Alkalinized lidocaine versus lidocaine gel as local anesthesia prior to intra-vesical botulinum toxin (BoNTA) injections: A prospective, single center, randomized, double-blind, parallel group trial of efficacy and morbidity.

AIMS: To assess the efficacy and morbidity of alkalinized lidocaine solution compared to lidocaine gel for intra-vesical anesthesia during botulinum toxin (BoNTA) injections in a statistically powered, prospective, parallel group, double-blind randomized controlled trial. METHODS: Fifty-four patients of either sex were randomized to receive either alkalinized lidocaine (AL) solution (10 ml 8.4% sodium bicarbonate + 20 ml 2% lidocaine solution + 22 ml sterile Aquagel®) or lidocaine gel (LG) (22 ml standard 2% lidocaine gel Instillagel® + 30 ml 0.9% normal saline solution). Primary outcome was average pain (assessed by 100 mm visual analog score) felt during intra-vesical BoNTA injections performed at least 20 min after instillation. Secondary outcome was the rate of adverse events. RESULTS: Of 60 randomized patients 54 received the allocated intervention and were analyzed. Mean pain score in the AL group was 17.11 mm (95%CI 8.65-25.57 mm) and in the LG group was 19.53 mm (95%CI 13.03-26.03mm) with no significant difference between the groups. Cost of interventional medication in the AL group was almost double that of the LG group. No adverse events were attributable to local anesthetic instillation in either group. CONCLUSIONS: Alkalinized lidocaine solution is not superior to lidocaine gel for anesthesia during intra-vesical BoNTA injections, and the higher cost precludes its use over lidocaine gel at our centre. We have used the results of this study to adapt our local protocol for BoNTA injections and continue to use lidocaine gel as the local anesthetic of choice. Neurourol. Urodynam. 35:522-527, 2016. © 2015 Wiley Periodicals, Inc.

A mixed methods study to assess the feasibility of a randomised controlled trial of invasive urodynamic testing versus clinical assessment and non-invasive tests prior to surgery for stress urinary incontinence in women: the INVESTIGATE-I study.

BACKGROUND: The position of invasive urodynamic testing (IUT) in diagnostic pathways for urinary incontinence is unclear, and systematic reviews have called for further trials evaluating clinical utility. The objective of this study was to inform the decision whether to proceed to a definitive randomised trial of IUT compared to clinical assessment with non-invasive tests, prior to surgery in women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI). METHODS: A mixed methods study comprising a pragmatic multicentre randomised pilot trial, a qualitative face-to face interview study with patients eligible for the trial, an exploratory economic evaluation including value of information study, a survey of clinicians' views about IUT, and qualitative telephone interviews with purposively sampled survey respondents. Only the first and second of these elements are reported here. Trial participants were randomised to either clinical assessment with non-invasive tests (control arm) or clinical assessment with non-invasive tests plus IUT (intervention arm). The main outcome measures of these feasibility studies were confirmation that units can identify and recruit eligible women, acceptability of investigation strategies and data collection tools, and acquisition of outcome data to determine the sample size for a definitive trial. The primary outcome proposed for a definitive trial was ICIQ-FLUTS (total score) 6 months after surgery or the start of nonsurgical treatment. RESULTS: Of 284 eligible women, 222 (78%) were recruited, 165/219 (75%) returned questionnaires at baseline, and 125/200 returned them (63%) at follow-up. Most women underwent surgery; management plans were changed in 19 (19%) participants following IUT. Participants interviewed were positive about the trial and the associated documentation. CONCLUSIONS: All elements of a definitive trial were rehearsed. Such a trial would require between 232 and 922 participants, depending on the target difference in the primary outcome. We identified possible modifications to our protocol for application in a definitive trial including clarity over inclusion/exclusions, screening processes, reduction in secondary outcomes, and modification to patient questionnaire booklets and bladder diaries. A definitive trial of IUT versus clinical assessment prior to surgery for SUI or stress predominant MUI is feasible and remains relevant. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN 71327395, registered 7 June 2010.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): a mixed-methods study to assess the feasibility of a future randomised controlled trial of invasive urodynamic testing prior to surgery for stress urinary incontinence in women.

