Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT.

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.

Women with recurrent urine infections often require preventative treatment to reduce the frequency of infection episodes. Daily low-dose antibiotic medication is a guideline-recommended treatment option for these women. There is increasing concern globally regarding antibiotic-resistant infections, which has led researchers to look at alternative treatments. This trial was conducted to find out whether or not taking an alternative treatment that is not an antibiotic [i.e. methenamine hippurate (Hiprex^®; Mylan NV, Canonsburg, PA, USA)] was as effective as the standard daily low-dose antibiotics. A total of 240 women from across the UK took part in the trial. They were divided equally into two groups; half of the women were given methenamine hippurate and the other half were given standard low-dose antibiotics. Both treatments were prescribed to be taken every day for 1 year. To make a fair comparison, people were put into the two groups at random using a computer program. Aspects of the trial that could be improved were identified through telephone interviews with patients and recruiting staff. Feedback from these telephone interviews helped to ensure the successful conduct of the trial. Patients were followed up for 18 months, comprising the 12 months when they were taking treatment and a 6-month follow-up phase after they had finished treatment. We found that the non-antibiotic option of methenamine hippurate was no worse than the current standard treatment of daily antibiotics in preventing urinary tract infection episodes in adult women. For both treatments, patients expressed high levels of satisfaction. One advantage of the methenamine hippurate treatment was that infecting bacteria were slightly less likely to develop resistance to antibiotics. We also evaluated health-care costs of both treatments and found that methenamine hippurate seemed worthwhile to the NHS in the short term, but there was uncertainty over longer-term costs and benefits. These results will help patients with repeated urinary tract infections to decide on treatment options, particularly if they want to avoid prolonged courses of preventative antibiotics.

Open urethroplasty versus endoscopic urethrotomy for recurrent urethral stricture in men: the OPEN RCT.

BACKGROUND: Men who suffer recurrence of bulbar urethral stricture have to decide between endoscopic urethrotomy and open urethroplasty to manage their urinary symptoms. Evidence of relative clinical effectiveness and cost-effectiveness is lacking. OBJECTIVES: To assess benefit, harms and cost-effectiveness of open urethroplasty compared with endoscopic urethrotomy as treatment for recurrent urethral stricture in men. DESIGN: Parallel-group, open-label, patient-randomised trial of allocated intervention with 6-monthly follow-ups over 24 months. Target sample size was 210 participants providing outcome data. Participants, clinicians and local research staff could not be blinded to allocation. Central trial staff were blinded when needed. SETTING: UK NHS with recruitment from 38 hospital sites. PARTICIPANTS: A total of 222 men requiring operative treatment for recurrence of bulbar urethral stricture who had received at least one previous intervention for stricture. INTERVENTIONS: A centralised randomisation system using random blocks allocated participants 1 : 1 to open urethroplasty (experimental group) or endoscopic urethrotomy (control group). MAIN OUTCOME MEASURES: The primary clinical outcome was control of urinary symptoms. Cost-effectiveness was assessed by cost per quality-adjusted life-year (QALY) gained over 24 months. The main secondary outcome was the need for reintervention for stricture recurrence. RESULTS: The mean difference in the area under the curve of repeated measurement of voiding symptoms scored from 0 (no symptoms) to 24 (severe symptoms) between the two groups was -0.36 [95% confidence interval (CI) -1.78 to 1.02; p = 0.6]. Mean voiding symptom scores improved between baseline and 24 months after randomisation from 13.4 [standard deviation (SD) 4.5] to 6 (SD 5.5) for urethroplasty group and from 13.2 (SD 4.7) to 6.4 (SD 5.3) for urethrotomy. Reintervention was less frequent and occurred earlier in the urethroplasty group (hazard ratio 0.52, 95% CI 0.31 to 0.89; p = 0.02). There were two postoperative complications requiring reinterventions in the group that received urethroplasty and five, including one death from pulmonary embolism, in the group that received urethrotomy. Over 24 months, urethroplasty cost on average more than urethrotomy (cost difference £2148, 95% CI £689 to £3606) and resulted in a similar number of QALYs (QALY difference -0.01, 95% CI -0.17 to 0.14). Therefore, based on current evidence, urethrotomy is considered to be cost-effective. LIMITATIONS: We were able to include only 69 (63%) of the 109 men allocated to urethroplasty and 90 (80%) of the 113 men allocated to urethrotomy in the primary complete-case intention-to-treat analysis. CONCLUSIONS: The similar magnitude of symptom improvement seen for the two procedures over 24 months of follow-up shows that both provide effective symptom control. The lower likelihood of further intervention favours urethroplasty, but this had a higher cost over the 24 months of follow-up and was unlikely to be considered cost-effective. FUTURE WORK: Formulate methods to incorporate short-term disutility data into cost-effectiveness analysis. Survey pathways of care for men with urethral stricture, including the use of enhanced recovery after urethroplasty. Establish a pragmatic follow-up schedule to allow national audit of outcomes following urethral surgery with linkage to NHS Hospital Episode Statistics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98009168. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 61. See the NIHR Journals Library website for further project information.

