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PubMed2000

Advancements in pharmacologic management of the overactive bladder.

Continued developments in the understanding of lower urinary tract function have led to improvements in the pharmacologic manipulation of bladder dysfunction. Drug delivery changes have produced drugs that provide better efficacy and tolerability, thus improving patient compliance. Improvements in drug delivery systems have altered drug bioavailability and pharmacokinetics. Active current investigation in new agents and delivery systems for intravesical delivery has yielded intriguing early results that may substantially add to the armamentarium for the management of the overactive bladder (urgency, frequency, urge incontinence). New developments in the understanding of the neuropharmacology of the bladder, peripheral pelvic nerves, and sacral cord may provide agents with entirely new drug effects, either as primary agents or agents to be used in combination with currently available drugs. We herein review newer agents and drug delivery systems.

Adrenergic alpha-Antagonists↗

PubMed2006

Minimal clinically important change in urinary incontinence detected by a quality of life assessment tool in overactive bladder syndrome with urge incontinence.

AIMS: The objective of this research was to detect a minimal clinically important change (MCIC) in frequency of incontinence episodes in Japanese patients with overactive bladder syndrome (OAB) based on the change in domain scores of health-related quality of life (HRQoL). METHODS: The patients (n = 659) enrolled for the 8 weeks, randomized, double-blind, placebo-controlled study of an oxybutynin transdermal patch were used for the analysis. The endpoints of the study were the change in frequency of incontinence episodes and the domain scores of King's health questionnaire (KHQ) from baseline to the end of treatment. To search a threshold of the change of incontinence frequency that apparently improves patient's quality of life (QOL), we calculated mean changes of selected five KHQ domain scores for nine patient groups divided by the amount of change of incontinence frequency. A minimum value of the change of incontinence frequency in the groups with apparent improvement in the QOL scores was defined as an MCIC of incontinence frequency. RESULTS: The apparent improvement of KHQ domain scores was seen in the patient groups whose incontinence episodes decreased more than three times per week (/w) after treatment. This result was common in almost all domain scores, but more relevant for the domains related to patients' life limitations. CONCLUSION: Japanese OAB patients can feel their QOL improved if their incontinence episodes decrease more than 3 times/w. This suggests that the reduction of '3 times /w' is an MCIC of incontinence frequency for Japanese OAB patients.

Administration, Cutaneous↗

PubMed2002

Overactive bladder in the female patient: the role of estrogens.

The prevalence of urinary incontinence is known to increase with age, affecting 15% to 35% of community-dwelling women over 60 years of age. Other studies report a prevalence of 49% in women over 65 years of age. Epidemiologic studies have implicated estrogen deficiency in the etiology of lower urinary tract symptoms, although the role of estrogen replacement therapy remains controversial. This review presents recent evidence regarding the role of estrogen in lower urinary tract dysfunction, with a particular emphasis on the management of postmenopausal women with symptoms suggestive of overactive bladder.

Estrogens↗

PubMed2002

Overactive bladder in men: special considerations for evaluation and management.

Lower urinary tract symptoms (LUTS) in men may arise from a variety of underlying causes, including benign prostatic hyperplasia. LUTS may have a significant component of storage symptoms (urgency, frequency, urge incontinence) at presentation; however, the absence of overactive bladder (OAB) symptoms does not necessarily imply pure outlet obstruction nor does their presence indicate the lack thereof. Symptomatic correlates to urodynamic findings are high when considering isolated OAB symptoms. However, mixed presentations or more overtly obstructive scenarios have less correlation with baseline symptom appraisal instruments. The ideal approach for diagnosis and management is predicated on a graded approach, with more invasive evaluation withheld for those men in whom presumptive therapy fails or who present with associated complex symptoms and in whom a higher level of intervention is being considered. The increasing incidence of LUTS with age implies a partial detrusor contribution, which must be considered in the overall management schema.

Adult↗

PubMed2006

Tolterodine for treatment of overactive bladder.

