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1.  Tolterodine extended release in the treatment of male oab/storage luts: a systematic review 
BMC Urology  2014;14(1):84.
Background
Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS.
Methods
A wide Medline search was performed including the combination of following words: “LUTS”, “BPH”, “OAB”, “antimuscarinic”, “tolterodine”, “tolterodine ER”. IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER.
Results
Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of α-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment.
Conclusion
Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.
doi:10.1186/1471-2490-14-84
PMCID: PMC4230346  PMID: 25348235
Lower urinary tract symptoms; Overactive bladder; Storage LUTS; Tolterodine; Urge incontinence; Frequency; Nocturia
2.  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
3.  Association of overactive bladder and C-reactive protein levels. Results from the Boston Area Community Health (BACH) Survey 
Bju International  2011;110(3):401-407.
OBJECTIVE
To investigate the association between overactive bladder (OAB) and C-reactive protein (CRP) in a population-based sample of men and women.
SUBJECTS AND METHODS
Epidemiological survey of urological symptoms among men and women aged 30–79 years. A multi-stage stratified cluster design was used to randomly sample 5503 adults from the city of Boston. Analyses were conducted on 1898 men and 1854 women with available CRP levels.
The International Continence Society defines OAB as ‘Urgency with or without urge incontinence, usually with frequency and nocturia.’ OAB was defined as: (1) urgency, (2) urgency with frequency, and (3) urgency with frequency and nocturia.
Odds ratios (OR) and 95% confidence intervals (95% CI) of the CRP and OAB association were estimated using logistic regression.
RESULTS
Prevalence of OAB increased with CRP levels in both men and women.
In men, adjusted ORs (95% CI) per log10(CRP) levels were 1.90 (1.26–2.86) with OAB defined as urgency, 1.65 (1.06–2.58) with OAB defined as urgency and frequency, and 1.92 (1.13–3.28) with OAB defined as urgency, frequency and nocturia.
The association was more modest in women with ORs (95% CI) of 1.53 (1.07–2.18) for OAB as defined urgency, 1.51 (1.02–2.23) for OAB defined as urgency and frequency, and 1.34 (0.85–2.12) for OAB defined as urgency, frequency and nocturia.
CONCLUSIONS
Results show a consistent association of increasing CRP levels and OAB among both men and women.
These results support our hypothesis for the role of inflammation in the development of OAB and a possible role for anti-inflammatory agents in its treatment.
doi:10.1111/j.1464-410X.2011.10769.x
PMCID: PMC3325364  PMID: 22176817
C-reactive protein; epidemiology; inflammation; overactive bladder
4.  Cerebral control of the bladder in normal and urge-incontinent women 
NeuroImage  2007;37(1):1-7.
Aim:
To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 – 85 years): 11 “cases” with urge incontinence and DO (proven previously) and 10 normal “controls”. Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In “controls”, increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger “cases”, ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly “cases” showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase.
Conclusion:
Among normal “controls”, increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent “cases” and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older “cases” reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO).
doi:10.1016/j.neuroimage.2007.04.061
PMCID: PMC2075467  PMID: 17574871
functional magnetic resonance imaging; aging; urge incontinence; detrusor overactivity; urgency; overactive bladder; insula; anterior cingulate
5.  Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder 
Purpose
The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, α1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats.
Methods
Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted.
Results
Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment.
Conclusions
Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.
doi:10.5213/inj.2012.16.1.13
PMCID: PMC3321398  PMID: 22500249
Overactive bladder; Cyclophosphamide; Tamsulosin; Rats
6.  Perceptions of “Urgency” in Women With Interstitial Cystitis/Bladder Pain Syndrome or Overactive Bladder 
Neurourology and urodynamics  2010;30(3):402-405.
Purpose
To compare urgency symptoms in women with interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB).
