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Background Lower urinary tract symptoms particularly affect older men and their quality of life. General practitioners currently have no easily available assessment tools to diagnose lower urinary tract symptom causes. Referrals to urology specialists are increasing. General practitioner access to simple, accurate tests and clinical decision tools could facilitate management of lower urinary tract symptoms in primary care. Objectives To determine which of several index tests in combination, best predicted three diagnoses (detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity) in men presenting with lower urinary tract symptoms in primary care. To develop and validate three diagnostic prediction models, and a prototype primary care clinical decision support tool. Design Prospective diagnostic accuracy study. Two participant cohorts, for development and validation, underwent simple index tests and a reference standard (invasive urodynamics). Setting General practices in England and Wales. Participants Men (16 years and over) consulting their general practitioner with lower urinary tract symptoms. Sample size Separate calculations for model development and validation cohorts, from literature estimates of detrusor overactivity, bladder outlet obstruction and detrusor underactivity prevalences of 57%, 31% and 16%, respectively. Predictors and index tests Twelve potential predictors considered for three diagnostic models. Main outcome measures The primary outcome was diagnostic model sensitivity and specificity for detecting bladder outlet obstruction, detrusor underactivity and detrusor overactivity, with 75.0% considered minimum clinically useful performance. Statistical analysis Three separate logistic regression models generated with index test variables to predict the presence of bladder outlet obstruction, detrusor overactivity, detrusor underactivity conditions in men with lower urinary tract symptoms. Results One model each was developed and validated for bladder outlet obstruction and detrusor underactivity, two for detrusor overactivity (detrusor overactivity main, detrusor overactivity sensitivity analysis 2). Age, voiding symptoms subscore, prostate-specific antigen level, median maximum flow rate, median voided volume were predictors for bladder outlet obstruction. Median maximum flow rate and post-void residual volume were predictors for detrusor underactivity. Age, post-void residual volume and median voided volume were included in detrusor overactivity main model, while age and storage symptoms subscore predicted detrusor overactivity sensitivity analysis 2. For all four models, sensitivity of 75.0% could be achieved with a specificity of 74.2%, 47.3%, 45.6% and 46.2% for bladder outlet obstruction, detrusor underactivity, detrusor overactivity main and detrusor overactivity sensitivity analysis 2 models, respectively. Similarly, a specificity of 75.0% could be achieved with a sensitivity of 71.3%, 39.8%, 33.3% and 62.7% for bladder outlet obstruction, detrusor underactivity, detrusor overactivity main and detrusor overactivity sensitivity analysis 2 models, respectively. The prototype tool (not yet intended for use in practice) is available at Primary care Management of lower Urinary tract Symptoms decision aid for lower urinary tract symptoms (shinyapps.io). General practitioner feedback during tool development and small-scale user-testing in simulated consultation scenarios was favourable. Patients supported such management in primary care. Strengths/limitations This was a prospective, multicentre study in an appropriate primary care population. Most of the index tests are possible routinely in primary care or at home by patients. The diagnostic models were validated in a separate cohort from the same population. Limitations include that target condition prevalences may differ in other populations. Conclusion We identified sensitivities and specificities of diagnostic models for detrusor overactivity, bladder outlet obstruction and detrusor underactivity in routine United Kingdom practice and developed a prototype clinical decision support tool. Future work Economic modelling, a feasibility trial and powered randomised controlled trial are needed to evaluate the Primary care Management of lower Urinary tract Symptoms tool in practice. Study registration Current Controlled Trials ISRCTN10327305. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/40/05) and is published in full in Health Technology Assessment; Vol. 29, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary Urinary symptoms such as a weak flow and frequent urination are common in older men and often bothersome. Men visiting their general practitioner with these symptoms are often referred to a specialist because good diagnostic tools are not available in primary care. Three common causes of symptoms are: bladder obstruction due to non-cancerous growth of the prostate, reduced power of the bladder muscle and bladder overactivity. We aimed to create a tool to help general practitioners manage men with urinary symptoms. This required first to develop mathematical models, which combined results from several simple tests that general practitioners could organise. The web-based tool then constructed would indicate the most likely diagnosis and provide recommendations for treating and managing the condition. The tests included prostate examination, prostate-specific antigen blood test, symptoms questionnaires and home-based urine flow measurements. To develop the mathematical models, 350 men with urinary symptoms underwent the simple tests and a specialist invasive test called urodynamics, which is currently regarded as providing the best diagnosis. A second group of 251 men also had the simple tests and urodynamics. Their results were used to measure the performance of the models. The model to diagnose bladder obstruction performed well (close to the invasive urodynamics ‘gold standard’ test), and those to diagnose reduced power of the bladder muscle and bladder over-activity performed moderately but less well. A prototype version of the web-based tool was developed. We consulted patients and general practitioners to assess the tool’s acceptability. General practitioners confirmed their enthusiasm because they find managing bladder symptoms challenging, and patients said they would prefer to be managed in primary care. We received good feedback about the prototype tool and gained ideas for refining it. Following this project, it would be valuable to estimate the cost, benefits and practicalities of implementing the tool, aided by data from the study, and trial its effectiveness compared with current care. Scientific summary This summary contains text reproduced with permission from Pell et al. Primary care Management of lower Urinary tract Symptoms in men: protocol for development and validation of a diagnostic and clinical decision support tool (the PriMUS study). BMJ Open 2020;10:e037634; Milosevic et al. Conducting invasive urodynamics in primary care: qualitative interview study examining experiences of patients and healthcare professionals. Diagn Progn Res 2021;5:10; and Milosevic et al. Managing lower urinary tract symptoms in primary care: qualitative study of GPs’ and patients’ experiences. Br J Gen Pract 2021;71:E685–92. These are Open Access articles distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text. Background Lower urinary tract symptoms (LUTS) particularly affect older men and can lead to poor quality of life, often referred to as the degree of ‘bother’ experienced. General practitioners (GPs) currently have no easily available assessment tools to effectively diagnose the causes of LUTS and aid discussion of treatment with patients. Men are increasingly referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinical decision tools could facilitate faster and more effective patient management of LUTS in primary care. The reference standard test for investigation of LUTS, and thus diagnosis of detrusor overactivity (DO), bladder outlet obstruction (BOO) and detrusor underactivity (DU), is invasive urodynamics, which takes place in secondary care. However, National Institute for Health and Care Excellence (NICE) guidelines suggest that many men referred to specialist care with LUTS are eventually managed conservatively, and so could have remained within primary care. Further, GPs do not have access to validated clinical decision tools giving an indication of the most likely cause of symptoms to guide treatment and management. Making such a tool available should improve treatment efficacy, standardise treatment, reduce unnecessary referrals, expedite referral of those requiring specialist care, and thus improve cost-effectiveness of NHS care. A primary care-based clinical decision support tool with defined accuracy would, firstly, mean that the men could undergo the necessary simple tests straightaway, organised through the GP surgery and, secondly, would get a quicker result regarding predicted diagnosis and choice of management options that are most likely to be effective. For GPs, a clinical decision support tool could allay uncertainty around both diagnosis and best management. Objectives The primary objectives of the Primary care Management of lower Urinary tract Symptoms (PriMUS) study were to: Develop statistical models to predict the likelihood of each urological condition (BOO, DU and DO), based on a series of non-invasive index tests, with urodynamics as the reference standard. Estimate the diagnostic accuracy of the above models in an independent validation cohort. The study incorporated an internal pilot phase with ‘Stop/go’ criteria that included quantitative and qualitative assessments. The progression criteria were designed to allow for mitigating strategies to be discussed to allow for some adaptation to recruitment processes in the main study. The secondary objectives were to: Develop a series of patient management recommendations and thresholds for clinically useful diagnostic prediction by expert consensus and with reference to current clinical guidelines that map to the diagnoses predicted by the statistical model. Combine the statistical model and management recommendations into an online tool that will form the prototype clinical decision support tool. Complete a qualitative study to explore the feasibility of introducing the clinical decision support tool into primary care, including potential acceptability to primary care staff and patients. Collect NHS costs involved in delivering the new pathway and compare with cost of standard pathway calculated from NHS and other sources. Objectives 1 and 2: development of statistical models and diagnostic accuracy Methods Men presenting to their GP with LUTS were recruited prospectively from GP practices in Bristol, Newcastle upon Tyne and Wales. Participants underwent a series of simple index tests and the invasive reference standard (urodynamics). To determine which index tests used in combination best predicted three urodynamic observations (BOO, DU and DO) in men, diagnostic prediction models were developed for each target condition using logistic regression modelling. Multiple imputation by chain equations was used to handle missing data and fractional polynomial functions were used to fit continuous variables. The discriminative ability of the models was assessed using the c-index, and calibration was assessed using calibration plots and the calibration slope. Internal validation was conducted to assess optimism of the performance statistics using the bootstrapping procedure. External validation was conducted to assess model performance in another sample from a similar population as the development cohort. In both forms of validation, the models were recalibrated using the calibration slope as a shrinkage factor to re-estimate the intercept and model coefficients. Sensitivity and specificity were plotted on a receiver operating characteristic plot for each model. Risk thresholds were identified at a sensitivity and specificity of 75%, which was deemed to be the minimum clinically useful performance. Sensitivity analyses were performed by fitting two alternative models for each target condition. In sensitivity analysis 1, predictors that may be difficult to obtain in practice were excluded from the list of candidate predictors (mean urgency score and mean 24-hour fluid intake from the bladder diary) and in sensitivity analysis 2 (SA2), alternative measures or methods of measurement of candidate predictors were considered. Results Between March 2018 and June 2022, 350 and 251 men were respectively recruited into the development and validation cohorts. In the development cohort (median age 69), 163 (46.6%), 141 (40.3%) and 253 (72.3%) participants were diagnosed with BOO, DU and DO, respectively. In the validation cohort (median age 67), 112 (44.6%), 87 (34.7%) and 166 (66.1%) participants were diagnosed with BOO, DU and DO, respectively. Two models were developed and validated for DO (DO main and DO SA2), while one model each was developed and validated for BOO (BOO model 3) and DU. Age (participant demographics), voiding symptoms subscore (International Consultation on Incontinence Questionnaire – male LUTS questionnaire), prostate-specific antigen (PSA) test result (blood test), median maximum flow rate (uroflowmetry) and median voided volume (uroflowmetry) were predictors for BOO. Median maximum flow rate and post-void residual volume (bladder ultrasound) were predictors for DU. Age, post-void residual volume and median voided volume were included in DO main model, while age and storage symptoms subscore (International Prostate Symptom Score questionnaire) were predictors in DO SA2 model. Bladder outlet obstruction model 3 demonstrated good discriminative performance with an optimism-corrected c-index of 0.80. The models for DU, DO main and DO SA2 demonstrated moderate discriminative ability with an optimism-corrected c-index of respectively 0.64, 0.67 and 0.65. Similar estimates of c-index were observed for each model with the validation cohort. The optimism-corrected calibration slope for each model was

