Outcome measures for research of lower urinary tract dysfunction in frail older people.
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Aged↗
Biomedical subjects
A Mattiasson
Publications and source records attributed to A Mattiasson.
Cost-effectiveness of new treatments for overactive bladder: the example of tolterodine, a new muscarinic agent: a Markov model.
Economic analyses of interventions for chronic diseases require evaluations over a long timeframe to illustrate the benefits and costs of treatments. Clinical trials are generally short and carried out in strictly controlled conditions. They are therefore of limited value for economic evaluation aimed at facilitating decisions about resource allocation. The objective of this study was to develop a simulation model that allows integration of data from different sources to calculate the incremental cost-effectiveness and cost-utility of new treatments for overactive bladder. The model compares tolterodine, a new treatment that aims at alleviating symptoms and improving patients' quality of life, to no treatment. Simulations for Sweden are presented as an example. The Markov model combines clinical, observational, and economic data. Markov states are defined based on severity of symptoms of overactive bladder (frequency of voids and leaks). Specific costs for drug treatment and use of sanitary protections as well as utilities are assigned for each state. The effectiveness of tolterodine is based on controlled clinical trials and open long-term extensions of these trials. Outcome is measured as quality-adjusted life years (QALYs) and as the number of months spent in a state with no or very limited symptoms. During the course of 1 year, patients treated with tolterodine spend more time in states with no or limited symptoms compared to those receiving no treatment. Tolterodine-treated patients having a better quality of life during the year. The mean utility of the treated cohort is 0.70, compared to 0.67 in the no-treatment cohort, which is equivalent to the entire cohort moving by one level to a state with less severe symptoms. Mean total costs per patient in the tolterodine arm are SEK8,595 (US $1,131; 1 US$ = 7.6 SEK) compared to SEK3,286 (US$432) in the no-treatment arm. The extra cost due to tolterodine is SEK380 (US$50) per month, which falls within the range of monthly amounts that patients were willing to pay out of pocket for a 25 or 50% improvement of their symptoms in a previous study. The cost for pads is reduced by 23%. The marginal cost per QALY gained with tolterodine is estimated at SEK213,000 (US$28,000). Based on this simulation model, it appears that treatment of overactive bladder with a well-tolerated pharmacological treatment such as tolterodine is cost-effective.
Benzhydryl Compounds↗
Shortening velocity is different in longitudinal and circular muscle layers of the rabbit urethra.
The aim of the study was to investigate whether the functional difference between circular and longitudinal muscles in the female rabbit urethra is reflected in their shortening properties and lactate dehydrogenase (LDH) activity. For mechanical experiments the preparations were chemically skinned to avoid influence of membrane-related mechanisms and to enable maximal activation. Force velocity relations and the maximal shortening velocity (v(max)) were determined using the isotonic quick-release method. The v(max) was three times higher in longitudinal muscle. LDH isoform pattern was determined on agarose gels. The M-subunit, favourable for lactate formation, constituted 70% of the total in both types of muscle. There was no difference in the LDH isoform pattern despite the marked difference in v(max). We conclude that the difference in v(max) reflects differences in the contractile machinery itself. These mechanical characteristics are advantageous for the role of the circular as a tonic muscle contracting during bladder filling, and the longitudinal as a phasic muscle active in opening up the urethra during micturition.
Animals↗
Optimizing transurethral microwave thermotherapy: a model for studying power, blood flow, temperature variations and tissue destruction.
OBJECTIVE: To examine the role of microwave power and blood flow on temperature variations and tissue destruction in the prostate, using a theoretical model of transurethral microwave thermotherapy (TUMT), and thus compare fixed-energy TUMT with no intraprostatic temperature monitoring (constant microwave power applied over a fixed period) with 'feedback' TUMT in which the microwave power is adjusted according to the monitored intraprostatic temperature. MATERIALS AND METHODS: The temperature distribution in the prostate was modelled for a typical TUMT catheter at various blood flow rates. The volume of tissue destroyed was simultaneously calculated from cell survival data after thermal exposure. The calculated quantity of tissue destroyed at the different microwave power levels and blood flow rates was used to describe qualitatively the simulated treatments. RESULTS: Treatment monitoring and consistency were better during feedback TUMT than fixed-energy TUMT, in that the former compensated for variations in blood flow rate. The modelled values agreed with observations during real TUMT. CONCLUSIONS: Blood flow rate is a key factor in the outcome of TUMT. Only by measuring intraprostatic temperature is it possible to compensate for the large variations in prostatic blood flow and obtain consistent treatment results. Repeated interruptions prompted by high rectal temperatures should be minimized and preferably avoided, as the quantity of tissue destroyed is then greatly reduced, and in extreme cases the treatment is totally ineffective.
