Cost-Effectiveness of 2 Models of Pessary Care for Pelvic Organ Prolapse: Findings From the TOPSY Randomized Controlled Trial.

OBJECTIVES: Pelvic organ prolapse is the descent of one or more reproductive organs from their normal position, causing associated negative symptoms. One conservative treatment option is pessary management. This study aimed to to investigate the cost-effectiveness of pessary self-management (SM) when compared with clinic-based care (CBC). A decision analytic model was developed to extend the economic evaluation. METHODS: A randomized controlled trial with health economic evaluation. The SM group received a 30-minute SM teaching session, information leaflet, 2-week follow-up call, and a local helpline number. The CBC group received routine outpatient pessary appointments, determined by usual practice. The primary outcome for the cost-effectiveness analysis was incremental cost per quality-adjusted life year (QALY), 18 months post-randomization. Uncertainty was handled using nonparametric bootstrap analysis. In addition, a simple decision analytic model was developed using the trial data to extend the analysis over a 5-year period. RESULTS: There was no significant difference in the mean number of QALYs gained between SM and CBC (1.241 vs 1.221), but mean cost was lower for SM (£578 vs £728). The incremental net benefit estimated at a willingness to pay of £20 000 per QALY gained was £564, with an 80.8% probability of cost-effectiveness. The modeling results were consistent with the trial analysis: the incremental net benefit was estimated as £4221, and the probability of SM being cost-effective at 5 years was 69.7%. CONCLUSIONS: Results suggest that pessary SM is likely to be cost-effective. The decision analytic model suggests that this result is likely to persist over longer durations.

Total trans-obturator tape (TOT) removal; a case series including pain and urinary continence outcomes.

INTRODUCTION AND HYPOTHESIS: For many years, mid-urethral mesh tape (MUT) was the gold-standard procedure for management of stress urinary incontinence (SUI). However, significant concerns were raised over its safety. We present a case series of total trans-obturator tape (TOT) removals, performed in a tertiary unit over a 3-year period. We aim to evaluate improvement of pain and change in urinary continence symptoms following mesh explantation. METHODS: This is a retrospective case series of the outcomes of total TOT removal. Primary outcome is the change in pain scores following total removal, assessed preoperatively, at discharge and follow-up. Secondary outcomes were perioperative complications, including return to theatre, re-admission rates and incidence of worsening SUI and overactive bladder symptoms (OAB) postoperatively. Statistical analyses were performed using SPSS 27.0 package (IBM, Chicago, IL) and the GraphPad Prism 9 statistical packages. RESULTS: Nineteen women were identified. Mean age was 52 years and mean BMI was 31. Indications for mesh removal were: chronic pain (95%), vaginal exposure (37%) and pelvic sepsis (5%). No patients had return to theatre. Median intraoperative blood loss was 200 ml (interquartile range [IQR]: 150-288). Mean length of mesh excised was 22 cm. Mean postoperative hospital stay was 2 days. At follow-up, most patients (72%) reported "improvement" of their mesh-related pain at follow-up, while 6% reported "worsening" of pain. Eighty-three per cent of patients reported worsening SUI, and 50% reported worsening OAB symptoms. CONCLUSIONS: In the absence of sepsis, significant intraoperative complications are rare during total TOT removals. While 72% of patients reported improvement of their mesh-related pain, 6% still reported worsening pain after total mesh excision.

Impact of covid-19 on subspecialty training in obstetrics and gynaecology.

The Covid-19 pandemic brought substantial changes in clinical practice in Obstetrics and Gynaecology (O and G). Redeployment of staff and restrictions in elective services raised training concerns. We sought to assess the impact on subspecialty training, to identify issues to help mitigate the impact. We conducted cross-sectional anonymous electronic surveys of UK subspecialty trainees at three time points: June 2020, February 2021, September 2021. Surveys were analysed by descriptive statistics and thematic analysis of free-text responses. Response rates ranged from 30% to 40%, with higher response rates from urogynaecology trainees. Up to 72% reported an impact on training, most notable in gynaecological subspecialties, and particularly urogynaecology, which persisted over time. More than a third anticipated needing extra time to complete training. This raises serious future workforce and patient care concerns. Clinical recovery should consider training needs as essential when re-establishing services. Subspecialty trainees may need additional time to achieve competencies required of future consultants.IMPACT STATEMENTWhat is already known on the subject? Covid-19 led to dramatic changes in clinical practice in Obstetrics and Gynaecology. Previous studies on training in O and G during the pandemic in the UK and internationally highlighted issues from redeployment, trainee absence, and changes in service provision, that had potential to severely impact training.What do the results of this study add? Subspecialty training in Obstetrics and Gynaecology has been affected by the pandemic. Urogynaecology was worst affected and continues to be affected over the course of the pandemic.What are the implications of these findings for clinical practice and/or further research? Covid-19 recovery plans need to incorporate training requirements. Extended training due to the pandemic may affect consultant workforce numbers and thus service provision in tertiary care.

