Biomedical subjects
Publications and source records attributed to J G Malone-Lee.
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OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of chronic pelvic pain patients were established. METHOD: Guidelines were compiled by a working group and based on current literature following a systematic review using MEDLINE. References were weighted by the panel of experts. RESULTS: The full text of the guidelines is available through the EAU Central Office and the EAU website (www.uroweb.org). This article is a short version of this text and summarises the main conclusions from the guidelines on management of chronic pelvic pain. CONCLUSION: A guidelines text is presented including chapters on prostate pain and bladder pain syndromes, urethral pain, scrotal pain, pelvic pain in gynaecological practice, role of the pelvic floor and pudendal nerve, general treatment of chronic pelvic pain and neuromodulation. These guidelines have been drawn up to provide support in the management of the large and difficult group of patients suffering from chronic pelvic pain.
OBJECTIVE: To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group, multinational, phase III study. SETTING: Incontinence, older care, urological, and urogynecological clinics in the United Kingdom, France, and the Republic of Ireland. PARTICIPANTS: One hundred and seventy-seven older patients (age > or =65 years) with symptoms of urinary urgency, increased frequency of micturition (> or =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours). INTERVENTION: Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4 weeks. MEASUREMENTS: Safety and tolerability were evaluated through spontaneously reported adverse events, electrocardiogram, and blood pressure measurements. Efficacy was assessed using micturition diary variables: mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours. RESULTS: The mean age of the patient population was 75 years. Overall, > or =87% of patients completed the study. Neither dosage of tolterodine was associated with serious drug-related adverse events during the study. No cardiac arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the most common adverse event in both the placebo and tolterodine treatment groups. Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth, compared with 2% of placebo-treated patients. Compared with placebo, statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups. Furthermore, patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo. CONCLUSION: Tolterodine (taken for 4 weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the treatment of older patients with urinary symptoms attributable to overactive bladder.
OBJECTIVE: To compare the efficacy of a controlled-release (CR) formulation of oxybutynin with that of conventional oxybutynin in patients with detrusor instability or detrusor hyper-reflexia whose symptoms were stabilized on conventional oral oxybutynin tablets. PATIENTS AND METHODS: The study comprised a randomized, double-blind, parallel-group trial involving 130 patients drawn from 15 centres in the UK. The study was of 6 weeks' duration, i.e. 2 weeks of screening whilst taking conventional oxybutynin tablets (5 mg twice daily) followed by 4 weeks of double-blind treatment with either CR oxybutynin tablets (10 mg once daily) or conventional oxybutynin tablets (5 mg twice daily). Outcome measures were changes in 24-h frequency and 24-h incontinence episodes recorded throughout the study on diary charts. Adverse events were recorded by patients in their diary charts and serum concentrations of oxybutynin and its active metabolite, N-desethyloxybutynin, were measured at baseline and at completion of the study to detect possible drug accumulation. RESULTS: The treatments did not differ significantly in any of the outcome measures. The primary efficacy criterion was the daytime continence at completion of the study; 53% and 58% of patients were continent on CR and conventional oxybutynin treatments, respectively (the 95% confidence interval of the difference in the proportion being - 22% to 13%; P = 0.62). The total number of side-effects experienced by those patients receiving treatment with the CR formulation was 57% of that for patients receiving treatment with conventional oxybutynin. Individual side-effects showed a similar distribution within treatment groups. There was no evidence of the accumulation of oxybutynin or N-desethyloxybutynin during the multiple dosing of CR or conventional oxybutynin tablets. CONCLUSION: The CR and conventional formulations of oxybutynin did not differ in their efficacy, and the CR formulation was associated with fewer side-effects. In addition, CR oxybutynin appeared to maintain therapeutic blood levels over the 24 h dosing interval with no accumulation of oxybutynin or its active metabolite. Once-daily dosing with a CR tablet is seen as convenient for the patient and is expected to result in improved compliance in patients already stabilized on conventional oxybutynin treatment.
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OBJECTIVE: To compare urodynamic indices of isometric and isotonic detrusor contractile function between patients with idiopathic detrusor instability and patients with multiple sclerosis (MS) and detrusor hyper-reflexia and thus determine whether the different types of detrusor instability share a common pathophysiological pathway. PATIENTS AND METHODS: Two groups of women were studied; 1139 neurologically normal patients with detrusor instability (mean age 55 years, SD 17) and 141 with multiple sclerosis (MS) and detrusor hyper-reflexia (mean age 45 years, SD 11). Patients were assessed using static water cystometry, examining storage function, isometric and isotonic detrusor contractile function and voiding outflow function. RESULTS: Bladder capacities were lower in the MS group, with a median of 357 mL, 95% confidence interval (CI) 305-400 mL, compared with the neurologically normal patients (median 450 mL, 95% CI 425-450, P < 0.001, Mann-Whitney U-test). Voiding was incomplete in the MS group, with a median (95% CI) residual volume of 100 (100-125) mL, but complete in the normal group, at 10 (10-10) mL. Higher median (95% CI) detrusor pressures at urethral opening (P(det open)) and closing (P(det close)) were recorded in the MS group than in the neurologically normal group, at 35.5 (33.2-46.6) cmH2O and 30 (27.6-31.6) cmH2O for P(det open), respectively (P = 0.003), and 25.3 (20.9-31.6)cmH2O and 16.6 (15.0-18.1) for P(det close), respectively, (P = 0.001). In the MS group, the median (95% CI) isometric unstable contractions were less well maintained, but were more powerful, at 17.6 (15.6-18.9) N, compared to the neurologically intact group at 14.4 (14.0-14.9) N (P = 0.002). In the MS group, contractions frequently did not relax back to baseline, whereas in the group with detrusor instability, full relaxation after contraction was more usual. There was no significant difference in the maximum speed of detrusor shortening (isotonic activity), measured by the velocity constant Q*, between the groups (median for both groups 20 mL/s, 95% CI 17-23). CONCLUSION: These results show differences in storage function, isometric detrusor contractile function and voiding outflow function between detrusor instability and detrusor hyper-reflexia, indicating that the two conditions may not share a common pathophysiological pathway.
