UK National Institute of Health Research.

Wellbeing of Women charity, the New Zealand Continence Association, and the Dean's Bequest Fund of Dunedin School of Medicine.

BackgroundThe use of mesh in prolapse surgery is controversial, leading to a number of enquiries into its safety and efficacy.ObjectiveTo compare synthetic non-absorbable mesh inlay, biological graft and mesh kit with a standard repair in terms of clinical effectiveness, adverse effects, quality of life (QoL), costs and cost-effectiveness.DesignTwo randomised controlled trials within a comprehensive cohort (CC) study. Allocation was by a remote web-based randomisation system in a 1 :1 : 1 ratio (Primary trial) or 1 : 1 : 2 ratio (Secondary trial), and was minimised on age, type of prolapse repair planned, need for a concomitant continence procedure, need for a concomitant upper vaginal prolapse procedure and surgeon. Participants and outcome assessors were blinded to randomisation; participants were unblinded if they requested the information. Surgeons were not blinded to allocated procedure.SettingThirty-five UK hospitals.ParticipantsPrimary study: 2474 women in the analysis (including 1348 randomised) having primary anterior or posterior prolapse surgery.Secondary study: 398 in the analysis (including 154 randomised) having repeat anterior or posterior prolapse surgery.CC3: 215 women having either uterine or vault prolapse repair.InterventionsAnterior or posterior repair alone, or with mesh inlay, biological graft or mesh kit.Main outcome measuresProlapse symptoms [Pelvic Organ Prolapse Symptom Score (POP-SS)]; prolapse-specific QoL; cost-effectiveness [incremental cost per quality-adjusted life-year (QALY)].ResultsPrimary trials: adjusting for baseline and minimisation covariates, mean POP-SS was similar for each comparison {standard 5.4 [standard deviation (SD) 5.5] vs. mesh 5.5 (SD 5.1), mean difference (MD) 0.00, 95% confidence interval (CI) –0.70 to 0.71; standard 5.5 (SD 5.6) vs. graft 5.6 (SD 5.6), MD –0.15, 95% CI –0.93 to 0.63}. Serious non-mesh adverse effects rates were similar between the groups in year 1 [standard 7.2% vs. mesh 7.8%, risk ratio (RR) 1.08, 95% CI 0.68 to 1.72; standard 6.3% vs. graft 9.8%, RR 1.57, 95% CI 0.95 to 2.59]. There were no statistically significant differences between groups in any other outcome measure. The cumulative mesh complication rates over 2 years were 2 of 430 (0.5%) for standard repair (trial 1), 46 of 435 (10.6%) for mesh inlay and 2 of 368 (0.5%) for biological graft. The CC findings were comparable. Incremental costs were £363 (95% CI –£32 to £758) and £565 (95% CI £180 to £950) for mesh and graft vs. standard, respectively. Incremental QALYs were 0.071 (95% CI –0.004 to 0.145) and 0.039 (95% CI –0.041 to 0.120) for mesh and graft vs. standard, respectively. A Markov decision model extrapolating trial results over 5 years showed standard repair had the highest probability of cost-effectiveness, but results were surrounded by considerable uncertainty.Secondary trials: there were no statistically significant differences between the randomised groups in any outcome measure, but the sample size was too small to be conclusive. The cumulative mesh complication rates over 2 years were 7 of 52 (13.5%) for mesh inlay and 4 of 46 (8.7%) for mesh kit, with no mesh exposures for standard repair.ConclusionsIn women who were having primary repairs, there was evidence of no benefit from the use of mesh inlay or biological graft compared with standard repair in terms of efficacy, QoL or adverse effects (other than mesh complications) in the short term. The Secondary trials were too small to provide conclusive results.LimitationsWomen in the Primary trials included some with a previous repair in another compartment. Follow-up is vital to identify any long-term potential benefits and serious adverse effects.Future workLong-term follow-up to at least 6 years after surgery is ongoing to identify recurrence rates, need for further prolapse surgery, adverse effects and cost-effectiveness.TriaI registrationCurrent Controlled Trials ISRCTN60695184.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 95. See the NIHR Journals Library website for further project information.