The urethra carries urine from the bladder to the tip of the penis. Men can develop a condition called urethral stricture when part of the urethra narrows due to scarring. This can lead to difficulties in passing urine and can recur. There are two operations for urethral stricture. The standard approach is endoscopic urethrotomy. The alternative is open urethroplasty. This study wanted to find out which operation was preferable in terms of symptom control, time before further surgery and which operation was best value for the NHS. All aspects of the study were informed by patients. Two hundred and twenty-two men who had received at least one previous operation for stricture took part. The choice of operation was decided by chance (randomisation). Of these men, 113 were randomised to urethrotomy and 109 were randomised to urethroplasty. Following their operation, the men filled in questionnaires every 3­6 months for 2 years about their symptoms and if any further surgery was needed. The two groups were then compared. Of the 222 men who took part, 159 provided enough information for inclusion in the comparison (90 were in the urethrotomy group and 69 were in the urethroplasty group). The improvement over time in urinary symptoms was similar for the two groups. Men in the urethrotomy group were twice as likely to need a further operation over the 2-year study period. Very few men experienced serious complications. This study showed that both operations led to symptom improvement for men with recurrent urethral stricture. Urethroplasty, however, appears unlikely to offer good value for money for the NHS. Men needing treatment for recurrent urethral stricture can use this information to weigh up the pros and cons of each operation to decide with their clinical team which one to undergo.

Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial).

BACKGROUND: Urethral stricture affects 0.9% of men. Initial treatment is urethrotomy. Approximately, half of the strictures recur within 4 yr. Options for further treatment are repeat urethrotomy or open urethroplasty. OBJECTIVE: To compare the effectiveness and cost-effectiveness of urethrotomy with open urethroplasty in adult men with recurrent bulbar urethral stricture. DESIGN, SETTING, AND PARTICIPANTS: This was an open label, two-arm, patient-randomised controlled trial. UK National Health Service hospitals were recruited and 222 men were randomised to receive urethroplasty or urethrotomy. INTERVENTION: Urethrotomy is a minimally invasive technique whereby the narrowed area is progressively widened by cutting the scar tissue with a steel blade mounted on a urethroscope. Urethroplasty is a more invasive surgery to reconstruct the narrowed area. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the profile over 24 mo of a patient-reported outcome measure, the voiding symptom score. The main clinical outcome was time until reintervention. RESULTS AND LIMITATIONS: The primary analysis included 69 (63%) and 90 (81%) of those allocated to urethroplasty and urethrotomy, respectively. The mean difference between the urethroplasty and urethrotomy groups was -0.36 (95% confidence interval [CI] -1.74 to 1.02). Fifteen men allocated to urethroplasty needed a reintervention compared with 29 allocated to urethrotomy (hazard ratio [95% CI] 0.52 [0.31-0.89]). CONCLUSIONS: In men with recurrent bulbar urethral stricture, both urethroplasty and urethrotomy improved voiding symptoms. The benefit lasted longer for urethroplasty. PATIENT SUMMARY: There was uncertainty about the best treatment for men with recurrent bulbar urethral stricture. We randomised men to receive one of the following two treatment options: urethrotomy and urethroplasty. At the end of the study, both treatments resulted in similar and better symptom scores. However, the urethroplasty group had fewer reinterventions.

The clinical and cost effectiveness of surgical interventions for stones in the lower pole of the kidney: the percutaneous nephrolithotomy, flexible ureterorenoscopy and extracorporeal shockwave lithotripsy for lower pole kidney stones randomised controlled trial (PUrE RCT) protocol.

