs, the first line treatment for OAB, are far from being able to fully control urgency, the opportunity to test other therapeutic approaches is created. The present work was, therefore, designed as an exploratory investigation to evaluate the effect of bladder desensitization on urinary urgency.
Methods
Twenty-three OAB patients with refractory urgency entered, after given informed consent, a 30 days run-in period in which medications influencing the bladder function were interrupted. At the end of this period patients filled a seven-day voiding chart where they scored, using a 0–4 scale, the bladder sensations felt before each voiding. Then, patients were instilled with 100 ml of 10% ethanol in saline (vehicle solution) and 30 days later a second seven-day voiding chart was collected. Finally, patients were instilled with 100 ml of 50 nM RTX in 10% ethanol in saline. At 1 and 3 months additional voiding charts were collected.
At the end of the vehicle and 3 months period patients were asked to give their subjective impression about the outcome of the treatment and about the willingness to repeat the previous instillation.
Results
At the end of the run-in period the mean number of episodes of urgency per week was 71 ± 12 (mean ± SEM). After vehicle instillation, the mean number of episodes of urgency was 56 ± 11, but only 4 patients (17%) considered that their urinary condition had improved enough to repeat the treatment. At 1 and 3 months after RTX the number of episodes of urgency decreased to 39 ± 9 (p = 0.002) and 37 ± 6 (p = 0.02), respectively (p indicates statistical differences against vehicle). The percentage of patients with subjective improvement after RTX and willing to repeat the instillation at a later occasion was 69%.
Conclusion
In OAB patients with refractory urgency bladder desensitization should be further investigated as an alternative to the standard management. Additionally, the specific effect of RTX on TRPV1 receptors suggests that urothelium and sub-urothelial C-fibers play an important role to the generation of urgency sensation.
doi:10.1186/1471-2490-7-9
PMCID: PMC1903357  PMID: 17561998
24.  Urinary ATP May Be a Dynamic Biomarker of Detrusor Overactivity in Women with Overactive Bladder Syndrome 
PLoS ONE  2013;8(5):e64696.
Background
Nowadays, there is a considerable bulk of evidence showing that ATP has a prominent role in the regulation of human urinary bladder function and in the pathophysiology of detrusor overactivity. ATP mediates nonadrenergic-noncholinergic detrusor contractions in overactive bladders. In vitro studies have demonstrated that uroepithelial cells and cholinergic nerves from overactive human bladder samples (OAB) release more ATP than controls. Here, we compared the urinary ATP concentration in samples collected non-invasively from OAB women with detrusor overactivity and age-matched controls.
Methods
Patients with neurologic diseases, history of malignancy, urinary tract infections or renal impairment (creatinine clearance <70 ml/min) were excluded. All patients completed a 3-day voiding diary, a 24 h urine collection and blood sampling to evaluate creatinine clearance. Urine samples collected during voluntary voids were immediately freeze-preserved for ATP determination by the luciferin-luciferase bioluminescence assay; for comparison purposes, samples were also tested for urinary nerve growth factor (NGF) by ELISA.
Results
The urinary content of ATP, but not of NGF, normalized to patients’ urine creatinine levels (ATP/Cr) or urinary volume (ATP.Vol) were significantly (P<0.05) higher in OAB women with detrusor overactivity (n = 34) than in healthy controls (n = 30). Significant differences between the two groups were still observed by boosting urinary ATP/Cr content after water intake, but these were not detected for NGF/Cr. In OAB patients, urinary ATP/Cr levels correlated inversely with mean voided volumes determined in a 3-day voiding diary.
Conclusion
A high area under the receiver operator characteristics (ROC) curve (0.741; 95% CI 0.62–0.86; P<0.001) is consistent with urinary ATP/Cr being a highly sensitive dynamic biomarker for assessing detrusor overactivity in women with OAB syndrome.
doi:10.1371/journal.pone.0064696
PMCID: PMC3669404  PMID: 23741373
25.  Outcomes of Intravesical Botulinum Toxin for Idiopathic Overactive Bladder Symptoms: A Systematic Review of the Literature 
The Journal of urology  2010;183(6):2258-2264.
Purpose
To systematically review the evidence for the efficacy and safety of botulinum toxin in the management of OAB.
Materials and Methods
We performed a systematic review of the literature to identify articles published between 1985 and March 2009 on intravesical botulinum toxin A (BTX) injections for the treatment of refractory idiopathic overactive bladder in both men and women. Database searched included MEDLINE, CENTRAL, and EMBASE. Data were tabulated from case series and from randomized controlled trials (RCTs). Data were pooled where appropriate.
Results
Our literature search identified 432 titles. Twenty-three full articles were included in the final review. Three randomized placebo-controlled trials addressing the use of botulinum toxin-A were identified (99 patients total). The pooled random effects estimate of effect across all three studies was 3.88 (95% C.I. -6.15, -1.62), meaning that patients treated with BTX had 3.88 fewer incontinence episodes per day. UDI data revealed significant improvements in quality of life compared with placebo, with a standardized mean difference of -0.62 (CI -1.04, -0.21). Data from case series demonstrated significant improvements in OAB symptoms and quality of life, despite heterogeneity in methodology and case mix. However, based on the randomized controlled trials, there was a nine-fold increased risk of elevated post-void residual after BTX compared with placebo (8.55, 95% CI 3.22-22.71).
Conclusions
Intravesical injection of botulinum toxin resulted in improvement in medication-refractory OAB symptoms. However, the risk of elevated post-void residual and symptomatic urinary retention was significant. Several questions remain concerning the optimal administration of BTX for the OAB patient.
doi:10.1016/j.juro.2010.02.009
PMCID: PMC3152380  PMID: 20400142

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