Tolterodine was developed as an antimuscarinic agent specifically for the treatment of overactive bladder. Initial in vivo studies demonstrated a functional selectivity for the muscarinic receptors in the urinary bladder over the salivary glands, and subsequent clinical trials showed an overall superior tolerability profile compared with other drugs in the same class (ie, oxybutynin). With immediate- and extended-release formulations and sustained clinical efficacy during long-term treatment, tolterodine gas become an important treatment option for the symptoms of overactive bladder.

Benzhydryl Compounds↗

PubMed1993

[Vesicourethral function study and application of urinary alarm in progressive supranuclear palsy].

We performed a vesicourethral function study on seven patients with progressive supranuclear palsy. In storage phase, 6 patients had decreased urinary sensation and overactive detrusor. Although bladder compliance was normal in all patients, maximum cystometric capacity was decreased in 3 patients. In micturition phase, detrusor contraction was underactive in 4 patients and acontractile in 1 patient. Sphincter electromyogram showed detrusor-sphincter-dyssynergia in 1 patient, no decrease in 3 patients and synergistic decrease in 1 patient. Six patients had urinary incontinence partially due to those neurological abnormality, partially due to dementia and lower activity of daily living. To facilitate the care of such functional incontinence, we devised a urinary alarm. The urinary alarm is a device to detect urine in a diaper. One can know the micturition in a diaper without being informed of micturition by the patient and change diapers as soon as possible. It was also useful to examine their frequency/volume chart.

Activities of Daily Living↗

PubMed2003

A review of condition-specific instruments to assess the impact of urinary incontinence on health-related quality of life.

To date, severity of symptoms of urinary tract conditions, such as overactive bladder (OAB) and stress incontinence, have been the main indicators used to understand the burden on the patient. However, there is also an impact on patients' health-related quality of life (HRQoL) that should also be assessed. A literature search was conducted and all HRQoL instruments published in peer-reviewed journals were evaluated. Ten instruments were identified: general use (five); urinary urge (OAB) incontinence (four); and stress incontinence (one). Several were identified as valid instruments for assessing HRQoL in urinary incontinence patients.

Health Status Indicators↗

PubMed1998

Overactive bladder.

Explore the source record for details and available documents.

Humans↗

PubMed2004

Bladder training for urinary incontinence in adults.

BACKGROUND: Urinary incontinence is a common and distressing problem. Bladder training aims to increase the interval between voids and is widely used for the treatment of urinary incontinence. OBJECTIVES: To assess the effects of bladder training for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register (January 2003). The reference lists of relevant articles were searched, and trialists contacted for details of other trials. Date of the most recent search: January 2003. SELECTION CRITERIA: Randomised or quasi-randomised trials of bladder training for the treatment of any type of urinary incontinence. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and independently extracted data. Five primary outcomes were prespecified: participant's perception of cure of urinary incontinence; participant's perception of improvement of urinary incontinence; number of incontinent episodes; number of micturitions; and quality of life. Adverse events were also noted. Three hypotheses were tested: bladder training is better than no bladder training; bladder training is better than other treatments; and combining bladder training with another treatment is better than that other treatment alone. MAIN RESULTS: We assessed 73 reports of 36 potentially relevant trials; 28 reports of ten trials were eligible for inclusion with a total of 1366, predominantly female, participants. Not all participants' with overactive bladder, in five trials had urinary incontinence. Data from five trials with 467 participants, all female, are therefore included in the review. The quality of trials was variable. Few data describing long term follow up are available.Is bladder training better than no bladder training? Data were available for 149 women from two trials comparing bladder training with no bladder training. These described only a limited number of prespecified outcomes, which varied across the two trials. Point estimates of effect favoured bladder training however confidence intervals were wide and no statistically significant differences were found for primary outcome variables.Is bladder training better than other treatments? Only two trials including 125 women compared bladder training with drugs: one with oxybutynin and one with imipramine plus flavoxate. In the former trial the only outcomes demonstrating a statistically significant difference were participant's perception of cure at six months (RR 1.69; 95% CI 1.21 to 2.34) and adverse events (RR 0.03; 95% CI 0.00 to 0.44), both favouring bladder training. In the latter trial participant's perception of cure immediately after treatment just achieved statistical significance (RR 1.50; 95% CI 1.02 to 2.21) favouring bladder training, and this difference was maintained at approximately two months post treatment. One comparison of bladder training with pelvic floor muscle training plus biofeedback included 132 women: none of the differences in the primary outcomes achieved statistical significance.Is combining bladder training with another treatment better than that other treatment alone? One trial compared pelvic floor muscle training plus biofeedback supplemented with bladder training versus pelvic floor muscle training plus biofeedback alone and included 125 women. Of the primary outcomes both participants' perception of improvement and quality of life, both immediately after treatment, achieved statistical significance, favouring the bladder training combined with pelvic floor muscle training and biofeedback group (perception of improvement: RR 1.18; 95% CI 1.01 to 1.39; quality of life: MD -47.20; 95% CI -87.03 to -7.37), this was not sustained at three months. REVIEWER'S CONCLUSIONS: The limited evidence available suggests that bladder training may be helpful for the treatment of urinary incontinence, but this conclusion can only be tentative as the trials were of variable quality and of small size with wide confidence intervals around the point estimates of effect. There was also not enough evidence to determine w evidence to determine whether bladder training was useful as a supplement to another therapy. Definitive research has yet to be conducted: more research is required.