Blood Flow Velocity↗
Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder.
OBJECTIVE: To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition. RESULTS: After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily. CONCLUSION: Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.
Adult↗
Effects of spinal alpha 1-adrenoceptor antagonism on bladder activity induced by apomorphine in conscious rats with and without bladder outlet obstruction.
To test the hypothesis that the spinal control of micturition involves alpha 1-adrenoceptors, the urodynamic effects of intrathecal and intraarterial alpha 1-adrenoceptor blockade on apomorphine-induced bladder activity in rats were studied. Continuous cystometry was performed in conscious female Sprague-Dawley rats with and without bladder outflow obstruction. In normal rats, subcutaneous apomorphine, 30 micrograms/kg, induced bladder activity that was abolished or attenuated by the alpha 1-adrenoceptor antagonists indoramin and doxazosin given intrathecally or intra-arterially. In rats with outlet obstruction, apomorphine 30 micrograms/kg caused no change in cystometric parameters. However, at a dose of 100 micrograms/kg the drug induced bladder activity, which was attenuated by intrathecal indoramin or doxazosin. These results suggest that the bladder activity evoked by apomorphine-stimulation of bulbospinal pathways can be influenced by alpha 1-adrenoceptors at the spinal and peripheral levels, both in normal rats and in rats with bladder hypertrophy secondary to outlet obstruction.
Adrenergic alpha-Antagonists↗
Stimulation of bladder activity by volume, L-dopa and capsaicin in normal conscious rats--effects of spinal alpha 1-adrenoceptor blockade.
To study possible differences in alpha 1-adrenoceptor involvement in the spinal mechanisms mediating bladder activity induced by volume (bladder filling), central (L-dopa), and peripheral (capsaicin) stimulation, we investigated if these types of bladder activity were modified by intrathecal (i.t.) or intra-arterial (i.a.) administration of the alpha 1-adrenoceptor antagonist, indoramin. Indoramin is selective for the alpha 1A-adrenoceptor subtype, whereas most clinically used alpha 1-adrenoceptor antagonists, including doxazosin, have no subtype selectivity. The drug effects were studied by continuous cystometry in normal, conscious rats and rats with bladder activity evoked by intraperitoneal L-dopa (50 mg/kg after carbidopa pretreatment), or by intravesical capsaicin (30 microM). I.t. indoramin (50 nmol) significantly decreased micturition pressure, and increased bladder capacity and micturition volume. Dribbling incontinence due to urinary retention was observed in one of ten rats. L-dopa-stimulated bladder overactivity was significantly attenuated by i.t. or i.a. indoramin (50 nmol). Similar effects of i.t. and i.a. doxazosin (50 nmol) have been reported previously. Intravesical capsaicin (30 microM) caused bladder activity, which was attenuated by i.t. indoramin (50 nmol), but not by i.t. doxazosin (50 nmol). I.a. indoramin did not reduce capsaicin-induced bladder activity; doxazosin was moderately effective. The results suggest that the bulbospinal micturition reflex evoked by bladder filling and L-dopa involves a descending pathway where transmission is partly mediated by spinal alpha 1-adrenoceptors. Bladder overactivity evoked by intravesical capsaicin, which elicits a vesicospinal-vesical reflex, was not affected by i.t. doxazosin in a dose that attenuates activity mediated through the bulbo-spinal pathway. This suggests less involvement of spinal alpha 1-adrenoceptors in the vesico-spinal-vesical than in the bulbo-spinal voiding reflex.
Adrenergic alpha-1 Receptor Antagonists↗
Management of overactive bladder--looking to the future.
