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).

Effects of oxybutynin transdermal system on health-related quality of life and safety in men with overactive bladder and prostate conditions.

AIMS: Overactive bladder (OAB) is common in men and may exist concomitantly with benign prostatic hyperplasia (BPH) and obstruction. We present a subanalysis of results from men with OAB in a 6-month, open-label study of treatment with the oxybutynin transdermal system (OXY-TDS). Broad entry criteria were incorporated to yield a clinically representative population. METHODS: All participants received OXY-TDS 3.9 mg/day. Effectiveness was assessed by changes in scores on validated questionnaires, which included the single-item Patient Perception of Bladder Condition (PPBC), the King's Health Questionnaire (KHQ) and the Beck Depression Inventory-II (BDI-II). RESULTS: The proportion of men (n=369; mean age=69.6 years) who reported that their bladder condition caused moderate, severe or many severe problems (PPBC>or=4) improved from 77.3% at baseline to 38.1-53.6% in subsequent months. Mean KHQ scores decreased significantly (p12 (associated with a diagnosis of depression) decreased from 23.9% to 17.9% (p=0.0055). Men with a history of 'prostate problems' or use of 'BPH medication' (32.2%) had KHQ domain changes that were similar (p>or=0.1016) to those of other men. Most men (76.2%) reported no treatment-related adverse events; two men (0.5%) experienced symptoms of mild urinary retention, but neither required catheterisation. CONCLUSIONS: Oxybutynin transdermal system treatment of men with OAB was effective and well tolerated, regardless of history of prostate condition.

Clinical aspects of detrusor instability and the value of urodynamics.

According to the International Continence Society, detrusor instability (DI) is not a disease, it is a condition found only by urodynamic examination. Thus, the word instability is misleading. It implies that the bladder is abnormal. We do not think of unstable situations as being normal. It is inappropriate to use the term because it makes it too easy for clinicians to feel they have made a diagnosis when they have not. It curtails further thinking and does not promote the scientific pursuit of fact. What is the evidence that DI is abnormal? As described by the ICS in 1981, the patient must have no neurological bladder abnormality. Studies show it can be provoked in asymptomatic individuals and can be found 'naturally' with ambulatory urodynamic testing. A person may be clinically asymptomatic and totally unaware that the contraction is occurring. The findings are simply phasic pressure increases reflecting typical rhythmic contractions of visceral structures such as bowel and urinary bladder. This paper proposes the term 'phasic detrusor contractions' (PDCs). It has no connotation, describes the finding, and frees the clinician and scientist to explore the matter without prejudice.

Treatment of bacterial prostatitis. Comparison of cephalexin and minocycline.

The relative safety and efficacy of minocycline and cephalexin were examined in patients with acute or chronic prostatitis. The multicenter study was of single-blind, parallel-group design. Forty-two men received minocycline (200-mg initial dose followed by 100 mg twice daily) and 44, cephalexin (500 mg four times daily); each antibiotic was administered orally for four weeks. A follow-up period of patient assessment extended for an additional six weeks. Evaluable data were available for 20 minocycline-treated patients and for 24 cephalexin-treated patients. Clinical cure or improvement without recurrence was seen in 65 per cent of the patients who received minocycline and in 46 per cent of those given cephalexin. Bacteriologic cure without relapse or reinfection occurred in 45 per cent of the minocycline-treated men and in 21 per cent of the cephalexin-treated men. Serious adverse clinical experiences were not encountered in either treatment group. Although several factors, mainly the small number of patients, precluded a statistical analysis of comparative efficacy, it was evident that more patients in the minocycline-treated group had both clinical and bacteriologic cures (35%) than did those in the cephalexin-treated group (21%).

Measuring softness of inner female urethra. Part I. Simple new device.