Materials and Methods
Women with diagnoses of IC/BPS (n = 194) and OAB (n = 85) were recruited from the clinical practices of Urologists (n = 8) and Gynecologists (n = 16) with recognized expertise in the diagnosis and management of these conditions. Subjects completed a comprehensive telephone survey about their current symptoms. The questionnaire included 11 questions about urinary urgency. Responses were compared between the two groups.
Results
Urgency was commonly reported as a symptom by women with both conditions (81% IC/BPS and 91% OAB). Compared with IC/BPS, urgency in OAB more often resulted in leakage, and was perceived to be more of a problem. In IC/BPS, the urgency was primarily reported as due to pain, pressure, or discomfort, while in OAB the urgency was more commonly due to fear of leakage. However, approximately 40% of women with OAB also report urgency due to pain, pressure, or discomfort. Similar proportions of both groups (~60%) indicated that the urgency occurred “suddenly” instead of more gradually over a period of minutes or hours.
Conclusions
Urgency symptoms differed in women diagnosed with IC/BPS versus those diagnosed with OAB, but there was significant overlap. This suggests that “urgency” is not a well-defined and commonly understood symptom that can be utilized to clearly discriminate between IC/BPS and OAB. These findings reinforce the clinical observation that it is often challenging to differentiate between these two conditions.
doi:10.1002/nau.20974
PMCID: PMC3513332  PMID: 21412821
sensations; specificity; symptoms
7.  Association of Urinary Urgency and Delay Time of Micturition in Women With Overactive Bladder 
Purpose
Accurately measuring urinary urgency is important for diagnosing overactive bladder (OAB) and quantifying improvements in treatment outcome. Various methods have been recommended for evaluating urinary urgency, but these methods assess individual perceptions and preferences. To overcome the subjectivity in measuring urinary urgency, we evaluated the relationship between uroflowmetric parameters and urinary urgency in women with OAB.
Methods
Consecutive female patients with lower urinary tract symptoms (n=110) were prospectively enrolled in this study between April 2011 and September 2012. Individuals with a history of using medications that are known to affect bladder function were excluded. All enrolled patients completed uroflowmetry with a delayed time to voiding (T2V). After urination was completed, patients were asked whether they experienced any urinary hesitancy or urgency at that time.
Results
The mean patient age was 56.1 years; 70 out of 110 patients reported some degree of urinary urgency. T2V decreased with increased urgency. Several uroflowmetric parameters were observed to have a significant correlation with urinary urgency. T2V had a meaningful correlation coefficient for individuals with urgency, regardless of the voided volume. There was no significant correlation between the presence of urinary hesitancy and T2V.
Conclusions
We believe that T2V would be a complementary tool for diagnosing and determining the degree of urinary urgency in women with OAB.
doi:10.5213/inj.2014.18.3.150
PMCID: PMC4180166  PMID: 25279243
Analysis; Women; Overactive urinary bladder; Questionnaire; Urodynamics
8.  Effect of caffeine on bladder function in patients with overactive bladder symptoms 
Urology Annals  2011;3(1):14-18.
Objectives:
To evaluate the effect of caffeine at the dose of 4.5 mg/kg on bladder function in overactive bladder (OAB) adults.
Materials and Methods:
Nine women and three men aged 21-40 years with OAB symptoms were included. Each subject drank 8 ml/kg of water with and without caffeine at two separate sessions. Cystometry and uroflowmetry were performed 30 minutes after each drink. The effects of caffeine on urodynamic parameters were compared.
Results:
After caffeine ingestion, the mean volume at bladder filling phase decreased at first desire to void and normal desire to void (P<0.05), compared to the mean volume after taking water (control) drink. The mean volume at strong desire to void, urgency and maximum cystometric capacity also tended to decrease. No change in the detrusor pressure at filling phase was found. At voiding phase, the maximal flow rate, average flow rate and voided volume were increased (P<0.05). The urine flow time and time to maximal flow rate were not changed.