Adult↗

PubMed2003

Clinical diagnosis of bladder outlet obstruction in men with lower urinary tract symptoms: reliability of commonly measured parameters and the role of idiopathic detrusor overactivity.

AIMS: There is no generally accepted consensus how to evaluate patients with lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction (BOO). We have tried to determine whether the most frequently used objective variables as prostate volume, IPS-score, maximum flow rate, residual urine volume, functional bladder capacity, and pressure-flow study are reliable for diagnosis of BOO and we investigated the influence of idiopathic detrusor overactivity (IDO) on this condition. METHODS: A total of 153 men with LUTS and suspected BOO were systematically examined with routine investigation including digital rectal examination, transrectal ultrasound (TRUS), post-void residual urine volume measurement, uroflowmetry, and pressure-flow study. All patients completed IPS-score. Patients were divided into groups based on Schäfer's grade of obstruction and incidence of IDO and clinical and urodynamical variables were compared. RESULTS: At baseline, 45.8% of the patients were urodynamically moderately obstructed and 37.9% were found to be severely obstructed. The grade of obstruction did not correlate with age. Prostate volume, post-void residual volume (PVR), and maximum flow rate correlated significantly with the degree of obstruction. The mean IPS-score remained almost unchanged throughout all obstruction groups. The incidence of IDO was 40.5% and increased from 16% in the minor obstruction group to 38.6% and 53.4% in the moderate and severe obstruction group, respectively. The patients with IDO were older, had larger prostates and were more obstructed. There was no impact of IDO on symptomatology of BOO. CONCLUSIONS: These data indicate that IPS-score does not achieve sufficient diagnostic accuracy and its role in the assessment of BOO is limited. The grade of obstruction is more related to prostate volume, PVR, and maximum flow rate. BOO and IDO seem to be related and have numerous mutual interactions.

Aged↗

PubMed2004

Long-term bladder function in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy and type 3-4 radical hysterectomy.

BACKGROUND: The objective of the current study was to evaluate the incidence of long-term bladder dysfunction after type 3-4 radical hysterectomy in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy (NACT). METHODS: A case-control study was conducted to evaluate the occurrence of long-term bladder dysfunction in 76 patients with International Federation of Gynecology and Obstetrics Stage IB-IIA (> 4 cm), Stage IIB, and Stage III cervical carcinoma who underwent type 3-4 radical hysterectomy after NACT. Preoperative assessment included acquisition of a standardized urogynecologic history, evaluation of severity of urinary incontinence symptoms, maintenance of a 3-day voiding diary, pelvic examination, urogynecologic physical examination, urodynamic assessment, and estimation of hydronephrosis. Follow-up was carried out at least 12 months after surgery. RESULTS: Urinary symptoms (sensory loss, difficult micturition, severe urinary incontinence) were reported by 20 patients (26%). Eighteen patients (24%) had a normal urodynamic profile, 16 patients (21%) had detrusor overactivity, 22 patients (29%) had urodynamic stress incontinence, 2 patients (2%) had aconctractile detrusor, and 18 patients (24%) had mixed urinary incontinence. The length of vagina removed was significantly greater among patients who had detrusor overactivity and mixed urinary incontinence compared with patients who had a normal diagnosis. CONCLUSIONS: The observed rate of bladder dysfunction was higher than the corresponding rate reported in the literature (76%). Three main disturbances were found: detrusor overactivity (21%), mixed urinary incontinence (24%), and de novo stress incontinence (21%). Detrusor overactivity was related to a prevalence of hypertonic bladder. Among patients who underwent type 4 radical hysterectomy, the extent of caudal resection of rectovaginal ligaments and vaginal tissue was found to be more strongly associated with bladder dysfunction than was the extent of lateral parametrial resection. Despite the fact that 76% of patients had abnormal urodynamic parameters, most patients were satisfied with their voiding condition.

