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Context Understanding men’s values and preferences in the context of personal, physical, emotional, relational, and social factors is important in optimising patient counselling, facilitating treatment decision-making, and improving guideline recommendations. Objective To systematically review the available evidence regarding the values, preferences, and expectations of men towards the investigation and treatment (conservative, pharmacological, and surgical) of male lower urinary tract symptoms (LUTS). Evidence acquisition We searched electronic databases until August 31, 2020 for quantitative and qualitative studies that reported values and preferences regarding the investigation and treatment of LUTS in men. We assessed the quality of evidence and risk of bias using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) and GRADE Confidence in the Evidence from Reviews of Qualitative Research (CERQual) approaches. Evidence synthesis We included 25 quantitative studies, three qualitative studies, and one mixed-methods study recruiting 9235 patients. Most men reported urodynamic testing to be acceptable, despite discomfort or embarrassment, as it significantly informs treatment decisions (low certainty evidence). Men preferred conservative and less risky treatment options, but the preference varied depending on baseline symptom severity and the risk/benefit characteristics of the treatment (moderate certainty). Men preferred pharmacological treatments with a low risk of erectile dysfunction and those especially improving urgency incontinence (moderate certainty). Other important preference considerations included reducing the risk of acute urinary retention or surgery (moderate certainty). Conclusions Men prefer lower-risk management options that have fewer sexual side effects and are primarily effective at improving urgency incontinence and nocturia. Overall, the evidence was rated to be of low to moderate certainty. This review can facilitate the treatment decision-making process and improve the trustworthiness of guideline recommendations. Patient summary We thoroughly reviewed the evidence addressing men’s values and preferences regarding the management of urinary symptoms and found that minimising adverse effects is particularly important. Further research to understand other factors that matter to men is required.

Context: The role of overactive bladder (OAB) treatment in women beyond antimuscarinics has been evaluated extensively. Beta-3 agonists, botulinum toxin-A (BTX-A), and nerve stimulation are indicated in these patients. However, data on male patients in this clinical scenario are scarce.Objective: The aim of this systematic review was to evaluate the evidence on treatment options beyond antimuscarinics in men with OAB.Evidence acquisition: A search of PubMed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases was performed for relevant articles published between January 2000 and October 2020, using the following Medical Subject Headings: "male/man," "LUTS," "overactive bladder," "storage symptoms," "urgency," "nocturia," "incontinence," "beta-3 agonist," "PDE-5 inhibitors," "botulinum toxin," "sacral nerve stimulation/neurostimulation," "percutaneous/transcutaneous tibial nerve stimulation," "PTENS," and "combination therapy." Evidence acquisition was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PROSPERO registration number is CRD42020201223.Evidence synthesis: Overall, 24 studies were retrieved. In male OAB, mirabegron (MIRA) is the most intensively investigated pharmacological option. A pooled analysis of five randomized clinical trials (RCTs), including 1187 patients, concluded that MIRA 50 mg was associated with a greater reduction in frequency versus placebo (-0.37, 95% confidence interval [CI]: -0.74, -0.01, p < 0.05). A pooled analysis of three RCTs, including 1317 male patients, has also shown that the addition of MIRA 50 mg in men receiving the alpha(1)-blocker tamsulosin improved the mean number of micturitions per day (-0.27, 95% CI: -0.46 to -0.09, p < 0.05), urgency episodes (-0.50, 95% CI: -0.77 to -0.22, p < 0.05), total OAB symptom score (-0.66, 95% CI: -1.00 to -0.38, p < 0.05), and mean volume voided (+10.76 ml, 95% CI: 4.87-16.64, p < 0.05). MIRA treatment is well tolerated in men. Other pharmacological treatment options, such as phosphodiesterase-5 (PDE-5) inhibitors, should be considered investigational. BTX-A seems to be effective as third-line treatment in male OAB patients. A higher rate of intermittent self-catheterization (5-42%) is observed in male than in female patients. Data on nerve stimulation are scarce.Conclusions: MIRA has the most robust data in terms of safety and efficacy in this patient population. Preliminary data in men suggest that BTX-A is indicated as an interventional treatment. Evidence for PDE-5 inhibitors and nerve stimulation is too limited to provide recommendations. Future studies in this population should aim to better define the best treatment sequence and to identify predictors for treatment response and failure, to determine a therapeutic approach tailored to patients' characteristics.Patient summary: Overactive bladder is highly prevalent in men. Mirabegron 50 mg is the treatment option supported by the highest level of evidence when antimuscarinics failed. Botulinum toxin A injections seems to be an effective treatment as interventional option. Roles of nerve stimulation and phosphodiesterase inhibitors in male OAB patients are still to be defined. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

We established severity banding ranges, bother assessment and key item content in principal patient reported outcomes measures in men seeking therapy for lower urinary tract symptoms.Data for International Prostate Symptom Score (I-PSS) and International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) were derived from a study evaluating 820 men at 26 United Kingdom hospitals. ROC curves were used to establish severity bandings.Classification tree showed that thresholds between mild-moderate and moderate-severe severity bands were 15 and 27 for I-PSS, 16 and 26 for ICIQ-MLUTS/severity, and 22 and 81 for ICIQ-MLUTS/bother, respectively. Highest area under the ROC curve and lowest Akaike's information criteria of univariate logistic regression indicated that ICIQ-MLUTS/bother was more related to global quality of life than were I-PSS and ICIQ-MLUTS/severity. The symptoms affecting I-PSS-quality of life (QoL) were only fully identified by ICIQ-MLUTS, because 2 key symptoms (urinary incontinence and post-micturition dribble) are not measured by I-PSS. ICIQ-MLUTS demonstrated that bother of some lower urinary tract symptoms is disproportionate to severity, and that persisting high bother levels following surgery are more likely due to storage (18% to 25%) and post-voiding (18% to 28%) lower urinary tract symptoms than voiding lower urinary tract symptoms (5% to 13%). Symptom improvement after surgery was uncertain if baseline I-PSS-QoL score was less than 3.The severity threshold scores were measured for the 2 key lower urinary tract symptoms patient reported outcomes measures, and the results indicate suitable categories of symptom severity for use in men referred for urological care. The ICIQ-MLUTS measures all the lower urinary tract symptoms affecting quality of life and includes individual symptom bother scores.

Aims To inform and guide patient-centred care for men with lower urinary tract symptoms (LUTS), by providing in-depth qualitative evidence regarding men's perspectives on treatment decision-making for LUTS. Methods An interview study of men recruited from 26 English urology departments. Purposive sampling captured surgical/nonsurgical treatment decisions, and diversity in demographics and symptom burden, in men who had urodynamics and those who did not. After diagnostic assessments, men were interviewed either pre-treatment or after LUTS surgery. Thematic analysis was conducted. Participants' descriptions of how LUTS treatment decisions were made were categorised as patient-led, doctor-led, or shared. Results A total of 41 men participated (25 pre-treatment, 16 post-surgery), ages 52-89. Twenty out of 41 described the treatment decision as shared with their consultant, 14 as doctor-led, and seven as patient-led. There was no obvious association between treatment decision-making style and patients' satisfaction with either clinicians' role in their decision or their treatment decision. Incomplete or rushed discussions and misperceptions of LUTS and its treatment were reported, indicating a risk of suboptimal decision-making support by clinicians. As well as clinician opinion, men's treatment decision-making was influenced by the results of urological assessments, comparing current symptoms with possible side-effects of surgery, and others' experiences and opinions. Conclusions Men with LUTS report and prefer different kinds of decision-making support from their clinicians, who must tailor their input to patients' preferences and needs. Patients' treatment decision-making involves multiple factors and can be challenging, and areas of inadequate clinician support were identified. Recommendations for patient-centred consultations about LUTS treatment are presented.