Conclusion:
Caffeine at 4.5 mg/kg caused diuresis and decreased the threshold of sensation at filling phase, with an increase in flow rate and voided volume. So, caffeine can promote early urgency and frequency of urination. Individuals with lower urinary tract symptom should avoid or be cautious in consuming caffeine containing foodstuffs.
doi:10.4103/0974-7796.75862
PMCID: PMC3036994  PMID: 21346827
Caffeine; overactive bladder; uroflowmetry
9.  Increased Bladder Wall Thickness in Diabetic and Nondiabetic Women With Overactive Bladder 
Purpose
Bladder wall thickness has been reported to be associated with overactive bladder (OAB) in women. Diabetic women have an increased risk for OAB syndrome and may have an increased risk for bladder wall thickness.
Methods
A total of 235 female patients aged 40 to 75 years were categorized into four groups. The first group consisted of women free of urgency or urge urinary incontinence. The second group included nondiabetic women with idiopathic OAB. The third group consisted of women with diabetes and clinical OAB, and women with diabetes but without OAB constituted the fourth group. Bladder wall thickness at the anterior wall was measured by ultrasound by the suprapubic approach with bladder filling over 250 mL.
Results
The diabetic (third group) and nondiabetic (second group) women with OAB had significantly greater bladder wall thickness at the anterior bladder wall than did the controls. However, the difference was not significant between the diabetic (third group) and the nondiabetic (second group) women with OAB. Women with diabetes but without OAB (fourth group) had greater bladder wall thickness than did the controls but this difference was not significant. Additionally, the difference in bladder wall thickness between diabetic women with (third group) and without (fourth group) OAB was not significant.
Conclusions
This is the first study to show that bladder wall thickness is increased in diabetic women with and without OAB. Additionally, nondiabetic women with OAB had increased bladder wall thickness. Further studies may provide additional information for diabetic and nondiabetic women with OAB, in whom the etiopathogenesis of the disease may be similar.
doi:10.5213/inj.2013.17.2.67
PMCID: PMC3713244  PMID: 23869270
Overactive urinary bladder; Urinary bladder; Diabetes mellitus
10.  Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study 
Aims:
To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.
Methods:
This was a 12-week, open-label, flexible-dose study of adults with OAB (≥ 8 micturitions and ≥ 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject’s and physician’s subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed.
Results:
Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p< 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement ≥ 2 points. Significant improvements from baseline (p< 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified.
Conclusion:
Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.
doi:10.1111/j.1742-1241.2009.02035.x
PMCID: PMC2705818  PMID: 19348029
11.  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
12.  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
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.  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
15.  Medical management of overactive bladder 
Overactive bladder (OAB), as defined by the International Continence Society, is characterized by a symptom complex including urinary urgency with or without urge incontinence, usually associated with frequency and nocturia. OAB syndrome has an incidence reported from six European countries ranging between 12-17%, while in the United States; a study conducted by the National Overactive Bladder Evaluation program found the incidence at 17%. In Asia, the prevalence of OAB is reported at 53.1%. In about 75%, OAB symptoms are due to idiopathic detrusor activity; neurological disease, bladder outflow obstruction (BOO) intrinsic bladder pathology and other chronic pelvic floor disorders are implicated in the others. OAB can be diagnosed easily and managed effectively with both non-pharmacological and pharmacological therapies. The first-line treatments are lifestyle interventions, bladder training, pelvic floor muscle exercises and anticholinergic drugs. Antimuscarinics are the drug class of choice for OAB symptoms; with proven efficacy, and adverse event profiles that differ somewhat.