Learning from the report of the independent medicines and medical devices safety review: "first do no harm".

This is a review of the learning points from the Independent Medicines and Medical Devices Safety Review,1 chaired by Baroness Julia Cumberlege CBE DL. This system-wide review was initiated by the then Secretary of State for Health and Social Care, following patient-led campaigns. It looked at how the "healthcare system reacted as a whole, and how that response can be made more robust, speedy and appropriate".We aim to highlight the learning points for doctors in Obstetrics and Gynaecology as these are relevant to our current practice and future changes in our healthcare system. These are: Aims of the review: why it was initiated and how it was conductedOverarching themes and missed opportunities to prevent avoidable harmThree clinical scenarios: their histories, issues and adverse events associated with their use and the current response in Scotland The hormone pregnancy test - PrimodosThe anti-epileptic drug - sodium valproateSurgical mesh for prolapse & incontinenceThe recommendations made by the review and implementation guidanceResponses to the review, such as apologies issued by BSUG2/BAUS3/RCOG,4 and compensations schemes such as the Scottish scheme as recommended by the review.

Urethral bulking agents: a retrospective review of primary versus salvage procedure outcomes.

PURPOSE: Urethral bulking agents (UBA) have traditionally been offered as salvage procedures for recurrent stress urinary incontinence (SUI). We compare the success of UBA in patients that had undergone a previous procedure for SUI (Salvage-UBA) to the SUI surgery naïve (Primary-UBA). We hypothesised a positive effect in both Primary and Salvage-UBA with potentially poorer rates of response in the salvage group. METHODS: Retrospective case series of patients having their first UBA (2010-2018). Primary outcome was to assess any difference in patient reported success between groups. Patient-reported improvement was assessed on a 4-point scale: 'cured, improved, no change, worse' and treatment 'success' defined as 'cured' or 'improved'. A multivariate analysis, adjusting for plausible differences between groups, was undertaken in IBM SPSS Statistics (2016). RESULTS: 135 Primary-UBA and 38 Salvage-UBA were performed. Complete follow-up was obtained for 114 patients (66%): 86 Primary and 28 Salvage. Median follow-up time: 33 months. In 2012, 47% (8/17) of all UBA were Salvage-UBA, whilst in 2018, the majority were Primary-UBA (92%, 46/50). Success was not significantly different between Salvage-UBA 75% (21/28) versus Primary-UBA 67% (58/86) (Wald χ2 = 0.687, df = 1, p = 0.407). Top-up rates were similar: 14% (n = 4/28, Salvage-UBA) versus 15% (n = 13/86, Primary-UBA) (χ2 = 0.011, df = 1, p = 0.914). CONCLUSION: The number of women opting for UBA has increased substantially. No significant differences were noted for success with Salvage-UBA compared to Primary-UBA.

Self-management of overactive bladder at home using transcutaneous tibial nerve stimulation: a qualitative study of women's experiences.

BACKGROUND: Transcutaneous tibial nerve stimulation (TTNS) has been used to treat overactive bladder (OAB), however patient experiences and views of this treatment are lacking. The aim of this study was to explore women's experiences of OAB and TTNS treatment and the perceived factors influencing participation and adherence. METHODS: Semi-structured, individual interviews conducted as part of a mixed-methods, randomised, feasibility trial of self-managed versus HCP-led TTNS. Interviews were audio recorded and transcribed verbatim. Reflexive thematic analysis was undertaken using Booth et al. (Neurourol Urodynam. 2017;37:528-41) approach. RESULTS: 16 women were interviewed, 8 self-managing TTNS at home and 8 receiving TTNS in twice-weekly hospital clinic appointments. Women self-managing OAB considered TTNS easy to administer, flexible and favourably 'convenient', especially when the participant was bound by work and other life commitments. In contrast to OAB symptoms 'dominating life', self-managing bladder treatment was empowering and fitted around home life demands. Flexibility and control engendered by self-management, facilitated women's willingness to participate in TTNS. Women attending a hospital clinic for TTNS enjoyed the social aspects but found the routine appointments constrained their lives. Motivation to continue TTNS in the longer term was dependent on perception of benefit. CONCLUSIONS: This study provides novel insights into women's experiences of self-managing their OAB using TTNS compared to HCP-led management in the clinical setting. It highlights positive experiences self-managing TTNS at home and a willingness to continue in the longer term, facilitated by ease of use and convenience. Trial Registration 1/11/2018: ClinicalTrials.gov Identifier: NCT03727711.