Aim Lower urinary tract symptoms (LUTS) are a common urological referral, which sometimes can have a neurological basis in a patient with no formally diagnosed neurological disease (“occult neurology”). Early identification and specialist input is needed to avoid bad LUTS outcomes, and to initiate suitable neurological management. Methods The International Continence Society (ICS) established a neurological working group to consider;1. Which neurological conditions may include LUTS as an early feature?2. What diagnostic evaluations should be undertaken in the LUTS clinic?A shortlist of conditions was drawn up by expert consensus and discussed at the annual congress of the International Neurourology Society. A multidisciplinary working group then generated recommendations for identifying clinical features and management. Results The relevant conditions are multiple sclerosis (MS), multiple system atrophy (MSA), normal pressure hydrocephalus (NPH), early dementia, Parkinsonian syndromes (including early Parkinson’s Disease and Multiple System Atrophy) and spinal cord disorders (including spina bifida occulta with tethered cord, and spinal stenosis). In LUTS clinics, the need is to identify additional atypical features; new onset severe LUTS (excluding infection), unusual aspects (e.g. enuresis without chronic retention) or “suspicious” symptoms (e.g. numbness, weakness, speech disturbance, gait disturbance, memory loss/ cognitive impairment, and autonomic symptoms). Where occult neurology is suspected, healthcare professionals need to undertake early appropriate referral; central nervous system (CNS) imaging booked from LUTS clinic is not recommended. Conclusions Occult neurology is an uncommon underlying cause of LUTS, but it is essential to intervene promptly if suspected, and to establish suitable management pathways.

Background:Penile clamps provide a means of preventing urinary incontinence in males following radical prostatectomy. In order for the devices to function, significant mechanical loads need to be applied to the penile tissues to close the urethra. However, such loads have the potential to cause damage to the vulnerable skin and underlying soft tissues. Accordingly, the study aimed to estimate the magnitudes of tissue deformations resulting from penile clamp application in three individual cases.Methods:Three individuals were recruited who currently use penile clamps to manage urinary incontinence following radical prostatectomy. Magnetic resonance images (MRI) of the penis were taken to produce a series of high contrast coronal and sagittal images both before and during the application of two commercially available clamps, modified for MRI compatibility. Tissue thickness measurements were estimated with the clamps in-situ and normalised to the unloaded baseline state.Results:The estimated magnitude of tissue deformations resulting from clamp application ranged between 68% and 84%. There were minimal differences in these deformations between the clamp designs, both of which appeared effective in closing the urethra. Local stress concentrations were observed in the tissues, which were deformed around the shape of the clamp.Conclusions:MRI enabled quantification of local tissue deformation during penile clamp application. The results revealed that clamps created large tissue deformations in all three cases, regardless of design. This information could inform the development of new clamp designs and materials to minimise the potential for tissue damage.Level of evidence:4

AIM: The International Continence Society (ICS) has standardized quality control and interpretation of uroflowmetry and urodynamics. We evaluated traces from two large studies of male lower urinary tract symptoms (UPSTREAM and UNBLOCS) against ICS standards of urodynamic equipment and practice.METHODS: Ten percent of uroflowmetry and urodynamics traces were selected at random from hospital sites. A data capture template was designed from the ICS Fundamentals of Urodynamic Practice checklist. Two pretrained blinded assessors extracted the data, with a third assessor to arbitrate. Departmental records of calibration checks and equipment maintenance were scrutinized.RESULTS: Seven out of twenty-five (28%) departments reported no calibration checks. Four sites (16%) could not provide annual service records. In 32 out of 296 (10.8%) uroflowmetry traces, findings were affected by artifact. One hundred ten urodynamic study traces were reviewed; in 11 records (10%), key pressure traces were incompletely displayed. In 30 (27.2%), reference zero was not set to atmospheric pressure. Resting pressures were outside the expected range for 36 (32.7%). Pressure drift was seen in 18 traces (16.4%). At pressure-flow study commencement, permission to void was omitted in 15 (13.6%). Cough testing after voiding was done in 71.2%, but the resulting cough spikes were significantly different in 16.5%. Erroneous diagnosis of bladder outlet obstruction (BOO) was identified in six cases (5.5%).CONCLUSIONS: Erroneous diagnosis of BOO is a serious error of interpretation, as it could lead to unnecessary surgery. Other errors of standardization, testing, and interpretation were identified with lower risk of adverse implications. Inconsistent documentation of service records mean equipment accuracy is uncertain.

Background Lower urinary tract symptoms (LUTS) can relate to urinary storage or voiding. In men, the prevalence and severity of LUTS increases with age, with a significant impact on quality of life. The majority of men presenting with LUTS are managed by their general practitioner (GP) in the first instance, with conservative therapies recommended as the initial treatment. However, the provision of conservative therapies in primary care is variable and can be time and resource limited. GPs require practical resources to enhance patient engagement with such interventions. TRIUMPH aims to determine whether a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for LUTS versus usual care. Methods/design TRIUMPH is a two-arm, cluster randomised controlled trial (RCT) being conducted in 30 National Health Service (NHS) general practices in England. The TRIUMPH intervention comprises a standardised LUTS advice booklet developed for the trial with patient and healthcare professional (HCP) consultation. The booklet is delivered to patients by nurses/healthcare assistants following assessment of their urinary symptoms. Patients are directed to relevant sections of the booklet, providing the manualised element of the intervention. To encourage adherence, HCPs provide follow-up contacts over 12 weeks. Practices are randomised 1:1 to either deliver the TRIUMPH intervention or a usual care pathway. The patient-reported International Prostate Symptom Score (IPSS) at 12 months post consent is the primary outcome. Secondary outcomes include cost-effectiveness, patient-reported outcomes on LUTS, quality of life, and patient and HCP acceptability and experience of the intervention. Primary analyses will be conducted on an intention-to-treat basis. Discussion It is unclear whether conservative therapies for male LUTS are effectively delivered in primary care using current approaches. This can lead to men being inappropriately referred to secondary care or experiencing persistent symptoms. Primary care, therefore, holds the key to effective treatment for these men. The TRIUMPH intervention, through its standardised and manualised approach, has been developed to support GP practices in delivering effective conservative care. This pragmatic, cluster RCT should provide robust evidence in a primary-care setting to inform future guidelines. Trial registration ISCRTN registry, ID: ISRCTN11669964. Registered on 12 April 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3648-1) contains supplementary material, which is available to authorized users.

Background: Penile compression devices (PCD) or clamps are applied to compress the urethra and prevent urinary incontinence (UI). PCDs are more secure and less likely to leak than pads, allowing men the opportunity to participate in short-term, vigorous activities. However, they are uncomfortable, can cause pressure ulcers (PU) and affect penile blood flow. No objective assessment of tissue health has been undertaken to assess and compare different PCD designs and to provide guidance on safe use. Objective: This study was designed to evaluate existing PCDs in terms of their physiological response and potential for pressure-induced injury. Design, setting and participants: Six men with post-prostatectomy UI tested four selected PCDs at effective pressures, in a random order, in a controlled laboratory setting. Outcome measurements and statistical analysis: Using objective methods for assessing skin injury, PCDs were measured in situ for their effects on circulatory impedance, interface pressures and inflammatory response. Results and limitations: There was evidence for PCD-induced circulatory impedance in most test conditions. Interface pressures varied considerably between both PCDs and participants, with a mean value of 137.4±69.7 mmHg. In some cases, penile skin was noted to be sensitive to loading with elevated concentration of the cytokine IL-1α after 10 mins wear, indicating an inflammatory response. IL-1α levels were restored to baseline 40 mins following PCD removal. Conclusion: Skin health measures indicated tissue and blood flow compromise during the 50 mins of testing using all PCDs. Although there was an elevation in pro-inflammatory cytokines, PCDs did not cause sustained irritation and skin health measures recovered 40 mins after PCD removal. This research indicates that application of a clamp for one hour with an equal clamp free time before reapplication is likely to be safe. Longer periods are often recommended by manufacturers but have yet to be tested.

