Background:Renal tract stone disease is common. The three intervention options are shockwave lithotripsy, flexible ureteroscopic stone treatment and keyhole surgery. Objectives:To determine which of shockwave lithotripsy, flexible ureteroscopic stone treatment and keyhole surgery offer the best outcomes in terms of health and quality of life, clinical effectiveness and cost-effectiveness for people with lower pole kidney stones. Design:The PUrE study comprised two pragmatic multicentre, open-label, superiority randomised controlled trials: RCT1 for lower pole stones ≤ 10 mm and RCT2 for lower pole stones > 10 and ≤ 25 mm. Setting:National Health Service Urology departments. Participants:Adults presenting with lower pole renal stones, able to undergo any of the treatments and complete trial procedures. Intervention:Eligible participants were randomised in RCT1 to flexible ureteroscopic stone treatment or shockwave lithotripsy; and in RCT2 to flexible ureteroscopic stone treatment or keyhole surgery. Main outcome measures:The primary outcome measure was health status 'area under the curve', measured weekly to 12 weeks post intervention with the EuroQol-5 Dimensions, five-level version. The primary economic outcome was the incremental cost per quality-adjusted life-year gained at 12 months from randomisation. Results:RCT1: A total of 461 participants were randomised: 231 to flexible ureteroscopic stone treatment; and 230 to shockwave lithotripsy. RCT2: A total of 159 participants were randomised: 73 to flexible ureteroscopic stone treatment; and 86 to keyhole surgery. Primary outcome:RCT1: The mean health status area under the curve was 0.807 (standard deviation 0.205) in the flexible ureteroscopic stone treatment group (n = 164) and 0.826 (standard deviation 0.207) in the shockwave lithotripsy group (n = 188). The between-group difference, 0.024 (95% confidence interval -0.004 to 0.053), was a small difference in favour of flexible ureteroscopic stone treatment after correcting for a baseline imbalance. Complete stone clearance was higher with flexible ureteroscopic stone treatment (72%) than shockwave lithotripsy (36%). RCT2: The mean health status area under the curve was 0.794 (standard deviation 0.198) in the flexible ureteroscopic stone treatment group (n = 57) and 0.818 (standard deviation 0.217) in the keyhole surgery group (n = 63). The between-group difference, -0.07 (95% confidence interval -0.11 to -0.02), was a borderline meaningful difference favouring keyhole surgery. Complete stone clearance was higher with keyhole surgery (71%) than flexible ureteroscopic stone treatment (48%). Economic evaluation:RCT1: Flexible ureteroscopic stone treatment is more costly (£1138; 95% confidence interval £646 to £1631) and produces 0.017 (95% confidence interval -0.008 to 0.043) additional quality-adjusted life-years; with an incremental cost-effectiveness ratio of £65,163 per quality-adjusted life-year gained. Shockwave lithotripsy has a 99.9% chance of being cost-effective at a £20,000 threshold value. RCT2: Flexible ureteroscopic stone treatment is more costly (£733; 95% confidence interval -£508 to £1973) and produces fewer quality-adjusted life-years (-0.001; 95% confidence interval -0.044 to 0.042). Keyhole surgery has an 87% chance of being cost-effective at a £20,000 threshold value. Limitations:Blinding of participants and healthcare providers was not possible. There were differential waiting times between interventions in RCT1; however, adjusting for this gave similar treatment effect estimates. Conclusions:The PUrE study found in RCT1 that shockwave lithotripsy was more cost-effective than flexible ureteroscopic stone treatment, with no meaningful difference in patient health status even though complete stone-free rates were higher with flexible ureteroscopic stone treatment. In RCT2, keyhole surgery was more cost-effective than flexible ureteroscopic stone treatment on a micro-costing basis, which better reflects treatment cost differences to the NHS. Keyhole surgery was marginally beneficial for health status with higher complete stone-free rates. Future work:What effect will suction devices, improvements in laser technology, and intraoperative pressure monitoring have on postoperative pain, quality of life, stone-free rates, complications, and costs of flexible ureteroscopic stone treatment? What effect does miniaturisation of keyhole surgery have on postoperative pain, length of stay, complications, stone-free rates and costs? Trial registration:This trial is registered as ISRCTN98970319. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/152/02) and is published in full in Health Technology Assessment; Vol. 29, No. 40. See the NIHR Funding and Awards website for further award information.

