Nocturia: state of the art and critical analysis of current assessment and treatment strategies.

This editorial of the topic issue of the World Journal of Urology provides a state of the art on nocturia which includes descriptions of the terminology, epidemiology, health-related quality of life, medical and financial consequences, pathophysiology, assessment tools and treatment strategies of nocturia. This summary also includes a flowchart on the pathophysiology of nocturia with illustration of the various causes of reduced bladder capacity, increased fluid intake or increased diuresis; a flowchart with the key findings of frequency-volume charts to determine the underlying pathophysiology; and a flowchart on the treatment of the various causes of nocturia. The editorial critically discusses current assessment and treatment strategies in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and nocturia. The outcome of nocturia remains hidden in drug trials of patients with LUTS/BPH because nocturia-specific measures were not included. The authors recommend using frequency-volume charts, measurement of the hours of undisturbed sleep, and nocturia-specific quality of life questionnaires (e.g., ICIQ-N or N-Qol) in all future studies in patients with LUTS/BPH and nocturia.

Clinical value of a patient-reported goal-attainment measure: the global development of self-assessment goal achievement (SAGA) questionnaire for patients with lower urinary tract symptoms.

AIMS: To discuss the importance of patients' treatment goals and perceived goal attainment to better address expectations in the treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB). METHODS: The development of the Self-Assessment Goal Achievement (SAGA) questionnaire was driven by measurement principles from the field of qualitative and psychometric research adapted to elicit patients' treatment goals. At baseline, SAGA solicits individualized responses of patient's treatment expectations and goals, and at follow-up SAGA uses a goal-attainment scale (GAS) to document goal achievement. RESULTS: The SAGA questionnaire provides a basis for the patient and physician to discuss realistic treatment expectations and to measure the alignment between patients' expectations and treatment outcomes in terms of improvement in symptoms and impact on function. Therefore, incorporating the SAGA questionnaire into clinical trials may provide an additional dimension of treatment efficacy by incorporating data on treatment satisfaction from the patient's perspective. CONCLUSIONS: The SAGA questionnaire is a useful tool for patient-centered discussions about the treatment and management of LUTS, including OAB, and assisting physicians in tracking progress and managing patient expectations during therapy.

European content validation of the Self-Assessment Goal Achievement (SAGA) questionnaire in patients with overactive bladder.

INTRODUCTION AND HYPOTHESIS: The Self-Assessment Goal Achievement (SAGA) questionnaire is a patient-completed instrument designed to assess goal attainment in the behavioral or pharmacologic treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB). The SAGA questionnaire allows patients to identify and rank the importance of treatment goals before treatment is initiated; the follow-up SAGA questionnaire quantifies the achievement of these patient-identified goals. The objective of this qualitative research was to confirm the content validity of the German, Spanish, Swedish, and English (UK) language versions of the SAGA questionnaire in patients with OAB with or without other LUTS. METHODS: The SAGA questionnaire was translated to each language in accordance with a well-established forward and backward harmonization method. Patient interviews were then conducted according to a cognitive debriefing methodology. Qualitative analysis of patients' input allowed assessment of content validity of each linguistically adapted SAGA questionnaire. RESULTS: All patients (n = 29; six to eight per targeted country) found the SAGA questionnaire easy to understand and to complete. Most patients completed the nine prespecified (fixed) treatment goals and were able to add up to five personal goals in the open-ended portion and rate each goal by importance. Differences were identified in how the various languages communicated some of the concepts assessed with the SAGA questionnaire. Rewording of the translated versions of the questionnaire was necessary in some cases. CONCLUSIONS: This linguistic content validation study in four European languages indicates that SAGA is a comprehensive, easy-to-understand, and relevant questionnaire for patient-completed evaluation of LUTS/OAB symptoms and treatment goal attainment.

Flexible-dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double-blind, placebo-controlled study of fesoterodine in an aging population trial.