INTRODUCTION: The terminology for nocturia and nocturnal lower urinary tract function is reviewed and updated in a clinically and practically-based consensus report.METHODS: This report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardisation Steering Committee (SSC). All relevant definitions were updated on the basis of research over the last 16 years since the publication of the first nocturia standardization document in 2002. An extensive process of 16 rounds of internal and external reviews was involved to examine each definition exhaustively, with decision-making by collective opinion (consensus).RESULTS: A clinically-based terminology report for nocturia and nocturnal lower urinary tract function, encompassing five key definitions divided into signs and symptoms has been developed. Clarity and user-friendliness have been key aims to make it interpretable by healthcare professionals and allied healthcare practitioners involved in the care of individuals with nocturnal lower urinary tract function.CONCLUSION: A consensus-based terminology report for nocturia and nocturnal lower urinary tract function has been produced to aid clinical practice and research.

Introduction: Prevalence of urinary symptoms such as incontinence (UI) in patients with dementia is estimated to exceed 50%. The resultant psychological and socio-economic burden can be substantial. Our aim was to develop a dedicated urology service within a cognitive impairment clinic in order to treat and better understand the bothersome urinary symptoms suffered by persons with dementia.Methods: Patients attending this clinic were invited to be assessed and interviewed by urologist, together with their family and/or carer. In addition, formal history, examination and relevant investigations, themes of importance such as quality of life, and select question items were drawn from validated questionnaires. Multidisciplinary team (MDT) meeting was carried out on the same day. Outcomes of the first 75 patients with UI and dementia have been reported.Results: Average age was 70 years (range 58-98). Majority of persons had a diagnosis of Alzheimer's disease (n = 43, 57%). Average score for how much urine leakage interferes with everyday life was 7.7/10 (range 2-10). 58.7% (n = 44) revealed some degree of sleep disturbance due to UI. 83% (n = 62) stated daily activities were limited due to UI. Two-thirds of persons with dementia (n = 50) stated their bladder problem makes them feel anxious. 88% (n = 67) felt the topic was socially embarrassing. All carers stated that the person's continence issues affect the care they provide. Less than one-third of carers (30.7%, n = 23) were aware of or had been in contact with any bladder and bowel community service. More than half of the carers (n = 46, 65%) were concerned incontinence may be a principal reason for future nursing home admission.Conclusion: UI can be distressing for persons with dementia. Care partners were concerned about loss of independence and early nursing home admission. Awareness of bladder and bowel services should be increased.

BackgroundStress urinary incontinence (SUI) is common after radical prostatectomy and likely to persist despite conservative treatment. The sling is an emerging operation for persistent SUI, but randomised controlled trial (RCT) comparison with the established artificial urinary sphincter (AUS) is lacking.ObjectiveTo compare the outcomes of surgery in men with bothersome urodynamic SUI after prostate surgery.Design, setting, and participantsA noninferiority RCT was conducted among men with bothersome urodynamic SUI from 27 UK centres. Blinding was not possible due the surgeries.InterventionParticipants were randomly assigned (1:1) to the male transobturator sling (n = 190) or the AUS (n = 190) group.Outcome measurements and statistical analysisThe primary outcome was patient-reported SUI 12 mo after randomisation, collected from postal questionnaire using a composite outcome from two items in validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form questionnaire (ICIQ-UI SF). Noninferiority margin was 15%, thought to be of acceptable lower effectiveness, in return for reduced adverse events (AEs) and easier operation, for the sling. Secondary outcomes were operative and postoperative details, patient-reported measures, and AEs, up to 12 mo after surgery.Results and limitationsA total of 380 participants were included. At 12 mo after randomisation, incontinence rates were 134/154 (87.0%) for male sling versus 133/158 (84.2%) for AUS (difference 3.6% [95% confidence interval {CI} –11.6 to 4.6], pNI = 0.003), showing noninferiority. Incontinence symptoms (ICIQ-UI SF) reduced from scores of 16.1 and 16.4 at baseline to 8.7 and 7.5 for male sling and AUS, respectively (mean difference 1.4 [95% CI 0.2–2.6], p = 0.02). Serious AEs (SAEs) were few: n = 6 and n = 13 for male sling and AUS (one man had three SAEs), respectively. Quality of life scores improved, and satisfaction was high in both groups. All other secondary outcomes that show statistically significant differences favour the AUS.ConclusionsUsing a strict definition, urinary incontinence rates remained high, with no evidence of difference between male sling and AUS. Symptoms and quality of life improved significantly in both groups, and men were generally satisfied with both procedures. Overall, secondary and post hoc analyses were in favour of AUS.Patient summaryUrinary incontinence after prostatectomy has considerable effect on men’s quality of life. MASTER shows that if surgery is needed, both surgical options result in fewer symptoms and high satisfaction, despite most men not being completely dry. However, most other results indicate that men having an artificial urinary sphincter have better outcomes than those who have a sling.

ObjectiveProstate surgery can improve lower urinary tract symptoms (LUTS) by relieving bladder outlet obstruction (BOO). However, surgery is less effective without BOO, or if detrusor underactivity (DU) is present. Urodynamics (UDS) can identify BOO and measure detrusor activity, but evidence in clinical practice is lacking. UPSTREAM (Urodynamics for Prostate Surgery Trial: Randomised Evaluation of Assessment Methods) evaluated whether a carepathway including UDS would reduce surgery without increasing urinary symptoms.Design, setting and participantsUPSTREAM is a pragmatic, non-inferiority randomised controlled trial in 26 hospitals in England (ISRCTN56164274) in men with bothersome LUTS where surgery was an option. InterventionParticipants were randomised (1:1) to routine care (RC) diagnostic tests, or routine care plus urodynamics (UDS).Outcome measuresThe primary outcome was International Prostate Symptom Score (IPSS; patient reported outcome scale from 0 to 35 points) 18-months post-randomisation, with a non-inferiority margin of one point. Urological surgery rates were a key secondary outcome.Statistical analysisThe primary outcome was compared between the arms using linear regression, analysed on an intention-to-treat basis.Results and limitationsBetween October 2014 and December 2016, 820 men (median age 68 years) were randomised (393 and 427 in RC and UDS arms, respectively). The UDS arm showed noninferiority of mean IPSS scores (UDS 12·6; RC 13.1; adjusted difference at 18 months -0·33 (95% CI -1·47, +0·80)). In the UDS arm, 153/408 (38%) received surgery compared with 138/384 (36%) for RC (adjusted OR 1·05; 95% CI 0·77, 1·43). 428 adverse events (UDS 234; RC 194) were recorded, with related events similar in both arms, and 11 unrelated deaths.Conclusion In this population, the UDS randomised group was non-inferior to RC for IPSS but did not reduce surgical rates. The study shows that routine use of UDS in evaluation of uncomplicated LUTS has a limited role and should be used selectively. Patient summaryFor men with uncomplicated lower urinary tract symptoms, the symptom improvements after treatment and the number of operations done are similar, whether or not urodynamic tests aredone in addition to routine tests. Accordingly, routine use of UDS has a limited role in this population group.

Background Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. Objectives The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. Design This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. Setting Urology departments of 26 NHS hospitals in England. Participants Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. Interventions Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). Main outcome measures The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. Results A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (–0.33, 95% CI –1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43–44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. Limitations The trial met its predefined recruitment target, but surgery rates were lower than anticipated. Conclusions Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. Future work Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. Trial registration Current Controlled Trials ISRCTN56164274. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

IntroductionLower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care.Methods and analysisPRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool.Ethics and disseminationEthics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders.Trial registration numberISRCTN10327305.

Micturition requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. This involves a spino-bulbospinal control circuit incorporating Barrington’s nucleus in the pons (Barr). Ponto-spinal glutamatergic neurons that express corticotrophin-releasing hormone (CRH) form one of the largest Barr cell populations. BarrCRH neurons can generate bladder contractions, but it is unknown whether they act as a simple switch or provide a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with multisite extracellular recordings in urethane anaesthetised CRHCre mice show that BarrCRH neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. CRH itself provides negative feedback regulation of this process. These findings inform a new inferential model of autonomous micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.