OBJECTIVES: To offer a perspective on potential future advances in the understanding and management of the overactive bladder. METHODS: Consideration is given to potential developments in the areas of pathophysiology, prevention, early intervention, and new pharmacologic targets for the treatment of overactive bladder. RESULTS: The future will likely reveal that motor urgency is usually a premature micturition reflex with a limited and variable degree of penetrance. Overactivity of all types in the lower urinary tract (LUT) will be regarded as the result of a partially uncontrolled on-off mechanism in the nervous system. Neurogenic factors will be found to initiate a premature activation of urethral and bladder activity, whereas myogenic factors will be recognized as serving as facilitators. As is the case today, we will probably be unable to cure or normalize the overactive bladder in the future. However, our growing understanding of the pathophysiology of the LUT will open up new possibilities for prophylactic, diagnostic, and therapeutic measures. Advances in cellular and molecular biology may allow early intervention or even prevention of the overactive bladder. Pharmacologic treatment will not only aim at functional intervention, but will attempt to influence the structure of the organs by means of trophically active drugs. Prevention of muscle cell hypertrophy and induction of nerve growth might become therapeutic realities. CONCLUSIONS: The future holds the promise of important advances that will improve our understanding of the overactive bladder and will hopefully lead to more effective treatments.
Adrenergic Antagonists↗
Willingness to pay for reduced incontinence symptoms.
OBJECTIVE: To measure the willingness to pay for a reduction in the number of micturitions and urinary leakages for patients with urge incontinence. PATIENTS AND METHODS: A self-administered questionnaire with a binary willingness-to-pay question was administered to 541 patients in Sweden with urge or mixed incontinence; 461 questionnaires were returned. The reduction in micturitions and urinary leakages valued in the willingness-to-pay question was varied randomly between 25% and 50% in two different subsamples. Information was also collected about the number of micturitions and urinary leakage, health-related quality of life and socio-economic characteristics of the patients in the study. RESULTS: Quality of life was significantly related to the severity of the symptoms and was worse than that of the sex- and age-matched general Swedish population. The median (mean) willingness to pay per month was 240 (530) Swedish krona (SEK, 1 Pound = SEK 11.50) for a 25% reduction in micturitions and leakages and SEK 470 (1030) for a 50% reduction in micturitions and leakages. As hypothesized, the willingness to pay was significantly related to the size of the reduction in micturitions and leakages, the initial number of micturitions and leakages, and income. CONCLUSIONS: Patients with incontinence problems are willing to pay substantial amounts for a reduction in the number of micturitions and leakages.
Female↗
Lack of association between cystopathy and progression of diabetic nephropathy in insulin-dependent diabetes mellitus.
Whether an association exists between cystopathy and progression of diabetic nephropathy has never been clarified. The aim of the present study was to measure the degree of cystopathy in relation to the rate of progression of diabetic nephropathy. To that end, 17 insulin-dependent diabetic patients with diabetic nephropathy but without voiding symptoms were investigated urodynamically. The median age of the patients was 45 years (range 27-67 years), diabetes duration 23 years (range 14-44 years) and the serum creatinine level was 162 mumol/L (median, range 65-449 mumol/L) at the time of the study. The progression rate of diabetic nephropathy was analysed retrospectively by measuring changes in yearly mean values of Log10 serum creatinine for a period of 13 years (3-15 years) before the investigation. The progression rate was 0.028 mumol/L/year (median). Patients with a progression rate above and below the median rate were considered to be rapid (n = 8) and slow (n = 9) progressors, respectively. More women than men had a rapid progression rate of nephropathy. Rapid progressors were found to have smaller volume or residual urine (90 vs 165 ml; p < 0.05), larger volume voided (440 vs 270 ml; p < 0.05), lower opening pressure (18 vs 48 cm H2O; p < 0.05) and lower pressure at maximum flow (37 vs 64 cm H2O; p < 0.05) compared to slow progressors. However, these variables were not related to the progression rate of nephropathy (MANOVA). Furthermore, these results should be interpreted with caution because of the natural gender differences in pressure conditions. In conclusion, rapid progression of diabetic nephropathy does not seem to be associated with dysfunction of the urinary bladder measured with cystometry and pressure flow.
Adult↗
Transurethral microwave thermotherapy.
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Humans↗
Standardization of terminology and assessment of functional characteristics of intestinal urinary reservoirs.
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Evaluation Studies as Topic↗
The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction.
This article presents a standard system of terminology recently approved by the International Continence Society, the American Urogynecologic Society, and the Society of Gynecologic Surgeons for the description of female pelvic organ prolapse and pelvic floor dysfunction. An objective site-specific system for describing, quantitating, and staging pelvic support in women is included. It has been developed to enhance both clinical and academic communication regarding individual patients and populations of patients. Clinicians and researchers caring for women with pelvic organ prolapse and pelvic floor dysfunction are encouraged to learn and use the system.
Female↗
The standardization of terminology and assessment of functional characteristics of intestinal urinary reservoirs. International Continence Society Committee on Standardization of Terminology. Subcommittee on Intestinal Urinary Reservoirs.