OBJECTIVES: To assess the efficacy and safety of flexible-dose fesoterodine in elderly adults with overactive bladder (OAB). DESIGN: Twelve-week, randomized, double-blind, placebo-controlled trial. SETTING: Sixty-one outpatient clinics in Europe, Israel, and Turkey. PARTICIPANTS: Seven hundred ninety-four individuals aged 65 and older (47% male) with OAB symptoms for 3 months or longer, mean of eight or more micturitions and three or more urgency episodes per 24 hours, at least some moderate problems on Patient Perception of Bladder Condition (PPBC), and Mini-Mental State Examination (MMSE) score of 20 or greater. INTERVENTIONS: Participants were randomized to fesoterodine or placebo for 12 weeks, with stratification according to age (>75 vs ≤ 75) and dosing time (morning vs evening). Participants receiving fesoterodine started on 4 mg and could increase to 8 mg at week 4 or 8 and de-escalate to 4 mg at week 8 (sham escalation for placebo). MEASUREMENTS: Changes from baseline in bladder-diary variables (primary endpoint, urgency episodes) and patient-reported outcomes including OAB Questionnaire, Treatment Benefit Scale (TBS), PPBC, Urgency Perception Scale (UPS), and OAB Satisfaction Questionnaire (OAB-S); all observed or reported adverse events. RESULTS: By week 8, 64% of fesoterodine-treated and 71% of placebo-treated participants opted for dose escalation. At week 12, the fesoterodine group had statistically significantly greater improvement than the placebo group in urgency episodes, micturitions, nocturnal micturitions, incontinence pad use, and OAB Questionnaire scores but not urgency urinary incontinence episodes. Responder rates on TBS, PPBC, UPS, and OAB-S were statistically significantly higher with fesoterodine. Improvements in most diary variables and participant-reported outcomes were greater with fesoterodine than placebo in participants in both age groups and when administered in the morning and evening. Rates of dry mouth and constipation were 34% and 9% with fesoterodine and 5% and 3% with placebo, respectively. Rates of adverse events and discontinuations were generally similar in participants in both age groups. There was no change in MMSE score. CONCLUSION: Fesoterodine was associated with significantly greater improvements in most diary variables and participant-reported outcomes than placebo and was generally well tolerated in older people.

Practical consensus guidelines for the management of enuresis.

UNLABELLED: Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment. CONCLUSION: This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis.

Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years.

AIMS: To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof-of-concept study. METHODS: Double-blind, double-dummy, three-armed comparison of flupirtine extended release (400 mg/day, titrated to 600 mg/day), tolterodine extended release (4 mg/day) and placebo for 12 weeks. RESULTS: When major elevations of liver enzymes (more than three times the upper normal limit) were detected in several flupirtine-exposed patients, the study was prematurely discontinued. Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥ 6 weeks. CONCLUSIONS: Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication.

Urinary incontinence in children.

BACKGROUND: Urinary incontinence (bedwetting, enuresis) is the commonest urinary symptom in children and adolescents and can lead to major distress for the affected children and their parents. Physiological and non-physiological types of urinary incontinence are sometimes hard to tell apart in this age group. METHODS: This article is based on selected literature retrieved by a PubMed search and on an interdisciplinary expert consensus. RESULTS AND CONCLUSION: Nocturnal enuresis has a variety of causes. The main causative factors in monosymptomatic enuresis nocturna (MEN) are an impaired ability to wake up when the bladder is full, due to impaired or absent perception of fullness during sleep, and an imbalance between bladder capacity and nocturnal urine production. On the other hand, non-monosymptomatic enuresis nocturna (non-MEN) is usually traceable to bladder dysfunction, which is also the main cause of diurnal incontinence. A basic battery of non-invasive diagnostic tests usually suffices to determine which type of incontinence is present. Further and more specific testing is indicated if an organic cause is suspected or if the treatment fails. The mainstay of treatment is urotherapy (all non-surgical and non-pharmacological therapeutic modalities). Some patients, however, will need supportive medication in addition. Urinary incontinence has different causes in children and adults and must therefore be diagnosed and treated differently as well. All physicians who treat the affected children (not just pediatricians and family doctors, but also pediatric nephrologists, urologists, pediatric surgeons, and child psychiatrists) must be aware of the specific features of urinary incontinence in childhood.

Efficacy, tolerability and safety of propiverine hydrochloride in comparison to oxybutynin in children with urge incontinence due to overactive bladder: Results of a multicentre observational cohort study.

