Clinical safety, tolerability and efficacy of combination tolterodine/pilocarpine in patients with overactive bladder.

AIMS: The purpose of this study was to assess the safety, tolerability and impact on overactive bladder (OAB) symptoms of a novel combination of tolterodine immediate-release (IR) 2 mg and delayed-release pilocarpine 9 mg in patients with OAB. METHODS: Eligible patients with OAB were randomised to each of three treatments [tolterodine/pilocarpine (2/9 mg), tolterodine IR 2 mg or placebo] twice daily for 4 weeks in a double-blind, crossover fashion. At the end of the 12-week, double-blind treatment period, patients could enter an open-label extension during which they were re-randomised to either tolterodine/pilocarpine (3/13.5 mg) twice daily or tolterodine extended-release 4 mg once daily for 12 weeks. RESULTS: A total of 138 patients were randomised to double-blind medication. Both tolterodine/pilocarpine (2/9) and tolterodine IR 2 mg significantly reduced incontinence episodes and daily micturitions (p < 0.001 vs. placebo), with similar reductions in symptoms observed between active treatment groups. Tolterodine/pilocarpine (2/9) was associated with consistently lower Visual Analogue Scale (VAS) scores for all dry mouth parameters compared with tolterodine alone. Salivary flow over a 3 h period remained fairly constant after tolterodine/pilocarpine (2/9) administration, similar to placebo, but decreased markedly after administration of tolterodine alone. In the extension study, patients receiving tolterodine/pilocarpine (3/13.5) reported comparable dry mouth VAS scores to tolterodine extended-release alone without additional side effects or loss of efficacy. The combination was well tolerated, and the adverse effects observed were consistent with the known safety profiles of tolterodine and pilocarpine. CONCLUSIONS: A combination of tolterodine/pilocarpine (2/9) effectively reduced the incidence of dry mouth compared with tolterodine IR alone while maintaining treatment efficacy in OAB.

STEP: simplified treatment of the enlarged prostate.

We propose a simple and practical approach to the identification, evaluation and treatment of lower urinary tract symptoms (LUTS) resulting from an enlarging and obstructive prostate. The proposed Simplified Treatment for Enlarged Prostate (STEP) plan is a logical guide to patient management by the primary care provider (PCP). Symptoms of enlarged prostate (EP) are common and may frequently progress into a condition with profound adverse effects on quality of life. Despite the high prevalence, EP is underdiagnosed and undertreated. This situation may result from patient- and provider-related issues. Assessment of symptoms of EP should be initiated with a discussion of LUTS. Evaluation includes a focused history, physical examination and selected laboratory tests. Certain factors put the symptomatic patient at risk for disease progression; however, not all factors can be readily evaluated in the PCP setting. The serum prostate-specific antigen (PSA) level acts both as an indicator of prostatic size and a screening tool for prostatic cancer, and thereby provides an important tool for PCPs. The STEP plan is a logical guide to patient management. Step 1, watchful waiting, is appropriate in patients with symptoms that are not bothersome. If symptoms cause bother, the initiation of an alpha-blocker (AB) in step 2, provides relatively rapid symptom improvement. Patients with bothersome symptoms and a PSA > or = 1.5 ng/ml are at risk for progression and consideration should be given to combination treatment with an AB and a 5alpha-reductase inhibitor (step 3). Patients with refractory symptoms should be referred to a urologist (step 4). Identification, evaluation and management of EP are within the domain of the primary care setting. The STEP approach provides a simple and practical framework for PCPs to manage most men with symptoms of EP.

Baseline incontinence severity is predictive of the percentage of patients continent after receiving once-daily trospium chloride extended release.

OBJECTIVE: It has been assumed that a patient's underlying baseline overactive bladder (OAB) incontinence severity is predictive of the resulting efficacy of pharmacological treatment. The objective of this study was to stratify and analyse the effects of baseline incontinence disease severity on the treatment outcome of the percentage of patients continent (PPC) during treatment with once-daily trospium chloride 60 mg extended release (XR). METHODS: A post hoc analysis was conducted on pooled data from two 12-week, randomised, double-blind phase III studies in the USA in which 1165 patients with baseline urgency, and an average of >or= 1 urge urinary incontinence (UUI) episode/day and >or= 10 toilet voids/day on a 3-day bladder diary, received once-daily trospium chloride 60 mg XR (n = 578) or placebo (n = 587). Patients were stratified by the mean number of UUIs/day (1.0, > 1.0-2.0, > 2.0-5.0 or > 5.0) at baseline. The efficacy parameter that was analysed was complete continence (defined as no UUIs on a 3-day bladder diary collected at week 12 of treatment). RESULTS: Baseline UUI levels were inversely correlated with the week 12 PPC (p < 0.0001). Post-treatment PPCs were higher with trospium chloride XR vs. placebo at all degrees of severity. Complete continence was achieved in 75% of trospium chloride XR recipients with 1.0 UUI/day at baseline and 48% of those with > 1.0-2.0 UUIs/day at baseline. CONCLUSIONS: These findings support the assumption that baseline incontinence severity affects the likelihood of achieving continence from OAB therapy, and that patients with less severe OAB (e.g. 1 UUI/day) can expect higher 'dry rates' following treatment (e.g. up to 75%) than those with more severe OAB. This information can provide a useful tool for the physician and patient in establishing expectations during therapy.

