David Castro-Diaz

EAU Guidelines on Neurogenic Lower Urinary Tract Dysfunction

CONTEXT Most patients with neurogenic lower urinary tract dysfunction (NLUTD) require life-long care to maintain their quality of life (QoL) and to maximise life expectancy. OBJECTIVE To provide a summary of the 2008 version of the European Association of Urology (EAU) guidelines on NLUTD and to assess the effectiveness of currently available diagnostic tools, particularly ultrasound imaging and urodynamics. EVIDENCE ACQUISITION The recommendations provided in the 2008 EAU guidelines on NLUTD are based on a review of the literature, using online searches of Medline and other source documents published between 2004 and 2007. A level of evidence and/or a grade of recommendation have been assigned to the guidelines where possible. EVIDENCE SYNTHESIS NLUTD encompasses a wide spectrum of pathologies, and patients often require life-long, intensive medical care to maximise their life-expectancy and to maintain their QoL. Treatment must be tailored to the needs of the individual patient and, in many cases, involves a multidisciplinary team of experts. Timely diagnosis and treatment are essential if irreversible deterioration of both the upper and lower urinary tracts are to be avoided. Therapeutic decisions are made on the basis of a comprehensive medical assessment, including urodynamics to identify the type of dysfunction. Advances in investigative technologies have facilitated the noninvasive and conservative management of patients who have NLUTD. CONCLUSIONS The diagnosis and treatment of NLUTD, which is a highly specialised and complex field involving both urology and medicine, requires up-to-date expert advice to be readily available. The current guidelines are designed to fulfil this need.

The role of urinary urgency and its measurement in the overactive bladder symptom syndrome: current concepts and future prospects

To review the concept of urinary urgency and its practical measurement in clinical trials, and advance the hypothesis that while urge is experienced by normal people, urgency is always pathological.

A Phase III, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of the β3 Adrenoceptor Agonist, Mirabegron, in Patients With Symptoms of Overactive Bladder

OBJECTIVE To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder (OAB). MATERIALS AND METHODS Patients ≥18 years with OAB symptoms were recruited to a 2-week, single-blind, placebo run-in. Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were randomized 1:1:1 to once-daily mirabegron 25 mg or 50 mg, or placebo for 12 weeks. Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours. Key secondary endpoints were changes to final visit in mean volume voided or micturition, change to week 4 in mean number of incontinence episodes and micturitions per 24 hours, changes to final visit in mean level of urgency, number of urgency incontinence episodes, and urgency (grade 3 or 4) episodes per 24 hours. Patient-reported outcomes were assessed using the OAB-questionnaire, Patient Perception of Bladder Condition, and Treatment-Satisfaction-Visual Analog Scale. RESULTS Both mirabegron groups demonstrated statistically significant improvements in coprimary endpoints vs placebo. Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following: change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours. Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo. CONCLUSION Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency. Mirabegron was well tolerated vs placebo.

A review of adherence to drug therapy in patients with overactive bladder.

Drug therapy for overactive bladder (OAB) is associated with improvements in symptoms and quality of life, but the short‐ and long‐term adherence and persistence is suboptimal. In this review we outline methods of measuring, and factors affecting, adherence to pharmacotherapy in patients with OAB. Clinical practice suggests that adherence rates reported in clinical trials are much greater than in real practice. Factors affecting adherence include psychological and social variables that might alter patients’ perception of the benefits of taking medication, and the effect of comorbidity and polypharmacy. Whilst there is some evidence that lack of efficacy and side‐effects are contributory, these additional factors are also important.

The efficacy and tolerability of the β3-adrenoceptor agonist mirabegron for the treatment of symptoms of overactive bladder in older patients

INTRODUCTION mirabegron is a β3-adrenoceptor agonist developed for the treatment of symptoms of overactive bladder (OAB). As the prevalence of OAB increases with age, a prospective subanalysis of individual and pooled efficacy and tolerability data from three 12-week, randomised, Phase III trials, and of tolerability data from a 1-year safety trial were conducted in order to evaluate the efficacy and tolerability of mirabegron in subgroups of patients aged ≥65 and ≥75 years. METHODS primary efficacy outcomes were change from baseline to final visit in the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h. Tolerability was assessed by the incidence of treatment-emergent adverse events (TEAEs). RESULTS over 12 weeks mirabegron 25 mg and 50 mg once-daily reduced the mean numbers of incontinence episodes and micturitions/24 h from baseline to final visit in patients aged ≥65 and ≥75 years. Mirabegron was well tolerated: in both age groups, hypertension and urinary tract infection were among the most common TEAEs over 12 weeks and 1 year. The incidence of dry mouth, a typical anticholinergic TEAE, was up to sixfold higher among the older patients randomised to tolterodine than any dose of mirabegron. CONCLUSIONS these analyses have demonstrated the efficacy of mirabegron over 12 weeks and the tolerability of mirabegron over 12 weeks and 1 year in OAB patients aged ≥65 and ≥75 years, supporting mirabegron as a therapeutic option in older patients with OAB.

Overactive bladder: Is there a link to the metabolic syndrome in men?

It is becoming increasingly clear that a variety of metabolic, cardiovascular, and endocrine factors contribute to male pelvic health. In particular, a growing body of evidence suggests a relationship between lower urinary tract symptoms, benign prostatic hyperplasia, overactive bladder, erectile dysfunction, and the metabolic syndrome. This article explores these relationships, focusing on the role of the autonomic nervous system and hyperinsulinemia, together with their implications for urological practice. Neurourol. Urodynam. 29:1360–1364, 2010.

Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014)

Aim: we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification. Methods: to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process. Results: for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin. Conclusions: dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D).

The 3‐day bladder diary is a feasible, reliable and valid tool to evaluate the lower urinary tract symptoms in women

To evaluate the feasibility (% of completion), reliability (test–retest and inter‐observer) and validity (convergent vs. questionnaires and vs. urodynamic study‐UDS) of the 3‐day bladder diary (3dBD) in women with lower urinary tract symptoms (LUTS).

Diagnosis and medical treatment of lower urinary tract symptoms in adult men: applying specialist guidelines in clinical practice.

Study Type – Therapy (case series)

Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics

Abstract Objective Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice. Methods Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described. Results Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years. Conclusions Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.