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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. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies made such data difficult to interpret. There was no evidence of any statistically significant difference between pazopanib and best supportive care (HR 0.501; 95 % CI 0.136, 2.348). In the indirect comparison, there were no statistically significant differences between pazopanib and IFN-α (HR 0.627; 95 % CI 0.173, 2.269) or between pazopanib and sunitinib (HR 0.969; 95 % CI 0.359, 2.608). Based upon the work presented including a 12.5 % discount for pazopanib, sunitinib was extendedly dominated by a combination of pazopanib and IFN-α. As a consequence, the incremental cost per QALY for pazopanib versus IFN-α was £38,925. The results were not greatly altered over the range of univariate deterministic sensitivity analyses conducted by the manufacturer but pair-wise probabilistic sensitivity analyses suggested that given a threshold value of £30,000, there is a 54 % probability that pazopanib was preferred to sunitinib, 40 % chance against IFN-α and 47 % chance against best supportive care. The Appraisal Committee concluded that pazopanib should be recommended as a first-line treatment option for people with advanced renal cell carcinoma who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and if the manufacturer provides pazopanib with a 12.5 % discount on the list price and provides a possible future rebate linked to the outcome of the head-to-head COMPARZ trial, as agreed under the terms of the patient access scheme and to be confirmed when the COMPARZ trial data are made available. [ABSTRACT FROM AUTHOR]

Abstract Background Observational studies have frequently reported an association between cognitive function and nutrition in later life but randomised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect. We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline. Methods The study was carried out as part of a randomised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotland. 910 men and women aged 65 years and over living in the community were recruited and randomised: 456 to active treatment and 454 to placebo. The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50–210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months. Digit span forward and verbal fluency tests, which assess immediate memory and executive functioning respectively, were conducted at the start and end of the intervention period. Risk of micronutrient deficiency at baseline was assessed by a simple risk questionnaire. Results For digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency. For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups: in those aged 75 years and over (n 290; mean difference between supplemented and placebo groups 2.8 (95% CI -0.6, 6.2) units) and in those at increased risk of micronutrient deficiency assessed by the risk questionnaire (n 260; mean difference between supplemented and placebo groups 2.5 (95% CI -1.0, 6.1) units). Conclusion The results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years. However, the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention.

Background: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital. We aimed to establish whether short-term routine use of antimicrobial catheters reduced risk of CAUTI compared with standard polytetrafluoroethylene (PTFE) catheterisation.Methods: In our parallel, three group, multicentre, randomised controlled superiority trial, we enrolled adults (aged ≥16 years) requiring short-term (≤14 days) catheterisation at 24 hospitals in the UK. Participants were randomly allocated 1:1:1 with a remote computer allocation to receive a silver alloy-coated catheter, a nitrofural-impregnated catheter, or a PTFE-coated catheter (control group). Patients undergoing unplanned catheterisation were also included and consent for participation was obtained retrospectively. Participants and trial staff were unmasked to treatment assignment. Data were collected by trial staff and by patient-reported questionnaires for 6 weeks after randomisation. The primary outcome was incidence of symptomatic urinary tract infection for which an antibiotic was prescribed by 6 weeks. We postulated that a 3·3% absolute reduction in CAUTI would represent sufficient benefit to recommend routine use of antimicrobial catheters. This study is registered, number ISRCTN75198618.Findings: 708 (10%) of 7102 randomly allocated participants were not catheterised, did not confirm consent, or withdrew, and were not included in the primary analyses. Compared with 271 (12·6%) of 2144 participants in the control group, 263 (12·5%) of 2097 participants allocated a silver alloy catheter had the primary outcome (difference -0·1% [95% CI -2·4 to 2·2]), as did 228 (10·6%) of 2153 participants allocated a nitrofural catheter (-2·1% [-4·2 to 0·1]). Rates of catheter-related discomfort were higher in the nitrofural group than they were in the other groups.Interpretation: Silver alloy-coated catheters were not effective for reduction of incidence of symptomatic CAUTI. The reduction we noted in CAUTI associated with nitrofural-impregnated catheters was less than that regarded as clinically important. Routine use of antimicrobial-impregnated catheters is not supported by this trial.Funding: UK National Institute for Health Research Health Technology Assessment Programme. [ABSTRACT FROM AUTHOR]