Trospium chloride once-daily extended release is effective and well tolerated for the treatment of overactive bladder syndrome: an integrated analysis of two randomised, phase III trials.

BACKGROUND: Trospium chloride is an antimuscarinic agent with a hydrophilic polar quaternary amine structure that is minimally metabolised by hepatic cytochrome P450 and is actively excreted in the urine, each of which confers a potential benefit with regard to efficacy and tolerability. PURPOSE: We analysed pooled data from two identically designed phase III trials of a once-daily, extended-release (XR) formulation of trospium chloride (trospium XR 60-mg capsules) in subjects with overactive bladder syndrome (OAB). METHODS: Adults with OAB of > or = 6 months' duration with urinary urgency, frequency and > or = 1 urge urinary incontinence (UUI) episode/day were enrolled in these multicentre, parallel-group, double-blind trials. Participants were randomised (1 : 1) to receive trospium XR 60 mg or placebo for 12 weeks. Primary efficacy variables were changes in urinary frequency and the number of UUI episodes/day. Adverse events (AEs) were recorded throughout. RESULTS: In total, 1165 subjects were randomised (trospium XR, 578; placebo, 587). At baseline, subjects averaged 12.8 toilet voids/day and 4.1 UUI episodes/day. Compared with placebo, subjects treated with trospium XR had significantly greater reductions from baseline in the mean number of toilet voids/day (-1.9 vs. -2.7; p < 0.001) and UUI episodes/day (-1.8 vs. -2.4; p < 0.001) at week 12. The most frequent AEs considered possibly related to study treatment were dry mouth (trospium XR, 10.7%; placebo, 3.7%) and constipation (trospium XR, 8.5%; placebo, 1.5%). Notably, rates of central nervous system (CNS) AEs were lower with trospium XR vs. placebo (dizziness: 0.2% vs. 1.0%; headache: 1.4% vs. 2.4%). CONCLUSIONS: Treatment with trospium XR resulted in statistically significant improvements in both of the dual primary and all of the secondary outcome variables. Trospium XR demonstrated favourable rates of AEs, particularly CNS AEs (numerically lower than with placebo) and dry mouth (lower than previously reported with trospium immediate-release, although not compared in a head-to-head study).

Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study.

OBJECTIVE: To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS: The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS: A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS: Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study.

Pentosan polysulfate sodium (PPS) was compared with placebo for the symptomatic therapy of interstitial cystitis in a double-blind, multicenter study. A total of 110 patients were enrolled and treated for three months. In this study, overall improvement of greater than 25 percent was reported by 28 percent of the PPS-treated patients and by 13 percent of the placebo-treated patients (p = 0.03). The investigators' overall evaluation provided similar results, 26 percent vs 11 percent in favor of PPS (p = 0.04). Improvement in pain and pressure to urinate also favored PPS over placebo and approached statistical significance (p = 0.07 and 0.08). The incidence of adverse reactions was 6 percent in the PPS-treated group and 13 percent in the placebo-treated group. All adverse reactions were minor, and treatment was discontinued by 1 patient in the PPS group and 2 in the placebo group. In this study, PPS was found to be significantly more effective than, and equally as safe as, placebo.

Pelvic floor electrical stimulation for the treatment of urge and mixed urinary incontinence in women.