Implementing pelvic floor muscle training for women with pelvic organ prolapse: a realist evaluation of different delivery models.

BACKGROUND: Pelvic Floor Muscle Training (PFMT) has been shown to be effective for pelvic organ prolapse in women, but its implementation in routine practice is challenging due to lack of adequate specialist staff. It is important to know if PFMT can be delivered by different staff skill mixes, what barriers and facilitators operate in different contexts, what strategies enable successful implementation and what are the underlying mechanisms of their action. PROPEL intervention was designed to maximise the delivery of effective PFMT in the UK NHS using different staff skill mixes. We conducted a realist evaluation (RE) of this implementation to understand what works, for whom, in what circumstances and why. METHODS: Informed by the Realist and RE-AIM frameworks, the study used a longitudinal, qualitative, multiple case study design. The study took place in five, purposively selected, diverse NHS sites across the UK and proceeded in three phases to identify, test and refine a theory of change. Data collection took place at 4 time points over an 18 month implementation period using focus groups and semi-structured interviews with a range of stakeholders including service leads/managers, senior practitioners, newly trained staff and women receiving care in the new service models. Data were analysed using thematic framework approach adapted to identify Context, Mechanism and Outcome (CMO) configurations of the RE. RESULTS: A heightened awareness of the service need among staff and management was a mechanism for change, particularly in areas where there was a shortage of skilled staff. In contrast, the most established specialist physiotherapist-delivered PFMT service activated feelings of role protection and compromised quality, which restricted the reach of PFMT through alternative models. Staff with some level of prior knowledge in women's health and adequate organisational support were more comfortable and confident in new role. Implementation was seamless when PFMT delivery was incorporated in newly trained staff's role and core work. CONCLUSION: Roll-out of PFMT delivery through different staff skill mixes is possible when it is undertaken by clinicians with an interest in women's health, and carefully implemented ensuring adequate levels of training and ongoing support from specialists, multi-disciplinary teams and management.

Women's experiences of receiving care for pelvic organ prolapse: a qualitative study.

BACKGROUND: Pelvic organ prolapse is a common urogenital condition affecting 41-50% of women over the age of 40. To achieve early diagnosis and appropriate treatment, it is important that care is sensitive to and meets women's needs, throughout their patient journey. This study explored women's experiences of seeking diagnosis and treatment for prolapse and their needs and priorities for improving person-centred care. METHODS: Twenty-two women receiving prolapse care through urogynaecology services across three purposefully selected NHS UK sites took part in three focus groups and four telephone interviews. A topic guide facilitated discussions about women's experiences of prolapse, diagnosis, treatment, follow-up, interactions with healthcare professionals, overall service delivery, and ideals for future services to meet their needs. Data were analysed thematically. RESULTS: Three themes emerged relating to women's experiences of a) Evaluating what is normal b) Hobson's choice of treatment decisions, and c) The trial and error of treatment and technique. Women often delayed seeking help for their symptoms due to lack of awareness, embarrassment and stigma. When presented to GPs, their symptoms were often dismissed and unaddressed until they became more severe. Women reported receiving little or no choice in treatment decisions. Choices were often influenced by health professionals' preferences which were subtly reflected through the framing of the offer. Women's embodied knowledge of their condition and treatment was largely unheeded, resulting in decisions that were inconsistent with women's preferences and needs. Physiotherapy based interventions were reported as helping women regain control over their symptoms and life. A need for greater awareness of prolapse and physiotherapy interventions among women, GPs and consultants was identified alongside greater focus on prevention, early diagnosis and regular follow-up. Greater choice and involvement in treatment decision making was desired. CONCLUSIONS: As prolapse treatment options expand to include more conservative choices, greater awareness and education is needed among women and professionals about these as a first line treatment and preventive measure, alongside a multi-professional team approach to treatment decision making. Women presenting with prolapse symptoms need to be listened to by the health care team, offered better information about treatment choices, and supported to make a decision that is right for them.

Adverse events after first, single, mesh and non-mesh surgical procedures for stress urinary incontinence and pelvic organ prolapse in Scotland, 1997-2016: a population-based cohort study.

