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Biomedical subjects

L Cardozo

Publications and source records attributed to L Cardozo.

At least 19 recordsLinked to original sources
PubMed2006

Solifenacin significantly improves all symptoms of overactive bladder syndrome.

Overactive bladder syndrome (OAB) is a chronic condition characterised by urgency, with or without associated urge incontinence. Solifenacin succinate is a once daily, bladder selective antimuscarinic available in two doses (5 and 10 mg). The recommended dose is 5 mg once daily and can be increased to 10 mg once daily if 5 mg is well tolerated. This article presents pooled efficacy and safety data from four large, placebo-controlled, multinational phase III trials of solifenacin succinate with a total enrolment of over 2800 patients. Data from these trials show that solifenacin 5 and 10 mg once daily is significantly more effective than placebo at reducing urgency, incontinence, micturition frequency and nocturia and at increasing volume voided per micturition. Adverse events were mainly mild-to-moderate in all treatment groups. The results of these phase III trials support the use of solifenacin in the treatment of OAB.

Adolescent↗
PubMed2006

Overactive bladder: The importance of new guidance.

Overactive bladder (OAB) affects an estimated 49 million people in Europe, but only a minority receive appropriate treatment. Others are bothered by unacceptable levels of symptoms that severely impair their quality of life and represent a significant financial burden to themselves and to their healthcare providers. Recently updated guidelines from the International Consultation on Incontinence (ICI) and the European Association of Urology (EAU) take account of important new developments in the management of bladder problems in both primary and secondary care. However, local implementation of previous guidance has been variable, with many patients with OAB and other bladder problems failing to gain full benefit from current clinical and scientific understanding of these conditions. The recent expansion of the range of treatments available for OAB and stress urinary incontinence makes it especially important that physicians become aware of the differential diagnosis of these conditions - the questions they need to ask, and the investigations which will help determine the most appropriate course of action.

Algorithms↗
PubMed2005

Long-term open-label solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome.

OBJECTIVE: To examine safety and tolerability findings as primary endpoints, and efficacy outcomes as secondary endpoints, of solifenacin treatment over a period of up to 1 year. Long-term efficacy in the treatment of overactive bladder (OAB) syndrome depends in part on the patient's persistence with pharmacologic therapy. Agents with a favourable therapeutic index supporting high levels of patient satisfaction and persistence are needed. METHODS: The present study was a 40-week open-label extension of two 12-week, placebo-controlled, double-blind studies of solifenacin treatment in patients with OAB. Patients who completed the 12-week studies were offered participation in the open-label extension study. All patients who entered the open-label extension study initially received solifenacin 5 mg daily for 4 weeks, after which a flexible dosing regimen allowed patients to individualise their treatment (5 mg or 10 mg) at each of the 3 study visits. Safety and tolerability assessments (the primary variable) included adverse event reporting. Efficacy data were collected from micturition diaries completed at weeks 16, 28, 40, and 52. RESULTS: Ninety-one percent (1637/1802) of patients who completed the two 12-week randomised studies chose to participate in the long-term open-label extension study. A total of 81% of patients completed 40 weeks of open-label treatment. Solifenacin treatment was safe and well tolerated, and rates of anticholinergic side effects were relatively low. Only 4.7% of patients discontinued treatment owing to adverse events. Improvements in major symptoms of OAB were noted for all patients for up to 52 weeks of treatment. In patients randomised to solifenacin in the double-blind studies, there were small incremental improvements in all efficacy parameters (reductions in episodes per 24 hours of urgency, reductions in frequency and urge incontinence, and increases in volume voided per micturition) over the course of the extension study. Efficacy was confirmed when outcomes were assessed as a function of total solifenacin exposure. Patient satisfaction with solifenacin tolerability (85%) and efficacy (74%) were high. These results indicate that long-term treatment with solifenacin was well tolerated and associated with improvements in efficacy parameters based on patient diary data recorded over the 12-month treatment period. Moreover, the high level of patient satisfaction reported appeared to correlate well with the quantified improvements in key symptoms demonstrated in this study. CONCLUSIONS: Long-term therapy with solifenacin resulted in a favourable tolerability profile, and was associated with improvements in efficacy parameters based on diary data recorded over a 12-month period. This balance of tolerability and efficacy with solifenacin was associated with excellent persistence with therapy. These results suggest that solifenacin may be useful for the long-term treatment of the chronic symptoms associated with OAB.