BACKGROUND: The position of invasive urodynamic testing in the diagnostic pathway for urinary incontinence (UI) is unclear. Systematic reviews have called for further trials evaluating clinical utility, although a preliminary feasibility study was considered appropriate. OBJECTIVES: To inform the decision whether or not to proceed to a definitive randomised trial of invasive urodynamic testing compared with clinical assessment with non-invasive tests, prior to surgery in women with stress UI (SUI) or stress predominant mixed UI (MUI). DESIGN: A mixed-methods study comprising a pragmatic multicentre randomised pilot trial; economic evaluation; survey of clinicians' views about invasive urodynamic testing; qualitative interviews with clinicians and trial participants. SETTING: Urogynaecology, female urology and general gynaecology units in Newcastle, Leicester, Swansea, Sheffield, Northumberland, Gateshead and South Tees. PARTICIPANTS: Trial recruits were women with SUI or stress predominant MUI who were considering surgery after unsuccessful conservative treatment. Relevant clinicians completed two online surveys. Subsets of survey respondents and trial participants took part in separate qualitative interview studies. INTERVENTIONS: Pilot trial participants were randomised to undergo clinical assessment with non-invasive tests (control arm); or assessment as controls, plus invasive urodynamic testing (intervention arm). MAIN OUTCOME MEASURES: Confirmation that units can identify and recruit eligible women; acceptability of investigation strategies and data collection tools; acquisition of outcome data to determine the sample size for a definitive trial. The proposed primary outcome for the definitive trial was International Consultation on Incontinence Modular Questionnaire (ICIQ) Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) (total score) 6 months after surgery or the start of non-surgical treatment; secondary outcomes included: ICIQ-FLUTS (subscales); ICIQ Urinary Incontinence Short Form; ICIQ Lower Urinary Tract Symptoms Quality of Life; Urogenital Distress Inventory; EuroQol-5D; costs, quality-adjusted life-years (QALYs) and incremental cost per QALY, Short Form 12; 3-day bladder diary. RESULTS: Of 284 eligible women, 222 (78%) were recruited; 165/219 (75%) returned questionnaires at baseline and 125/200 (63%) who were sent questionnaires at follow-up. There were few missing data items in returned questionnaires, with individual outcome scales calculable for 81%-94%. Most women underwent surgery; management plans were changed in 19 (19%) participants following invasive urodynamic testing. Participant Costs Questionnaires were returned by 53% 6 months after treatment; complete data to undertake cost-utility analysis were available in 27% (intervention) and 47% (control). While insufficient to recommend changes in practice, the results suggest further research would be valuable. All clinicians responding to the survey had access to invasive urodynamic testing, and most saw it as essential prior to surgery in women with SUI with or without other symptoms; nevertheless, 70% considered the research question underlying INVESTIGATE important and most were willing to randomise patients in a definitive trial. Participants interviewed were positive about the trial and associated documentation; the desire of some women to avoid invasive urodynamic testing contrasted with opinions expressed by clinicians through both survey and interview responses. CONCLUSIONS: All elements of a definitive trial and economic evaluation were rehearsed; several areas for protocol modification were identified. Such a trial would require to 400-900 participants, depending on the difference in primary outcome sought. FUTURE WORK: A definitive trial of invasive urodynamic testing versus clinical assessment prior to surgery for SUI or stress predominant MUI should be undertaken. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71327395. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Long-term follow-up of a multicentre randomised controlled trial comparing tension-free vaginal tape, xenograft and autologous fascial slings for the treatment of stress urinary incontinence in women.