OBJECTIVES: To determine the efficacy of daily or every-other-day electrical stimulation in treating detrusor instability (urge) or urge plus genuine stress (mixed) urinary incontinence in women. METHODS: A multicenter, prospective, nonrandomized study enrolled subjects with urge and mixed urinary incontinence assigned to daily or every-other-day treatments (15 minutes twice daily) using pelvic floor stimulation. Outcome measures assessed were (1) leakage episodes, nocturnal episodes, voiding frequency, total voids, and pad count, and (2) patient subjective assessment and quality of life. RESULTS: Seventy-two subjects were enrolled. Sixty-eight subjects completed the 20-week protocol: 33 treated daily and 35 treated every other day. The entire study group (n = 68) experienced a significant decrease in total leaks (P < 0.001), nocturnal episodes (P = 0.001), pad count (P = 0.002), and total voids (P = 0.003) and on visual analog scales. Sixty-nine percent (n = 46) of subjects with urge or mixed incontinence were cured or improved by at least 50%, with 28% (n = 19) being cured. There were no significant differences between daily and every-other-day users. Nonresponse was correlated with number of previous therapies (P < 0.001) and number of vaginal deliveries (P = 0.007). Overall, subjects were 93% compliant with device use, and 72% (n = 47) were satisfied with the therapy. CONCLUSIONS: Twenty weeks of pelvic floor electrical stimulation therapy is effective in treating urge and mixed urinary incontinence, regardless of daily or every-other-day treatments.

Pelvic floor electrical stimulation: a comparison of daily and every-other-day therapy for genuine stress incontinence.

OBJECTIVES: To compare the effectiveness of daily and every-other-day electrical stimulation in treating genuine stress incontinence. METHODS: Subjects with genuine stress incontinence were enrolled in a multicenter, prospective, nonrandomized study and underwent daily or every-other-day pelvic floor stimulation treatments for 15 minutes twice a day. Outcome measures assessed were (1) leakage episodes and pad count; (2) leakage amount, and (3) subject subjective assessment and quality of life. Thirteen subjects treated daily and 15 treated every other day completed the 20-week protocol. One-year follow-up data were available for 21 subjects. RESULTS: No significant differences in primary outcome variables were found between the groups. Subjects treated every other day had significant decreases in total leakage episodes (P = 0.04), pad count (P = 0.04), total voids (P = 0.02), and visual analog scale scores, with stress incontinence cured or improved by 50% in 73% (n = 11). Subjects treated every day had significant decreases in urge episodes (P = 0.03), pad count (P = 0.05), and visual analog scale scores, with 62% (n = 8) cured or improved by 50%. Compliance was higher for subjects treated every other day (P = 0.05). Satisfaction with therapy was 75% (n = 10) for daily treatment and 77% (n = 12) for every-other-day treatment. At 1 year, 70% (n = 7) of subjects who continued device use maintained their cure or improvement status. CONCLUSIONS: Both daily and every-other-day therapy with pelvic floor electrical stimulation are effective in treating genuine stress incontinence. Subjects who continue device use maintain a higher curve or improvement rate.

Hydroureteronephrosis after spinal cord injury. Effects of lower urinary tract dysfunction on upper tract anatomy.

The hypothesis that upper tract changes in the absence of vesicoureteral reflux are a function of chronically elevated intravesical pressure has had increasing impact on the management of the lower urinary tract in patients with lower tract dysfunction secondary to neurogenic bladder disease. The application of our growing ability to measure bladder and bladder outlet function objectively and in a more physiologic manner through expanding urodynamic techniques will continue to provide information that can be applied to the diagnosis and treatment of lower urinary tract dysfunction and hydroureteronephrosis after spinal cord injury. Current methods of classifying lower urinary tract behavior have not provided the ability to identify accurately those patients at greatest risk for upper tract deterioration. The application of new techniques and the use of new measures may increase our ability to identify these patients.

History, physical examination, and classification of neurogenic voiding dysfunction.

Although exceptions exist, clinical and urodynamic findings can be predicted on the basis of the location of the neurologic lesions. Conversely, these findings can be used to predict the location of the lesion. Recognition of similar patterns allows for classification, and classification allows the physician more readily to devise a diagnostic and therapeutic plan. Furthermore, a simple and practical classification system facilitates communication between physicians.

The pathophysiology of stress incontinence.

The factors contributing to stress incontinence of urine are reviewed and categorized with respect to their effects on coaptation and compression of the urethra. Intrinsic urethral dysfunction and poor anatomic support are discussed from both a functional and a pathophysiologic approach.

Transvaginal needle bladder neck suspension.

Like the transabdominal bladder neck suspension, the aim of the transvaginal needle suspension of the bladder neck is to suspend the bladder neck and urethra in a fixed retropubic position. Because the transvaginal technique does not require the splitting of the abdominal wall fascia, postoperative discomfort and convalescence may be lessened. Different techniques of transvaginal needle bladder neck suspension, including suspension of the bladder neck with a fascial sling, are discussed in detail.

Genitourinary fistulae. Vaginal approach for repair of vesicovaginal fistulae.

