Interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women.

BACKGROUND: Surgery is a common treatment modality for stress urinary incontinence (SUI), usually offered to women for whom conservative treatments have failed. Midurethral tapes have superseded colposuspension because cure rates are comparable and recovery time is reduced. However, some women will not be cured after midurethral tape surgery. Currently, there is no consensus on how to manage the condition in these women.This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To assess the effects of interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women; and to summarise the principal findings of economic evaluations of these interventions. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 9 November 2018). We also searched the reference lists of relevant articles. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials in women who had recurrent stress urinary incontinence after previous minimally invasive midurethral tape surgery. We included conservative, pharmacological and surgical treatments. DATA COLLECTION AND ANALYSIS: Two review authors checked the abstracts of identified studies to confirm their eligibility. We obtained full-text reports of relevant studies and contacted study authors directly for additional information where necessary. We extracted outcome data onto a standard proforma and processed them according to the guidance in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included one study in this review. This study was later reported in an originally unplanned secondary analysis of 46 women who underwent transobturator tape for recurrent SUI after one or more previous failed operations. We were unable to use the data, as they were not presented according to the nature of the first operation.We excluded 12 studies, five because they were not randomised controlled trials (RCTs) and four because previous incontinence surgery was not performed using midurethral tape. We considered a further three to be ineligible because neither the trial report nor personal communication with the trialists could confirm whether any of the participants had previously undergone surgery with tape.We had also planned to develop a brief economic commentary summarising the principal findings of relevant economic evaluations but supplementary systematic searches did not identify any such studies. AUTHORS' CONCLUSIONS: There were insufficient data to assess the effects of any of the different management strategies for recurrent or persistent stress incontinence after failed midurethral tape surgery. No published papers have reported exclusively on women whose first operation was a midurethral tape. Evidence from further RCTs and economic evaluations is required to address uncertainties about the effects and costs of these treatments.

Surgery for recurrent stress urinary incontinence: the views of surgeons and women.

INTRODUCTION AND HYPOTHESIS: The objectives were to explore the views of women with recurrent stress incontinence (SUI) with regard to treatment preferences and the acceptability of randomisation to a future trial, and to survey the views of UK specialists on treatment preferences and equipoise regarding different treatment alternatives. METHODS: An online survey of the British Society of Urogynaecology (BSUG) and British Society of Urological Surgeons (BAUS) was carried out. Qualitative semi-structured interviews with a purposive sample of surgeons and women suffering from recurrent SUI from three UK centres. RESULTS: Two hundred fifty-six survey replies were received (176 gynaecology; 80 urology). Comparing the treatments offered, urogynaecologists were more likely to offer pelvic floor exercises (p < 0.05), and repeat midurethral tape (MUT) (p < 0.001). From the Surgical Equipoise Scale (SES) responses, "no preference" was rarely the commonest response. Marked differences for several options existed; midurethral tape dominated responses whenever it appeared. Twenty-one clinicians were interviewed. Treatment preferences were complex, influenced by a range of factors (reason for failure, patient comorbidity, investigations, personal experience, training). A future trial was regarded as important. Eleven women were interviewed. Most had considered more than one option, but felt that decision-making was more a process of elimination rather than a positive process. Randomisation to a study was regarded as unacceptable by most. CONCLUSIONS: No consensus exists among surgeons about preferred treatment options for recurrent SUI, and personal experience and training dominate decision-making. For patients, choices were usually based on an elimination of options, including that of a repeat failed procedure. This contrasts with surgeons, who mostly preferred a repeat MUT above other options. Any future comparative study will be challenging.

Trends in the aetiology of urogenital fistula: a case of 'retrogressive evolution'?

It has long been held as conventional wisdom that urogenital fistulae in low-income and middle-income countries are almost exclusively of obstetric aetiology, related to prolonged neglected obstructed labour, whereas those seen in high-income countries are largely iatrogenic in nature. There is, however, a growing perception amongst those working in the field that an increasing proportion of urogenital fistulae in low-income and middle-income countries may be iatrogenic, resulting from caesarean section. Recent studies suggest that adverse patterns of care may also be emerging in high-income countries; an increase in the risk of both vesicovaginal and ureterovaginal fistulae following hysterectomy has been reported, concurrently with the reduction in overall use of the procedure. These apparent secular trends are discussed in the context of evolution of practice, teaching and training in obstetrics and gynaecology.