Adenocarcinoma↗

PubMed2006

Antimuscarinic therapy in men with lower urinary tract symptoms: what is the evidence?

Lower urinary tract symptoms (LUTS) in men have, until recently, been assumed to arise from bladder outlet obstruction (BOO) caused by benign prostatic hyperplasia. Given this presumption, all manifestations (obstructive and irritative) of LUTS have been presumed to be responsive to therapy for prostatic disorders such as alpha-blockade (with or without the relatively recent addition of 5alpha-reductase inhibitors) or surgical intervention for benign prostatic hyperplasia. However, evidence demonstrates that persistence of irritative urinary symptoms is often encountered in men despite presumed adequate management of their obstructive complaints. Although antimuscarinic drugs have been found to be effective for irritative urinary symptoms attributed to the overactive bladder syndrome, concern regarding the use of this class of drugs in men with even potential coexistent BOO has limited the use of these drugs. Data are now accumulating that suggest that the antimuscarinic class may be used in men with bothersome, irritative symptoms, despite the presence of BOO (as defined by symptoms and urodynamics) and with a reasonable expectation of efficacy and little added risk. Critical evaluation of this evidence suggests that a role may exist for the antimuscarinic class in management of LUTS in men. However, areas of incomplete knowledge, including the risk associated with long-term (greater than 3 months) use of these drugs and the value of the antimuscarinic class as monotherapy in men with LUTS, still remain to be investigated.

Humans↗

PubMed2006

Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders.

BACKGROUND: The Bladder cooling reflex (BCR) i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO) and painful bladder syndrome (PBS), but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders. METHODS: The BCR, elicited by ice water test (IWT) was performed in patients with painful bladder syndrome (PBS, n = 17), idiopathic detrusor overactivity (IDO, n = 22), neurogenic detrusor overactivity (NDO, n = 4) and stress urinary incontinence (as controls, n = 21). The IWT was performed by intravesical instillation of cold saline (0 - 4 degrees C). A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test. RESULTS: A positive IWT was observed in IDO (6/22, 27.3%) and NDO (4/4, 100%) patients, but was negative in all control and PBS patients. Thirteen (76.5%) PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002), or equivalent amount of bladder filling (100 mls) with saline at room temperature (P = 0.015). None of the control or overactive (NDO/IDO) patients reported any pain during the IWT. CONCLUSION: The BCR in DO may reflect loss of central inhibition, which appears necessary to elicit this reflex; the pain elicited in PBS suggests afferent sensitisation, hence sensory symptoms are evoked but not reflex detrusor contractions. The ice water test may be a useful and simple marker for clinical trials in PBS, particularly for novel selective TRPM8 antagonists.

Adult↗

PubMed2001

Directions in urological research and drug therapies.

This meeting report summarizes advances and notable developments in the pharmaceutical management of urological diseases presented at various sessions during the Annual Meeting of the American Urological Association held in Anaheim, California, June 2-7, 2001. More than 10,000 attendees drawn from clinical and preclinical research deliberated on the latest trends in surgical and pharmacotherapeutic management in diverse areas of urology. In particular, several forums were dedicated to reviewing scientific trends, emerging concepts and therapies in urological diseases, such as overactive bladder, erectile dysfunction and lower urinary tract symptoms, which are the focus of this report.

Journal Article↗

PubMed2006

Transvaginal urethrolysis for obstruction after antiincontinence surgery.

