Abstract: Aims This prospective, randomized, multicenter trial evaluated the 6-month success rate of sacral neuromodulation (SNM) with InterStim® Therapy versus standard medical therapy (SMT) for overactive bladder (OAB) Methods Enrolled subjects discontinued OAB medications prior to and during baseline data collection and were randomized 1:1 to SNM or SMT Subjects had bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (≥2 leaks/72 hr) and/or urgency-frequency (≥8 voids/day) Subjects failed at least one anticholinergic medication, and had at least one medication not yet attempted The primary objective was to compare OAB therapeutic success rate at 6 months between SNM and SMT Results Overall, 147 subjects were randomized (70 to SNM and 77 to SMT); 93% were female and mean age was 58 The primary intent to treat analysis showed OAB therapeutic success was significantly greater in the SNM group (61%) than the SMT group (42%; P = 002) In the as treated analysis, OAB therapeutic success was 76% for SNM and 49% for SMT (P = 0002) The SNM group showed significant improvements in quality of life versus the SMT group (all P < 0001) and 86% of SNM subjects reported improved or greatly improved urinary symptom interference score at 6 months, compared to 44% for SMT subjects The device-related adverse event rate was 305% and the medication-related adverse event rate was 273% Conclusions This study demonstrates superior objective and subjective success of SNM compared to SMT SNM is shown to be a safe and effective treatment for OAB patients with mild to moderate symptoms Neurourol Urodynam 34:224–230, 2015 © 2014 Wiley Periodicals, Inc

Abstract: Background Evidence based guidelines for the management of frail older persons with urinary incontinence are rare. Those produced by the International Consultation on Incontinence represent an authoritative set of recommendations spanning all aspects of management. Aims To update the recommendations of the 4th ICI. Materials and Methods A series of systematic reviews and evidence updates were performed by members of the working group in order to update the 2009 recommendations. The resulting guidelines were presented at the 2012 meeting of the European Associatioon of Urology. Results Along with the revision of the treatment algorithm and accompanying text. There have been significant advances in several areas including pharmacological treatment of overactive bladder. Discussion The committee continue to notes the relative paucity of data concerning frail older persons and draw attention to knowledge gaps in this area. Neurourol. Urodynam. 34:398–406, 2015. © 2014 Wiley Periodicals, Inc.

Abstract: Objective The decline in available oestrogen after menopause is a possible etiological factor in pelvic floor disorders like vaginal atrophy (VA), urinary incontinence (UI), overactive bladder (OAB) and pelvic organ prolapse (POP). This systematic review will examine the evidence for local oestrogen therapy in the treatment of these pelvic floor disorders. Evidence Acquisition We performed a systematic search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the non-MEDLINE subset of PubMed from inception to May 2014. We searched for local oestrogens and VA (I), UI/OAB (II) and POP (III). Part I was combined with broad methodological filters for randomized controlled trials (RCTs) and secondary evidence. For part I and II two reviewers independently selected RCTs evaluating the effect of topical oestrogens on symptoms and signs of VA and UI/OAB. In part III all studies of topical oestrogen therapy in the treatment of POP were selected. Data extraction and the assessment of risk of bias using the Cochrane Risk of Bias Tool was undertaken independently by two reviewers. Evidence Synthesis The included studies varied in ways of topical application, types of oestrogen, dosage and treatment durations. Objective and subjective outcomes were assessed by a variety of measures. Overall, subjective and urodynamic outcomes, vaginal maturation and vaginal pH changed in favor of vaginal oestrogens compared to placebo. No obvious differences between different application methods were revealed. Low doses already seemed to have a beneficial effect. Studies evaluating the effect of topical oestrogen in women with POP are scarce and mainly assessed symptoms and signs associated with VA instead of POP symptoms. Conclusion Topical oestrogen administration is effective for the treatment of VA and seems to decrease complaints of OAB and UI. The potential for local oestrogens in the prevention as well as treatment of POP needs further research.