The "learning curve" for retropubic mid-urethral sling procedures: a retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Mid-urethral tape procedures brought a paradigm shift in surgery for stress incontinence; little research into the development and maintenance of surgical competence for the procedure exists. The hypothesis behind this study is that the "learning curve" for retropubic mid-urethral sling procedures, judged by the surrogate of bladder perforation, is longer than previously thought. METHODS: This was a retrospective single-centre database and case note review of retropubic mid-urethral tape procedures. Unadjusted rates of bladder perforation, operating time, postoperative voiding difficulty, tape extrusion, and patient reported outcome were calculated; progress was evaluated using the cumulative sum method. Outcomes were assessed for 1 consultant, 2 subspecialty trainees (fellows), 7 advanced training skills module (ATSM) trainees (senior residents) and 6 core specialty trainees (residents) in years 4-7 of training. RESULTS: A total of 1,568 women were identified as having mid-urethral tape procedures; 568 (36 %) had additional procedures concurrently; 259 (20 %) were secondary procedures. The overall perforation rate for individual surgeons varied between 0 and 31 % and averaged 10.3 % amongst the core and ATSM trainees (a mean of 11 procedures), 4.5 % amongst the subspecialty trainees (a mean of 66 procedures) and 1.3 % for the consultant (1,284 procedures). The number of perforations for individual surgeons peaked at between 10 and 30 procedures undertaken. The number of cases performed to reach a target level of ≤ 5 % perforations varied between 20 and 80. CONCLUSIONS: Whilst seductively simple in concept, mid-urethral tape procedures are not without risk; their inherently "blind" nature makes them difficult to teach. The "learning curve" to independent practice may be longer than previously considered.

Trial participation as avoidance strategy: a qualitative study.

BACKGROUND: Trial participation decisions are often influenced by expectations of potential benefit. Attention has focused on trial participation as a means of securing something seen as desirable, such as experimental treatment. In contrast, we consider a case in which one trial arm involved receiving less than usual care. We explore how this influenced participants' decisions to participate. METHODS: Semi-structured interviews with 29 women participating in a pilot trial comparing invasive urodynamic testing (typically normal care) to basic clinical assessment with non-invasive tests, prior to surgical treatment for stress urinary incontinence. Analysis was based on the constant comparative method. RESULTS: Invasive tests were something many were aware of and worried about. Participants understood that trial participation meant they might avoid having these tests, and for about one-third, this was the primary factor motivating participation. A further third mentioned they were not looking forward to tests (if allocated to them) or were lucky to have missed them (if allocated to basic clinical assessment). None of the women appeared to have discussed their desire to avoid having invasive tests with their clinicians. CONCLUSIONS: In contrast to cases in which trial participation is motivated by the wish to secure an intervention not otherwise available, this study reports the opposite - trial participation as an opportunity to avoid having something regarded as undesirable. The option to decline a particular intervention should always be available, and care must be taken to ensure that potential participants are aware that trial participation is not the only possible means of avoidance.

Efficacy and duration of response to botulinum neurotoxin A (onabotulinumA) as a treatment for detrusor overactivity in women.

INTRODUCTION AND HYPOTHESIS: Overactive bladder syndrome with urinary incontinence has a number of treatment options. The National Institute for Health and Care Excellence (NICE) in the UK, the American Urological Association (AUA) and the European Association of Urology (EAU) recommend intradetrusor botulinum neurotoxin A (onabotulinumA) injections in women with proven detrusor overactivity (DO) in whom conservative therapies have failed to improve symptoms. However, the effects of individual onabotulinumA treatments are of short duration and patients usually require further treatments. There is little evidence to inform long-term management strategies using onabotulinumA for DO. METHODS: A retrospective review of patients receiving intradetrusor onabotulinumA injections for DO over a 7-year period was conducted. The primary outcome measures included patient's subjective reports of symptom change following injections (efficacy) and the duration of symptomatic relief following each treatment. RESULTS: The analysis included 136 patients. The mean time between patients receiving intradetrusor onabotulinumA and being added to the surgical waiting list for re-treatment varied between 8.5 and 10.4 months for the first five cycles of treatment with the longest time between the third and fourth cycles. This decreased to 5.5 and 5.25 (ANOVA p = 0.015) between the fifth and sixth cycles and between the sixth and seventh cycles of treatment, respectively. Only 19.9% of patients continued treatment beyond this, with four patients receiving a seventh treatment. CONCLUSIONS: Our results suggest that in patients who respond to onabotulinumA treatment, the duration of response declines after the fifth treatment, suggesting a possible tolerance effect and a subsequent decline in efficacy.