Background Urinary stone disease affects 2–3% of the general population. Ureteric stones are associated with severe pain and can have a significant impact on a patient’s quality of life. Most ureteric stones are expected to pass spontaneously with supportive care; however, between one-fifth and one-third of patients require an active intervention. The two standard interventions are shockwave lithotripsy and ureteroscopic stone treatment. Both treatments are effective, but they differ in terms of invasiveness, anaesthetic requirement, treatment setting, number of procedures, complications, patient-reported outcomes and cost. There is uncertainty around which is the more clinically effective and cost-effective treatment. Objectives To determine if shockwave lithotripsy is clinically effective and cost-effective compared with ureteroscopic stone treatment in adults with ureteric stones who are judged to require active intervention. Design A pragmatic, multicentre, non-inferiority, randomised controlled trial of shockwave lithotripsy as a first-line treatment option compared with primary ureteroscopic stone treatment for ureteric stones. Setting Urology departments in 25 NHS hospitals in the UK. Participants Adults aged ≥ 16 years presenting with a single ureteric stone in any segment of the ureter, confirmed by computerised tomography, who were able to undergo either shockwave lithotripsy or ureteroscopic stone treatment and to complete trial procedures. Intervention Eligible participants were randomised 1 : 1 to shockwave lithotripsy (up to two sessions) or ureteroscopic stone treatment. Main outcome measures The primary clinical outcome measure was resolution of the stone episode (stone clearance), which was operationally defined as ‘no further intervention required to facilitate stone clearance’ up to 6 months from randomisation. This was determined from 8-week and 6-month case report forms and any additional hospital visit case report form that was completed by research staff. The primary economic outcome measure was the incremental cost per quality-adjusted life-year gained at 6 months from randomisation. We estimated costs from NHS resources and calculated quality-adjusted life-years from participant completion of the EuroQol-5 Dimensions, three-level version, at baseline, pre intervention, 1 week post intervention and 8 weeks and 6 months post randomisation. Results In the shockwave lithotripsy arm, 67 out of 302 (22.2%) participants needed further treatment. In the ureteroscopic stone treatment arm, 31 out of 302 (10.3%) participants needed further treatment. The absolute risk difference was 11.4% (95% confidence interval 5.0% to 17.8%); the upper bound of the 95% confidence interval ruled out the prespecified margin of non-inferiority (which was 20%). The mean quality-adjusted life-year difference (shockwave lithotripsy vs. ureteroscopic stone treatment) was –0.021 (95% confidence interval 0.033 to –0.010) and the mean cost difference was –£809 (95% confidence interval –£1061 to –£551). The probability that shockwave lithotripsy is cost-effective is 79% at a threshold of society’s willingness to pay for a quality-adjusted life-year of £30,000. The CEAC is derived from the joint distribution of incremental costs and incremental effects. Most of the results fall in the south-west quadrant of the cost effectiveness plane as SWL always costs less but is less effective. Limitations A limitation of the trial was low return and completion rates of patient questionnaires. The study was initially powered for 500 patients in each arm; however, the total number of patients recruited was only 307 and 306 patients in the ureteroscopic stone treatment and shockwave lithotripsy arms, respectively. Conclusions Patients receiving shockwave lithotripsy needed more further interventions than those receiving primary ureteroscopic retrieval, although the overall costs for those receiving the shockwave treatment were lower. The absolute risk difference between the two clinical pathways (11.4%) was lower than expected and at a level that is acceptable to clinicians and patients. The shockwave lithotripsy pathway is more cost-effective in an NHS setting, but results in lower quality of life. Future work (1) The generic health-related quality-of-life tools used in this study do not fully capture the impact of the various treatment pathways on patients. A condition-specific health-related quality-of-life tool should be developed. (2) Reporting of ureteric stone trials would benefit from agreement on a core outcome set that would ensure that future trials are easier to compare. Trial registration This trial is registered as ISRCTN92289221. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 19. See the NIHR Journals Library website for further project information.

