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1.  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.
PMCID: PMC2964005  PMID: 20981257
2.  An animal study to compare the degree of the suppressive effects on the afferent pathways of micturition between tamsulosin and sildenafil 
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).
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.
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.
PMCID: PMC3871018  PMID: 24160992
Overactive bladder syndrome; Tamsulosin; Sildenafil; Neuronal activity; Afferent pathways of micturition
3.  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.
PMCID: PMC3819880  PMID: 24235970
4.  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.
PMCID: PMC2938554  PMID: 20877608
Antimuscarinics; bladder training; overactive bladder
5.  How Dry is “OAB-Dry”?: Perspectives from Patients and Physician Experts 
The Journal of urology  2012;188(5):1811-1815.
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.
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.
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.
PMCID: PMC3571660  PMID: 22999694
focus groups; qualitative research; urge urinary incontinence; grounded theory; overactive bladder
6.  Systematic review of therapy for men with overactive bladder 
Canadian Urological Association Journal  2011;5(5 Suppl 2):S143-S145.
Lower urinary tract symptoms (LUTS) can have multiple causes in men. Overactive bladder (OAB) is an empirical diagnosis used as the basis for initial management after assessing symptoms, physical findings, urinalysis and other indicated evaluations. In men, the diagnosis is complicated by the potential of benign prostatic hyperplasia (BPH), which is a histological diagnosis. Although storage symptoms (i.e., those associated with OAB) are the most bothersome group of LUTS in men with BPH, these patients are usually treated with BPH rather than OAB drugs. The standard pharmacologic treatment of patients with bothersome voiding and storage LUTS at low risk of progression should be an α1-AR antagonist. The combination α1-AR antagonist + antimuscarinic agent is an appropriate and valid option for male patients with voiding symptoms and persistent storage symptoms.
PMCID: PMC3193387  PMID: 21989528
7.  Effects of Spinal and Peripheral Injection of α1A or α1D Adrenoceptor Antagonists on Bladder Activity in Rat Models with or without Bladder Outlet Obstruction 
Antagonists of α1-adrenergic receptors (α1ARs) relax prostate smooth muscle and relieve voiding and storage symptoms. Recently, increased expression of α1ARs with change of its subtype expression has been proved in bladder outlet obstruction (BOO). To search for the evidence of changes in α1ARs subtype expression and activity in the peripheral and spinal routes, the effects of spinal and peripheral administration of tamsulosin (an α1A/D-selective AR), naftopidil (an α1A/D-selective AR), and doxazosin (non-selective AR) on bladder activity were investigated in a rat model with or without BOO.
A total of 65 female Sprague-Dawley rats were divided into the BOO surgery group (n=47) and the sham surgery group (n=18). After 6 weeks, cystometry was assessed before and after intrathecal and intra-arterial administrations of tamsulosin, naftopidil, and doxazosin.
After intra-arterial administrations of all three drugs, bladder capacity (BC) was increased and maximal intravesical pressure (Pmax) was decreased in both BOO and the sham rat models (P<0.05). After intrathecal administration of all three drugs, BC was increased and Pmax was decreased in only the BOO group. The episodes of involuntary contraction in the BOO rat models were decreased by intra-arterial administration (P=0.031). The increase of BC after intrathercal and intra-arterial administrations of α1ARs was significantly greater in the BOO group than in the sham group (P=0.023, P=0.041). In the BOO group, the increase of BC and decrease in Pmax were greater by intra-arterial administration than by intrathecal administration (P=0.035). There were no significant differences of the degrees of changes in the cystometric parameters among the three different α1ARs.
Up-regulations of the α1ARs in BOO were observed by the greater increases of BC after α1AR antagonist administrations in the BOO group than in the sham group. However, there were no subtype differences of the α1ARs in functional parameters of bladder activity. In addition, α1ARs also act on the lumbosacral cord which implies that the sensitivity of α1ARs is increased in pathologic models such as BOO. Further evaluation including differential expression of α1ARs in BOO models are need.
PMCID: PMC3256304  PMID: 22259733
Urinary bladder; Urinary bladder neck obstruction; Adrenergic alpha-antagonists; Rats
8.  "Ejaculatory disorders and α1-adrenoceptor antagonists therapy: clinical and experimental researches" 
It is well known that the use of the α-adrenergic receptor antagonists in the BPH therapy may induce ejaculatory disorder. A review of clinical literature shows a greater incidence of ejaculatory disorder during the use of tamsulosin compared with alfuzosin. Anejaculation has been until now referred to retrograde ejaculation due to relaxation of prostatic and bladder neck smooth muscle tone. In a recent researches was evaluated the effect of tamsulosin and alfuzosin on rat vas deferent "in vitro", concluding that tamsulosin may "cause ejaculatory dysfunction by altering the progression and emission of sperm". An abnormal increase of contraction would be the cause of ejaculatory disorder. The aim of our paper is to compare human and rat vas deferens contractile activity and to evaluate with a clinical study if tamsulosin causes retrograde ejaculation disorder.