Background New surgical approaches for apical prolapse have gradually been introduced, with few prospective randomised controlled trial data to evaluate their safety and efficacy compared with traditional methods. Objective To compare surgical uterine preservation with vaginal hysterectomy in women with uterine prolapse and abdominal procedures with vaginal procedures in women with vault prolapse in terms of clinical effectiveness, adverse events, quality of life and cost-effectiveness. Design Two parallel randomised controlled trials (i.e. Uterine and Vault). Allocation was by remote web-based randomisation (1 : 1 ratio), minimised on the need for concomitant anterior and/or posterior procedure, concomitant incontinence procedure, age and surgeon. Setting UK hospitals. Participants Uterine trial – 563 out of 565 randomised women had uterine prolapse surgery. Vault trial – 208 out of 209 randomised women had vault prolapse surgery. Interventions Uterine trial – uterine preservation or vaginal hysterectomy. Vault trial – abdominal or vaginal vault suspension. Main outcome measures The primary outcome measures were women’s prolapse symptoms (as measured using the Pelvic Organ Prolapse Symptom Score), prolapse-specific quality of life and cost-effectiveness (as assessed by incremental cost per quality-adjusted life-year). Results Uterine trial – adjusting for baseline and minimisation covariates, the mean Pelvic Organ Prolapse Symptom Score at 12 months for uterine preservation was 4.2 (standard deviation 4.9) versus vaginal hysterectomy with a Pelvic Organ Prolapse Symptom Score of 4.2 (standard deviation 5.3) (mean difference –0.05, 95% confidence interval –0.91 to 0.81). Serious adverse event rates were similar between the groups (uterine preservation 5.4% vs. vaginal hysterectomy 5.9%; risk ratio 0.82, 95% confidence interval 0.38 to 1.75). There was no difference in overall prolapse stage. Significantly more women would recommend vaginal hysterectomy to a friend (odds ratio 0.39, 95% confidence interval 0.18 to 0.83). Uterine preservation was £235 (95% confidence interval £6 to £464) more expensive than vaginal hysterectomy and generated non-significantly fewer quality-adjusted life-years (mean difference –0.004, 95% confidence interval –0.026 to 0.019). Vault trial – adjusting for baseline and minimisation covariates, the mean Pelvic Organ Prolapse Symptom Score at 12 months for an abdominal procedure was 5.6 (standard deviation 5.4) versus vaginal procedure with a Pelvic Organ Prolapse Symptom Score of 5.9 (standard deviation 5.4) (mean difference –0.61, 95% confidence interval –2.08 to 0.86). The serious adverse event rates were similar between the groups (abdominal 5.9% vs. vaginal 6.0%; risk ratio 0.97, 95% confidence interval 0.27 to 3.44). The objective anterior prolapse stage 2b or more was higher in the vaginal group than in the abdominal group (odds ratio 0.38, 95% confidence interval 0.18 to 0.79). There was no difference in the overall prolapse stage. An abdominal procedure was £570 (95% confidence interval £459 to £682) more expensive than a vaginal procedure and generated non-significantly more quality-adjusted life-years (mean difference 0.004, 95% confidence interval –0.031 to 0.041). Conclusions Uterine trial – in terms of efficacy, quality of life or adverse events in the short term, no difference was identified between uterine preservation and vaginal hysterectomy. Vault trial – in terms of efficacy, quality of life or adverse events in the short term, no difference was identified between an abdominal and a vaginal approach. Future work Long-term follow-up for at least 6 years is ongoing to identify recurrence rates, need for further prolapse surgery, adverse events and cost-effectiveness. Trial registration Current Controlled Trials ISRCTN86784244. 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. 24, No. 13. See the National Institute for Health Research Journals Library website for further project information.

This paper will describe the development and application of a methodology for assessing the progress being made by companies in addressing the challenges of sustainable development. The methodology is based on the identification of a number of attributes that provide indicators of progress in pursuit of sustainable development. Each attribute is then further described in terms of several key characteristics. Publicly available information from leading companies can then be analysed in terms of these attributes and characteristics and each company's relative progress can be assessed.The methodology has been applied to a number of leading companies. The companies were chosen to cover a range of different sectors and by reference to relevant indicators, including the Dow Jones Sustainability Index and the FTSE4Good. An initial study carried out in 2000 was repeated during 2002. The results can be used to identify the relative strengths and weaknesses of a particular company versus best practice in its sector and overall, and to show the progress that has been made by individual companies and by sectors between 2000 and 2002. The paper will present some illustrative results from the studies.