BACKGROUND: Concerns have been raised about the safety of surgery for stress urinary incontinence and pelvic organ prolapse using transvaginal mesh. We assessed adverse outcomes after first, single mesh procedures and comparable non-mesh procedures. METHODS: We did a cohort study of women in Scotland aged 20 years or older undergoing a first, single incontinence procedure or prolapse procedure during 1997-98 to 2015-16 identified from a national hospital admission database. Primary outcomes were immediate postoperative complications and subsequent (within 5 years) readmissions for later postoperative complications, further incontinence surgery, or further prolapse surgery. Poisson regression models were used to compare outcomes after procedures carried out with and without mesh. FINDINGS: Between April 1, 1997, and March 31, 2016, 16 660 women underwent a first, single incontinence procedure, 13 133 (79%) of which used mesh. Compared with non-mesh open surgery (colposuspension), mesh procedures had a lower risk of immediate complications (adjusted relative risk [aRR] 0·44 [95% CI 0·36-0·55]) and subsequent prolapse surgery (adjusted incidence rate ratio [aIRR] 0·30 [0·24-0·39]), and a similar risk of further incontinence surgery (0·90 [0·73-1·11]) and later complications (1·12 [0·98-1·27]); all ratios are for retropubic mesh. During the same time period, 18 986 women underwent a first, single prolapse procedure, 1279 (7%) of which used mesh. Compared with non-mesh repair, mesh repair of anterior compartment prolapse was associated with a similar risk of immediate complications (aRR 0·93 [95% CI 0·49-1·79]); an increased risk of further incontinence (aIRR 3·20 [2·06-4·96]) and prolapse surgery (1·69 [1·29-2·20]); and a substantially increased risk of later complications (3·15 [2·46-4·04]). Compared with non-mesh repair, mesh repair of posterior compartment prolapse was associated with a similarly increased risk of repeat prolapse surgery and later complications. No difference in any outcome was observed between vaginal and, separately, abdominal mesh repair of vaginal vault prolapse compared with vaginal non-mesh repair. INTERPRETATION: Our results support the use of mesh procedures for incontinence, although further research on longer term outcomes would be beneficial. Mesh procedures for anterior and posterior compartment prolapse cannot be recommended for primary prolapse repair. Both vaginal and abdominal mesh procedures for vaginal vault prolapse repair are associated with similar effectiveness and complication rates to non-mesh vaginal repair. These results therefore do not clearly favour any particular vault repair procedure. FUNDING: None.

Prospective observational study of the impact of vaginal surgery (pelvic organ prolapse with or without urinary incontinence) on female sexual function.

INTRODUCTION AND HYPOTHESIS: There is a difference of opinion in the literature as to whether pelvic organ prolapse (POP) is a direct cause of female sexual dysfunction (FSD). Sexual function in women is negatively impacted by the presence of urinary symptoms. Thus, sexual dysfunction (SD) might be improved, unchanged, or worsened by pelvic floor surgery. METHODS: In this study, we observed SD and impact of surgical intervention on female sexual function (FSF) using a validated Prolapse/Urinary Incontinence Sexual Questionnaire Short Form (PISQ-12) in women undergoing surgery for POP with or without urinary incontinence. Two hundred women were recruited and followed up at 6 and 12 months postoperatively. RESULTS: Sexual function (SF) as measured by the PISQ-12 improved after surgery irrespective of the nature of surgery or the patient's past gynaecology history. Improvement in SF was seen by 6 months (97 patients) postsurgery (P < 0.05), after which (at 12 months; 80 patients) no further change was observed. Improved SF was associated with better patient satisfaction postoperatively. CONCLUSIONS: Sexual function improved in women following surgery for POP with or withour urinary incontinence, irrespective of the nature of surgery and the patient's past gynecologic history. Results of this study will assist when counselling women with POP with or without urinary incontinence regarding treatment options.

PROPEL: implementation of an evidence based pelvic floor muscle training intervention for women with pelvic organ prolapse: a realist evaluation and outcomes study protocol.

BACKGROUND: Pelvic Organ Prolapse (POP) is estimated to affect 41%-50% of women aged over 40. Findings from the multi-centre randomised controlled "Pelvic Organ Prolapse PhysiotherapY" (POPPY) trial showed that individualised pelvic floor muscle training (PFMT) was effective in reducing symptoms of prolapse, improved quality of life and showed clear potential to be cost-effective. However, provision of PFMT for prolapse continues to vary across the UK, with limited numbers of women's health physiotherapists specialising in its delivery. Implementation of this robust evidence from the POPPY trial will require attention to different models of delivery (e.g. staff skill mix) to fit with differing care environments. METHODS: A Realist Evaluation (RE) of implementation and outcomes of PFMT delivery in contrasting NHS settings will be conducted using multiple case study sites. Involving substantial local stakeholder engagement will permit a detailed exploration of how local sites make decisions on how to deliver PFMT and how these lead to service change. The RE will track how implementation is working; identify what influences outcomes; and, guided by the RE-AIM framework, will collect robust outcomes data. This will require mixed methods data collection and analysis. Qualitative data will be collected at four time-points across each site to understand local contexts and decisions regarding options for intervention delivery and to monitor implementation, uptake, adherence and outcomes. Patient outcome data will be collected at baseline, six months and one year follow-up for 120 women. Primary outcome will be the Pelvic Organ Prolapse Symptom Score (POP-SS). An economic evaluation will assess the costs and benefits associated with different delivery models taking account of further health care resource use by the women. Cost data will be combined with the primary outcome in a cost effectiveness analysis, and the EQ-5D-5L data in a cost utility analysis for each of the different models of delivery. DISCUSSION: Study of the implementation of varying models of service delivery of PFMT across contrasting sites combined with outcomes data and a cost effectiveness analysis will provide insight into the implementation and value of different models of PFMT service delivery and the cost benefits to the NHS in the longer term.