Constipation↗
PubMed2005

Neurobiology of stress urinary incontinence: new insights and implications for treatment.

Stress urinary incontinence (SUI) is a significant problem for millions of women, many of whom remain untreated for years, sometimes for life. One reason for this is the lack of effective pharmacologic therapy. The drugs used for urge incontinence have little or no effect on leakage occurring without detrusor contraction under conditions of increased intra-abdominal pressure. Recent studies suggest that extrinsic urethral sphincter closure may be controlled by enhancing neurotransmission in pudendal pathways. A new agent, duloxetine, which inhibits serotonin-norepinephrine re-uptake in these pathways, is now in clinical trials and appears to be the first effective pharmacologic therapy for SUI.

Adrenergic Uptake Inhibitors↗
PubMed2005

Darifenacin in the treatment of overactive bladder.

Antimuscarinic drug therapy has been shown to be effective in the management of patients with symptoms of the overactive bladder syndrome (OAB), but the bothersome antimuscarinic adverse effects of dry mouth, constipation, somnolence and blurred vision often affect compliance with medication. The development of bladder selective M3 specific antagonists offers the possibility of increasing efficacy whilst minimising adverse effects. The M3 specific antagonist solifenacin has recently been marketed, and darifenacin will soon be available. The purpose of this article is to review the pharmacology and clinical trial data available for darifenacin, in addition to examining its role in the treatment of the OBS.

Absorption↗
PubMed2005

Nocturia: morbidity and management in adults.

Nocturia is an increasingly prevalent and bothersome urinary symptom associated with considerable impact and morbidity in later life. Nocturnal frequency is associated with a number of underlying pathologies, both related and unrelated to the lower urinary tract. Following careful assessment, diagnosis and management, the condition is amenable to amelioration, if not complete cure in the majority of cases. This paper outlines the epidemiology, underlying pathophysiology and diseases associated with nocturia and reviews current treatment strategies.

Adrenergic alpha-Antagonists↗
PubMed2005

Solifenacin in the management of the overactive bladder syndrome.

Overactive bladder (OAB) is the term used to describe the symptom complex of urinary frequency and urgency, with or without urge incontinence. Whilst antimuscarinic drug therapy has proven to be effective in the management of patients with symptoms of the OAB syndrome, compliance with medication is often affected by the bothersome antimuscarinic adverse effects of dry mouth, constipation, somulence and blurred vision. The development of bladder selective M3 specific antagonists offers the possibility of increasing efficacy whilst minimising adverse effects. At present, there are no M3 specific antagonists currently available, although solifenacin and darifenacin are under development and are due to be registered in 2004-2005. The purpose of this article is to review the pharmacology and clinical trial data available for solifenacin in addition to examining its emerging role in the treatment of the OAB syndrome.

Clinical Trials as Topic↗
PubMed2005

New developments in the management of urinary incontinence.

Urinary incontinence is a common and distressing condition known to adversely affect quality of life. In this article the authors aim to highlight developments in the methods of classification, investigation and the treatment of incontinence. It gives a detailed description of the newer drugs and their mode of action, that have recently come on to the market. These include duloxetine for the treatment of stress incontinence and the newer M3 selective antagonists. It also describes the latest surgical procedures, for example the newer slings and injectables used to treat stress incontinence. They are compared with the standard forms of treatment used and the evidence in favour and against these have been given.

Female↗
PubMed2004

Correlating structure and function: three-dimensional ultrasound of the urethral sphincter.

OBJECTIVE: Three-dimensional (3D) ultrasound facilitates assessment of the anatomy of the urethral sphincter, a decrease in sphincter volume being associated with stress incontinence. Urethral pressure profilometry (UPP) is used to assess urethral sphincter function although it is not diagnostic of stress incontinence. The aim of this pilot study was to determine whether 3D sphincter volume can be correlated with the area under the UPP curve. METHODS: Primigravid women were recruited antenatally between 32 and 42 weeks' gestation. 3D transvaginal ultrasound scans of the urethra were performed in modified lithotomy position with a comfortably full bladder. Length and cross-sectional area were measured allowing the sphincter volume to be calculated. UPP measurements were performed with a Gaeltec solid-state pressure transducer and the area under the curve mapped out and calculated. All scans and measurements were repeated between 3 and 6 months postpartum. RESULTS: Nineteen women participated in the study. Antenatal and postnatal data were available in all cases. There was a statistically significant correlation between antenatal sphincter volumes and area under the UPP curve although this relationship was lost following delivery. CONCLUSIONS: There appears to be a correlation between structural anatomy and functional anatomy in the antenatal period although following delivery this is lost.

