Intramuscular injections of BTX-A into the detrusor can provide rapid, well tolerated, clinically significant decreases in the signs and symptoms of urinary incontinence caused by neurogenic detrusor overactivity during a 24-week study period.

OBJECTIVETo assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB)) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily. PATIENTS AND METHODSThe study was an international, multicentre, randomized, double-blind, tolterodine-and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for ≥ 3 months were eligible; after a singleblind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void. RESULTSIn all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline ( -1.41, -32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg ( -2.85, -51.9%) and 10 mg ( -3.07, -54.7%; both P < 0.001), but not with tolterodine ( -2.05, -37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine ( -1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 ( -1.42; P = 0.008) and 10 mg ( -1.45; P = 0.0038). Compared with placebo ( -1.20, -8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine ( -1.88, -15%; P = 0.0145), solifenacin 5 ( -2.19, -17%) and 10 mg ( -2.61, -20%; both A further phase 3 study into the effect of duloxetine was undertaken to assess whether the previous evidence of efficacy from North America and Europe could be sustained in other parts of the world. In this double-blind placebo-controlled study, the authors found that duloxetine improved continence and quality of life, in keeping with the findings in North America and Europe.

Introduction Patients with nocturia have to face many hurdles before being diagnosed and treated properly. The aim of this paper is to: summarize the nocturia patient pathway, explore how nocturia is diagnosed and treated in the real world and use the Delphi method to develop a practical algorithm with a focus on what steps need to be taken before prescribing desmopressin. Methods Evidence comes from existing guidelines (Google, PubMed), International Consultation on Incontinence‐Research Society (ICI‐RS) 2017, prescribing information and a Delphi panel (3 rounds). The International Continence Society initiated this study, the authors represent the ICI‐RS, European Association of Urology, and Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU). Results Diagnostic packages: consensus on, history taking for all causalities, intake diary (fluid, food) and bladder diary, not for its duration. Pelvic (women) or rectal (men) examination, prostate‐specific antigen, serum sodium check (SSC), renal function, endocrine screening: when judged necessary. Timing or empty stomach when SSC is not important. Therapeutic packages: the safe candidates for desmopressin can be phenotyped as no polydipsia, heart/kidney failure, severe leg edema or obstructive sleep apnea syndrome. Lifestyle interventions may be useful. Initiating desmopressin: risk management consensus on three clinical pictures. Follow‐up of desmopressin therapy: there was consensus on SSC day 3 to 7, and at 1 month. Stop therapy if SSC is <130 mmol/L regardless of symptoms. Stop if SSC is 130 to 135 mmol/L with symptoms of hyponatremia. Conclusion A summary of the nocturia patient pathway across different medical specialists is useful in the visualization and phenotyping of patients for diagnosis and therapy. By summarizing basic knowledge of desmopressin, we aim to ease its initiation and shorten the patient journey for nocturia.

SummaryAimTo raise awareness on nocturia disease burden and to provide simplified aetiologic evaluation and related treatment pathways.MethodsA multidisciplinary group of nocturia experts developed practical advice and recommendations based on the best available evidence supplemented by their own experiences.ResultsNocturia is defined as the need to void ≥1 time during the sleeping period of the night. Clinically relevant nocturia (≥2 voids per night) affects 2%‐18% of those aged 20‐40 years, rising to 28%‐62% for those aged 70‐80 years. Consequences include the following: lowered quality of life; falls and fractures; reduced work productivity; depression; and increased mortality. Nocturia‐related hip fractures alone cost approximately €1 billion in the EU and $1.5 billion in the USA in 2014. The pathophysiology of nocturia is multifactorial and typically related to polyuria (either global or nocturnal), reduced bladder capacity or increased fluid intake. Accurate assessment is predicated on frequency‐volume charts combined with a detailed patient history, medicine review and physical examination. Optimal treatment should focus on the underlying cause(s), with lifestyle modifications (eg, reducing evening fluid intake) being the first intervention. For patients with sustained bother, medical therapies should be introduced; low‐dose, gender‐specific desmopressin has proven effective in nocturia due to idiopathic nocturnal polyuria. The timing of diuretics is an important consideration, and they should be taken mid‐late afternoon, dependent on the specific serum half‐life. Patients not responding to these basic treatments should be referred for specialist management.ConclusionsThe cause(s) of nocturia should be first evaluated in all patients. Afterwards, the underlying pathophysiology should be treated specifically, alone with lifestyle interventions or in combination with drugs or (prostate) surgery.

Aims: To evaluate the potential of mirabegron, a selective b3-adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms. Methods: A multicenter, randomized, double-blind, double-dummy, parallel group, placebo and active-controlled, Phase 2, proof-of-concept study was conducted. Eligible patients (n ¼ 314) were enrolled into a singleblind, 2-week placebo run-in period followed by a randomized, double-blind, placebo-controlled treatment period. Patients received mirabegron 100 or 150 mg twice-daily (BID), placebo or tolterodine 4 mg extended release (ER) oncedaily for 4 weeks. Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24 hr. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes per 24 hr; severity of urgency; nocturia, and quality of life measures. Safety parameters included adverse events, laboratory tests, electrocardiogram parameters and post-void residual volume. Results: Mirabegron 100 and 150 mg BID resulted in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency (2.2 micturitions/24 hr vs. 1.2 micturitions/24 hr for both doses, adjusted P 0.01 for both comparisons). Mirabegron had a statistically significant effect versus placebo for most secondary endpoints, including quality of life variables. Despite a small increase in pulse rate, mirabegron demonstrated good safety and tolerability. Conclusions: Mirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years.