Pelvic floor muscle training as an adjunct to prolapse surgery: a randomised feasibility study.

INTRODUCTION AND HYPOTHESIS: There is evidence that in nonsurgical populations, pelvic floor muscle training (PFMT) and lifestyle advice improves symptoms and stage of pelvic organ prolapse (POP). Some women, however, require surgery, after which de novo symptoms can develop or additional surgery is required due to recurrence. Robust evidence is required as to the benefit of perioperative PFMT in the postsurgery reduction of symptoms and POP recurrence. The aim of this study was to assess the feasibility of and collect pilot data to inform sample size (SS) calculation for a multicentre randomised controlled trial (RCT) of perioperative PFMT following surgical intervention for POP. METHODS: Fifty-seven participants were recruited and randomised to a treatment group (one pre and six postoperative PFMT sessions) or a control group (usual care). The primary outcome measure was the Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months; secondary outcome measures included measurement of prolapse, the pelvic floor and questionnaires relating to urinary and bowel incontinence. All outcomes were measured at 0, 6 and 12 months. RESULTS: Information on recruitment, retention and appropriateness of outcome measures for a definitive trial was gathered, and data enabled us to undertake an SS calculation. When compared with the control group (n = 29), benefits to the intervention group (n = 28) were observed in terms of fewer prolapse symptoms at 12 months [mean difference 3.94; 95 % confidence interval (CI) 1.35-6.75; t = 3.24, p = 0.006]; however, these results must be viewed with caution due to possible selection bias. CONCLUSION: With modifications to design identified in this pilot study, a multicentre RCT is feasible.

Retrospective cohort study on patterns of care and outcomes of surgical treatment for lower urinary-genital tract fistula among English National Health Service hospitals between 2000 and 2009.

OBJECTIVES: To examine patterns of care among women with urogenital fistula treated in the English National Health Service (NHS) between 2000 and 2009. To assess whether failure of repair was associated with hospital or surgeon workload. PATIENTS AND METHODS: We conducted a retrospective cohort study using data from Hospital Episode Statistics on women undergoing vesicovaginal or urethrovaginal fistula repair between January 2000 and December 2009 in English NHS hospitals. The main outcome measure was the number of fistula repairs and the incidence of re-repair; re-repair rates were stratified by age, NHS trust and consultant team volume. RESULTS: Between 2000 and 2009, 1194 women underwent surgical repair (n = 905) or ileal conduit (n = 289) for urogenital fistula under the care of 490 consultant teams. A total of 281 teams performed only a single index procedure, and only three consultant teams performed a mean of >3 per year. The rate of unsuccessful repair was 11.9% (108/905). The rate of re-operation at NHS trusts who performed over 30 procedures over the 10-year study period was 7.4% compared with 13.2% at those undertaking fewer (P = 0.02). A similar difference in re-operations between consultant teams performing > or <30 procedures did not reach significance (8.4% v 12.7%, P = 0.13). CONCLUSIONS: One in nine women required re-operation after surgical repair of a urogenital fistula. Our results lend weight to the argument for a 'minimum workload' for fistula management; given the number of fistulae occurring in England currently, this would best be provided by a network of supra-regional centres.

Treatment of recurrent stress urinary incontinence after failed minimally invasive synthetic suburethral tape surgery in women.