INTRODUCTION: Renal stones are common, with a lifetime prevalence of 10% in adults. Global incidence is increasing due to increases in obesity and diabetes, with these patient populations being more likely to suffer renal stone disease. Flank pain from stones (renal colic) is the most common cause of emergency admission to UK urology departments. Stones most commonly develop in the lower pole of the kidney (in ~35% of cases) and here are least likely to pass without intervention. Currently there are three technologies available within the UK National Health Service to remove lower pole kidney stones: extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and flexible ureterorenoscopy (FURS) with laser lithotripsy. Current evidence indicates there is uncertainty regarding the management of lower pole stones, and each treatment has advantages and disadvantages. The aim of this trial is to determine the clinical and cost effectiveness of FURS compared with ESWL or PCNL in the treatment of lower pole kidney stones. METHODS: The PUrE (PCNL, FURS and ESWL for lower pole kidney stones) trial is a multi-centre, randomised controlled trial (RCT) evaluating FURS versus ESWL or PCNL for lower pole kidney stones. Patients aged ≥16 years with a stone(s) in the lower pole of either kidney confirmed by non-contrast computed tomography of the kidney, ureter and bladder (CTKUB) and requiring treatment for a stone ≤10 mm will be randomised to receive FURS or ESWL (RCT1), and those requiring treatment for a stone >10 mm to ≤25 mm will be randomised to receive FURS or PCNL (RCT2). Participants will undergo follow-up by questionnaires every week up to 12 weeks post-intervention and at 12 months post-randomisation. The primary clinical outcome is health status measured by the area under the curve calculated from multiple measurements of the EuroQol five dimensions five-level version (EQ-5D-5L) questionnaire up to 12 weeks post-intervention. The primary economic outcome is the incremental cost per quality-adjusted life year gained at 12 months post-randomisation. DISCUSSION: The PUrE trial aims to provide robust evidence on health status, quality of life, clinical outcomes and resource use to directly inform choice and National Health Service provision of the three treatment options. TRIAL REGISTRATION: ISRCTN: ISRCTN98970319. Registered on 11 November 2015.

Photodynamic versus white light-guided treatment of non-muscle invasive bladder cancer: a study protocol for a randomised trial of clinical and cost-effectiveness.

INTRODUCTION: Bladder cancer is the most frequently occurring tumour of the urinary system. Ta, T1 tumours and carcinoma in situ (CIS) are grouped as non-muscle invasive bladder cancer (NMIBC), which can be effectively treated by transurethral resection of bladder tumour (TURBT). There are limitations to the visualisation of tumours with conventional TURBT using white light illumination within the bladder. Incomplete resections occur from the failure to identify satellite lesions or the full extent of the tumour leading to recurrence and potential risk of disease progression. To improve complete resection, photodynamic diagnosis (PDD) has been proposed as a method that can enhance tumour detection and guide resection. The objective of the current research is to determine whether PDD-guided TURBT is better than conventional white light surgery and whether it is cost-effective. METHODS AND ANALYSIS: PHOTO is a pragmatic multicentre randomised controlled trial (open parallel group, non-masked and superiority trial) comparing the intervention of PDD-guided TURBT with standard white light resection in newly diagnosed intermediate and high risk NMIBC within the UK National Health Service setting. Clinical effectiveness is measured with time to recurrence. Cost-effectiveness is assessed within trial via the calculation of incremental cost per recurrence avoided and incremental cost per quality-adjusted life per year gained over 3 years and over long term through a modelling exercise over patients' lifetime. ETHICS AND DISSEMINATION: Formal ethics review was undertaken with a favourable opinion, in line with UK regulatory procedures (REC reference number: 14/NE/1062). If reductions in time to recurrence is associated with long-term patient benefits, the cost-effectiveness evaluation will provide further evidence to inform adoption of the technology. Findings will be shared in lay media such as patient and charity forums and will be presented at key meetings and published in academic literature.Trial registration number ISRCTN84013636.

Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT.

BACKGROUND: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. OBJECTIVE: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. DESIGN: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. SETTING: UK NHS, with recruitment of patients from 51 sites. PARTICIPANTS: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. INTERVENTIONS: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. MAIN OUTCOME MEASURES: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants' attitudes to antibiotic use. RESULTS: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1-4) in the no-prophylaxis group (n = 180) to 1 (0-2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. LIMITATIONS: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. CONCLUSIONS: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information.

TISU: Extracorporeal shockwave lithotripsy, as first treatment option, compared with direct progression to ureteroscopic treatment, for ureteric stones: study protocol for a randomised controlled trial.