OBJECTIVE: To compare the long-term outcomes of a tension-free vaginal tape (TVT; Gynecare™, Somerville, NJ, USA), autologous fascial sling (AFS) and xenograft sling (porcine dermis, Pelvicol™; Bard, Murray Hill, NJ, USA) in the management of female stress urinary incontinence (SUI). PATIENTS AND METHODS: A multicentre randomised controlled trial carried out in four UK centres from 2001 to 2006 involving 201 women requiring primary surgery for SUI. The women were randomly assigned to receive TVT, AFS or Pelvicol. The primary outcome was surgical success defined as 'women reporting being completely 'dry' or 'improved' at the time of follow-up'. The secondary outcomes included 'completely dry' rates, changes in the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) and EuroQoL EQ-5D questionnaire scores. RESULTS: In all, 162 (80.6%) women were available for follow-up with a median (range) duration of 10 (6.6-12.6) years. 'Success' rates for TVT, AFS and Pelvicol were 73%, 75.4% and 58%, respectively. Comparing the 1- and 10-year 'success' rates, there was deterioration from 93% to 73% (P < 0.05) in the TVT arm and 90% to 75.4% (P < 0.05) in the AFS arm; 'dry' rates were 31.7%, 50.8% and 15.7%, respectively. Overall, the 'dry' rates favoured AFS when compared with Pelvicol (P < 0.001) and TVT (P = 0.036). The re-operation rate for persistent SUI was 3.2% (two patients) in the TVT arm, 13.1% (five) in the Pelvicol arm, while none of the patients in the AFS arm required further intervention. CONCLUSIONS: Our study indicates there is not enough evidence to suggest a difference in long-term success rates between AFS and TVT. However, there is some evidence that 'dry' rates for AFS may be more durable than TVT.

Chapter 4: Guidelines for the diagnosis and treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO).

This chapter focuses on the position of botulinum toxin type A in the treatment pathway for overactive bladder (OAB) and neurogenic lower urinary tract dysfunction associated with neurogenic detrusor overactivity (NDO), and the recommendations of the major international guideline groups. Recommendations of different guideline groups may vary, especially when evidence is weak, often because of differences in methodology and panel composition. Relevant guidelines from the European Association of Urology, American Urological Association, and the UK National Institute for Care and Clinical Excellence were reviewed, and the recommendations that form the basis of the treatment algorithms have been discussed. Any differences between guidelines have been highlighted and special emphasis made on the position of botulinum toxin type A in these pathways. In all the reviewed guidelines, botulinum toxin type A is recommended, alongside sacral nerve neuromodulation, to treat OAB and NDO in patients who have failed oral therapy. The evidence base is consistent, but further evidence is required regarding optimal dosing regimens and injection technique.

A proof-of-concept study: mirabegron, a new therapy for overactive bladder.

AIMS: To evaluate the potential of mirabegron, a selective ß3-adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms. METHODS: A multicenter, randomized, double-blind, double-dummy, parallel group, placebo and active-controlled, Phase 2, proof-of-concept study was conducted. Eligible patients (n = 314) were enrolled into a single-blind, 2-week placebo run-in period followed by a randomized, double-blind, placebo-controlled treatment period. Patients received mirabegron 100 or 150 mg twice-daily (BID), placebo or tolterodine 4 mg extended release (ER) once-daily for 4 weeks. Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24 hr. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes per 24 hr; severity of urgency; nocturia, and quality of life measures. Safety parameters included adverse events, laboratory tests, electrocardiogram parameters and post-void residual volume. RESULTS: Mirabegron 100 and 150 mg BID resulted in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency (2.2 micturitions/24 hr vs. 1.2 micturitions/24 hr for both doses, adjusted P ≤ 0.01 for both comparisons). Mirabegron had a statistically significant effect versus placebo for most secondary endpoints, including quality of life variables. Despite a small increase in pulse rate, mirabegron demonstrated good safety and tolerability. CONCLUSIONS: Mirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years.

Assessing professional equipoise and views about a future clinical trial of invasive urodynamics prior to surgery for stress urinary incontinence in women: a survey within a mixed methods feasibility study.

