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PubMed2004

Botulinum toxin in the management of lower urinary tract dysfunction: contemporary update.

PURPOSE OF REVIEW: To review the most recent experience concerning the application of botulinum toxin in the human lower urinary tract. RECENT FINDINGS: Botulinum toxin was initially applied in the bladder of patients with spinal neurogenic detrusor overactivity and urinary incontinence, or in the urethra in cases of detrusor external sphincter dyssynergia. A large multicentric European study fully confirmed the initial expectancy in the former condition. In addition, the application of botulinum toxin was extended to the treatment of other urological disorders including non-neurogenic detrusor overactivity, non-relaxing urethral sphincter and detrusor underactivity. Interesting reports on the injection of botulinum toxin into the prostate of patients with benign prostatic hyperplasia are also reviewed. SUMMARY: Bladder injection of botulinum toxin is not yet an approved treatment for lower urinary tract dysfunction. Nevertheless, available data suggest that in the near future the toxin will become a standard therapeutic option in incontinent patients with neurogenic and non-neurogenic forms of overactive bladder, who do not respond to or do not tolerate anticholinergic medication. In addition, it might be expected that urethral botulinum toxin injections improve bladder emptying in patients with dysfunctional voiding problems besides detrusor external sphincter dyssynergia.

Adult↗

PubMed2002

Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence.

PURPOSE: We evaluated the efficacy and safety of an oxybutynin transdermal delivery system (TDS) in a general population of patients with overactive bladder and urge or mixed urinary incontinence. MATERIALS AND METHODS: Following symptom stabilization or treatment withdrawal 520 adult patients were randomized to 12 weeks of double-blind daily treatment with 1.3, 2.6 or 3.9 mg. oxybutynin TDS or placebo administered twice weekly, followed by a 12-week open-label, dose titration period to assess efficacy and safety further. Evaluations included patient urinary diaries, incontinence specific quality of life and safety. RESULTS: A dose of 3.9 mg. daily oxybutynin TDS significantly reduced the number of weekly incontinence episodes (median change -19.0 versus -14.5, p = 0.0165), reduced average daily urinary frequency (mean change -2.3 versus -1.7, p = 0.0457), increased average voided volume (median change 24 versus 6 ml., p = 0.0063) and significantly improved quality of life (Incontinence Impact Questionnaire total score, p = 0.0327) compared with placebo. Average voided volume increased in the daily 2.6 mg. group (19 ml., p = 0.0157) but there were no other significant differences between 1.3 and 2.6 mg. oxybutynin TDS and placebo. The most common adverse event was application site pruritus (oxybutynin TDS 10.8% to 16.8%, placebo 6.1%). Dry mouth incidence was similar in both groups (7.0% versus 8.3%, p not significant). In the open-label period a sustained reduction of nearly 3 incontinence episodes per day was reported for all groups. CONCLUSIONS: Doses of 2.6 and 3.9 mg. oxybutynin TDS daily improve overactive bladder symptoms and quality of life, and are well tolerated. Transdermal oxybutynin is an innovative new treatment for overactive bladder.

Administration, Cutaneous↗

PubMed2006

Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations.

BACKGROUND: The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1), provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. METHODS: Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16), idiopathic detrusor overactivity (IDO, n = 14), and asymptomatic microscopic hematuria (controls, n = 17), were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. RESULTS: TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated) fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249) and PBS (P < 0.0001) specimens, compared with controls. A significantly higher number of TRPM8-immunoreactive axons were also seen in the IDO (P = 0.0246) and PBS (P < 0.0001) groups. Urothelial TRPM8 and TRPM8-immunoreactive thick myelinated fibres appeared unchanged in IDO and PBS. The relative density of TRPM8-immunoreactive nerve fibres significantly correlated with the Frequency (r = 0.5487, P = 0.0004) and Pain (r = 0.6582, P < 0.0001) scores, but not Urgency score. CONCLUSION: This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

Adult↗

PubMed2004

Percutaneous tibial nerve neuromodulation is well tolerated in children and effective for treating refractory vesical dysfunction.