Objectives To estimate the cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis in the management of recurrent urinary tract infections.Design Multicentre, open-label, randomised, non-inferiority trial.Setting Eight centres in the UK, recruiting from June 2016 to June 2018.Participants Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment.Interventions Women were randomised to receive once-daily antibiotic prophylaxis or twice-daily methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed.Primary and secondary outcome measures The primary economic outcome was the incremental cost per quality-adjusted life year (QALY) gained at 18 months. All costs were collected from a UK National Health Service perspective. QALYs were estimated based on responses to the EQ-5D-5L administered at baseline, 3, 6, 9, 12 and 18 months. Incremental costs and QALYs were estimated using an adjusted analysis which controlled for observed and unobserved characteristics. Stochastic sensitivity analysis was used to illustrate uncertainty on a cost-effectiveness plane and a cost-effectiveness acceptability curve. A sensitivity analysis, not specified in the protocol, considered the costs associated with antibiotic resistance.Results Data on 205 participants were included in the economic analysis. On average, methenamine hippurate was less costly (−£40; 95% CI: −684 to 603) and more effective (0.014 QALYs; 95% CI: −0.05 to 0.07) than antibiotic prophylaxis. Over the range of values considered for an additional QALY, the probability of methenamine hippurate being considered cost-effective ranged from 51% to 67%.Conclusions On average, methenamine hippurate was less costly and more effective than antibiotic prophylaxis but these results are subject to uncertainty. Methenamine hippurate is more likely to be considered cost-effective when the benefits of reduced antibiotic use were included in the analysis.Trial registration number ISRCTN70219762.