Combined linkage and association mapping identifies a major QTL (qRtsc8-1), conferring tar spot complex resistance in maize.

KEY MESSAGE: A major QTL ( qRtsc8 - 1 ) conditioning resistance to tar spot complex of maize and occurring at a frequency of 3.5 % across 890 maize inbred lines. Tar spot complex (TSC) is a highly destructive disease of maize found in some countries in America. Identification of TSC resistant germplasm and elucidating the genetic mechanism of resistance is crucial for the use of host resistance to manage this disease. We evaluated 890 elite maize inbred lines in multiple environments and used genome wide association analysis (GWAS) with genotypic data from Illumina MaizeSNP50 BeadChip containing 56 K SNPs to dissect the genetics of TSC resistance. GWAS results were validated through linkage analysis in three bi-parental populations derived from different resistant and susceptible parents. Through GWAS, three TSC resistance loci were identified on chromosome 2, 7 and 8 (-log10 (p) > 5.99). A major quantitative resistance locus (QTL) designated qRtsc8-1, was detected on maize chromosome bin 8.03. qRtsc8-1, was confirmed in three independent bi-parental populations and it accounted for 18-43 % of the observed phenotypic variation for TSC. A rare haplotype within the qRtsc8-1 region, occurring at a frequency of 3.5 % increased TSC resistance by 14 %. Candidate gene analysis revealed that a leucine-rich repeat receptor-like protein (LRR-RLKs) gene family maybe the candidate gene for qRtsc8-1. Identification and localization of a major locus conditioning TSC resistance provides the foundation for fine mapping qRtsc8-1 and developing functional markers for improving TSC resistance in maize breeding programs. To the best of our knowledge, this is the first report of a major QTL for TSC resistance.

Women's Experiences of Urinary Tract Infections and Impact on Life: An Exploratory Qualitative Study.

IMPORTANCE: Despite high incidences of urinary tract infections (UTIs), little is known about how bothersome symptoms are and the effects on women's life and sexual activity, leaving a gap in our understanding of the physical and emotional effects of UTIs on women. OBJECTIVES: This initial exploratory and descriptive study analyzes women's experiences of UTI and their perceived impact on quality of life. STUDY DESIGN: Qualitative interviews were undertaken with 23 women who had experienced at least 1 UTI, recruited from different settings-primary care, general gynecology clinics, urogynecology clinics, and online via social media. Data were analyzed thematically. RESULTS: Three themes described women's experiences of UTI: Women in all groups reported a wide range of physical symptoms and described the financial and psychological effects of UTIs. These effects seemed worse in women recruited via social media who also reported experiencing strong emotions and worries about close family members. Urinary tract infection support groups were considered useful, with women being grateful for consultations with alternative health practitioners and presuming safety of natural products. CONCLUSIONS: Having a UTI appeared to affect women in a variety of ways, ranging from having different physical symptoms to being psychologically affected by these symptoms, which affected their quality of life in different ways. This research contributes to the growing evidence on how UTIs affect women, specifically further expanding on the impact on women in a range of settings-in the community and different health care settings.

Clinical and cost-effectiveness of pessary self-management versus clinic-based care for pelvic organ prolapse in women: the TOPSY RCT with process evaluation.