BACKGROUND: Surgery is a common treatment modality for stress urinary incontinence (SUI), usually offered for women who fail conservative treatments. Suburethral tapes have superseded colposuspension because cure rates are comparable and recovery time reduced. However, some women will not be cured after suburethral tape surgery, and currently there is no consensus on how to manage these women. OBJECTIVES: To obtain and examine evidence supporting different management strategies for recurrent/persistent stress urinary incontinence (SUI) in women after failed suburethral tape surgery. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register of controlled trials (searched 18 December 2012), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and PreMEDLINE; and handsearched journals and conference proceedings, and the reference lists of included studies and previous Cochrane reviews for randomised or quasi-randomised studies treating patients with recurrent incontinence, either as the sole population or a subset. Conservative, medical and surgical treatments were included. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials in women who had recurrent urinary incontinence after previous minimally invasive suburethral tape surgery. DATA COLLECTION AND ANALYSIS: Abstracts of identified studies were checked by two authors to confirm eligibility. Full text reports of relevant studies were obtained, and authors were contacted directly where necessary. Outcome data were extracted onto a standard proforma and processed according to the methods in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: Twelve studies were identified, but all were excluded because they did not meet the eligibility criteria. Six were randomised controlled trials (RCTs) but were not eligible because the previous incontinence surgery was not a suburethral tape. A subset of one RCT may have been eligible for inclusion because some of the women were having repeat surgery, but we were unable to obtain from the authors the data according to primary surgery for this cohort. AUTHORS' CONCLUSIONS: There were no data to recommend or refute any of the different management strategies for recurrent or persistent stress incontinence after failed suburethral tape surgery. Evidence is urgently required to address this deficiency, ideally from RCTs.

Interventions for treating obstetric fistula: An evidence gap map.

Obstetric fistula is prevalent in low- and middle-income countries, with between 50,000 and 100,000 new cases each year. The World Health Organization aims to eradicate it by 2030 but a clear idea of the extant evidence is unavailable. This evidence map compiled evidence on treatments for obstetric fistula to identify potential knowledge gaps. The protocol for this work was published on the Open Science Framework (DOI: 10.17605/OSF.IO/H7J35). A survey was developed, piloted and distributed online through organisations with an interest in obstetric fistula and snowballing. Results informed the evidence map framework. Searches were run on MEDLINE, Embase, CENTRAL, Global Index Medicus and ScanMedicine on 16 February 2022 to identify potentially eligible systematic reviews, randomised controlled trials, cohort studies and case-control studies. Forward and backward citation chaining was undertaken on relevant systematic reviews and included studies. Studies were screened, coded and assessed for risk of bias by a single reviewer, with a second checking a proportion. The evidence map results were compared to survey results. Thirty-nine people responded to the survey, half of which were clinicians. Of 9796 records identified, 37 reports of 28 studies were included in the evidence map. Many included studies were at some risk of bias; for observational studies, this was predominantly due to lack of controlling for confounders. Most studies (71%) assessed surgical interventions alone. Reporting on other intervention types was limited. Regarding outcome measures most important to survey respondents, 24 studies reported on cure/improvement in obstetric fistula and 20 on cure/improvement in urinary incontinence. Reporting on quality of life, faecal incontinence and sexual function was limited. There is currently little robust evidence to guide patients and practitioners on the most effective treatment option for obstetric fistula. Further research is required to address evidence gaps identified.

