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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.