AIMS: To determine surgeons' views on invasive urodynamic testing (IUT) prior to surgery for stress (SUI) or stress predominant mixed urinary incontinence (MUI). METHODS: Members of British Society of Urogynaecology (BSUG) and British Association of Urological Surgeons Section of Female, Neurological and Urodynamic Urology (BAUS-SFNUU) were sent an email invitation to complete an online "SurveyMonkey®" questionnaire regarding their current use of IUT prior to surgical treatment of SUI, their view about the necessity for IUT in various clinical scenarios, and their willingness to randomize patients into a future trial of IUT. A purposive sample of respondents was invited for telephone interview to explore further how they use IUT to inform clinical decisions, and to contextualize questionnaire responses. RESULTS: There were 176/517 (34%) responses, 106/332 (32%) from gynecologists/urogynecologists and 67/185 (36%) from urologists; all respondents had access to IUT, and 89% currently arrange IUT for most women with SUI or stress predominant MUI. For a variety of scenarios with increasingly complex symptoms the level of individual equipoise ("undecided" about IUT) was very low (1-6%) and community equipoise was, at best, 66:34 (IUT "essential" vs. "unnecessary") even for the simplest scenario. Nevertheless, 70% rated the research question underlying the proposed studies "very important" or "extremely important;" 60% recorded a "willingness to randomize" score ≥8/10. CONCLUSIONS: Most urogynecologists and urologists consider IUT essential before surgery in SUI with or without other symptoms. Most however recognize the need for further research, and indicated a willingness to recruit into multicenter trials addressing this question.

EAU guidelines on surgical treatment of urinary incontinence.

CONTEXT: The European Association of Urology (EAU) guidelines on urinary incontinence published in March 2012 have been rewritten based on an independent systematic review carried out by the EAU guidelines panel using a sustainable methodology. OBJECTIVE: We present a short version here of the full guidelines on the surgical treatment of patients with urinary incontinence, with the aim of dissemination to a wider audience. EVIDENCE ACQUISITION: Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches based on Population, Intervention, Comparator, Outcome (PICO) questions. The appraisal of papers was carried out by an international panel of experts, who also collaborated in 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 guidance is available online (www.uroweb.org/guidelines/online-guidelines/). The guidance includes algorithms that refer the reader back to the supporting evidence and have greater accessibility in daily clinical practice. Two original meta-analyses were carried out specifically for these guidelines and are included in this report. 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 high-level evidence is lacking, they present a consensus of expert panel opinion.

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.

Applicability of a disposable home urinary flow measuring device as a diagnostic tool in the management of males with lower urinary tract symptoms.

INTRODUCTION: To investigate the accuracy of uroflowmetry with disposable Q(Single) compared to measurements with a home-based digital device and compared to a single clinical measurement. PATIENTS AND METHODS: 60 men with lower urinary tract symptoms were included in a prospective, open-label, multicenter study. Uroflowmetry measurements were done using three devices/methods: single clinic-based method, followed by up to 12 measurements using the disposable home-based Q(Single) and up to 12 measurements using a home-based digital device. Subjective data on ease of use of Q(Single) and preference of patients was investigated and objective measures of Q(max) and voided volume from the three devices were compared. RESULTS: Mean Q(max) values of 12, 13 and 16 ml/s were achieved with the Q(Single) device, standard clinic method, and digital device, respectively. Mean Q(max) obtained with the Q(Single) device did not differ from that obtained with the clinic method. A significantly higher mean Q(max) was recorded for the digital device. Mean voided volumes recorded with each device differed marginally. Handling capabilities of the Q(Single) device were considered good by all subjects. CONCLUSIONS: The accuracy of Q(max) and voided volume mean measurements with Q(Single) was comparable to one standard clinic recording. Q(Single) offers a viable alternative to reduce the number of clinic visits and can be used by other caregivers.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing.

BACKGROUND: Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness.The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. METHODS/DESIGN: This is a mixed methods pragmatic multicentre feasibility pilot study with four components:-(a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial.(b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience.(c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial.(d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. DISCUSSION: The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN71327395 assigned 7th June 2010.

Selection criteria for the radical treatment of locally advanced rectal cancer.

There are over 14,000 newly diagnosed rectal cancers per year in the United Kingdom of which between 50 and 64 percent are locally advanced (T(3)/T(4)) at presentation. Pelvic exenterative surgery was first described by Brunschwig in 1948 for advanced cervical cancer, but early series reported high morbidity and mortality. This approach was later applied to advanced primary rectal carcinomas with contemporary series reporting 5-year survival rates between 32 and 66 percent and to recurrent rectal carcinoma with survival rates of 22-42%. The Swansea Pelvic Oncology Group was established in 1999 and is involved in the assessment and management of advanced pelvic malignancies referred both regionally and UK wide. This paper will set out the selection, assessment, preparation, surgery, and outcomes from pelvic exenterative surgery for locally advanced primary rectal carcinomas.