Urogenital fistula in the UK: a personal case series managed over 25 years.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Whilst several very large series of obstetric fistulae from the developing world have been published, data on fistulae as seen in the developed world are relatively few. Most fistulae in the UK are known to follow hysterectomy, and several risk factors are recognised. We have confirmed the common association with pelvic surgery, and in particular hysterectomy, but also show the broad range of other associated operations, including so called 'minimally invasive' procedures. High rates of both anatomical fistula closure and continence are shown, when a consistent approach to assessment, selection of surgical procedure, and postoperative care are applied. Successful closure is seen more often in women who have not undergone previous attempts at repair before referral, and as a result a pattern of surpra-regional management is proposed. Whilst overall the number of urogenital fistulae seen in the UK appears to be decreasing, there is a suggestion from these data that the rate of fistula formation following hysterectomy may be increasing; we are currently investigating this possibility through detailed interrogation of a national dataset. OBJECTIVE: To review demography, aetiology, surgery and outcomes of women with urogenital fistula seen in one unit over the last 25 years; to provide data for comparison with a parallel study based on Hospital Episode Statistics. PATIENTS AND METHODS: This is a prospective case series from a tertiary urogynaecology centre providing a de facto supra-regional fistula service. The women included had confirmed urogenital fistula referred between January 1986 and December 2010. Index cases were identified from a surgical database; data were entered prospectively and updated as appropriate; statistics are largely descriptive. The primary outcome is the patient's report of absence of urinary leakage. Secondary outcomes include operative or postoperative complications, anatomical closure of the fistula, other residual or new urinary symptoms, and the need for further intervention. RESULTS: In all, 348 women with urogenital fistula were referred; two-thirds were of surgical aetiology, with almost half following hysterectomy. Although 11% followed childbirth, most of these followed operative obstetric interventions. Spontaneous closure occurred in 6.9% of women and 291 underwent surgical treatment. The anatomical closure rate at first operation was 95.7%, although 2.2% reported residual urinary incontinence. The success rates were similar regardless of aetiology, although successful fistula closure was significantly more likely in women who had not had attempts at closure before referral (98.2 vs 88.2%; Fisher's exact test; P= 0.003). CONCLUSION: High rates of fistula closure are reported regardless of aetiology, although previous unsuccessful repair militates against successful outcome; this emphasises the appropriateness of centralisation of the management of this increasingly rare condition in UK practice.

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.

Mullerianosis involving the urinary bladder.

We report a case of mullerianosis involving the urinary bladder. A 45-year-old woman presented with complaints of chronic pelvic pain, dysmenorrhoea, irritative lower urinary tract symptoms and cyclical haematuria. Cystoscopy and transurethral biopsy suggested mullerianosis involving the posterior bladder wall; she subsequently had surgery including partial cystectomy with complete excision of the lesion. Histology reported presence of endometrial, endocervical and endosalpingeal tissues within the bladder mass confirming mullerianosis. She made satisfactory postoperative recovery. Awareness of this lesion is necessary for proper diagnosis and appropriate treatment.

Defining cure.

This paper is a summary of the presentations made as Proposal 2-"Defining cure" to the 2nd Annual meeting of the ICI-Research Society, in Bristol, 16th June 2010. It reviews definitions of 'cure' and 'outcome', and considers the impact that varying definition may have on prevalence studies and cure rates. The difference between subjective and objective outcomes is considered, and the significance that these different outcomes may have for different stakeholders (e.g. clinicians, patients, carers, industry etc.) is discussed. The development of patient reported outcome measures and patient defined goals is reviewed, and consideration given to the use of composite end-points. A series of proposals are made by authors and discussants as to how currently validated outcomes should be applied, and where our future research activity in this area might be directed.

Constructing trials to show whether urodynamic studies are necessary in lower urinary tract dysfunction.

AIMS: This report reviews the evidence for the utility of urodynamic studies (UDS) in lower urinary tract dysfunction and tries to identify the necessity of constructing trials to show whether UDS are necessary. METHODS: An outline for a think tank discussion was prepared by the chairman of the session. Several experts selected relevant papers from a literature review of the Pubmed/Medline database (January 1966 to August 2010) and prepared a presentation of the evidence for the utility of UDS in the evaluation of several conditions, the prediction of treatment outcome, the prediction of complications and/or cost-effectiveness. The following conditions were considered: urinary incontinence, symptoms suggestive of benign prostatic obstruction (LUTS/BPO), overactive bladder (OAB) and urogenital prolapse. Summary presentations were discussed by a large group of opinion leaders and experts and audio-recorded. The proceedings of this process are the basis for this manuscript. RESULTS: The structured sessions resulted in detailed statements about the existing evidence for the utility of UDS in men after radical prostatectomy, men with uncomplicated LUTS/BPO, patients with OAB, female stress urinary incontinence (SUI) and urogenital prolapse. CONCLUSIONS: UDS should be used for investigation of new treatment modalities and establishment of diagnoses whenever they are in doubt. UDS do not appear to be necessary before pelvic floor muscle training, medical treatment of LUTS/BPO or OAB, surgical treatment of primary female SUI or prolapse. RCT's with non-inferiority design should be conducted to investigate UDS in patients before surgical treatment of the prostate, SUI or OAB.