Introduction: in severe post prostatectomy stress urinary incontinence (SUI), urodynamics may not identify crucial parameters because of inadequate bladder filling. This study describes evaluation of cystometry and pressure flow study (PFS) in men where severe SUI during attempted filling necessitated application of a penile clamp to allow filling to reach cystometric capacity. Methods: we identified all men who had undergone prior radical prostatectomy from a database of patients attending for videourodynamic testing between 2012-2017. Symptom scores, bladder diary and free flow rate tests were retrieved. We evaluated the measurements of the subgroup of men with severe SUI for whom a Thomson-Walker compression clamp was utilised to enable full urodynamic evaluation. Results: 166 radical prostatectomy patients were identified. In 30 (18%), severe SUI led to incomplete filling cystometry, i.e. failure to reach cystometric capacity. Following application of the penile compression clamp, it was possible to achieve further filling in each case. Applying the clamp did not alter vesical filling or impede pressure recording. These men had a lower maximum urethral closure pressure (31.6 vs 46.5cmH2O; p

Background. Multiple Sclerosis (MS) is a chronic neurological disorder caused by neurodegeneration within the central nervous system. It results in impaired physical, cognitive, and psychological functioning and can also lead to lower urinary tract symptoms including nocturia. While clinical trials have suggested an association between nocturia and melatonin secretion, to our knowledge, no qualitative research has been conducted on the experience of taking melatonin to treat nocturia in progressive MS within a clinical trial. Methods. 17 semistructured qualitative interviews were conducted as part of a double-blind, randomised, placebo controlled, crossover, clinical trial with consenting adults with MS. Interviews explored participants’ experiences of nocturia associated with MS and their experience of taking melatonin as a trial treatment for nocturia versus a placebo. Data was analysed using a thematic analysis. Results. Themes on the experience of nocturia revealed participants’ understandings of nocturia, the impact it had on their night, and increased daily fatigue. Themes on the intervention showed perceived improvements to nocturia, sleep, and energy and negative effects including lethargy, a lack of significant change, and physical side effects including vivid dreams. Conclusion. This qualitative exploration revealed an association between nocturia and increased levels of fatigue during the day by those with MS. However, perspectives towards the effectiveness of melatonin as a potential treatment varied as both placebo and melatonin were perceived as having very similar effects.

AIMS: To capture in-depth qualitative evidence regarding attitudes to and experiences of urodynamic testing among men with lower urinary tract symptoms (LUTS) at each end of the clinical pathway.METHODS: Semi-structured interview study conducted within the Urodynamics for Prostate Surgery: Randomized Evaluation of Assessment Methods (UPSTREAM) trial, which randomized men to a care pathway including urodynamics or routine non-invasive tests from 26 secondary care urology sites across England. Men were interviewed after assessments but prior to treatment, or after surgery for LUTS. Men were purposively sampled to include those who had urodynamics and those who did not, and diversity in demographic characteristics and symptom burden. Interviews were analyzed using inductive thematic analysis.RESULTS: Forty-one men participated (25 pre-treatment, 16 post-surgery), ages 52-89. The 16 men who had not previously experienced urodynamics said they would accept the test in their assessment, but some were apprehensive or wanted more information. The 25 men who had experienced urodynamics all found it acceptable, though some reported pain, infection, or embarrassment. Embarrassment was minimized by informing patients what the procedure would be like, and ensuring privacy. Urodynamics was valued for its perceived diagnostic insight. Information deficits were reported before, during, and after the test. How and when results were explained and the adequacy of explanations varied.CONCLUSIONS: Urodynamics is acceptable to men with LUTS and generally well-tolerated. To ensure patients are prepared and informed, good communication before and during the procedure is essential. Privacy should be prioritized, and test results discussed promptly and in sufficient detail. Staff require training and guidance in these areas.

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The International Continence Society (ICS) has sustained a drive to improve the clinical assessment of lower urinary tract function for many years. Increasingly, healthcare professionals (HCPs) engage with the guidance, and patients benefit from the precision that results when their carers apply a sensible and logical approach to assessment. The current supplementary issue of Neurourology and Urodynamics (NAU) summarizes the fundamentals derived from major ICS initiatives, emphasizing what HCPs must know when dealing with these patients, regardless of the medical discipline in which they work. It also introduces the basics of urodynamics testing to trainees and HCPs who may refer patients for testing. In this editorial review we draw out some additional points of consideration. We emphasize the need to avoid using terms in a clinical context that could imply causative mechanism, until the mechanism has actually been identified. We caution against the use of severity thresholds, until there is proper data to justify their application for any given patient group. Finally, we provide a description of the philosophical basis of urodynamics testing, including videourodynamics. This commentary should be read in the context of the other articles provided in the NAU supplement.

Aims To summarize basic definitions in the International Continence Society (ICS) Standardization of Terminology in lower urinary tract (LUT) function and their application. Methods Fundamental terminology in the ICS Standardization of Terminology LUT Function was identified and summarized. Results Evaluation of LUT requires appreciation of symptoms, signs and urodynamic observations. Symptoms are categorized according to their occurrence during the micturition cycle into storage symptoms (eg, increased daytime frequency [IDF], urgency, nocturia, or incontinence) or voiding and post-voiding symptoms (eg, slow stream or post micturition dribbling). Several problems may be present, giving rise to symptom syndromes, notably overactive bladder (during the storage phase) or underactive bladder (during the voiding phase). Signs may be derived from a bladder diary or may be elicited on physical examination. Urodynamic observations may be made by assessing flow rate, and this is combined with pressure measurement when undertaking filling cystometry and pressure flow studies. Key elements of flow and pressure measurement are described. Conclusions The review provides a succinct summary of symptoms, signs, and urodynamic observations as set out in the ICS Standard on LUT Function.

Aims Chronic pelvic pain (CPP) is defined as a noncyclical pain that has duration of at least 6 months and can lead to decreased quality of life and physical performance. The pain can be attributed to problems in the pelvic organs and/or problems in related systems, and possible psycho-social attributes may contribute to the manifestation. Due to the complex nature, CPP syndromes are multifactorial and the terminology needs to reflect the setting. Methods The current review is a synthesis of key aspects of the recent International Continence Society Standardization for Terminology in CPP Syndromes. Results Nine domains can be used for a detailed description of CPP. They include four domains specific to the pelvic organs (lower urinary tract, female genital, male genital, gastrointestinal), two related to other sources of pain which may be perceived in the pelvis (musculoskeletal, neurological) and three which may influence the response to the pain or its impact on the individual (psychological, sexual, and comorbidities). For an individual patient with CPP, each domain should be reviewed in terms of symptoms and signs, noting that positive findings could reflect either a primary cause or a secondary consequence. The findings will guide further evaluations and subsequent treatment. Conclusion We present a synthesis of the standard for terminology in CPP syndromes in women and men, which serves as a systematic framework to consider possible sources of pain (pelvic organs or other sources) and the individual responses and impact.

AIMS The process of identifying research questions, synthesizing and interpreting evidence, and weight given to health economics differs between the clinical guidelines (CGs) for neurogenic lower urinary tract dysfunction (NLUTD). Consequently, the quality also varies which can have implications for clinical practice. METHODS We used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to assess the quality of the National Institute for Health and Care Excellent (NICE), European Association of Urology (EAU), and the International Consultations on Incontinence (ICI) CGs on neurogenic bladder. RESULTS The NICE CGs were deemed to be of the highest quality (overall score of 92%). NICE were the only guidelines to systematically incorporate cost-effectiveness research into their recommendations. The EAU CGs received an overall score of 83% and the ICI CGs achieved the lowest overall score (75%). The highest scoring domain among all the CGs was scope purpose (86%) and the lowest scoring domain was applicability (69%). All guidelines were recommended for use (mostly with some modifications). CONCLUSIONS All CGs had their inherent advantages and disadvantages, though all were still deemed to be of high quality. Incorporating cost-effectiveness research would be near impossible for guidelines with a broad-country remit. Incorporating the AGREE II instrument in the development of CGs and better collaboration between the ICI, NICE, and EAU could improve the quality, and consistency between NLUTD CGs and ultimately improve health outcomes for this important patient group.