Objective: To report on the cost-effectiveness of adjustable anchored single-incision mini-slings (mini-slings) compared with tension-free standard mid-urethral slings (standard slings) in the surgical management of female stress urinary incontinence (SUI)., Patients and Methods: Data on resource use and quality were collected from women aged ≥18 years with predominant SUI undergoing mid-urethral sling procedures in 21 UK hospitals. Resource use and quality of life (QoL) data were prospectively collected alongside the Single-Incision Mini-Slings versus standard synthetic mid-urethral slings Randomised Control Trial (SIMS RCT), for surgical treatment of SUI in women. A health service provider's (National Health Service [NHS]) perspective with 3-year follow-up was adopted to estimate the costs of the intervention and all subsequent resource use. A generic instrument, EuroQol EQ-5D-3L, was used to estimate the QoL. Results are reported as incremental costs, quality adjusted life years (QALYs) and incremental cost per QALY., Results: Base case analysis results show that although mini-slings cost less, there was no significant difference in costs: mini-slings versus standard slings: £-6 [95% CI -228-208] or in QALYs: 0.005 [95% CI -0.068-0.073] over the 3-year follow-up. There is substantial uncertainty, with a 56% and 44% probability that mini-slings and standard slings are the most cost-effective treatment, respectively, at a £20 000 willingness-to-pay threshold value for a QALY., Conclusions: At 3 years, there is no significant difference between mini-slings and standard slings in costs and QALYs. There is still some uncertainty over the long-term complications and failure rates of the devices used in the treatment of SUI; therefore, it is important to establish the long-term clinical and cost-effectiveness of these procedures., Competing Interests: Dr. Dwayne Boyers reports grants from UK NIHR during the conduct of the study. Ms. Mary Kilonzo reports grants from UK NIHR during the conduct of the study. Kiron Bhal: I have been a speaker and trainer for the following companies in the past Astellas, Pfizer, AMS, Contura, Allergan and others, where I have received honorariums and sponsorship towards attending scientific conferences. Professor James N'Dow reports HTA General Committee 2016–2018. Professor Graeme MacLennan reports grants from UK NIHR during the conduct of the study. Professor John Norrie reports grants from the University of Edinburgh, outside the submitted work; and past and present member of the following: HTA Commissioning Sub‐Board (EOI), NIHR CTU Standing Advisory Committee, NIHR HTA & EME Editorial Board, Pre‐Exposure Prophylaxis Impact Review Panel, EME Strategy Advisory Committee, EME—Funding Committee Members, EME Funding Committee Sub‐Group Remit & Comp Check, HTA General Committee, HTA Funding Committee Policy Group (formerly CSG) and HTA Commissioning Committee. HTA post‐funding committee teleconference 2016–2019; COVID‐19 reviewing 2020. Professor Mohamed Abdel‐Fattah: None in the last 5 years. Before 2015, I have been a speaker, consultant and/or surgical trainer for a number of industrial companies (Astellas, Ethicon, Bard, Pfizer, AMS, Coloplast and others): I have been reimbursed my travel expenses; and on occasions received personal honorariums; proctorship fees and sponsorship towards attending scientific conferences. Research grant from Coloplast managed by the University of Aberdeen. A limited number of my trainees attended pharmaceutical‐sponsored educational/leadership workshops and/or received assistance in presenting their research work at scientific conferences. Was Chairman of the Scottish Pelvic Floor Network (SPFN), which at the time received financial sponsorship from various industrial companies (including all those mentioned above) and non‐profit organisations for its annual meetings and surgical workshops. The SPFN provided an educational grant funding the PI at the highest recruiting site to attend the International Continence Society annual scientific conference in Brazil in 2014. Ongoing: I receive travel sponsorship and occasionally speaker‘s fees from numerous national and international conferences and non‐profit organisations when invited as a guest speaker and/or expert surgeon. In 2019, and at request from NHS Grampian, I attended 2 educational meetings for setting up sacral nerve stimulation service partially funded by Medtronic. I am the Chief Investigator for four NIHR—HTA‐funded studies. I do not hold (and never held) any shares (or similar) in any of the industrial companies (medical or non‐medical). To the best of my knowledge, none of the above have influenced my research or clinical practice. No other authors declared any potential conflicts of interest., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background: Scotland has the highest rate of drug related deaths (DRD) in Europe. These are deaths in people who use drugs such as heroin, cocaine, benzodiazepines and gabapentinoids. It is a feature of deaths in Scotland that people use combinations of drugs which increases the chance of a DRD. Many deaths involve 'street' benzodiazepines, especially a drug called etizolam. Many of the 'street' benzodiazepines are not licensed in the UK so come from illegal sources. People who use opiates can be prescribed a safer replacement medication (e.g., methadone). While guidance on management of benzodiazepines use highlights that there is little evidence to support replacement prescribing, practice and evidence are emerging., Aim: To develop an intervention to address 'street' benzodiazepines use in people who also use opiates., Methods: The MRC Framework for Complex Interventions was used to inform research design. Co-production of the intervention was achieved through three online workshops with clinicians, academics working in the area of substance use, and people with lived experience (PWLE). Each workshop was followed by a PWLE group meeting. Outputs from workshops were discussed and refined by the PWLE group and then further explored at the next workshop., Results: After these six sessions, a finalised logic model for the intervention was successfully achieved that was acceptable to clinicians and PWLE. Key components of the intervention were: prescribing of diazepam; anxiety management, sleep, and pain; and harm reduction resources (locked box and a range of tips), personal safety conversations, as well as a virtual learning environment., Conclusion: A co-produced intervention was developed for next stage clinical feasibility testing., (© 2023. The Author(s).)