We have revaluated the human and rat vas deferens contractile activity in vitro according to our experience and literature. We have also performed a clinical study on 10 patients (48–72 y) affected by anejaculation. Post-coital urine was examined to search spermatozoa.
Human and rat vas deferens activity is not comparable. Contractile activity induced by norepinephrin after tamsulosin incubation in rat prostatic vas deferens strips is similar to the contractile activity evoked by norepinephrin in human strips. Spermatozoa were found in post coital urine of 6 patients.
In our opinion the treatment with tamsulosin may induce retrograde ejaculation but not other ejaculatory disorder due to abnormal sperm progression.
PMCID: PMC1550429  PMID: 16842616
9.  Overactive bladder in males 
Therapeutic Advances in Urology  2009;1(4):209-221.
The prevalence of overactive bladder (OAB) symptoms is considerable in both men and women and the impact on quality of life (QOL) is equally substantial. Ironically, despite nearly equal prevalence, OAB symptoms in men are infrequently treated, and often with medical therapies aimed at bladder outlet obstruction (BOO). In this review, we examine the pathophysiology of OAB and its evaluation in the context of benign prostatic hypertrophy and concomitant BOO. We then consider the efficacy and safety of individual therapeutic options for lower urinary tract symptoms in men, focusing on the mainstays of medical therapy: α-adrenergic blockers, 5-α reductase inhibitors, and antimuscarinic agents. Finally, we aim to comment on new therapeutic strategies and targets that may one day be available for the treatment of male OAB.
PMCID: PMC3126063  PMID: 21789068
anticholinergic; benign prostatic hypertrophy; overactive bladder
10.  The Urologist's View of Male Overactive Bladder: Discrepancy between Reality and Belief in Practical Setting 
Yonsei Medical Journal  2010;51(3):432-437.
In order to gain insight into the physicians' awareness of and attitude towards management of overactive bladder (OAB) in males, we performed a nationwide survey of the current strategies that urologists use to diagnose and manage OAB in male patients.
Materials and Methods
A probability sample was taken from the Korean Urological Association Registry of Physicians, and a random sample of 289 Korean urologists were mailed a structured questionnaire that explored how they manage benign prostatic hyperplasia (BPH).
A total of 185 completed questionnaires were returned. The consent rate in the survey was 64.5%. Eighty-one (44%) urologists believed that of all males with lower urinary tract symptoms (LUTS), 20% or more had OAB and 72 (39%) believed that 10-20% had OAB. Half of the urologists surveyed believed that the most bothersome symptom in male OAB patients was nocturia. Seventy-three percent of respondents reported that they prescribed alpha blockers with anticholinergics for first line management, while 19% of urologists prescribed alpha blocker monotherapy but not anticholinergics for OAB patients. Though acute urinary retention (AUR) was considered the anticholinergic adverse event of most concern, the most frequently observed adverse event was dry mouth (95%).
The present study provides insights into urologist views of male OAB. There is a discrepancy between the awareness of urologists and actual patterns of diagnosis and treatment of male OAB. This finding indicates the need to develop further practical guidelines based on solid clinical data.
PMCID: PMC2852801  PMID: 20376898
Overactive bladder; physician's practice patterns; bladder outlet obstruction; benign prostatic hyperplasia; anticholinergics
11.  Defining and Managing Overactive Bladder: Disagreement among the Experts 
Urology  2013;81(2):257-262.
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.
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.
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.
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.
PMCID: PMC3890251  PMID: 23374774
overactive bladder; urgency; urge incontinence; diagnosis; evaluation; management; definition
12.  Increased Bladder Wall Thickness in Diabetic and Nondiabetic Women With Overactive Bladder 
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.
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.
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.
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.
PMCID: PMC3713244  PMID: 23869270
Overactive urinary bladder; Urinary bladder; Diabetes mellitus
13.  Efficacy and Tolerability of Tamsulosin 0.4 mg in Patients with Symptomatic Benign Prostatic Hyperplasia 
Korean Journal of Urology  2011;52(7):479-484.
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.
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.
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.
PMCID: PMC3151636  PMID: 21860769
Prostatic hyperplasia; Tamsulosin
14.  Symptom-based diagnosis of overactive bladder: an overview 
Canadian Urological Association Journal  2011;5(5 Suppl 2):S135-S136.