Aims To test the significance of association between a validated index of detrusor contractility, vCE , the Watts Factor, and the Detrusor Contractility Parameter, t20-80 ; and to test whether t20-80 depends on outflow tract resistance as indicated by Bladder Outlet Obstruction Index (BOOI). Methods Thirty-seven pressure-flow traces from 20 male and 17 female patients were analyzed and forms of the Watts Factor, t20-80 and BOOI were compared with vCE . Results The Detrusor Contractility Parameter, t20-80 , is significantly associated with vCE for both women and men without a high degree of bladder outlet obstruction. The Watts Factor only had a significant association with vCE at the point of maximum flow in women. Conclusions The Detrusor Contractility Parameter (DCP) (t20-80 ), can be measured easily from the pressure flow curves of a urodynamic test. The Watts Factor at maximum urine flow, WFQmax , can be readily calculated, but is only applicable to women. In both women and men without a high degree of bladder outlet obstruction, DCP is better associated with true detrusor contractility than any Watts Factor analysis.

Introduction Surgeon-specific outcome data, or consultant outcome publication, refers to public access to named surgeon procedural outcomes. Consultant outcome publication originates from cardiothoracic surgery, having been introduced to US and UK surgery in 1991 and 2005, respectively. It has been associated with an improvement in patient outcomes. However, there is concern that it may also have led to changes in surgeon behaviour. This review assesses the literature for evidence of risk-averse behaviour, upgrading of patient risk factors and cessation of low-volume or poorly performing surgeons. Materials and methods A systematic literature review of Embase and Medline databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Original studies including data on consultant outcome publication and its potential effect on surgeon behaviour were included. Results Twenty-five studies were identified from the literature search. Studies suggesting the presence of risk-averse behaviour and upgrading of risk factors tended to be survey based, with studies contrary to these findings using recognised regional and national databases. Discussion and conclusion Our review includes instances of consultant outcome publication leading to risk-averse behaviour, upgrading of risk factors and cessation of low-volume or poorly performing surgeons. As UK data on consultant outcome publication matures, further research is essential to ensure that high-risk patients are not inappropriately turned down for surgery.

Aims: In recent years urodynamic innovations, although well researched, have failed to follow a standardized development pathway specifically in terms of clinical trials undertaken to demonstrate efficacy. This was discussed at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, United Kingdom, 2017 with the aim of defining minimum standards for future urodynamic research. Methods: The recent recommendations from the IDEAL (innovation, development, exploration, assessment, and long-term study) collaboration regarding surgical research were reviewed. Two examples of recent novel urodynamic technologies, the penile cuff test and air charged urodynamic catheters were used as case studies and the research programmes behind their development were critiqued. Results: The rigorous and standardized model of surgical research proposed by the IDEAL collaboration was endorsed as an appropriate model for future urodynamic research. A methodical approach to research can fulfil a host of objectives including illustration of the clinical need, help with design and refinement of technique and proving efficacy for any new test or device. The penile cuff test is a novel urodynamic measurement technique that has been well researched and is now used in clinical practice. Further research is needed before air charged catheters can be recommended for widespread clinical use and the IDEAL framework provides a template for ongoing development. Conclusions: In the future, these recommendations should lead to a more standardized and uniform programme of urodynamic research and enable a thorough evaluation of new technologies prior to wider clinical uptake.

The BESIDE study demonstrated that combination therapy (mirabegron and solifenacin 5mg) improved overactive bladder symptoms versus solifenacin 5mg or 10mg, and was well tolerated.To ensure efficacy and safety is maintained in older patients (65 yr), who usually experience greater symptom severity and comorbidities, a prespecified subanalysis stratified by age group was conducted.Patients remaining incontinent (≥1 episode during 3-d diary) following 4-wk single-blind daily solifenacin 5mg were randomized 1:1:1 to a daily double-blind combination (solifenacin 5mg and mirabegron 25mg, increased to 50mg at wk 4), solifenacin 5mg or 10mg for 12 wk. Four cohorts stratified by age (65 yr, ≥65 yr and75 yr, ≥75 yr) were investigated.Efficacy assessments: change from baseline to end of treatment in average daily incontinence (primary) and micturition frequency (key secondary), number of incontinence episodes during the 3-d diary (key secondary), and change from baseline in average daily urgency and urgency incontinence episodes. Safety included treatment-emergent adverse events and vital signs.Full analysis set included 2110 patients: 30.9% aged ≥65 yr and 8.9% aged ≥75 yr. At the end of treatment, daily, and 3-d incontinence daily micturitions, urgency, and urgency incontinence, were improved in each treatment group and age group; the largest reductions were observed with combination in each age cohort. There were no notable differences in vital signs or the incidence of treatment-emergent adverse events between treatment and age groups, with the exception of dry mouth, which was highest with solifenacin 10mg.Efficacy and safety in the overall population is maintained in older (≥65 yr) and elderly (≥75 yr) patients treated with a combination of solifenacin and mirabegron, or solifenacin monotherapy; irrespective of age, combination was associated with the greatest improvement in overactive bladder symptoms.This study investigated the effectiveness and safety of a combination of two different treatments (mirabegron 50mg and solifenacin 5mg) or solifenacin (5mg or 10mg) alone in patients aged65 yr or ≥65 yr, and75 yr or ≥75 yr with overactive bladder. Symptoms of overactive bladder, such as the urgent need to visit the toilet, incontinence, and frequent urination, were improved with all treatments regardless of the patient's age, but combination treatment demonstrated the greatest benefit, and was well tolerated.

Introduction The terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD) should be defined and organized in a clinically based consensus Report. Methods This Report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardization Steering Committee (SSC) assisted at intervals by external referees. All relevant definitions for ANLUTD were updated on the basis of research over the last 14 years. An extensive process of 18 rounds of internal and external review was involved to exhaustively examine each definition, with decision-making by collective opinion (consensus). Results A Terminology Report for ANLUTD, encompassing 97 definitions (42 NEW and 8 CHANGED, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different groups involved not only in lower urinary tract dysfunction but additionally in many other medical specialties. Conclusion A consensus-based Terminology Report for ANLUTD has been produced to aid clinical practice and research.

Underactive bladder (UAB) is a symptom syndrome reflecting the urodynamic observation of detrusor underactivity (DU), a voiding contraction of reduced strength and/or duration, leading to prolonged or incomplete bladder emptying. An International Continence Society Working Group has described UAB as characterised by a slow urinary stream, hesitancy and straining to void, with or without a feeling of incomplete bladder emptying and dribbling, often with storage symptoms. Since DU often coexists with bladder outlet obstruction, or storage dysfunction (detrusor overactivity or incontinence), the exact contribution of the DU to the presenting complaints can be difficult to establish. The presence of voiding and post voiding lower urinary tract symptoms (LUTS) is implicitly expected in UAB, but a reduced sensation of fullness is reported by some patients, and storage LUTS are also an important factor in many affected patients. These may result from a postvoid residual, but often they do not. The storage LUTS are often the key driver in leading the patient to seek healthcare input. Nocturia is particularly common and bothersome, but what the role of DU is in all the range of influences on nocturia has not been established. Qualitative research has established a broad impact on everyday life as a result of these symptoms. In general, people appear to manage the voiding LUTS relatively well, but the storage LUTS may be problematic.

Background:Current management for men with lower urinary tract symptoms (LUTS) is a pathway that results in prostate surgery in a significant proportion. While helpful in relieving benign prostatic obstruction (BPO), surgery may be ineffective for men suffering from difficulties not relating to BPO. The UPSTREAM trial started recruitment in October 2014 with the aim of establishing whether a care pathway including urodynamics (a diagnostic tool for BPO and thus an indication of whether surgery is needed) is no worse for men, in terms of symptomatic outcome, than one without (routine care). Methods/Design:This analysis plan outlines the main outcomes of the study as well as specific design choices, such as non-inferiority margins. The trial is currently recruiting in 26 hospitals across the UK, randomising men to either urodynamics or routine care, with recruitment set to end on the 31st of December 2016. All outcomes will be measured 18 months after randomisation to allow sufficient time for surgical procedures and recovery. The primary outcome is based on a non-inferiority design with a margin of 1 point on the International Prostate Symptom Score (IPSS) scale. The key secondary outcome for this trial is surgery rate per arm, which is estimated to be at least 18% lower in the urodynamics arm. Surgery rates, adverse events, flow rate, urinary symptoms and sexual symptoms are secondary outcomes to be assessed for superiority. This is an update to the UPSTREAM protocol which has already been published in this journal.Discussion:This a priori statistical analysis plan aims to reduce reporting bias by allowing access to the trial’s objectives and plans in advance of recruitment end. The results of the trial are expected to be published soon after the trial end date of 30th September 2018.Trial registrationTrial registered 8 April 2014; ISRCTN registry (ISRCTN56164274).