Objective To report complication rates following prolapse surgery using polypropylene mesh inlay, polypropylene mesh kit, biological collagen xenografts and native tissue repairs.Design Secondary analysis of the PROSPECT randomised controlled trial and cohort study.Setting Thirty-five UK hospitals.Population A total of 2632 women undergoing anterior and/or posterior vaginal prolapse repair.Methods Event rates were calculated for all complications. Analysis was by treatment received.Main outcome measures IUGA/ICS classification of complications and validated patient reported outcome measures.Results At baseline, 8.4% of women had 'generic' pain/discomfort; at 2 years following surgery, there was an improvement in all four groups; however, 3.0% of women developed de novo extreme generic pain. At 24 months de novo vaginal tightness occurred in 1.6% of native tissue, 1.2% of biological xenograft, 0.3% of mesh inlay and 3.6% of mesh kit. Severe dyspareunia occurred in 4.8% of native tissue, 4.2% of biological xenograft, 3.4% of mesh inlay repairs and 13.0% of mesh kits. De novo severe dyspareunia occurred in 3.5% of native tissue, 3.5% of biological xenograft, 1.4% of mesh inlays and 4.8% of mesh kits. Complications requiring re-admission to hospital, unrelated to mesh, affected 1 in 24 women; the most common reasons for re-admission were vaginal adhesions, urinary retention, infection and constipation.Conclusions This is the first study to address the complications of vaginal mesh used for prolapse surgery alongside data from both native tissue and biological xenograft. It demonstrates the complexity of assessing pain and that all types of prolapse surgery have low surgical morbidity and a low rate of severe complications.

Background Pelvic organ prolapse (or prolapse) is a common condition in women where the pelvic organs (bladder, bowel or womb) descend into the vagina and cause distressing symptoms that adversely affect quality of life. Many women will use a vaginal pessary to treat their prolapse symptoms. Clinic-based care usually consists of having a pessary fitted in a primary or secondary care setting, and returning approximately every 6 months for healthcare professional review and pessary change. However, it is possible that women could remove, clean and re-insert their pessary themselves; this is called self-management. This trial aims to assess if self-management of a vaginal pessary is associated with better quality of life for women with prolapse when compared to clinic-based care. Methods This is a multicentre randomised controlled trial in at least 17 UK centres. The intervention group will receive pessary self-management teaching, a self-management information leaflet, a follow-up phone call and access to a local telephone number for clinical support. The control group will receive the clinic-based pessary care which is standard at their centre. Demographic and medical history data will be collected from both groups at baseline. The primary outcome is condition-specific quality of life at 18 months’ post-randomisation. Several secondary outcomes will also be assessed using participant-completed questionnaires. Questionnaires will be administered at baseline, 6, 12 and 18 months’ post-randomisation. An economic evaluation will be carried out alongside the trial to evaluate cost-effectiveness. A process evaluation will run parallel to the trial, the protocol for which is reported in a companion paper. Discussion The results of the trial will provide robust evidence of the effectiveness of pessary self-management compared to clinic-based care in terms of improving women’s quality of life, and of its cost-effectiveness. Trial registration ISRCTN Registry ISRCTN62510577. Registered on June 10, 2017.

Objective To compare standard (native tissue) repair with synthetic mesh inlays or mesh kits. Design Randomised controlled trial. Setting Thirty‐three UK hospitals. Population Women having surgery for recurrent prolapse. Methods Women recruited using remote randomisation. Main outcome measures Prolapse symptoms, condition‐specific quality‐of‐life and serious adverse effects. Results A Mean Pelvic Organ Prolapse Symptom Score at 1 year was similar for each comparison (standard 6.6 versus mesh inlay 6.1, mean difference [MD] −0.41, 95% CI −2.92 to 2.11: standard 6.6 versus mesh kit 5.9, MD −1.21 , 95% CI −4.13 to 1.72) but the confidence intervals did not exclude a minimally important clinical difference. There was no evidence of difference in any other outcome measure at 1 or 2 years. Serious adverse events, excluding mesh exposure, were similar at 1 year (standard 7/55 [13%] versus mesh inlay 5/52 [10%], risk ratio [RR] 1.05 [0.66–1.68]: standard 3/25 [12%] versus mesh kit 3/46 [7%], RR 0.49 [0.11–2.16]). Cumulative mesh exposure rates over 2 years were 7/52 (13%) in the mesh inlay arm, of whom four women required surgical revision; and 4/46 in the mesh kit arm (9%), of whom two required surgical revision. Conclusions We did not find evidence of a difference in terms of prolapse symptoms from the use of mesh inlays or mesh kits in women undergoing repeat prolapse surgery. Although the sample size was too small to be conclusive, the results provide a substantive contribution to future meta‐analysis. Tweetable abstract There is not enough evidence to support use of synthetic mesh inlay or mesh kits for repeat prolapse surgery.