OBJECTIVE: To compare, in a retrospective observational cohort study, the efficacy, tolerability and safety of propiverine and oxybutynin in children with urge incontinence (UI) due to overactive bladder. PATIENTS AND METHODS: Medical records were scrutinized for children with UI. As a primary efficacy outcome variable the achievement of continence after treatment with variable doses of propiverine or oxybutynin was assessed. Weekly UI episodes and daily voiding frequency were evaluated as secondary efficacy outcomes. Tolerability was evaluated by the rate of adverse events, adverse drug reactions caused by antimuscarinics and premature treatment termination. RESULTS: At 16 study centres, 621 children aged 5-14 years with UI due to overactive bladder were enrolled. After anticholinergic treatment (437 propiverine, 184 oxybutynin) continence was achieved in 61.6% and 58.7% of the patients after 186 and 259 days, respectively. There were clinically relevant improvements in voiding frequency across treatment groups. Daily doses of propiverine were markedly below the recommendations (0.54 vs 0.8 mg/kg body weight), daily doses of oxybutynin were according to the recommendations (0.31 vs 0.2-0.4 mg/kg body weight) at treatment initiation. There was a significantly more favourable tolerability to propiverine than oxybutynin for the overall rate of adverse events (3.9% vs 16.3%, odds ratio 4.813), adverse drug reactions caused by propiverine or oxybutynin (2.8% vs 9.2%) and premature treatment termination due to adverse drug reactions (1.6% vs 4.4%). CONCLUSION: Propiverine and oxybutynin are effective in children with UI due to overactive bladder. Sufficient treatment periods of at least 2, preferably 3-4, months are the crucial factors for a successful treatment. The tolerability profile of propiverine is better than for oxybutynin.

Structured desmopressin withdrawal improves response and treatment outcome for monosymptomatic enuretic children.

PURPOSE: In this national, multicenter, retrospective survey we tested whether structured withdrawal of desmopressin, in which dose frequency rather than dose quantity was gradually decreased, would improve outcome. MATERIAL AND METHODS: Enrolled in the study were 487 monosymptomatic enuretic patients from a total of 181 centers (The Enuresis Algorithm of Marschall Survey Group). At study outset 41% of patients had 7 wet nights per week, 45% had 3 to 6 and 14% had fewer than 3. All patients were treated with desmopressin, which was abruptly terminated or tapered with analogue by a structured scheme. Response rates were compared in the groups according to International Children's Continence Society guidelines. RESULTS: The 173 children with abrupt termination had a 51% response rate, including a full and partial response in 44.1% and 27%, respectively, and no response in 22%. The 314 children with tapering had a 72% response rate, including a full and partial response in 66.8% and 24%, and no response in 4% (p <0.0001). Enuresis frequency with abrupt termination decreased from 21 wet nights per month before treatment to 6. The tapering group had 21 wet nights per months before and 2 after treatment (p <0.0001). Followup at 1 month showed fewer than 2 wet nights per month in 57% of cases with abrupt termination and in 80% with tapering (p <0.0001). Pretreatment had no influence. No severe side effects occurred. CONCLUSIONS: This national, multicenter, retrospective analysis proves that antidiuretic treatment followed by a structured withdrawal program is superior to regular treatment with abrupt termination in enuretic children. Hence, desmopressin followed by structured withdrawal should be the standard. It is also superior to published outcomes of alarm treatment.

Treatment with propiverine in children suffering from nonneurogenic overactive bladder and urinary incontinence: results of a randomized placebo-controlled phase 3 clinical trial.