Evidence-based assessment (EBA) in mental health is a critical aspect of improving patient outcomes and addressing the gaps in mental health care. EBA involves the use of psychometric instruments to gather data that can inform clinical decision-making, inform policymakers, and serve as a basis for research and quality management. Despite its potential, EBA is often hindered by barriers such as workload and cost, leading to its underutilization. Regarding low- and middle-income countries (LMIC), the implementation of EBA is recognized as a key strategy to address and close the prevalent mental health treatment gap.To simplify the application of EBA including in LMIC, an international team of researchers and practitioners from Tanzania, Kosovo, Chile, and Switzerland developed the Mental Health Information Reporting Assistant (MHIRA). MHIRA is an open-source electronic health record that streamlines EBA by digitising psychometric instruments and organising patient data in a user-friendly manner. It provides immediate and convenient reports to inform clinical decision-making.The current article provides a comprehensive overview of the features and technical details of MHIRA, as well as insights from four implementation scenarios. The experience gained during the implementations as well as the user-feedback suggests that MHIRA has the potential to be successfully implemented in a variety of clinical contexts and simplify the use of EBA. However, further research is necessary to establish its potential to sustainably transform healthcare services and impact patient outcomes.In conclusion, MHIRA represents an important step in promoting the widespread adoption of EBA in mental health. It offers a promising solution to the barriers that have limited the use of EBA in the past and holds the potential to improve patient outcomes and support the ongoing efforts to address gaps in mental health care., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To elicit and value patient preferences for the processes and outcomes of surgical management of stress urinary incontinence in women., Design: A discrete choice experiment survey to elicit preferences for type of anaesthesia, postoperative recovery time, treatment success, adverse events, impact on daily activities and cost. An experimental design generated 40 choice tasks, and each respondent completed 1 block of 10 and 2 validity tests. Analysis was by multinomial logistical regression., Setting: N=21 UK hospitals., Participants: N=325 adult women who were a subsample of those randomised to the single-incision mini-slings clinical trial., Outcomes: Patient preferences; valuation obtained using willingness to pay., Results: N=227 of 325 (70%) returned a questionnaire, and 94% of those completed all choice tasks. Respondents preferred general anaesthesia, shorter recovery times, improved stress urinary incontinence symptoms and avoidance of adverse events. Women were willing to pay (mean (95% CI)) £76 (£33 to £119) per day of reduction in recovery time following surgery. They valued increases in Patient Global Impression of Improvement, ranging from £8173 (£5459 to £10 887) for 'improved' to £11 706 (£8267 to £15 144) for 'very much improved' symptoms, compared with no symptom improvement. This was offset by negative values attached to the avoidance of complications ranging between £-8022 (£-10 661 to £-5383) and £-10 632 (£-14 077 to £-7187) compared to no complications. Women valued treatments that reduced the need to avoid daily activities, with willingness to pay ranging from £-967 (£-2199 to £266) for rarely avoiding activities to £-5338 (£-7258 to £-3417) for frequently avoiding daily activities compared with no avoidance., Conclusion: This discrete choice experiment demonstrates that patients place considerable value on improvement in stress urinary incontinence symptoms and avoidance of treatment complications. Trade-offs between symptom improvement and adverse event risk should be considered within shared decision-making. The willingness to pay values from this study can be used in future cost-benefit analyses., Trial Registration Number: ISRCTN: 93264234; Post-results., Competing Interests: Competing interests: DB reports grants from UK NIHR during the conduct of the study. KB has been a speaker and trainer for the following companies in the past: Astellas, Pfizer, AMS, Contura, Allergan and others, where he received honoraria and sponsorship towards attending scientific conferences. JN'D reports HTA General Committee 2016–2018. GM reports grants from UK NIHR during the conduct of the study. JN reports grants from University of Edinburgh, outside the submitted work; and past and present member of the following: HTA Commissioning Sub-Board (EOI), NIHR CTU Standing Advisory Committee, NIHR HTA & EME Editorial Board, Pre-Exposure Prophylaxis Impact Review Panel, EME Strategy Advisory Committee, EME-Funding Committee Members, EME Funding Committee Sub-Group Remit & Comp Check, HTA General Committee, HTA Funding Committee Policy Group (formerly CSG), HTA Commissioning Committee, HTA