PURPOSE: We evaluated pain tolerability and the preliminary results of percutaneous tibial nerve stimulation (PTNS) in children with unresponsive lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 23 children 4 to 17 years old with LUTS refractory to conventional treatment underwent PTNS at 12, 30-minute weekly sessions. Ten patients had idiopathic overactive bladder, 7 were in nonneurogenic urinary retention and 6 had neuropathic bladder. Ten children were carefully evaluated for pain during needle insertion and electrical stimulation using certain scoring systems, namely the faces pain rating scale, Children's Hospital of Eastern Ontario pain scale, visual analogue scale and Questionario Italiano del Dolore. Evaluation was done at the first, sixth and last sessions. An anxiety-depression test was administered. All 23 children underwent clinical and urodynamic evaluation before and after treatment. RESULTS: All except 1 patient completed treatment. An anxious-depressive trait was found in 7 of 10 children/parents on anxiety-depression testing. Regarding pain, the faces pain rating scale never showed the severe pain face, the Children's Hospital of Eastern Ontario scale showed signs of pain at the beginning of each stimulation but not at the end, and the visual analog scale generally showed a low score with a further decrease during the first (p = 0.05), sixth (p = 0.03) and twelfth (p = 0.02) sessions. The Questionario Italiano del Dolore score was significantly related to the affective component of pain (p = 0.002) and it decreased between the first and last sessions. The 10 children with overactive bladder had symptom improvement in 80%, incontinence was cured in 5 of 9 and urodynamics showed normalization of cystometric bladder capacity in 62.5% with no more unstable contractions in those who became continent. Symptoms improved in 71% of the children in urinary retention. One of 3 and 4 of 7 patients had incontinence and post-void residual urine cured, respectively. Urodynamics showed an improved detrusor pressure at maximum flow (p = 0.009) and flow rate (p = 0.005). Symptoms and urodynamics did not significantly change in the neuropathic bladder group. CONCLUSIONS: PTNS is safe, minimally painful and feasible in children. It seems helpful for treating refractive nonneurogenic LUTS.

Adolescent↗

PubMed2005

Urinary storage symptoms and comorbidities: a prospective population cohort study in middle-aged and older women.

OBJECTIVE: to identify predictive morbidities for urinary storage syndromes including indicators for neurological, musculoskeletal, cardiovascular, immune, lower bowel and psychological systems. This is the first study to test prior hypotheses, based on a literature review. DESIGN: this was a prospective cohort study involving 12,570 female respondents aged 40 or more registered with general practitioners and living at home in Leicestershire. Postal questionnaires were used at baseline and 1-year follow-up (response rates 65 and 79%, respectively). MEASURES: pure stress urinary incontinence (SUI) and overactive bladder syndrome (OAB) were defined using standardised symptom indicators. Specific morbidities included reported medical diagnoses, standardised symptoms and general health indicators. Associations were identified using logistic regression, adjusting for age and physical impairment, with separate models for general and specific morbidities. RESULTS: multivariate morbidities consistently associated (i.e. both longitudinally and cross-sectionally) were SUI-cystitis and obesity; and OAB-bowel urgency, osteoporosis, imbalance, ankle swelling, cystitis, poor health and old age. Other independent predictors were SUI-multiple sclerosis and joint pain; and OAB-deep vein thrombosis and diabetes. Consistent univariate indicators supported neurological, musculoskeletal, cardiovascular, immunological and psychological connections with both types of storage disorder plus an association with lower bowel problems for OAB. CONCLUSIONS: abnormal urinary storage symptoms were predicted by obesity and poor general health, involving a range of systems of the body. OAB showed more extensive links than SUI with specific morbidities, including more medically diagnosed as opposed to symptom-based conditions. These findings were independent of problems with physical impairment.

Adult↗

PubMed2005

Urinary stress incontinence treatment with Remeex in a patient with epispadias: a case report.

Epispadias is a rare condition in women. A postmenopausal 53-year-old woman with a known problem of epispadias came to our outpatient clinic complaining of persistent severe urinary stress incontinence without overactive bladder symptoms. She had previously undergone an inefficacious tension-free vaginal tape (TVT) procedure in another institution. We implanted a Remeex (Mechanic External Regulation) device without applying any tension to the sling. Two tape regulations were performed the day after surgery and 2 months later to gain continence. At 13 months of follow up, this woman was asymptomatic and satisfied. As documented by this case here, the Remeex procedure is particularly suitable in selected high-risk patients where TVT and TVT live slings are less effective.

Epispadias↗

PubMed2001

[Urinary incontinence: frequency and diagnostic and therapeutic approach in general practice in Italy].