Purpose of review There is an ongoing explosion in the amount and quality, of research in the field of Endourology. From a solid basis of systematic reviews and small, single centre trials it has been possible to design large randomised controlled trials in the UK and in the USA. This review will describe some of the more recent trials (small and large) that are helping to provide a solid evidence base for our practice in Endourology. On-going studies Randomised controlled trial (RCTs) include: The Therapeutic Interventions for Stones in the Ureter (TISU), the Percutaneous nephrolithotomy, flexible Ureterorenoscopy and extracorporeal Shockwave lithotripsy for lower pole kidney stones (PURE RCTs) and the Prevention of Urinary Stones with Hydration (PUSH). Quality of life (QoL) measures and studies include: the Wisconsin Stone QoL Questionnaire, the Cambridge Renal Stone PROM, the Cambridge Ureteral Stone PROM, the Urinary stone and Intervention QoL questionnaire and the Study to Enhance Understanding of sTent-associated Symptoms (STENTS). The Core Outcome Set in Trials on treatments for Renal and UreteriC sTones (COSTRUCT) study aims to define a core outcome set to be used in future trials. Summary On-going studies will provide higher quality evidence on the treatment of ureteric and renal stones to inform treatment decision making and guideline recommendations. They will also guide decisions relating to prevention and recurrence and give insight into the true impact of urinary stones and endourological interventions on patients' quality of life. Future studies will incorporate big data and artificial intelligence.

Abstract Objectives To assess the feasibility of conducting a randomised controlled trial (RCT) to assess whether avoiding ureteric drainage is superior to performing ureteric drainage after Uncomplicated Ureteroscopy and/or Flexible Ureterorenoscopy (URS/FURS) treatment of a urinary tract stone in improving patient reported outcome measures (PROMs) and 30‐day unplanned readmission rates. A secondary objective was to understand current practice of urologists regarding ureteric drainage after uncomplicated URS/FURS (UU). Material and methods We undertook an online survey of urologists, circulated amongst members of international urological societies and through social media platforms. Uncomplicated URS/FURS was defined as completion of URS/FURS treatment for a urinary tract stone, with the absence of: ureteral trauma, residual fragments requiring further lithotripsy procedures, significant bleeding, perforation, prior urinary tract infection or pregnancy. The ureteric drainage options considered included an indwelling stent, stent on a string or a ureteric catheter. The primary outcome was to determine the proportion of urologists willing to take part in a RCT, randomising patients after UU to a “no ureteric drainage” arm or ureteric drainage arm. Secondary outcomes included determining in their current practice, the proportion of clinicians performing routine ureteric drainage after UU, the reasons for performing ureteric drainage following UU and their preferred optimal duration for ureteric drainage if it is used. The study was reported according to the Checklist for Reporting Results of Internet E‐Surveys (CHERRIES). Results Total of 468 respondents from 45 countries took part in the survey, of whom 303 completed the entire survey (65%). The majority agreed that they would be willing to randomise patients (244/303, 81%) in the proposed RCT. Perceived lack of equipoise to randomise was the most common reason for not being willing to participate (59/303, 19%). 92% (308/335) reported that they use ureteric drainage after UU. This was most often due to wanting to prevent possible complications from post‐operative ureteric oedema (77%) or to aid passage of small fragments (43%). Complexity of the case (i.e. impacted stone 90%) and length of the procedure (46%) were the most important intraoperative factors influencing the decision to use ureteric drainage post procedure. If required, the median stated ideal duration of ureteric drainage was 5 days (IQR: 3–7 days) after UU. If having UU personally, 30% would want no stent postoperatively and over half would prefer a stent on a string. Conclusion We have highlighted wide variation in practice regarding ureteric drainage after UU. Our results support the feasibility of an RCT evaluating if no ureteric drainage is superior to ureteric drainage in improving PROMs and 30‐day unplanned readmission rates following UU.