Post-funding committee teleconference 2016–2019 and COVID-19 reviewing 2020. MA-F reports none in the last 5 years. Before 2015, he has been a speaker, consultant and/or surgical trainer for a number of industrial companies (Astellas, Ethicon, Bard, Pfizer, AMS, Coloplast and others); has reimbursed his travel expenses and on occasions received personal honoraria, proctorship fees and sponsorship towards attending scientific conferences; received research grant from Coloplast managed by University of Aberdeen. Moreover, his limited number of trainees attended pharmaceutical sponsored educational/leadership workshops and/or received assistance towards presenting their research work in scientific conferences. He was also Chairman of the Scottish Pelvic Floor Network (SPFN), which at the time, received financial sponsorship from various industrial companies (including all those mentioned above) and non-profit organisations for its annual meetings and surgical workshops. The SPFN provided an educational grant funding the PI at the highest recruiting site to attend the International Continence Society annual scientific conference in Brazil in 2014. At present, he receives travel sponsorship and occasionally speaker’s fees from numerous national and international conferences and non-profit organisations when invited as guest speaker and/or expert surgeon. In 2019, and at the request from NHS Grampian, he attended two educational meetings for setting up sacral nerve stimulation service partially funded by Medtronic. He is the Chief Investigator for four NIHR-HTA-funded studies. He does not hold (and never held) any shares (or similar) in any of the industrial companies (medical or non-medical). To the best of his knowledge, none of the above have influenced his research or clinical practice. No other authors declared any potential conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Hypothesis: Our aim was to compare the mid-term results of native tissue, biological xenograft and polypropylene mesh surgery for women with vaginal wall prolapse., Methods: A total of 1348 women undergoing primary transvaginal repair of an anterior and/or posterior prolapse were recruited between January 2010 and August 2013 from 35 UK centres. They were randomised by remote allocation to native tissue surgery, biological xenograft or polypropylene mesh. We performed both 4- and 6-year follow-up using validated patient-reported outcome measures., Results: At 4 and 6 years post-operation, there was no clinically important difference in Pelvic Organ Prolapse Symptom Score for any of the treatments. Using a strict composite outcome to assess functional cure at 6 years, we found no difference in cure among the three types of surgery. Half the women were cured at 6 years but only 10.3 to 12% of women had undergone further surgery for prolapse. However, 8.4% of women in the mesh group had undergone further surgery for mesh complications. There was no difference in the incidence of chronic pain or dyspareunia between groups., Conclusions: At the mid-term outcome of 6 years, there is no benefit from augmenting primary prolapse repairs with polypropylene mesh inlays or biological xenografts. There was no evidence that polypropylene mesh inlays caused greater pain or dyspareunia than native tissue repairs., (© 2022. The Author(s).)

Afforestation is providing the remedy for deforestation, which is among the greatest challenges of biodiversity conservation in Tanzania. Efforts for afforestation are taking place in Dodoma, which are anticipated to have social and ecological positive effects. This study provides information on the perception of local communities towards afforestation and how afforestation can harbor other wildlife species like lizards. A semi-structured questionnaire was used to collect information from respondents who were chosen at random in the afforestation area. Pitfalls and direct observation under constrained time intervals were used to sample lizards in two categories of vegetation (afforested and non-afforested areas; n = 1040 samples). Awareness of afforestation was significantly affected by age group (P < 0.005) and nature of course taking. In this case, those who studied natural courses like biology, forest, and aquatic science were more aware of afforestation and they had a likelihood of being involved in afforestation programs (P < 0.05). Eight species of lizards were identified in the study area where seven species were found in afforested areas while three were found in non-afforested areas, where Agama lionotus was the dominant species. The diversity of lizards was higher in afforested areas (Shannon Weiner index H = 1.37) than in non-afforested areas (Shannon Weiner index H = 0.99). More afforestation program awareness and conservation education are required to ensure the sustainability of afforestation efforts in Dodoma. Afforestation showed a significant contribution to the conservation of lizards. Lizards can be used as good indicator species to understand and monitor the success of afforestation., (© 2022. The Author(s).)