BACKGROUND: Until now no confirmatory clinical trial in children suffering from nonneurogenic overactive bladder (OAB) and urinary incontinence could demonstrate superiority for antimuscarinics over placebo. OBJECTIVES: The following study was conducted to prove efficacy and tolerability of propiverine compared to placebo. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled phase 3 trial with parallel-group design in children aged 5-10 yr was performed. Prior to the 8-wk medical therapy urologic baseline diagnostics, a 3-wk lifestyle advice (urotherapy) was established. INTERVENTION: After re-evaluation of in- and exclusion criteria and uroflowmetry, only children fulfilling the requested criteria were allocated to a body-weight-adjusted therapy (10 or 15 mg propiverine twice daily or corresponding placebo). MEASUREMENTS: Efficacy parameters derived from bladder diary and a micturition volume protocol. Decrease in voiding frequency per day was chosen as primary efficacy parameter; secondary endpoints included voided volume and incontinence episodes. A safety assessment was conducted. RESULTS AND LIMITATIONS: Of 171 randomized children, 87 were treated with propiverine and 84 with placebo. The primary efficacy parameter showed a decrease in voiding frequency (-2.0 episodes for propiverine versus -1.2 for placebo; p=0.0007). Superiority could also be demonstrated for voided volume (31.4 vs. 5.1 ml; p<0.0001) and incontinence episodes (-0.5 vs. -0.2 episodes per d; p=0.0005). The trial design did not allow for separate evaluation of the effect of urotherapy prior to medical treatment. Propiverine was well-tolerated in children. Altogether 23% of side-effects were reported for propiverine and 20% for placebo. CONCLUSIONS: This clinical trial showed superior efficacy of propiverine over placebo and good tolerability for the treatment of children suffering from OAB and urinary incontinence. An important additional factor for the success of the trial was a modified trial design with previous urotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00603343.

Efficacy and tolerability of tolterodine extended release in male and female patients with overactive bladder.

OBJECTIVES: To evaluate the efficacy and tolerability of tolterodine extended release (ER) in men and women with overactive bladder (OAB). METHODS: We analyzed data from two 12-wk, placebo-controlled trials of tolterodine ER (4mg QD). Patients completed 7-d bladder diaries and rated the urgency sensation associated with each micturition on a 5-point urgency rating scale. Micturitions were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-5), or severe OAB (4-5). Changes in micturitions during 24-h, daytime, and nocturnal intervals were assessed. RESULTS: At baseline, 73% (547 of 745) of men and 57% (539 of 953) of women were continent. By week 12, tolterodine ER (n=848) reduced OAB and severe OAB micturitions during 24-h, daytime, and nocturnal intervals in both sexes compared with placebo (n=850). Adverse event rates were low and similar across treatment and gender. CONCLUSIONS: In men and women with OAB, tolterodine ER reduced OAB and severe OAB micturitions, and was well tolerated.

Patient-reported outcomes in overactive bladder: the influence of perception of condition and expectation for treatment benefit.

Patient perceptions of overactive bladder (OAB) symptoms, expectations for treatment benefit, and overall treatment satisfaction share complex relations. Multiple studies have demonstrated associations between factors, such as age, sex, and ethnicity, and patient perceptions of OAB symptoms, especially urgency urinary incontinence. Perceptions of OAB are also shaped by symptom severity and impact on health-related quality of life, as well as by perceptions of family members, caregivers, and clinicians. The literature further suggests discrepancies in the reporting among patients, physicians, and family members/caregivers of the impact that urinary symptoms have on patients' emotional well-being, productivity, and daily life. Understanding the factors that affect patients' perceptions is important because these perceptions affect treatment expectations, which may predict treatment outcomes. Studies designed to evaluate the relations between expectations for OAB treatment and patient satisfaction have not been performed to date, but studies in other patient populations suggest that expectations of positive outcomes are associated with greater treatment satisfaction. We emphasize that patient satisfaction with treatment is directly related to fulfillment of positive expectations, and that patient expectations should be realistic and agreed on by patient and physician. We also discuss strategies that may be used by physicians managing patients with OAB to develop stronger patient-physician partnerships, including the effective communication required to make treatment decisions and set realistic expectations.

Update on nocturia: the best of rest is sleep.

Adequate sleep is a basic requirement for good health. Adults generally require 7 to 8 hours of sleep per night. Sleep deprivation is associated with a decreased ability to perform tasks controlled by the frontal lobe, such as planning, concentration, motor performance, and high-level intellectual skills. Constant poor-quality sleep can also cause excessive daytime sleepiness, depression, and immune function compromise. In addition, continued sleep disruption has been associated with an increased risk for mortality.