A new device is described to measure clinically the softness of the female urethra. It is a rod-shaped urethral sound with a longitudinal groove along its surface. The sound is constructed in sizes 12 to 24 French. Each has one groove which is 2 mm wide and either 2, 2.5, or 3 mm deep. The groove is 11 cm long. When inserted into the filled female bladder per urethram, the groove will span the urethra from the bladder to the outside. If the urethral inner lining is soft and deformable, it will fill itself into the groove and prevent leakage of urine from the bladder along the groove to the outside. If the urethra is relatively rigid, urine will leak from the bladder. This instrument permits testing of women to determine urethral properties in preventing leakage when studied with a range of probe sizes.

Evaluation of inner urethral softness. Part II. Clinical study using new grooved probe device.

This study, in incontinent women, evaluates the effectiveness of a new device to measure properties of urethral softness. The device is a straight sound with a longitudinal groove cut along its surface. It is inserted through the urethra and into the bladder. A soft, deformable urethra is expected to fill itself into the groove and prevent the loss of urine from the bladder along the groove to the outside. Using this instrument it is learned that (1) postmenopausal women are less able to seal the urethra than younger ones; (2) as the urethra is stretched it is less able to form a seal; and (3) the anterior urethra is the weakest link in sustaining continence when tested by methods used in this program.

Role of inner urethral softness in urinary continence.

Given adequate external squeeze upon suitable urethral geometry, continence depends on the mechanical properties of the outflow tract wall. Evidence indicates that these mechanical properties include an ability to deform and behave in a fluid-like manner.

Division of spermatic vessels in orchiopexy: radionuclide evidence of preservation of testicular circulation.

Satisfactory intrascrotal position of the testicles was achieved by dividing the spermatic vessels, leaving the vas deferens intact, in 3 patients with undescended testes. A postoperative scrotal scan provided objective means of evaluating the adequacy of testicular circulation. To determine the efficacy of various procedures for orchiopexy for undescended testes we suggest that postoperative evaluation include radionuclide imaging of the scrotum.

Physical information in the external urinary stream of the normal and obstructed adult male.

The qualitative status of physical information contained in the stream of the male lower urinary tract is traced from the bladder to the broken-up external stream. The progression of modifications of this information is discussed and it is argued that information remains in the drops. Electro-optical measurements of the drops leads to pulses which can be analysed for various types of information content. These confirms that there is potential clinical value in some aspects of the information.

The physical basis of some urodynamic measurements.

This report concerns certain principles of physics that are relevant to the clinical practice of Urology as well as the research urodynamicist. Supplemental material is available in previous publications for the physiologist, cardiovascular, dynamicist, anesthesiologist and the like. The material is fairly recent only in its application to the lower urinary tract. Pressure-volume relationships were applied to be cardiovascular system more than 20 years age. Indeed, for those interested in urodynamic methods, there is a vast fund of useful pertinent information in the literature on vascular dynamics. The problems of steady and unsteady flow in flexible structures are common to both specialties. It would be unfortunate if urodynamicists were required to learn of the phenomena and their implications by the drudgery of repeated measurements rather than taking guidance from previous work. This report is intended to serve as an introduction to the approach and, hopefully, will stimulate those who are interested in urodynamic methods to seek out this information and to interpret their measurements in the light of fundamental physical phenomena that have been described and analyzed.

Cystometrics during endoscopy of a ureterocele: determination of potential for reflux.

We describe a simple preoperative clinical test to determine whether a ureterocele that is unroofed will cause reflux postoperatively. The method is outlined and explained, and clinical examples are presented.

Complication from Plastibell circumcision ring.

We describe the cases of 4 neonates with retained Plastibell rings and discuss the potential seriousness of this problem. Removal of the rings was accomplished by use of wire cutters. Local wound care resulted in perfect healing in 3 and slight scarring with ventral curvature in 1. None of these patients required skin grafting.

Megestrol acetate in treatment of benign prostatic hypertrophy.

In this study we found no significant effect on benign prostatic hypertrophy due to megestrol using standard clinical criteria. However, there is evidence using urinary drop spectrometer data which makes one suspect that megestrol does have a positive effect. If there is an effect, it is apparently so small as to be undetectable using the clinical protocol of this investigation. Since the urodynamic evidence does indicate a possibility of a positive effect, it appears reasonable to investigate further using a different protocol - perhaps a higher dosage and/or a more controlled test population.