Background: Stress urinary incontinence is the most common type of urinary incontinence in premenopausal women. Until recently, synthetic mid-urethral slings (mesh/tape) were the standard surgical treatment, if conservative management failed. Adjustable anchored single-incision mini-slings are newer, use less mesh and may reduce perioperative morbidity, but it is unclear how their success rates and safety compare with those of standard tension-free mid-urethral slings., Objective: The objective was to compare tension-free standard mid-urethral slings with adjustable anchored single-incision mini-slings among women with stress urinary incontinence requiring surgical intervention, in terms of patient-reported effectiveness, health-related quality of life, safety and cost-effectiveness., Design: This was a pragmatic non-inferiority randomised controlled trial. Allocation was by remote web-based randomisation (1 : 1 ratio)., Setting: The trial was set in 21 UK hospitals., Participants: Participants were women aged ≥ 18 years with predominant stress urinary incontinence, undergoing a mid-urethral sling procedure., Interventions: Single-incision mini-slings, compared with standard mid-urethral slings., Main Outcome Measures: The primary outcome was patient-reported success rates on the Patient Global Impression of Improvement scale at 15 months post randomisation (≈ 1 year post surgery), with success defined as outcomes of 'very much improved' or 'much improved'. The primary economic outcome was incremental cost per quality-adjusted life-year gained. Secondary outcomes were adverse events, impact on other urinary symptoms, quality of life and sexual function., Results: A total of 600 participants were randomised. At 15 months post randomisation, adjustable anchored single-incision mini-slings were non-inferior to tension-free standard mid-urethral slings at the 10% margin for the primary outcome [single-incision mini-sling 79% (212/268) vs. standard mid-urethral sling 76% (189/250), risk difference 4.6, 95% confidence interval -2.7 to 11.8; p non-inferiority  < 0.001]. Similarly, at 3 years' follow-up, patient-reported success rates in the single-incision mini-sling group were non-inferior to those of the standard mid-urethral sling group at the 10% margin [single-incision mini-sling 72% (177/246) vs. standard mid-urethral sling 67% (157/235), risk difference 5.7, 95% confidence interval -1.3 to 12.8; p non-inferiority  < 0.001]. Tape/mesh exposure rates were higher for single-incision mini-sling participants, with 3.3% (9/276) [compared with 1.9% (5/261) in the standard mid-urethral sling group] reporting tape exposure over the 3 years of follow-up. The rate of groin/thigh pain was slightly higher in the single-incision mini-sling group at 15 months [single-incision mini-sling 15% (41/276) vs. standard mid-urethral sling 12% (31/261), risk difference 3.0%, 95% confidence interval -1.1% to 7.1%]; however, by 3 years, the rate of pain was slightly higher among the standard mid-urethral sling participants [single-incision mini-sling 14% (39/276) vs. standard mid-urethral sling 15% (39/261), risk difference -0.8, 95% confidence interval -4.1 to 2.5]. At the 3-year follow-up, quality of life and sexual function outcomes were similar in both groups: for the International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms Quality of Life, the mean difference in scores was -1.1 (95% confidence interval -3.1 to 0.8; p  = 0.24), and for the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, International Urogynecological Association-Revised, it was 0 (95% confidence interval -0.1, 0.1; p  = 0.92). However, more women in the single-incision mini-sling group reported dyspareunia [12% (17/145), compared with 4.8% (7/145) in the standard mid-urethral sling group, risk difference 7.0%, 95% confidence interval 1.9% to 12.1%]. The base-case economics results showed no difference in costs (-£6, 95% confidence interval -£228 to £208) or quality-adjusted life-years (0.005, 95% confidence interval -0.068 to 0.073) between the groups. There is a 56% probability that single-incision mini-slings will be considered cost-effective at the £20,000 willingness-to-pay threshold value for a quality-adjusted life-year., Limitations: Follow-up data beyond 3 years post randomisation are not available to inform longer-term safety and cost-effectiveness., Conclusions: Single-incision mini-slings were non-inferior to standard mid-urethral slings in patient-reported success rates at up to 3 years' follow-up., Future Work: Success rates, adverse events, retreatment rates, symptoms, and quality-of-life scores at 10 years' follow-up will help inform long-term effectiveness., Trial Registration: This trial was registered as ISRCTN93264234., 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. 47. See the NIHR Journals Library website for further project information.