BACKGROUND: Urinary stone disease is very common with an estimated prevalence among the general population of 2-3%. Ureteric stones are associated with severe pain as they pass through the urinary tract and have significant impact on patients' quality of life due to the detrimental effect on their ability to work and need for hospitalisation. Most ureteric stones can be expected to pass spontaneously with supportive care. However, between one-fifth and one-third of cases require an intervention. The two standard active intervention options are extracorporeal shockwave lithotripsy (ESWL) and ureteroscopic stone retrieval. ESWL and ureteroscopy are effective in terms of stone clearance; however, they differ in terms of invasiveness, anaesthetic requirement, treatment setting, complications, patient-reported outcomes (e.g. pain after intervention, time off work) and cost. There is uncertainty around which is the most clinically effective in terms of stone clearance and the true cost to the NHS and to society (in terms of impact on patient-reported health and economic burden). The aim of this trial is to determine whether, in adults with ureteric stones, judged to require active intervention, ESWL is not inferior and is more cost-effective compared to ureteroscopic treatment as the initial management option. METHODS: The TISU study is a pragmatic multicentre non-inferiority randomised controlled trial of ESWL as the first treatment option compared with direct progression to ureteroscopic treatment for ureteric stones. Patients aged over 16 years with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder (CTKUB) will be randomised to either ESWL or ureteroscopy. The primary clinical outcome is resolution of the stone episode (no further intervention required to facilitate stone clearance) up to six months from randomisation. The primary economic outcome is the incremental cost per quality-adjusted life years (QALYs) gained at six months from randomisation. DISCUSSION: Determining whether ESWL is not inferior clinically and is cost-effective compared to ureteroscopic treatment as the initial management in adults with ureteric stones who are judged to require active treatment is relevant not only to patients and clinicians but also to healthcare providers, both in the UK and globally. TRIAL REGISTRATION: ISRCTN registry, ISRCTN92289221 . Registered on 21 February 2013.

Adherence to European Association of Urology Guidelines on Prophylactic Antibiotics: An Important Step in Antimicrobial Stewardship.

BACKGROUND: The evolution of resistant pathogens is a worldwide health crisis and adherence to European Association of Urology (EAU) guidelines on antibiotic prophylaxis may be an important way to improve antibiotic stewardship and reduce patient harm and costs. OBJECTIVE: To evaluate the prevalence of antibiotic-resistant bacterial strains and health care costs during a period of adherence to EAU guidelines in a tertiary referral urologic institution. DESIGN, SETTING, AND PARTICIPANTS: A protocol for adherence to EAU guidelines for antibiotic prophylaxis for all urologic procedures was introduced in January 2011. Data for 3529 urologic procedures performed between January 2011 and December 2013 after protocol introduction were compared with data for 2619 procedures performed between January 2008 and December 2010 before protocol implementation. The prevalence of bacterial resistance and health care costs were compared between the two periods. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome measures were the proportion of resistant uropathogens and costs related to antibiotic consumption and symptomatic postoperative infection. We used χ2 and Fisher's exact tests to test the significance of differences. RESULTS AND LIMITATIONS: The proportion of patients with symptomatic postoperative infection did not differ (180/3529 [5.1%] vs. 117/2619 [4.5%]; p=0.27). A total of 342 isolates from all patients with symptomatic postoperative infections were analysed. The rate of resistance of Escherichia coli to piperacillin/tazobactam (9.1% vs. 5.4%; p=0.03), gentamicin (18.3% vs. 11.2%; p=0.02), and ciprofloxacin (32.3% vs. 19.1%; p=0.03) decreased significantly after protocol introduction. The defined daily dose (DDD) use of ciprofloxacin fell from 4.2 to 0.2 DDD per 100 patient-days after implementation (p<0.001). Antibiotic drug costs (€76,980 vs. €36,700) and costs related to postoperative infections (€45,870 vs. €29,560) decreased following introduction of the protocol (p<0.001). CONCLUSIONS: Adherence to EAU guidelines on antibiotic prophylaxis reduced antibiotic usage without increasing post-operative infection rate and lowered the prevalence of resistant uropathogens. PATIENT SUMMARY: We analysed the impact of adherence to European Association of Urology guidelines on antibiotic prophylaxis for all surgical urologic procedures on the prevalence of infections and resistant bacterial strains and on costs. We found that adherence to the guidelines reduced the rate of bacterial resistance, in particular against piperacillin/tazobactam, gentamicin, and ciprofloxacin, and reduced costs without increasing the risk of postoperative infection after urologic procedures. We recommend adherence to the guidelines as an important part of antibiotic stewardship programmes.

Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial).

BACKGROUND: Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. OBJECTIVES: To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. DESIGN: A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation. SETTING: Urology departments in 24 UK NHS hospitals. PARTICIPANTS: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. INTERVENTIONS: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. MAIN OUTCOME MEASURES: The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks. RESULTS: Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI -4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI -4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location. CONCLUSIONS: Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010-019469-26. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.

Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation.

BACKGROUND: For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT. DATA SOURCES: MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources. REVIEW METHODS: Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness. RESULTS: The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. LIMITATIONS: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS: The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002461. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. METHODS: For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 µg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. FINDINGS: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). INTERPRETATION: Tamsulosin 400 µg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Open urethroplasty versus endoscopic urethrotomy--clarifying the management of men with recurrent urethral stricture (the OPEN trial): study protocol for a randomised controlled trial.

BACKGROUND: Urethral stricture is a common cause of difficulty passing urine in men with prevalence of 0.5 %; about 62,000 men in the UK. The stricture is usually sited in the bulbar part of the urethra causing symptoms such as reduced urine flow. Initial treatment is typically by endoscopic urethrotomy but recurrence occurs in about 60% of men within 2 years. The best treatment for men with recurrent bulbar stricture is uncertain. Repeat endoscopic urethrotomy opens the narrowing but it usually scars up again within 2 years requiring repeated procedures. The alternative of open urethroplasty involves surgically reconstructing the urethra, which may need an oral mucosal graft. It is a specialist procedure with a longer recovery period but may give lower risk of recurrence. In the absence of firm evidence as to which is best, individual men have to trade off the invasiveness and possible benefit of each option. Their preference will be influenced by individual social circumstances, availability of local expertise and clinician guidance. The open urethroplasty versus endoscopic urethrotomy (OPEN) trial aims to better guide the choice of treatment for men with recurrent urethral strictures by comparing benefit over 2 years in terms of symptom control and need for further treatment. METHODS/DESIGN: OPEN is a pragmatic, UK multicentre, randomised trial. Men with recurrent bulbar urethral strictures (at least one previous treatment) will be randomised to undergo endoscopic urethrotomy or open urethroplasty. Participants will be followed for 24 months after randomisation, measuring symptoms, flow rate, the need for re-intervention, health-related quality of life, and costs. The primary clinical outcome is the difference in symptom control over 24 months measured by the area under the curve (AUC) of a validated score. The trial has been powered at 90% with a type I error rate of 5% to detect a 0.1 difference in AUC measured on a 0-1 scale. The analysis will be based on all participants as randomised (intention-to-treat). The primary economic outcome is the incremental cost per quality-adjusted life year. A qualitative study will assess willingness to be randomised and hence ability to recruit to the trial. DISCUSSION: The OPEN Trial seeks to clarify relative benefit of the current options for surgical treatment of recurrent bulbar urethral stricture which differ in their invasiveness and resources required. Our feasibility study identified that participation would be limited by patient preference and differing recruitment styles of general and specialist urologists. We formulated and implemented effective strategies to address these issues in particular by inviting participation as close as possible to diagnosis. In addition re-calculation of sample size as recruitment progressed allowed more efficient design given the limited target population and funding constraints. Recruitment is now to target. TRIAL REGISTRATION: ISRCTN98009168 Date of registration: 29 November 2012.

Cost effectiveness of antimicrobial catheters for adults requiring short-term catheterisation in hospital.

Catheter-associated urinary tract infection (CAUTI) is the second most common cause of hospital-acquired infection. A number of strategies have been put forward to prevent CAUTI, including the use of antimicrobial catheters. We aimed to assess whether the use of either a nitrofurazone-impregnated or a silver alloy-coated catheter was cost-effective compared with standard polytetrafluoroethylene (PTFE)-coated catheters. A decision-analytic model using data from a clinical trial conducted in the United Kingdom was used to calculate the incremental cost per quality-adjusted life-year (QALY). We assumed that differences in costs and QALYs were driven by difference in risk of acquiring a CAUTI. Routine use of nitrofurazone-impregnated catheters was, on average, £7 (€9) less costly than use of the standard catheter over 6 wk. There was a >70% chance that use of nitrofurazone catheters would be cost saving and an 84% chance that the incremental cost per QALY would be less than £30 000 (€36 851; a commonly used threshold for society's willingness to pay). Silver alloy-coated catheters were very unlikely to be cost-effective. The model's prediction, although associated with uncertainty, was that nitrofurazone-impregnated catheters may be cost-effective in the UK National Health System or a similar setting.