Abstract: Herein we review and discuss epidemiological, clinical, and experimental studies on diabetic cystopathy, a common chronic complication of diabetes mellitus with a variety of lower urinary tract symptoms, providing directions for future research. A search of published epidemiological, clinical, or preclinical trial literature was performed using the key words "diabetes", "diabetic cystopathy", "diabetic bladder dysfunction", "diabetic lower urinary tract dysfunction", "diabetic detrusor instability". The classic symptoms of diabetic cystopathy are decreased bladder sensation, increased bladder capacity, and impaired bladder emptying with resultant increased post-void residual volume. However, recent clinical evidence indicates a presence of storage symptoms, such as overactive bladder symptoms. The pathophysiology of diabetic cystopathy is multifactorial, including disturbances of the detrusor, neuron, urothelium, and urethra. Hyperglycemia, oxidative stress, and polyuria play important roles in inducing voiding dysfunction in diabetic individuals. Treatment choice depends on clinical symptoms and urodynamic abnormalities. Urodynamic evaluation is the cornerstone of diagnosis and determines management strategies. Diabetes mellitus could cause a variety of lower urinary tract symptoms, leading to diabetic cystopathy with broadly varied estimates of the prevalence rates. The exact prevalence and pathogenesis of diabetic cystopathy remains to be further investigated and studied in multicenter, large-scaled, or randomized basic and clinical trials, and a validated and standardized workup needs to be made, improving diabetic cystopathy management in clinical practice. Further studies involving only female diabetics are recommended.

Abstract: The relationship between psychological stress and interstitial cystitis/bladder pain syndrome (IC/BPS) has been well described. Even though there is some overlapping of symptoms between overactive bladder (OAB) and IC/BPS, there have been very few studies that specifically investigated the relationship between psychological stress and urinary symptoms in OAB patients who do not have pelvic pain. Here we examined the relationship between psychological stress levels and the severity of overactive bladder (OAB) symptoms.

Abstract: Introduction and hypothesis Risk of pelvic floor disorders increases after menopause and may be linked to estrogen deficiency. We aimed to systematically and critically assess the literature on vaginal estrogen in the management of pelvic floor disorders in postmenopausal women and provide evidence-based clinical practice guidelines. Methods MEDLINE and Cochrane databases were searched frominceptiontoJuly2014forrandomizedcontrolledtrialsof commercially available vaginal estrogen products compared with placebo, no treatment, or any medication for overactive bladder or urinary incontinence. We double-screened 1,805

Abstract: Key points ATP is released through pannexin channels into the lumen of the rat urinary bladder in response to distension or stimulation with bacterial endotoxins. Luminal ATP plays a physiological role in the control of micturition because intravesical perfusion of apyrase or the ecto-ATPase inhibitor ARL67156 altered reflex bladder activity in the anaesthetized rat. The release of ATP from the apical and basolateral surfaces of the urothelium appears to be mediated by separate mechanisms because intravesical administration of the pannexin channel antagonist Brilliant Blue FCF increased bladder capacity, whereas i.v. administration did not. Intravesical instillation of small interfering RNA-containing liposomes decreased pannexin 1 expression in the rat urothelium in vivo and increased bladder capacity. These data indicate a role for pannexin-mediated luminal ATP release in both the physiological and pathophysiological control of micturition and suggest that urothelial pannexin may be a viable target for the treatment of overactive bladder disorders. Abstract ATP is released from the bladder epithelium, also termed the urothelium, in response to mechanical or chemical stimuli. Although numerous studies have described the contribution of this release to the development of various bladder disorders, little information exists regarding the mechanisms of release. In the present study, we examined the role of pannexin channels in mechanically-induced ATP release from the urothelium. PCR confirmed the presence of pannexin 1 and 2 mRNA in rat urothelial tissue, whereas immunofluorescence experiments localized pannexin 1 to all three layers of the urothelium. During continuous bladder cystometry in anaesthetized rats, inhibition of pannexin 1 channels using carbenoxolone (CBX) or Brilliant Blue FCF (BB-FCF) (1–100 μm, intravesically), or by using intravesical small interfering RNA, increased the interval between voiding contractions. Intravenous administration of BB-FCF (1–100 μg kg−1) did not alter bladder activity. CBX or BB-FCF (100 μm intravesically) also decreased basal ATP concentrations in the perfusate from non-distended bladders and inhibited increases in ATP concentrations in response to bladder distension (15 and 30 cmH2O pressure). Intravesical perfusion of the ATP diphosphohydrolase apyrase (2 U ml−1), or the ATPase inhibitor ARL67156 (10 μm) increased or decreased reflex bladder activity, respectively. Intravesical instillation of bacterial lipopolysaccharides (LPS) (Escherichia coli 055:B5, 100 μg ml−1) increased ATP concentrations in the bladder perfusate, and also increased voiding frequency; these effects were suppressed by BB-FCF. These data indicate that pannexin channels contribute to distension- or LPS-evoked ATP release into the lumen of the bladder and that luminal release can modulate voiding function.