Medical expulsive therapy (MET) for ureteral stones has become a controversial area due to the contradictory results of high-quality trials and meta-analyses.We aimed to review the literature to evaluate the value of and future directions for MET for ureteral stone disease.A literature search of the MEDLINE database and the Cochrane Library was conducted to collect articles about MET for ureteral calculi published up to 28 October 2018. A total of 524 articles were screened. Sixty-nine publications that met the inclusion criteria for this review were chosen. Among the primary research articles on MET with stone clearance as the primary outcome, seven responded to high-quality requirements of Cochrane Collaboration's tool for assessing the risk of bias in randomised trials.The vast majority of randomised, double-blind, placebo-controlled trials without a high or an unclear risk of bias did not find a benefit of MET for increased ureteral stone passage rates. This is in contrast to results of meta-analyses that are skewed by low-quality trials.The strength of evidence for the benefit of MET in ureteral stones is low, even for distal ureteral stones >5 mm. In the absence of further high-quality data, individual clinicians are required to decide for themselves whether to believe high-quality single trials or meta-analyses.We evaluated the value of and future directions for medical expulsive therapy (MET) for ureteral stone disease. We found that outcomes varied between studies. Individual clinicians are required to decide for themselves which studies to believe. Alpha-blockers as MET may retain a role in a selective group of well-counselled patients with larger stones who understand the side effects and off-label use.

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.

BACKGROUND Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used for the treatment of stress urinary incontinence in adult women. OBJECTIVES To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. SEARCH METHODS We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. SELECTION CRITERIA All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. DATA COLLECTION AND ANALYSIS Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. MAIN RESULTS Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality.One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable with respect to continence grade (risk ratio (RR) 0.7, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (RR 0.54, 95% CI 0.16 to 0.92). Another, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in Revman) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. AUTHORS' CONCLUSIONS The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of mid-urethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects.

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 mu g, 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 mu g 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. Copyright (C) Pickard et al. Open Access article distributed under the terms of CC BY.

The prevalence of urolithiasis is increasing. Lower-pole stones (LPS) are the most common renal calculi and the most likely to require treatment. A systematic review comparing shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PNL) in the treatment of <= 20 mm LPS in adults was performed. Comprehensive searches revealed 2741 records; 7 randomised controlled trials (RCTs) recruiting 691 patients were included. Meta-analyses for stone-free rate (SFR) at <= 3 mo favoured PNL over SWL (risk ratio [RR]: 2.04; 95% confidence interval [CI], 1.50-2.77) and RIRS over SWL (RR: 1.31; 95% CI, 1.08-1.59). Stone size subgroup analyses revealed PNL and RIRS were considerably more effective than SWL for > 10 mm stones, but the magnitude of benefit was markedly less for <= 10 mm stones. The quality of evidence (Grading of Recommendations Assessment, Development, and Evaluation [GRADE]) for SFR was moderate for these comparisons. The median SFR from reported RCTs suggests PNL is more effective than RIRS. The findings regarding other outcomes were inconclusive because of limited and inconsistent data. Well-designed, prospective, comparative studies that measure these outcomes using standardised definitions are required, particularly for the direct comparison of PNL and RIRS. This systematic review, which used Cochrane methodology and GRADE quality-of-evidence assessment, provides the first level 1a evidence for the management of LPS.Patient summary: We thoroughly examined the literature to compare the benefits and harms of the different ways of treating kidney stones located at the lower pole. PNL and RIRS were superior to SWL in clearing the stones within 3 mo, but we were unable to make any conclusions regarding other outcomes. More data is required from reliable studies before firm recommendations can be made. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.