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial.

BACKGROUND: Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications.Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation.This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. METHODS/DESIGN: The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo.Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups. TRIAL REGISTRATION: ISRCTN69423238; EudraCT number: 2010-019469-26.

Practicalities of using a modified version of the Cochrane Collaboration risk of bias tool for randomised and non-randomised study designs applied in a health technology assessment setting.

UNLABELLED: We describe our experience of using a modified version of the Cochrane risk of bias (RoB) tool for randomised and non-randomised comparative studies. OBJECTIVES: To assess time to complete RoB assessment. To assess inter-rater agreement. To explore the association between RoB and treatment effect size METHODS: Cochrane risk of bias assessment was performed on a sample of full text primary reports included in a systematic review comparing operative techniques for radical prostatectomy. Inter-rater agreement was assessed using the kappa statistic. RESULTS: Twenty-four studies were judged as high overall RoB, 13 were judged as low RoB and 11 were unclear. The weighted Kappa value was 0.35 indicating fair agreement. The median (range) time taken to rate each study was 30 min (10-49). The effect estimate for all studies was 0.61 (95% credible interval (CrI) 0.46-0.83) and 0.73 (95% CrI 0.29-1.75) for low risk studies. CONCLUSIONS: Although the process was time consuming, using a modified version of the RoB tool proved useful for demonstrating conservative effect estimates. That we only achieved a fair agreement between reviewers demonstrates the urgent need for further validation to improve inter-rater agreement. We suggest additional RoB levels could improve inter-rater reliability.

Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis.

OBJECTIVE: To compare the effectiveness of robot-assisted and standard laparoscopic prostatectomy. METHODS: A care pathway was described. We performed a systematic literature review based on a search of Medline, Medline in Process, Embase, Biosis, Science Citation Index, Cochrane Controlled Trials Register, Current Controlled Trials, Clinical Trials, WHO International Clinical Trials Registry and NIH Reporter, the Health Technology Assessment databases, the Database of Abstracts of Reviews of Effects, and relevant conference abstracts up to 31st October 2010). Additionally, reference lists were scanned, an expert panel consulted, and websites of manufacturers, professional organisations, and regulatory bodies were checked. We selected randomised controlled trials (RCTs) and non-randomised comparative studies, published after 1st January 1995, including men with localised prostate cancer undergoing robot-assisted or laparoscopic prostatectomy compared with the other procedure or with open prostatectomy. Studies where at least 90% of included men had clinical tumour stages T1 to T2 and which reported at least one of our specified outcomes were eligible for inclusion. A mixed-treatment comparison meta-analysis was performed to generate comparative statistics on specified outcomes. RESULTS: We included data from 19 064 men across one RCT and 57 non-randomised comparative reports. Robotic prostatectomy had a lower risk of major intra-operative harms such as organ injury [0.4% robotic vs 2.9% laparoscopic], odds ratio ([OR] {95% credible interval [CrI]} 0.16 [0.03 to 0.76]), and a lower rate of surgical margins positive for cancer [17.6% robotic vs 23.6% laparoscopic], OR [95% CrI] 0.69 [0.51 to 0.96]). There was no evidence of a difference in the proportion of men with urinary incontinence at 12 months (OR [95% CrI] 0.55 [0.09 to 2.84]). There were insufficient data on sexual dysfunction. Surgeon learning rates for the procedures did not differ, although data were limited. CONCLUSIONS: Men undergoing robotic prostatectomy appear to have reduced surgical morbidity, and a lower risk of a positive surgical margin, which may reduce rates of cancer recurrence and the need for further treatment, but considerable uncertainty surrounds these results. We found no evidence that men undergoing robotic prostatectomy are disadvantaged in terms of early outcomes. We were unable to determine longer-term relative effectiveness.

Comparative cost-effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of men with localised prostate cancer: a health technology assessment from the perspective of the UK National Health Service.