The current definition of overactive bladder (OAB) is “urgency, with or without urge incontinence, usually with frequency and nocturia in the absence of an underlying metabolic or pathologic condition.” Urgency, in turn, is defined as a “sudden, compelling desire to pass urine that is difficult to defer.” While these definitions provide the framework for making a clinical diagnosis of OAB, they rely on subjective assessment of the symptoms by the patient. As well, the symptoms of OAB can be similar to those seen in other conditions, such as urinary tract infection, benign prostatic enlargement and bladder cancer. These other potential diagnoses should be ruled out in a noninvasive manner before making a diagnosis of OAB.
PMCID: PMC3193392  PMID: 21989525
15.  Development of oxybutynin chloride topical gel for overactive bladder 
Overactive bladder (OAB) is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG) is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo-controlled Phase III study.
PMCID: PMC3818935  PMID: 24198634
oxybutynin topical gel; overactive bladder; transdermal formulation
16.  Pharmacologic management of overactive bladder 
Clinical Interventions in Aging  2007;2(3):337-345.
Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.
PMCID: PMC2685261  PMID: 18044184
overactive bladder; urinary incontinence; pharmacologic management; antimuscarinic agents; anticholinergics
17.  Agents for treatment of overactive bladder: a therapeutic class review 
Overactive bladder (OAB) is a medical syndrome defined by symptoms of urgency, with or without urge urinary incontinence (any involuntary loss of urine), usually with frequency and nocturia. Although anticholinergic agents have been the first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Flavoxate was the first anticholinergic and antispasmodic agent approved by the Food and Drug Administration (FDA) to treat symptoms of OAB but is not routinely used today since newer agents are more effective. The more recent drugs, oxybutynin and tolterodine, have appeared to be equally efficacious in treating the symptoms of OAB in clinical trials; however, tolterodine has proven to be better tolerated with fewer adverse effects. In 2004, the FDA approved the three newest agents for the class: darifenacin, solifenacin, and trospium. Compared with oxybutynin and tolterodine, these agents have a more favorable side effect profile, which can enhance tolerability and patient compliance. Side effects are reduced in part because of the drugs' greater tissue selectivity for inhibiting the bladder muscle contraction over other anticholinergic receptors in the body. In recent clinical trials, darifenacin, solifenacin, and trospium have shown superiority to placebo and efficacy comparable to that of oxybutynin and tolterodine.
PMCID: PMC1906583  PMID: 17637888
18.  Perceptions of “Urgency” in Women With Interstitial Cystitis/Bladder Pain Syndrome or Overactive Bladder 
Neurourology and urodynamics  2010;30(3):402-405.
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.
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.
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.
PMCID: PMC3513332  PMID: 21412821
sensations; specificity; symptoms
19.  Clinical Factors Associated With Dose Escalation of Solifenacin for the Treatment of Overactive Bladder in Real Life Practice 
To determine the baseline clinical characteristics associated with dose escalation of solifenacin in patients with overactive bladder (OAB).
We analyzed the data of patients with OAB (micturition frequency ≥8/day and urgency ≥1/day) who were treated with solifenacin and followed up for 24 weeks. According to our department protocol, all the patients kept voiding diaries, and OAB symptom scores (OABSS) were monitored at baseline and after 4, 12, and 24 weeks of solifenacin treatment.
In total, 68 patients (mean age, 60.8±10.0 years) were recruited. The dose escalation rate by the end of the study was 41.2%, from 23.5% at 4 weeks and 17.6% at 12 weeks. At baseline, the dose escalator group had significantly more OAB wet patients (53.6% vs. 20.0%) and higher total OABSS (10.2±2.4 vs. 7.9±3.5, P=0.032) than the nonescalator group. OAB wet (odds ratio [OR], 4.615; 95% confidence interval [CI], 1.578-13.499; P<0.05) and total OABSS (OR, 1.398; 95% CI, 1.046-1.869; P<0.05) were found to be independently associated with dose escalation.
Patients who have urgency urinary incontinence and high total OABSS have a tendency for dose escalation of solifenacin.
PMCID: PMC3983505
Overactive urinary bladder; Muscarinic antagonists; Solifenacin
20.  Efficacy of combination therapy with tamsulosin and zolpidem on nocturia in patients with benign prostatic hyperplasia 
We examined the efficacy of combination therapy with α1-blocker tamsulosin and hypnotic zolpidem in patients who had suffered from sleep disturbance associated with nocturia.