OBJECTIVE: A large observational study was conducted to assess the frequency of urinary incontinence (UI) and overactive bladder (OAB) and to describe the diagnostic and therapeutic approach in General Medical Practice in Italy. MATERIALS AND METHODS: Subjects eligible for the study were men aged > 50 years and women aged > 40 years, observed consecutively by their own General Practitioner (GP) for a check-up or medical prescription examination during the recruitment period, who agreed to participate in the study. All the subjects included in the study were interviewed by their GP using a common questionnaire that included information about their general characteristics and a specific medical history. The subject was also asked: "Have you had involuntary loss of urine during the last 3 months?"; "Do you urinate more than 8 times a day on average and/or Do you have to get up more than once a night?"; "Have you urgency problems?". If the subject answered yes to the first question or to both the second and third, a urinary problem was diagnosed, in particular UI if the anser was yes to the first and OAB if to the second and third. In these subjects the interview was continued in order to define the type of UI, using the diagnostic flow chart proposed by Wean. RESULTS: On the whole, 9613 men (average age 64.8, range 50-98) and 13,365 women (average age 60.3 years, range 40-98) were interviewed by 774 GPs. A diagnosis of urinary problems was made in 1084 men (11.3%) and 1507 women (11.3%). Among the men the GP was already aware of the condition in 603 cases (55.6%) and a new diagnosis was made in 481 cases (44.4%). The corresponding figures for women were 560 (37.2%) and 947 (62.8%). The proportion of new diagnosis out of all the subjects with micturition problems tended to be greater in the younger age (chi square for trend p < 0.05). The presence of OAB without UI was found in 3.0% [95% Confidence Interval (CI) 1.7-3.5] of the men and 1.1% (95% CI 0.9-1.3) of the women. Over all, 8.3% (95% CI 7.7-8.9) of the men and 10.2% (95% CI 9.6-10.8) of the women reported UI. The frequency of OAB and UI conditions increased with age in both men and women. On the whole, a urine test was requested in 71.9% of the subjects with a new diagnosis of UI or OAB and the frequency of haematuria was equal to 15.7% of the cases, without marked differences by type of diagnosis of micturition problem. A urine culture was done in 60.7% of the cases and was positive in 17.7%. Further diagnostic investigations were prescribed in the majority of cases, 76.6%. This was observed in particular among the men (86.2% of the cases compared to 71.7% of the women) but with no substantial differences between the different diagnoses of UI. Pharmacological treatment was suggested to 68% of the men and 44.9% of the women. The condition for which pharmacological treatment was less often prescribed was stress UI, where it was suggested in 54.5% of the men and 27.3% of the women. For men, alpha-lytics were the drugs most often prescribed for all urinary problems, regardless of the type. For women, anticholinergics were the most commonly advised type of drug, followed by anti-infectives.

Adult↗

PubMed1998

Comparison of the in vitro and in vivo profiles of tolterodine with those of subtype-selective muscarinic receptor antagonists.

Tolterodine [(R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine ] is a new potent and competitive muscarinic receptor antagonist developed for the treatment of urinary urge incontinence and other symptoms of overactive bladder. In vivo, tolterodine exhibits functional selectivity for the urinary bladder over salivary glands, a profile that cannot be explained in terms of selectivity for a single muscarinic receptor subtype. The aim of this study was to compare the in vitro and in vivo antimuscarinic profiles of tolterodine with those of muscarinic receptor antagonists with distinct receptor subtype-selectivity profiles: darifenacin [(S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl]-2,2-d iphenylacetamide; selective for muscarinic M3 receptors]; UH-AH 37 (6-chloro-5,10-dihydro-5-[(1-methyl-4-piperidinyl)acetyl]-11H-dibenzo-[b ,e][1,4]diazepine-11-one; low affinity for muscarinic M2 receptors); and AQ-RA 741 (11-([4-[4-(diethylamino)butyl]-1-piperidinyl]acetyl)-5,11-dihydro-6H-py rido[2,3-b][1,4]benzodiazepine-6-one; high affinity for muscarinic M2 receptors). The in vitro profiles of these compounds were in agreement with previous reports; darifenacin and UH-AH 37 demonstrated selectivity for muscarinic M3/m3 over M2/m2 receptors, while the converse was observed for AQ-RA 741. In vivo, AQ-RA 741 was more potent (1.4-2.7-fold) in inhibiting urinary bladder contraction than salivation in the anaesthetised cat (i.e., a profile similar to that of tolterodine [2.5-3.3-fold]), while darifenacin and UH-AH 37 showed the reverse selectivity profile (0.6-0.8 and 0.4-0.5-fold, respectively). The results confirm that it is possible to separate the antimuscarinic effects on urinary bladder and salivary glands in vivo. The data on UH-AH 37 and darifenacin support the view that a selectivity for muscarinic M3/m3 over M2/m2 receptors may result in a more pronounced effect on salivation than on bladder contraction. The data on AQ-RA 741 may indicate that muscarinic M2/m2 receptors may have a role in bladder contraction.