Obstetric risk factors and pelvic floor dysfunction 20 years after first delivery.

INTRODUCTION AND HYPOTHESIS: Intrapartum events at first delivery and subsequent childbearing are associated with long-term pelvic floor dysfunction (PFD). METHODS: Primigravidae delivered between 1983-1986 were identified; current addresses traced through the UK National Health Service database (N = 3002). Women completed screening and Sheffield Pelvic Floor Questionnaires (Sheffield-PAQ). Maternity data were obtained from Standard Maternity Information System. Primary outcomes were urinary incontinence (UI), anal incontinence (AI), and prolapse (POP). RESULTS: Primary response was 62.1%; 53.8% (n = 985) had >or=1 PFD symptom and in 71.5% symptoms were bothersome. UI (OR 0.47 95% CI 0.28, 0.81) and fecal incontinence (FI; OR 0.32 95% CI 0.13, 0.77) risks were lower after first delivery by cesarean section (CS). However, 25% had UI and 12% had FI after delivering exclusively by CS. Obesity was a risk factor independent of obstetric history. CONCLUSIONS: CS provides incomplete or poorly sustained pelvic floor protection by middle age. Obese women were at highest risk and had the most severe symptoms.

RCT of urethral versus suprapubic catheterization.

OBJECTIVE: To compare the use of intermittent urethral catheterization with indwelling suprapubic catheterization in women undergoing surgery for urodynamic stress incontinence or uterovaginal prolapse. DESIGN: Randomized controlled trial. SETTING: Tertiary referral urogynaecology unit. POPULATION: Women undergoing surgery for pelvic organ prolapse and/or stress urinary incontinence. METHODS: Women were randomized into one of two groups. Group 1 had bladder drainage using a suprapubic catheter inserted in theatre. The catheter was left on free drainage for 48 hours post-operatively before clamping. Group 2 was catheterized intermittently post-operatively. MAIN OUTCOME MEASURES: Length of post-operative hospital stay: time to resume normal voiding (defined as voided volumes greater than 200 mls and residual urine volumes less than 100 mls on three occasions); number of urinary tract infections (UTIs); catheterization costs; patient experience (determined from questionnaire); and a pain score. RESULTS: 75 women were randomized; 38 to suprapubic catheterization; 37 to intermittent catheterization. Three were withdrawn from study, leaving 36 women in each group. Groups were closely matched for age and type of surgery undertaken. Length of hospital stay and total duration of catheterization were both significantly shorter for the intermittent catheterization group; although there was no difference in the rate of UTI between the two groups. There was no clear patient preference for a specific catheterization method. CONCLUSIONS: The use of intermittent catheterization following urogynaecological surgery is associated with a more rapid return to normal micturition and a shorter hospital stay, although the clinical significance of the difference is perhaps limited.

Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin.

The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic Escherichia coli (UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate, in vitro, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with E.coli flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17ß-estradiol (E) for seven days, 50 ng/ml E.coli flagellin (F) for 12 h, or 4 nM 17ß-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including DEFß4A, DEFB103A, LCN2 as well as those associated with keratinisation eg CNFN and SPRR family genes were significantly enhanced (P < 0.05) compared to either E or F treatments alone. Mutation of estrogen responsive elements (EREs) identified in the DEFß4 gene promoter abolished the augmented gene expression suggesting estrogen functioned directly through a regulatory mechanism involving ESR1/2. Ingenuity pathway analyses also suggested the pro-inflammatory cytokine IL-17A to regulate the vaginal host defences during infection. Pre-treating VK2 E6/E7 cells with estrogen (4 nM) and challenging with 1L-17A & F (12 h) significantly enhanced DEFß4, DEF103A and S100A7 expression (P < 0.05). Origins of vaginal IL-17 in vivo remain unclear, but patient biopsies support γδ T cells located within the vaginal epithelium. These data suggest that the vaginal antimicrobial response induced by flagellin activation of Toll-like Receptor 5 cell signalling is augmented following topical estrogen application.