Background: Pelvic organ prolapse is common, causes unpleasant symptoms and negatively affects women's quality of life. In the UK, most women with pelvic organ prolapse attend clinics for pessary care. Objectives: To determine the clinical effectiveness and cost-effectiveness of vaginal pessary self-management on prolapse-specific quality of life for women with prolapse compared with clinic-based care; and to assess intervention acceptability and contextual influences on effectiveness, adherence and fidelity. Design: A multicentre, parallel-group, superiority randomised controlled trial with a mixed-methods process evaluation. Participants: Women attending UK NHS outpatient pessary services, aged ≥ 18 years, using a pessary of any type/material (except shelf, Gellhorn or Cube) for at least 2 weeks. Exclusions: women with limited manual dexterity, with cognitive deficit (prohibiting consent or self-management), pregnant or non-English-speaking. Intervention: The self-management intervention involved a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a local clinic telephone helpline number. Clinic-based care involved routine appointments determined by centres' usual practice. Allocation: Remote web-based application; minimisation was by age, pessary user type and centre. Blinding: Participants, those delivering the intervention and researchers were not blinded to group allocation. Outcomes: The patient-reported primary outcome (measured using the Pelvic Floor Impact Questionnaire-7) was prolapse-specific quality of life, and the cost-effectiveness outcome was incremental cost per quality-adjusted life-year (a specifically developed health Resource Use Questionnaire was used) at 18 months post randomisation. Secondary outcome measures included self-efficacy and complications. Process evaluation data were collected by interview, audio-recording and checklist. Analysis was by intention to treat. Results: Three hundred and forty women were randomised (self-management, n = 169; clinic-based care, n = 171). At 18 months post randomisation, 291 questionnaires with valid primary outcome data were available (self-management, n = 139; clinic-based care, n = 152). Baseline economic analysis was based on 264 participants (self-management, n = 125; clinic-based care, n = 139) with valid quality of life and resource use data. Self-management was an acceptable intervention. There was no group difference in prolapse-specific quality of life at 18 months (adjusted mean difference -0.03, 95% confidence interval -9.32 to 9.25). There was fidelity to intervention delivery. Self-management was cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, with an estimated incremental net benefit of £564.32 and an 80.81% probability of cost-effectiveness. At 18 months, more pessary complications were reported in the clinic-based care group (adjusted mean difference 3.83, 95% confidence interval 0.81 to 6.86). There was no group difference in general self-efficacy, but self-managing women were more confident in pessary self-management activities. In both groups, contextual factors impacted on adherence and effectiveness. There were no reported serious unexpected serious adverse reactions. There were 32 serious adverse events (self-management, n = 17; clinic-based care, n = 14), all unrelated to the intervention. Skew in the baseline data for the Pelvic Floor Impact Questionnaire-7, the influence of the global COVID-19 pandemic, the potential effects of crossover and the lack of ethnic diversity in the recruited sample were possible limitations. Conclusions: Self-management was acceptable and cost-effective, led to fewer complications and did not improve or worsen quality of life for women with prolapse compared with clinic-based care. Future research is needed to develop a quality-of-life measure that is sensitive to the changes women desire from treatment. Study registration: This study is registered as ISRCTN62510577. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/82/01) and is published in full in Health Technology Assessment; Vol. 28, No. 23. See the NIHR Funding and Awards website for further award information.

Pelvic organ prolapse is a common and distressing condition experienced by large numbers of women. Prolapse is when the organs that are usually in the pelvis drop down into the vagina. Women experience a feeling of something coming down into the vagina, along with bowel, bladder and sexual problems. One possible treatment is a vaginal pessary. The pessary is a device that is inserted into the vagina and holds the pelvic organs back in their usual place. Women who use a vaginal pessary usually come back to clinic every 6 months to have their pessary removed and replaced; this is called clinic-based care. However, it is possible for a woman to look after the pessary herself; this is called self-management. This study compared self-management with clinic-based care. Three hundred and forty women with prolapse took part; 171 received clinic-based care and 169 undertook self-management. Each woman had an equal chance of being in either group. Women in the self-management group received a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a telephone number for their local centre. Women in the clinic-based care group returned to clinic as advised by the treating healthcare professional. Self-management was found to be acceptable. Women self-managed their pessary in ways that suited their lifestyle. After 18 months, there was no difference between the groups in women's quality of life. Women in the self-management group experienced fewer pessary complications than women who received clinic-based care. Self-management costs less to deliver than clinic-based care. In summary, self-management did not improve women's quality of life more than clinic-based care, but it did lead to women experiencing fewer complications and cost less to deliver in the NHS. The findings support self-management as a treatment pathway for women using a pessary for prolapse.

Clinical effectiveness of vaginal pessary self-management vs clinic-based care for pelvic organ prolapse (TOPSY): a randomised controlled superiority trial.