Background: Bersama abyssinica is a common herb in Africa, with diverse medical uses in different areas. The plant is well-known in Tanzania for treating respiratory disorders such as TB, tonsillitis, bronchitis, and asthma, and it has lately been utilized to treat COVID-19 symptoms. Water extract of leaf and stem bark has been registered as an herbal medication known as 'Coviba Dawa' in Tanzania for the relief of bacterial respiratory infections. The extracts, however, have not been scientifically tested for their anti-viral activities. The aim of this work was to test for the cytotoxicity and antiviral effects of bioactive ingredients from B. abyssinica extracts against the Delta variant of the SARS-CoV-2 coronavirus., Methods: B. abyssinica leaves and stem bark were dried under shade in room temperature and then pulverized to obtain small pieces before soaking into different solvents. One hundred grams of each, leaves and stem bark, were extracted in petroleum ether, dichloromethane, ethyl acetate and methanol. Water extract was obtained by decoction of stem bark and leaves into water. Phenols, flavonoids, tannins, and antioxidants were confirmed as components of the extracts. Analysis of polar extracts of bark stem bark and leaves was done. Antiviral screening and cytotoxicity experiments were conducted in a Biosafety Level 3 (BSL-3) Laboratory facility according to International Standard Operating Procedures (SOPs)., Results: By the use of LC-MS/MS analysis, this study confirmed the existence of four phenolic compounds in B. abyssinica water extract; 2,4-di-tert-butylphenol, 4-formyl-2-methoxyphenyl propionate, 7,8-Dihydroxy-4-methylcoumarin, and 2,3, 6-trimethoxyflavone with antioxidant activity. This study showed that, while the water extracts of B. abyssinica had significant antiviral activity against SARS Cov2 virus, it showed no cytotoxicity effect on Vero E6 cells. In particular, the water extract (Coviba dawa) showed 75% while ethylacetate fraction of B. abyssinica leaves showed a 50% in vitro viral inhibition, indicating that these substances may be useful for the development of future anti-viral agents., Conclusion: We therefore recommend isolation of compounds for further profiling and development with a broader concentration range. We further recommend studies that determine the antiviral activity of extracts of B.abyssinica on other viral pathogens of clinical concern., (© 2022. The Author(s).)

Background: Various washout policies are widely used in adults living with long-term catheters (LTC). There is currently insufficient evidence on the benefits and potential harms of prophylactic LTC washout policies in the prevention of blockages and other LTC-related adverse events, such as urinary tract infections. CATHETER II tests the hypothesis that weekly prophylactic LTC washouts (normal saline or citric acid) in addition to standard LTC care reduce the incidence of catheter blockage requiring intervention compared to standard LTC care only in adults living with LTC., Methods: CATHETER II is a pragmatic three-arm open multi-centre superiority randomised controlled trial with an internal pilot, economic analysis, and embedded qualitative study. Eligible participants are adults aged ≥ 18 years, who have had a LTC in use for ≥ 28 days, have no plans to discontinue the use of the catheter, are able to undertake the catheter washouts, and complete trial documentation or have a carer able to help them. Participants are identified from general practitioner practices, secondary/tertiary care, community healthcare, care homes, and via public advertising strategies. Participants are randomised 1:1:1 to receive a weekly saline (0.9%) washout in addition to standard LTC care, a weekly citric acid (3.23%) washout in addition to standard LTC care or standard LTC care only. Participants and/or carers will receive training to administer the washouts. Patient-reported outcomes are collected at baseline and for 24 months post-randomisation. The primary clinical outcome is catheter blockage requiring intervention up to 24 months post-randomisation expressed per 1000 catheter days. Secondary outcomes include symptomatic catheter-associated urinary tract infection requiring antibiotics, catheter change, adverse events, NHS/ healthcare use, and impact on quality of life., Discussion: This study will guide treatment decision-making and clinical practice guidelines regarding the effectiveness of various prophylactic catheter washout policies in men and women living with LTC. This research has received ethical approval from Wales Research Ethics Committee 6 (19/WA/0015)., Trial Registration: ISRCTN ISRCTN17116445 . Registered prospectively on 06 November 2019., (© 2022. The Author(s).)