Animals↗

PubMed1999

The usefulness of a minimal urodynamic evaluation and pelvic floor biofeedback in children with chronic voiding dysfunction.

OBJECTIVE: To report our experience of assessing children with chronic voiding dysfunction (>6 months' duration) using a minimal urodynamic evaluation, and the management of detrusor-sphincter dyscoordination (DSdc) using pelvic floor biofeedback. PATIENTS AND METHODS: From 1994 to 1997, 120 children (mean age 7.5 years) with three predominant and associated symptoms were referred to one urologist; they had nocturnal enuresis (28 children), urge incontinence (42) or urinary tract infection (50). All patients were assessed by urinary culture, renal ultrasonography and a minimal urodynamic evaluation, i.e. urinary flowmetry with sphincter electromyography (EMG) using perineal surface electrodes. If they had urinary tract infection and/or renal dilatation, they underwent voiding cysto-urethrography. In children with DSdc, urinary training with frequent voiding was instituted initially, with subsequent pelvic floor biofeedback exercises if the improvement was deemed unsatisfactory. RESULTS: DSdc was diagnosed in 33 children (28%), none of whom had isolated nocturnal enuresis. Pelvic floor biofeedback was undertaken by 15 children (12 girls and three boys); it was well accepted because it was administered as a computer game. In all affected patients the DSdc resolved on EMG and there was a significant clinical improvement. Vesico-ureteric reflux was detected in 24 patients, associated with DSdc in 10. The reflux resolved spontaneously on antibiotic prophylaxis in six children and after urinary re-education in four. CONCLUSION: A minimal urodynamic evaluation seems to be useful in the diagnosis of DSdc which caused urinary tract infection and/or bladder overactivity. The results with pelvic floor biofeedback were excellent in these children.

Biofeedback, Psychology↗

PubMed1999

Tolterodine, a new antimuscarinic drug for treatment of bladder overactivity.

Tolterodine is a nonsubtype selective antimuscarinic agent recently approved as therapy in patients with overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence. It acts by muscarinic receptor blockade in the bladder wall and detrusor muscle. Despite short terminal disposition half-lives of 2-3 and 3-4 hours for tolterodine and its active 5-hydroxy metabolite, respectively, twice/day dosing is effective due to the drug's prolonged pharmacodynamic effects. Dosage adjustment is recommended in the presence of hepatic impairment and during concurrent therapy with drugs that inhibit cytochrome P450 2D6 and 3A4 isozymes. Tolterodine significantly reduces clinically relevant end points such as number of micturitions and number of incontinence episodes/day. In general, it is superior to placebo and equivalent to oxybutynin in this regard. As might be expected from its pharmacologic profile, the principal adverse effects of the drug are anticholinergic. In clinical trials, tolterodine was tolerated significantly better than oxybutynin. Its relative merits as a first- or second-line agent for patients intolerant of oxybutynin are unclear. Until pharmacoeconomic analyses are conducted that clearly justify use of this more expensive agent, tolterodine is perhaps best reserved for patients who are intolerant of or fail oxybutynin therapy.

Benzhydryl Compounds↗

PubMed2006

Oxybutynin in detrusor overactivity.

Oxybutynin has been used for the management of detrusor overactivity for over 30 years and has withstood medical scrutiny and the test of time throughout the world. Although several agents in the class of bladder relaxants have only recently been studied, oxybutynin's effectiveness in reducing urinary frequency and urge urinary incontinence is unquestioned in the medical literature. Oxybutynin is extremely safe and effective in almost every population including children, the elderly, and those who have neurogenic bladder. With more preparations available and more dosing flexibility than any other anticholinergic medication on the market, oxybutynin remains the "gold standard" for first-line therapy for patients who have detrusor overactivity.

Humans↗

PubMed2002

State of the science: pathology and management of the patient with overactive bladder.

A relatively new term, overactive bladder is used to describe urinary frequency, urgency, and nocturia with or without urinary incontinence. Normal micturition involves coordination among the nervous system, the bladder, and the sphincter. Theories about pathogenesis include disorders of the central and peripheral nervous system, lowered levels of neurotransmitters, and structural problems of the bladder and sphincter. Assessing the patient with overactive bladder incorporates a thorough history and focused physical exam. Current treatments for this condition include lifestyle changes, behavioral interventions, pharmacologic management, and neuromodulation therapy. Research into different medications and delivery systems proves promising for the patient with overactive bladder.

Aged↗

PubMedDate not supplied

Effects of drugs used in the therapy of detrusor hyperactivity on the volume-induced contractions of the rat urinary bladder.