Background: Prolapse affects 30-40% of women. Those using a pessary for prolapse usually receive care as an outpatient. This trial determined effectiveness and cost-effectiveness of pessary self-management (SM) vs clinic-based care (CBC) in relation to condition-specific quality of life (QoL). Methods: Parallel-group, superiority randomised controlled trial, recruiting from 16 May 2018 to 7 February 2020, with follow-up to 17 September 2021. Women attending pessary clinics, ≥18 years, using a pessary (except Shelf, Gellhorn or Cube), with pessary retained ≥2 weeks were eligible. Limited manual dexterity; cognitive deficit; pregnancy; or requirement for non-English teaching were exclusions. SM group received a 30-min teaching session; information leaflet; 2-week follow-up call; and telephone support. CBC group received usual routine appointments. The primary clinical outcome was pelvic floor-specific QoL (PFIQ-7), and incremental net monetary benefit for cost-effectiveness, 18 months post-randomisation. Group allocation was by remote web-based application, minimised on age, user type (new/existing) and centre. Participants, intervention deliverers, researchers and the statistician were not blinded. The primary analysis was intention-to-treat based. Trial registration: https://doi.org/10.1186/ISRCTN62510577. Findings: The requisite 340 women were randomised (169 SM, 171 CBC) across 21 centres. There was not a statistically significant difference between groups in PFIQ-7 at 18 months (mean SM 32.3 vs CBC 32.5, adjusted mean difference SM-CBC -0.03, 95% CI -9.32 to 9.25). SM was less costly than CBC. The incremental net benefit of SM was £564 (SE £581, 95% CI -£576 to £1704). A lower percentage of pessary complications was reported in the SM group (mean SM 16.7% vs CBC 22.0%, adjusted mean difference -3.83%, 95% CI -6.86% to -0.81%). There was no meaningful difference in general self-efficacy. Self-managing women were more confident in self-management activities. There were no reported suspected unexpected serious adverse reactions, and 31 unrelated serious adverse events (17 SM, 14 CBC). Interpretation: Pessary self-management is cost-effective, does not improve or worsen QoL compared to CBC, and has a lower complication rate. Funding: National Institute for Health and Care Research, Health Technology Assessment Programme (16/82/01).

Prospective multi-centre study of adjustable single-incision mini-sling (Ajust(®) ) in the management of stress urinary incontinence in women: 1-year follow-up study.

OBJECTIVES: To determine whether an adjustable single-incision mini-sling (SIMS, Ajust(®) ) is safe and effective in the management of female stress urinary incontinence (SUI) at 12 months follow-up. To determine whether it is feasible to be performed under local anesthesia (LA). MATERIALS AND METHODS: The present study is a multicentre prospective cohort study in which 90 female patients underwent SIMS-Ajust(®) using a standardized insertion technique. The last 45 women were offered the procedure under LA. All patients completed their 12-month follow-up. RESULTS: The patient-reported success rate, using Patient Global Impression of Improvement (PGI-I), was 80% at 12 months follow-up and a further 6% (n= 5) reported themselves to be 'improved'. In all, 32/45 (71%) patients agreed to undergo the procedure under LA while one patient required conversion to general anaesthetic. There was no organ damage or requirement for blood transfusion. Significantly lower rates of blood loss (P= 0.025) and postoperative voiding difficulties (P= 0.026) were seen in the LA group. The re-operation rate for SUI was 6% at 12 months. CONCLUSIONS: SIMS (Ajust) appears to be a safe procedure, which is feasible under LA. SIMS (Ajust) have an 80% patient-reported success rate at 12 months follow-up.

Use of Magnetic Resonance Imaging in women with suspected complications following insertion of implants for pelvic organ prolapse and stress urinary incontinence surgery.

OBJECTIVE: To evaluate the role of Magnetic Resonance Imaging (MRI) in women presenting with suspected implant complications following surgery for pelvic organ prolapse (POP) and stress urinary incontinence (SUI). STUDY DESIGN: Retrospective single-centre cohort study in a designated tertiary referral centre. All women with vaginally and/or abdominally placed implants for POP or SUI who were referred with suspected mesh complications, and investigated with an MRI scan, between January 2018-October 2020 were included in the study. RESULTS: 97 women were identified over this time-period with a total of 123 implants, a median age of 55 years (Range: 34-79) and an average insertion to presentation time of 84 months (Range: 2-300). 78% (74) had one implant in situ, with the remainder having at least 2 in situ. Transobturator tapes (TVT-O/TOT) were the most common implants [35% (43)]. Chronic Pelvic or abdominal pain was the most common clinical symptom [73.2% (71/112 primary complaints)] with provoked tenderness on examination being the most common clinical finding [27.8% (32/115 clinical findings)]. MRI was more likely to detect abdominally placed implants [100% (all 30)] and Retropubic Tapes [89% (16/18)] when compared to Transvaginal POP implants [87.5% (28/32)] and TVT-O/TOT [67% (29/43)]. MRI identified both cases of Sacrocolpopexy mesh rupture as well as all 11 cases of infection (100%). In 91% (10/11) of these cases, MRI revealed the infection to be more widespread than clinical findings initially suspected. Cohen's Kappa demonstrated excellent correlation between MRI and surgical findings in cases with implant related infection, rupture and normal findings (κ = 1; z = 4.58; p = 0.00000459). CONCLUSION(S): MRI can be a useful tool in assessment and management of patients with complications from implants. MRI can detect infection that may be more extensive that is initially clinically apparent in the outpatient setting. Abdominal implants appear to be easier to detect than transvaginal meshes and trans obturator tapes.