Material and methods
A total of 35 patients diagnosed with nocturia with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) were studied. After treatment with tamsulosin for 4 weeks, 16 patients dissatisfied with nocturia (nocturiaquality of life index ≥4) and suspected to have sleep disturbance (Athens Insomnia Scale ≥6) received additional treatment with tamsulosin and zolpidem for 2 weeks. Outcomes were evaluated by the International Prostate Symptom Score (IPSS) and quality of life index (QOL), Athens Insomnia Scale (AIS) and nocturia-quality of life index (nocturia-QOL).
After monotherapy with tamsulosin, significant reductions in IPSS (18.9 ±3.8 to 9.9 ±3.0, p <0.001), QOL (4.5 ±0.9 to 3.2 ±0.9, p <0.001) and nocturia episodes (3.4 ±0.7 to 2.6 ±1.0, p <0.001) were observed. However 20 patients were dissatisfied with nocturia (nocturia- QOL ≥4). Among 20 patients, 16 patients were suspected to have sleep disturbances (AIS ≥6). In these patients, additional therapy with tamsulosin and zolpidem significantly reduced nocturia episodes (3.3 ±0.8 to 1.9 ±0.7, p <0.001), AIS (10.6 ±2.9 to 6.8 ±25, p <0.001) and nocturia – QOL (5.6 ±0.5 to 3.6 ±1.1, p <0.001) compared with patients after treatment with tamsulosin only.
Combination therapy with tamsulosin and zolpidem may be useful for patients with BPH dissatisfied with nocturia and suspected to have sleep disturbance.
PMCID: PMC3921753  PMID: 24578900
nocturia; tamsulosin; zolpidem; benign prostatic hyperplasia
21.  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
22.  Effectiveness of Retropubic Tension-Free Vaginal Tape and Transobturator Inside-Out Tape Procedures in Women With Overactive Bladder and Stress Urinary Incontinence 
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).
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.
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.
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.
PMCID: PMC3797895  PMID: 24143294
Overactive urinary bladder; Stress urinary incontinence
23.  Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia 
BMC Urology  2013;13:30.
Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study.
Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon.
The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events.
Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH.
PMCID: PMC3687682  PMID: 23758651
Ramelteon; Melatonin; Nocturia; Benign prostate hyperplasia; α1-blocker
24.  Impact of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Treatment with Tamsulosin and Solifenacin Combination Therapy on Erectile Function 
Korean Journal of Urology  2011;52(1):49-54.
To examine the effects on erectile function of concomitant treatment with an alpha-blocker (tamsulosin) and an antimuscarinic agent (solifenacin) in patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH).
Materials and Methods
Fifty-seven male patients with LUTS/BPH were assessed for the degree of LUTS and erectile function. In group 1 (tamsulosin) and group 2 (tamsulosin and solifenacin), changes in the International Prostate Symptom Score [IPSS: total scores, storage symptoms (ST), voiding symptoms (VD), and quality of life (QoL)], prostate-specific antigen, trans-rectal ultrasonography, urine flowmetry, residual urine, and a 5-item version of the International Index of Erectile Function (IIEF-5) were assessed after a 3-month treatment period. In both groups, it was determined whether treatment was associated with changes in LUTS and erectile function and whether improvement in the IPSS was correlated with the IIEF-5. Comparative analysis was also done to examine the linear relationship between improved IPSS scores and IIEF-5 scores.
A comparison of the degree of improvement in all the parameters indicated that both groups showed significant improvement in total IPSS, IPSS-ST, IPSS-VD, and IPSS-QoL (p<0.05). A comparison of the degree of improved sexual function associated with improved LUTS in each patient showed significant improvement in the IIEF-5 score associated with the degree of improvement in the IPSS-ST domain in group 1, but no significant associations were found in group 2. In cases in which tamsulosin was administered, the IIEF-5 score significantly improved as the IPSS-ST domain score improved. In the group in which tamsulosin and solifenacin were concomitantly administered, improvement of the IPSS-ST domain score had no significant effect on the IIEF-5 score.
In patients with LUTS/BPH, tamsulosin and solifenacin combination therapy was effective for LUTS, but erectile function was not significantly improved. Therefore, although effective for improving LUTS, combination therapy with an alpha-blocker and an antimuscarinic agent was not effective for improving erectile function.
PMCID: PMC3037507  PMID: 21344031
Prostatic hyperplasia; Sexual dysfunction, physiological; Solifenacin; Tamsulosin
25.  Urodynamic Detrusor Overactivity in Patients with Overactive Bladder Symptoms 
To evaluate the relationship between urodynamic detrusor overactivity (DO) and overactive bladder (OAB) symptoms in men and women.
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.
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.
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.
PMCID: PMC3070227  PMID: 21468287
Overactive bladder; Urodynamic investigation; Urinary incontinence; Detrusor overactivity

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