BACKGROUND: Reductions in detrusor shortening velocity and detrusor contractility have been observed in association with aging. The reasons for these changes are unclear. METHODS: We examined the isometric and isotonic responses of detrusor, taken from the bladder body, to adenosine 5'-triphosphate (ATP), noradrenaline (NA), serotonin, and acetylcholine (Ach) in vitro, using bladders from young (30 days) and old (365 days) Sprague-Dawley rats, to determine whether there were any significant age-related differences. RESULTS: Isometric contractions with ATP at doses of 10(-3) to 10(-2) molar concentrations produced greater contractile forces in old rats when compared to young rats (p = .0136 at 10(-2) mole of ATP). Isotonic contractions at similar concentrations also produced significant differences between the young and the old rats, the latter being faster (p = .0225). Isometric contraction with noradrenaline produced significant differences between young and old rats, the latter being stronger. This became apparent at 10(-4) molar concentration of noradrenaline (p = .0043). Isometric contractions with serotonin also produced significantly greater contractions in the old rats when compared to young rats. The differences became apparent at 10(-4) molar concentration of serotonin (p = .045). There were no age-related differences in isotonic and isometric contractile responses to acetylcholine in the doses used in our experimental setup. CONCLUSIONS: Age-related differences in isometric function were detected in response to ATP, NA, and serotonin. Differences in isotonic function were only found in response to ATP and Ach.
This study examined changes in bladder sensation which occur with age in women. 1381 women (age range 20-95 years, mean 54.9) with symptoms of lower urinary tract dysfunction underwent urodynamic study. The bladder capacity at which they first became aware of the desire to void was taken as a quantitative measure of bladder sensation. Maximum bladder capacity fell in the eighth and ninth decades (H = 95.84, df = 7, P = 0.00), but by contrast bladder capacity at first desire to void rose progressively in association with age, both in the group as a whole (H = 17.13, df = 7, P = 0.017) and in a subgroup with detrusor instability (n = 952, H = 15.42, df = 7, P = 0.032). This rise in capacity points to a decrease in bladder sensation in association with age. This is not due to neurological disease, anti-muscarinic drugs or oestrogens, as the median capacity at first desire to void of these three subgroups did not differ significantly from that of the group as a whole.
PURPOSE: The urethral resistance relation was studied in relation to stress incontinence and detrusor instability, and used to examine age related differences in women. MATERIALS AND METHODS: We investigated women with lower urinary tract symptoms and analyzed pressure-flow plot data. RESULTS: Women with pure detrusor instability had greater detrusor pressures at urethral opening and closure than those with a stable bladder and no stress incontinence. The latter women had greater detrusor opening and closing pressures than those with a stable bladder and genuine stress incontinence at all ages. Detrusor pressures at urethral opening and closure were less in absolute terms in association with greater age. Urethral resistance was lower during voiding in women with stress incontinence. CONCLUSIONS: Our analysis showed a distinct difference in detrusor pressures at urethral opening and closure between women with and without stress incontinence. Differences were also demonstrated between women with and without detrusor instability. We found lower values of these indirect measures of urethral function in association with greater age. There was no evidence of lower urethral compliance in older women with lower urinary tract symptoms.
The aim of this study was to examine the efficacy of oxybutynin plus bladder training in the treatment of detrusor instability in frail elderly patients living independently in the community. It was a randomized, double-blind, placebo-controlled parallel-group trial of oxybutynin in 57 elderly patients (mean age 82.2, SD 6.06), with frequency and incontinence due to detrusor instability. After a 2-week run-in period patients received a bladder training and drug or placebo for the next 6 weeks. Outcome measures were changes in frequency and incontinence, recorded throughout on diary charts, and subjective evaluation of symptoms ('better'/'not better', and using a four-point scale 'cure' to 'no change'). Oxybutynin was superior to placebo in reducing daytime frequency [95% confidence interval (CI) of difference in change in frequencies totalled over 14 days was -27.0, -6.0; p = 0.003] and in producing subjective benefit (at day 29 only), when 24/28 (86%) patients on oxybutynin described benefit compared with 16/29 (55%) on placebo (p = 0.02). There was no difference between the groups in reduction of incontinent episodes. The median dose of oxybutynin titrated for therapeutic effect was 5 mg/day, and for placebo 10 mg/day (CI of difference 0.001, 5.001; p = 0.05). Side-effects reported were of similar frequency (50%) in the two groups. We conclude that oxybutynin with bladder training is superior to bladder training alone in reducing frequency due to detrusor instability in very elderly people living at home.
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