Minimum standards for urodynamic practice in the UK.

AIM: This paper reports on the recent publication and wide distribution of a joint statement on minimum standards for urodynamic practice in the UK. METHODS: A multidisciplinary working party were tasked with creating standards for both training and certification in urodynamics, as well as explicit standards for a framework of service delivery. This was done through a process of extensive consultation with relevant professional bodies. RESULTS: The standards suggest a modular structure to urodynamics training, and make recommendations on minimum workload for individuals and departments, the need for multidisciplinary team working and for regular audit. CONCLUSIONS: This is the first attempt to standardise urodynamics practice nationally. The document is available on the United Kingdom Continence Society websitewww.ukcs.uk.net.

Management of male urinary incontinence.

The majority of male urinary incontinence seen is secondary to sphincter weakness following prostatic surgery. As there is a rising elderly population and increasing numbers of surgical interventions for prostate cancer, incidence of male incontinence is increasing. Hence, management of male incontinence has become a subject of increased interest for urologists. Various non-surgical and surgical approaches have been suggested for this devastating condition. Non-invasive therapies are suggested for early postoperative and mild incontinence. For surgical treatment the artificial urinary sphincter is still labeled the gold standard despite the introduction of several more minimally invasive treatments. However, as yet there is no consensus on the optimal timing and best modality for managing these men. Well designed, centrally funded clinical trials are required to establish which treatment modality to offer and when in the broad spectrum of male incontinence. This review focuses mainly on the management of post-prostatectomy incontinence since the management of other types varies little from the modalities of treatment in women.

Do nonautologous biological slings have a future?

PURPOSE OF REVIEW: The purpose of this paper is to review the literature published during 2005 on nonautologous biological slings for the treatment of stress urinary incontinence. RECENT FINDINGS: Little has been done by the way of research to assess adequately whether nonautologous biological slings perform better or worse than other types of slings. Three cohort studies and two comparative studies have been reported, but no randomized controlled trials have been published during the last year comparing biological slings with synthetic slings. Sporadic reports of unexpectedly high recurrent stress incontinence rates with some biological slings have come into light. SUMMARY: Nonautologous biological slings are safe and simple to implant. Long-term outcomes, however, remain uncertain. A risk of complete failure is possible.

Tamsulosin in the management of patients in acute urinary retention from benign prostatic hyperplasia.

OBJECTIVE: To evaluate the efficacy of tamsulosin compared to placebo for treating catheterized patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH), by comparing the numbers of patients who voided successfully after removing their catheter. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study. Men with AUR secondary to BPH were catheterized and then, if they fulfilled the entry criteria, were randomly assigned to receive either 0.4 mg tamsulosin hydrochloride in a modified-release capsule once daily, or a placebo. After up to eight doses the catheter was removed and the ability to void unaided assessed. RESULTS: In all, 149 men (mean age 69.4 years) were randomly assigned to receive tamsulosin (75) or placebo (74); eight were not evaluable, so the intent-to-treat population was 141 men. Thirty-four men taking tamsulosin and 18 taking placebo did not require re-catheterization on the day of the trial without catheter (48% and 26% respectively, P = 0.011; odds ratio 2.47, 95% confidence interval, CI, 1.23-4.97). Success using free-flow variables was also higher in the men who received tamsulosin, at 37 (52%) vs 24 (34%) on placebo (P = 0.019; odds ratio 2.34, 95% CI 1.15-4.75). Withdrawals were high (120 men, 81%), mostly because of a need for re-catheterization (89 men, 60%). Dizziness and somnolence occurred in seven (10%) and four (6%) men who received tamsulosin, and two (3%) who received placebo, but overall the incidence of adverse events was similar in the two groups. One patient died from carcinomatosis. CONCLUSION: Men catheterized for AUR can void more successfully after catheter removal if treated with tamsulosin, and are less likely to need re-catheterization. The side-effect profile was similar for tamsulosin and placebo, and consistent with known pharmacology. From these results tamsulosin can be recommended for treating men after catheterization for AUR, and can reduce the likelihood of the need for re-catheterization.