Abstract: Objective:To compare the efficacy and safety of mirabegron 50 mg and solifenacin 5 mg in overactive bladder (OAB) patients dissatisfied with previous antimuscarinic treatment due to lack of efficac...

Abstract: Aims To assess the efficacy and safety of mirabegron 50 mg once daily compared with placebo and the active control, tolterodine extended-release (ER) 4 mg once daily, in patients with symptoms of overactive bladder (OAB) in Taiwan, Korea, China, and India. Methods A 12-week multinational, randomized, double-blind, parallel-group placebo- and active-controlled trial. The primary efficacy endpoint was change from baseline to final visit in mean number of micturitions/24 hr. Secondary endpoints were: mean number of urgency episodes, incontinence episodes and urge incontinence episodes/24 hr, mean number of nocturia episodes per night, mean volume voided per micturition, and quality-of-life (QoL) scores as assessed by the King's Health Questionnaire (KHQ). Results Of 1,126 patients who were randomized to receive double-blind study drug, 921 patients (300, 311, and 310 in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively) completed the treatment period. Demographic characteristics were similar across treatment groups. A statistically significant improvement versus placebo in mean number of micturitions/24 hr was seen with mirabegron 50 mg at all timepoints (P < 0.05) as well as final visit (−0.57 with 95% confidence intervals [CIs] of [−1.04, −0.09], P = 0.019). There was no significant difference between treatment groups in improvement from baseline to final visit in any of the secondary outcome measures except volume voided per micturition. The overall incidence of drug-related adverse events was 17.2%, 15.8%, and 21.3%, in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively. Conclusions Mirabegron 50 mg once daily for 12 weeks was superior to placebo in reducing the frequency of micturitions in patients with symptoms of OAB in Taiwan, Korea, China, and India. Neurourol. Urodynam. 34:???–???, 2015. © 2014 Wiley Periodicals, Inc.

Abstract: The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.

Abstract: The International Children’s Continence Society (ICCS) has undertaken an enormous effort to standardize both the terminology and management of various aspects of incontinence in children, including enuresis, bladder overactivity, dysfunctional voiding and psychological comorbidities. A number of guidelines have been published to aid those involved in the care of children with lower urinary tract symptoms. This review addresses a number of recommended diagnostic and therapeutic strategies, including urotherapy and pharmacological treatment, with emphasis on a focused medical history, information acquired from bladder diaries and uroflow evaluations. The major role of urotherapy is underlined with supportive pharmacotherapy, when indicated. The article provides both a summary of ICCS guidelines and a brief review of recently published papers related to the contemporary management of childhood incontinence, a health issue still underestimated by both the child’s caregivers and healthcare providers.