Abstract Background Invasive urodynamics is used to investigate the causes of lower urinary tract symptoms; a procedure usually conducted in secondary care by specialist practitioners. No study has yet investigated the feasibility of carrying out this procedure in a non-specialist setting. Therefore, the aim of this study was to explore, using qualitative methodology, the feasibility and acceptability of conducting invasive urodynamic testing in primary care. Methods Semi-structured interviews were conducted during the pilot phase of the PriMUS study, in which men experiencing bothersome lower urinary tract symptoms underwent invasive urodynamic testing along with a series of simple index tests in a primary care setting. Interviewees were 25 patients invited to take part in the PriMUS study and 18 healthcare professionals involved in study delivery. Interviews were audio-recorded, transcribed verbatim and analysed using a framework approach. Results Patients generally found the urodynamic procedure acceptable and valued the primary care setting due to its increased accessibility and familiarity. Despite some logistical issues, facilitating invasive urodynamic testing in primary care was also a positive experience for urodynamic nurses. Initial issues with general practitioners receiving and utilising the results of urodynamic testing may have limited the potential benefit to some patients. Effective approaches to study recruitment included emphasising the benefits of the urodynamic test and maintaining contact with potential participants by telephone. Patients’ relationship with their general practitioner was an important influence on study participation. Conclusions Conducting invasive urodynamics in primary care is feasible and acceptable and has the potential to benefit patients. Facilitating study procedures in a familiar primary care setting can impact positively on research recruitment. However, it is vital that there is a support network for urodynamic nurses and expertise available to help interpret urodynamic results.