doi:10.4103/0970-1591.65403
PMCID: PMC2938554  PMID: 20877608
Antimuscarinics; bladder training; overactive bladder
16.  Role of fesoterodine in the treatment of overactive bladder 
Muscarinic receptors have long been the target receptors for treatment of patients with overactive bladder (OAB). These patients experience symptoms of urgency, urinary frequency and nocturia, with or without urge incontinence (the involuntary leakage of urine associated with urge). Fesoterodine, a pro-drug, structurally and functionally related to tolterodine, is the newest agent developed for the treatment of OAB. Fesoterodine is broken down to the active metabolite, 5-hydroxy-methyl-tolterodine (5-HMT) by non-specific esterases. This metabolism results in the complete breakdown of the parent compound and is responsible for dose related improvements in clinical efficacy and health related quality of life. Like other antimuscarinic agents including tolterodine, fesoterodine is associated with improvements in clinical variables related both to bladder filling (decreasing micturition frequency and increasing mean voided volume) and urgency (urgency and urge incontinence episodes). Improvements in health related quality of life following treatment with fesoterodine is indicated by improvements in 7 of the 9 variables measured by the King’s Health Questionnaire. Also like other antimuscarinic agents, fesoterodine use is associated with adverse events including dry mouth. However the incidence of dry mouth is reduced with fesoterodine, compared to oxybutynin, due to the improved bladder selectivity of 5-HMT.
PMCID: PMC3818872  PMID: 24198608
fesoterodine; 5-hydroxymethy1-tolterodine; muscarinic; overactive bladder; urgency; incontinence
17.  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
18.  How frequent are overactive bladder symptoms in women with urodynamic verification of an overactive bladder? 
Objective
To determine the relationship between overactive bladder symptoms and urodynamic verification of overactive bladder.
Material and Methods
Between June 2011 and November 2011, 159 patients underwent urodynamics (UDS) at our urogynecology unit in the Ege University Hospital. Of these, 95 patients who complained of urgency, did not have any overt neurological diseases, bladder outlet obstruction and did not take any medication affecting the lower urinary tract function were evaluated. SPSS (ver. 15.0) was used to evaluate the data and the chi-square test and t test for independent samples were used for analysis.
Results
The mean age was found to be 54.5±12. Frequency was the most frequent symptom in women with overactive bladder (OAB) (82.1%), nocturia (57.8%) and (57.8%) urgency urinary incontinence followed in frequency. Detrusor over activity incidence was found to be 38.9%. There was no significant relationship between the presence of detrusor over activity (DOA) and OAB symptoms. Leak at urodynamics was found in 46.3% and there is no significant association with detrusor overactivity. Total bladder capacity was found to be significantly lower in women who had DOA (p=0.000).
Conclusion
It appears that overactive bladder symptoms do not predict detrusor over activity. Urodynamic investigation is not mandatory in the initial management of women with only OAB symptoms.
doi:10.5152/jtgga.2012.11
PMCID: PMC3939145  PMID: 24592016
Overactive bladder; urodyamics; urgency urinary incontinence; detrussor over activity
19.  Analysis of the Risk Factors for Overactive Bladder on the Basis of a Survey in the Community 
Korean Journal of Urology  2012;53(8):541-546.
Purpose
To evaluate the risk factors for overactive bladder (OAB) in a population aged 40 years and over in the community.
Materials and Methods
We conducted a community-based survey of OAB in a population aged 40 years and over in Guri City and Yangpyeong County, South Korea, by use of the overactive bladder symptom score (OABSS) questionnaire. A total of 926 subjects were included in the final analysis. The definition of OAB was more than 2 points for the urgency score and 3 points for the sum of scores. In addition, the subjects were asked about age, dwelling place, marital status, educational status, behavioral factors (smoking, drinking, etc), and medical history. Categorical variables were analyzed by using the logistic regression model and were adjusted for age by using the logistic regression model.
Results
Overall OAB prevalence was 14.1% (130/926), made up of 49/403 males (12.2%) and 81/523 females (15.5%). OAB prevalence increased with age (p<0.0001). Risk factors for OAB were educational status (age-adjusted p=0.0487), stroke (p=0.0414), osteoporosis (p=0.0208), asthma (p=0.0091), rhinitis (p=0.0008), and cataract. Other factors (dwelling place, marital status, smoking, drinking, hypertension, diabetes, hyperlipidemia, myocardial infarction, angina, tuberculosis, atopic dermatitis, hepatitis B, and depression) were not associated with OAB.