Our objective was to determine our success in relieving bladder outlet obstruction (BOO) with a transvaginal urethrolysis (TVU). This was a chart review that included 55 patients who underwent 61 TVU procedures between 2001 and 2005. Twenty-three patients had at least one prior TVU. Outcomes evaluated included obstructive symptoms, need for catheterization, postvoid residual (PVR), irritative symptoms, and stress urinary incontinence (SUI). Of the 46 patients with obstructive voiding preoperatively, 87% were cured. Of the 47 patients with irritative symptoms, 45% were cured, 34% improved, and 21% were left unchanged. SUI, generally mild, was noted postoperatively in 16% patients. Similar success was seen among patients with prior procedures. Aggressive TVU is very successful in relieving urinary retention and improving or curing overactive bladder symptomatology due to iatrogenic obstruction, even when a prior urethrolysis had been unsuccessful. SUI is an infrequent complication.

Aged↗

PubMed2001

Bladder injection of "naked" hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo.

The goal of these studies was to examine the potential utility of bladder instilled K+ channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 microg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSlo injection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.

Administration, Intravesical↗

PubMed2005

Darifenacin in the treatment of overactive bladder.

Darifenacin is a novel muscarinic M(3) selective receptor antagonist developed for the once-daily treatment of overactive bladder, a chronic, debilitating and highly prevalent condition affecting adults of all ages. Preclinical research has confirmed the pharmacological profile of darifenacin as a potent antimuscarinic agent with up to 59-fold higher affinity for M(3) receptors than other muscarinic receptor subtypes and selectivity for the bladder over other tissues expressing these receptors. Extensive research in large, randomized, placebo-controlled trials have demonstrated that darifenacin, at doses of 7.5 and 15 mg once daily (q.d.), is efficacious in the treatment of overactive bladder, improving the core symptoms of urinary urgency, urge incontinence, increased micturition frequency and bladder capacity. In addition, post-hoc analyses have shown that many patients can achieve clinically meaningful continence levels, e.g., > or =90% reduction in incontinence episodes or > or =7 consecutive dry days. These results are supported by significant improvements in quality of life, which have paralleled the overactive bladder symptom reductions. Both fixed and flexible darifenacin dosing regimens produce these beneficial effects, which extend to the more vulnerable population of older patients. Hence, in conjunction with data showing that this agent has a good safety and tolerability profile, these findings indicate that darifenacin may provide an effective alternative pharmacotherapy for the treatment of patients with overactive bladder.

Animals↗

PubMed2000

Biofeedback training for detrusor overactivity in children.

PURPOSE: We evaluated biofeedback training for incontinence due to detrusor overactivity in children. MATERIALS AND METHODS: Included in our study were 22 boys and 17 girls with a mean age of 11.2 years. We noted nighttime incontinence in 3 patients, nighttime incontinence and daytime urinary symptoms in 26, and daytime incontinence in 10. All patients had detrusor overactivity and incontinence refractory to conventional treatment, including bladder training, tricyclic antidepressants, anticholinergics, desmopressin and/or conditioning therapy. Urodynamic study was performed using an 8Fr double lumen transurethral catheter for cystometry, a double balloon transrectal catheter for rectal pressure and external anal sphincter pressure measurement, and surface electrodes for sphincter electromyography. During biofeedback training patients were instructed to contract the anal sphincter without raising abdominal pressure to inhibit overactive bladder contractions. Biofeedback training was repeated monthly until cystometry revealed a stable bladder or lower urinary tract symptoms improved considerably. RESULTS: Four patients were lost to followup. Of the remaining 35 children urinary symptoms were cured in 23 and improved in 4. Urodynamic studies after 6 months of biofeedback training in 33 cases showed that bladder overactivity disappeared in 10 and improved in 18. Bladder capacity at the initial desire to void and maximum cystometric capacity increased significantly (p = 0.0115 and <0.0001, respectively). Detrusor-sphincter dyssynergia in 2 patients before biofeedback training resolved in each after therapy. CONCLUSIONS: Biofeedback training for detrusor overactivity is effective even in pediatric cases refractory to conventional treatment.

Biofeedback, Psychology↗