In this study we examined the effects of the drugs most commonly utilized in the therapy of overactive detrusor, on the volume-induced contractions of rat urinary bladder. Anticholinergics such as propantheline bromide and emepronium bromide, as well as oxybutynin decreased the amplitude of the voiding contractions after intravenous (i.v.) administration in a dose-dependent way. These anticholinergics, on the other hand, generally increased the frequency of the contractions. Nifedipine dose-dependently reduced the amplitude of the contractions. Flavoxate induced a dose-related decrease in the frequency without effects on the amplitude of the peaks. Its main metabolite 3-methylflavone-8-carboxylic acid (MFCA) was inactive after i.v. administration. Terodiline was active on the amplitude and apparently on the frequency of the voiding contractions. The alpha-adrenoceptor antagonist prazosin, as well as indomethacin, inhibited only the frequency of the voiding contractions. All the drugs active in reducing the frequency of the voiding contractions after i.v. administration, proved effective also after intracerebroventricular (i.c.v.) injection. The model of the volume-induced contractions of rat urinary bladder, seems to be a useful tool to evaluate in vivo the effects of a compound on the bladder, allowing the possibility of distinguishing among antimuscarinics and calcium antagonists, which peripherally decrease bladder contractility, and other drugs inducing a decrease in the frequency of the voiding reflex acting on the micturition centre(s) in the central nervous system (CNS).

Animals↗

PubMedDate not supplied

Correlation between the Overactive Bladder questionnaire (OAB-q) and urodynamic data of Parkinson disease patients affected by neurogenic detrusor overactivity during antimuscarinic treatment.

INTRODUCTION: Parkinson disease (PD) patients present urinary symptoms during the course of the disease, very often suggestive of overactive bladder and sustained by neurogenic detrusor overactivity. These symptoms cause a severe lowering of quality of life determining social withdrawal and they need to be early diagnosed to restore social interaction and prevent urinary tract complications. Today overactive bladder diagnosis is easier, thanks to the availability of new investigative tools, particularly voiding questionnaires. The aim of the present study was to evaluate the reliability of the Overactive Bladder screener (OAB screener/OAB-questionnaire), a new voiding questionnaire specifically developed for the overactive bladder diagnosis in PD subjects suffering from overactive bladder symptoms. Clinical data obtained by the questionnaire were compared with urodynamic outcomes, at basal conditions and after antimuscarinic treatment, to better explorate the questionnaire reliability. MATERIALS AND METHODS: Forty PD patients have been enrolled in the protocol, and submitted to the OAB screener, voiding diary and urodynamic investigation before and after antimuscarinic treatment. OAB-score and urodynamic parameters were statistically analyzed and compared. RESULTS: The OAB-q well correlated with voiding diary and urodynamic data of Parkinson subjects either at baseline or after the antimuscarinic treatment. The study suggests that this clinical tool might be used for neurogenic overactive bladder diagnosis and that it seems to be a useful outcome measure for treatments of neurogenic OAB.

Aged↗

PubMed2004

Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel.

BK large conductance voltage- and calcium-activated potassium channels respond to elevations in intracellular calcium and membrane potential depolarization, braking excitability of smooth muscle. BK channels are thought to have a particularly prominent role in urinary bladder smooth muscle function and therefore are candidate targets for overactive bladder therapy. To address the role of the BK channel in urinary bladder function, the gene mSlo1 for the pore-forming subunit of the BK channel was deleted. Slo(-/-) mice were viable but exhibited moderate ataxia. Urinary bladder smooth muscle cells of Slo(-/-) mice lacked calcium- and voltage-activated BK currents, whereas local calcium transients ("calcium sparks") and voltage-dependent potassium currents were unaffected. In the absence of BK channels, urinary bladder spontaneous and nerve-evoked contractions were greatly enhanced. Consistent with increased urinary bladder contractility caused by the absence of BK currents, Slo(-/-) mice demonstrate a marked elevation in urination frequency. These results reveal a central role for BK channels in urinary bladder function and indicate that BK channel dysfunction leads to overactive bladder and urinary incontinence.

Alleles↗

PubMed2002

Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET).

Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder, a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence, usually in combination with urinary frequency and nocturia. This study consisted of two trials; in one, patients with overactive bladder were randomized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release oxybutynin (OER). The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other, or for geographical location. A total of 1289 patients were enrolled, 669 in the tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients prematurely withdrew from the trial in the TER 4 mg group (12%) than either the OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group perceived an improved bladder condition, compared with 60% in the TER 2 mg group, 59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4 mg). Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10 mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although differences between doses only reached statistical significance in the oxybutynin trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg. In conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg.

Adult↗

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↗