Conclusions
The prevalence of OAB in our study was about 14.1% and the risk factors for OAB were educational status, stroke, osteoporosis, asthma, rhinitis, and cataract. Knowledge of these risk factors may help in the diagnosis and treatment of OAB.
doi:10.4111/kju.2012.53.8.541
PMCID: PMC3427838  PMID: 22949998
Overactive bladder; Risk factors
20.  Fesoterodine for overactive bladder: A review of the literature 
Background: Overactive bladder (OAB) is a chronic condition affecting both men and women, with prevalence increasing with age. Antimuscarinics form the cornerstone of treatment of OAB. Fesoterodine, a nonselective muscarinic-receptor antagonist, was approved by the US Food and Drug Administration in late 2008 for once daily, oral administration in the treatment of OAB to relieve the symptoms of urinary urge incontinence, urgency, and frequency.
Objective: The aim of this review was to provide an overview of the mechanism of action of and clinical trial data for fesoterodine, and to discuss the present status of fesoterodine in the management of OAB.
Methods: The MEDLINE and Google Scholar databases were searched (June 1, 1999–December 1, 2009) using the terms fesoterodine, overactive bladder, and muscarinic antagonists. Full-text articles in English were selected for reference, and articles presenting the mechanism of action, pharmacokinetics, and data from clinical trials were included. The parameters measured were tolerability, efficacy, and health-related quality of life (HRQoL). Trials involving animals and Phase I studies were excluded.
Results: The initial literature search yielded 48 papers. A total of 20 articles fulfilled the inclusion criteria. In two 12-week, randomized, multicenter, Phase III clinical trials involving patients with increased micturition frequency and urgency and/or urinary urge incontinence (n = 836 and 1132 in each trial), both fesoterodine 4 and 8 mg were associated with significantly improved symptoms of OAB (frequency of micturition, urgency, and urge incontinence) compared with placebo (P < 0.05). In a post hoc analysis of pooled data of the Phase III trials, HRQoL improved significantly with both doses. In a 12-week, Phase Illb trial, fesoterodine 4 and 8 mg led to treatment satisfaction in ∼80% of patients (of 516 enrolled) who were initially unsatisfied with their previous treatment.
Conclusion: A review of the literature suggests that fesoterodine is an efficacious and well-tolerated treatment option for patients with OAB.
doi:10.1016/j.curtheres.2010.10.003
PMCID: PMC3969610  PMID: 24688149
overactive bladder; fesoterodine; muscarinic antagonists
21.  Relationship between Body Mass Index and Overactive Bladder in Women and Correlations with Urodynamic Evaluation 
Purpose
Overactive bladder (OAB) is a common condition. In women, studies have shown that the prevalence of OAB is positively related to increasing body mass index (BMI). Our objective was to define a relationship between BMI and OAB through correlation with urodynamic study (UDS).
Methods
A prospective study was conducted. Ambulatory women aged 18 years or older who had symptoms of OAB for at least 3 months were enrolled. Patients answered a questionnaire, had their weight and height recorded, and underwent UDS. Patients were categorized into 3 groups as follows: group 1, BMI<25; group 2, BMI 25 to 29.9; and group 3, BMI≥30.
Results
A total of 113 patients were examined (group 1, n=32; group 2, n=40; group 3, n=41). The patients' mean ages were 50, 55, and 59 years for groups 1, 2, and 3, respectively (P<0.05). Group 3 showed a significant increase in the incidence of subjective mixed leakage and the number of pads used compared with groups 1 and 2. No significant differences were seen among the groups in duration of symptoms, OAB V-8 score, or the incidence of subjective urgency or stress leakage. The UDS parameters of groups 1, 2, and 3 showed no statistically significant differences for most variables. Group 3 showed a significant increase in the incidence of urge leakage by UDS compared with group 2 only.