Theoretical and practical development of the TOPSY self-management intervention for women who use a vaginal pessary for pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) is a common condition in women, where the downward descent of pelvic organs into the vagina causes symptoms which impacts quality of life. Vaginal pessaries offer an effective alternative to surgery for the management of POP. However, the need for regular follow-up can be burdensome for women and requires significant healthcare resources. The TOPSY study is a randomised controlled trial which aims to determine the clinical and cost-effectiveness of self-management of vaginal pessaries. This paper describes the theoretical and practical development of the self-management intervention. METHODS: The intervention was developed using the MRC complex intervention framework, normalisation process theory (NPT) and self-management theory. The intervention aims to boost perceived self-efficacy in accordance with Bandura's social cognitive theory and is guided by the tasks and skills Lorig and Hollman describe as necessary to self-manage a health condition. RESULTS: The TOPSY intervention was designed to support women to undertake the medical management, role management and emotional management of their pessary. The six self-management skills described by Lorig and Hollman: problem-solving, decision-making, resource utilisation, formation of a patient-provider partnership role, action planning and self-tailoring, are discussed in detail, including how women were supported to achieve each task within the context of pessary self-management. The TOPSY intervention includes a self-management support session with a pessary practitioner trained in intervention delivery, a follow-up phone call 2 weeks later and ongoing telephone or face-to-face support as required by the woman initiated by contacting a member of the research team. CONCLUSIONS: The TOPSY study intervention was developed utilising the findings from a prior service development project, intervention development and self-efficacy theory, relevant literature, clinician experience and feedback from pessary using women and members of the public. In 2022, the findings of the TOPSY study will provide further evidence to inform this important aspect of pessary management. TRIAL REGISTRATION: ISRCTN Registry ISRCTN62510577 . Registered on June 10, 2017.

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

BACKGROUND: Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex®; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women. DESIGN: Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. SETTING: Eight UK NHS secondary care sites. PARTICIPANTS: A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. INTERVENTIONS: A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. MAIN OUTCOME MEASURES: The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. RESULTS: Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (p-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) (p = 0.06). All other secondary outcomes and adverse events were similar in both arms. LIMITATIONS: This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. CONCLUSIONS: This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. RECOMMENDATIONS FOR RESEARCH: Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. TRIAL REGISTRATION: This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

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

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial.

OBJECTIVE: To test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose antibiotics. DESIGN: Multicentre, open label, randomised, non-inferiority trial. SETTING: Eight centres in the UK, recruiting from June 2016 to June 2018. PARTICIPANTS: Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment. INTERVENTIONS: Random assignment (1:1, using permuted blocks of variable length via a web based system) to receive antibiotic prophylaxis or methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed. MAIN OUTCOME MEASURE: Absolute difference in incidence of symptomatic, antibiotic treated, urinary tract infections during treatment. A patient and public involvement group predefined the non-inferiority margin as one episode of urinary tract infection per person year. Analyses performed in a modified intention-to-treat population comprised all participants observed for at least six months. RESULTS: Participants were randomly assigned to antibiotic prophylaxis (n=120) or methenamine hippurate (n=120). The modified intention-to-treat analysis comprised 205 (85%) participants (antibiotics, n=102 (85%); methenamine hippurate, n=103 (86%)). Incidence of antibiotic treated urinary tract infections during the 12 month treatment period was 0.89 episodes per person year (95% confidence interval 0.65 to 1.12) in the antibiotics group and 1.38 (1.05 to 1.72) in the methenamine hippurate group, with an absolute difference of 0.49 (90% confidence interval 0.15 to 0.84) confirming non-inferiority. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the methenamine group and most reactions were mild. CONCLUSION: Non-antibiotic prophylactic treatment with methenamine hippurate might be appropriate for women with a history of recurrent episodes of urinary tract infections, informed by patient preferences and antibiotic stewardship initiatives, given the demonstration of non-inferiority to daily antibiotic prophylaxis seen in this trial. TRIAL REGISTRATION: ISRCTN70219762.