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Humans↗
The heat is on--but how? A comparison of TUMT devices.
OBJECTIVE: To compare the heat characteristics of the microwave antennae, the absorbed energy in the target volume and the cooling capacity of the catheters of three common devices for transurethral microwave thermotherapy (TUMT), i.e. the Prostcare, Prostatron and ProstaLund. MATERIALS AND METHODS: The microwave emission from the respective catheters or antennae was measured in a tissue-equivalent 'phantom' prostate. From these measurements the distribution of absorbed energy from the respective catheters and antennae was calculated from the characteristics of the phantom, the absorbed energy and the temperature difference before and after heating. The cooling capacity of the different catheters were measured by submerging each catheter in a thermally isolated water bath at a known temperature and determining the cooling of the water bath caused by the catheter. RESULTS: The design of the microwave antenna influenced the heating profile significantly. The energy absorbed by the prostate model varied among the devices, but was between 13 and 21% of the stated applied energy. The cooling capacity also varied, being least in the Prostcare and greatest in the ProstaLund catheters. CONCLUSIONS: Users of TUMT should be aware of possible back-heating along the catheter, as this limits the microwave power that can be used safely. Furthermore, the 'treatment energy', which is commonly used as an indicator to describe the intensity of TUMT treatments, is ambiguous and not stringent, in that the microwave energy absorbed in the prostate is only a small fraction of this value.
Catheter Ablation↗
Micturition in conscious rats with and without bladder outlet obstruction: role of spinal alpha 1-adrenoceptors.
1. In normal rats and rats with bladder hypertrophy secondary to outflow obstruction, undergoing continuous cytometry, we examined the responses to the selective alpha 1-adrenoceptor antagonist doxazosin given intrathecally (i.t.) and intra-arterially (i.a.). In addition, we investigated the effects of the drug on L-dopa-induced bladder hyperactivity in normal, unobstructed rats. 2. Doxazosin 50 nmol (approximately 60 micrograms kg-1), given i.t., decreased micturition pressure in normal rats and in animals with post-obstruction bladder hypertrophy. The effect was much more pronounced in the animals with hypertrophied/overactive bladders. Doxazosin did not markedly affect the frequency or amplitude of the unstable contractions observed in obstructed rats. In contrast, however, doxazosin reduced L-dopa-induced bladder overactivity. When tested, the enantiomers of doxazosin produced qualitatively similar effects to doxazosin, but there was no evidence of stereoselectivity. 3. The results suggest that in addition to the well documented action on prostatic and lower urinary tract smooth muscle, and an effect on the sympathetic outflow to the bladder, bladder neck, prostate, and external urethral sphincter, doxazosin may have an action at the level of the spinal cord and ganglia, thereby reducing activity in the parasympathetic nerves to the bladder. This effect is more pronounced in rats with bladder hypertrophy than in normal rats.
Adrenergic alpha-Antagonists↗
The standardization of terminology and assessment of functional characteristics of intestinal urinary reservoirs.
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Animals↗
Role of spinal and peripheral alpha 2 adrenoceptors in micturition in normal conscious rats.
PURPOSE: To explore the potential of alpha 2-adrenoceptors in modulating vesicourethral function at the spinal and bladder levels. MATERIAL AND METHODS: Continuous cystometry was performed in normal, conscious rats, and the urodynamic effects of alpha 2-adrenoceptor stimulation and blockade were recorded. RESULTS: Given intrathecally, the selective alpha 2-adrenoceptor agonist, dexmedetomidine (dex) 3 nmol., decreased micturition pressure, bladder capacity, micturition volume and residual volume. These effects were counteracted by the selective alpha 2-adrenoceptor antagonist, atipamezole 30 nmol. Intrathecally dex 10 nmol. caused total incontinence in 9 of 9 rats. Given intra-arterially near the bladder, dex 6 nmol. Decreased micturition pressure, bladder capacity, micturition volume, residual urine and basal pressure. Atipamezole 30 nmol. intrathecally increased micturition pressure, bladder capacity and residual urine, and decreased micturition volume. Similar effects were obtained when atipamezole 60 nmol. was given intra-arterially. The selective alpha 2-adrenoceptor antagonist, rauwolscine 200 nmol., had effects similar to those of atipamezole. CONCLUSIONS: The results show that alpha 2-adrenoceptors can modulate micturition in normal conscious rats both at the spinal and the peripheral levels.
Adrenergic alpha-Agonists↗