Conclusions
Increasing BMI was age related. A BMI≥30 showed a higher incidence of subjective urinary mixed leakage and pad use. UDS showed no significant correlation between OAB and any BMI category for most UDS parameters.
doi:10.5213/inj.2012.16.3.126
PMCID: PMC3469831  PMID: 23094218
Overactive urinary bladder; Body mass index; Urodynamics; Risk factors
22.  Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection on Elderly Patients with Chronic Central Nervous System Lesions and Overactive Bladder 
PLoS ONE  2014;9(8):e105989.
Purpose
Intravesical injection of onabotulinumtoxinA is an effective treatment for overactive bladder (OAB). Nonetheless, the treatment outcome is unclear in OAB patients with central nervous system (CNS) lesions. This study evaluated the efficacy and safety of intravesical onabotulinumtoxinA treatment in elderly patients with chronic cerebrovascular accidents (CVAs), Parkinson’s disease (PD) and dementia.
Materials and Methods
Patients with CVA, PD, dementia, and OAB refractory to antimuscarinic therapy were consecutively enrolled in the study group. Age-matched OAB patients without CNS lesions were selected to serve as a control group. OnabotulinumtoxinA (100 U) was injected into the bladder suburothelium at 20 sites. The clinical effects, adverse events, and urodynamic parameters were assessed at baseline and 3 months post-treatment. The Kaplan-Meier method was used to compare long-term success rates between groups.
Results
A total of 40 patients with OAB due to CVA (23), PD (9), dementia (8) and 160 control patients were included in this retrospetive analysis. Improvement of urgency severity scale, increased bladder capacity and increased post-void residual volume were comparable between the groups at 3 months. Patients with CNS lesions did not experience increased risks of acute urinary retention and urinary tract infection; nonetheless, patients with CVA experienced a higher rate of straining to void. Long-term success rates did not differ between the patients with and without CNS lesions.
Conclusion
Intravesical injection of 100 U of onabotulinumtoxinA effectively decreased urgency symptoms in elderly OAB patients with CNS lesions. The adverse events were acceptable, and long-term effects were comparable to OAB patients in general. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization need careful evaluation for this very vulnerable population before choosing intravesical onabotulinumtoxinA treatment.
doi:10.1371/journal.pone.0105989
PMCID: PMC4141863  PMID: 25148378
23.  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
24.  Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence 
Behavioural interventions are effective treatments for overactive bladder (OAB) and urgency urinary incontinence (UUI). They are in part aimed at improving symptoms with patient education on healthy bladder habits and lifestyle modifications, including the establishment of normal voiding intervals, elimination of bladder irritants from the diet, management of fluid intake, weight control, management of bowel regularity and smoking cessation. Behavioural interventions also include specific training techniques aimed at re-establishing normal voiding intervals and continence. Training techniques include bladder training, which includes a progressive voiding schedule together with relaxation and distraction for urgency suppression, and multicomponent behavioural training, which, in conjunction with pelvic floor muscle (PFM) exercises, includes PFM contraction to control urgency and increase the interval between voids. Guidelines for the conservative treatment of OAB and UUI have been published by several organisations and the physiological basis and evidence for the effectiveness of behavioural interventions, including lifestyle modifications, in the treatment of OAB and UUI have been described. However, many primary care clinicians may have a limited awareness of the evidence supporting the often straight-forward treatment recommendations and guidance for incorporating behavioural interventions into busy primary care practices, because most of this information has appeared in the specialty literature. The purpose of this review is to provide an overview of behavioural interventions for OAB and UUI that can be incorporated with minimal time and effort into the treatment armamentarium of all clinicians that care for patients with bladder problems. Practical supporting materials that will facilitate the use of these interventions in the clinic are included; these can be used to help patients understand lifestyle choices and voiding behaviours that may improve function in patients experiencing OAB symptoms and/or UUI as well as promote healthy bladder behaviours and perhaps even prevent future bladder problems. Interventions for stress urinary incontinence are beyond the scope of this review.
doi:10.1111/j.1742-1241.2009.02078.x
PMCID: PMC2734927  PMID: 19575724
25.  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

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