Background: Stress urinary incontinence is common in men after prostate surgery and can be difficult to improve. Implantation of an artificial urinary sphincter is the most common surgical procedure for persistent stress urinary incontinence, but it requires specialist surgical skills, and revisions may be necessary. In addition, the sphincter is relatively expensive and its operation requires adequate patient dexterity. New surgical approaches include the male synthetic sling, which is emerging as a possible alternative. However, robust comparable data, derived from randomised controlled trials, on the relative safety and efficacy of the male synthetic sling and the artificial urinary sphincter are lacking. Objective: We aimed to compare the clinical effectiveness and cost-effectiveness of the male synthetic sling with those of the artificial urinary sphincter surgery in men with persistent stress urinary incontinence after prostate surgery. Design: This was a multicentre, non-inferiority randomised controlled trial, with a parallel non-randomised cohort and embedded qualitative component. Randomised controlled trial allocation was carried out by remote web-based randomisation (1 : 1), minimised on previous prostate surgery (radical prostatectomy or transurethral resection of the prostate), radiotherapy (or not, in relation to prostate surgery) and centre. Surgeons and participants were not blind to the treatment received. Non-randomised cohort allocation was participant and/or surgeon preference. Setting: The trial was set in 28 UK urological centres in the NHS. Participants: Participants were men with urodynamic stress incontinence after prostate surgery for whom surgery was deemed appropriate. Exclusion criteria included previous sling or artificial urinary sphincter surgery, unresolved bladder neck contracture or urethral stricture after prostate surgery, and an inability to give informed consent or complete trial documentation. Interventions: We compared male synthetic sling with artificial urinary sphincter. Main outcome measures: The clinical primary outcome measure was men’s reports of continence (assessed from questions 3 and 4 of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form) at 12 months post randomisation (with a non-inferiority margin of 15%). The primary economic outcome was cost-effectiveness (assessed as the incremental cost per quality-adjusted life-year at 24 months post randomisation). Results: In total, 380 men were included in the randomised controlled trial (n = 190 in each group), and 99 out of 100 men were included in the non-randomised cohort. In terms of continence, the male sling was non-inferior to the artificial urinary sphincter (intention-to-treat estimated absolute risk difference –0.034, 95% confidence interval –0.117 to 0.048; non-inferiority p = 0.003), indicating a lower success rate in those randomised to receive a sling, but with a confidence interval excluding the non-inferiority margin of –15%. In both groups, treatment resulted in a reduction in incontinence symptoms (as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form). Between baseline and 12 months’ follow-up, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score fell from 16.1 to 8.7 in the male sling group and from 16.4 to 7.5 in the artificial urinary sphincter group (mean difference for the time point at 12 months 1.30, 95% confidence interval 0.11 to 2.49; p = 0.032). The number of serious adverse events was small (male sling group, n = 8; artificial urinary sphincter group, n = 15; one man in the artificial urinary sphincter group experienced three serious adverse events). Quality-of-life scores improved and satisfaction was high in both groups. Secondary outcomes that showed statistically significant differences favoured the artificial urinary sphincter over the male sling. Outcomes of the non-randomised cohort were similar. The male sling cost less than the artificial sphincter but was associated with a smaller quality-adjusted life-year gain. The incremental cost-effectiveness ratio for male slings compared with an artificial urinary sphincter suggests that there is a cost saving of £425,870 for each quality-adjusted life-year lost. The probability that slings would be cost-effective at a £30,000 willingness-to-pay threshold for a quality-adjusted life-year was 99%. Limitations: Follow-up beyond 24 months is not available. More specific surgical/device-related pain outcomes were not included. Conclusions: Continence rates improved from baseline, with the male sling non-inferior to the artificial urinary sphincter. Symptoms and quality of life significantly improved in both groups. Men were generally satisfied with both procedures. Overall, secondary and post hoc analyses favoured the artificial urinary sphincter over the male sling. Future work: Participant reports of any further surgery, satisfaction and quality of life at 5-year follow-up will inform longer-term outcomes. Administration of an additional pain questionnaire would provide further information on pain levels after both surgeries. Trial registration: This trial is registered as ISRCTN49212975. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 36. See the NIHR Journals Library website for further project information.

