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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., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

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.

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)., Competing Interests: All authors declare a grant from National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme relating to the research described in the manuscript. In addition Lucy Dwyer reports being a member of the NICE guideline committee for non-surgical management and prevention of pelvic floor dysfunction and a member of the UK Clinical Guideline for best practice in the use of vaginal pessaries for pelvic organ prolapse committee; Aethele Khunda reports receiving an educational grant from Olympus Medical Systems to cover travel and accommodation costs to attend a laparoscopic urogynaecology workshop; Wael Agur reports grants from NIHR, consulting fees and payment for testimony from Oaklaw Consultancy Ltd., for Medico-legal Consultancy and financial/non-financial interest associated with Medical Innovation Systems; Karen Guerrero reports payment for expert testimony for the Medical Advisor NHS Scotland Central Legal Office and for NHS-funded study leave; Christine Hemming reports grants from NIHR HTA for two RCTs (11/129/183 and 07/60/18); John Norrie reports being a member of the following committees: NIHR CTU Standing Advisory Committee (2018-23), NIHR HTA & EME Editorial Board (2015–2019), EME Funding Committee Member (2019–2022), HTA General Committee (2016–2019), HTA Post-Funding Committee (2016–2019), HTA Funding Committee Policy Group (2016–2019), COVID-19 Reviewing (2020); Ranee Thakar reports a voluntary role at Royal College of Obstetricians and Gynaecologists; Rohna Kearney reports being topic lead for prolapse on NICE guideline NG123 published 2019; Angela Forrest reports payment for attending project meetings relating to the research; Suzanne Breeman reports grants from NIHR HTA for the VUE trial (11/129/183) and the PROSPECT trial (07/60/18 and NIHR133665). Suzanne Hagen, Carol Bugge, Andrew Elders, Helen Mason, Kirsteen Goodman, Doreen McClurg, Melanie Dembinsky, Lynn Melone, Catherine Best, Sarkis Manoukian, Margaret Graham, Jane Culverhouse and Mark Forrest have no additional disclosures to report relating to the manuscript., (© 2023 The Authors.)

This paper reports the synthesis, characterization and in vivo application of water-soluble supramolecular contrast agents (Mw: 5-5.6 kDa) for MRI obtained from β-cyclodextrin functionalized with different kinds of nitroxide radicals, both with piperidine structure (CD2 and CD3) and with pyrrolidine structure (CD4 and CD5). As to the stability of the radicals in presence of ascorbic acid, CD4 and CD5 have low second order kinetic constants (≤0.05 M -1  s -1 ) compared to CD2 (3.5 M -1  s -1 ) and CD3 (0.73 M -1  s -1 ). Relaxivity (r 1 ) measurements on compounds CD3-CD5 were carried out at different magnetic field strength (0.7, 3, 7 and 9.4 T). At 0.7 T, r 1 values comprised between 1.5 mM -1  s -1 and 1.9 mM -1  s -1 were found while a significant reduction was observed at higher fields (r 1 ≈0.6-0.9 mM -1  s -1 at 9.4 T). Tests in vitro on HEK293 human embryonic kidney cells, L929 mouse fibroblasts and U87 glioblastoma cells indicated that all compounds were non-cytotoxic at concentrations below 1 μmol mL -1 . MRI in vivo was carried out at 9.4 T on glioma-bearing rats using the compounds CD3-CD5. The experiments showed a good lowering of T 1 relaxation in tumor with a retention of the contrast for at least 60 mins confirming improved stability also in vivo conditions., (© 2023 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

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., (© 2022. The Author(s).)

Pectin has found extensive interest in biomedical applications, including wound dressing, drug delivery, and cancer targeting. However, the low viscosity of pectin solutions hinders their applications in 3D bioprinting. Here, we developed multicomponent bioinks prepared by combining pectin with TEMPO-oxidized cellulose nanofibers (TOCNFs) to optimize the inks' printability while ensuring stability of the printed hydrogels and simultaneously print viable cell-laden inks. First, we screened several combinations of pectin (1%, 1.5%, 2%, and 2.5% w/v) and TOCNFs (0%, 0.5%, 1%, and 1.5% w/v) by testing their rheological properties and printability. Addition of TOCNFs allowed increasing the inks' viscosity while maintaining shear thinning rheological response, and it allowed us to identify the optimal pectin concentration (2.5% w/v). We then selected the optimal TOCNFs concentration (1% w/v) by evaluating the viability of cells embedded in the ink and eventually optimized the writing speed to be used to print accurate 3D grid structures. Bioinks were prepared by embedding L929 fibroblast cells in the ink printed by optimized printing parameters. The printed scaffolds were stable in a physiological-like environment and characterized by an elastic modulus of E = 1.8 ± 0.2 kPa. Cells loaded in the ink and printed were viable (cell viability >80%) and their metabolic activity increased in time during the in vitro culture, showing the potential use of the developed bioinks for biofabrication and tissue engineering applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pitton, Fiorati, Buscemi, Melone, Farè and Contessi Negrini.)