Controversy still remains concerning the timing of repair, the type of approach, and the technical guidelines most likely to prevent recurrence of both radiated and nonradiated vesicovaginal fistulae. The authors advocate the transvaginal approach because it avoids a cystotomy and involves minimal blood loss and consequently is followed by less postoperative discomfort and a shorter hospital stay. Included in this discussion are the techniques and results of the transvaginal approach for simple vesicovaginal fistulae as well as for complex cases and radiation fistulae.

Use of synthetic material in sling surgery: a minimally invasive approach.

Traditionally, autologous material has been favored over synthetic material in the construction of pubovaginal slings for the treatment of female stress urinary incontinence (SUI). This preference arose largely because of concern about an increased incidence of infection or sling erosion when synthetic materials are used. However, when care is taken to minimize the amount of synthetic material, reduce total operative time, and limit exposure of the material to the operative field, female SUI can be treated effectively with synthetic material with an acceptably low complication rate. Furthermore, utilization of slings constructed with artificial graft material can be minimally invasive, cost effective, and well tolerated.

Age-related physiologic and pathologic changes affecting lower urinary tract function.

The physiologic changes and pathologic conditions that are frequently seen in the elderly population create a clinical challenge requiring knowledge of the "normal" voiding function, as well as commonly observed alterations. This article reviews the more common physiologic changes, disease states, and iatrogenic causes associated with aging that affect urinary tract function.

Office evaluation of female urinary incontinence.

The diagnosis and therapy of urinary incontinence in the female patient demand an orderly approach to this complex problem. In this article, the authors suggest a classification that can simplify the approach to the differential diagnosis; review the "catheterization test," a simple diagnostic modality; and briefly discuss some of the surgical and nonsurgical options for therapy. The primary emphasis is on the evaluation of the loss of urine per urethra.

Artificial urinary sphincter: evolution and development.

The first hydraulic artificial urinary sphincter came into clinical use in 1972. The original prototype has undergone many modifications resulting from advances in mechanical design, applications of new technology, and clinical experience. This evolutionary process has culminated in the AS800, the most frequently used hydraulic artificial urinary sphincter in the U.S. today. Although the AS800 device most closely approximates the biological urinary sphincter, clinical demands for an ever more ideal urinary sphincter require the ongoing improvement of this device.

Experience with the penile prosthesis and artificial urinary sphincter.

The therapy of two common urologic problems, erectile dysfunction and urinary stress incontinence, has been revolutionized over the last 20 years by the incorporation of principles of hydraulic mechanics into the field of silicone prosthesis implantation. The inflatable penile prosthesis is surgically implanted into men with impotence due to organic or psychogenic etiology. The artificial urinary sphincter has found widespread use in males and females in both the adult and pediatric populations with stress incontinence from a variety of causes. Associated with these popular devices are various complications relating to the anatomic site as well as the host's immunologic response. The use of these implants, as well as the technologic innovations resulting from various adverse effects, are reviewed herein.

Hydronephrosis and renal deterioration in the elderly due to abnormalities of the lower urinary tract and ureterovesical junction.

The geriatric population presents a unique challenge to the health care provider. The incidence of common lower urinary tract disorders, such as benign prostatic hypertrophy (BPH), prostate cancer and incontinence increase dramatically with aging. In their more severe forms, these disorders may predispose to hydronephrosis and ultimately to renal deterioration. This review of lower urinary tract and ureterovesical junction (UVJ) physiology and pathophysiology, will focus on: (1) anatomic UVJ obstruction from prostate cancer, or severe bladder hypertrophy, (2) functional obstruction from compression or stretching of the UVJ during bladder distention from urinary retention, and (3) bladder decompensation in the female. We will present a diagnostic and treatment algorithm and discuss future trends in the geriatric population. Clearly, the geriatric health care provider always must consider the lower urinary tract when confronted with acute renal deterioration, because prompt diagnosis and treatment of significant, lower-urinary-tract disease can maximize recovery of renal function.

Urinary incontinence: steps to evaluation, diagnosis, and treatment.

In this era of rapid, scientific medical advances, we still live with the myth that urinary incontinence should be accepted as a normal part of aging. Urinary incontinence, however, should not be considered a disease but rather a symptom or sign of an underlying problem. Patients with urinary incontinence now have many places to turn for advice and medical treatment. In addition to urologists, gynecologists, and geriatricians, nurses are actively involved in the evaluation and management of patients with urinary incontinence. The purpose of this article is to outline a systematic nursing approach to the evaluation, diagnosis, and treatment of patients with urinary incontinence in an office setting.