Background: Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. Objective: To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex®; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women. Design: Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months’ treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. Setting: Eight UK NHS secondary care sites. Participants: A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. Interventions: A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. Main outcome measures: The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient’s expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. Results: Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months’ data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (p-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) (p = 0.06). All other secondary outcomes and adverse events were similar in both arms. Limitations: This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. Conclusions: This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. Recommendations for research: Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. Trial registration: This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

Objective:: To use existing clinical trial data to assess the impact of prophylactic antibiotics on the 1-year UTI rate among people with different neurologic diseases, and to determine if UTIs impact renal function. Methods:: We conducted a secondary analysis of community dwelling participants with a neurologic disease and intermittent catheter use who participated in a 12-month randomized trial (AnTIC) of low dose antibiotic prophylaxis. We calculated incident rate ratios (IRR) of symptomatic UTIs that required antibiotics. Renal function was assessed using the estimated glomerular filtration rate. Results:: We identified 138 patients who had a neurologic disease (multiple sclerosis (25%), spinal cord injury (21%), spina bifida (18%), and other disorders (36%)). The incidence of symptomatic, antibiotic treated urinary infections was 1.48 per person–year in the prophylaxis group, and 2.51 per person–year in the usual care group; the IRR was 0.59 (95% CI 0.46, 0.76) in favor of continuous antibiotic prophylaxis. The IRR was lowest (most protective) among those with spinal cord injury (IRR 0.23, p