Adult↗
PubMed2004

Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder.

PURPOSE: In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder. In addition, we assessed the safety and acceptability of solifenacin. MATERIALS AND METHODS: The study was a multicenter, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to 12-week once daily treatment with solifenacin 5 mg, solifenacin 10 mg or placebo. The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours. Secondary efficacy variables included changes from baseline in mean number of urgency, nocturia and incontinence episodes per 24 hours, and mean volume voided per micturition. RESULTS: Compared with changes obtained with placebo (-1.59), micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg (-2.37, p = 0.0018) and solifenacin 10 mg (-2.81, p = 0.0001). A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses (5 mg, p = 0.002 and 10 mg, p = 0.016). This effect was also seen for episodes of urge incontinence (5 mg, p = 0.014 and 10 mg, p = 0.042). Of patients reporting incontinence at baseline, fully 50% achieved continence after treatment with solifenacin. Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg (-0.71, -38.5%) versus placebo (-0.52, -16.4%, p = 0.036). Episodes of urgency were statistically significantly reduced with solifenacin 5 mg (-2.84, -51%, p = 0.003) and solifenacin 10 mg (-2.90, -52%, p = 0.002). Mean volume voided per micturition was statistically significantly increased with both solifenacin doses (p = 0.0001). Treatment with solifenacin was well tolerated. Dry mouth, mostly mild in severity, was reported in 7.7% of patients receiving solifenacin 5 mg and 23% receiving solifenacin 10 mg (vs 2.3% with placebo). CONCLUSIONS: In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency, urgency and incontinence. Solifenacin 10 mg also decreased the frequency of nocturia. Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.

Adolescent↗
PubMed2004

Antidiuresis: a new concept in managing female daytime urinary incontinence.

OBJECTIVE: To investigate the efficacy of desmopressin nasal spray on daytime urinary incontinence in women. PATIENTS AND METHODS: A multicentre, multinational, randomized, double-blind, placebo-controlled, cross-over exploratory study of women (aged 18-80 years) complaining of severe daytime urinary incontinence was conducted in three centres (King's College Hospital; Boras County Hospital and Skejby Hospital). Seventy-five patients were screened of whom 64 were randomized. In all, 60 women received study medication (safety population) and 57 completed the study. The intention-to-treat population comprised 59 patients and there were 41 in the per protocol analysis. The primary efficacy endpoint was the number of periods with no leakage for 4 h after dosing. Women were instructed to take the drug at a time of their choosing, but >/= 4 h before bedtime. Secondary efficacy variables included the time to first void or incontinence episode, volume leaked per incontinence episode, total volume voided and number of periods with no leakage. All measurements were made over 7 days on desmopressin and 3 days on placebo. RESULTS: There was a higher mean (sd) incidence of periods with no leakage in the first 4 h on desmopressin, at 62 (35)%, than on placebo, at 48 (40)%, and during the first 8 h, at 55 (37)% vs 40 (41)%. There was also a higher frequency of dry days on desmopressin than on placebo; 36% of patients had no leakage on virtually all treatment days (6 or 7) for 4 h after dosing. At 4-8 h the incidence of periods with no leakage on desmopressin was 68 (35)% vs 63 (41)% on placebo, and thereafter the incidence was similar. The time from dosing to first incontinence episode was longer on desmopressin, at 6.3 (2.5) h, vs 5.2 (3.3) h, whilst the volume leaked per incontinence episode was lower on desmopressin than placebo. The total volume voided was consistently lower on desmopressin, at 1180 (58) mL vs 1375 (57) mL, over the 24-h period after administration. There were no serious or severe adverse events reported. Seven women (11%) withdrew from the study, of whom five did not attend for the final visit and two (3%) because of mild adverse events. CONCLUSIONS: The results of this exploratory study suggest that desmopressin is an effective and safe treatment in women with daytime urinary incontinence, and allows them to choose when they need treatment, thus improving motivation, which may aid compliance with therapy.

Administration, Intranasal↗