Abstract: A review of functional brain imaging studies of bladder control in participants with normal control and pathological conditions. In the normal condition, bladder and urethral afferents received in the periaqueductal gray relay the information to the insula, the anterior cingulate cortex and the prefrontal cortex. During the storage phase, these superior regions control the pontine micturition center to inhibit voiding. In overactive bladder patients, brain responses are different. Cortical responses become exaggerated, especially in the anterior cingulate cortex and the supplementary motor area. That is what presumably evokes the "urgency". The supplementary motor area is activated during contraction of the pelvic floor muscles, and provides protection against incontinence. We believe that functional brain imaging studies are promising not only for the understanding of bladder dysfunction, but also as an aid to the development of therapeutic options for chronic disorders.

Abstract: Introduction and hypothesis Lower urinary tract symptoms (LUTS) and urinary incontinence (UI) may have a major impact on quality of life. However, not all individuals with urological complaints seek medical advice. The aim of this study was to investigate the prevalence of LUTS in young otherwise healthy nulligravid women and the accompanying burden.

Abstract: Introduction Benign prostatic hyperplasia (BPH) is a common disease that affects men as they age. Historically the treatment has been primarily surgical in nature, but over the past 25 years significant advances in medical therapy have been made, sparing some men from interventional procedures. Materials and methods This article highlights the current state-of-the-art with respect to medical therapy for lower urinary tract symptoms secondary to BPH (BPH-LUTS) including a review of landmark studies and recent areas of research in the field. Results Alpha blockers are considered first line when treating BPH-LUTS in men with small prostates and 5-alpha reductase inhibitors (5-ARIs) are recommended in men with large symptomatic prostates. While, phosphodiesterase-5 (PDE-5) inhibitors are the mainstay of erectile dysfunction therapy, they also play a role in treating BPH-LUTS. If men have persistent irritative storage symptoms after first line BPH therapy then overactive bladder (OAB) medications can be added or substituted. Combination therapies can be used to provide short term symptom relief with long term disease management. Conclusions Medical therapy remains the main treatment option for men suffering from BPH-LUTS. Numerous medical options are available that can be tailored to meet the individual's needs depending on their personal and prostate characteristics. An algorithmic approach, as we have defined within this article, can be a helpful guide to this decision-making process.

Abstract: Although posterior tibial nerve stimulation (PTNS) has been shown in both clinical and animal studies to elicit bladder-inhibitory reflexes, our understanding of the role of posterior tibial nerve ...

Abstract: To critically analyse available phase II and III randomised control trials (RCTs) reporting clinical data about the efficacy and tolerability of Mirabegron (a β3-adrenoceptor agonist) in the treatment of overactive bladder (OAB) syndrome. A review of the literature was performed in September 2013 using the MEDLINE database. A ‘free text’ protocol was used for the search strategy using ‘overactive bladder’ and ‘Mirabegron’ as keywords. Subsequently, the searches were pooled and limited to phase II and III RCTs. Two phase II and five phase III RCTs were selected and analysed. The available phase II studies showed the efficacy and tolerability of different doses of Mirabegron compared with placebo. Moreover, a dose-ranging study showed that 50 mg once daily should be considered the most promising dose for clinical use. The 12-week phase III studies confirmed the effectiveness of Mirabegron to significantly reduce the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h compared with placebo. A post hoc analysis confirmed that favourable results with Mirabegron were reported both in patients with OAB who were antimuscarinic naive and in those who had discontinued prior antimuscarinic therapy. Moreover, a phase III trial showed the safety and tolerability of 12-month treatment of Mirabegron. Discontinuation due to adverse events was low both using the 50 and 100 mg dose of Mirabegron. Mirabegron is the first of a new class of drugs for the treatment of OAB able to influence non-voiding activity and produce an increased storage capacity and inter-void interval. Recently published phase II and III RCTs have shown that the β3-adrenoceptor-selective agonist, Mirabegron, is an effective and safe drug for the symptomatic treatment of OAB syndrome. Mirabegron represents a valid medical option both for patients with OAB who are antimuscarinic naive, as well as in those where antimuscarinics are ineffective or not tolerated.