Abstract Background At least half of all adult women will experience infective cystitis (urinary tract infection: UTI) at least once in their life and many suffer from repeated episodes. Recurrent urinary tract infection (rUTI) in adult women is usually treated with long-term, low-dose antibiotics and current national and international guidelines recommend this as the ‘gold standard’ preventative treatment. Although they are reasonably effective, long-term antibiotics can result in bacteria becoming resistant not only to the prescribed antibiotic but to other antimicrobial agents. The problem of antimicrobial resistance is recognised as a global threat and the recent drive for antibiotic stewardship has emphasised the need for careful consideration prior to prescribing antibiotics. This has led clinicians and patients alike to explore potential non-antibiotic options for recurrent UTI prevention. Design /methods This is a multicentre, pragmatic, patient-randomised, non-inferiority trial comparing a non-antibiotic preventative treatment for rUTI in women, methenamine hippurate, against the current standard of daily low-dose antibiotics. Women who require preventative treatment for rUTI are the target population. This group is comprised of those with a diagnosis of rUTI, defined as three episodes in 1 year or two episodes in 6 months, and those with a single severe infection requiring hospitalisation. Participants will be recruited from secondary care urology / urogynaecology departments in the UK following referral with rUTI. Participants will be followed up during a 12-month period of treatment and in the subsequent 6 months following completion of the prophylactic medication. Outcomes will be assessed from patient recorded symptoms, quality of life questionnaires and microbiological examination of urine and perineal swabs. The primary outcome is the incidence of symptomatic antibiotic-treated UTI self-reported by participants during the 12-month period of preventative treatment. Health economic outcomes will also be assessed to define the cost-effectiveness of both treatments. A qualitative study will be conducted in the first 8 months of the trial to explore with participants/non-participants’ and recruiting clinicians’ views on trial processes and identify potential barriers to recruitment, reasons for participating and non-participation and for dropping out of the study. Discussion The study was commissioned and funded by the National Institute for Health Research (NIHR) and approved under the Medicines and Healthcare products Regulatory Agency (MHRA) notification scheme as a ‘Type A’ study. Trial registration International Standard Randomised Controlled Trial Number (ISRCTN), registry number: ISRCTN70219762. Registered on 31 May 2016.

Abstract Background Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed – a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness. Methods/design Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to identify problems or need for further treatment. Discussion A robust examination of the comparative effectiveness of the male synthetic sling will provide high-quality evidence to determine whether or not it should be adopted widely in the NHS. Trial registration International Standard Randomised Controlled Trial Registry: Number ISRCTN49212975. Registered on 22 July 2013. First patient randomised on 29 January 2014.

TouchTerrain is a simple-to-use web application that makes creating 3D printable terrain models from anywhere on the globe accessible to a wide range of users, from people with no GIS expertise to power users. For coders, a Python-based standalone version is available from the open-source project’s GitHub repository. Analyzing 18 months of web analytics gave us a preliminary look at who is using the TouchTerrain web application and what their models are used for; and to map out what terrains on the globe they chose to 3D print. From July 2019 to January 2021, more than 20,000 terrain models were downloaded. Models were created for many different use cases, including education, research, outdoor activities and crafting mementos. Most models were realized with 3D printers, but a sizable minority used CNC machines. Our own experiences with using 3D printed terrain in a university setting have been very positive so far. Anecdotal evidence points to the strong potential for 3D printed terrain models to provide significant help with specific map-related tasks. For the introductory geology laboratory, 3D printed models were used as a form of “training wheels” to aid beginning students in learning to read contour maps, which are still an important tool for geology.