BACKGROUND: Robot-assisted laparoscopic prostatectomy is increasingly used compared with a standard laparoscopic technique, but it remains uncertain whether potential benefits offset higher costs. OBJECTIVE: To determine the cost-effectiveness of robotic prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: We conducted a care pathway description and model-based cost-utility analysis. We studied men with localised prostate cancer able to undergo either robotic or laparoscopic prostatectomy for cure. We used data from a meta-analysis, other published literature, and costs from the UK National Health Service and commercial sources. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Care received by men for 10 yr following radical prostatectomy was modelled. Clinical events, their effect on quality of life, and associated costs were synthesised assuming 200 procedures were performed annually. RESULTS AND LIMITATIONS: Over 10 yr, robotic prostatectomy was on average (95% confidence interval [CI]) £1412 (€1595) (£1304 [€1473] to £1516 [€1713]) more costly than laparoscopic prostatectomy but more effective with mean (95% CI) gain in quality-adjusted life-years (QALYs) of 0.08 (0.01-0.15). The incremental cost-effectiveness ratio (ICER) was £18 329 (€20 708) with an 80% probability that robotic prostatectomy was cost effective at a threshold of £30 000 (€33 894)/QALY. The ICER was sensitive to the throughput of cases and the relative positive margin rate favouring robotic prostatectomy. CONCLUSIONS: Higher costs of robotic prostatectomy may be offset by modest health gain resulting from lower risk of early harms and positive margin, provided >150 cases are performed each year. Considerable uncertainty persists in the absence of directly comparative randomised data.

Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital. We aimed to establish whether short-term routine use of antimicrobial catheters reduced risk of CAUTI compared with standard polytetrafluoroethylene (PTFE) catheterisation. METHODS: In our parallel, three group, multicentre, randomised controlled superiority trial, we enrolled adults (aged ≥16 years) requiring short-term (≤14 days) catheterisation at 24 hospitals in the UK. Participants were randomly allocated 1:1:1 with a remote computer allocation to receive a silver alloy-coated catheter, a nitrofural-impregnated catheter, or a PTFE-coated catheter (control group). Patients undergoing unplanned catheterisation were also included and consent for participation was obtained retrospectively. Participants and trial staff were unmasked to treatment assignment. Data were collected by trial staff and by patient-reported questionnaires for 6 weeks after randomisation. The primary outcome was incidence of symptomatic urinary tract infection for which an antibiotic was prescribed by 6 weeks. We postulated that a 3·3% absolute reduction in CAUTI would represent sufficient benefit to recommend routine use of antimicrobial catheters. This study is registered, number ISRCTN75198618. FINDINGS: 708 (10%) of 7102 randomly allocated participants were not catheterised, did not confirm consent, or withdrew, and were not included in the primary analyses. Compared with 271 (12·6%) of 2144 participants in the control group, 263 (12·5%) of 2097 participants allocated a silver alloy catheter had the primary outcome (difference -0·1% [95% CI -2·4 to 2·2]), as did 228 (10·6%) of 2153 participants allocated a nitrofural catheter (-2·1% [-4·2 to 0·1]). Rates of catheter-related discomfort were higher in the nitrofural group than they were in the other groups. INTERPRETATION: Silver alloy-coated catheters were not effective for reduction of incidence of symptomatic CAUTI. The reduction we noted in CAUTI associated with nitrofural-impregnated catheters was less than that regarded as clinically important. Routine use of antimicrobial-impregnated catheters is not supported by this trial. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

EAU guidelines on assessment and nonsurgical management of urinary incontinence.

CONTEXT: The previous European Association of Urology (EAU) guidelines on urinary incontinence comprised a summary of sections of the 2009 International Consultation on Incontinence. A decision was made in 2010 to rewrite these guidelines based on an independent systematic review carried out by the EAU guidelines panel, using a sustainable methodology. OBJECTIVE: We present a short version of the full guidelines on assessment, diagnosis, and nonsurgical treatment of urinary incontinence, with the aim of increasing their dissemination. EVIDENCE ACQUISITION: Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches, based on Population, Intervention, Comparator, Outcome questions. Appraisal of papers was carried out by an international panel of experts, who also collaborated on a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. EVIDENCE SUMMARY: The full version of the guidelines is available online (http://www.uroweb.org/guidelines/online-guidelines/). The guidelines include algorithms that refer the reader back to the supporting evidence, and they are more immediately useable in daily clinical practice. CONCLUSIONS: These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where such evidence does not exist, they present a consensus of expert opinion.