Objectives To compare the efficacy of onabotulinumtoxinA, mirabegron, and anticholinergics in adults with idiopathic overactive bladder (OAB) using network meta-analysis (NMA). Subjects and Methods Information sources were searched for randomized blinded controlled trials, of at least 2 weeks duration, comparing any dose of onabotulinumtoxinA, eligible oral/transdermal anticholinergics, or mirabegron, with each other or placebo, in adults with OAB. Bayesian random-effects models were used to synthesize the results at week 12: NMA for responder analyses and network meta-regression (NMR) for change from baseline analyses. The NMR was used to adjust for differences in baseline severity between studies. Sensitivity analysis, excluding studies considered to be at a high risk of methodological bias, was conducted. Results 56 randomized trials were included in the networks. For each outcome, results are reported for all licensed treatment doses. For each NMR, results are based on patients with an average number of episodes of the outcome at baseline. After 12 weeks, all treatments are more efficacious than placebo. Patients who received onabotulinumtoxinA (100U) had, on average, the greatest reductions in urinary incontinence episodes (UIE), urgency, and micturition frequency, and the highest odds of achieving decreases of 100% and ≥50% in the daily number of UIE. When comparing onabotulinumtoxinA with other pharmacotherapies, mean differences favoured onabotulinumtoxinA 100U over all comparators for UIE and urgency (credible intervals excluded zero) and all but two of the comparators for micturition frequency. OnabotulinumtoxinA 100U was also associated with higher odds of achieving a 100% and ≥50% decrease in daily UIE than most other licensed treatments in the network. The exclusion of studies with a high risk of bias had little impact on the conclusions. Conclusion The results indicate that, after 12 weeks, onabotulinumtoxinA 100U provides greater relief of OAB symptoms compared with most other licensed doses of other pharmacotherapies in the network. This article is protected by copyright. All rights reserved.

Aims: The microbiome is the term used for the symbiotic microbial colonisation of healthy organs. Studies have found bacterial identifiers within voided urine which is apparently sterile on conventional laboratory culture, and accordingly there may be health and disease implications. Methods: The International Consultation on Incontinence Research Society (ICI-RS) established a literature review and expert consensus discussion focussed on the increasing awareness of the urinary microbiome, and potential research priorities. Results: The consensus considered the discrepancy between findings of conventional clinical microbiology methods, which generally rely on culture parameters predisposed towards certain ‘‘expected’’ organisms. Discrepancy between selective culture and RNA sequencing to study speciesspecific 16S ribosomal RNA is increasingly clear, and highlights the possibility that protective or harmful bacteria may be overlooked where microbiological methods are selective. There are now strong signals of the existence of a ‘‘core’’ urinary microbiome for the human urinary tract, particularly emerging with ageing. The consensus reviewed the potential relationship between a patient’s microbiome and lower urinary tract dysfunction, whether low-count bacteriuria may be clinically significant and mechanisms which could associate micro-organisms with lower urinary tract symptoms. Conclusions: Key research priorities identified include the need to establish the scope of microbiome across the range of normality and clinical presentations, and gain consensus on testing protocols. Proteomics to study enzymatic and other functions may be necessary, since different bacteria may have overlapping phenotype. Longitudinal studies into risk factors for exposure, cumulative risk, and emergence of disease need to undertaken. Neurourol. Urodynam. 36:850–853, 2017.

Background: Nocturia is common and associated with multiple disease states. Many potential mechanisms have been proposed for nocturia, which also remains challenging to manage. Purpose: To use multivariate analysis to determine which combinations of factors can accurately discriminate clinically significant nocturia in patients to facilitate clinical management and treatment decisions. Patients and methods: Data analysis was based on frequency volume charts from three randomized controlled trials. There were 1479 patients included, of which 215 patients had no/mild nocturia and 1264 had clinically significant nocturia with at least two voids per night. Factors studied that may influence nocturia were demographics, sleep duration, functional bladder capacity, 24 h urine volume and literature-suggested definitions of nocturnal polyuria. We used univariate analysis and cross-validated multivariate modelling to assess association between factors and nocturia status, redundancy between factors and whether the combined use of factors could explain patients&prime, nocturia status. Results: The multivariate analyses showed that the most useful definitions of nocturia are &rsquo, Nocturia Index&rsquo, (NI) and &lsquo, Nocturnal Urine Production per hour&rsquo, (NUPh) in combination with functional bladder capacity and sleep duration. Published definitions providing binary nocturnal polyuria outcomes had lower performance than continuous indices. These analyses also showed that NI was not specific to nocturnal polyuria as it also captured nocturia due to low functional bladder capacity. By contrast, NUPh was demonstrated to be specific to nocturnal polyuria. Conclusion: NUPh has previously been shown among elderly males to be essential in nocturia and a very valid measure of nocturnal polyuria. However, the current, large and independent dataset now confirms that it can be applied in an adult population with a complaint of nocturia covering both males and females.

INTRODUCTION The quality of urodynamic measurements in clinical practice has been debated as a matter of concern. It is considered plausible that this has a direct bearing on patient care and the perceived value of urodynamic testing. METHODS This is a report of the proceedings of the Think Tank: "Is the value of urodynamics undermined by poor technique?" from the Annual International Consultation on Incontinence-Research Society, which took place in June 2018 in Bristol, UK. The Think Tank discussed the evidence for deficiencies in urodynamic test quality and considered the implications of improvements for clinical diagnosis and practice. RESULTS There is evidence that technique affects urodynamic quality, and that urodynamic practice is variable. Factors such as team skill set, technologies used, and training received will also affect the quality of urodynamic service. Questions exist regarding the influence of technique on the utility and perceived value of urodynamics. CONCLUSIONS We suggest research questions that will provide the necessary evidence on the link between technique, reporting, and outcome, and clarify the role of good practice in the utility of urodynamic testing.

AIM: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms.METHODS: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB.RESULTS: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide-dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1 , TRPV4 , TRPA1 , and TRPM4 ) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+ -activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway-the canonical fibrosis pathway.CONCLUSIONS: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.

© 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. Background and purpose: PDE inhibitors such as sildenafil alleviate lower urinary tract symptoms; however, a complete understanding of their action on the bladder remains unclear. We are investigating the effects of sildenafil, on post and preganglionic nerve-mediated contractions of the mouse bladder, and neuronal and urothelial ATP release. Experimental approach: Bladders were used from young (12weeks), aged (24months), and spinal cord transected (SCT), mice, for in vitro contractility experiments. An arterially perfused in situ whole mouse model was used to record bladder pressure. Nerve-mediated contractions were generated by electrical field stimulation (EFS) of postganglionic nerve terminals or the pelvic nerve. ATP release during EFS in intact detrusor strips, and during stretch of isolated mucosa strips, was measured using a luciferin-luciferase assay. Key results: Sildenafil (20μM) inhibited nerve-mediated contractions in young mice, with an increase in f1/2 values in force–frequency relationships, demonstrating a greater effect at low frequencies. Sildenafil reduced the atropine-resistant, purinergic component of nerve-mediated contractions, and suppressed neuronal ATP release upon EFS in vitro. Sildenafil reduced the preganglionic pelvic nerve stimulated bladder pressure recordings in situ; comparable to in vitro experiments. Sildenafil reduced stretch-induced urothelial ATP release. Sildenafil also relaxed nerve-mediated contractions in aged and SCT mice. Conclusion and implications: Sildenafil has a greater effect on the low-frequency, purinergic-mediated contractions and suppresses neuronal ATP release. In addition, sildenafil reduces stretch-induced urothelial ATP release. These results demonstrate a novel action of sildenafil to selectively inhibit ATP release from nerve terminals innervating detrusor smooth muscle and the urothelium.