Sudden death syndrome (SDS) is one of the major yield-limiting soybean diseases in the Midwestern United States. Effective management for SDS requires accurate detection in soybean fields. Since traditional scouting methods are time-consuming, labor-intensive, and often destructive, alternative methods to monitor SDS in large soybean fields are needed. This study explores the potential of using high-resolution (3 m) PlanetScope satellite imagery for detection of SDS using the random forest classification algorithm. Image data from blue, green, red, and near-infrared (NIR) spectral bands, the calculated normalized difference vegetation index (NDVI), and crop rotation information were used to detect healthy and SDS-infected quadrats in a soybean field experiment with different rotation treatments, located in Boone County, Iowa. Datasets collected during the 2016, 2017, and 2018 soybean growing seasons were analyzed. The results indicate that spectral features, when combined with ground-based information, can detect areas in soybean plots that are at risk for disease, even before foliar symptoms develop. The classification of healthy and diseased soybean quadrats was >75% accurate and the area under the receiver operating characteristic curve (AUROC) was >70%. Our results indicate that high-resolution satellite imagery and random forest analyses have the potential to detect SDS in soybean fields, and that this approach may facilitate large-scale monitoring of SDS (and possibly other economically important soybean diseases). It may also be useful for guiding recommendations for site-specific management in current and future seasons.

This paper contributes to the literature on travel survey methods by quantifying the relationship between land use, data collection protocol and trip under-reporting in regional travel surveys. While under-reporting more broadly is a recognized problem, the significant increase in underreporting in denser, more urban-type environments identified here has never before been demonstrated or measured. Consequences of this land use-related bias for transportation planning and modelling are explored. The work is carried out by comparing the results of two very similar household travel surveys conducted in 2011 and 2013, in Toronto and Montreal respectively. Using data on over 350,000 persons, a binary logit model for discretionary trip making is estimated and the effects of land use and data collection protocol on under-reporting are isolated. This is done by controlling for mobility tool access, household type and other key determinants of travel demand. Counterintuitive effects for urban type environments found indicate the under-reporting effect is equivalent to a reduction in the pre-existing odds of reporting discretionary trip making in more urban environments of 19 to 29%. When combined with Toronto’s data collection protocol effect, the range increases to 39 to 55%. Results should be of use to transportation planning authorities wishing to make better use of the data collected in large surveys. Recognizing some of the flaws and biases in what is reported, these authorities can complement existing sources of data or modify their approaches to demandbased infrastructure provision to better account for the large number of, largely pedestrian, unreported trips.

Augmentation cystoplasty (AC) has traditionally been used in the treatment of the low capacity, poorly compliant or refractory overactive bladder (OAB). The use of intravesical botulinum toxin and sacral neuromodulation in detrusor overactivity has reduced the number of AC performed for this indication. However, AC remains important in the pediatric and renal transplant setting and still remains a viable option for refractory OAB. Advances in surgical technique have seen the development of both laparoscopic and robotic augmentation cystoplasty. A variety of intestinal segments can be used although ileocystoplasty remains the most common performed procedure. Early complications include thromboembolism and mortality, whereas long-term problems include metabolic disturbance, bacteriuria, urinary tract stones, incontinence, perforation, the need for intermittent self-catheterization and carcinoma. This article examines the contemporary indications, published results and possible future directions for augmentation cystoplasty.

Since the original description of the trans-appendicular continent cystostomy by Mitrofanoff in 1980, a variety of techniques have been described for creating a continent catheterisable channel leading to the bladder, which avoids the native urethra. The Mitrofanoff principle involves the creation of a conduit going into a low pressure reservoir, which can emptied through clean intermittent catheterization through an easily accessible stoma. A variety of tissue segments have been used for creating the conduit, but the two popular options in current urological practice remain the appendix and Yang-Monti transverse ileal tube. The Mitrofanoff procedure has an early reoperation rate for bleeding, bowel obstruction, anastomotic leak or conduit breakdown of up to 8% and the most common long-term complication noted is stomal stenosis resulting in difficulty catheterizing the conduit. However, in both pediatric and adult setting, reports imply that the procedure is durable although it is associated with an overall re-operation rate of up to 32% in contemporary series. Initial reports of laparoscopic and robotic-assisted Mitrofanoff procedures are encouraging, but long-term outcomes are still awaited.