Abstract: Botulinum toxin subtype A (BoNT-A) is a potent neurotoxin that can selectively modulate neurotransmitter release from nerve endings, resulting in muscular paralysis. BoNT-A might also act on sensory nerves, and have an anti-inflammatory effect. In the first urological use of BoNT-A, injection into the urethral sphincters of patients with detrusor-sphincter dyssynergia resulted in a reduction of urethral resistance and improved voiding efficiency. Subsequently, intravesical BoNT-A injections have received regulatory approval for treatment of neurogenic detrusor overactivity owing to spinal cord lesions or multiple sclerosis, and idiopathic overactive bladder in adults. BoNT-A has also been widely used to treat patients with the off-label indications of neurogenic or non-neurogenic voiding dysfunction and male lower urinary tract symptoms owing to BPH and bladder-neck dysfunction. Other indications for which urologists have applied BoNT-A injections include interstitial cystitis/bladder pain syndrome, bladder oversensitivity and chronic pelvic pain syndrome. BoNT-A is currently delivered as an intravesical injection; however, use of liposome encapsulated formulations is also beginning to show some therapeutic potential.

Abstract: Aims To quantify changes in pudendal nerve function with sacral neuromodulation (SNM). To understand the relationship of pudendal nerve function to SNM treatment response for overactive bladder. To assess the relationship between female sexual function and pudendal nerve function after SNM. Methods Women undergoing SNM between January 2010 and May 2011 were enrolled. Baseline pudendal nerve terminal motor latencies (PNTML) were measured bilaterally. Subjects underwent peripheral nerve evaluation (PNE) prior to SNM therapy. PNTML was measured at 1 and 6 weeks after sacral neuromodulator implant. Women who did not undergo permanent implantation were reassessed at the end of the 1-week PNE testing phase. Pelvic floor and sexual function questionnaires were administered at baseline and follow-up to assess pelvic floor and sexual function. Results Of 34 women enrolled, 31 were evaluated. Mean age was 67.4 ± 14.2 years with 29/34 (85.3%) treated for refractory overactive bladder. Thirty of 31 (96.7%) went on to a permanent implant. PNE success rate was 73.5% (25/33). Mean PNTML changed from 2.74 ± 0.52 msec at baseline to 2.57 ± 0.50 msec at 6 weeks postop (P = 0.198). Baseline amplitude remained stable at 1 and 6 weeks. At 6 weeks PISQ-12 scores showed improved sexual function (P = 0.034) and PFDI-20 and PFIQ-7 scores showed improved pelvic floor, colorectal and urinary symptoms (P < 0.05). Conclusions Women with refractory overactive bladder and non-obstructive urinary retention have abnormal pudendal nerve function, which showed a non-significant trend toward improvement after SNM. Sexually active women undergoing sacral neuromodulation experienced improvement in sexual function. Quality of life improved due to improvement in urinary and colorectal function. Neurourol. Urodynam. 34:456–460, 2015. © 2014 Wiley Periodicals, Inc.

Abstract: There are various forms of treatment for prostate cancer. In addition to oncologic outcomes, physicians, and increasingly patients, are focusing on functional and adverse outcomes. Symptoms of overactive bladder (OAB), including urinary frequency, urgency and incontinence, can occur regardless of treatment modality. This article examines the prevalence, pathophysiology and options for treating OAB after radical prostate cancer treatment. OAB seems to be more common and severe after radiation therapy than after surgical therapy and even persisted longer with complications, suggesting an advantage for surgery over radiotherapy. Because OAB that occurs after radical prostate surgery or radiotherapy can be difficult to treat, it is important that patients are made aware of the potential development of OAB during counselling before decisions regarding treatment choice are made. To ensure a successful outcome of both treatments, it is imperative that clinicians and non-specialists enquire about and document pretreatment urinary symptoms and carefully evaluate post-treatment symptoms.