Micturition, the co-ordinated process of expulsion of urine from the bladder, requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. In adult mammals this involves a spinobulbospinal control circuit incorporating Barrington’s nucleus in the pons (Barr). The largest Barr cell population is comprised of pontospinal glutamatergic neurons that express corticotrophin-releasing hormone. There is evidence that BarrCRH neurons can generate bladder contractions but it is unknown whether they act as a simple switch or a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with recordings in mice shows that BarrCRH neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. These findings inform a new inferential model of micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.

AIM: To characterize patients with neurogenic bladder (NGB), their treatment patterns, healthcare resource utilization, and associated costs based on records from a primary care database in the United Kingdom. METHODS: This was a retrospective, descriptive, observational study of anonymized data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases (selection period, 1 January 2004 to 31 December 2016). Adults with a definitive or probable diagnosis of NGB and ≥1 referral to a urologist were included. RESULTS: The study cohort included 3913 patients with definitive (n = 363) or probable (n = 3550) NGB. Patients had a mean of 8.6 (standard deviation [SD], 7.6) comorbidities, and mean Anticholinergic Cognitive Burden Scale score of 6.6 (SD, 5.9). During 12 months' follow-up, urinary tract infection (UTI) and urinary incontinence were the most common complications. Most patients (92.2%) received ≥1 prescription for an antimuscarinic agent or mirabegron, and 53.9% of patients received prescriptions for UTI-specific antibiotics. The mean number of visits to a general practitioner for any cause was 67.7 (SD, 42.6) per individual. Almost half (46.7%) of the study cohort visited a specialist during the 12-month follow-up period, and 11.0% had ≥1 hospital admission. Total mean per patient costs for healthcare resource utilization was £2395. CONCLUSIONS: The burden of illness, healthcare resource needs, and associated costs among patients with NGB are considerable. Drug prescribing patterns are consistent with the symptoms and complications of NGB, although increased awareness of drugs with anticholinergic activity among prescribers may help to reduce the cumulative anticholinergic burden in this vulnerable population. ispartof: Neurourology And Urodynamics vol:38 issue:5 pages:1278-1289 ispartof: location:United States status: published

Background Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). Objective To report participants’ sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. Design, setting, and participants A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. Intervention Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). Outcome measurements and statistical analysis The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick’s test, and questionnaire items were compared using Pearson’s correlation coefficient. Results and limitations Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. Conclusions Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. Patient summary We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

CONTEXT: Practice patterns for the management of urinary retention (UR) secondary to benign prostatic obstruction (BPO; UR/BPO) vary widely and remain unstandardized.OBJECTIVE: To review the evidence for managing patients with UR/BPO with pharmacological and nonpharmacological treatments included in the European Association of Urology guidelines on non-neurogenic male lower urinary tract symptoms.EVIDENCE ACQUISITION: Search was conducted up to April 22, 2018, using CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. This systematic review included randomized controlled trials (RCTs) and prospective comparative studies. Methods as detailed in the Cochrane handbook were followed. Certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.EVIDENCE SYNTHESIS: Literature search identified 2074 citations. Twenty-one studies were included (qualitative synthesis). The evidence for managing patients with UR/BPO with pharmacological or nonpharmacological treatments is limited. CoE for most outcomes was low/very low. Only α1-blockers (alfuzosin and tamsulosin) have been evaluated in more than one RCT. Pooled results indicated that α1-blockers provided significantly higher rates of successful trial without catheter compared with placebo [alfuzosin: 322/540 (60%) vs 156/400 (39%) (odds ratio {OR} 2.28, 95% confidence interval {CI} 1.55 to 3.36; participants=940; studies=7; I2=41%; low CoE); tamsulosin: 75/158 (47%) vs 40/139 (29%) (OR 2.40, 95% CI 1.29 to 4.45; participants=297; studies=3; I2=30%; low CoE)] with rare adverse events. Similar rates were achieved with tamsulosin or alfuzosin [51/87 (59%) vs 45/84 (54%) (OR 1.28, 95% CI 0.68 to 2.41; participants=171; studies=2; I2=0%; very low CoE)]. Nonpharmacological treatments have been evaluated in RCTs/prospective comparative studies only sporadically.CONCLUSIONS: There is some evidence that usage of α1-blockers (alfuzosin and tamsulosin) may improve resolution of UR/BPO. As most nonpharmacological treatments have not been evaluated in patients with UR/BPO, the evidence is inconclusive about their benefits and harms.PATIENT SUMMARY: There is some evidence that alfuzosin and tamsulosin may increase the rates of successful trial without catheter, but little or no evidence on various nonpharmacological treatment options for managing patients with urinary retention secondary to benign prostatic obstruction.

Our aim was to estimate the prevalence-based cost of illness imposed by nocturia (a 2 nocturnal voids per night) in Germany, Sweden, and the UK in an average year. Information obtained from a systematic review of published literature and clinicians was used to construct an algorithm depicting the management of nocturia in these three countries. This enabled an estimation of (1) annual levels of healthcare resource use, (2) annual cost of healthcare resource use, and (3) annual societal cost arising from presenteeism and absenteeism attributable to nocturia in each country. In an average year, there are an estimated 12.5, 1.2, and 8.6 million patients a 20 years of age with nocturia in Germany, Sweden, and the UK, respectively. In an average year in each country, respectively, these patients were estimated to have 13.8, 1.4, and 10.0 million visits to a family practitioner or specialist, similar to 91,000, 9000, and 63,000 hospital admissions attributable to nocturia and 216,000, 19,000, and 130,000 subjects were estimated to incur a fracture resulting from nocturia. The annual direct cost of healthcare resource use attributable to managing nocturia was estimated to be approximately a,notsign2.32 billion in Germany, 5.11 billion kr (a,notsign0.54 billion) in Sweden, and A 1.35 pound billion (a,notsign1.77 billion) in the UK. The annual indirect societal cost arising from both presenteeism and absenteeism was estimated to be approximately a,notsign20.76 billion in Germany and 19.65 billion kr (a,notsign2.10 billion) in Sweden. In addition, in the UK, the annual indirect cost due to absenteeism was an estimated A 4.32 pound billion (a,notsign5.64 billion). Nocturia appears to impose a substantial socioeconomic burden in all three countries. Clinical and economic benefits could accrue from an increased awareness of the impact that nocturia imposes on patients, health services, and society as a whole. Funding Agencies|Ferring Pharmaceuticals, Copenhagen, Denmark

Purpose: We investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10 mg.Materials and Methods: Patients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8 micturitions per 24 hours with minimal important differences in OAB-q and PPBC.Results: Overall 2,174 patient...

Chronic pelvic pain (CPP) presents an etiology that is often unknown, difficult to classify and multifactorial, which leads to difficult therapeutic management. The symptoms often suggest dysfunction of one or more systems in the pelvis, accompanied by negative consequences from a cognitive, behavioral, sexual and emotional point of view, with a significant impact on the quality of life. In a patient with CPP, there are many factors involved, a number of different pathologies or phenomena of peripheral and central sensitization, so it is recommended to initially focus the study on the location and characteristics of the pain, without ruling out the study of other organs, Hence the importance of an interdisciplinary and multidisciplinary approach for a correct diagnosis and treatment. Myofascial pelvic pain should be considered in all women who consult for pelvic pain. Musculoskeletal changes may be related to CPP, either as the primary problem or as a secondary reaction to pelvic pain. The importance of musculoskeletal pain is often underestimated. Considering myofascial syndrome early in the management of pelvic pain may prevent the performance of certain unnecessary procedures.