Glacitectonic deformation in the Upper Weichselian led to the tectonic framework of large-scale folds and displaced thrust sheets of Maastrichtian (Upper Cretaceous) chalk and Pleistocene glacial deposits in the southwestern Baltic Sea region. They form surface expressions of sub-parallel ridges and elongated valleys in between and on the Jasmund Peninsula. Geomorphological mapping and detailed landform analyses give another insight into the arrangement and the formation history of these proglacial surface structures. Light detection and ranging (LiDAR) digital elevation models (DEM) analysis techniques were applied to a proglacial rather than a subglacial environment. Results suggest a division into a northern part with morphological ridges striking NW–SE and a southern part with SW–NE trending ridges. The observation of partly truncated northerly ridges and their superimposition by the southern sub-complex suggest that the northern part was generated earlier than the southern part. The applied spatial analyses tools were used to develop a new, self-consistent genetic model integrating all parts of the 100 km2 large Jasmund Glacitectonic Complex. Results suggest a more consistent terminology for the tectonic setting and a revised genetic model for Jasmund, including three evolutional stages that are characterized by different ice flow patterns.

Context : Urodynamic evaluation in the assessment of women complaining of urinary incontinence remains controversial with recent UK National Institute of Health and Clinical Excellence guidance maintaining that it is unnecessary prior to surgery for women with a primarily stress leakage. Other experts contend it should be part of routine preoperative assessment since it establishes a diagnosis, allows more careful patient counseling and predicts surgical outcome. Objectives : To summarize current literature to define the evidence level on which these conflicting opinions are based. Materials and Methods : A systematic literature search was performed and retrieved publications summarized in a narrative evidence review using both original papers and previous reviews. Results : Five hundred and one primary research papers and 65 previous reviews were retrieved. The findings were summarized in a narrative comprising overview, description of methods of bladder and urethral pressure measurement, and a summary of the literature concerning four key questions. Conclusion : The level of evidence was low regarding answering each of the questions posed, preventing firm conclusions. Urodynamic findings do correlate with relevant symptoms and, to some extent, with symptom severity, giving reasonable diagnostic accuracy. There is no reliable evidence that preoperative urodynamic diagnosis improves outcome from surgery for stress incontinence although it is likely to facilitate preoperative discussion. Tests to differentiate sphincter deficiency and urethral hypermobility are not currently recommended due to poor validity and reproducibility. This along with the current use of mid-urethral tapes as the universal primary surgical procedure means differentiation is not a necessity. Preoperative diagnosis of detrusor overactivity does not appear to worsen surgical outcome in women with a primary symptom of stress leakage. Large, well-designed prospective studies are now underway to provide a definitive answer to these questions.

Abstract  The Åknes rockslide site in western Norway has gained much attention due to the potentially catastrophic consequences of a rock slope failure which could trigger a tsunami in the fjord below and endanger local villages and visiting tourists. An extensive monitoring and investigation programme was initiated in 2004 and a large amount of data has been gathered. A careful understanding of the complex rock slope geometry, based on these combined datasets, is essential for detailed stability analyses of the Åknes rockslide site and for prediction of the size of the potential slope failure. This paper reports on an integral part of this effort, the geovisualization, geometric modelling and volume estimation of the potentially unstable parts of the site. A custom-written, 3D software application formed the interactive platform used for visually analysing combinations of geophysical, geological and engineering geological data and for estimating the geometric extent of the basal sliding surface(s) on which the slope failure may potentially occur. Three scenarios were developed for different geometries of the sliding surface and the overall volumes of rock involved in each scenario were calculated. [ABSTRACT FROM AUTHOR]