© 2016 Wiley Periodicals, Inc. Aims: To describe parameters from urodynamic pressure recordings that describe urinary bladder contractility through the use of principles of muscle mechanics. Methods: Subtracted detrusor pressure and voided flow were recorded from patients undergoing filling cystometry. The isovolumetric increase of detrusor pressure, P, of a voluntary bladder contraction before voiding was used to generate a plot of (dP/dt)/P versus P. Extrapolation of the plot to the y-axis and the x-axis generated a contractility parameter, vCE (the maximum rate of pressure development) and the maximum isovolumetric pressure, P0, respectively. Similar curves were obtained in ex vivo pig bladders with different concentrations of the inotropic agent carbachol and shown in a supplement. Results: Values of vCE, but not P0, diminished with age in female subjects. vCE was most significantly associated with the 20–80% duration of isovolumetric contraction t20–80; and a weaker association with maximum flow rate and BCI in women. P0 was not associated with any urodynamic variable in women, but in men was with t20–80 and isovolumetric pressure indices. Conclusions: The rate of isovolumetric subtracted detrusor pressure (t20–80) increase shows a very significant association with indices of bladder contractility as derived from a derived force–velocity curve. We propose that t20–80 is a detrusor contractility parameter (DCP). Neurourol. Urodynam. 36:1009–1014, 2017. © 2016 Wiley Periodicals, Inc.

BACKGROUND: Evidence-based guidelines for the management of neurological disease and lower bowel dysfunction have been produced by the International Consultations on Incontinence (ICI). These are comprehensive guidelines, and were developed to have world-wide relevance. AIMS: To update clinical management of neurogenic bowel dysfunction from the recommendations of the 4th ICI, 2009. MATERIALS AND METHODS: A series of evidence reviews and updates were performed by members of the working group. The resulting guidelines were presented at the 2012 meeting of the European Association of Urology for consultation, and modifications applied to deliver evidence based conclusions and recommendations for the scientific report of the 5th edition of the ICI in 2013. RESULTS: The current review is a synthesis of the conclusions and recommendations, including the algorithms for initial and specialized management of neurogenic bowel dysfunction. The pathophysiology is described in terms of spinal cord injury, multiple sclerosis, and Parkinson's disease. Assessment requires detailed history and clinical assessment, general investigations, and specialized testing, if required. Treatment primarily focuses on optimizing stool consistency and regulating bowel evacuation to improve quality of life. Symptom management covers conservative and interventional measures to promote good habits and assist stool evacuation, along with prevention of incontinence. Education is essential to achieving optimal bowel management. DISCUSSION: The review offers a pragmatic approach to management in the context of complex pathophysiology and varied evidence base.

Objectives To investigate the influence of low-dose sildenafil, a phosphodiesterase type 5 inhibitor (PDE5-I), on the function of the mouse lower urinary tract (LUT). Materials and methods Adult male mice were decerebrated and arterially perfused with a carbogenated Ringer's solution to establish the decerebrate arterially perfused mouse (DAPM). To allow distinction between central neural and peripheral actions of sildenafil, experiments were conducted in both the DAPM and in a 'pithed' DAPM, which has no functional brainstem or spinal cord. The action of systemic and intrathecal sildenafil on micturition was assessed in urethane-anaesthetised mice. Results In the DAPM, systemic perfusion of sildenafil (30 pm) decreased the voiding threshold pressure [to a mean (sem) 84.7 (3.8)% of control] and increased bladder compliance [to a mean (sem) 140.2 (8.3)% of control, an effect replicated in the pithed DAPM]. Sildenafil was without effect on most voiding variables but significantly increased the number of bursts of the external urethral sphincter (EUS) per void in DAPM [to a mean (sem) 130.1 (6.9)% of control at 30 pm] and in urethane-anaesthetised mice [to a mean (sem) 117.5 (5.8)% of control at 14 ng/kg]. Sildenafil (10 and 30 pm) increased pelvic afferent activity during both bladder filling and the isovolumetric phase [to a mean (sem) 205.4 (30.2)% of control at 30 pm]. Intrathecal application of sildenafil (5 μL of either 150 pm or 1.5 nm) did not alter cystometry and EUS-electromyography variables in urethane-anaesthetised mice. Conclusions Low-dose sildenafil increases bladder compliance, increases pelvic nerve afferent activity, and augments the bursting activity of the EUS. We propose that the novel actions on afferent traffic and sphincter control may contribute to its beneficial actions to restore storage and voiding efficiency in LUT dysfunction.

Introduction Research for management of benign prostate obstruction (BPO) for adult males remains a cornerstone of urology research. This landscape has witnessed the rise and fall of multiple therapies, both surgical and medical. Our aim was to formally evaluate the publication trends for these interventions over the past 20 years. Material and methods A systematic search was performed in a Cochrane style. Data was analysed using the independent t-test and Pearson's correlation coefficient (SPSS version 24). To observe changes in trends more effectively, data was sub-divided into two time periods: 1997 to 2006 and 2007 to 2016. Results Over the past 20 years, 4236 papers have been published concerning for BPO (surgical, n = 2177 and medical, n = 2059). For surgical treatments, these included articles on monopolar transurethral resection of prostate (TURP) (n = 340), bipolar TURP (n = 260), HoLEP (n = 293) and Greenlight laser (n = 395). For medical therapies, these included alpha blockers (848), 5-alpha reductase inhibitors (n = 618) and PDE5I (n = 91). Between the two time periods the change was +18.8% (p = 0.108) for monopolar TURP, +497.1% (

AIMS: To assess efficacy and safety as well as predictive factors of dry rate and freedom from surgical revision in patients underwent AUS placement. The artificial urinary sphincter (AUS) is still considered the standard for the treatment of moderate to severe post-prostatectomy stress urinary incontinence (SUI). However, data reporting efficacy and safety from large series are lacking. METHODS: A multicenter, retrospective study was conducted in 16 centers in Europe and USA. Only primary cases of AUS implantation in non-neurogenic SUI after prostate surgery, with a follow-up of at least 1 year were included. Efficacy data (continence rate, based on pad usage) and safety data (revision rate in case of infection and erosion, as well as atrophy or mechanical failure) were collected. Multivariable analyses were performed in order to investigate possible predictors of the aforementioned outcomes. RESULTS: Eight hundred ninety-two men had primary AUS implantation. At 32 months mean follow-up overall dry rate and surgical revision were 58% and 30.7%, respectively. Logistic regression analysis showed that patients without previous incontinence surgery had a higher probability to be dry after AUS implantation (OR: 0.51, P = 0.03). Moreover institutional case-load was positively associated with dry rate (OR: 1.18; P = 0.005) and freedom from revision (OR: 1.51; P = 0.00). CONCLUSIONS: The results of this study showed that AUS is an effective option for the treatment of SUI after prostate surgery. Moreover previous incontinence surgery and low institutional case-load are negatively associated to efficacy and safety outcomes. ispartof: NEUROUROLOGY AND URODYNAMICS vol:38 issue:2 pages:710-718 ispartof: location:United States status: published

Micromotions are phasic contractions of the bladder wall. During urine storage, such phasic activity has little effect on intravesical pressure, however, changed motile activity may underlie urodynamic observations such as detrusor overactivity. The potential for bladder motility to affect pressure reflects a summation of the overall movements, comprising the initiation, propagation, and dissipation components of micromotions. In this study, the influence of initiation of micromotions was investigated using calcium activated chloride channel blocker niflumic acid, and the effect of propagation using blockers of gap junctions. The overall bladder tone was modulated using isoprenaline. Isolated tissue strips and whole bladder preparations from juvenile rats were used. 18β-glycyrrhetinic acid was used to block gap junctions, reducing the amplitude and frequency of micromotions in in vitro and ex vivo preparations. Niflumic acid reduced the frequency of micromotions but had no effect on the amplitude of pressure fluctuations. Isoprenaline resulted in a reduction in pressure fluctuations and a decrease in pressure baseline. Using visual video data analysis, bladder movement was visible, irrespective of lack of pressure changes, which persisted during bladder relaxation. However, micromotions propagated over shorter distances and the overall bladder tone was reduced. All these results suggest that phasic activity of the bladder can be characterised by a combination of initiation and propagation of movement, and overall bladder tone. At any given moment, intravesical pressure recordings are an integration of these parameters. This synthesis gives insight into the limitations of clinical urodynamics, where intravesical pressure is the key indicator of detrusor activity.